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10,900 | 26,069,611 | Other noninvasive or less invasive strategies are available that have varying degrees of effect .
Conclusions : Although the evidence supporting many of the clinical management options might be considered modest , those effects are sufficient to permit an active lifestyle and have , given the prevalence of the disease , a public health impact | Purpose : Osteoarthritis of the knee is a complex interaction of biological , mechanical , and biochemical factors that are further complicated by injury , which accelerates pathological processes within the joint .
As a result , athletes , particularly those with a history of knee injury , have an earlier onset and higher prevalence of osteoarthritis that would be expected based on their age .
This can present a clinical dilemma to the physician managing the patient who , despite the presence of radiologically confirmed disease , has few symptoms and wishes to maintain an active lifestyle . | OBJECTIVES Patients with knee osteoarthritis ( OA ) often suffer pain that is not fully controlled by analgesics and often require intra-articular therapies . The aim of this study was to compare the benefits of intra-articular corticosteroid injections ( CSIs ) and tidal irrigation ( TI ) in patients with OA of the knee . METHODS We performed a dual-centre , single blind , r and omised , parallel group trial comparing TI and CSI . Patients with knee OA were r and omised to either irrigation using a 3.2 mm arthroscope under local anaesthesia or an intra-articular injection of 40 mg triamcinolone acetonide and 1 % lidocaine . Patients were followed for 6 months . The primary outcome measure was the Western Ontario and McMaster Universities OA Index total pain score ( visual analogue scale , VAS ) . RESULTS One hundred and fifty patients were recruited of whom 71 received TI and 79 CSI . In both treatment groups , over 80 % of patients reported improvement at 2 and 4 weeks . After this time , the benefit of CSI decreased whereas that of TI was maintained : at 26 weeks the pain relief afforded by TI was significantly greater than that of CSI . At 26 weeks 29 % of the CSI group reported improvement vs 64 % of the TI group ( P<0.001 ) . Patients with a knee effusion responded better to both treatments , however , this was most apparent for CSI . Patients with less severe radiographic OA also obtained the greatest improvement from both treatments . CONCLUSION Both procedures lead to significant short-term pain relief of at least 4 weeks , however , TI displayed a significantly greater duration of benefit . Patients with effusions and milder radiographic change obtained the best response to treatment Osteoarthritis of the knee is the most common cause of chronic disability among older persons in the United States [ 1 ] . In persons with symptomatic osteoarthritis of the knee , quadriceps muscle weakness is common and is widely believed to result from disuse atrophy secondary to joint pain . Although exercises to strengthen the quadriceps may relieve joint pain in persons with osteoarthritis of the knee [ 2 - 6 ] , the role of periarticular muscle weakness in the pathogenesis of joint pain and disability in these persons is poorly understood . The basis for the beneficial effect of strengthening exercises is unclear , and the duration of the improvement has not been studied . Furthermore , the possibility that muscle weakness is an etiologic factor underlying the pathologic changes of osteoarthritis has seldom been considered . Elucidation of the role of muscle weakness in osteoarthritis is particularly important given our growing underst and ing of safe and effective methods for increasing strength in elderly persons [ 7 , 8 ] . A substantial proportion of persons who have radiographic evidence of osteoarthritis of the knee have no joint pain [ 9 ] . Because asymptomatic persons with radiographic changes seldom seek medical attention for osteoarthritis , muscle weakness has not been studied previously in this group . Thus , it is not known whether quadriceps weakness precedes or follows joint pain or ( if it follows joint pain ) whether it is mediated by disuse atrophy or by physiologic mechanisms that may inhibit muscle contraction [ 10 ] . To address this issue , we studied the relation among lower-extremity muscle strength , lower-extremity lean tissue mass , and osteoarthritis of the knee in men and women 65 years of age and older . Methods Study Group To obtain a sample of elderly persons living in the community , we conducted brief telephone interviews with residents of households in central Indiana . Potential participants were selected through modified r and om-digit dialing to increase the sample d proportion of persons 65 years of age and older . Persons were eligible if they met the minimal criteria for participation : They were willing and able to provide informed consent and to undergo the necessary strength assessment s and other evaluations . Persons were excluded if they had had amputations of both lower extremities , had undergone total knee arthroplasty , or had recently had a cerebrovascular accident or myocardial infa rct ion . A total of 462 persons ( approximately 55 % of all who were eligible ) agreed to participate and completed the following evaluations . Evaluations Radiography of the Knee St and ing anteroposterior and lateral radiographs of both knees of each study participant were obtained , and the severity of osteoarthritis in the tibiofemoral compartment was grade d by a musculoskeletal radiologist according to the criteria of Kellgren and Lawrence . Similar criteria , based on the presence of osteophytes and joint space narrowing , were used for the patellofemoral compartment [ 11 ] . The radiologist was blinded to the clinical status and characteristics of all patients . A participant had to have a Kellgren and Lawrence grade of 2 or more in either knee to be classified as having osteoarthritis . Knee Pain and Function The Western Ontario and McMaster Universities Arthritis Index was used to evaluate knee pain and function [ 12 ] . This index assesses the severity of knee pain during 5 activities or situations ( walking on a flat surface , going up or down stairs , at night while in bed , sitting or lying , and st and ing upright ) and the severity of impairment of lower-extremity function during 17 activities . Pain and functional impairment were assessed in each knee separately . Responses to each question about the severity of knee pain and level of impairment were recorded on a categorical scale as none , mild , moderate , severe , or extreme . Each category was assigned a corresponding numeric score from 1 to 5 ( 5 = extreme ) . Hence , the range on the pain scale was 5 to 25 and the range on the physical impairment scale was 17 to 85 ( 85 = greatest functional limitation ) . For the purpose s of analysis , participants who rated the severity of their knee pain as moderate or greater ( 3 ) with any of the 5 activities on more than half of the days in the month preceding the evaluation were considered to have knee pain . Thus , pain in the more distant past that had resolved was not included . Participants were also question ed about current and previous regular ( 5 times per week ) or occasional use of over-the-counter and prescription analgesics and nonsteroidal anti-inflammatory drugs ( NSAIDs ) in the past year . Lower-Extremity Muscle Strength The strength of each leg was evaluated by using an isokinetic dynamometer ( KIN-COM 500H , Chattecx Corp. , Hixson , Tennessee ) . Peak torque was recorded in both the concentric ( contractions during muscle shortening ) and eccentric ( contractions during muscle lengthening ) modes . Participants were allowed several submaximal or maximal practice efforts to familiarize themselves with the operation of the dynamometer . Once formal testing began , the best of three maximal efforts was recorded for flexion and extension at both 60 degrees per second and 120 degrees per second . Aborted efforts were repeated in order to obtain the best possible representation of strength for each participant . Concentric and eccentric testing yielded similar results , but because of greater variability in eccentric testing , only the concentric test results are shown . Lower-Extremity Lean Tissue Mass Total-body dual-energy x-ray absorptiometry was done in all participants by using a Lunar-DPX-L instrument ( Lunar Corp. , Madison , Wisconsin ) . Results were analyzed for total and regional body composition , including body fat , mineral , and lean components ( lean components were components other than fat or mineral ) . The right and left lower extremities were analyzed separately . The lower extremity was defined as all tissue below a diagonal line drawn outward and upward from the groin area through the femoral neck . Statistical Analysis Participants were divided into four groups on the basis of presence or absence of radiographic evidence of osteoarthritis of the knee and presence or absence of knee pain , as defined above . Men and women were compared by using the t-test . Comparisons of Arthritis Index pain and functional impairment scores were done by using nonparametric approaches . For analyses of continuous data involving more than two groups of participants ( for example , osteoarthritis with or without knee pain ) , analysis of variance was used to determine whether an overall difference was present . The Fisher protected least-significant-difference procedure was used for pairwise comparisons . Comparisons within participants ( for example , comparison of the two legs in a person with unilateral osteoarthritis of the knee ) were done by using paired t-tests . Regression models were constructed with the generalized estimating equations approach of Zeger and Liang [ 13 ] . This approach inflates the st and ard errors to adjust for correlations in both independent variables ( such as strength ) and dependent variables ( such as radiographic grade ) within participants . Statistically significant differences ( P < 0.05 ) in the above analyses are specifically noted below . Results The characteristics of the 462 men and women in the cohort are shown in Table 1 . As expected , men were taller , were heavier , and had greater lower-extremity strength and lean tissue mass in the lower extremities compared with women ( P < 0.001 for all comparisons ) . Table 1 . Age , Height , Weight , and Lower-Extremity Strength and Lean Tissue Mass * One hundred forty-five participants ( 31 % ; 33 % of the women and 30 % of the men ) had radiographic evidence of osteoarthritis involving the tibiofemoral compartment , the patellofemoral compartment , or both . In 62 participants ( 43 % ) , the radiographic changes were unilateral . Table 2 shows the association between osteoarthritis and obesity [ 14 - 16 ] . Women in the cohort who had osteoarthritis were approximately 15 % heavier than women with normal radiographs and no knee pain . Men with osteoarthritis were also slightly heavier than men without osteoarthritis . Table 2 . Body Weight and Summed Arthritis Index Scores for Recent Pain and Function in the Left Knee in Participants with and without Radiographic Evidence of Osteoarthritis * Among those with radiographic evidence of tibiofemoral osteoarthritis , women were slightly more likely than men to report knee pain ( P = 0.10 ; Table 3 ) . Table 3 . Radiography and Recent Pain in the Left Knee Table 2 also shows the mean summed and the distribution of scores for left knee pain and functional impairment ( data for the right knee were similar ) . Among men and women with radiographic evidence of osteoarthritis who reported having knee pain , the mean summed pain score for the knee with osteoarthritis was approximately 12 ( median score , 2 of 5 ) . In comparison , the mean pain score of participants who reported knee pain but did not have radiographic evidence of osteoarthritis in the painful knee was approximately 10 ( median score , 2 of 5)-only slightly lower than the mean pain score of participants with radiographic changes . Consistent with their relatively low pain scores , these community-dwelling participants with osteoarthritis reported moderately low use of NSAIDs ( Table 4 ) . Table 4 . Participants Reporting Regular Current or Previous Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs Related to the Presence of Radiographic Evidence of Osteoarthritis of the Knee and Recent Knee Pain * Arthritis Index scores for functional impairment paralleled those for pain ( Table 2 ) . Participants with osteoarthritis had the greatest functional impairment ( P < 0.001 for the comparison with patients who did not have pain or radiographic evidence of osteoarthritis ) . Functional impairment in participants who had pain but no radiographic evidence of OBJECTIVE To determine the relationship between change in body mass and knee-joint moments and forces during walking in overweight and obese older adults with knee osteoarthritis ( OA ) following an 18-month clinical trial of diet and exercise . METHODS Data were obtained from 142 sedentary , overweight , and obese older adults with self-reported disability and radiographic evidence of knee OA who underwent 3-dimensional gait analysis . Gait kinetic outcome variables included peak knee-joint forces and peak internal knee-joint moments . Mixed regression models were created to predict followup kinetic values , using followup body mass as the primary explanatory variable . Baseline body mass was used as a covariate , and thus followup body mass was a surrogate measure for change in body mass ( i.e. , weight loss ) . RESULTS There was a significant direct association between followup body mass and peak followup values of compressive force ( P = 0.001 ) , result ant force ( P = 0.002 ) , abduction moment ( P = 0.03 ) , and medial rotation moment ( P = 0.02 ) . A weight reduction of 9.8 N ( 1 kg ) was associated with reductions of 40.6 N and 38.7 N in compressive and result ant forces , respectively . Thus , each weight-loss unit was associated with an approximately 4-unit reduction in knee-joint forces . In addition , a reduction in body weight of 9.8 N ( 1 kg ) was associated with a 1.4 % reduction ( 0.496 Nm ) in knee abduction moment . CONCLUSION Our results indicate that each pound of weight lost will result in a 4-fold reduction in the load exerted on the knee per step during daily activities . Accumulated over thous and s of steps per day , a reduction of this magnitude would appear to be clinical ly meaningful OBJECTIVE . To compare the safety and efficacy of a topical diclofenac solution versus oral diclofenac in relieving the symptoms of primary osteoarthritis ( OA ) of the knee , in a r and omized , double-blind , double-dummy equivalence trial . METHODS A total of 622 men and women with radiological evidence of primary knee OA and mild to severe symptoms were r and omly assigned to treatment with a topical diclofenac solution plus placebo oral capsules , or placebo topical solution plus oral diclofenac ( 50 mg ) capsules . Patients applied 50 drops of study solution and took 1 study capsule 3 times daily for 12 weeks . Efficacy variables were pain and physical function , measured by the Western Ontario and McMaster Universities ( WOMAC ) VA 3.1 OA Index , and patient global assessment ( PGA ) . Equivalence in the per- protocol group was based on previously defined ranges of clinical ly significant difference . Safety was assessed by evaluation of adverse events , vital signs , and laboratory data . RESULTS The difference in mean ( 95 % CI ) change scores ( final minus baseline ) between treatments was 13.3 mm ( -8.6 to 35.2 ) for pain ( total scale 500 mm ) , 71.0 mm ( -2.4 to 144.5 ) for physical function ( total scale 1700 mm ) , and 4.3 mm ( -1.2 to 9.8 ) for PGA ( total scale 100 mm ) . The CI for each efficacy variable fell within the predefined equivalence ranges ( pain , + /- 75 mm ; physical function , + /- 255 mm ; PGA , + /- 20 mm ) , indicating that no clinical ly relevant difference was found between the 2 treatment arms . Safety analyses of patients applying topical diclofenac solution revealed some minor skin irritation at the application site -- mostly skin dryness in 83/311 ( 27 % ) patients --but a significantly reduced incidence , relative to oral diclofenac , of total and severe gastrointestinal ( GI ) adverse events , including dyspepsia , abdominal pain , diarrhea , and nausea . The number of patients developing abnormal liver function tests ( including clinical ly significant elevation ) , hemoglobin , and creatinine clearance was significantly higher in the oral diclofenac group . CONCLUSION Application of this topical diclofenac solution to the knee of patients with OA produced relief of symptoms equivalent to oral diclofenac , with minor local skin irritation , but significantly reduced incidence of diclofenac-related GI complaints and abnormal laboratory values The knee joints of 81 veteran soccer players between ages 40 and 74 were examined . An analysis of and relationships between soccer practice at a top level , osteoarthritis , meniscectomy , and leg axes were evaluated . One-hundred and sixty-two knees were assessed through clinical examination and X-ray examination using a large table in order to observe the entire lower extremity 's axis in weight bearing . First , it appears that radiological signs of osteoarthritis in soccer players increase with age in a much greater percentage than in a r and om population of the same age . Second , all players who have had a meniscectomy presented with radiological signs of osteoarthritis . In this series , 91 knees ( 56 % ) had X-ray signs of osteoarthritis . 64 knees ( 70 % ) in which the roentgenograms showed significant osteoarthritic changes were clinical ly asymptomatic . Third , the lower extremities displayed a varus angulation of both knees in 73 % ( meaning that 59 veteran players have a varus of both legs ) , while 81 % of all the knees showed a varus deviation |
10,901 | 24,598,477 | RESULTS Interventions focusing on advance directives as well as interventions that also included communication about end-of-life care increased the completion of advance directives and the occurrence of end-of-life care discussion s between patients and healthcare professionals .
In addition , interventions that also included communication about ACP , improved concordance between preferences for care and delivered care and may improve other outcomes , such as quality of communication . | null | null |
10,902 | 29,721,817 | Conclusions Hyperoxia had minimal impact on organ dysfunction , length of stay , and mortality in adult cardiac surgery .
Conclusions L’hyperoxie a eu des répercussions minimes sur le dysfonctionnement des organes , la durée de séjour et la mortalité au cours de la chirurgie cardiaque de l’adulte . | Purpose Historically , cardiac surgery patients have often been managed with supraphysiologic intraoperative oxygen levels to protect against the risks of cellular hypoxia inherent in the un-physiologic nature of surgery and cardiopulmonary bypass .
This may result in excessive reactive oxygen species generation and exacerbation of ischemia-reperfusion injury .
In this review , we synthesize all available data from r and omized controlled trials ( RCTs ) to investigate the impact that hyperoxia has on postoperative organ dysfunction , length of stay , and mortality during adult cardiac surgery .
ont souvent été gérés avec une oxygénothérapie peropératoire supraphysiologique pour protéger contre le risque d’hypoxie cellulaire inhérent à la nature non physiologique de la chirurgie et de la circulation extracorporelle .
Ceci peut entraîner la formation de dérivés réactifs de l’oxygène et l’exacerbation des lésions d’ischémie-reperfusion . | Background — Oxygen is commonly administered to patients with ST-elevation – myocardial infa rct ion despite previous studies suggesting a possible increase in myocardial injury as a result of coronary vasoconstriction and heightened oxidative stress . Methods and Results — We conducted a multicenter , prospect i ve , r and omized , controlled trial comparing oxygen ( 8 L/min ) with no supplemental oxygen in patients with ST-elevation – myocardial infa rct ion diagnosed on paramedic 12-lead ECG . Of 638 patients r and omized , 441 patients had confirmed ST-elevation – myocardial infa rct ion and underwent primary end-point analysis . The primary end point was myocardial infa rct size as assessed by cardiac enzymes , troponin I , and creatine kinase . Secondary end points included recurrent myocardial infa rct ion , cardiac arrhythmia , and myocardial infa rct size assessed by cardiac magnetic resonance imaging at 6 months . Mean peak troponin was similar in the oxygen and no oxygen groups ( 57.4 versus 48.0 & mgr;g/L ; ratio , 1.20 ; 95 % confidence interval , 0.92–1.56 ; P=0.18 ) . There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group ( 1948 versus 1543 U/L ; means ratio , 1.27 ; 95 % confidence interval , 1.04–1.52 ; P=0.01 ) . There was an increase in the rate of recurrent myocardial infa rct ion in the oxygen group compared with the no oxygen group ( 5.5 % versus 0.9 % ; P=0.006 ) and an increase in frequency of cardiac arrhythmia ( 40.4 % versus 31.4 % ; P=0.05 ) . At 6 months , the oxygen group had an increase in myocardial infa rct size on cardiac magnetic resonance ( n=139 ; 20.3 versus 13.1 g ; P=0.04 ) . Conclusion — Supplemental oxygen therapy in patients with ST-elevation – myocardial infa rct ion but without hypoxia may increase early myocardial injury and was associated with larger myocardial infa rct size assessed at 6 months . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01272713 BACKGROUND The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infa rct ion who do not have hypoxemia at baseline is uncertain . METHODS In this registry‐based r and omized clinical trial , we used nationwide Swedish registries for patient enrollment and data collection . Patients with suspected myocardial infa rct ion and an oxygen saturation of 90 % or higher were r and omly assigned to receive either supplemental oxygen ( 6 liters per minute for 6 to 12 hours , delivered through an open face mask ) or ambient air . RESULTS A total of 6629 patients were enrolled . The median duration of oxygen therapy was 11.6 hours , and the median oxygen saturation at the end of the treatment period was 99 % among patients assigned to oxygen and 97 % among patients assigned to ambient air . Hypoxemia developed in 62 patients ( 1.9 % ) in the oxygen group , as compared with 254 patients ( 7.7 % ) in the ambient‐air group . The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient‐air group . The primary end point of death from any cause within 1 year after r and omization occurred in 5.0 % of patients ( 166 of 3311 ) assigned to oxygen and in 5.1 % of patients ( 168 of 3318 ) assigned to ambient air ( hazard ratio , 0.97 ; 95 % confidence interval [ CI ] , 0.79 to 1.21 ; P=0.80 ) . Rehospitalization with myocardial infa rct ion within 1 year occurred in 126 patients ( 3.8 % ) assigned to oxygen and in 111 patients ( 3.3 % ) assigned to ambient air ( hazard ratio , 1.13 ; 95 % CI , 0.88 to 1.46 ; P=0.33 ) . The results were consistent across all predefined subgroups . CONCLUSIONS Routine use of supplemental oxygen in patients with suspected myocardial infa rct ion who did not have hypoxemia was not found to reduce 1‐year all‐cause mortality . ( Funded by the Swedish Heart – Lung Foundation and others ; DETO2X‐AMI Clinical Trials.gov number , NCT01787110 . Background Postoperative cognitive dysfunction ( POCD ) is a common complication of cardiac surgery . Studies have identified potentially injurious roles for cardiopulmonary bypass ( CPB ) and subsequent reperfusion injury . Cognitive dysfunction has also been linked to the deleterious effects of hyperoxia following ischemia-reperfusion injuries in several disease states , but there has been surprisingly little study into the role of hyperoxia in reperfusion injury after CPB . The potential for tightly regulated intraoperative normoxia to ameliorate the neurocognitive decline following cardiac surgery has not been investigated in a prospect i ve manner . We hypothesize that the use of a protocol ized management strategy aim ed towards maintenance of an intraoperative normoxic level of oxygen , as opposed to hyperoxia , will reduce the incidence of POCD in older patients undergoing cardiac surgery . Methods / Design One hundred patients aged 65 years and older undergoing non-emergency coronary artery bypass grafting surgery on cardiopulmonary bypass will be enrolled in this prospect i ve , r and omized , controlled trial . Subjects will be r and omized to receive a fraction of inspired oxygen of either 35 % or 100 % while under general anesthesia throughout the intraoperative period . The primary outcome measure will be the incidence of POCD in the acute postoperative phase and up to 6 months . The assessment of neurocognition will be undertaken by trained personnel , blinded to study group , with the telephone Montreal Cognitive Assessment ( t-MoCA ) tool . Secondary outcome measures will include assessment of delirium using the Confusion Assessment Method ( CAM and CAM-ICU ) , as well as time to extubation , days of mechanical ventilation , length of ICU and hospital stay and mortality at 6 months . With the aim of later identifying mechanistic aspects of the effect of oxygen tension , blood , urine , and atrial tissue specimens will be taken at various time points during the perioperative period and later analyzed . Discussion This trial will be one of the first r and omized controlled studies to prospect ively assess the relationship between intraoperative oxygen levels and postoperative neurocognition in cardiac surgery . It addresses a promising biological avenue of intervention in this vulnerable aging population .Trial registration Clinical Trials.gov Identifier : NCT02591589 , registered February 13 , 2015 Although an adverse influence of hyperoxemia during cardiopulmonary bypass is well documented , there is a wide range of oxygen setting s during cardiopulmonary bypass , based mostly on trial and error . The aim of this study was to determine the optimal inspired oxygen fraction during cardiopulmonary bypass . Ninety patients undergoing isolated coronary artery bypass operations were r and omly allocated to one of 3 groups of 30 each . In group 1 , cardiopulmonary bypass was started with an inspired oxygen fraction of 0.40 , increased to 0.60 during rewarming . These setting s were 0.40 and 0.50 in group 2 , and 0.35 and 0.45 in group 3 . Sample s for blood gas analysis were collected at defined time periods during the operation . PaO2 was significantly higher in groups 1 and 2 compared to group 3 . All patients in group 1 and 88 % of patients in group 2 suffered at least one episode of hyperoxemia during cardiopulmonary bypass , compared to 30 % of patients in group 3 . The differences were significant , and we concluded that to avoid hyperoxemia , inspired oxygen fraction should be kept at 0.35 during cardiopulmonary bypass and increased to 0.45 during rewarming Objective : To determine whether higher levels of PaO2 are associated with in-hospital mortality and poor neurological status at hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest . Design : Retrospective analysis of a prospect i ve cohort . Patients : A total of 170 consecutive patients treated with therapeutic hypothermia in the cardiovascular care unit of an academic tertiary care hospital . Interventions : None . Measurements and Main Results : Of 170 patients , 77 ( 45.2 % ) survived to hospital discharge . Survivors had a significantly lower maximum PaO2 ( 198 mm Hg ; interquartile range , 152.5–282 ) measured in the first 24 hrs following cardiac arrest compared to nonsurvivors ( 254 mm Hg ; interquartile range , 172–363 ; p = .022 ) . A multivariable analysis including age , time to return of spontaneous circulation , the presence of shock , byst and er cardiopulmonary resuscitation , and initial rhythm revealed that higher levels of PaO2 were significantly associated with increased in-hospital mortality ( odds ratio 1.439 ; 95 % confidence interval 1.028–2.015 ; p = .034 ) and poor neurological status at hospital discharge ( odds ratio 1.485 ; 95 % confidence interval 1.032–2.136 ; p = .033 ) . Conclusions : Higher levels of the maximum measured PaO2 are associated with increased in-hospital mortality and poor neurological status on hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest Background The safety of perioperative hyperoxia is currently unclear . Previous studies in patients undergoing coronary artery bypass surgery suggest reduced myocardial damage when avoiding extreme perioperative hyperoxia ( > 400 mmHg ) . In this study we investigated whether an oxygenation strategy from moderate hyperoxia to a near-physiological oxygen tension reduces myocardial damage and improves haemodynamics , organ dysfunction and oxidative stress . Methods This was a single-blind , single-centre , open-label , r and omised controlled trial in patients undergoing elective coronary artery bypass surgery . Fifty patients were r and omised to a partial pressure of oxygen in arterial blood ( PaO2 ) target of 200–220 mmHg during cardiopulmonary bypass and 130–150 mmHg during intensive care unit ( ICU ) admission ( control group ) versus lower targets of 130–150 mmHg during cardiopulmonary bypass and 80–100 mmHg at the ICU ( conservative group ) . Primary outcome was myocardial injury ( CK-MB and Troponin-T ) at ICU admission and 2 , 6 and 12 hours thereafter . Results Weighted PaO2 during cardiopulmonary bypass was 220 mmHg ( interquartile range ( IQR ) 211–233 ) vs. 157 ( 151–162 ) in the control and conservative group , respectively ( P < 0.0001 ) . During ICU admission , weighted PaO2 was 107 mmHg ( 86–141 ) vs. 90 ( 84–98 ) ( P = 0.03 ) , respectively . Area under the curve of CK-MB was median 23.5 μg/L/h ( IQR 18.4–28.1 ) vs. 21.5 ( 15.8–26.6 ) ( P = 0.35 ) and 0.30 μg/L/h ( 0.25–0.44 ) vs. 0.39 ( 0.24–0.43 ) ( P = 0.81 ) for Troponin-T. Cardiac index , systemic vascular resistance index , creatinine , lactate and F2-isoprostane levels were not different between groups . Conclusions Compared to moderate hyperoxia , a near-physiological oxygen strategy does not reduce myocardial damage in patients undergoing coronary artery bypass surgery . Conservative oxygen administration was not associated with increased lactate levels or hypoxic events . Trial registration Netherl and s Trial Registry NTR4375 , registered on 30 January Background Valvular heart surgery ( VHS ) utilizing cardiopulmonary bypass ( CPB ) is inevitably associated with ischemic-reperfusion injury , which is known to depend on oxygen tension during reperfusion . The aim of this study was to evaluate the effect of arterial oxygen tension during reperfusion on myocardial recovery in patients undergoing VHS . Methods Fifty-six patients undergoing isolated VHS were r and omly exposed to an oxygen fraction of 0.7 ( hyperoxic group , n = 28 ) or 0.5 ( normoxic group , n = 28 ) during reperfusion . All patients received an oxygen fraction of 0.7 during CPB . In the normoxic group , the oxygen fraction was lowered to 0.5 from the last warm cardioplegia administration to 1 minute after aortic unclamping , and was then raised back to 0.7 . Hemodynamic data were measured after induction of anesthesia , weaning from CPB , and sternum closure . The frequency of cardiotonic medications used during and after weaning from CPB , and the short-term outcomes during the hospital stay were also assessed . Results The frequency of vasopressin and milrinone use during weaning from CPB , but not norepinephrine , was significantly less in the normoxic group . The post-operative cardiac enzyme levels and short-term outcomes were not different between the groups . Conclusions Normoxic reperfusion from the last cardioplegia administration to 1 minute after aortic unclamping in patients undergoing VHS result ed in significantly less frequent use of vasopressin and inotropics during weaning from CPB than hyperoxic reperfusion , although it did not affect the post-operative myocardial enzyme release or short-term prognosis OBJECTIVE Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult . This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide . Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy ( normoxic cardiopulmonary bypass ) . METHODS During elective coronary artery bypass grafting , 40 consecutive patients underwent either hyperoxic ( oxygen tension = 400 mm Hg ) or normoxic ( oxygen tension = 140 mm Hg ) cardiopulmonary bypass . At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase , nitrate , creatine kinase , and lactic dehydrogenase , antioxidant levels , and malondialdehyde in coronary sinus blood . Cardiac index was measured before and after cardiopulmonary bypass . RESULTS There was no difference between groups with regard to age , sex , severity of disease , ejection fraction , number of grafts , duration of cardiopulmonary bypass , or ischemic time . Hyperoxic bypass result ed in higher levels of polymorphonuclear leukocyte elastase ( 377 + /- 34 vs 171 + /- 32 ng/ml , p = 0.0001 ) , creatine kinase 672 + /- 130 vs 293 + /- 21 U/L , p = 0.002 ) , lactic dehydrogenase ( 553 + /- 48 vs 301 + /- 12 U/L , p = 0.003 ) , antioxidants ( 1.97 + /- 0.10 vs 1.41 + /- 0.11 mmol/L , p = 0.01 ) , malondialdehyde ( 1.36 + /- 0.1 micromol/L , p = 0.005 ) , and nitrate ( 19.3 + /- 2.9 vs 10.1 + /- 2.1 micromol/L , p = 0.002 ) , as well as reduction in lung vital capacity ( 66 % + /- 2 % vs 81 % + /- 1%,p = 0.01 ) and forced 1-second expiratory volume ( 63 % + /- 10 % vs 93 % + /- 4 % , p = 0.005 ) compared with normoxic management . Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups ( 3.1 + /- 0.2 vs 3.3 + /- 0.3 L/min per square meter ) . [ Data are mean + /- st and ard error ( analysis of variance ) , with p values compared with an oxygen tension of 400 mm Hg . ] CONCLUSIONS Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide . These adverse effects can be markedly limited by reduced oxygen tension management . The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations BACKGROUND Most cardiac operations with cardiopulmonary bypass ( CPB ) are conducted with high oxygen partial pressure . The hyperoxic reoxygenation of the ischemic heart induced by aortic declamping may be an important component of cardiac reperfusion injury . The present clinical study assessed the preventive effect of grade d reoxygenation on lipid peroxidation . Malondialdehyde ( MDA ) levels reflect lipid peroxidation , and therefore can be used to quantify reoxygenation damage . MATERIAL / METHODS 19 patients with coronary artery disease were enrolled consecutively and divided into two groups . In Group I , grade d reoxygenation was initiated 1 min before , and continued for 9 min after aortic declamping ( paO2 : 50 - 70 mmHg , n=10 ) . Patients undergoing conventional hyperoxic reoxygenation ( paO2 : > 250 mmHg ) on CPB ( Group II , n=9 ) served as controls . Blood was collected before commencement of CPB , 2 min before release of the aortic crossclamp , 1 min and 10 min after release of the aortic crossclamp , and 3 hours after CPB . RESULTS MDA levels [ KM/l ] did not differ between groups before CPB , but 1 min after aortic declamping MDA increased significantly more in group II ( 11.02 + /- 1.05 ; p=0.04 ) as compared to group I ( 8.16 + /- 0.74 ) . There was no difference between groups late after reperfusion . CONCLUSIONS Hyperoxic reoxygenation by release of the aortic crossclamp is associated with increased MDA levels immediately after aortic declamping . Grade d normoxic reoxygenation therefore limits lipid peroxidation in the early reperfusion period OBJECTIVE To investigate the effect of ventilation with 100 % oxygen on lung injury associated with surgery involving cardiopulmonary bypass ( CPB ) . DESIGN A prospect i ve r and omized study . SETTING University hospital . PARTICIPANTS Thirty patients undergoing coronary artery bypass graft surgery with CPB . INTERVENTIONS Patients were r and omized to receive 100 % oxygen ( Oxygen group ) or 50 % oxygen ( Air group ) throughout surgery . During CPB , patients ' lungs in the Air group were flushed with air and in the Oxygen group with 100 % oxygen . MEASUREMENTS AND MAIN RESULTS Lung injury was evaluated by arterial oxygen tension-inspired oxygen concentration ( PaO2-FIO2 ) ratio and cytokine levels ( tumor necrosis factor-alpha and interleukin-8 ) in blood and bronchoalveolar lavage fluid measured before and after CPB . The lowest PaO2-FIO2 value was observed after 40 minutes following the completion of CPB in both groups . PaO2-FIO2 values 6 hours after CPB were not different from baseline in the Air group but remained lower ( 359+/-63 mmHg and 298+/-78 mmHg ; p = 0.013 ) in the Oxygen group . Blood cytokine levels rose during surgery in both groups . Bronchoalveolar lavage levels of interleukin-8 did not change , whereas tumor necrosis factor-alpha increased only in the Oxygen group ( p = 0.035 ) . CONCLUSIONS A significant decrease of oxygenation was observed in the early post-CPB period in both groups of patients , with delay in recovery in patients treated with 100 % oxygen . A larger increase of the proinflammatory cytokines was found in patients treated with 100 % oxygen . High oxygen concentrations during surgery with CPB should be used only when specifically required Purpose The efficacy of myocardial conditioning strategies is compromised in patients with advanced age , diabetes , or low ejection fraction . We conducted a single-centre parallel-arm blinded r and omized-controlled trial to determine whether propofol provides perioperative myocardial protection . Methods Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass ( CPB ) with blood cardioplegia . The participants were stratified by diabetic status and left ventricular ejection fraction and r and omly assigned to receive either an elevated dose of propofol –previously associated with experimental cardioprotection– or an isoflurane preconditioning regime . The primary endpoint was the coronary sinus ( CS ) concentration of 15-F2t-isoprostane ( isoP ) . Secondary endpoints included in-hospital low cardiac output syndrome ( LCOS ) and major adverse cardiac events , 12- and 24-hr CS cardiac troponin I ( cTnI ) release , and myocardial B-cell lymphoma 2 ( Bcl-2 ) protein expression . Results Data were analyzed from 125 of 137 r and omized participants . Participants receiving propofol experienced a greater mean ( SD ) increase from baseline in CS 15-F2t-isoP levels compared with those receiving isoflurane [ 26.9 ( 10.9 ) pg·mL−1vs 12.1 ( 10.4 ) pg·mL−1 , respectively ; mean difference , 14.8 ; 95 % confidence interval ( CI ) , 11.0 to 18.6 ; P < 0.001 ] but a decreased incidence of LCOS ( 20.9 % vs 57.1 % , respectively ; relative risk [RR],0.37 ; 95 % CI , 0.22 to 0.62 ; P < 0.001 ) . The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus ( DM2 ) ( P = 0.382 ) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup ( 17.9 % vs 70.3 % , respectively ; RR , 0.26 ; 95 % CI , 0.13 to 0.52 ; P < 0.001 ) . Propofol was associated with an increase in myocardial Bcl-2 protein expression ( P = 0.005 ) , a lower incidence of a CS cTnI threshold for myocardial infa rct ion ( P = 0.014 ) , and fewer heart failure events ( P < 0.001 ) . Conclusion Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest . The study is registered at www . clinical trials.gov ( NCT00734383 ) and www.controlled-trials.com ( IS RCT N70879185).RésuméObjectifL’efficacité des stratégies de conditionnement myocardique est compromise chez les patients âgés ainsi que chez ceux atteints de diabète ou présentant une fraction d’éjection faible . Nous avons réalisé une étude r and omisée contrôlée unicentrique à bras parallèles et en aveugle afin de déterminer si le propofol procurait une protection myocardique en période périopératoire . MéthodeLes patients enrôlés dans cette étude devaient subir une chirurgie de pontage aorto-coronarien primaire avec circulation extracorporelle ( CEC ) normothermique et cardioplégie sanguine . Les participants ont été stratifiés par statut diabétique et fraction d’éjection ventriculaire gauche , puis aléatoirement répartis en deux groupes , do nt l’un recevrait une dose élevée de propofol – un agent précédemment associé à une cardioprotection expérimentale – et l’autre un régime de préconditionnement à l’isoflurane . Le critère d’évaluation principal était la concentration dans le sinus coronaire ( SC ) de 15-F2t-isoprostane ( isoP ) . Les critères d’évaluation secondaires comprenaient la survenue d’un syndrome de bas débit cardiaque ( SBDC ) pendant le séjour hospitalier et les complications cardiaques majeures , la libération de troponine I cardiaque ( cTnI ) du SC à 12 et 24 h , et l’expression protéinique du lymphome 2 à cellules B ( Bcl-2 ) myocardique . RésultatsLes données de 125 des 137 patients r and omisés ont été analysées . Les participants ayant reçu du propofol ont subi une augmentation moyenne ( ÉT ) plus importante depuis les valeurs de base en matière de niveaux au SC de 15-F2t-isoP par rapport aux patients ayant reçu de l’isoflurane [ 26,9 ( 10,9 ) pg·mL−1vs 12,1 ( 10,4 ) pg·mL−1 , respectivement ; différence moyenne , 14,8 ; intervalle de confiance ( IC ) 95 % , 11,0 à 18,6 ; P < 0,001 ] , mais une incidence moindre de SBDC ( 20,9 % vs 57,1 % , respectivement ; risque relatif [ RR ] , 0,37 ; IC 95 % , 0,22 à 0,62 ; P < 0,001 ) . L’incidence de SBDC était semblable dans les deux groupes chez les participants qui n’étaient pas atteints de diabète de type 2 ( DT2 ) ( P = 0,382 ) , mais significativement réduite dans le sous-groupe DT2 propofol par rapport au sous-groupe DT2 isoflurane ( 17,9 % vs 70,3 % , respectivement ; RR , 0,26 ; IC 95 % , 0,13 à 0,52 ; P < 0,001 ) . Le propofol a été associé à une augmentation de l’expression protéinique du Bcl-2 myocardique ( P = 0,005 ) , une incidence moindre de seuil de cTnI du SC pour un infa rct us du myocarde ( P = 0,014 ) , et moins d’épisodes d’insuffisance cardiaque ( P < 0,001 ) . Conclusion Le propofol pourrait constituer un cardioprotecteur peropératoire préventif pour les patients atteints de DT2 sous CEC normothermique et en arrêt cardioplégique sanguin . Cette étude est enregistrée au www . clinical trials.gov ( NCT00734383 ) et au www.controlled-trials.com ( IS RCT N70879185 ) The effect on myocardial reperfusion injury of reducing oxygen tension during reperfusion on cardiopulmonary bypass ( CPB ) in coronary artery bypass grafting ( CABG ) was examined at the same time as the influence of diltiazem during CPB was evaluated . A prospect i ve , r and omized trial evaluated the hemodynamic and myocardial metabolic recovery in 3 groups of patients undergoing elective CABG ; subjects were r and omly allocated on the basis of oxygen tension during reperfusion after aortic unclamping : group 1 ( n=10 ) hyperoxic reperfusion ( oxygen tension [PO2]=450 - 550 mmHg ) ; group 2 ( n=10 ) : hyperoxic reperfusion and subsequent continuous infusion of diltiazem ( 0.5 microg/kg ) ; group 3 ( n=10 ) : lowering reperfusate PO2 ( PO2=200 - 250 mmHg ) . Hemodynamic and myocardial metabolic measurements were taken at 6 preset times : before starting the surgical procedure and at 30 min and 3 , 9 , 21 , and 45 h after discontinuation of CPB . The cardiac index in the lowering reperfusate PO2 group was higher than that of the hyperoxic reperfusion groups at 30 min and 3 h after CPB , and malondialdehyde and troponin-T were significantly lower at 30 min and 3 h , respectively . In comparison with the hyperoxic + diltiazem group , the hemodynamic and myocardial recovery in the lowering reperfusate PO2 group was improved for about 3 h after CPB . Reduced oxygen tension during reperfusion after aortic unclamping on CPB is more effective against myocardial injury than a calcium antagonist in the short term . It is a convenient and safe management technique that can reduce morbidity and mortality , especially in the severely compromised heart 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 To investigate whether the established reductions in heart rate and cardiac output with hyperoxia in humans are primary effects or secondary to increases in systemic vascular resistance , we paced the hearts of nine patients with permanent pacemakers at a fixed rate when breathing either medical air ( inspired O2 fraction 0.21 ) or oxygen ( inspired O2 fraction 0.80 ) in a r and omised , double‐blind fashion . A thoracic bio‐impedance machine was used to measure heart rate , stroke volume and blood pressure and calculate cardiac index and systemic vascular resistance index . Oxygen caused no change in cardiac index ( p = 0.18 ) , stroke index ( p = 0.44 ) or blood pressure ( p = 0.52 ) but caused a small ( 5.5 % ) increase in systemic vascular resistance index ( p = 0.03 ) . This suggests that hyperoxia has no direct myocardial depressant effects , but that the changes in cardiac output reported in previous studies are secondary to changes in systemic vascular resistance |
10,903 | 27,356,122 | Meta‐regression showed duration of follow‐up was not a source of heterogeneity for most associations .
There was no evidence that lifestyle factors were associated with metachronous CRC or polyp risk .
Conclusion : A comprehensive list of risk factors identified for metachronous CRC or polyp may have important clinical implication | Background and Aim : We conducted a systematic review and meta‐ analysis to identify personal , lifestyle , and tumor‐related risk factors for metachronous colorectal cancer ( CRC ) and polyp . | Analysis of prospect i ve follow-up data usually includes a Cox regression model . When a hazard rate ratio , obtained as the exponential of an estimated regression coefficient from the Cox model , is greater than 1.0 , it consistently exceeds relative risk , and is exceeded by the odds ratio . The divergence of these distinct epidemiologic measures increases with the product of three factors : ( 1 ) the length of follow-up , ( 2 ) the average rate of the end point occurence over the follow-up period , and ( 3 ) the magnitude of risk , either above or below 1 . Cornfield 's rare disease assumption is basically the product of the first two of these factors . However , risks in excess of 2.5 have a powerful effect on the divergence of these measures , and this point has received less emphasis . Conversely , and as seen frequently in applications , relative risk , hazard rate ratio , and odds ratio numerically approximate one another with shorter follow-up , rarer end points , and risks closer to 1 . Although the hazard rate ratio is not always distinguished from relative risk , it is commonly close to , and is always between , relative risk and the odds ratio . Consistent and accurate terminology would have us use hazard rate ratio with Cox regression and odds ratio with logistic regression . The term " relative risk " seems to be a default choice , regardless of the model being used . However , when relative risk is the object of the model chosen , as in a Poisson regression approximation of two binomial proportions or an equivalent weighted least squares , then for us , relative risk is the accurate terminology Background : Patients who have had a colorectal adenoma are likely to develop a metachronous adenoma and therefore need to be kept under surveillance . It is essential to avoid unnecessary examinations by tailoring the frequency of follow up examinations to individual risk . Methods : A total of 3134 patients undergoing endoscopic removal of colorectal adenomas were prospect ively recorded on the Erlangen Registry of Colorectal Polyps between 1978 and 1996 . A multivariate analysis of 1159 patients on long term follow up was performed to identify risk factors determining surveillance intervals for patients with metachronous adenomas of advanced pathology — that is , adenomas > 10 mm or with high grade dysplasia or invasive carcinoma . Results : Univariate analysis revealed that sex , parental history of colorectal carcinoma , and characteristics of the initial findings —that is , size , multiplicity , and amount of villous structure — were significant predictors of metachronous adenomas of advanced pathology . On the basis of multivariate analysis , two risk groups were identified : ( 1 ) patients with no parental history of colorectal carcinoma with only small ( ≤10 mm ) tubular adenomas at the initial clearing examination have a very low risk , and we estimated that 10 % will develop advanced metachronous adenomas after 10 years ; ( 2 ) the high risk group contained all other patients , 10 % of whom will show metachronous adenomas of advanced pathology at follow up after only three years . Conclusions : The risk of developing metachronous adenomas with advanced pathology can be stratified for various patient and adenoma characteristics . Surveillance intervals can be scheduled for low risk ( 10 years ) and high risk ( three years ) patients . Risk related follow up thus helps to avoid unnecessary examinations PURPOSE : The value of routine colonoscopy in the prevention or early detection of metachronous carcinoma of the colon and rectum remains unproven . This study attempts to clarify this issue . METHODS : An analysis of a personal series of 460 patients with primary colorectal carcinoma treated by the second author between 1972 and 1990 was review ed . After various exclusions , there remained 231 patients who had been prospect ively followed by colonoscopy with a mean follow-up period of 56 years . RESULTS : In 48 ( 21 percent ) patients , there were synchronous adenomas present at the time of the initial resection for carcinoma and 35 ( 73 percent ) of these patients subsequently developed metachronous adenomas , being recurrent in 22 . Ninety-five ( 52 percent ) of the 183 patients without synchronous adenomas eventually developed metachronous adenomas , so that overall 130 ( 56 percent ) patients developed metachronous adenomas . Four patients developed a metachronous carcinoma that was either Dukes A or B , and all remain well at the time of final follow-up . These metachronous carcinomas were found after a mean interval of seven and three-quarter years . All four patients had synchronous adenomas and all developed metachronous adenomas on multiple occasions before the metachronous carcinoma was detected . Thus , a subset consisting of only 22 patients produced all four metachronous malignancies — a rate of 18 percent . CONCLUSION : It would appear that the presence of synchronous adenomas with the subsequent development of recurring metachronous adenomas is significant and warrants a more intensive follow-up program to ensure the early diagnosis and more likely cure of any metachronous carcinoma BACKGROUND & AIMS Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk . METHODS We pooled individual data from 8 prospect i ve studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance . RESULTS During a median follow-up period of 47.2 months , advanced colorectal neoplasia was diagnosed in 1082 ( 11.8 % ) of the patients , 58 of whom ( 0.6 % ) had invasive cancer . Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas ( 24.1 % ; st and ard error , 2.2 ) and those with an adenoma 20 mm in size or greater ( 19.3 % ; st and ard error , 1.5 ) . Risk factor patterns were similar for advanced adenomas and invasive cancer . In multivariate analyses , older age ( P < .0001 for trend ) and male sex ( odds ratio [ OR ] , 1.40 ; 95 % confidence interval [ CI ] , 1.19 - 1.65 ) were associated significantly with an increased risk for metachronous advanced neoplasia , as were the number and size of prior adenomas ( P < .0001 for trend ) , the presence of villous features ( OR , 1.28 ; 95 % CI , 1.07 - 1.52 ) , and proximal location ( OR , 1.68 ; 95 % CI , 1.43 - 1.98 ) . High- grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics . CONCLUSIONS Occurrence of advanced colorectal neoplasia is common after polypectomy . Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas Acquired or inherited mutations in the adenomatous polyposis coli ( APC ) tumor suppressor gene are causally linked to colorectal cancer . Given the significance of APC in colorectal cancer , we investigated the association between common single-nucleotide polymorphisms ( SNP ) in the APC gene and the odds of developing metachronous colorectal adenomas as a surrogate measure of colorectal cancer risk . Coding SNPs at codons 486 , 1678 , 1822 , 1960 , and 2502 were analyzed in a total of 1,399 subjects who participated in two r and omized clinical trials for the prevention of colorectal adenomas . No association was found for any single SNP and the odds of metachronous adenoma . In contrast , a TA haplotype ( codons 486 and 1822 ) was associated with a statistically significant 27 % and 26 % reduction in the odds of any and nonadvanced metachronous adenoma after adjustment for baseline adenoma characteristics [ odds ratio ( OR ) , 0.73 ; 95 % confidence interval ( 95 % CI ) , 0.59 - 0.91 and OR , 0.74 ; 95 % CI , 0.57 - 0.94 ] , respectively . No significant reduction in odds was observed for advanced metachronous lesions . Diplotype analysis revealed a strong gene dose effect with carriers of two alleles containing TT-AA ( codons 486 and 1822 , respectively ) having an 89 % lower odds for advanced metachronous adenomas ( OR , 0.11 ; 95 % CI , 0.01 - 0.80 ) when compared with the common CC-AA diplotype ( codons 486 and 1822 , respectively ) . Our findings support an important role for germ-line allele sequence in the APC gene and individual risk of metachronous adenomatous polyps PURPOSE : The aim of this study was to identify the high-risk groups for metachronous colorectal carcinoma among patients who undergo colorectal cancer surgery . METHODS : Three hundred forty-one patients undergoing colorectal cancer surgery who had undergone surveillance colonoscopy at least twice during a period of more than three years were analyzed . A metachronous colorectal carcinoma was defined as a new colorectal carcinoma detected by surveillance colonoscopy after surgery . RESULTS : Surveillance colonoscopy was performed 4.6 times per patient during an average of 6.2 years . Twenty-two metachronous colorectal carcinomas in 19 patients were detected , and 14 ( 64 percent ) of 22 were detected within five years of surgery . The cumulative incidence of developing colorectal carcinomas during a five-year period was 5.3 percent . Seventeen ( 77 percent ) of 22 carcinomas were 10 mm or less in size . Ten ( 71 percent ) of the 14 carcinomas in early stages showed a flat appearance . Univariate analysis showed that extracolonic malignancy , coexistence of adenoma , and synchronous multiple colorectal carcinoma were significant predictive factors for detecting colorectal carcinomas in surveillance colonoscopy and that family history of colorectal carcinoma was a possible predictive factor . Multivariate analysis performed with Cox proportional hazards regression model showed that extracolonic malignancy and the coexistence of adenoma were significant predictive factors . CONCLUSION : We recommend that patients with the above predictive factors receive surveillance colonoscopy meticulously and regularly BACKGROUND : Compared with the general population , patients with a previous colorectal cancer are at higher risk for a second colorectal cancer , but detailed risk analysis by subsite is scarce . OBJECTIVE : Our goal was to investigate the risk of a second cancer in relation to subsite as a basis for planning surveillance strategies , . DESIGN , SETTING , AND PATIENTS : This was a retrospective analysis of a prospect ively design ed , population -based cancer registry ( The Netherl and s Cancer Registry ) . Patients with a stage I , II , or III colorectal cancer diagnosed between 1989 and 2008 were included . MAIN OUTCOME MEASURES : Cumulative incidence , st and ardized incidence ratio , and absolute excess risk for second primary cancers in subsites of the colon and rectum were estimated for follow-up periods of 2 to 5 , 6 to 10 , and more than 10 years after the index cancer in patients older than 50 years and in those aged 50 years or younger . RESULTS : A total of 123,347 patients had a first invasive colorectal cancer diagnosed between 1989 and 2008 . Of these , 1849 patients ( 1.5 % ) had a second colorectal lesion that was found more than 1 year after the initial cancer and diagnosed as a second primary colorectal cancer . In patients older than 50 years , the 20-year cumulative incidence for second cancers was 3.4 % in the proximal colon , 1.2 % in the distal colon , and 1.2 % in the rectum . More than 60 % of second cancers occurred within 5 years after the index cancer . The st and ardized incidence ratio was highest in the proximal-colon ( 1.9 ; 95 % CI , 1.8–2.0 ) , followed by the distal-colon ( 1.0 , 95 % CI , 0.9–1.1 ) , and the rectum ( 0.9 , 95 % CI , 0.8–1.0 ) . The corresponding absolute excess risks per 10 000 person years were 9 in the proximal colon , 0.1 in the distal colon , and 1 in the rectum . After 5 years of follow-up , elevated risk was observed only in the proximal colon . A similar risk pattern was observed in patients younger than 50 years . The absolute excess risk for a second cancer in the proximal colon increased over time . The proportion of stage III and stage IV second cancers increased from 31 % during the first 5 years of follow-up to 38 % after 10 years of follow-up . LIMITATIONS : Limitations of this study included lack of data regarding polypectomy rates and interval of surveillance colonoscopies . CONCLUSIONS : Compared with the general population , individuals with previous colorectal cancer have a higher risk for a second cancer in all subsites of the colon and rectum . Among long-term survivors older than 50 years , risk remains elevated only in the proximal colon . Further studies should be encouraged to develop a suitable surveillance method for aging , high-risk , long-term colorectal cancer survivors |
10,904 | 30,699,412 | Higher fidelity to the ACT model appears to improve outcomes .
Substance use reduced only in half of the data sets , of which only one showed a significant reduction in the ACT group .
Overall , ACT is a promising approach that may be useful for promoting treatment engagement for patients with SUD .
According to earlier studies on patients with severe mental illness , patients with high inpatient service use benefit most from this assertive approach .
We hypothesize that a similar high need user group among patients with SUD might benefit most from ACT . | Purpose : Substance use disorders ( SUD ) are an important health issue internationally .
Traditional outpatient programmes often do not adequately address the substantial medical and social needs and in addition many patients have difficulties accessing the care needed .
The assertive community treatment ( ACT ) model was originally developed for patients with a severe mental illness but has been adapted for patients with SUD by integrating specific SUD treatments into the traditional ACT model .
This paper aims to assess the effectiveness of ACT for patients with SUD on a number of measures . | Abstract Aims A pilot r and omized controlled trial ( RCT ) to assess the feasibility and potential efficacy of assertive community treatment ( ACT ) in adults with alcohol dependence . Methods Single blind , individually r and omized , pilot RCT of 12 months of ACT plus treatment as usual ( TAU ) versus TAU alone in adults ( age 18 + years ) with alcohol dependence and a history of previous unsuccessful alcohol treatment attending specialist community alcohol treatment services . ACT aim ed to actively engage participants for 12 months with assertive , regular , minimum weekly contact . ACT was combined with TAU . TAU comprised access to the full range of services provided by the community teams . Primary outcome is mean drinks per drinking day and percent days abstinent at 12 months follow up . Analysis of covariance was conducted using 80 % confidence intervals , appropriate in the context of a pilot trial . Results A total of 94 participants were r and omized , 45 in ACT and 49 in TAU . Follow-up was achieved with 98 and 88 % , respectively at 12 months . Those in ACT had better treatment engagement , and were more often seen in their homes or local community than TAU participants . At 12 months the ACT group had more problems related to drinking and lower quality of life than TAU but no differences in drinking measures . The ACT group had a higher percentage of days abstinent but lower quality of life at 6 months . The ACT group had less unplanned healthcare use than TAU . Conclusions An trial of ACT was feasible to implement in an alcohol dependent treatment population . Trial registration IS RCT BACKGROUND People with mental illness and substance use disorder are over-represented in prisons . Injury-related mortality is elevated in people released from prison , and both mental illness and substance use disorder are risk factors for injury . Effective care coordination during the transition between criminal justice and community service providers improves health outcomes for people released from prison . However , the health outcomes and support needs of people with dual diagnosis ( co-occurring mental illness and substance use disorder ) released from prison are poorly understood . Here we aim to examine the association between dual diagnosis and non-fatal injury in adults released from prison . METHODS Pre-release interview data collected between Aug 1 , 2008 , and July 31 , 2010 , from a representative sample of sentenced adults ( ≥18 years ) in Queensl and , Australia , were linked , retrospectively and prospect ively , to person-level , state-wide emergency department and hospital records . We identified dual diagnoses from inpatient , emergency department , and prison medical records . We modelled the association between mental health status and all injury result ing in hospital contact by fitting a multivariate Cox regression , adjusting for sociodemographic , health , and criminogenic covariates , and replacing missing covariate data by multiple imputation . FINDINGS In 1307 adults released from prison , there were 2056 person-years of follow-up ( median 495 days , IQR 163 - 958 ) . The crude injury rates were 996 ( 95 % CI 893 - 1112 ) per 1000 person-years for the dual diagnosis group , 538 ( 441 - 657 ) per 1000 person-years for the mental illness only group , 413 ( 354 - 482 ) per 1000 person-years for the substance use disorder only group , and 275 ( 247 - 307 ) per 1000 person-years for the no mental disorder group . After adjusting for model covariates , the dual diagnosis ( adjusted hazard rate ratio 3·27 , 95 % CI 2·30 - 4·64 ; p<0·0001 ) and mental illness only ( 1·87 , 1·19 - 2·95 ; p=0·0071 ) groups were at increased risk of injury after release from prison compared with the group with no mental health disorders . INTERPRETATION People released from prison experience high rates of injury compared with the general population . Among people released from prison , dual diagnosis is associated with an increased risk of injury . Contact with the criminal justice system is a key opportunity to prevent subsequent injury morbidity in people with co-occurring mental health disorders . Engagement with integrated psychiatric and addiction treatment delivered without interruption during the transition from prison into the community might prevent the injury-related disparities experienced by this vulnerable group . The development of targeted injury prevention strategies for people with dual diagnosis released from prison is warranted . FUNDING National Health and Medical Research Council Integrated mental health and substance abuse treatment within an assertive community treatment ( ACT ) approach was compared to that within a st and ard case management approach for 223 patients with dual disorders over three years . ACT patients showed greater improvements on some measures of substance abuse and quality of life , but the groups were equivalent on most measures , including stable community days , hospital days , psychiatric symptoms , and remission of substance use disorder At three community mental health centers ( CMHCs ) in Indiana , 167 clients at risk for rehospitalization were r and omly assigned to experimental groups receiving assertive case management ( ACM ) or to control groups eligible to receive all other aftercare services at the centers . During a six-month follow-up period , experimental clients received an average of one visit a week from the ACM team , usually in the client 's home or in community setting s. Overall , ACM clients were rehospitalized an average of 9.2 days , significantly less than the 30.8 days for controls . In two of the three centers , significant rehospitalization differences were also found between ACM and control groups . No differences were found between groups in quality of life , medication compliance , involvement in CMHC programs , or contacts with the legal system in any of the centers . The most cost-effective center had savings of about + 5,500 for each ACM client We conducted secondary analyses of data from a r and omized trial testing the effectiveness of Assertive Community Treatment ( ACT ) in delivery of integrated dual disorder treatment ( IDDT ) to explore the impact of IDDT delivered through ACT teams compared with st and ard clinical case management for dually-disordered persons with and without antisocial personality disorder ( ASPD ) . This analysis included 36 individuals with ASPD and 88 individuals without ASPD . Participants with ASPD assigned to ACT showed a significantly greater reduction in alcohol use and were less likely to go to jail than those in st and ard clinical case management , whereas participants without ASPD did not differ between the 2 case management approaches . There were no significant differences for other substance use or criminal justice outcomes . This study provides preliminary evidence that persons with co-occurring serious mental illness , substance use disorders , and ASPD may benefit from delivery of IDDT through ACT teams OBJECTIVE : This study analyzed data from a r and omized trial to examine the impact on medication adherence of integrated treatment delivered via assertive community treatment ( ACT ) versus st and ard clinical case management ( SCCM ) . METHOD : Data from the original study included 198 study participants with co-occurring psychotic and substance use disorders who were r and omly assigned to receive integrated treatment via ACT or SCCM and were followed for 3 years . We applied mixed-effects logistic regression to estimate group ( ACT vs. SCCM ) by time effects on a self-report measure of medication adherence . Adherence was dichotomized as 20 % or more missed medication days ( “ poor adherence ” ) versus less than 20 % missed medication days ( “ adequate adherence ” ) . RESULTS : Participants who were assigned to ACT reported significant improvement in medication adherence compared with those assigned to SCCM . CONCLUSIONS : Integrated treatment delivered via ACT may benefit persons with co-occurring psychotic and substance use disorders who are poorly adherent to medications BACKGROUND People with severe mental illness and substance use disorders ( dual disorder ) often have considerable contact with the criminal justice system . AIMS To test the effects of client characteristics on six criminal justice outcomes among homeless ( at intake ) people with mental illness and substance misuse disorders . METHODS The sample was of participants in a r and omized controlled trial comparing st and ard treatment , assertive community treatment ( ACT ) and integrated treatment ( IT ) . Data were analysed using hierarchical logistic regression . RESULTS Half the sample was arrested and a quarter incarcerated during the two-year follow-up period . The regression models explained between 22 % and 35 % of the variance of the following criminal justice measures : ( 1 ) major offences , ( 2 ) minor offences , ( 3 ) substance-use-related offences , ( 4 ) incarcerations , ( 5 ) arrests , and ( 6 ) summons . Prior criminal behaviour was the strongest predictor of all of the dependent variables ; in general , demographic and diagnostic variables were not . Similarly , neither the type nor the amount of mental health treatment received predicted subsequent criminal behaviour . CONCLUSION Elsewhere the authors have shown that ACT and IT had advantages for health and stability of accommodation but these analyses suggest that more specialized interventions are needed to reduce criminal behaviour in dual disorder individuals OBJECTIVE The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment ( ACT ) as part of integrated care compared to st and ard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release . METHOD Two catchment areas in Hamburg , Germany , with similar population size and health care structures were assigned to offer 12-month ACT as part of integrated care ( n = 64 ) or st and ard care ( n = 56 ) to 120 patients with first- or multiple-episode schizophrenia spectrum disorders ( Structured Clinical Interview for DSM-IV Axis I Disorders criteria ) ; multiple-episode patients were restricted to those with a history of relapse due to medication nonadherence . The primary outcome was time to service disengagement . Secondary outcomes comprised medication nonadherence , improvements of symptoms , functioning , quality of life , satisfaction with care from patients ' and relatives ' perspectives , and service use data . The study was conducted from April 2005 to December 2008 . RESULTS 17 of 120 patients ( 14.2 % ) disengaged with service , 4 patients ( 6.3 % ) in the ACT and 13 patients ( 23.2 % ) in the st and ard care group . The mean Kaplan-Meier estimated time in service was 50.7 weeks in the ACT group ( 95 % CI , 49.1 - 52.0 ) and 44.1 weeks in the st and ard care group ( 95 % CI , 40.1 - 48.1 ) . This difference was statistically significant ( P = .0035 ) . Mixed models repeated measures indicated larger improvements for ACT compared to st and ard care regarding symptoms ( P < . 01 ) , illness severity ( P < . 001 ) , global functioning ( P < . 05 ) , quality of life ( P < . 05 ) , and client satisfaction as perceived by patients and family ( both P < . 05 ) . Logistic regression analyses revealed that ACT was associated with a higher likelihood of being employed/occupied ( P = .001 ) , of living independently ( P = .007 ) , and of being adherent with medication ( P < . 001 ) and a lower likelihood of persistent substance misuse ( P = .027 ) . CONCLUSIONS Compared to st and ard care , intensive therapeutic ACT as part of integrated care could improve 1-year outcome . Future studies need to address in which setting s these improvements can be sustained . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01081418 CONTEXT Intensive early treatment for first-episode psychosis has been shown to be effective . It is unknown if the positive effects are sustained for 5 years . OBJECTIVE To determine the long-term effects of an intensive early-intervention program ( OPUS ) for first-episode psychotic patients . DESIGN Single-blinded , r and omized , controlled clinical trial of 2 years of an intensive early-intervention program vs st and ard treatment . Follow-up periods were 2 and 5 years . SETTING Copenhagen Hospital Corporation and Psychiatric Hospital , Aarhus , Denmark . Patients A total of 547 patients with a first episode of psychosis . Of these , 369 patients were participating in a 2-year follow-up , and 301 were participating in a 5-year follow-up . A total of 547 patients were followed for 5 years . INTERVENTIONS Two years of an intensive early-intervention program vs st and ard treatment . The intensive early-intervention treatment consisted of assertive community treatment , family involvement , and social skills training . St and ard treatment offered contact with a community mental health center . MAIN OUTCOME MEASURES Psychotic and negative symptoms were recorded . Secondary outcome measures were use of services and social functioning . RESULTS Analysis was based on the principles of intention-to-treat . Assessment was blinded for previous treatment allocation . At the 5-year follow-up , the effect of treatment seen after 2 years ( psychotic dimension odds ratio [ OR ] , -0.32 ; 95 % confidence interval [ CI ] , -0.58 to -0.06 ; P = .02 ; negative dimension OR , -0.45 ; 95 % CI , -0.67 to -0.22 ; P = .001 ) had equalized between the treatment groups . A significantly smaller percentage of patients from the experimental group were living in supported housing ( 4 % vs 10 % , respectively ; OR , 2.3 ; 95 % CI , 1.1 - 4.8 ; P = .02 ) and were hospitalized fewer days ( mean , 149 vs 193 days ; mean difference , 44 days ; 95 % CI , 0.15 - 88.12 ; P = .05 ) during the 5-year period . CONCLUSIONS The intensive early-intervention program improved clinical outcome after 2 years , but the effects were not sustainable up to 5 years later . Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program Use of nonprescribed mood altering substances is pervasive and problematic in young adults with serious mental illnesses in community care . Fifty-eight percent of young adult clients with clearly defined schizophrenia or schizophrenia-related disorders participating in a long-term community treatment study were rated by staff or themselves as using alcohol , cannabis , or other street drugs several times a week or more . We interviewed in depth a r and om sample of these " significant users " to obtain their perspective on their frequencies , patterns , histories , contributing factors to , and effects of substance use and their related treatment experiences . Results revealed these clients ' substance use to be of long duration and deeply entrenched , with current use often involving multiple substances including both street drugs and substances of " everyday life " ( e.g. , caffeine , nicotine ) . Clients reported compelling reasons for use including anxiety reduction , relief of boredom , and a means for social contact . Staff and clients clearly view substance use quite differently , with the latter focusing at least as much on consequences of symptom relief as symptom exacerbation . Treatment implication s are discussed OBJECTIVE The study examined the association between fidelity of programs to the assertive community treatment model and client outcomes in dual disorders programs . METHODS Assertive community treatment programs in the New Hampshire dual disorders study were classified as low-fidelity programs ( three programs ) or high-fidelity programs ( four programs ) based on extensive longitudinal process data . The study included 87 clients with a dual diagnosis of severe mental illness and a comorbid substance use disorder . Sixty-one clients were in the high-fidelity programs , and 26 were in the low-fidelity programs . Client outcomes were examined in the domains of substance abuse , housing , psychiatric symptoms , functional status , and quality of life , based on interviews conducted every six months for three years . RESULTS Clients in the high-fidelity assertive community treatment programs showed greater reductions in alcohol and drug use and attained higher rates of remission from substance use disorders than clients in the low-fidelity programs . Clients in high-fidelity programs had higher rates of retention in treatment and fewer hospital admissions than those in low-fidelity programs . No differences between groups were found in length of hospital stays and other residential measures , psychiatric symptoms , family and social relations , satisfaction with services , and overall life satisfaction . CONCLUSIONS Faithful implementation of , and adherence to , the assertive community treatment model for persons with dual disorders was associated with superior outcomes in the substance use domain . The findings underscore the value of measures of model fidelity , and they suggest that local modifications of the assertive community treatment model or failure to comply with it may jeopardize program success OBJECTIVE To study patterns of co-occurrence of lifetime DSM-III-R alcohol disorders in a household sample . METHODS Data came from the National Comorbidity Survey ( NCS ) , a nationally representative household survey . Diagnoses were based on a modified version of the Composite International Diagnostic Interview . RESULTS Respondents with lifetime NCS/DSM-III-R alcohol abuse or dependence had a high probability of carrying at least 1 other lifetime NCS/DSM-III-R diagnosis . Retrospective reports have suggested that most lifetime co-occurring alcohol disorders begin at a later age than at least 1 other NCS/DSM-III-R disorder . Earlier disorders are generally stronger predictors of alcohol dependence than alcohol abuse and stronger among women than men . Lifetime co-occurrence is positively , but weakly , associated with the persistence of alcohol abuse among men and of alcohol dependence among both men and women . CONCLUSIONS Caution is needed in interpreting the results due to the fact that diagnoses were made by nonclinicians and results are based on retrospective reports of the age at onset . Within the context of these limitations , though , these results show that alcohol abuse and dependence are often associated with other lifetime DSM-III-R disorders and suggest that , at least in recent cohorts , the alcohol use disorders are usually temporally secondary . Prospect i ve data and data based on clinical ly confirmed diagnoses are needed to verify these findings ABSTRACT This study compared the costs and outcomes associated with three treatment programs that served 149 individuals with dual disorders ( i.e. , individuals with co-occurring severe mental illness and substance use disorders ) who were homeless at baseline . The three treatment programs were : Integrated Assertive Community Treatment ( IACT ) , Assertive Community Treatment only ( ACTO ) , and st and ard care ( Control ) . Participants were r and omly assigned to treatment and followed for a period of 24 months . Clients in the IACT and ACTO programs were more satisfied with their treatment program and reported more days in stable housing than clients in the Control condition . There were no significant differences between treatment groups on psychiatric symptoms and substance use . The average total costs associated with the IACT and Control conditions were significantly less than the average total costs for the ACTO condition OBJECTIVE To determine the cost-effectiveness of Assertive Community Treatment ( ACT ) in comparison to St and ard Case Management ( SCM ) for persons with severe mental illness and substance use disorders . DATA SOURCES AND STUDY SETTING Original data on the effectiveness and social costs of ACT and SCM that were collected between 1989 and 1995 . Seven community mental health centers in New Hampshire provided both types of treatment . STUDY DESIGN Persons with schizophrenia , schizoaffective disorder , or bipolar disorder and a concurrent substance use disorder were r and omly assigned to ACT or SCM and followed for three years . The primary variables assessed were substance use , psychiatric symptoms , functioning , quality of life , and social costs . DATA COLLECTION METHODS Effectiveness data were obtained from interviews at six-month intervals with persons enrolled in treatment and with their service providers . Social cost and service utilization data came from client reports ; interviews with informal caregivers ; provider information systems and Medicaid cl aims ; law enforcement agencies ; courts ; and community service providers . PRINCIPAL FINDINGS Participants in both groups showed significant reductions in substance use over time . Focusing on quality of life and substance use outcomes , ACT and SCM were not significantly different in cost-effectiveness over the entire three-year study period . Longitudinal analyses showed that SCM tended to be more efficient during the first two years but that ACT was significantly more efficient than SCM during the final year of the study . CONCLUSIONS In an adequately funded system , ACT is not more cost-effective than SCM . However , ACT efficiency appears to improve over time |
10,905 | 10,796,821 | No differences were detected in postabortal infection rates with routine prophylaxis or control .
However , compliance with antibiotic treatment was also low .
REVIEW ER 'S CONCLUSIONS There is not enough evidence to evaluate a policy of routine antibiotic prophylaxis to women with incomplete abortion | OBJECTIVES The value of routine antibiotics before surgical evacuation of the uterus in women incomplete abortion is controversial .
In some health centres antibiotic prophylaxis is advised in others antibiotics are only prescribed when there is signs of infection .
The objective of this review is to evaluate the effectiveness of routine antibiotic prophylaxis to women with incomplete abortion . | OBJECTIVES To determine lower genital tract carriage rates of C. trachomatis , N. gonorrhoeae and bacterial vaginosis among women seeking termination of pregnancy . To compare two clinical management strategies for minimising the risks of infective morbidity after induced abortion . DESIGN Prevalence of infections was assessed by screening women undergoing abortion . Clinical management strategies were compared by a r and omised trial . SETTING The gynaecology departments of four hospitals in Scotl and . PARTICIPANTS 1672 women undergoing induced abortion . INTERVENTIONS Women r and omised to prophylaxis received metronidazole 1 g rectally before abortion plus doxycycline 100 mg twice daily for seven days . Women r and omised to screen- and -treat received appropriate antibiotics only if screening proved positive for one or more infection . MAIN OUTCOME MEASURES Prevalences of infections ; morbidity in the eight weeks following abortion as assessed by reported symptoms , general practitioner consultation and prescription rates and hospital re-attendances ; costs to the NHS of alternative managements . RESULTS Prevalence rates : C. trachomatis 5.6 % ; N gonorrhoeae 0.19 % ; bacterial vaginosis 17.5 % . Overall , women allocated to receive prophylaxis had lower rates of measures of short term infective morbidity than those allocated to screen- and -treat . These differences only reached statistical significance for women who were reported negative on screening . The direct costs to the NHS of prophylaxis and screen- and -treat were calculated to be 8.17 and 18.34 per woman , respectively . CONCLUSIONS Prevalences of lower genital tract infections which have been implicated in increased rates of infective morbidity after abortion are similar to those reported elsewhere . Universal antibiotic prophylaxis is at least as effective as a policy of screen- and -treat in minimising the risk of short term infective morbidity and is far more cost efficient OBJECTIVE To describe the epidemiology of incomplete abortion ( spontaneous miscarriage and illegally induced ) in South Africa . DESIGN Multicentre , prospect i ve , descriptive study . SETTING Fifty-six public hospitals in nine provinces ( a stratified , r and om sample of all hospitals treating gynaecological emergencies ) . PATIENTS All women of gestation under 22 weeks who presented with incomplete abortion during the 2-week study period . MAIN OUTCOME MEASURES Incidence of , morbidity associated with and mortality from incomplete abortion . MAIN RESULTS An estimated 44686 ( 95 % CI 35633 - 53709 ) women per year were admitted to South Africa 's public hospitals with incomplete abortion . An estimated 425 ( 95 % CI 78 - 735 ) women die in public hospitals from complications of abortion . Fifteen per cent ( 95 % CI 13 - 18 ) of patients have severe morbidity while a further 19 % ( 95 % CI 16 - 22 ) have moderate morbidity , as assessed by categories design ed for the study which largely reflect infection . There were marked inter-provincial differences and inter-age group differences in trimester of presentation and proportion of patients with appreciable morbidity . CONCLUSIONS Incomplete abortions and , in particular , unsafe abortions are an important cause of mortality and morbidity in South Africa . The methods used in this study underestimate the true incidence for reasons that are discussed . A high priority should be given to the prevention of unsafe abortion This r and omised controlled trial of 357 patients who had had an incomplete abortion compared suction curettage with conventional curettage for evacuation of the uterus . The 179 patients undergoing suction curettage had a significantly lower intra-operative blood loss ( P < 0.0001 ) and a significantly higher mean haemoglobin level at follow-up compared with the 178 patients who had conventional curettage . Suction curettage was a faster procedure and less painful . No difference was found between the two groups with regard to the incidence of post-abortal sepsis , or the re-evacuation rate . No problems were encountered with the use of suction curettage in the presence of uterine sepsis . In an era where blood transfusions should be kept to an absolute minimum , suction curettage will help to save blood in several ways In 1994 , a national hospital-based study was undertaken of cases of incomplete abortion presenting to public hospitals in South Africa . Data were collected for all women admitted to a r and om sample of hospitals with incomplete abortion during a two-week period . The WHO protocol for such studies was used as a basis for developing the methods to describe the epidemiology of incomplete abortion and hospital management of cases . Attempts were made to estimate the proportion of cases that might have been induced . This report focuses on method ological issues arising from the study that have implication s for future research . The findings demonstrate that only a small proportion of the women acknowledged having had an induced abortion and that only a few of those who did showed evidence of interference with pregnancy . Clinical opinion of sepsis and the likelihood of induction were found to be highly unreliable . These findings considerably reduce the usefulness of the WHO- protocol method of estimating the likely origin of incomplete abortions . Results presented in terms of three partially overlapping descriptive categories are judged to better reflect the limitations of the data collected The responses to therapy with either clindamycin alone or penicillin plus chloramphenicol in 77 patients with septic abortions were compared in a r and omized , double-blind study . Although fever index and duration of hospitalization were similar for both groups of patients , significantly more patients in the group that received clindamycin developed major complications ( P less than 0.05 ) . This is believed to result from clindamycin 's lack of activity against aerobic gram-negative bacilli . Aggressive management that included early uterine evacuation and broad-spectrum antibiotics effective against both aerobic and anaerobic bacteria was the key to reduced morbidity and mortality rates in treatment of septic abortion . For patients treated with clindamycin , early uterine evacuation appeared more important than antibiotic therapy ( P less than 0.005 ) . Bacteremia was documented in a total of 29 patients ( 38 % ) . Bacteremia was polymicrobial in eight patients ( 28 % ) and involved anaerobes exclusively in 18 ( 62 % ) , aerobes exclusively in nine ( 31 % ) , and both aerobes and anaerobes in two ( 7 % ) . The organisms most frequently isolated were Bacteroides ( other than Bacteroides fragilis ) , Peptostreptococcus , and Escherichia coli Opinion is divided as to the advisability of routine use of prophylactic antibiotics for curettage abortion . Six studies , including three r and omized clinical trials , suggest that prophylaxis reduces infectious morbidity associated with curettage abortions by about one half . Three other studies , two involving prophylaxis for instillation abortions and one involving a vaginal antiseptic for curettage abortion , support the hypothesis that antimicrobial prophylaxis reduces morbidity . Tetracyclines are commonly used for this purpose . The cost of routine prophylaxis even with an expensive tetracycline would appear to be offset by the savings in direct and indirect costs . Prophylaxis may help prevent both short-term morbidity and potential late sequelae , such as ectopic pregnancy and infertility OBJECTIVE The objective of this report was to review and describe the management of incomplete abortion by public sector hospitals . DESIGN A descriptive study in which data were collected prospect ively from routine hospital records on all women admitted with incomplete abortion to a stratified r and om sample of hospitals between 14 and 28 September 1994 . SETTING Public sector hospitals in South Africa . PATIENTS Women with incomplete abortions . MAIN OUTCOME MEASURES Length of hospital stay , details of medical management , details of surgical management , determinants of the above . MAIN RESULTS Data were collected on 803 patients from the 56 participating hospitals . Of these , 767 ( 95.9 % ) were in hospital for 1 day or more , and 753 ( 95.3 % ) women underwent evacuation of the uterus . Sharp curettage was the method employed in 726 ( 96.9 % ) and general anaesthesia was used for 601 ( 68 % ) of the women requiring uterine evacuation . Antibiotics were prescribed for 396 ( 49.5 % ) and blood transfusions were administered to 125 ( 17 % ) women . Statistical analysis showed length of stay to be longer in small hospitals ( under 500 beds ) and when the medical condition was more severe . Antibiotic usage and blood transfusion were more common with increasing severity and a low haemoglobin level on admission . However , some inappropriate management was identified with regard to both . MAIN CONCLUSIONS It is suggested that uncomplicated incomplete abortion can be more effectively and safely managed using the manual vacuum aspiration technique with sedation/analgesia as an outpatient procedure . Attention should be directed at the introduction of this management routine at all types of hospital and to the ensuring of appropriate management of women with complicated abortion Objective To investigate the incidence of post‐operative infection after first trimester abortion in women treated with a long‐acting cephalosporin ( ceftriaxone ) compared with low risk patients receiving no treatment and with high risk patients receiving our st and ard treatment of ampicillin/pivampicillin and metronidazole complications . Three patients had haemoptysis and two slight epistaxis . Three patients vomited , including the one in whom the procedure was ab and oned . There were 39 visible tumours . In 29 out of the 38 of these that were examined the histological opinion was definitive . Failure to make a positive diagnosis was associated with necrotic tumour tissue , previous radiotherapy , or a difficult biopsy . Where the appearance was of extrinsic compression a positive diagnosis was possible in only two out of 11 cases . In 11 cases examination showed non-malignant disease The efficacy of prophylactic antibiotic therapy in induced first-trimester abortions was investigated in a double-blind study . Of the 493 women in the study , 254 received doses of 2 million IU of penicillin G intramuscularly one-half hour before and 3 hours after the procedure , followed by 350 mg of pivampicillin three times daily for 4 days , and 239 women received corresponding doses of placebo . The incidence of pelvic infectious complications was 5.5 % in the treated group and 10.9 % in the control group ( p = 0.05 ) . The difference could be attributed to a selective prophylactic effect in women who had earlier suffered from pelvic inflammatory disease ( N = 105 ) . The rate of infection in this group was 22.4 % among those receiving placebo and 2.1 % among those receiving antibiotics ( p = 0.006 ) . Prophylactic administration of antibiotics for first-trimester abortions should be used in women who have earlier had pelvic inflammatory disease A prospect i ve double-blind study was performed to evaluate the effect of prophylactic antibiotic treatment before induced abortion . Eight hundred consecutive women admitted for first-trimester abortion , without signs of genital infection or antibiotic use in the last three weeks , were included in the study . Doxycycline 400 mg or placebo was given as a single oral dose ten to 12 hours before vacuum aspiration . Ninety-one women ( 11.8 % ) returned to the hospital with suspected complications . Thirty-two of these women were diagnosed as having pelvic inflammatory disease , eight of whom ( 2.1 % ) had received doxycycline before the abortion and 24 of whom ( 6.2 % ) had received placebo , a statistically significant difference ( P < .01 ) . A history of pelvic inflammatory disease increased the risk of developing it again after an abortion A r and omized prospect i ve double-blind study was conducted to determine the efficacy of prophylactic antibiotics as compared with placebo in 198 women undergoing secondtrimester intraamniotic injection abortions . Patients received either sodium cephalothin or placebo intravenously before the procedure and for up to 8 additional doses . In 11 patients postabortion endometritis developed ; 2 had received the antibiotic and 9 had received a placebo ( P<.05 ) . Prophylactic cephalothin decreases the incidence of endometritis in patients undergoing midtrimester injection abortion . An injection-abortion interval greater than 24 hours appears to identify patients at increased risk for the development of postabortion endometritis Objective To determine whether prophylactic doxycycline at suction curettage for incomplete abortion decreases the rate of postoperative pelvic infection . Methods We r and omized 240 patients to receive intravenous doxycycline or placebo at curettage . Cervical specimens for gonorrhea and chlamydia were obtained preoperatively . Two weeks post-procedure , we evaluated all patients for infectious morbidity and repeated gonorrhea and chlamydia cultures . Statistical analysis used Mann-Whitney U test , McNemar test , or Fisher exact test , as appropriate . Results There were no statistically significant differences in age , parity , gestational age , history of sexually transmitted disease , pelvic inflammatory disease , or multiple sex partners between the doxycycline and placebo groups . Preoperative gonorrhea or chlamydia isolates were positive in five ( 4.2 % ) and six ( 5 % ) of 120 doxycycline patients and four ( 3.3 % ) and eight ( 6.6 % ) of 120 controls ( not significant ) . All preoperative gonorrhea isolates remained positive postoperatively . Seven ( 5.8 % ) controls had positive postoperative chlamydia isolates , as did one ( 0.8 % ) in the doxycycline group ( P = .06 ) . We diagnosed eight ( 6.6 % ) of 120 doxycycline patients and seven ( 5.8 % ) of 120 controls with infectious morbidity ( not significant ) . Conclusion In our population of patients with incomplete abortion , the prevalence of gonorrhea and chlamydia was low , and prophylactic doxycycline did not decrease the rate of postoperative febrile morbidity |
10,906 | 25,857,376 | Several systems such as Second Life , VisCube and Oculus Rift provide the users with an opportunity to don the role of a virtual avatar and enable users to respond to different situations and circumstances in a virtual world .
This provides an opportunity for the users to gain knowledge and experience specific situations that , under normal circumstances , might not always be possible .
VRE offers several advantages , especially in healthcare professional education .
For example , the simulation of a virtual disaster site could help medical trainees experience the intricacies and difficulties faced during a disaster and can help prepare them in a virtual world .
Study ing anatomy structures in a VRE could help trainees underst and and appreciate the structural complexities of certain organs such as the inner ear . | The paper aptly states that the e-learning has moved from simple text based learning to more interactive , multimedia social learning re sources .
While e-learning has been around ever since the internet was formally established , advanced techniques in e-learning , such as digital game based learning , virtual patients and virtual reality environments have only recently begun to take center stage .
Within the simulation schema , I would specifically like to focus on virtual reality environments and their potential role in e-learning for healthcare professionals in the future .
Over the last two decades , there has been a rapid advancement in the field of simulation and healthcare professional education .
Virtual reality environments ( VREs ) , which provide an immersive experience to the user , is an area which possesses tremendous potential in the field of healthcare professional education .
Several studies have quantified the improvement in knowledge for healthcare professionals via VRE based interventions [ 2 - 6 ] . | Introduction Virtual environments offer a variety of benefits and may be a powerful medium with which to provide nursing education . The objective of this study was to compare the achievement of learning outcomes of undergraduate nursing students when a virtual patient trainer or a traditional lecture was used to teach pediatric respiratory content . Methods This was a r and omized , controlled , posttest design . A virtual pediatric hospital unit was populated with four virtual pediatric patients having different respiratory diseases that were design ed to meet the same learning objectives as a traditional lecture . The study began in Spring 2010 with 93 Senior I , baccalaureate nursing students . Students were r and omized to receive either a traditional lecture or an experience with a virtual patient trainer . Students ’ knowledge acquisition was evaluated using multiple-choice questions , and knowledge application was measured as timeliness of care in two simulated clinical scenarios using high-fidelity mannequins and st and ardized patients . Results Ninety-three students participated in the study , of which 46 were in the experimental group that received content using the virtual patient trainer . After the intervention , students in the experimental group had significantly higher knowledge acquisition ( P = 0.004 ) and better knowledge application ( P = 0.001 ) for each of the two scenarios than students in the control group . Conclusions The purpose of this project was to compare a virtual patient trainer to a traditional lecture for the achievement of learning outcomes for pediatric respiratory content . Although the virtual patient trainer experience produced statistically better outcomes , the differences may not be clinical ly significant . The results suggest that a virtual patient trainer may be an effective substitute for the achievement of learning outcomes that are typically met using a traditional lecture format . Further research is needed to underst and how best to integrate a virtual patient trainer into undergraduate nursing education Objective . To determine whether using 3-dimensional ( 3D ) technology to teach pharmacy students about the molecular basis of the interactions between drugs and their targets is more effective than traditional lecture using 2-dimensional ( 2D ) graphics . Design . Second-year students enrolled in a 4-year masters of pharmacy program in the United Kingdom were r and omly assigned to attend either a 3D or 2D presentation on 3 drug targets , the β-adrenoceptor , the Na+-K+ ATPase , and the nicotinic acetylcholine receptor . Assessment . A test was administered to assess the ability of both groups of students to solve problems that required analysis of molecular interactions in 3D space . The group that participated in the 3D teaching presentation performed significantly better on the test than the group who attended the traditional lecture with 2D graphics . A question naire was also administered to solicit students ’ perceptions about the 3D experience . The majority of students enjoyed the 3D session and agreed that the experience increased their enthusiasm for the course . Conclusions . Viewing a 3D presentation of drug-receptor interactions improved student learning compared to learning from a traditional lecture and 2D graphics Objective : This study examined the independent effect of a patient 's weight on medical students ’ attitudes , beliefs and interpersonal behavior toward the patient , in addition to the clinical recommendations they make for her care . Design : A total of 76 clinical -level medical students were r and omly assigned to interact with a digital , virtual female patient who was visibly either obese or non-obese . Methods : Interactions with the patient took place in an immersive virtual ( virtual reality ) clinical environment that allowed st and ardization of all patient behaviors and characteristics except for weight . Visual contact behavior was automatically recorded during the interaction . Afterward , participants filled out a battery of self-report question naires . Results : Analyses revealed more negative stereotyping , less anticipated patient adherence , worse perceived health , more responsibility attributed for potentially weight-related presenting complaints and less visual contact directed toward the obese version of a virtual patient than the non-obese version of the patient . In contrast , there was no clear evidence of bias in clinical recommendations made for the patient 's care . Conclusion : Biases in attitudes , beliefs and interpersonal behavior have important implication s because they can influence the tone of clinical encounters and rapport in the patient – provider relationship , which can have important downstream consequences . Gaining a clear underst and ing of the nature and source of weight bias in the clinical encounter is an important first step toward the development of strategies to address it Virtual reality ( VR ) simulation provides a means of making experiential learning reproducible and reusable . This study was design ed to determine the efficiency and satisfaction components of usability . Previously , it was found that first year medical students using a VR simulation for medical education demonstrated effectiveness in learning as measured by knowledge structure improvements both with and without a head mounted display ( HMD ) but students using a HMD showed statistically greater improvement in knowledge structures compared to those not using a HMD . However , in this current analysis of other components of usability , there were no overall significance differences in efficiency ( ease of use ) , nor in satisfaction , within this same group of r and omized subjects comparing students using a HMD to those not using a HMD . These types of studies may be important in determining the most appropriate , cost effective VR simulation technology needed to achieve specific learning goals and objectives |
10,907 | 15,534,012 | Twelve studies ( five r and omized controlled trials , one quasi-experimental study , and six uncontrolled cohort studies ) found that home and community-based treatment of psychiatric symptoms were associated with improved or maintained psychiatric status .
CONCLUSIONS Limited data supported the effectiveness of outreach services in identifying isolated older adults with mental illness .
A more substantial evidence base indicated that home-based mental health treatment is effective in improving psychiatric symptoms . | OBJECTIVES Psychiatric outreach services that provide mental health assessment and treatment to older adults in their homes or communities are widely promoted as improving access and outcomes for older adults .
However , a systematic review of the efficacy of these services has not been done .
This review evaluates the evidence base for the effectiveness of outreach services for older adults with mental illness in noninstitutional community setting s. End points of interest include the ability of the outreach program to increase access to mental health services and improve psychiatric outcomes . | CONTEXT Elderly persons with psychiatric disorders are less likely than younger adults to be diagnosed as having a mental disorder and receive needed mental health treatment . Lack of access to care is 1 possible cause of this disparity . OBJECTIVE To determine whether a nurse-based mobile outreach program to seriously mentally ill elderly persons is more effective than usual care in diminishing levels of depression , psychiatric symptoms , and undesirable moves ( eg , nursing home placement , eviction , board and care placement ) . DESIGN Prospect i ve r and omized trial conducted between March 1993 and April 1996 to assess the effectiveness of the Psychogeriatric Assessment and Treatment in City Housing ( PATCH ) program . SETTING Six urban public housing sites for elderly persons in Baltimore , Md. PARTICIPANTS A total of 945 ( 83 % ) of 1195 residents in the 6 sites underwent screening for psychiatric illness . Among those screened , 342 screened positive and 603 screened negative . All screen-positive subjects aged 60 years and older ( n=310 ) and a 10 % r and om sample of screen-negative subjects aged 60 years and older ( n=61 ) were selected for a structured psychiatric interview . Eleven subjects moved or died ; 245 ( 82 % ) of those who screened positive and 53 ( 88 % ) of those who screened negative were evaluated to determine who had a psychiatric disorder . Data were weighted to estimate the prevalence of psychiatric disorders at the 6 sites . INTERVENTION Among the 6 sites , residents in 3 buildings were r and omized to receive the PATCH model intervention , which included educating building staff to be case finders , performing assessment in residents ' apartments , and providing care when indicated ; and residents in the remaining 3 buildings were r and omized to receive usual care ( comparison group ) . MAIN OUTCOME MEASURES Number of undesirable moves and scores on the Montgomery-Asberg Depression Rating Scale ( MADRS ) , a measure of depressive symptoms , and the Brief Psychiatric Rating Scale ( BPRS ) , a measure of psychiatric symptoms and behavioral disorder , in intervention vs comparison sites . RESULTS Based on weighted data , at 26 months of follow-up , psychiatric cases at the intervention sites had significantly lower ( F(1)=31.18 ; P<.001 ) MADRS scores ( 9.1 vs 15.2 ) and significantly lower ( F(1)=17.35 ; P<.001 ) BPRS scores ( 27.4 vs 33.9 ) than those at the nontreatment comparison sites . There was no significant difference between the groups in undesirable moves ( relative risk , 0.97 ; 95 % confidence interval , 0 . 44 - 2.17 ) . CONCLUSIONS These results indicate that the PATCH intervention was more effective than usual care in reducing psychiatric symptoms in persons with psychiatric disorders and those with elevated levels of psychiatric symptoms . JAMA . 2000;283:2802 - CONTEXT Older adults with social isolation , medical comorbidity , and physical impairment are more likely to be depressed but may be less able to seek appropriate care for depression compared with older adults without these characteristics . OBJECTIVE To determine the effectiveness of a home-based program of detecting and managing minor depression or dysthymia among older adults . DESIGN AND SETTING R and omized controlled trial with recruitment through community senior service agencies in metropolitan Seattle , Wash , from January 2000 to May 2003 . PATIENTS One hundred thirty-eight patients aged 60 years or older with minor depression ( 51.4 % ) or dysthymia ( 48.6 % ) . Patients had a mean of 4.6 ( SD , 2.1 ) chronic medical conditions ; 42 % of the sample belonged to a racial/ethnic minority , 72 % lived alone , 58 % had an annual income of less than 10 000 dollars , and 69 % received a form of home assistance . INTERVENTIONS Patients were r and omly assigned to the Program to Encourage Active , Rewarding Lives for Seniors ( PEARLS ) intervention ( n = 72 ) or usual care ( n = 66 ) . The PEARLS intervention consisted of problem-solving treatment , social and physical activation , and potential recommendations to patients ' physicians regarding antidepressant medications . MAIN OUTCOME MEASURES Assessment s of depression and quality of life at 12 months compared with baseline . RESULTS At 12 months , compared with the usual care group , patients receiving the PEARLS intervention were more likely to have at least a 50 % reduction in depressive symptoms ( 43 % vs 15 % ; odds ratio [ OR ] , 5.21 ; 95 % confidence interval [ CI ] , 2.01 - 13.49 ) , to achieve complete remission from depression ( 36 % vs 12 % ; OR , 4.96 ; 95 % CI , 1.79 - 13.72 ) , and to have greater health-related quality -of-life improvements in functional well-being ( P = .001 ) and emotional well-being ( P = .048 ) . CONCLUSIONS The PEARLS program , a community-integrated , home-based treatment for depression , significantly reduced depressive symptoms and improved health status in chronically medically ill older adults with minor depression and dysthymia The effects of a multifaceted secondary prevention intervention in residential homes in the Netherl and s were examined , using a quasi-experimental design . In five experimental residential homes , the caregivers received three training sessions on detecting depression and on supporting depressed residents . Furthermore , an information session was organized for all personnel , a further session was organized for residents and their relatives , and several group interventions were offered . 213 residents participated in the study . 211 residents of five other residential homes , matched on basic variables , served as a comparison group . Effects on depressive symptoms ( geriatric depression scale ) and health related quality of life ( MOS-SF-36 ) were measured at pretest and after the intervention , one year later . Because the drop-out rate was high and drop-outs differed significantly from the remaining population , the scores of drop-outs were imputed . Since we used a quasi-experimental design , we controlled for confounding variables . Regression analyses result ed in significant effects of the intervention on the GDS and on role functioning in the total population . When the analyses were limited to those scoring high on the GDS at pretest , significant effects were found on the GDS , and on four domains of health-related quality of life : psychological distress , role functioning , pain and social functioning . The improvement in GDS scores in GDS cases was significantly larger than in other subjects . Our results suggest that general approaches aim ed at a residential home are capable of influencing depressive symptoms in inhabitants . Possibly , it may not be necessary to wait until depressive symptoms have escalated and inhabitants need extensive treatment Abstract Objective : To investigate the efficacy of intervention by a psychogeriatric team in the treatment of depression in elderly disabled people receiving home care from their local authority . Design : R and omised controlled trial with blind follow up six months after recruitment . Setting : Community of south east London . Subjects : 69 people aged 65 or over who received home care and were depressed according to criteria of the st and ardised automatic geriatric examination for computer assisted taxonomy ( AGECAT ) . 33 were r and omly allocated to an intervention group and 36 to a control group . Intervention : Members of the intervention group received an individual package of care that was formulated by the community psychogeriatric team in their catchment area and implemented by a research er working as a member of that team . The control group received normal general practitioner care . Main outcome measures : Recovery from depression ( AGECAT case at recruitment but non-case at follow up ) . Results : Data were analysed on an intention to treat basis . 19 ( 58 % ) of the intervention group recovered compared with only nine ( 25 % ) of the control group , a difference of 33 % ( 95 % confidence interval 10 % to 55 % ) . This powerful treatment effect persisted after controlling for possible confounders in logistic regression analysis , with members of the intervention group more likely than members of the control group to have recovered at follow up ( odds ratio 9.0 ( 2.0 to 41.5 ) ) . This did not seem to be a simple effect of antidepressant prescription : use of antidepressants at follow up did not have a significant effect ( multiply adjusted odds ratio 0.3 ( 0.0 to 1.9 ) ) . Conclusions : Depression is treatable in elderly people receiving home care . Therapeutic nihilism based on an assumed poor response to treatment in these socially isolated , disabled elderly people in the community is not supported . Key messages This r and omised controlled trial evaluated whether intervention by a psychi- atric team would improve depression in elderly people receiving home care Overall , 58 % of those receiving the intervention had recovered from their depression six months later compared with only 25 % of those receiving unsup- plemented general practitioner care These results should be achievable by other community old age psychiatry services The current comparative inaction on the part of health and social services needs to be Abstract Objective : To evaluate the effectiveness of a population based , multifaceted shared care intervention for late life depression in residential care . Design : R and omised controlled trial , with control and intervention groups studied one after the other and blind follow up after 9.5 months . Setting : Population of residential facility in Sydney living in self care units and hostels . Participants : 220 depressed residents aged ≥65 without severe cognitive impairment . Intervention : The shared care intervention included : ( a ) multidisciplinary consultation and collaboration , ( b ) training of general practitioners and carers in detection and management of depression , and (c)depression related health education and activity programmes for residents . The control group received routine care . Main outcome measure : Geriatric depression scale . Results : Intention to treat analysis was used . There was significantly more movement to “ less depressed ” levels of depression at follow up in the intervention than control group ( Mantel-Haenszel stratification test , P=0.0125 ) . Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders , with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group ( 95 % confidence interval 0.76 to 2.97 , P=0.0011 ) . Conclusions : The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration , by enhancing the clinical skills of general practitioners and care staff , and by providing depression related health education and activity programmes for residents . Key messages Large numbers of depressed elderly people live in residential care but few receive appropriate management A population based , multifaceted shared care intervention for late life depression was more effective than routine care in improving depression outcome The outcome of late life depression can be improved by enhancing the clinical skills of general practitioners and care staff and by providing depression related health education and activity programmes for residents The intervention needs further refining and evaluation to improve its effectiveness and to determine how best to implement it in other residential care setting OBJECTIVE To examine whether depressive symptoms in older adults contribute to increased cost of general medical services . DESIGN A 4-year prospect i ve cohort study . SETTING Four primary care clinics of a large staff-model health maintenance organization ( HMO ) in Seattle , Wash. PATIENTS A total of 5012 Medicare enrollees older than 65 years were invited to participate in the study ; 2558 subjects ( 51 % ) were successfully enrolled . Non- participants were somewhat older and had a higher level of chronic medical illness . MAIN OUTCOME MEASURES Depressive symptoms as measured by the Center for Epidemiological Studies Depression scale , which was administered as part of a mail survey at baseline , at 2 years , and at 4 years ; and total cost of medical services from the perspective of the HMO . Data were obtained from the cost accounting system of the HMO . RESULTS In this cohort of older adults , depressive symptoms were common , persistent , and associated with a significant increase in the cost of general medical services . This increase was seen for every component of health care costs and was not accounted for by an increase in specialty mental health care . The increase in health care costs remained significant after adjusting for differences in age , sex , and chronic medical illness . CONCLUSIONS Depressive symptoms in older adults are associated with a significant increase in the cost of medical services , even after adjusting for the severity of chronic medical illness Depression in elderly people is a common yet treatable psychiatric problem . The Gospel Oak depression study research ed this much overlooked group and has shown that a community psychiatric nurse ( CPN ) was able significantly to improve the mental state of depressed elderly people . A multifaceted package of care was co-ordinated and delivered by one CPN over a study period of 3 months . A detailed account is given of those interventions implemented , highlighting those which were of most benefit for the patient . Outcome was assessed independently and it was found that those patients allocated to CPN care improved significantly compared to the non-intervention control group . Ways in which nurses can enhance care given to patients in the community are discussed OBJECTIVE To examine treatment for depression among older adults in a large staff model health maintenance organization ( HMO ) . DESIGN A 4-year prospect i ve cohort study ( 1989 - 1993 ) . SETTING Four primary care clinics of a large staff model HMO in Seattle , Washington . PATIENTS A total of 2558 Medicare enrollees aged 65 and older . MAIN OUTCOME MEASURES Treatment of depression was defined as primary care visits result ing in depression diagnoses , use of antidepressant medications , or specialty mental health services . MAIN RESULTS The older adults in our sample had low rates of treatment for depression , ranging from 4 to 7 % in the entire sample and from 12 to 25 % among those with probable depressive disorders . Predictors of treatment included female gender , severity , and persistence of depressive symptoms , and severity of comorbid medical illness . Even when patients were treated for depression , the intensity of treatment was very low . Overall likelihood of treatment for depression increased somewhat from 1989 to 1993 , but among those treated , the rate of adequate antidepressant use remained below 30 % . CONCLUSIONS There is still considerable need to improve care for older adults with depression in primary care |
10,908 | 16,161,740 | DISCUSSION AND CONCLUSIONS There were no clinical differences among implant systems . | PURPOSE To test the null hypothesis that there is no difference in failure rates between various root-formed osseointegrated dental implant systems after 5 years of loading . | In earlier studies of Astra Tech and Brånemark System implants , high survival rates and small marginal bone changes have been demonstrated . The aim of this study was to compare the two systems , primarily with regard to marginal bone changes , but also with regard to other clinical variables of interest . The present paper describes the results after three years . Sixty-six patients were included in the study and r and omly assigned to treatment with Astra Tech implants ( n = 184 ) or Brånemark System implants ( n=187 ) . The marginal bone level was radiographically examined at fixture insertion , at abutment connection , at baseline ( delivery of the prosthetic construction ) and at 1- and 3-year follow-up examinations . Between fixture insertion and the baseline examination , the pattern of marginal bone resorption differed between the two systems . However , there was no significant marginal bone change between baseline and the 1-year examination or between the 1- and 3-year examinations . Nor were there any differences between the systems . The mean bone loss in the upper jaw between BL ( baseline ) and 3 years was 0.2 + /- 0.3 mm for Astra Tech implants and 0.2 + /- 0.1 mm for Brånemark System implants . The corresponding figures for the lower jaw were 0.3 + /- 0.2 mm and 0.2 + /- 0.1 mm . The survival rate of Astra Tech implants was significantly higher ( 98.9 % ) than for Brånemark System implants ( 95.2 % ) . However , five of the nine implant losses in the Brånemark group occurred in one patient . For that reason , this result must be interpreted with caution . The number of patients with implant losses did not differ significantly between the systems . Few complications were recorded up to 3 years This paper describes the 5-year results of a comparative study between Astra Tech and Brånemark system implants . The aim was to compare the systems primarily with regard to bone level changes , and also with regard to other variables of interest . Sixty-six patients with edentulous jaws were included in the study . R and omisation schedules were used to allocate the patients to the two implant systems . 184 Astra Tech implants with a titanium-blasted surface and 187 Brånemark implants with a turned surface were used . The implants were inserted with a two-stage technique and the insertion followed the routines for the respective implant system . All patients were provided with full-arch fixed bridges . All patients were followed up with clinical and radiographic examinations from fixture insertion to the 5-year follow-up . The total mean bone level change in the upper jaw between fixture insertion and the 5-year examination was -1.74+/-0.45 mm at the Astra implants and -1.98+/-0.21 at the Brånemark implants . The corresponding values for the lower jaw were -1.06+/-0.19 for Astra and -1.38+/-0.17 for Brånemark . The major postoperative changes of the marginal bone level took place between fixture insertion and baseline . During this period , there was also a different pattern of bone remodelling between the implant systems . Between baseline ( prosthesis connection ) and the 5-year examination , the marginal bone level changes were small , with no difference between the implant systems . The implant stability was examined with the supraconstructions removed . At the 5-year examination , the survival rate for Astra Tech implants was 98.4 % and for the Brånemark implants it was 94.6 % . The difference was not statistically significant OBJECTIVE The purpose of this article was to present the preliminary results of a prospect i ve clinical trial comparing titanium plasma-sprayed versus hydroxyapatite-coated titanium plasma-sprayed cylinder ( press fit ) implants in different regions of the mouth . STUDY DESIGN Sixty-five subjects met the inclusion requirements . Surgery was done in two phases by four experienced surgeons . Implant placement and abutment connection were separated by 3 to 4 months in the m and ible , 6 to 7 months in the maxilla . Patients were assigned to either titanium plasma-sprayed or hydroxyapatite-coated implants on the day of surgery . Implant placement was not stratified for the region of the jaws . Outcome assessment was failure ( loss ) of an implant before or within 3 months of second phase surgery . RESULTS Three hundred fifty-two implants equally distributed between titanium plasma-sprayed and hydroxyapatite-coated titanium plasma-sprayed implants were placed in four different sites ; anterior maxilla , posterior maxilla , anterior m and ible , and posterior m and ible . There were a total of 15 failures ( 4.26 % ) . Overall , titanium plasma-sprayed implants showed a higher but not significant failure rate compared with hydroxyapatite-coated implants ( p = 0.06 ) . Although not statistically significant , we believe that a smoking history played an important role in the failure of implants . CONCLUSION This study suggests that an hydroxyapatite-coating of an implant allows superior initial integration when compared with a titanium plasma-sprayed surface BACKGROUND Step-wise reduction in loading protocol s is necessary to evaluate early loading of implants with m and ibular overdentures . PURPOSE To compare the success rates of two different dental implant systems following conventional or early loading protocol s in patients being rehabilitated with m and ibular overdentures . MATERIAL S AND METHODS Forty-eight edentulous participants were r and omly allocated to two different implant systems : one with a machined titanium implant surface ( Sterioss , Nobel Biocare , Yorba Linda , California , USA ) and the other with a roughened titanium surface ( Southern Implants , Irene , South Africa ) . For each system , the participants were further divided into control groups , in whom m and ibular implant overdentures and their respective matrices were inserted following a st and ard 12-week healing period , and test groups , in whom a 6-week healing period was followed prior to identical loading . Two unsplinted implants to support implant overdentures were placed in the anterior m and ible of all participants , using a st and ardized one-stage surgical procedure . Mobility tests and marginal bone levels , as well as peri-implant parameters , were evaluated at each baseline and 52 and 104 weeks after surgery . RESULTS There was no statistically significant difference in the success rates of the two systems in either control or test groups . At the 2-year evaluation , a success rate was found of 87.5 % and 70.8 % for the control and test Sterioss groups , respectively , and 83.3 % and 100 % for the control and test Southern Implants groups were observed . For the Sterioss groups , eight implants were lost at an early stage : seven in the test group and one in the control group . For the Southern Implants control and test groups , no failures were seen at any time interval . There were no significant differences in marginal bone loss , Periotest values , and peri-implant parameters between implant systems or between any of the control or test groups . CONCLUSIONS Early loading , with step-wise reductions in loading protocol s , of unsplinted machined Sterioss and roughened Southern Implants fixtures with m and ibular overdentures is possible for up to 2 years BACKGROUND Evidence -based reports are needed to support the application of a one-stage surgical protocol for unsplinted implants supporting m and ibular overdentures . PURPOSE To examine the feasibility and success of using two different dental implant systems ( originally design ed for two-stage operative technique ) using a one-stage operative procedure in patients being rehabilitated with implant m and ibular overdentures . MATERIAL S AND METHODS The study sample involved 24 edentulous subjects ( aged 55 - 80 yr ) r and omly allocated to two different implant systems , one with a machined titanium implant surface ( Steri-Oss , Nobel Biocare , Göteborg , Sweden ) and the other with a roughened titanium surface ( Southern Implants , Ltd. , Irene , South Africa ) . Two unsplinted implants to support implant overdentures were placed in the anterior m and ible of all patients , using a st and ardized one-stage surgical and prosthodontic procedure . Primary stability and bicortical anchorage of the implants was m and atory before healing abutments were connected at the time of implant placement . Implant overdentures and their respective matrices were inserted following a st and ard 12-week healing period . Data relating to mobility tests , radiographs , and peri-implant parameters were documented at 12 , 16 , and 52 weeks after surgery . RESULTS A success rate of 95.8 % for the Steri-Oss and 100 % for the Southern Implants was found , without any statistically significant differences in the marginal bone loss . Significant changes in Periotest values were observed for both types between 12 and 52 weeks ( p < .001 ) . Minor changes were observed in the peri-implant parameters evaluated . CONCLUSIONS These preliminary findings show a successful application of this one-stage approach for unsplinted implants supporting m and ibular overdentures with Steri-Oss and Southern Implant Systems BACKGROUND Many longitudinal studies of different implant systems have been published but few controlled r and omized investigations have been reported . A 1-year report of a comparative study of ITI Dental Implant System implants ( Straumann AG , Waldenburg , Switzerl and ) and Brånemark System implants ( Nobel Biocare AB , Gothenburg , Sweden ) has been published by the present authors . This paper is a 3-year follow-up of that r and omized study . PURPOSE The aim of the study was to compare the outcome of fixed partial prostheses supported by ITI or Brånemark implants . The outcome was evaluated primarily in terms of survival rates and changes in marginal bone level . MATERIAL AND METHODS The study group comprised 28 patients with anterior residual dentition in the maxilla . The patients were provided with two to four implants on each side of the dentition and were r and omly allocated to Brånemark implants or ITI implants ; 77 ITI implants and 73 Brånemark implants were inserted . After 6 months abutment connections were made to both ITI and Brånemark implants . All patients were provided with fixed partial prostheses of gold-ceramic . The patients were followed up annually with clinical and radiographic examinations for 3 years RESULTS Two Brånemark implants and two ITI implants were lost . The Brånemark implants were lost before loading whereas the ITI implants were lost because of periimplantitis . The survival rate for both groups was 97.3 % . The mean marginal bone level of the Brånemark implants was situated 1.8 mm from the reference point at both the baseline and the 3-year examinations . The corresponding values for the ITI implants were 1.4 mm at baseline and 1.3 mm after 3 years . There was no significant difference between the implant systems with regard to bone level or bone level change . A steady state of the marginal bone level was calculated to have been reached after 3 years for 95.5 % of the Brånemark implants and 87.1 % of the ITI implants . Periimplantitis ( infection including pus and bone loss ) was observed with seven ITI implants but with none of the Brånemark implants . This difference was statistically significant . CONCLUSIONS No statistically significant differences were found between the implants studied , except for the frequency of periimplantitis , which was higher for the ITI implants . The survival rates were high , and the marginal bone loss was small for both systems The aim of this prospect i ve comparative study was to evaluate the condition of the peri-implant tissues of three different implant systems supporting a m and ibular overdenture . Ninety edentulous patients ( Cawood class V-VI ) participated in this study . After r and omization , 30 patients were treated with 2 Brånemark implants , 30 patients with 2 IMZ implants and 30 patients with 2 ITI implants . The implants were inserted in the canine region of the m and ible . After 3 months overdentures were fabricated supported by a round bar and clip attachment . A st and ardized clinical and radiographic evaluation was performed 0,6 and 12 months after insertion of the denture . The intraoral radiographs were made , using the long-cone technique with an aim ing device . Two implants were lost ( 1 Brånemark , 1 IMZ ) during the healing period . None of the patients showed any sensory change in lip or chin region . The pocket depth in the Brånemark group decreased significantly whereas the mucosa recession increased significantly in both the Brånemark as well as in the IMZ group . After 12 months , there was significantly less bone loss in the ITI group . From our study it was concluded that 2 ( Brånemark , IMZ or ITI ) 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 ( Cawood V-VI ) edentulous patient . The ITI implant appears to be the implant of choice for m and ibular overdenture therapy , because only one operation is required for a comparable result PURPOSE Although no currently available technique for the measurement of osseointegration is entirely satisfactory , 3 clinical variables can be reasonably associated with the process : probing depth , micromobility , and crestal bone height . Micromobility can be quantified to some extent with the use of the Periotest , a commercially available instrument In this investigation , the influence of surface characteristics and geometry upon Periotest value ( PTV ) and probing depth measurements was studied . MATERIAL S AND METHODS In a multicenter trial , 120 healthy edentulous patients received 5 or 6 implants in the anterior m and ible and were followed for 3 years . A total of 634 implants were placed . Every patient received at least 1 implant of each of 3 types : threaded titanium plasma-sprayed ( TPS ) , threaded hydroxyapatite-coated ( HA ) , and cylindric HA-coated . A r and omization schedule assured that approximately equal numbers of each type of implant were placed and that they were uniformly distributed over the arch . RESULTS Of the 4 tested combinations of dependent and independent variables , the only statistically significant ( P < .05 ) effect was that of coating on PTV . At 1 year after prosthetic restoration , the mean PTV for HA-coated threaded implants was -5.36 + /- 1.24 , compared with -4.86 + /- 1.70 for TPS implants . This difference steadily declined in magnitude and significance , until , after 3 years , the groups were indistinguishable . DISCUSSION This study agrees with the previous observations that HA coating tends to accelerate the initial rate of osseointegration . The absence of a difference between threaded and cylindric implants confirms that the PTV responds to micromobility near the surface , on a scale much smaller than such gross geometric features . CONCLUSION On the basis of these results , one may conclude that HA-coated implants exhibit a more rapid decrease in micromobility than do TPS implants of identical geometry PURPOSE The purpose of this study was to compare the success of hydroxyapatite ( HA ) -coated and machined titanium ( Ti ) implants in a 5-year r and omized , controlled clinical trial conducted at 2 centers . MATERIAL S AND METHODS Each of 120 edentulous patients received HA-coated threaded , HA-coated cylindric , and machined Ti threaded implants in a r and omized design using 5 or 6 implants . Digital radiographs allowed for yearly measurements of bone loss . Calibrated clinicians also measured mobility , Gingival Index , Plaque Index , probing depth , and recession . A Kaplan-Meier analysis was used to compare the proportion of ailing implants ( defined as less than 2 mm of alveolar bone loss over 5 years ) for each type of implant design . The criteria employed to assess implant outcome included the need for successful implants to lose less than 2 mm of bone support over the 5 years following placement of the prosthesis . RESULTS This analysis revealed that 95.2 % of machined Ti threaded implants and 97.92 % of HA-coated threaded implants were successful , while 99.0 % of HA-coated cylindric implants experienced less than 2 mm of bone loss ( P < .06 ) . DISCUSSION All types of implants placed in this study had success rates above 95 % . CONCLUSION Over 5 years , the success rate tended to favor HA-coated implants 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 The aim of this prospect i ve r and omized controlled clinical trial was to evaluate the clinical outcomes and prosthetic aftercare of edentulous patients with a m and ibular overdenture retained by two IMZ implants or two Brånemark implants during a 10-year period . Patients were allocated to the IMZ group ( n=29 ) or the Brånemark group ( n=32 ) by a computerized balancing method . In the IMZ group , four implants were lost during the 10-year follow-up ( survival rate : 93 % ) . In the Brånemark group , nine implants were lost ( survival rate : 86 % ) . All patients were re-operated successfully . Multiple prosthetic revisions were necessary in both groups ; especially the precision attachment system in the overdenture ( 23 % of the total number of revisions ) and the denture base and teeth ( 26 % of the total number of revisions ) were subject to frequent fracture . From this study , it can be concluded that both the IMZ implant and the Brånemark implant systems supporting an overdenture are functioning well after 10 years of follow-up . There are no indications of a worsening of clinical or radiographical state after 10 years Intramobile cylinder ( IMZ ) implants with either of two coatings , hydroxyapatite ( HA ) or titanium plasma-flame ( TPF ) , as distal abutments for combined tooth implant-supported restorations , were compared in 313 partially edentulous m and ibles with respect to postprosthetical failure patterns and complication frequencies in a r and omized multicenter clinical trial . Within the treatment protocol s , the two coatings do not show evidence of different efficacy with respect to occurrence of postprosthetical integration deficiency ( ID ) or functional deficiency ( FD ) . Statistical equivalence for an absolute effect of + /-15 % in event-free survival could only be demonstrated for FD , not for ID , however . Intent-to-treat and per- protocol population analyses gave consistent results . Hazards of occurrence of ID and FD , adjusted for years of follow-up , were estimated for ID as 7 % per year ( 95%CI 4 - 10 % per year ) with HA and 5 % per year ( 95%CI 3 - 7 % per year ) with TPF , and for FD as 5 % per year ( 95%CI 3 - 7 % per year ) with HA and 4 % per year ( 95%CI 2 - 6 % per year ) with TPF . The 5-year cumulative success rates for no ID were 69.5 % ( 95%CI 58 - 81 % ) with HA and 82.2 % ( 95%CI 74 - 91 % ) with TPF . With respect to frequencies of complications , there was no relevant statistically significant difference between the two coatings In a controlled clinical trial , treatment effects of m and ibular overdentures on two different implant-systems in edentulous patients were compared one year after insertion of the new dentures . The implant-systems used were the Brånemark system ( Brå ) and the IMZ-system . Treatment was r and omly assigned to 60 patients according to a balanced allocation method . Evaluation included peri-implant and radiographical parameters . According to the Delphi method a clinical implant performance scale ( CIP ) was constructed based on all conceivable complications of the different implant systems . During the osseointegration period , five Brå- and one IMZ-implants were lost . The results of one of the peri-implant parameters and the radiographical score showed significant differences considering the ( pseudo ) pocket probing depth ( Brå better than IMZ , P < 0.001 ) and the radiographic-score ( IMZ better than Brå , P < 0.003 ) . The results for the CIP-scale were less favourable for the Brå-group than for the IMZ-group ; however , these differences were not significant OBJECTIVE To compare three implant systems in patients with severely resorbed m and ibles 1 year after insertion of the m and ibular denture . DESIGN A prospect i ve multicenter r and omized clinical trial . SETTING Centers at University of Nijmegen and Groningen . METHODS Three different implant systems were used : the transm and ibular implant , the IMZ and the Brånemark system . Treatment was assigned to 88 patients according to a balanced allocation method . Evaluation included clinical and radiographic parameters . A Clinical Implant Performance scale ( CIP ) was constructed based on all conceivable complications of the different implant systems . RESULTS During the healing period 1 IMZ- and 1 BRA-implant were lost . One TMI was removed after functional loading . The results of the clinical and radiographic parameters and the CIP-scale showed no significant differences between the three implant systems . CONCLUSION Taking the one year evaluation into account the three systems used did not differ in clinical and radiographic performance In 50 partially edentulous patients , 133 ( 48 maxillary ; 85 m and ibular ) Astra Tech dental implants of 2 different surface textures ( machined ; TiO-blasted ) were alternately installed , supporting 52 fixed partial dentures ( FPDs ) . Before abutment connection 2 machined implants ( 1 m and ibular ; 1 maxillary ) were found to be non-osseointegrated and were replaced . Another implant could not be restored due to a technical complication . Two FPDs were remade because of technical complications , both because of abutment fractures . Thus , after 2 years in function , the cumulative survival rates were 97.7 % and 95.7 % for implants and prostheses , respectively . There was no statistically significant difference in survival rate between the 2 types of implants , 100 % ( TiO-blasted ) vs 95.3 % ( machined ) , P = 0.24 . After 2 years in function , when both jaw and type of implants were combined , the mean ( SD ) marginal bone loss was 0.24 ( 0.69 ) mm . No statistically significant difference in bone loss was found between the 2 types of implant after 2 years of loading , 0.04 ( 0.82 ) mm , P > 0.30 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 The aim of this prospect i ve r and omized controlled clinical trial was to evaluate a set of clinical items and prosthetic aftercare of edentulous patients with a m and ibular overdenture retained by 2 IMZ implants or 2 Brånemark implants during a 5-years ' period . Patients were allocated to the IMZ group ( n = 29 ) or the Brånemark group ( n = 32 ) by a computerized balancing method . In the IMZ group 4 implants were lost during the 5-years ' follow-up ( survival rate : 93 % ) . In the Brånemark group 9 implants were lost ( survival rate : 86 % ) . All patients were re-operated successfully . Multiple prosthetic revisions were necessary in both groups , especially the precision attachment system in the overdenture was subject to frequent fracture or loosening . From this study can be concluded that there is no difference in clinical state , radiographical state , survival rate and clinical implant performance between the IMZ implant system and the Brånemark implant system supporting an overdenture on 2 implants after 5 years of follow-up OBJECTIVE A preliminary report from this study showed that hydroxyapatite-coated ( HA ) titanium plasma-sprayed ( TPS ) cylinder implants had fewer failures than TPS cylinder implants before prosthetic loading . The purpose of this article is to report the long-term success associated with the 2 systems . In addition , local and systemic factors that may influence the success or failure of the implants were analyzed . STUDY DESIGN Each of 65 subjects was r and omized to either HA-coated TPS or TPS cylinder implants . Loss of an implant was considered a failure . Failures were analyzed in terms of the coating of the implant , age and gender of the patient , location and length of the implant , opposing dentition , and smoking status . Data were statistically analyzed through use of chi-square tests . RESULTS Of 351 implants that were placed , 13 were lost before prosthetic loading and 17 were lost after prosthetic loading . The overall success rate was 92.8 % . Three hundred thirty-eight implants were prosthetically loaded . The implant success rate after prosthetic loading was 95.3 % . There was an overall nonsignificant higher failure rate for the TPS implants ( 8.0 % ) . Patient age and patient gender were nonsignificant variables . Ten-mm implants had a significantly higher failure rate ( 17.4 % ; chi-square , 1.00 ; P = .39 ) . Before prosthetic loading , more implants failed in the posterior m and ible ; after prosthetic loading , more implants failed in the anterior maxilla ( chi-square , 8.97 ; P = .03 ) . More implants failed when they were opposed by natural dentition or hybrids ( chi-square , 7.36 ; P = .007 ) . Smoking history was a significant factor ( chi-square , 5.2 ; P = .002 ) . CONCLUSIONS Statistically , there is little difference between the 2 systems . Local and systemic factors appear to play a greater role in implant failure than does the surface of the implant OBJECTIVES The aim of this prospect i ve comparative study was to evaluate the survival rate and the condition of the peri-implant tissues of the IMZ implant system ( two-stage cylindertype ) , the Brånemark implant system ( two-stage screwtype ) and the ITI implant system ( one-stage screwtype ) supporting a m and ibular overdenture during a 5-year follow-up period . MATERIAL 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 , 2 , 3 , 4 and 5 years of functional loading . RESULTS The five-year survival rate is 98.3 % for the IMZ group , 98.3 % for the Brå group and 100 % for the ITI group . Mean scores on indices for plaque , calculus , gingiva and bleeding were very low at all evaluation periods . Mean marginal bone loss over a period of 5 years , was 1.4 mm for the IMZ group , 0.7 mm for the Brå group and 0.9 mm for the ITI group . 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 . After 5 years no clinical ly relevant and statistically significant radiographic changes had developed between the three implant systems BACKGROUND Endosseous dental implants are used frequently , and many implant systems are available . The scientific documentation of the implant system presents a great variation , and it is often difficult to compare studies of different systems . PURPOSE The aim of this study was to compare two Swedish implant systems ( Astra Tech and Brånemark System implants ) , in a prospect i ve r and omized study . MATERIAL S AND METHODS Sixty-six patients were equally distributed between the two implant systems ; 184 Astra Tech and 187 Brånemark System implants were used . The patients have been followed annually with clinical and radiographic examinations . The results after 1 year are reported . RESULTS The abutment procedure was found to be easier and less time-consuming with Astra Tech than with Brånemark implants . The operation times in minutes ( mean + /- SEM ) were for the respective implant 35 + /- 4.0 and 51 + /- 4.8 in the maxilla and 32 + /- 3.8 and 43 + /- 2.4 in the m and ible . The differences in both cases were significant : p < .02 and p < .05 , respectively . The failure rate for Astra Tech implants was 0.5 % and for Brånemark implants 4.3 % . The difference was significant ( p < .05 ) ; however , taking into account that five of the eight implant losses in the Brånemark implant group occurred in one patient , an intraindividual correlation can not be excluded . Therefore , this result should be interpreted with caution . The marginal bone level changes were examined already from the fixture installation . The major bone loss was found between fixture installation and baseline . This bone loss was several times greater than the bone loss between the baseline and the 1-year follow-up . The total bone loss during the observation period did not differ significantly between the systems , but they had different resorption patterns . The bone loss in the upper jaw between baseline and 1-year follow-up was 0.22 + /- 0.14 and 0.03 + /- 0.09 mm for the Astra Tech and Brånemark implants , respectively . In the lower jaw , the loss was -0.31 for both systems . The frequency of plaque accumulation and bleeding on probing did not differ between the implant systems . CONCLUSIONS Abutment connection with Astra Tech implants was simpler than the corresponding surgery with Brånemark System implants and the survival rate of Astra Tech implants was higher than that of Brånemark system implants PURPOSE The aim of the present study was to evaluate whether there was a difference between machined and TiO(2)-blasted implants regarding survival rate and marginal bone loss during a 5-year observation period . MATERIAL S AND METHODS A total of 133 implants ( Astra Tech Dental Implants ; Astra Tech AB , Mölndal , Sweden ) were placed in 50 patients at 6 centers in 4 Sc and inavian countries . Forty-eight implants were installed in the maxilla and 85 implants in the m and ible . A r and omization and a stratification were done , so that each fixed partial prosthesis was supported by at least 1 machined and 1 TiO(2)-blasted implant . The implant-supported fixed partial prostheses ( ISFPP ) were fabricated within 2 months after postoperative healing . A total of 52 ISFPP ( 17 maxillary , 35 m and ibular ) were inserted . The patients were clinical ly examined once a year for 5 years . At the annual follow-up , biological as well as technical complications were recorded . RESULTS Of the 133 implants placed , 3 were reported as failed after 5 years of follow-up , result ing in an overall cumulative survival rate of 97.6 % . The cumulative implant survival rates were 100 % for the TiO(2)-blasted implants and 95.1 % for the machined implants . No significant difference in survival was , however , found between the machined and TiO(2)-blasted implants after 5 years . The mean marginal bone loss in the maxilla was 0.21 + /- 0.83 mm ( SD ) for the machined implants and 0.51 + /- 1.11 mm ( SD ) for the TiO(2)-blasted implants during the 5-year observation period . In the m and ible , the mean marginal loss was 0.22 + /- 1.13 mm for the machined implants and 0.52 + /- 1.07 mm for the TiO(2)-blasted implants from baseline to the 5-year examination . No significant difference in marginal bone loss between the 2 surface groups was found during the 5-year observation period . CONCLUSIONS The present study shows good 5-year results with small ISFPP in the m and ible , as well as in the maxilla . No significant differences were found in failure rate and marginal bone loss around implants with a machined rather than a TiO(2)-blasted surface . J Prosthodont 2001;10:2 - 7 |
10,909 | 25,228,806 | RESULTS The findings of some studies indicate that alcoholics have greater impairment in facial expression recognition tasks , while others could not differentiate the clinical group from controls .
However , there was a trend toward greater deficits in alcoholics .
Alcoholics displayed less accuracy in recognition of sadness and disgust and required greater emotional intensity to judge facial expressions corresponding to fear and anger . | BACKGROUND Alcohol abuse and dependence can cause a wide variety of cognitive , psychomotor , and visual-spatial deficits .
It is question able whether this condition is associated with impairments in the recognition of affective and /or emotional information .
Such impairments may promote deficits in social cognition and , consequently , in the adaptation and interaction of alcohol abusers with their social environment .
The aim of this systematic review was to systematize the literature on alcoholics ' recognition of basic facial expressions in terms of the following outcome variables : accuracy , emotional intensity , and latency time . | Facial expression recognition is a central feature of emotional and social behaviour and previous studies have found that alcoholics are impaired in this skill when presented with single emotions of differing intensities . The aim of this study was to explore biases in alcoholics ' recognition of emotions when they were a mixture of two closely related emotions . The amygdala is intimately involved in encoding of emotions , especially those related to fear . In animals an increased number of withdrawals from alcohol leads to increased seizure sensitivity associated with facilitated transmission in the amygdala and related circuits . A further objective therefore was to explore the effect of previous alcohol detoxifications on the recognition of emotional facial expressions . Fourteen alcoholic in patients were compared with 14 age and sex matched social drinking controls . They were asked to rate how much of each of six emotions ( happiness , surprise , fear , sadness , disgust and anger ) were present in morphed pictures portraying a mix of two of those emotions . The alcoholic group showed enhanced fear responses to all of the pictures compared to the controls and showed a different pattern of responding on anger and disgust . There were no differences between groups on decoding of sad , happy and surprised expressions . In addition the enhanced fear recognition found in the alcoholic group was related to the number of previous detoxifications . These results provide further evidence for impairment in facial expression recognition present in alcoholic patients . In addition , since the amygdala has been associated with the processing of facial expressions of emotion , particularly those of fear , the present data furthermore suggest that previous detoxifications may be related to changes within the amygdala Most studies investigating the recognition of facial expressions have focused on static displays of intense expressions . Consequently , research ers may have underestimated the importance of motion in deciphering the subtle expressions that permeate real-life situations . In two experiments , we examined the effect of motion on perception of subtle facial expressions and tested the hypotheses that motion improves affect judgment by ( a ) providing denser sampling of expressions , ( b ) providing dynamic information , ( c ) facilitating configural processing , and ( d ) enhancing the perception of change . Participants viewed faces depicting subtle facial expressions in four modes ( single-static , multi-static , dynamic , and first-last ) . Experiment 1 demonstrated a robust effect of motion and suggested that this effect was due to the dynamic property of the expression . Experiment 2 showed that the beneficial effect of motion may be due more specifically to its role in perception of change . Together , these experiments demonstrated the importance of motion in identifying subtle facial expressions OBJECTIVE To describe patterns of alcohol consumption in the adult Brazilian population . METHOD Multicluster r and om sample of 2,346 subjects 18 years of age or older , selected nationwide . Interviews were conducted in respondents ' homes between November 2005 and April 2006 . RESULTS About 48 % of the sample had not drunk alcoholic beverages in the past year , with variations by gender , age , marital status , education , income and region of the country . Among drinkers , 29 % reported drinking 5 or more drinks per occasion ( men , 38 % ) . Sociodemographic variables are associated with the frequency and amount of drinking , alcohol problems , and alcohol abuse and dependence . Among the whole sample ( including drinkers and non drinkers ) , 28 % reported binge drinking , 25 % reported at least one kind of alcohol related problem , 3 % were alcohol abusers and another 9 % were alcohol dependent . DISCUSSION Abstinence is high in the Brazilian population . However , elevated proportions of those who drink consume alcohol in a high risk pattern ( binge-drinking ) , report a high level of alcohol problems , alcohol abuse and dependence . National public policies must consider these factors , as well as the regional Brazilian differences |
10,910 | 20,467,807 | Other studies revealed that audio narration , video clips , interactive models , and animations increase learning time but also facilitate higher knowledge and /or satisfaction .
Conclusions On average , Internet-based instruction and non-computer instruction require similar time .
Instructional strategies to enhance feedback and interactivity typically prolong learning time , but in many cases also enhance learning outcomes .
Isolated examples suggest potential for improving efficiency in Internet-based instruction | Authors have cl aim ed that Internet-based instruction promotes greater learning efficiency than non-computer methods .
Objectives Determine , through a systematic synthesis of evidence in health professions education , how Internet-based instruction compares with non-computer instruction in time spent learning , and what features of Internet-based instruction are associated with improved learning efficiency . | CONTEXT Despite evidence that a variety of continuing medical education ( CME ) techniques can foster physician behavioral change , there have been no r and omized trials comparing performance outcomes for physicians participating in Internet-based CME with physicians participating in a live CME intervention using approaches documented to be effective . OBJECTIVE To determine if Internet-based CME can produce changes comparable to those produced via live , small-group , interactive CME with respect to physician knowledge and behaviors that have an impact on patient care . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted from August 2001 to July 2002 . Participants were 97 primary care physicians drawn from 21 practice sites in Houston , Tex , including 7 community health centers and 14 private group practice s. A control group of 18 physicians from these same sites received no intervention . INTERVENTIONS Physicians were r and omly assigned to an Internet-based CME intervention that could be completed in multiple sessions over 2 weeks , or to a single live , small-group , interactive CME workshop . Both incorporated similar multifaceted instructional approaches demonstrated to be effective in live setting s. Content was based on the National Institutes of Health National Cholesterol Education Program -- Adult Treatment Panel III guidelines . MAIN OUTCOME MEASURES Knowledge was assessed immediately before the intervention , immediately after the intervention , and 12 weeks later . The percentage of high-risk patients who had appropriate lipid panel screening and pharmacotherapeutic treatment according to guidelines was documented with chart audits conducted over a 5-month period before intervention and a 5-month period after intervention . RESULTS Both interventions produced similar and significant immediate and 12-week knowledge gains , representing large increases in percentage of items correct ( pretest to posttest : 31.0 % [ 95 % confidence interval { CI } , 27.0%-35.0 % ] ; pretest to 12 weeks : 36.4 % [ 95 % CI , 32.2%-40.6 % ] ; P<.001 for all comparisons ) . Chart audits revealed high baseline screening rates in all study groups ( > or = 93 % ) with no significant postintervention change . However , the Internet-based intervention was associated with a significant increase in the percentage of high-risk patients treated with pharmacotherapeutics according to guidelines ( preintervention , 85.3 % ; postintervention , 90.3 % ; P = .04 ) . CONCLUSIONS Appropriately design ed , evidence -based online CME can produce objective ly measured changes in behavior as well as sustained gains in knowledge that are comparable or superior to those realized from effective live activities Purpose To evaluate a five-year experience ( 1995–2000 ) developing and integrating computer cases into a required clerkship . Method In Study 1 , 54 volunteer students were r and omly assigned to study articles , a paper case , or a computer case on low back pain/kidney stones . Students were given an exam immediately after the exercise and one week later . In Study 2 , 325 clerkship students were asked to select and complete two computer cases or to prepare assignments on unrelated topics . Among the cases offered were two test cases on low back pain/kidney stones and pneumonia . Questions specific to the computer test cases ( CC ) and other noncomputer cases ( NCC ) were in the final exam . Exam scores related to CC questions and NCC questions were compared between the groups of students who did and did not complete the computer cases . Students also rated the computer cases on a question naire . Results In Study 1 , reading articles required the most time and received the most negative comments . The students who completed the computer case scored the best on the exam one week later . In Study 2 , the students who completed the two computer cases scored significantly higher on the CC questions than did students who studied only one or none of the computer cases ( p < .001 ) . There was no difference among groups for the NCC scores ( p = .76 ) . Students rated the computer cases with a mean of 6 on a seven-point scale ( 7 = strongly agree ) . Conclusion Computer cases are effective learning tools , are well-received by students , and can be successfully integrated into existing clerkships INTRODUCTION The use of computer-generated 3-dimensional ( 3-D ) anatomical models to teach anatomy has proliferated . However , there is little evidence that these models are educationally effective . The purpose of this study was to test the educational effectiveness of a computer-generated 3-D model of the middle and inner ear . METHODS We reconstructed a fully interactive model of the middle and inner ear from a magnetic resonance imaging scan of a human cadaver ear . To test the model 's educational usefulness , we conducted a r and omised controlled study in which 28 medical students completed a Web-based tutorial on ear anatomy that included the interactive model , while a control group of 29 students took the tutorial without exposure to the model . At the end of the tutorials , both groups were asked a series of 15 quiz questions to evaluate their knowledge of 3-D relationships within the ear . RESULTS The intervention group 's mean score on the quiz was 83 % , while that of the control group was 65 % . This difference in means was highly significant ( P < 0.001 ) . DISCUSSION Our findings st and in contrast to the h and ful of previous r and omised controlled trials that evaluated the effects of computer-generated 3-D anatomical models on learning . The equivocal and negative results of these previous studies may be due to the limitations of these studies ( such as small sample size ) as well as the limitations of the models that were studied ( such as a lack of full interactivity ) . Given our positive results , we believe that further research is warranted concerning the educational effectiveness of computer-generated anatomical models Background : Although animations may intuitively seem more effective than static graphics for teaching , there is no clear-cut evidence for the superiority of simple computer-based animations in medical education . Aims : We investigated whether simple animations are better than static graphics as an aid to medical students in learning home safety assessment , an important part of geriatric curriculum . Methods : We used two versions of an interactive online module , one that depicted common home safety issues in static graphics and the other in animations . We r and omized first-year medical students who agreed to participate into two groups . After the module , students completed a cognitive burden scale and a st and ardized competency assessment test in which they had to identify the salient home safety issues and give recommendations based on the hazards . We also captured time spent on task . Results and conclusions : We found no significant differences between the groups in the cognitive burden level , competency assessment scores , and time spent on task . The much cheaper-to-produce static graphics were equally effective as simple animations in this medical education scenario BACKGROUND Video-based instructions for clinical procedures have been used frequently during the preceding decades . AIM To investigate in a r and omised controlled trial the learning effectiveness of fragmented videos vs. the complete sequential video and to analyse the attitudes of the user towards video as a learning aid . MATERIAL S AND METHODS An instructional video on surgical h and wash was produced . The video was available in two different forms in two separate web pages : one as a sequential video and one fragmented into eight short clips . Twenty-eight dental students in the second semester were r and omised into an experimental ( n = 15 ) and a control group ( n = 13 ) . The experimental group used the fragmented form of the video and the control group watched the complete one . The use of the videos was logged and the students were video taped whilst undertaking a test h and wash . The videos were analysed systematic ally and blindly by two independent clinicians . The students also performed a written test concerning learning outcome from the videos as well as they answered an attitude question naire . RESULTS The students in the experimental group watched the video significantly longer than the control group . There were no significant differences between the groups with regard to the ratings and scores when performing the h and wash . The experimental group had significantly better results in the written test compared with those of the control group . There was no significant difference between the groups with regard to attitudes towards the use of video for learning , as measured by the Visual Analogue Scales . Most students in both groups expressed satisfaction with the use of video for learning . CONCLUSION The students demonstrated positive attitudes and acceptable learning outcome from viewing CAL videos as a part of their pre- clinical training . Videos that are part of computer-based learning setting s would ideally be presented to the students both as a segmented and as a whole video to give the students the option to choose the form of video which suits the individual student 's learning style OBJECTIVE To determine the impact of adding audio-feed to an online lecture on screening given to medical students who were participating in an outpatient clerkship . DESIGN Prospect i ve , r and omised , controlled study . SETTING V and erbilt University School of Medicine , Nashville and Wake Forest Medical School , Winston-Salem . PARTICIPANTS A total of 59 Years 3 and 4 medical students . MAIN OUTCOME MEASURES Students ' use of time , satisfaction with the lecture experience , and knowledge . Educational intervention The online lecture was developed at V and erbilt University . At V and erbilt , 16 Year 4 medical students were r and omised to the lecture on screening with audio and 17 Year 4 medical students were r and omised to the same lecture without audio . At Wake Forest , 13 Year 3 medical students were r and omised to the lecture on screening with audio and 13 Year 3 students were r and omised to the same lecture without audio . RESULTS The audio lecture required 20 more minutes to complete than the non-audio lecture . Students in the audio group were more satisfied with their experience than students in the non-audio group . Students in the audio-feed group achieved a trend for higher post-intervention knowledge scores , with the difference attributed to the students at V and erbilt . CONCLUSION Audio narration is an important aspect of an online lecture . The distribution of online lectures to students at different sites and different training levels requires further study Purpose To determine whether internal medicine residents prefer learning from Web-based ( WB ) modules or printed material , and to compare the effect of these teaching formats on knowledge . Method The authors conducted a r and omized , controlled , crossover study in the internal medicine resident continuity clinics of the Mayo School of Graduate Medical Education during the 2002–03 academic year . Participants studied two topics of ambulatory medicine using WB modules and two topics using paper practice guidelines in r and omly assigned sequences . Primary outcomes were format preference ( assessed by an end-of-course question naire ) and score changes from pre- to postintervention tests of knowledge . Results A total of 109 consented and 75 ( 69 % ) completed the postintervention test . Fifty-seven of 73 ( 78 % “ 95 % CI , 67–86 % ” ) preferred the WB format ( p < .001 ) . Test scores improved for both formats ( 67.7 % to 75.0 % for WB , 66.0 % to 73.3 % for paper ) , but score change was not different between formats both before ( p = .718 ) and after ( p = .080 ) adjusting for topic , clinic site , study group , postgraduate year , and gender . Residents spent less time on WB modules ( mean = 47 ± 26 minutes ) than paper ( mean = 59 ± 35 , p = .024 ) . Difficulties with passwords limited their use of WB modules for 71 % ( 59–80 % ) of residents . Conclusion No difference was found between WB and paper-based formats in knowledge-test score change , but residents preferred learning with WB modules and spent less time doing so . Passwords appeared to impede use of WB modules . WB learning is effective , well accepted , and efficient . Research should focus on aspects of WB instruction that will enhance its power as a learning tool and better define its role in specific setting Multimedia instruction offers many potential advantages over traditional methods of instruction . Multimedia programs can interact with the learner , use graphic images , sound , and video , and keep track of progress . Students complete programs at their own pace while accessing material both at school and at home . Multimedia instruction can provide an interactive alternative to lectures and textbooks by quizzing the student over concepts as they are presented and requiring that the student think about the material before proceeding . While several studies have found that multimedia instruction can be more efficient by reducing instructor and classroom time , few have been able to show an increase in learning when compared with traditional methods of instruction . Santer and colleagues compared a multimedia textbook with a lecture presentation on the same material and found an increase in the post-test scores of the multimedia group , but no difference when they compared the multimedia group with a group using a printed textbook . Studies comparing multimedia and traditional approaches to learning in the areas of psychology and computer science instruction suggest an improvement in students ’ performances using the multimedia versions . Thus , there is a need for well- design ed studies to determine whether multimedia instruction more effectively facilitates students ’ learning — including medical students ’ learning — than do traditional methods . Multimedia instruction is particularly well suited to help students learn physical diagnosis . Sound , pictures , and movies augment the learning of examination skills and diagnosis findings by allowing students to hear heart and lung sounds , watch videos of physical examination procedures , and see more pictures of pathologic findings than can be included in a textbook or lecture . These visual and audio aids should increase students ’ recognition of these findings when encountered in patients . We wished to test whether a Web-based multimedia program using interactive learning and virtual reality would be more efficient and effective than traditional print-based self- study by medical students . To accomplish this , we design ed a course on physical examination of the eye and ear . Using this material , we conducted a controlled study of first-year medical students to determine whether having students use a multimedia version of the course result ed in a change in the time spent with the material and an increase in knowledge gained when compared with having students study a printed version of the same material OBJECTIVES A case-based , worked example approach was realised in a computer-based learning environment with the intention of facilitating medical students ' diagnostic knowledge . In order to enhance the effectiveness of the approach , two additional measures were implemented : erroneous examples and elaborated feedback . In the context of an experimental study , the two measures were varied experimentally . METHODS A total of 153 medical students were r and omly assigned to four experimental conditions of a 2 x 2-factor design ( errors versus no errors , elaborated feedback versus knowledge of correct result [ KCR ] ) . In order to verify the sustainability of the effects , a subgroup of subjects ( n = 52 ) was compared with a control group of students who did not participate in the experiment ( n = 145 ) on a regular multiple-choice question ( MCQ ) test . RESULTS Results show that the acquisition of diagnostic knowledge is mainly supported by providing erroneous examples in combination with elaborated feedback . These effects were independent from differences in time-on-task and prior knowledge . Furthermore , the effects of the learning environment proved sustainable . CONCLUSIONS Our results demonstrate that the case-based , worked example approach is effective and efficient Summary BACKGROUND Increased clinical dem and s and decreased available time accentuate the need for efficient learning in postgraduate medical training . Adapting Web-based learning ( WBL ) to learners ’ prior knowledge may improve efficiency . OBJECTIVE We hypothesized that time spent learning would be shorter and test scores not adversely affected for residents who used a WBL intervention that adapted to prior knowledge . DESIGN R and omized , crossover trial . SETTING Academic internal medicine residency program continuity clinic . PARTICIPANTS 122 internal medicine residents . INTERVENTIONS Four WBL modules on ambulatory medicine were developed in st and ard and adaptive formats . The adaptive format allowed learners who correctly answered case-based questions to skip the corresponding content . MEASUREMENTS and Main Results The measurements were knowledge posttest , time spent on modules , and format preference . One hundred twenty-two residents completed at least 1 module , and 111 completed all 4 . Knowledge scores were similar between the adaptive format ( mean ± st and ard error of the mean , 76.2 ± 0.9 ) and st and ard ( 77.2 ± 0.9 , 95 % confidence interval [ CI ] for difference −3.0 to 1.0 , P = .34 ) . However , time spent was lower for the adaptive format ( 29.3 minutes [ CI 26.0 to 33.0 ] per module ) than for the st and ard ( 35.6 [ 31.6 to 40.3 ] ) , an 18 % decrease in time ( CI 9 to 26 % , P = .0003 ) . Seventy-two of 96 respondents ( 75 % ) preferred the adaptive format . CONCLUSIONS Adapting WBL to learners ’ prior knowledge can reduce learning time without adversely affecting knowledge scores , suggesting greater learning efficiency . In an era where reduced duty hours and growing clinical dem and s on trainees and faculty limit the time available for learning , such efficiencies will be increasingly important . For clinical trial registration , see http://www . clinical trials.gov NCT00466453 ( http://www . clinical trials.gov/ct/show/NCT00466453?order=1 ) Purpose The comparative efficacy of case-based ( CB ) and non-CB self- assessment questions in Web-based instruction is unknown . The authors sought to compare CB and non-CB questions . Method The authors conducted a r and omized crossover trial in the continuity clinics of two academic residency programs . Four Web-based modules on ambulatory medicine were developed in both CB ( periodic questions based on patient scenarios ) and non-CB ( questions matched for content but lacking patient scenarios ) formats . Participants completed two modules in each format ( sequence r and omly assigned ) . Participants also completed a pretest of applied knowledge for two modules ( r and omly assigned ) . Results For the 130 participating internal medicine and family medicine residents , knowledge scores improved significantly ( P < .0001 ) from pretest ( mean : 53.5 ; SE : 1.1 ) to posttest ( 75.1 ; SE : 0.7 ) . Posttest knowledge scores were similar in CB ( 75.0 ; SE : 0.1 ) and non-CB formats ( 74.7 ; SE : 1.1 ) ; the 95 % CI was −1.6 , 2.2 ( P = .76 ) . A nearly significant ( P = .062 ) interaction between format and the presence or absence of pretest suggested a differential effect of question format , depending on pretest . Overall , those taking pretests had higher posttest knowledge scores ( 76.7 ; SE : 1.1 ) than did those not taking pretests ( 73.0 ; SE : 1.1 ; 95 % CI : 1.7 , 5.6 ; P = .0003 ) . Learners preferred the CB format . Time required was similar ( CB : 42.5 ; SE : 1.8 minutes , non-CB : 40.9 ; SE : 1.8 minutes ; P = .22 ) . Conclusions Our findings suggest that , among postgraduate physicians , CB and non-CB questions have similar effects on knowledge scores , but learners prefer CB questions . Pretests influence posttest scores Background Adaptation to learning styles has been proposed to enhance learning . Objective We hypothesized that learners with sensing learning style would perform better using a problem-first instructional method while intuitive learners would do better using an information-first method . Design R and omized , controlled , crossover trial . Setting Resident ambulatory clinics . Participants 123 internal medicine residents . Interventions Four Web-based modules in ambulatory internal medicine were developed in both “ didactic ” ( information first , followed by patient problem and questions ) and “ problem ” ( case and questions first , followed by information ) format . Measurements Knowledge posttest , format preference , learning style ( Index of Learning Styles ) . Results Knowledge scores were similar between the didactic ( mean ± st and ard error , 83.0 ± 0.8 ) and problem ( 82.3 ± 0.8 ) formats ( p = .42 ; 95 % confidence interval [ CI ] for difference , −2.3 to 0.9 ) . There was no difference between formats in regression slopes of knowledge scores on sensing-intuitive scores ( p = .63 ) or in analysis of knowledge scores by styles classification ( sensing 82.5 ± 1.0 , intermediate 83.7 ± 1.2 , intuitive 81.0 ± 1.5 ; p = .37 for main effect , p = .59 for interaction with format ) . Format preference was neutral ( 3.2 ± 0.2 [ 1 strongly prefers didactic , 6 strongly prefers problem ] , p = .12 ) , and there was no association between learning styles and preference ( p = .44 ) . Formats were similar in time to complete modules ( 43.7 ± 2.2 vs 43.2 ± 2.2 minutes , p = .72 ) . Conclusions Starting instruction with a problem ( versus employing problems later on ) may not improve learning outcomes . Sensing and intuitive learners perform similarly following problem-first and didactic-first instruction . Results may apply to other instructional media BACKGROUND In this study , we compared the educational value of a multimedia module about aortic valve replacement as a preparation for the operating room with a print medium of identical content . METHODS One hundred twenty-six students were r and omly assigned in a prospect i ve study to either use the multimedia course ( n = 69 ) or a print version ( n = 57 ) . A 20-item multiple-choice test was performed before and after learning with the respective medium . Both groups participated in an operation during which they were evaluated with 28 st and ardized tasks and questions . Individual motivation , computer literacy , and didactic quality of both media were assessed with psychometric tests . RESULTS There were no significant differences in the multiple-choice pretest ( multimedia , 30.6 % + /- 12.4 % versus print , 27.9 % + /- 11.4 % ) and posttest responses ( multimedia , 76.7 % + /- 13.3 % versus print , 76.9 % + /- 11.1 ) . Mean percentage of correct answers during the operation was 82.9 % + /- 10 % in the online group and 64.7 % + /- 12 % in the print group ( p < 0.0001 ) . The multimedia group needed significantly ( p < 0.001 ) less study time ( 105 + /- 24 minutes ) when compared with the text group ( 122 + /- 30 minutes ) . There were no statistically significant differences in motivation , computer literacy , and didactic quality of either medium . CONCLUSIONS Regarding factual knowledge , there is no difference between multimedia-driven learning and a print medium . During heart operations , when underst and ing of complex temporal and spatial events is essential , students ' performance is significantly improved by multimedia-enhanced teaching . The latter further proved to be more efficient in terms of study time A r and omised controlled trial was design ed to test an Internet-based interactive application as a st and -alone support for the development of self- assessment skills among second-year dental students at the Faculty of Dentistry , University of Malmö , Sweden . Fifty-two students were r and omised into an experimental ( n = 26 ) and a control group ( n = 26 ) . Both groups went through four identical learning cases in elementary clinical Periodontology during a period of 1 month . The experimental group received the cases with the interactive software , while the control group received them through a static web page . After the end of the learning phase , both groups were assessed blindly by two assessors during the interactive examination methodology . There was a moderate agreement between the two assessors , but both failed to find any significant differences between the two groups with regard to self- assessment skills and overall performance of the students . Students positively received the Internet support , but several attitude differences were observed between the two groups during the study . Time on task and competence with computers were positively correlated to assessment results for both groups . On the basis of these findings , it remains unclear if computer-based applications with automated feedback can constitute an effective remedial support for the improvement of self- assessment skills of students . In addition , for such applications to be successfully accepted , two factors are critical : students must have a clear perception of the benefits deriving from the use of the software and the use of the software should be integrated in the curriculum , replacing some of the existing workload OBJECTIVE : To determine the impact of an online lecture versus a live lecture on screening given to medical students who are participating in an outpatient clerkship . DESIGN : Prospect i ve , r and omized , controlled study . PARTICIPANTS AND SETTING : Ninety-five senior medical students in a primary care medicine clerkship based at university and distant clinic sites . INTERVENTION AND MEASUREMENTS : Forty-eight medical students were r and omized to the live lecture on screening ( live lecture group ) , and forty-seven medical students were r and omized to the online lecture on screening ( online lecture group ) . Outcome measures included students ’ knowledge , use of time , and satisfaction with the lecture experience . RESULTS : Compared to students in the live lecture group , students in the online lecture group demonstrated equal post-intervention knowledge of screening ( P=.91 ) and expended 50 minutes less time to complete the lecture . Online lecture students who used the audio feed of the lecture were equally satisfied with the lecture as the live lecture students . Without the audio feed , online lecture students were less satisfied . CONCLUSIONS : An online lecture on screening is a feasible , efficient , and effective method to teach students on outpatient clerkships about principles of screening PURPOSE There is limited experimental evidence concerning how best to train students to perform differential diagnosis . We compared 2 different methods for training 2nd-year medical students to perform differential diagnosis ( DDX ) of heart failure : a traditional classroom-based lecture ( control group ) versus a cognitive sciences-based approach to DDX instruction implemented through a computer-based tutor ( treatment group ) . METHODS Following r and om assignment to either group , students were trained for 75 minutes , and then given a 40-item examination comprised of cases that varied along a typicality gradient from prototypical ( easy ) to less typical ( hard ) . RESULTS The treatment group diagnosed correctly significantly more test cases than the control group ( 74 % versus 60 % , respectively ) . The treatment group also diagnosed correctly significantly more cases at the extremes of the typicality gradient : 81 % versus 65 % , respectively , for the prototypical cases ; 65 % versus 48 % , respectively , for the most difficult cases . CONCLUSION The ability to perform differential diagnosis is enhanced by training based upon principles of cognitive sciences Many primary care physicians have not learned about key advances in caring for patients after acute myocardial infa rct ion , including the use of -blockers ( 1 ) and angiotensin-converting enzyme inhibitors ( 2 ) . Although professional organizations have disseminated guidelines for the care of acute myocardial infa rct ion ( 3 , 4 ) , important therapies continue to be underused ( 5 ) . Physicians read guidelines to stay up-to- date ( 6 ) , but reading without additional interaction is relatively ineffective for learning ( 7 ) and has little effect on practice ( 8) . Physicians therefore need better methods for learning from guidelines . Self- assessment tests are often used to enhance self- study of printed material s ( 9 , 10 ) , but physicians can now choose from a growing number of World Wide Web sites that offer on-line self- study ( 11 ) . Since the 1960s , computer-assisted instruction has been explored as a method for medical education ( 12 - 15 ) . In theory , computer-assisted instruction can enhance self- study by tailoring presentations to learners ' individual needs and by including interactive simulations ( 16 ) . Two previous studies comparing computer-assisted instruction systems with carefully constructed self- study controls found mixed results ( 17 , 18 ) . In both of these studies , the systems were developed for and tested among medical students before the advent of the Web . Therefore , physicians have little direct evidence to inform their choices among currently available self- study methods . We conducted a r and omized trial to compare the educational outcomes produced by a Web-based tutorial on myocardial infa rct ion guidelines with those produced by self- assessment based and study from print versions of the same guidelines . We hypothesized that print-based self- study would result in substantial learning but Web-based self- study would produce incrementally greater knowledge gains , retention , learning efficiency , and satisfaction . We conducted this trial among residents rather than community physicians because residents frequently use self- study material s and because we anticipated that they would be more feasible to recruit . Methods Design of Self- Study Alternatives Guidelines and Learning Objectives The American College of Cardiology ( ACC ) , the American Heart Association ( AHA ) , and the American College of PhysiciansAmerican Society of Internal Medicine ( ACPASIM ) allowed us to use their guidelines for this trial . We wrote 20 cognitive learning objectives ( 19 ) , covering knowledge from one or both guidelines that would be important for physicians who provide primary care to patients after myocardial infa rct ion . One of the authors , an expert in evidence -based cardiology , edited the objectives for content validity and importance . The final set of learning objectives is shown in the Appendix Table . Knowledge Tests We wrote multiple-choice questions that had one correct response demonstrating the knowledge in a single learning objective . Thirty attending physicians and fellows in internal medicine , family medicine , and cardiology critiqued the clarity and difficulty of prospect i ve questions by using an electronic mail quiz system that tracked each question 's average score ( 20 ) . These data were used to assemble a 20- question pretest and a different 20- question post-test . The tests included one question per learning objective and were approximately equivalent in overall difficulty . Expected scores on the final pretest and post-test differed by less than 6 % . For each question on the final test forms , participants could place a check mark next to the statement , I would like to review available evidence or recommendations on this topic . We referred to this feature as the review flag . For both of the self- study alternatives in this trial , learners initially completed the pretest on paper . Web-Based Self- Study Material s We constructed a Web-based learning system called SAGE ( Self- Study Acceleration with Graphic Evidence ) . Participants who used SAGE copied their pretest answers into the system and were then taken to the main tutorial page , which presents an overview of the user 's pretest results for each learning objective . By clicking on hyperlinks , users could view a sequence of learning re sources for each objective . The first re source for each objective was the relevant pretest answer . From there , users could click on hyperlinks to view the relevant guideline passages ( highlighted segments of text in an on-line version of the complete guideline document ) . When guidelines referred to l and mark clinical trials , users could click on a link to open a graphic evidence browser ( Figure 1 ) . Complete instructions for using SAGE were provided in the system . The program was intended to combine two strategies of computer-assisted instruction : a tutorial strategy , which focuses the learner on deficits in previous knowledge , and a simulation strategy , which reinforces knowledge through interaction with graphic models of r and omized trial evidence . We wrote software for SAGE in Server-side JavaScript , using the Netscape Enterprise Server ( Mountain View , California ) running on a Sun Ultrasparc2 workstation ( Mountain View , California ) . For animated statistical graphics , we wrote a Java applet . Figure 1 . The SAGE ( Self- Study Acceleration with Graphic Evidence ) r and omized trial viewer . Printed Self- Study Material s Printed material s for the control group included the same self- assessment test and guidelines as the Web-based material s. The printed material s included 1 ) a booklet showing the correct answer for each pretest question and the learning objective each question was intended to evaluate and 2 ) complete reprints of the ACPASIM and ACC/AHA guidelines . Learners were instructed to compare their pretest answers with the correct answers and look up the evidence or guideline recommendations for each learning objective that they may not have met by using the outline structure of the ACPASIM guidelines and the index of the ACC/AHA guidelines . Material s in the control group were intended to provide learning through self- assessment and study from the actual guideline documents as distributed by the specialty societies . The control material s contained the same pretest answers and guideline content as SAGE but lacked the hypermedia navigation features and the detailed , interactive , graphic presentations of l and mark trial evidence . Of note , however , the guideline material s for both self- study groups contained all of the information that learners would need to meet each learning objective , including narrative descriptions of the key trial results that were available graphically in SAGE . Study Sample We recruited residency programs in family and internal medicine at four universities . Approval for research involving humans was obtained from each university 's institutional review board . A total of 5 family medicine and 7 internal medicine programs agreed to participate . We recorded the name , sex , and training year of every resident across all 12 programs in a confidential recruitment data base . Letters were placed in residents ' mailboxes inviting them to attend a 1.25-hour learning session in which they would be r and omly assigned to study from computer or printed material s on the care of myocardial infa rct ion . An honorarium of $ 30 was offered for completing the trial . The trial was also announced at resident conferences . All residents who attended a session and gave consent became eligible participants . Self- Study Sessions Participants used the self- study material s in a single session that began with the pretest and ended with an immediate post-test . After completing the pretest , participants kept carbon copies of their answers , returned their originals , and received their r and omly generated study group assignment . Those assigned to the control group were given the printed material s , and those assigned to SAGE went to an adjacent computer classroom , where they logged on and entered their pretest answers . Participants in both groups were asked to study until they felt that they had met the learning objectives , at which point the self- study material s were removed and they immediately took the post-test on paper . Each session was proctored to ensure that all learning was attributable to self- study from the assigned material without use of extraneous material s or discussion with colleagues . No irregularities occurred . Participants could not attend more than one session and were not allowed to keep the printed self- study material s or to access SAGE after completing their session . Study Group Assignment Individual participants were r and omly assigned to study groups by a computer program that generated blocked r and omization stratified by the participants ' sex and residency year . As each resident arrived at a session , he or she was registered on a laptop computer that contained coded records from the recruitment data base . As the first participants finished the pretest , a r and omization program run on the laptop generated a balanced pool of assignments for each sexresidency year category ( using a block size of 2 [ 21 ] ) . For each registered participant , the program chose an assignment at r and om from the appropriate pool . As participants turned in their pretests , they and the investigators looked up their assignments on the laptop screen . Study group assignment was therefore simultaneously revealed to the participants and to the investigators . Outcome Measures Knowledge scores from multiple-choice tests were calculated by assigning 1 point per correct answer ; unanswered items were considered incorrect . This created scores that could range from 0 to 20 points . The primary outcome of the trial was knowledge on the immediate post-test . The time spent study ing was measured by using a time-stamp machine for participants in the control group and the server log for participants in the SAGE group . Learning efficiency was calculated as the point gain from pretest to immediate post-test divided by the |
10,911 | 20,796,216 | These findings from clinical trials , along with those from epidemiologic and intervention studies , suggest water has a potentially important role to play in reducing energy intake , and consequently in obesity prevention . | The effects of consuming water with meals rather than drinking no beverage or various other beverages remain under-studied .
This systematic review of studies reported in the English- language literature was performed to compare the effects of drinking water and various beverage alternatives on energy intake and /or weight status . | OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas BACKGROUND Epidemiologic studies have shown alcohol consumption to be inversely as well as positively related to body weight and body fat . Metabolic studies have shown an increase in energy intake as well as compensation after alcohol consumption . OBJECTIVE Our objective was to assess the effects on energy intake of an apéritif compared with those of a water appetizer and 3 fruit juice appetizers . DESIGN Fifty-two men and women aged 20 - 45 y with a body mass index ( in kg/m2 ) between 20 and 32 were r and omly given 1 MJ ( 340 mL ) alcohol ( wine or beer ) , fat ( cream fruit juice ) , protein ( protein fruit juice ) , carbohydrate ( grape juice ) , or water , or no preload 30 min before an ad libitum lunch consumed from the universal eating monitor . RESULTS Energy intake ( 3.5+/-0.3 MJ compared with 2.7+/-0.2 MJ , P < 0.001 ) and eating rate were higher ( 44+/-3 g/min compared with 38+/-3 g/min , P < 0.01 ) , meal duration was longer ( 14 min compared with 12.0 min , P < 0.01 ) , satiation started to increase later ( 3.5 min compared with 1.5 min , P < 0.01 ) , and eating was prolonged after maximum satiation ( 2.5 min compared with 0.6 min , P < 0.01 ) after an apéritif than after a fat , protein , or carbohydrate appetizer , . Twenty-four-hour energy intake was higher on a day that an apéritif was consumed than after water or no preload . CONCLUSION Twenty-four-hour energy intake was elevated with a 1-MJ apéritif but not with a 1-MJ liquid carbohydrate , fat , or protein appetizer We studied the effects of xylitol , the pentose-sugar alcohol , on gastric emptying of the solid-food component of a complex meal . Gastric emptying was measured in human volunteers by utilizing a st and ardized radiolabeled scrambled-egg meal . After ingestion of 25 g xylitol , gastric emptying was markedly prolonged ( T-1/2 58 + /- 5 min control vs 91 + /- 7 min after xylitol [ p less than 0.01 ] ) . Since delayed gastric emptying may affect food intake , we evaluated the effects of xylitol on calorie intake . Food intake after oral preloading with water result ed in intake of 920 + /- 60 kcal vs 690 + /- 45 kcal after 25 g of xylitol . In contrast , a preload of glucose , fructose , or sucrose failed to suppress food intake . Although xylitol decreased food intake and also delayed gastric emptying , these effects may be unrelated . Our data suggest a role for xylitol as a potentially important agent in dietary control Using a within-subjects design , we gave over-weight and normal-weight subjects a 500-mL drink of fructose , glucose , or aspartame diluted in lemon-flavored water or plain water in a r and omized fashion at about weekly intervals . Food intake was assessed at a buffet lunch that began 38 min after the preload was completed . Blood was drawn throughout and assayed for concentrations of glucose , insulin , glucagon , and free fatty acid . When subjects drank the fructose preload , they subsequently ate fewer overall calories and fewer grams of fat than when they drank any of the other preloads . The aspartame load did not stimulate intake beyond the plain-water control . The effects of the oxidation of fructose as a possible mechanism for the reduction in food intake is discussed . The effects of insulin in stimulating intake are also discussed BACKGROUND Previous studies have linked full-calorie sugar-sweetened beverages ( SSBs ) with greater weight gain and an increased risk of type 2 diabetes . OBJECTIVE We prospect ively examined the association between consumption of SSBs and the risk of coronary heart disease ( CHD ) in women . DESIGN Women ( n = 88,520 ) from the Nurses ' Health Study aged 34 - 59 y , without previously diagnosed coronary heart disease ( CHD ) , stroke , or diabetes in 1980 , were followed from 1980 to 2004 . Consumption of SSBs was derived from 7 repeated food-frequency question naires administered between 1980 and 2002 . Relative risks ( RRs ) for CHD were calculated by using Cox proportional hazards models and adjusted for known cardiovascular disease risk factors . RESULTS During 24 y of follow-up , we ascertained 3105 incident cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . After st and ard and dietary risk factors were adjusted for , the RRs ( and 95 % CIs ) of CHD according to categories of cumulative average of SSB consumption ( < 1/mo , 1 - 4/mo , 2 - 6/wk , 1/d , and > or = 2 servings/d ) were 1.0 , 0.96 ( 0.87 , 1.06 ) , 1.04 ( 0.95 , 1.14 ) , 1.23 ( 1.06 , 1.43 ) , and 1.35 ( 1.07 , 1.69 ) ( P for trend < 0.001 ) . Additional adjustment for body mass index , energy intake , and incident diabetes attenuated the associations , but they remained significant . Artificially sweetened beverages were not associated with CHD . CONCLUSION Regular consumption of SSBs is associated with a higher risk of CHD in women , even after other unhealthful lifestyle or dietary factors are accounted for BACKGROUND Type 2 diabetes mellitus is an increasingly serious health problem among African American women . Consumption of sugar-sweetened drinks was associated with an increased risk of diabetes in 2 studies but not in a third ; however , to our knowledge , no data are available on African Americans regarding this issue . Our objective was to examine the association between consumption of sugar-sweetened beverages , weight gain , and incidence of type 2 diabetes mellitus in African American women . METHODS A prospect i ve follow-up study of 59,000 African American women has been in progress since 1995 . Participants reported on food and beverage consumption in 1995 and 2001 . Biennial follow-up question naires ascertained new diagnoses of type 2 diabetes . The present analyses included 43,960 women who gave complete dietary and weight information and were free from diabetes at baseline . We identified 2713 incident cases of type 2 diabetes mellitus during 338,884 person-years of follow-up . The main outcome measure was the incidence of type 2 diabetes mellitus . RESULTS The incidence of type 2 diabetes mellitus was higher with higher intake of both sugar-sweetened soft drinks and fruit drinks . After adjustment for confounding variables including other dietary factors , the incidence rate ratio for 2 or more soft drinks per day was 1.24 ( 95 % confidence interval , 1.06 - 1.45 ) . For fruit drinks , the comparable incidence rate ratio was 1.31 ( 95 % confidence interval , 1.13 - 1.52 ) . The association of diabetes with soft drink consumption was almost entirely mediated by body mass index , whereas the association with fruit drink consumption was independent of body mass index . CONCLUSIONS Regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk of type 2 diabetes mellitus in African American women . While there has been increasing public awareness of the adverse health effects of soft drinks , little attention has been given to fruit drinks , which are often marketed as a healthier alternative to soft drinks Objective : The purpose of this study was to compare the dietary strategies , and use of fat- and sugar-modified foods and beverages in a weight loss maintainer group ( WLM ) and an always-normal weight group (NW).Subjects : WLM ( N=172 ) had maintained ⩾10 % weight loss for 11.5 years , and had a body mass index ( BMI ) of 22.0 kg m−2 . NW ( N=131 ) had a BMI of 21.3 kg m−2 and no history of being overweight . Three , 24-h recalls on r and om , non-consecutive days were used to assess dietary intake . Results : WLM reported consuming a diet that was lower in fat ( 28.7 vs 32.6 % , P<0.0001 ) and used more fat-modification strategies than NW . WLM also consumed a significantly greater percentage of modified dairy ( 60 vs 49 % ; P=0.002 ) and modified dressings and sauces ( 55 vs 44 % ; P=0.006 ) than NW . WLM reported consuming three times more daily servings of artificially sweetened soft drinks ( 0.91 vs 0.37 ; P=0.003 ) , significantly fewer daily servings of sugar-sweetened soft drinks ( 0.07 vs 0.16 ; P=0.03 ) and more daily servings of water ( 4.72 vs 3.48 ; P=0.002 ) than NW . Conclusions : These findings suggest that WLM use more dietary strategies to accomplish their weight loss maintenance , including greater restriction on fat intake , use of fat- and sugar-modified foods , reduced consumption of sugar-sweetened beverages and increased consumption of artificially sweetened beverages . Ways to promote the use of fat-modified foods and artificial sweeteners merits further research in both prevention- and treatment-controlled trials Water consumed before a meal has been found to reduce energy intake among nonobese older adults . However , it is unknown whether this effect is evident among overweight and obese older adults , a population who would benefit from strategies to improve energy intake regulation . Our purpose was to determine whether premeal water consumption reduces meal energy intake in overweight and obese older adults . Twenty-four overweight and obese adults ( body mass index=34.3+/-1.2 ) , mean age 61.3+/-1.1 years , were given an ad libitum st and ardized breakfast meal on two r and omly assigned occasions . Thirty minutes before the meal , subjects were given either a 500-mL water preload or no preload . Energy intake at each meal was covertly measured . Meal energy intake was significantly less in the water preload condition as compared with the no-preload condition ( 500+/-32 vs 574+/-38 , respectively ; P=0.004 ) , representing an approximate 13 % reduction in meal energy intake . The percentage reduction in meal energy intake following the water preload was not related to sex , age , body mass index , or habitual daily water consumption ( all P>0.05 ) . Given the high prevalence of overweight and obesity among older adults , future studies should determine whether premeal water consumption is an effective long-term weight control strategy for older adults CONTEXT Recently , we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women . OBJECTIVE We now repeated these studies in a r and omized , controlled , crossover trial in overweight or obese otherwise healthy subjects ( eight men and eight women ) , comparing also the effects of 500 ml isoosmotic saline or 50 ml water . RESULTS Only 500 ml water increased energy expenditure by 24 % over the course of 60 min after ingestion , whereas isoosmotic saline and 50 ml water had no effect . Heart rate and blood pressure did not change in these young , healthy subjects . CONCLUSIONS Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking . Instead , we hypothesize the existence of a portal osmoreceptor , most likely an ion channel This study investigated the influence of sensory stimulation , with and without post-ingestive consequences , on satiation by varying the form of a preload and the timing of a mixed meal presented after the preload . Twenty-four , normal-weight , non-dieting , college-aged women were r and omized to different preload groups : water preload ( Water ) , sip- and -spit energy-dense preload ( Taste ) , or energy-dense preload ( Taste/kcal ) . Volume of fluid consumed prior to the meal was controlled . All participants had sessions in which a meal was provided immediately ( 0 min ) or 30 min after the preload . Results showed equal suppression of intake for participants receiving sensory stimulation from an energy-dense preload ( Taste and Taste/kcal groups ) in comparison to a water preload ( Water group ) . No effect of time from preload to food consumption was found ; the suppression of intake was similar whether the meal immediately followed the preload or was 30 min after the preload . These findings suggest that sensory aspects of food can influence satiation , and in the conditions of this study , had a larger influence on satiation than post-ingestive consequences In two experiments , 2 - 5-year-old children 's responsiveness to caloric density cues was examined . In a preloading protocol , consumption of fixed volumes of drinks ( 205 ml in Experiment 1 ; 150 ml in Experiment 2 ) , sweetened with sucrose , aspartame , aspartame plus low glucose maltodextrin , or a water control , was followed by ad lib consumption from among a variety of foods . Caloric drinks had about 90 kcal in Experiment 1 , 65 kcal in Experiment 2 . The delay interval between the preload and the ad lib consumption was 0 , 30 or 60 minutes . In Experiment 1 , 24 4- and 5-year-old children participated in only one delay interval , while in Experiment 2 , all 20 2- and 3-year-old children were seen in all conditions . Results revealed evidence of caloric compensation , but no evidence of preload x time delay interaction . In both experiments , aspartame also produced a significant suppression of intake relative to water , primarily due to the pattern at 30 min following the preload . Across conditions , the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks , providing evidence for postingestive effects . In Experiment 1 , suppression of intake was related to the children 's preferences for the foods , not to macronutrient content ; consumption of nonpreferred foods was most suppressed . Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake , and this common feeding practice may also reduce dietary variety OBJECTIVE Reduced intake of sweetened caloric beverages ( SCBs ) is recommended to lower total energy intake . Replacing SCBs with non-caloric diet beverages does not automatically lower energy intake , however . Compensatory increases in other food or beverages reportedly negate benefits of diet beverages . The purpose of this study was to evaluate drinking water as an alternative to SCBs . RESEARCH METHODS AND PROCEDURES Secondary analysis of data from the Stanford A TO Z intervention evaluated change in beverage pattern and total energy intake in 118 overweight women ( 25 to 50 years ) who regularly consumed SCBs ( > 12 ounces/d ) at baseline . At baseline and 2 , 6 , and 12 months , mean daily beverage intake ( SCBs , drinking water , non-caloric diet beverages , and nutritious caloric beverages ) , food composition ( macronutrient , water , and fiber content ) , and total energy intake were estimated using three 24-hour diet recalls . Beverage intake was expressed in relative terms ( percentage of beverages ) . RESULTS In fixed effects models that controlled for total beverage intake , non-caloric and nutritious caloric beverage intake ( percentage of beverages ) , food composition , and energy expenditure [ metabolic equivalent ( MET ) ] , replacing SCBs with drinking water was associated with significant decreases in total energy intake that were sustained over time . The caloric deficit attributable to replacing SCBs with water was not negated by compensatory increases in other food or beverages . Replacing all SCBs with drinking water was associated with a predicted mean decrease in total energy of 200 kcal/d over 12 months . DISCUSSION The results suggest that replacing SCBs with drinking water can help lower total energy intake in overweight consumers of SCBs motivated to diet BACKGROUND : Beverages are contributing an increased proportion of energy to the diet . Because they elicit a weak compensatory dietary response , they may increase risk of positive energy balance . OBJECTIVES : This study aim ed to document the differential effects of matched liquid and solid carbohydrate loads on diet and body weight . DESIGN : In a cross-over design , seven males and eight females consumed dietary carbohydrate loads of 1880 kJ/day as a liquid ( soda ) or solid ( jelly beans ) during two 4 week periods separated by a 4 week washout . Subjects were permitted to consume the loads however they chose . In addition to baseline measurements , diet records were obtained on r and om days throughout the study , body composition was measured weekly , physical activity was assessed before and after treatments and hunger was assessed during washout and midway through each treatment . RESULTS : Free-feeding energy intake during the solid period was significantly lower than intake prior to this period . Dietary energy compensation was precise ( 118 % ) . No decrease in free-feeding energy intake occurred during the liquid period . Total daily energy intake increased by an amount equal to the load result ing in dietary compensation of −17 % . Consequently , body weight and BMI increased significantly only during the liquid period . Physical activity and hunger were unchanged . CONCLUSIONS : This study indicates that liquid carbohydrate promotes positive energy balance , whereas a comparable solid carbohydrate elicits precise dietary compensation . Increased consumption of energy-yielding fluids may promote positive energy balance Despite some reports that aspartame (APM)-sweetened beverages may increase subjective appetite , previously we demonstrated that drinking 280 ml of an APM-sweetened soft drink ( 170 mg APM ) had no effect on appetite , and 560 ml of the same soft drink ( 340 mg APM ) reduced appetite . The present study examined this appetite reduction to determine its cause . Eighteen normal weight young adult males received five treatments ( beverage preloads ) at 1100 h in a r and omized order , one per week : 280 ml of carbonated mineral water ( CMW ) ( control ) , 560 ml of CMW , 280 ml of CMW with 340 mg of encapsulated APM , 280 ml of CMW sweetened with 340 mg APM , 560 ml of an APM-sweetened soft drink ( 340 mg APM ) . Subjective hunger and food appeal were measured from 0930 a.m. to 1230 h , and food intake from a buffet lunch offered at 1205 h was measured . Treatment had no effect on food intake or macronutrient selection . Both 560 ml of CMW or soft drink suppressed appetite , although 280 ml of APM-sweetened mineral water significantly increased subjective appetite relative to the control . Encapsulated APM had no effect on appetite . Therefore , appetite reduction following consumption of an APM-sweetened drink is likely due to drink volume and not the APM content . In addition , consuming APM-sweetened CMW produces a short-term increase in subjective appetite This study compared the effects of equal volumes of sugar-rich and sugar-free beverages on feelings of hunger and fullness and the ad libitum consumption of a palatable , fat-rich snack . Eleven healthy males consumed equal volumes ( 375 mL ) of three drinks ( sugar-rich cola , sugar-free cola , mineral water ) in r and om order on separate mornings . After 20 min , the subjects were able to snack freely on potato crisps during the next 90 min . Each subject 's individual bowl of potato crisps was covertly replenished at 15 min intervals while the subjects were completing appetite and mood ratings . After the 110 min experimental period , the subjects ' ad libitum food intake from a buffet-style lunch was covertly recorded . On leaving the laboratory , the subjects filled in a weighed food dairy for the rest of the day . The equal-volume preloads initially decreased hunger to a similar degree and potato crisp intake during the first 15 min interval was not significantly different among the three preloads . On average , total energy intakes from the crisps and lunch were not significantly different among the preloads , and by the end of the day , total energy intakes were similar for the three test conditions . Therefore , the low-calorie/low-sugar drinks did not facilitate a reduced energy intake by the lean , non-dieting male subjects Dietary compensation for energy provided as ethanol is reportedly limited . Whether this is a function of the ethanol or other aspect of the medium in which it is ingested is not known . Eight male and eight female adults ingested 1.08 liters of beer ( 5.0 % ethanol w/v , 1891kJ ) , light beer ( 2.9 % ethanol w/v , 1197kJ ) , no-alcohol beer ( 0.1 % ethanol w/v , 816kJ ) , cola ( 1749kJ ) or carbonated water ( 0kJ ) every 3 - 4 days with a midday meal . Diet records were kept the preceding day and day of beverage ingestion . Energy intake was significantly higher each day an energy-bearing beverage was consumed relative to its preceding day . A literature review revealed dietary compensation for modifications of energy intake via fluids is less precise than when solid foods are manipulated . These findings demonstrate dietary adjustment for energy derived from ethanol is imprecise , but also indicate energy from carbohydrate elicits little dietary response when ingested in a beverage Objective : To investigate the influence of ingestion of beverages with sucrose or with intense sweeteners on food intake ( FI ) and on hunger ratings in before and after a month of daily consumption of beverages . Design : Experimental study . Setting : Department of Physiology , University Hospital , Dijon , France . Subjects : In all , 12 men and 12 women , aged 20–25 y. Interventions : Four beverages contained either sucrose ( E+:100 g/l , 1672 kJ ) or intense sweeteners ( E− : null energy content ) and were flavoured with either orange ( O ) or raspberry ( R ) . FI was measured in the lab during two 2-consecutive-day periods , carried out on 2 successive weeks ( session 1 ) . The subjects drank 2 l of either E+ or E− beverages on the first day of both weekly periods , according to a balanced r and omised design . E+ was paired with O for 50 % of subjects and with R for the other 50 % . Subjects were then habituated over a 4-week period to both beverages , consuming 1 l of E+ beverage on odd days and 1 l of E– drink on even days . After this period , the measurements of session 1 were repeated ( session 2 , weeks 7–8 ) . Finally , FI was measured for two more 2-day periods ( weeks 9–10 ) after the association between flavour and energy content was reversed ( session 3 ) . Results : The E– drinks were less palatable than the E+ drinks . Besides , we observed that FI was not reduced in response to a liquid extra caloric load and there was no change in hunger ratings after the beverages in any of the sessions . Conclusion : Ingestion of caloric beverages induced a positive energy balance and the continuous exposure phase to these beverages over 1 month did not improve FI adaptation in response to the extra energy provided by the beverages . Sponsorship : This study was sponsored by SEV , Bourg la Reine , France ; the French Ministère de la Recherche et de la Technologie ( Programme AGROBIO-Aliments Demain ) and the Regional Council of Burgundy ( Dijon , France ) Whereas soft drinks are described as primarily thirst-quenching liquids , juices and milk are said to be liquid foods , with a greater satiating power . This study was conducted to compare the effects of orange juice , low-fat milk ( 1 % ) , regular cola , and sparkling water on hunger , thirst , satiety , and energy intakes at the next meal . Thirty-two volunteers ( 14 men and 18 women ) , ages 18 - 35 years , consumed a breakfast preload composed of 590 ml ( 20 oz ) of an energy-containing beverage ( 1036 kJ ) or water ( 0 kJ ) and a slice of toast ( 418 kJ ) on four different occasions . Participants rated hunger , thirst , fullness , and desire to eat at baseline and at 20-min intervals for 2 h following preload ingestion . A tray lunch was presented at 2 h , 15 min and food consumption was measured . Compared to sparkling water , the three energy-containing beverages were associated with higher fullness and reduced hunger rating and desire to eat . However , energy intakes at lunch ( 4511+/-151 kJ for men and 3183+/-203 kJ for women ) were the same across all four beverage conditions and no compensation for breakfast energy was observed . The three beverages of equal energy value were significantly different from sparkling water , but not from each other , in their effects on hunger and satiety ratings . All four beverages satisfied thirst equally well . Whether energy-containing cola , juice , and low-fat milk facilitate a positive energy balance remains a topic for further study Exercise is known to cause physiological changes that could affect the impact of nutrients on appetite control . This study was design ed to assess the effect of drinks containing either sucrose or high-intensity sweeteners on food intake following exercise . Using a repeated- measures design , three drink conditions were employed : plain water ( W ) , a low-energy drink sweetened with artificial sweeteners aspartame and acesulfame-K ( L ) , and a high-energy , sucrose-sweetened drink ( H ) . Following a period of challenging exercise ( 70 % VO2 max for 50 min ) , subjects consumed freely from a particular drink before being offered a test meal at which energy and nutrient intakes were measured . The degree of pleasantness ( palatability ) of the drinks was also measured before and after exercise . At the test meal , energy intake following the artificially sweetened ( L ) drink was significantly greater than after water and the sucrose ( H ) drinks ( p < 0.05 ) . Compared with the artificially sweetened ( L ) drink , the high-energy ( H ) drink suppressed intake by approximately the energy contained in the drink itself . However , there was no difference between the water ( W ) and the sucrose ( H ) drink on test meal energy intake . When the net effects were compared ( i.e. , drink + test meal energy intake ) , total energy intake was significantly lower after the water ( W ) drink compared with the two sweet ( L and H ) drinks . The exercise period brought about changes in the perceived pleasantness of the water , but had no effect on either of the sweet drinks . The remarkably precise energy compensation demonstrated after the higher energy sucrose drink suggests that exercise may prime the system to respond sensitively to nutritional manipulations . The results may also have implication s for the effect on short-term appetite control of different types of drinks used to quench thirst during and after exercise The relationship between alcohol intake and obesity remains uncertain . Evidence suggesting that alcohol-derived energy may be unregulated points to an inability to maintain appetite , energy balance and , hence , body weight when alcohol is introduced to the diet . This study investigated the short-term effects of alcohol on hunger and energy intake in 20 lean women . On 4 occasions , subjects were given a r and omised preload drink ( ' alcohol ' , ' no alcohol ' , ' carbohydrate ' , ' water ' ) followed by visual analogue scales ( VAS ) rating hunger and an ad lib test meal . There was no difference in hunger ratings ( p > 0.05 ) nor in the amount of energy consumed during the test meal ( F = 1.66 , p > 0.05 ) following any of the 4 preloads . Consumption of the 2 high energy preload drinks ( ' alcohol ' , 0.91 MJ ; ' CHO ' , 0.72 MJ ) did not result in a compensatory decrease in the amount of energy subsequently eaten ( ad lib intake : ' alcohol ' = 2.62 MJ , 0.32 SEM ; ' no alcohol ' = 2.98 MJ , 0.28 SEM ; ' CHO ' = 2.93 MJ , 0.21 SEM ; ' water ' = 2.82 MJ , 0.25 SEM ) , suggesting either no physiological recognition or no regulation of energy consumed within a drink in quantities of less than 1 MJ . The addition of either alcoholic or CHO-containing carbonated beverages into the diet will result , in the short-term , to an overall increase in energy intake In order to evaluate the effects of alcohol on appetite , 12 unrestrained and 10 restrained men ate lunch 20 min after consuming preloads consisting of water , an alcoholic fruit juice ( alcohol ) and a non-alcoholic fruit juice ( juice ) . The unrestrained men ate significantly less after the juice preload , and ate most after alcohol . Intake was not altered significantly in the restrained men . However , both the alcohol and juice preloads reduced rated hunger and increased fullness , relative to the water control , in both restrained and unrestrained men . When the relationship between rated appetite and intake within the test meal was modelled mathematically , it was found that hunger increased more during the initial stages of the test meal in the unrestrained men who had consumed alcohol than in any other condition . No such effects were seen in the restrained subjects . Overall , these results suggest that alcohol has a complex action on appetite , which includes some form of appetite stimulation , and this may explain the excess energy intake reported previously in moderate alcohol consumers |
10,912 | 28,807,638 | Fruits and vegetables were the most research ed dietary component on the lunch tray and yielded the greatest amount of waste across studies . | BACKGROUND Food waste studies have been used for more than 40 years to assess nutrient intake , dietary quality , menu performance , food acceptability , cost , and effectiveness of nutrition education in the National School Lunch Program ( NSLP ) .
OBJECTIVE Describe methods used to measure food waste and respective results in the NSLP across time . | BACKGROUND Soyfoods provide healthful options for school breakfasts and lunches that are lower in saturated fat , cholesterol , fat , and calories and can help meet dem and s for vegetarian choices . Research ers tested acceptance of soy-based options substituted for popular lunch items with a diverse student population . METHODS Research ers conducted a plate waste study in 5 middle schools in Montgomery County , Maryl and , to test the comparability of soy-based alternatives to 4 popular meat-based menu items . Initially , students ranked taste , appearance , and texture of 15 soyfoods to narrow to " hybrid " beef patties , soy-based nuggets , soy-based chicken-less slices , and soy macaroni and cheese . After the meal , trained observers r and omly tagged and collected trays with and without test items and weighed leftover entrées . Research ers used a proportional odds model to compare amounts and proportions of food consumed , and a mixed model to account for differences between schools . RESULTS Students consumed the same amount of soy-based and traditional patties , nuggets , and pasta , and less soy than regular chicken in the salad ( odds ratio 0.122 , p value < .0001 ) . Students consumed higher proportions ( p value < .05 ) of traditional chicken nuggets , beef patties , chicken slices , and pasta compared to soy-based alternative products . On average , soy-based entrées had fewer calories ; less total fat , saturated fat , and cholesterol ; and more iron , fiber , and sodium compared to traditional menu items . CONCLUSIONS This study indicates that middle school students readily consume almost equal numbers of soy-based products compared to popular school lunch items . Soyfoods provide nutritional advantages Recent changes in nutrition st and ards for the National School Lunch and School Breakfast Programs assume that modification of the nutritional serving practice s of school cafeterias will result in improved childhood nutrition in the school environment . The primary aim of this paper is to summarize the findings from two recent cluster r and omized controlled trials ( Wise Mind and LA Health ) that tested the hypothesis that modification of school cafeteria environments , including changes in nutrition st and ards , would yield beneficial changes in childhood nutrition and healthy eating in the school lunch environment . A secondary aim was to investigate the association of participant characteristics and changes in nutrition and healthy eating . A third aim was to investigate the relationships between the food intake of children and : ( 1 ) foods selected by the children and ( 2 ) food that was uneaten during the lunch meal ( plate waste ) . The studies used similar approaches for modifying the school cafeteria environment and both studies used the digital photography method to measure changes in food intake , food selection , and plate waste . Both studies reported significant improvements in childhood nutrition , and the LA Health study reported improved healthy eating , following introduction of the cafeteria modification program in comparison to baseline and /or control arms . These studies confirm the hypothesis that interventions that modify the school cafeteria environment can beneficially impact childhood nutrition Project FIT was a two-year multi-component nutrition and physical activity intervention delivered in ethnically-diverse low-income elementary schools in Gr and Rapids , MI . This paper reports effects on children ’s nutrition outcomes and process evaluation of the school component . A quasi-experimental design was utilized . 3rd , 4th and 5th- grade students ( Yr 1 baseline : N = 410 ; Yr 2 baseline : N = 405 ; age range : 7.5–12.6 years ) were measured in the fall and spring over the two-year intervention . Ordinal logistic , mixed effect models and generalized estimating equations were fitted , and the robust st and ard errors were utilized . Primary outcomes favoring the intervention students were found regarding consumption of fruits , vegetables and whole grain bread during year 2 . Process evaluation revealed that implementation of most intervention components increased during year 2 . Project FIT result ed in small but beneficial effects on consumption of fruits , vegetables , and whole grain bread in ethnically diverse low-income elementary school children BACKGROUND It is often assumed that children avoid fruit in school cafeterias because of higher relative prices and preferences for other foods . Interviews with children reveal that eating whole fresh fruit can be difficult for those with small mouths or braces . Older girls find whole fruits messy and unattractive to eat . PURPOSE To determine the effect of offering pre-sliced fruit in schools on selection and intake . DESIGN Three of six schools were assigned r and omly to serve apples in slices . Three control schools served apples whole . Selection , consumption , and waste of apples were measured prior to and during treatment . SETTING / PARTICIPANTS Cafeterias in six public middle schools in Wayne County NY in 2011 . Participants included all students who purchased lunch on days when data were collected . INTERVENTION Treatment schools were provided with a st and ard commercial fruit slicer , and cafeteria staff members were instructed to use it when students requested apples . Trained research ers recorded how much of each apple was consumed and how much was wasted in both control and treatment schools . MAIN OUTCOME MEASURES Daily apple sales , percentage of an apple serving consumed per student , and percentage of an apple serving wasted per student . RESULTS Data were analyzed in 2012 . Schools that used fruit slicers to pre-slice fruit increased average daily apple sales by 71 % compared to control schools ( p<0.01 ) . The percentage of students who selected apples and ate more than half increased by 73 % ( p=0.02 ) at schools that served pre-sliced fruit , and the percentage that wasted half or more decreased by 48 % ( p=0.03 ) . CONCLUSIONS Sliced fruit is more appealing to children than whole fruit because it is easier and tidier to eat . This study applies the principle of convenience from behavioral economics and provides an example of a scalable , low-cost environmental change that promotes healthy eating and decreases waste OBJECTIVE We sought to characterize student receptivity to new menu offerings in the Los Angeles Unified School District by measuring the levels of fruit and vegetable waste after implementation of changes to the school lunch menu in fall 2011 . METHODS We measured waste at four r and omly selected middle schools in the school district , using two sources : a ) food prepared and left over after service ( production waste ) ; and b ) food that was selected but not eaten by students ( plate waste ) . RESULTS 10.2 % of fruit and 28.7 % of vegetable items prepared at the four schools were left over after service . Plate waste data , collected from 2228 students , suggest that many of them did not select fruit ( 31.5 % ) or vegetable ( 39.6 % ) items . Among students who did , many threw fruit and vegetable items away without eating a single bite . CONCLUSIONS Our findings suggest that fruit and vegetable waste was substantial and that additional work may be needed to increase student selection and consumption of fruit and vegetable offerings . Complementary interventions to increase the appeal of fruit and vegetable options may be needed to encourage student receptivity to these healthier items in the school meal program OBJECTIVE To assess whether a Smarter Lunchroom intervention based on behavioural economics and adapted for students with intellectual and developmental disabilities would increase the selection and consumption of fruits , vegetables and whole grains , and reduce the selection and consumption of refined grains . DESIGN The 3-month intervention took place at a residential school between March and June 2012 . The evaluation employed a quasi-experimental , pre-post design comparing five matched days of dietary data . Selection and plate waste of foods at lunch were assessed using digital photography . Consumption was estimated from plate waste . SETTING Massachusetts , USA . SUBJECTS Students ( n 43 ) aged 11 - 22 years with intellectual and developmental disabilities attending a residential school . RESULTS Daily selection of whole grains increased by a mean of 0·44 servings ( baseline 1·62 servings , P = 0·005 ) and refined grains decreased by a mean of 0·33 servings ( baseline 0·82 servings , P = 0·005 ) . The daily consumption of fruits increased by a mean of 0·18 servings ( baseline 0·39 servings , P = 0·008 ) , whole grains increased by 0·38 servings ( baseline 1·44 servings , P = 0·008 ) and refined grains decreased by a mean of 0·31 servings ( baseline 0·68 servings , P = 0·004 ) . Total kilojoules and total gram weight of food selected and consumed were unchanged . Fruit ( P = 0·04 ) and vegetable ( P = 0·03 ) plate waste decreased . CONCLUSIONS A Smarter Lunchroom intervention significantly increased whole grain selection and consumption , reduced refined grain selection and consumption , increased fruit consumption , and reduced fruit and vegetable plate waste . Nudge approaches may be effective for improving the food selection and consumption habits of adolescents and young adults with intellectual and developmental disabilities IMPORTANCE Little is known about the long-term effect of a chef-enhanced menu on healthier food selection and consumption in school lunchrooms . In addition , it remains unclear if extended exposure to other strategies to promote healthier foods ( eg , choice architecture ) also improves food selection or consumption . OBJECTIVE To evaluate the short- and long-term effects of chef-enhanced meals and extended exposure to choice architecture on healthier school food selection and consumption . DESIGN , SETTING , AND PARTICIPANTS A school-based r and omized clinical trial was conducted during the 2011 - 2012 school year among 14 elementary and middle schools in 2 urban , low-income school districts ( intent-to-treat analysis ) . Included in the study were 2638 students in grade s 3 through 8 attending participating schools ( 38.4 % of eligible participants ) . INTERVENTIONS Schools were first r and omized to receive a professional chef to improve school meal palatability ( chef schools ) or to a delayed intervention ( control group ) . To assess the effect of choice architecture ( smart café ) , all schools after 3 months were then r and omized to the smart café intervention or to the control group . MAIN OUTCOMES AND MEASURES School food selection was recorded , and consumption was measured using plate waste methods . RESULTS After 3 months , vegetable selection increased in chef vs control schools ( odds ratio [ OR ] , 1.75 ; 95 % CI , 1.36 - 2.24 ) , but there was no effect on the selection of other components or on meal consumption . After long-term or extended exposure to the chef or smart café intervention , fruit selection increased in the chef ( OR , 3.08 ; 95 % CI , 2.23 - 4.25 ) , smart café ( OR , 1.45 ; 95 % CI , 1.13 - 1.87 ) , and chef plus smart café ( OR , 3.10 ; 95 % CI , 2.26 - 4.25 ) schools compared with the control schools , and consumption increased in the chef schools ( OR , 0.17 ; 95 % CI , 0.03 - 0.30 cups/d ) . Vegetable selection increased in the chef ( OR , 2.54 ; 95 % CI , 1.83 - 3.54 ) , smart café ( OR , 1.91 ; 95 % CI , 1.46 - 2.50 ) , and chef plus smart café schools ( OR , 7.38 , 95 % CI , 5.26 - 10.35 ) compared with the control schools , and consumption also increased in the chef ( OR , 0.16 ; 95 % CI , 0.09 - 0.22 cups/d ) and chef plus smart café ( OR , 0.13 ; 95 % CI , 0.05 - 0.19 cups/d ) schools ; however , the smart café intervention alone had no effect on consumption . CONCLUSIONS AND RELEVANCE Schools should consider both collaborating with chefs and using choice architecture to increase fruit and vegetable selection . Efforts to improve the taste of school foods through chef-enhanced meals should remain a priority because this was the only method that also increased consumption . This was observed only after students were repeatedly exposed to the new foods for 7 months . Therefore , schools should not ab and on healthier options if they are initially met with resistance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT02309840 The object of this study was to determine whether students attending schools with self-service salad bars consume a greater amount of fruits and vegetables compared with students using preportioned servings and to evaluate the relationship between number of items offered and fruit and vegetable consumption . Two hundred ninety-four students in first through fifth grade were r and omly selected from two schools with salad bars and two with preportioned servings . Weights of fruit and vegetable items were measured pre- and postconsumption and interobserver agreement + /-1 g was > or = 95 % . Presence of a salad bar was not associated with greater fruit and vegetable consumption . Fruit and vegetable consumption was positively related to the number of fruit and vegetable items offered at salad bars ( P < .05 ) , adjusting for sex and grade . Fruit and vegetable variety was associated with elementary school-age children 's fruit and vegetable consumption when using salad bars OBJECTIVE To examine the effects of a multi-component , theory-based , 2.5-year intervention on children 's fruit and vegetable consumption , preferences , knowledge and body mass index . METHODS Four inner city elementary schools in the Northeastern United States were r and omized to an intervention ( n=149 ) or control group ( n=148 ) in 2005 . Fruit and vegetable consumption during school lunch ( measured by plate waste ) , preferences , and knowledge , as well as body mass index , were assessed five times across 3.5 years ( pre-intervention , spring 2006 , 2007 , 2008 and 2009 ) . Hierarchical linear modeling was used to analyze program outcomes . RESULTS At the first post-test assessment , children in the experimental group ate 0.28 more servings/lunch of fruit and vegetable relative to children in the control group and changes in fruit and vegetable consumption were found in each year throughout the program . However , this effect declined steadily across time so that by the delayed one-year follow-up period there was no difference between the groups in fruit and vegetable consumption . There were persistent intervention effects on children 's knowledge . There were no effects on fruit and vegetable preferences and body mass index throughout the study . CONCLUSION Although there was initial fruit and vegetable behavior change , annual measurements indicated a gradual decay of behavioral effects . These data have implication s for the design of school-based fruit and vegetable interventions |
10,913 | 26,621,809 | Evidence for CPFA in severe sepsis is sparse , of poor quality and further research is required , however , this meta- analysis noted improvements in survival rates of those patients treated with CPFA | INTRODUCTION Coupled plasma filtration and adsorption ( CPFA ) has been used in the treatment of severe sepsis with the intention of removing the proinflammatory and anti-inflammatory mediators from the systemic circulation .
It is believed that this interrupts and moderates the septic cascade , but there is uncertainty about the benefits of this therapy . | Objective To test the hypothesis that nonselective plasma adsorption by a hydrophobic resin ( coupled plasmafiltration and adsorption ) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock . Design Prospect i ve , pilot , crossover clinical trial . Setting General intensive care unit in a teaching hospital . SubjectsTen patients with hyperdynamic septic shock . Interventions Patients were r and omly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis ( treatment A ) or continuous venovenous hemodiafiltration ( treatment B ) in r and om order . We measured the change in mean arterial pressure , norepinephrine requirements , and leukocyte tumor necrosis factor-&agr ; ( TNF-&agr ; ) production ( both spontaneous and lipopolysaccharide-stimulated ) after 10 hrs of each treatment . We also tested TNF-&agr ; production from normal human adherent monocytes incubated with patients ’ plasma obtained before and after the resin , both with or without incubation with an anti-interleukin-10 monoclonal antibody . Results Mean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B ( p = .001 ) . There was an average decrease of norepinephrine requirement of 0.08 & mgr;g/kg/min with treatment A and 0.0049 & mgr;g/kg/min with treatment B ( p = .003 ) . All patients but one survived . Spontaneous and lipopolysaccharide-induced TNF-&agr ; production from patients ’ whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device ( plasmafiltrate-sorbent plus hemodialyzer ) ( p = .009 ) . Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-&agr ; by 1 × 106 cultured adherent monocytes from healthy donors . This suppressive effect was significantly reduced after passage of plasma through the resin ( p = .019 ) and after incubation with anti-interleukin-10 monoclonal antibodies ( p = .028 ) . Conclusions In patients with septic shock , coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration . This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide . These findings suggest a potential role for blood purification in the treatment of septic shock In a prospect i ve non-r and omized trial , 59 patients with sepsis ( n = 43 ) and SIRS ( n = 16 ) were treated on a surgical intensive care unit . In 22 patients plasmapheresis in combination with continuous venovenous hemofiltration ( CVVHF ) was administered . Lethality was 56 % in the sepsis group ; in the therapy group lethality was significantly lower in patients with plasmapheresis , even though in this population the organic failure rate was higher . Finally the dependency of lethality and age was similar in both groups . Lethality at 22 % in the plasmapheresis group with double organ failure was significantly lower ( P > 0.01 ) than in controls . Reduction of lethality seemed to be as high as 18 % in patients with sepsis , while patients with SIRS did not profit from the additional therapy . A prospect i ve r and omized trial in sepsis and double organic failure should be projected Aim : The aim of this study was to observe the effects of coupled plasma filtration adsorption ( CPFA ) on septic patients with multiple organ dysfunction syndrome ( MODS ) . Methods : A total of 14 patients were r and omly divided into two groups , and , respectively , received 10 h of CPFA or high-volume hemofiltration ( HVHF ) . The mean arterial pressure ( MAP ) , electrolytes and acid – base balance , the sequential organ failure assessment ( SOFA ) score , and the acute physiology and chronic health evaluation II ( APACHE II ) score were analyzed . Serum levels of high-mobility group box-1 ( HMGB-1 ) protein , tumor necrosis factor-α ( TNF-α ) , and intercellular adhesion molecule-1 ( ICAM-1 ) were also measured by enzyme-linked immunosorbent assay . Results : After CPFA and HVHF , temporary reduction in blood urea nitrogen and serum creatinine , electrolytes and acid – base metabolism balance were well maintained . Both the SOFA and the APACHE II scores were markedly reduced after CPFA ( p < 0.01 ) , while only the SOFA score was significantly decreased after HVHF ( p < 0.05 ) . After 10-h treatment with CPFA , the MAP and oxygen index ( PaO2/FiO2 ) were significantly higher than those at 0 h. Furthermore , the serum levels of HMGB-1 , ICAM-1 , and TNF-α decreased after 10 h of CPFA ( p < 0.05 ) , while the serum levels of HMGB-1 declined at 5 h of HVHF , but rebounded at 10 h , and the serum levels of TNF-α and ICAM-1 were no significant change after treatment with HVHF . Conclusions : The study indicated that CPFA could be superior to HVHF in improving the clinical manifestations and eliminating inflammatory mediators , which had implication s in the optimal treatment of septic patients with MODS Objective The objective was to examine the effect of repeated applications of coupled plasmafiltration-adsorption on the hemodynamic response in septic shock patients hospitalized in intensive care units ( ICUs ) . Design Prospect i ve , intention-to-treat . Setting General ICU of a tertiary care , non-teaching , 400-bed , city hospital . Patients and participants Twelve consecutive mechanically ventilated septic shock patients , with or without concomitant acute renal failure (ARF).InterventionA median of 10 consecutive sessions ( prescribed treatment time : 10 h/session ; delivered duration : 8.43±1.37 h/min ) of coupled plasmafiltration-adsorption for each patient . Measurements and results Mean arterial pressure ( 77.2±12.5 [ CI 95 % ; 74.5–79.8 ] vs. 83.3±14.1 [ CI 95 % ; 80.3–86.3 ] mm Hg ; [ p<0.001 ] ) , cardiac index ( 4.03±0.89 [ CI 95 % ; 3.83–4.22 ] vs. 3.46±0.82 [ CI 95 % ; 3.28–3.64 ] L/m2/min ; [ p<0.001 ] ) , systemic vascular resistance index ( 1,388±496 [ CI 95 % ; 1,278–1,497 ] vs. 1,753±516 [ CI 95 % ; 1,639–1,867 ] dynes × s/cm5 ; [ p<0.001 ] ) , PO2/FIO2 ratio ( 204±87 [ CI 95 % ; 185–223 ] vs. 238±82 [ CI 95 % ; 220–256 ] ; [ p<0.001 ] ) , significantly improved during 100 global treatments ( pre- vs. post-treatment values ) . Intra-thoracic blood volume and extra-vascular lung water did not change across treatments . Vasopressor requirement was reduced : norepinephrine decrease from an infusion rate of 0.13±0.07 ( CI 95 % ; 0.06–0.16 ) to 0 γ/kg/min after a mean of 5.3±2.7 sessions . C reactive protein ( CRP ) significantly decreased ( from 29.3±7.3 vs. 7.9±4.8 ; p<0.0001 ) during treatment . Survival was 90 % at day 28 and 70 % at day 90 . Conclusion Coupled plasmafiltration-adsorption was a feasible and safe extracorporeal treatment and exerted a remarkable improvement in the hemodynamics , the pulmonary function , and the outcome in septic shock patients with or without concomitant ARF ABSTRACT Early compliance with the sepsis resuscitation bundle has been suggested to reduce mortality . However , few data are available about the impact of late compliance with the bundle on outcomes . The aim of this study was to assess whether the completion of the resuscitation bundle within the first 6 h after admission to the intensive care unit ( ICU ) , but beyond the specific time limit of the various bundle interventions , is related to an improvement in survival . This prospect i ve , cohort study included 753 patients recruited from September 2005 until August 2010 with severe sepsis/septic shock in the three medical-surgical ICUs of a tertiary academic medical center . We assessed the compliance with the different tasks included in the resuscitation bundle . Furthermore , we ascertained within the first 6 h after ICU admission the compliance with those tasks not carried out within their specific time limits ; we have termed this variable “ bundle improvement in the ICU . ” Septic shock was present in 88.1 % . The overall in-hospital mortality was 31.6 % . In 51.5 % , there was bundle improvement in the ICU ; this variable was associated with a lower risk of mortality ( adjusted hazard ratio , 0.52 [ 95 % confidence interval , 0.34–0.78 ] ) . That association was observed only when the time from severe sepsis onset to ICU admission was 6 h or less . Importantly , similar results were found after excluding all patients with severe sepsis ( rapid responders ) and those with refractory shock ( nonresponders ) . The task with highest improvement was the achievement of central venous oxygen saturation 70 % or greater in 39 % of patients . Compliance with the resuscitation bundle even beyond the recommended time is associated with improvement in survival in patients with severe sepsis/septic shock Despite the use of potent antibiotics and intensive supportive care , the mortality among patients with sepsis and Gram-negative bacteremia remains high . In recent years , endotoxin adsorption therapy ( PMX-DHP , polymyxin-direct hemoperfusion ) has been widely used in Japan to remove endotoxin , a causative agent of sepsis . In septic patients whose clinical condition may change at any moment , the decision of when to perform blood purification in addition to conventional intensive care is a critical factor in the therapeutic strategy and prognosis . In the present study , we investigated the effect over time of PMX-DHP in sepsis . The subjects were 16 patients with systemic inflammatory response syndrome ( SIRS ) who required surgical treatment including a surgical operation and drainage . The following six parameters were compared between the first and second PMX-DHP : mean blood pressure and time-restricted urine at four time points - at baseline and at 6 , 24 and 72 h after PMX-DHP ; and white blood cell count , platelet count , base excess and Septic Severity Score ( SSS ) at 24 and 72 h after PMX-DHP . Mean blood pressure improved over time up to 24 h after both the first and second PMX-DHP . Time-restricted urine volume improved only at 6 h after the first PMX-DHP . White blood cell count improved over time up to 24 h after both the first and second PMX-DHP . The SSS improved at all time points studied except for 3 days after the second PMX-DHP . We conclude that PMX-DHP is expected to have important implication s in terms of ( i ) correction of clinical conditions ( by severity assessment ) ; ( ii ) improvement of hemodynamics ; ( iii ) possible anti-inflammatory effect ; and ( iv ) possible improvement of oxygen metabolism in tissues Severe sepsis is known to cause multiple organ failure , including renal dysfunction . During sepsis , endotoxin targets the renal proximal tubular cells , the function of which can be evaluated on the basis of urinary N-acetyl-&bgr;-glucosaminidase ( NAG ) . We investigated whether urinary NAG activity is altered in patients with severe sepsis and whether treatment with polymyxin B immobilized fibers ( PMX-F ) affects this activity . Subjects of this study were 120 patients with severe sepsis and 60 healthy volunteers matched for age and gender . Patients were r and omly assigned to one of two treatments : PMX-F treatment ( n = 70 ) or conventional treatment ( n = 50 ) . The plasma endotoxin level was significantly reduced , from 34.6 ± 10.2 to 6.8 ± 2.4 pg/ml ( p < 0.01 ) in patients treated with PMX-F , and the urinary NAG/creatinine ratio was reduced from 46.5 ± 26.8 U/gm to 18.6 ± 13.6 U/gm ( p < 0.01 ) . The plasma endotoxin level and urinary NAG/creatinine ratio were unchanged in patients who received conventional treatment . The increased urinary NAG/creatinine ratio in patients with severe sepsis may reflect proximal tubular dysfunction . PMX-F is effective in reducing proximal tubular dysfunction , in part owing to reduced plasma endotoxin levels Many kinds of blood purifying technologies have been applied to the treatment of critically ill patients since 1979 when plasma exchange with hollow-fiber membranes was developed . These technologies have been applied not only to the removal of toxic substances , but also to the treatment of objective diseases and the removal of the factors relating to the associated inflammation . This article summarizes these methods and their efficacies for critically ill patients , especially those with severe sepsis . Attempts have been made to remove endotoxin , the main cause of sepsis , from the circulation using polymyxin B immobilized fiber , charcoal hemoperfusion , and plasma or whole blood exchange . Attempts have also been made to remove proinflammatory cytokines , eicosanoides , and coagulative factors from the circulation in the human body . Continuous hemofiltration or hemodiafiltration is the representative technology . The efficacy of these methods has been established , but several issues remain unresolved . All methods of the treatment of severe sepsis are discussed with reference to treatment indications , efficacy , and outcome parameters . In particular , the clinical results of endotoxin removal with polymyxin B immobilized fiber are summarized in this article Objective To investigate the effects of coupled plasma filtration adsorption ( CPFA ) on the immune function of patients with multiple organ dysfunction syndrome ( MODS ) . Methods This study was a prospect i ve , pilot , before- and -after self-crossover , clinical trial . Seven patients diagnosed with MODS and severe infection were r and omly allocated to both 10 hours of CPFA and 10 hours of high-volume hemofiltration ( HVHF ) with a 12-hour interval and in r and om order . Serum concentrations of 7 cytokines including tumor necrosis factor-α ( TNF-α ) , interleukin-6 ( IL-6 ) , interleukin-1β ( IL-1β ) , interleukin-10 ( IL-10 ) , interleukin-1 receptor antagonist ( IL-1Ra ) , and soluble tumor necrosis factor receptors 1 and 2 ( sTNFR1 and sTNFR2 ) were measured during each treatment . The HLA-DR expression by the blood monocytes and the TNF-α production by the patients ’ blood ( both spontaneous and lipopolysaccharide stimulated ) were tested before and after the treatment . TNF-α production of normal human monocytes ( THP-1 cells ) incubated in vitro with the patient plasma was also measured . Results During CPFA , the fall in serum TNF-α and rise in serum IL-1Ra coincided with the rise in ratios of sTNFR2/TNF-α and IL-1Ra/IL-1β ( p<0.05 ) , which were different from those seen within HVHF ( p<0.05 ) . HLA-DR expression increased after CPFA ( 84.32 % ± 4.63 % vs. 73.65 % ± 11.52 % , p=0.037 ) , but there was no change after HVHF ( p>0.05 ) . Spontaneous and lipopolysaccharide-induced TNF-α production increased over time with CPFA ( p=0.038 , p=0.034 , respectively ) , but did not change with HVHF ( p>0.05 ) . Patient plasma suppressed the production of TNF-α by cultured normal monocytes . This effect decreased over time with CPFA ( p=0.041 ) , but there was no effect with HVHF ( p>0.05 ) . Conclusions CPFA was superior to HVHF in increasing the ratios of antiinflammatory to proinflammatory mediators , improving antigen presentation ability , and restoring leukocyte responsiveness . These findings suggest a potential role for CPFA in the treatment of MODS We explored the effects of norepinephrine on blood flow distribution and oxygen extraction capabilities during hyperdynamic endotoxic shock . Twelve anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin followed by a general saline infusion and were then r and omly divided into two groups : six received norepinephrine ( 1 microg/kg/min ) , and six served as control subjects . The norepinephrine group maintained higher mean arterial pressure , cardiac index , left ventricular stroke work index , and hepatic arterial blood flow without altering blood flow to portal , mesenteric , and renal beds . When cardiac tamponade was induced to study tissue oxygen extraction capabilities , the norepinephrine group had a lower critical oxygen delivery in whole body ( 11.5 + /- 5.2 versus 14.3 + /- 1.4 ml/kg/min , p < 0.05 ) and in liver ( 25.0 + /- 11.3 versus 38.0 + /- 9.0 ml/min , p = NS ) and a higher critical oxygen extraction ratio in whole body ( 53.8 + /- 17.7 versus 32.0 + /- 6.1 % , p < 0.05 ) , and in liver ( 57.0 + /- 11.9 versus 35.2 + /- 4.3 % , p < 0.05 ) . We conclude that during endotoxic shock in dogs , norepinephrine hardly influences blood flow distribution and could even increase hepatic artery blood flow , and it can also improve whole body and liver oxygen extraction capabilities |
10,914 | 23,375,662 | Risk factors emerging most frequently as independent predictors of pressure ulcer development included three primary domains of mobility/activity , perfusion ( including diabetes ) and skin/pressure ulcer status .
Skin moisture , age , haematological measures , nutrition and general health status are also important , but did not emerge as frequently as the three main domains .
There is limited evidence that either race or gender is important .
Overall there is no single factor which can explain pressure ulcer risk , rather a complex interplay of factors which increase the probability of pressure ulcer development . | OBJECTIVE To identify risk factors independently predictive of pressure ulcer development in adult patient population s ? | Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items OBJECTIVES To compare black and white nursing home residents with respect to the incidence of nursing home (NH)-acquired pressure ulcers ( PUs ) and to examine the role of resident characteristics and facility characteristics in explaining differences between the racial groups . DESIGN Prospect i ve cohort study conducted between 1992 and 1995 . SETTING Fifty-nine Maryl and NHs . PARTICIPANTS A total of 1,938 residents ( 301 black , 1,637 white ) aged 65 and older newly admitted to participating NHs . MEASUREMENTS The outcome variable was the first occurrence of a Stage 2 , 3 , or 4 PU as determined based on medical record review . The predictor variable was race ( black , white ) . Eight resident characteristics ( age , sex , number of activity of daily living dependencies , bedfast , PU on admission to facility , incontinence , dementia , and whether the resident was on Medicaid ) and three facility characteristics ( number of beds , for-profit ownership status , and urban/nonurban location ) were considered as possible confounding variables . RESULTS The incidence of PUs was 0.38 per person-year in the NH . The rate for blacks was significantly higher than for whites ( 0.56 vs 0.35 per person-year ) ( P<.001 ) . In multivariate analysis , controlling for eight resident characteristics and three facility characteristics , race was significantly associated with PU incidence ( hazard ratio comparing blacks with whites=1.31 , 95 % confidence interval=1.02 - 1.66 ) . CONCLUSION Blacks have a higher incidence of NH-acquired PUs than whites ; resident characteristics appear to mediate the higher risk . Future research should aim to identify modifiable factors that explain differences between racial groups in PU risk and to develop solutions to prevent the suffering and cost associated with PUs Patients undergoing surgery are prone to develop pressure ulcers during surgery . The aim of this study was to identify pressure ulcer risk indicators in patients undergoing surgery which lasted more than four hours . A prospect i ve follow-up study was conducted in 208 patients . Data on presence or absence of pressure ulcers and risk indicators were collected preoperatively , during surgery , and postoperatively . The results show that of the many indicators recorded , the only predictor of pressure ulcers was length of surgery . Because it is not possible to influence the length of the surgery , prevention should primarily be aim ed at decreasing pressure and shearing forces during surgery The purpose of this prospect i ve study was to determine the incidence of pressure ulcers and to examine factors related to pressure ulcer development in patients in an acute care setting . Adult medical and surgical patients who were free of pressure ulcers at admission were assessed within 36 hours of admission and then three times per week for 2 weeks or until discharge . Instruments included a demographic data form , a skin assessment form , and the Braden Scale for Predicting Pressure Sore Risk . Most subjects had 46 assessment s completed . The sample consisted of 149 subjects , with a pressure ulcer incidence rate of 13.4 % ( n = 20 ) . Subjects who acquired pressure ulcers had lower hemoglobin levels ( t = 2.17 , p = 0.03 ) , spent more time in bed ( t = 3.90 , p = 0.0001 ) , and spent less time in a chair ( t = 3.2 , p = 0.002 ) than those who did not acquire pressure ulcers . A stepwise logistic regression analysis was used to calculate risk of pressure ulcer development . In the final model , hemoglobin level and hours spent in bed continued to be predictors of pressure ulcer development ( chi 2 = 9.306 , df = 2 , p = 0.0095 ) . All 20 subjects who acquired pressure ulcers were further categorized into groups with stage I ( n = 12 ) or stage II ( n = 8) ulcers . Patients with stage I pressure ulcers were primarily receiving post-surgical care ( 67 % ) , whereas patients who acquired stage II ulcers had medical conditions that affected tissue perfusion , such as respiratory diseases ( 50 % ) and diabetes mellitus ( 12 % ) DESIGN Nonexperimental-Descriptive . SAMPLE The inclusion criteria were trauma patients , ages 15 and older , who were hospitalized for > 2 days , and who did not have preexisting skin breakdown . A total of 148 consecutive trauma patients admitted to the study institution meeting the inclusion criteria were prospect ively enrolled . METHODS Patients were assessed every 3 days for skin breakdown . Information on the patient 's bed type , therapies , medical devices , and nutrition was collected . The Braden Scale for predicting pressure ulcer risk was completed at each assessment . FINDINGS Of the 148 patients enrolled , 30 developed at least one area of skin breakdown for a prevalence of 20.3 % in patients hospitalized more than 2 days . The most common cause of breakdown was positional pressure ( 47.4 % ) . Cervical collars were the second leading cause at 23.7 % , followed by tracheostomy/endotracheal tubes at 10.5 % . The mobility subscale of the Braden Pressure Ulcer Risk Assessment tool was significantly predictive of skin breakdown ( p < .001 ) . IMPLICATION S FOR NURSING RESEARCH Skin breakdown is a significant problem in trauma patients who are hospitalized for more than 2 days . Aggressive protocol s on positioning , cervical collar use , and airway adjuncts , as well as additional active nursing interventions for immobile patients , may be ways to decrease the skin breakdown prevalence in this population Previously healthy , critically injured survivors of serious trauma are at risk for developing pressure ulcers . A prospect i ve , descriptive , clinical research study was design ed to identify the factors associated with the incidence , number , stage , and location of pressure ulcers and to assess the predictive validity of the Braden Scale for Predicting Pressure Sore Risk in this population . A sample of 36 patients was assessed biweekly throughout hospitalization and showed a pressure ulcer incidence of 30.6 % . The small sample size in this study precludes generalization of results . However , several findings have potential implication s for clinical practice if they can be replicated in larger studies . Total Braden Scale scores were lower for all assessment points in all subjects who developed pressure ulcers . Subscale scores varied in predictive ability from 100 % to 0 % . Logistic regression using the first two assessment points produced a model that combined mobility and moisture subscale scores . This model correctly predicted 77.78 % of those subjects who developed pressure ulcers This experimental study was design ed to identify the etiology of pressure ulcers in a surgical sample and to evaluate a special OR mattress overlay in preventing pressure ulcer development . Surgical patients ( N = 413 ) were r and omized to receive " usual perioperative care " or the new mattress overlay . Over six postoperative days , 89 patients ( 21.5 % ) developed pressure ulcers , primarily stage I. Only 2 % developed stage II or IV ulcers . Patients with ulcers were statistically older , had diabetes , were smaller in body mass , had lower Braden Scale scores on admission , and used the new mattress overlay ( P < .02 ) . Pressure ulcers that presented as " burns " or ecchymosis did not deteriorate to stage III or IV ulcers during the study . The mattress overlay was not effective in preventing pressure ulcer development AIMS To determine the incidence of pressure ulcers occurring at least 48 hours after admission and risk factors for pressure ulcers grade 2 - 4 in a long-stay surgical Intensive Care Unit ( ICU ) population . BACKGROUND The incidence of pressure ulcers in intensive care units is larger than in non-intensive environments . DESIGN Prospect i ve descriptive research design . METHODS Using pressure ulcers grade 2 - 4 as an outcome measure , a multivariate logistic regression analysis was used to identify the risk factors . Data were obtained on a daily basis in a surgical intensive care unit of the University Hospital Leuven between November 2003-March 2004 . A total of 520 long-stay ( > or= 24 hours ) intensive care patients were included . RESULTS Cumulative incidence of pressure ulcers grade 2 - 4 was 20.1 % . The following variables were positively associated with pressure ulcers grade 2 - 4 : history of vascular disease , treatment with Dopamine or Dobutamine , intermittent haemodialysis ( IHD ) or continuous veno-venous haemofiltration ( CVVH ) , mechanical ventilation . Also preventive measures were statistically positively associated with pressure ulcers grade 2 - 4 : turning , floating heels , alternating mattresses , adequate prevention . The use of sedatives , body temperature above 38.5 degrees C and sitting in chair where negatively associated with pressure ulcers . Pressure ulcers are statistically associated with different risk factors and preventive measures . CONCLUSION The identified risk factors are eligible to be included in a new risk assessment scale for patients admitted to intensive care units . RELEVANCE TO CLINICAL PRACTICE The novel insights have implication s for risk assessment for patients in intensive care units . Patients admitted to intensive care units have other risk factors for pressure ulcers which are eligible to be included in a new risk assessment scale OBJECTIVE : To estimate the incidence and identify risk factors for lower-extremity pressure ulcers in bedfast older adult patients . DESIGN : Prospect i ve cohort study . SETTING : A 500-bed long-term-care facility in Japan . PATIENTS : A total of 259 patients who were aged 65 years or older , confined to bed , and without lower-extremity pressure ulcers at enrollment participated in the study . MAIN OUTCOME MEASURES : Incidence of occurrence , wound characteristics , and risk factors for lower-extremity pressure ulcers . The incidence of lower-extremity pressure ulcers per 100 person-years was 16.8 ( n = 33 ) . The most common sites of lesions were the toes and heels . Cox regression analysis indicated that 3 factors were independently related to new lower-extremity pressure ulcer risk : low ankle-brachial index value ( hazards ratio 0.075 ; 95 % confidence interval [ CI ] , 0.023 - 0.242 ) , length of bedfast period ( hazards ratio 1.010 ; 95 % CI , 1.004 - 1.015 ) , and male gender ( hazards ratio 2.951 ; 95 % CI , 1.450 - 6.009 ) . Receiver operating characteristic curve analysis showed the area under the curve was 0.760 ( 95 % CI , 0.675 - 0.844 ) for the ankle-brachial index . Therefore , an ankle-brachial index cutoff level of 0.8 provided high sensitivity and adequate specificity . CONCLUSION : Lower-extremity pressure ulcers are a significant problem in bedfast older adult patients aged 65 years or older . Bedfast older adult patients who developed lower-extremity pressure ulcers in this study were believed to have arteriosclerosis ; the patients ' ulcers exhibited features of ischemic ulcers . The findings of the present study suggest that bedfast older adult patients with a low ankle-brachial index value , a long bedfast period , or male gender should be closely monitored for lower-extremity pressure ulcer development on admission to long-term-care facilities . In particular , the ankle-brachial index is recommended as a screening tool in this practice setting This is the last in a series of four articles Prognostic studies include clinical studies of variables predictive of future events as well as epidemiological studies of aetiological risk factors . As multiple similar studies accumulate it becomes increasingly important to identify and evaluate all of the relevant studies to develop a more reliable overall assessment . For prognostic studies this is not straightforward . Box 1 summarises the clinical importance of information on prognostic factors . Many of the issues discussed are also relevant to aetiological studies , especially cohort ones . Some features of prognostic studies lead to particular difficulties for the systematic review er . Firstly , in most clinical prognostic studies the outcome of primary interest is the time to an event , often death . Meta- analysis of such studies is rather more difficult than that for binary data or continuous measurements . Secondly , in many context s the prognostic variable of interest is often one of several prognostic variables . When examining a variable of interest research ers should consider other prognostic variables with which it might be correlated . Thirdly , many prognostic factors are continuous variables , for which research ers use a wide variety of methods of analysis . # # # # Summary points Systematic review s are applicable to all types of research design , and studies of prognostic variables are an important additional area where appropriate methodology should be applied Prognostic variables should be evaluated in a representative sample of patients assembled at a common point in the course of their disease — ideally they should all have received the same medical treatment or been in a r and omised trial When examined critically , a high proportion of prognostic studies are found to be method ologically poor Meta- analysis of published data is hampered by difficulties in extraction of data and variation in the characteristics of the study and patients The poor quality of the published literature is a strong argument in favour OBJECTIVE To identify specific demographic , medical , functional status , and nutritional characteristics that predict the development of stage 2 or greater pressure ulcers among patients whose activity is limited to bed or chair . DESIGN Prospect i ve inception cohort study . SETTING Tertiary care , urban , university teaching hospital . PATIENTS A total of 286 patients fulfilling the following criteria : admitted to the hospital within the previous 3 days , age 55 years or more , expected to be confined to bed or chair for at least 5 days or had a hip fracture , and without a stage 2 or greater pressure ulcer . MAIN OUTCOME MEASURE Time to in-hospital development of a stage 2 or greater pressure ulcer . RESULTS Total cumulative incidence of pressure ulcers was 12.9 % ( n = 37 ) after a median time of 9 days from admission to final skin examination . Age of 75 years or more , dry skin , nonblanchable erythema ( a stage 1 pressure ulcer ) , previous pressure ulcer history , immobility , fecal incontinence , depleted triceps skinfold , lymphopenia ( lymphocyte count < 1.50 x 10(9)/L ) , and decreased body weight ( < 58 kg ) were significantly associated with pressure ulcer development by univariate Kaplan-Meier survival analyses ( P < .05 by log-rank test ) . Risk ratios ( and 95 % confidence intervals ) for predictors ( P < or = .05 ) of pressure ulcer development after multivariable Cox regression analysis included the following : nonblanchable erythema , 7.52 ( 1.00 to 59.12 ) ; lymphopenia , 4.86 ( 1.70 to 13.89 ) ; immobility , 2.36 ( 1.14 to 4.85 ) ; dry skin , 2.31 ( 1.02 to 5.21 ) ; and decreased body weight , 2.18 ( 1.05 to 4.52 ) . The 3-week cumulative incidence of pressure ulcers with none , one , two , or three or more of these characteristics was 0 % , 11.4 % , 39.6 % , and 67.9 % , respectively ( P < .001 by log-rank test ) . CONCLUSIONS These results suggest that nonblanchable erythema , lymphopenia , immobility , dry skin , and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activity is limited to bed or chair The analytical effect of the number of events per variable ( EPV ) in a proportional hazards regression analysis was evaluated using Monte Carlo simulation techniques for data from a r and omized trial containing 673 patients and 252 deaths , in which seven predictor variables had an original significance level of p < 0.10 . The 252 deaths and 7 variables correspond to 36 events per variable analyzed in the full data set . Five hundred simulated analyses were conducted for these seven variables at EPVs of 2 , 5 , 10 , 15 , 20 , and 25 . For each simulation , a r and om exponential survival time was generated for each of the 673 patients , and the simulated results were compared with their original counterparts . As EPV decreased , the regression coefficients became more biased relative to the true value ; the 90 % confidence limits about the simulated values did not have a coverage of 90 % for the original value ; large sample properties did not hold for variance estimates from the proportional hazards model , and the Z statistics used to test the significance of the regression coefficients lost validity under the null hypothesis . Although a single boundary level for avoiding problems is not easy to choose , the value of EPV = 10 seems most prudent . Below this value for EPV , the results of proportional hazards regression analyses should be interpreted with caution because the statistical model may not be valid AIMS AND OBJECTIVES To compare the predictive value of two pressure ulcer risk assessment scales ( Braden and Norton ) and of clinical judgement . To evaluate the impact of effective preventive measures on the predictive validity of the two risk assessment scales . METHODS Of the 1772 participating older patients , 314 were r and omly selected and assigned to the ' turning ' group ; 1458 patients were assigned to the " non-turning " group . Using the Braden and the Norton scale the pressure ulcer risk was scored twice weekly during a four-week period . Clinical assessment was monitored daily . The patients at risk in the " turning " group ( Braden score < 17 or Norton score < 12 ) were r and omly assigned to a two-hour turning schedule or to a four-hour turning schedule in combination with a pressure-reducing mattress . The " non-turning " group received preventive care based on the clinical judgement of the nurses . RESULTS The diagnostic accuracy was similar for both scales . If nurses act according to risk assessment scales , 80 % of the patients would unnecessarily receive preventive measures . The use of effective preventive measures decreased the predictive value of the risk assessment scales . Nurses predicted pressure ulcer development less well than the Braden and the Norton scale . Only activity , sensory perception , skin condition and existence of old pressure ulcers were significant predictors of pressure ulcer lesions . RELEVANCE TO CLINICAL PRACTICE The effectiveness of the Norton and Braden scales is very low . Much needless work is done and expensive material is wrongly allocated . The use of effective preventive measures decreases the predictive value of the risk assessment scales . Although the performance of the risk assessment scales is poor , using a risk assessment tool seems to be a better alternative than relying on the clinical judgement of the nurses Patients in intensive care units ( ICU ) are at high risk of developing pressure sores and the use of pressure sore risk tools has been advocated as a means of identifying patients at risk . A prospect i ve multi-site observational study was conducted to define the incidence of pressure sores , assess two pressure sore risk scales and to define risk factors relevant to intensive care . Patients ( n = 534 ) were assessed for the presence of pressure sores . The Waterlow and Jackson/Cubbin risk scales were completed each day for 314 and 188 of these patients respectively . A total of 75 pressure sores were recorded . Of these , 34 were present on admission . Of the remaining 41 , 16 were classified as Grade 1 and 24 as Grade 2 sores . The pressure sore ( PS ) incidence was 5.2 per cent . Expressed as PS/1000 patient days there were 18.48 pressure sores per 1000 patient days . The ability of the risk scores to predict pressure sores was tested using a Receiver Operating Characteristic ( ROC ) analysis . The association of risk score with pressure sores was analysed using a survival function ( Kaplan Meier ) and variables compared using a logrank test ( Mantel-Cox ) . Factors associated with pressure sore occurrence were developed and tested using a survival regression model . Both risk scales were poor predictors of pressure sores ( ROC curve area approximately 70 per cent for both ) . The factors , coma/unresponsiveness/paralysed & se date d and cardiovascular instability were significantly associated with pressure sores with relative risks of 4.2 and 2.5 respectively . Risk increased as a function of time such that the cumulative risk was 50 per cent at 20 days OBJECTIVE To determine the incidence of pressure ulcers in varied population s , and whether demographic characteristics ( age , gender , race ) and primary diagnosis are factors in pressure ulcer development when the level of risk for developing ulcers is considered . To determine if there is a difference in the type of preventive services prescribed for persons who do or do not develop pressure ulcers when risk is controlled and whether differences can be related to demographic characteristics . DESIGN Cohort study . SETTING Two skilled nursing homes , two university operated tertiary care hospitals , and two Veteran 's Administration Medical Centers ( VAMCs ) in Omaha , NE , Durham , NC , and Chicago , IL . PATIENTS A total of 843 r and omly selected patients more than 19 years of age who did not have pressure ulcers on admission to their place of care . Subjects were 63 % male , 79 % white , and had a mean age of 63 ( + /- 16 ) years . MEASURES A head-to-toe skin assessment for pressure ulcers recording site and stage of ulcers , scores for the Braden Scale for Predicting Pressure Sore Risk , demographic characteristics ( age , sex , race ) , and primary diagnosis and preventive interventions ( turning or repositioning orders and pressure reduction surface ) were documented on the patient record . Observations were made every 48 to 72 hours for a minimum of 1 to a maximum of 4 weeks . MAIN OUTCOME MEASURES Presence/absence and stage of pressure ulcers . MAIN RESULTS One hundred eight of 843 ( 12.8 % ) subjects developed pressure ulcers . The incidence was 8.5 % , 7.4 % , and 23.9 % in tertiary care , VAMCs , and nursing homes , respectively . Logistic regression demonstrated that lower Braden Scale scores , older age and white race predicted pressure ulcers ; gender was not predictive . Primary diagnoses were not significant predictors of pressure ulcer risk when the Braden Scale score was entered into the regression . Prescription of turning was predicted by Braden Scale scores and by white race , whereas prescription of pressure reduction was predicted by Braden Scale scores , white race , and female sex . CONCLUSIONS Risk assessment , rather than diagnoses or demographic characteristics , is recommended as the basis for prescriptive decisions . Risk assessment should cue health care providers to make more judicious use of turning and support surfaces to prevent pressure ulcers . Persons who are at risk for pressure ulcers should have turning and pressure reduction surfaces consistently prescribed and implemented . The costs and goals of preventive prescription for those not at risk for pressure ulcers should be considered In medical research , continuous variables are often converted into categorical variables by grouping values into two or more categories . We consider in detail issues pertaining to creating just two groups , a common approach in clinical research . We argue that the simplicity achieved is gained at a cost ; dichotomization may create rather than avoid problems , notably a considerable loss of power and residual confounding . In addition , the use of a data -derived ' optimal ' cutpoint leads to serious bias . We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a r and omized trial in primary biliary cirrhosis . Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models The purpose of this study was to identify risk factors associated with the presence of pressure ulcer development in adult patients at an intensive care unit hospital in Indonesia . The prospect i ve cohort design was conducted in this study . A total of 105 patients participated and a pressure ulcer developed in 35 patients . The initial analysis identified several variables as significant risk factors for pressure ulcer development ( interface pressure , fecal incontinence , skin moisture , diastolic blood pressure , smoking and body temperature ) . However , when entered into a final multivariate analysis , four factors , interface pressure [ odds ratio ( OR ) 17.6 , 95 % confidence interval ( CI ) 4.1 , 74.3 ] , skin moisture ( OR 8.2 , 95 % CI 2.2 , 30.9 ) , smoking ( 12.7 , 95 % CI 2.8 , 56.7 ) and body temperature ( OR 102.0 , 95 % CI 7.7 , 98.8 ) were found to be significant . The results suggest that interface pressure measured using a multipad pressure evaluator , skin moisture measured by a moisture checker , thermometer for body temperature and smoking status are adequate instruments for the prediction of pressure ulcer development Abstract Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers , healing of existing pressure ulcers , and patient acceptability . Design Pragmatic , open , multicentre , r and omised controlled trial . Setting 11 hospitals in six NHS trusts . Participants 1972 people admitted to hospital as acute or elective patients . Interventions Participants were r and omised to an alternating pressure mattress ( n = 982 ) or an alternating pressure overlay ( n = 990 ) . Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse ; time to development of new pressure ulcers ; proportions of participants developing a new ulcer within 30 days ; healing of existing pressure ulcers ; and patient acceptability . Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse ( 10.7 % overlay patients , 10.3 % mattress patients ; difference 0.4 % , 95 % confidence interval - 2.3 % to 3.1 % , P = 0.75 ) . More overlay patients requested change owing to dissatisfaction ( 23.3 % ) than mattress patients ( 18.9 % , P = 0.02 ) . Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer . Trial registration IS RCT N OBJECTIVE To compare the clinical utility , in terms of incidence of pressure ulcer ( PU ) development , and economic impact of 2 programs of patient surface assignment for PU prevention . DESIGN R and omized controlled clinical trial with economic evaluation . SETTING 30-bed multidisciplinary intensive care unit ( ICU ) , serving as the regional trauma center . PATIENTS 144 consecutive eligible patients at risk for the development of PUs . INTERVENTION PU risk was assessed on admission using the Skin Ulcer Risk Evaluation ( SURE ) Score , and patients were r and omized to either the experimental ( purchase ) or control group ( purchase/rent ) . Based on their SURE Score , patients were assigned a specialty surface if needed . Patients received head-to-toe skin assessment s twice weekly , new PUs were documented , a new SURE Score was calculated , and specialty surfaces were up grade d or down grade d as necessary . OUTCOMES The incidence of PUs by site and severity , and cost . ANALYSES Multivariate logistic regression and decision modeling . RESULTS No significant differences were detected between groups with respect to baseline population characteristics , nor in the development of PUs . Predictors of PU development were ICU length of stay and SURE Score . The experimental ( purchase ) group was the less costly strategy . Under baseline assumptions , surface costs per at-risk patient were $ 76 CDN and $ 171 CDN in the experimental and control groups , respectively . The savings of $ 95 CDN per at-risk patient translates into conservative annual savings of $ 47,500 CDN . CONCLUSIONS Using an objective , risk-based method of patient surface assignment , the authors compared the clinical and economic outcomes of 2 programs of PU prevention . In a direct comparison of alternatives , the strategy that emphasized purchased rather than rented products proved to be the more economical . Finally , this approach illustrates how by prospect ively capturing data on both the costs and consequences of competing alternatives , a more objective and informed decision-making process can result The accurate prediction of pressure ulcer ( PU ) development among hospitalized elderly patients is a complex endeavour . A prospect i ve , longitudinal , cohort study of 330 patients over age 65 in 2 Canadian tertiary-care teaching hospitals and 2 long-term-care facilities examined the association between risk- assessment scores , prevention strategies , and PU incidence . The overall PU incidence rate was 9.7 % , with half of the subjects who developed a PU doing so in the first week of hospitalization . The incidence rate for " at risk " patients ( 10.1 % ) was similar to the rate for " not at risk " patients ( 9.3 % ) . The number of prevention strategies used was related to risk- assessment scores and to PU development . Paradoxically , the incidence rate increased with the number of prevention strategies employed . The total risk- assessment score that appeared to have the best balance of sensitivity ( 69 % ) and specificity ( 55 % ) was 19 . Four of the 6 risk- assessment subscales were associated with PU development . Logistic regression modelling confirmed the univariate results that the number of prevention strategies used was the best single predictor of PU development . The data confirm that predicting PU development for individual patients is difficult at best . Results suggest that use of a risk- assessment scale alone is not sufficient to accurately predict PU development . The clinical judgement and experience of nurses are required in providing supplementary information to st and ard measurement instruments AIMS AND OBJECTIVES The study aim ed to evaluate the predictive validity and accuracy of a new pressure ulcer risk assessment scale in two Indonesia intensive care units ( ICUs ) . BACKGROUND Several risk assessment scales have been design ed to identify patients at risk of developing pressure ulcers in ICU . However , the relative weight of each variable that contributes to pressure ulcer development in these scales is not described to enable design ing of a risk assessment scale . Currently , the risk factors contributing to pressure ulcer development include interface pressure , body temperature and cigarette smoking . DESIGN A prospect i ve cohort study was conducted in two ICUs in Pontianak , Indonesia . METHODS A total of 253 patients were recruited to the study from both hospitals . Data collection included new risk assessment scale [ i.e. the Suriadi and Sanada ( S.S. ) scale ] scoring , demographic , pressure ulcer severity scores ( based on the National Pressure Ulcer Advisory Panel ) and skin condition measures . Using the S.S. scale , trained data collectors scored patients once and assessed the body temperature daily until patients were discharged . Additionally , daily data were also collected in relation to the patient 's skin condition and stage of pressure ulcer . RESULTS Out of the 253 patients , 72 ( 28.4 % ) developed pressure ulcers . In ICU A , the incidence was 27 % ; pressure ulcers developed into stage I ( 41.7 % ) , stage II ( 45.8 % ) , stage III ( 10.4 % ) and stage IV ( 2.1 % ) . In ICU B , the incidence was 31.6 % ; the development of pressure ulcers was 48 % in stage I and 52 % in stage II . Using the predictive validity test , the S.S. scale balanced sensitivity ( 81 % ) and specificity ( 83 % ) at a cut-off score of 4 . The area under the receiver-operating characteristic curve was 0.888 ( confidence interval : 0.84 - 0.93 ) . CONCLUSION The S.S. scale was found to be a valid risk assessment tool to identify the patients at risk of developing pressure ulcers in Indonesia ICU The purpose of this study was to identify prospect ively risk factors for pressure sores and to compare these results with a cross-sectional analysis in the same population . Medical records on all admissions to a chronic care hospital over a 13-month period were review ed . Data on potential risk factors were abstract ed from the initial history , physical examination , nursing assessment , and laboratory studies . Pressure sore status on admission and at three weeks was determined from a st and ardized from completed on all patients with a score . The cross-sectional analysis was performed by comparing patients with and without a pressure sore at the time of admission . The cohort analysis used patients initially without a pressure sore and monitored for a new sore at three weeks . Factors associated with pressure sores on univariate testing were entered into a stepwise logistic regression model . One hundred of the 301 admissions presented with a pressure sore . Factors significantly associated with the presence of a sore were altered level of consciousness ( OR = 4.1 ) , bed- or chair-bound ( OR = 2.4 ) , impaired nutritional intake ( OR = 1.9 ) , and hypoalbuminemia ( OR = 1.8 for 10 mg/mL decrease ) . Of the 185 patients without a pressure sore , 20 ( 10.8 % ) developed a sore . Factors significantly associated with the development of a new pressure sore were a history of cerebrovascular accident ( OR = 5.0 ) , bed- or chair-bound ( OR = 3.8 ) , and impaired nutritional intake ( OR = 2.8 ) . Neither urinary nor fecal incontinence , nor the presence of hypoalbuminemia , was associated with sore development . We have prospect ively identified risk factors for pressure sores . ( ABSTRACT TRUNCATED AT 250 WORDS AIMS AND OBJECTIVE The objective of this study was to identify prognostic factors associated with the development of pressure ulcer lesions ( grade 2 - 4 ) in nursing home patients with non-blanchable erythema . BACKGROUND No studies could be found that identify risk factors for further development of pressure ulcer in patients with non-blanchable erythema . For some patients with non-blanchable erythema , st and ard preventive measures do not suffice to prevent pressure ulcers from deterioration . Identifying these patients beforeh and can considerably contribute to the efficiency of pressure ulcer prevention . DESIGN Secondary data analyses of a previously conducted r and omised controlled trial were performed . METHODS Eighty-four wards of 16 Belgian nursing homes participated in the study . In total , 235 nursing home residents with a grade 1 pressure ulcer ( non-blanchable erythema ) were included . All the residents received st and ard preventive care . Potential prognostic factors were collected using a st and ardised form . The incidence of pressure ulcers was recorded according to the European pressure ulcer classification system . RESULTS The cumulative pressure ulcer incidence was 18.7 % ( 44/235 ) . Hypotension ( relative risk = 3.42 , 95 % CI = 1.56 - 7.49 ) , a history of a cerebral vascular accident ( relative risk = 1.94 , 95 % CI = 1.10 - 3.70 ) and contractures ( relative risk = 2.02 , 95 % CI 1.03 - 3.95 ) were identified as independent predictive factors for developing pressure ulcers . Remarkably , being urinary incontinent decreased the risk of developing a pressure ulcer by 76 % . CONCLUSIONS In nursing home residents with non-blanchable erythema , hypotension , contractures , and a history of cerebral vascular accident were independent risk factors for the development of pressure ulcer lesions . RELEVANCE TO CLINICAL PRACTICE Patients with non-blanchable erythema who have hypotension , contractures or a history of cerebral vascular accident are in need of more intensive preventive measures . Identifying these patients can contribute considerably to a more efficient pressure ulcer prevention policy , result ing in a lower pressure ulcer lesion incidence and in lower costs The aims of the study were to investigate the relationship between nutritional state and the development of pressure sores and to test the hypothesis that supplementary nutritional support might prevent pressure sore development and improve healing . Newly admitted long-term care patients hospitalised for more than 3 weeks were included and r and omised into an experimental and a control group . The nutritional state was evaluated using serum protein analyses , anthropometry and the delayed hypersensitivity skin test . Further , the patients ' condition was assessed weekly using a modified Norton scale . The experimental group received extra nutritional support . Significantly more patients with protein-energy malnutrition had , or developed , pressure sores . Regression analyses indicated albumin , mobility , activity and food intake as predictors for pressure sores . Patients who received extra nutritional support tended to develop fewer pressure sores and to heal existing pressure sores to a greater extent than the control group , although this did not reach statistical significance OBJECTIVE In 2002 the hospital under study implemented a pressure ulcer st and ard care plan . This follow-up study aim ed to determine the prevalence and incidence of pressure ulcers , whether demographic characteristics and medical diagnosis differed between those individuals who did and those who did not develop ulcers and the predictors of pressure-ulcer formation . METHOD The prevalence study used a cross-sectional design , while the incidence study was a prospect i ve cohort study . Participants were scored using the Braden scale and were examined for the presence of pressure ulcers . Those who were ulcer free were monitored twice weekly until they were discharged or for 28 days . RESULTS The prevalence of pressure ulcers was 18.1 % ( 95 % CI : 15.5 - 20.9 % ) , while the incidence was 8.1 % ( 95 % CI : 6.1 - 10.4 % ) . Participants with ulcers were older , had a longer mean length of hospital stay , lower Braden scores and were diagnosed with or had a history of cardiovascular diseases or sepsis . Logistic regression found that the total Braden score was the only significant predictor of pressure ulcers . Compared with scores 16 - 23 , the odds ratios were 7.7 ( 95 % CI : 3.5 - 17.1 , p < 0.001 ) and 12.5 ( 95 % CI : 4.5 - 34.6 , p < 0.001 ) for scores 12 - 15 and 6 - 11 respectively . Demographic characteristics , diagnosis and length of hospital stay were not significant predictors . CONCLUSION The study identified a modest decrease in incidence and improvements in nursing care following the implementation of the care plan . It suggests that Braden scores are predictive of those at-risk of developing pressure ulcers AIMS To determine incidence of pressure ulcers in patients at risk according to the Waterlow scale in intensive care units and to evaluate the effects of risk factors in critically ill patients . BACKGROUND Pressure ulcers continue to be an important health problem that increases the risk of illness and death , extends patients ' length of hospital stay and increases healthcare expenses . DESIGN The study was conducted as a descriptive and prospect i ve study . METHOD The sample consisted of 140 patients . Data were collected using a data collection form , the skin assessment instrument and the Waterlow scale . RESULTS The incidence of pressure ulcers in intensive care unit patients was found to be 14.3 % . The majority of pressure ulcers ( 74 % ) were grade I. The mean length of time for pressure ulcer development was found to be 10.4 ( SD 1.85 ) days . A statistically significant difference was found in the patients for pressure ulcer development according to their level of consciousness , activity , cooperation , length of stay , Waterlow scale score and C-reactive protein level . In the multiple stepwise logistic regression analysis , the most influential factors for pressure ulcer development were determined to be length of stay and activity level . CONCLUSIONS Extra care needs to be taken to prevent pressure ulcer development in intensive care unit patients who have an extended length of stay , are dependent for activities , have high Waterlow scores , are unconscious and are not cooperative . RELEVANCE TO CLINICAL PRACTICE This study determined the incidence of and factors that can affect the development of pressure ulcers in intensive care unit patients who are in a high risk group for the development of pressure ulcers and presented the importance of having Turkish nurses implement interventions directed at these factors The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients . The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients ; 9 wards were r and omly selected for nutritional intervention ( nutritional intervention group ) , consisting of the daily distribution of two oral supplements , with each supplement containg 200 kcal , for 15 d. Pressure ulcer incidence was prospect ively recorded for grade s I ( erythema ) , II ( superficial broken skin ) , and III ( subcutaneous lesion ) for 15 d. Nutritional intake was monitored by using estimates in units of quarters vali date d by comparison with weight measurement . There were 672 subjects older than 65 y , and 295 were in the nutritional intervention group versus 377 in the control group . The patients were similar for age , sex ratio , and C-reactive protein . In comparison with the control group , the nutritional intervention group included more patients with stroke , heart failure , and dyspnea and fewer with antecedent falls , delirium , lower limb fractures , and digestive disease . The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent ( Kuntzman score ) and had a lower serum albumin level . During the trial , energy and protein intakes were higher in the nutritional intervention group ( day 2 : 1081 + /- 595 kcal versus 957 + /- 530 kcal , P = 0.006 ; 45.9 + /- 27.8 g protein versus 38.3 + /- 23.8 g protein in the control group , P < 0.001 ) . At 15 d , the cumulative incidence of pressure ulcers was 40.6 % in the nutritional intervention group versus 47.2 % in the control group . The proportion of grade I cases relative to the total number of cases was 90 % . Multivariate analysis , taking into account all diagnoses , potential risk factors , and the intra-ward correlation , indicated that the independent risk factors of developing a pressure ulcer during this period were : serum albumin level at baseline , for 1 g/L decrease : 1.05 ( 95 % confidence interval : 1.02 to 1.07 , P < 0.001 ) ; Kuntzmann score at baseline , for 1-point increase : 1.22 ( 0.32 to 4.58 , P = 0.003 ) ; lower limb fracture : 2.68 ( 1.75 to 4.11 , P < 0.001 ) ; Norton score < 10 versus > 14 : 1.28 ( 1.01 to 1.62 , P = 0.04 ) ; and belonging to the control group : 1.57 ( 1.03 to 2.38 , P = 0.04 ) . In conclusion , it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements . This intervention was associated with a decreased risk of pressure ulcer incidence OBJECTIVE To evaluate objective parameters and subjective nursing assessment as pressure ulcer risk factors for intensive care unit ( ICU ) patients , and compared them with the performance of a general assessment tool ( Waterlow scale ) . To vali date the newly developed assessment method . METHOD This prospect i ve epidemiological study involved 698 patients admitted to an ICU between April 2001 and December 2004 without pressure ulcers and who stayed in the ICU for more than 72 hours . Objective parameters routinely determined during the first 24 hours in the ICU as well as subjective nursing assessment on admission were analysed for their significance as pressure ulcer risk predictors . RESULTS Of the 698 patients 121 ( 17 % ) developed pressure ulcers in the ICU . With univariate analysis , a variety of objective ly measurable parameters relating to organ dysfunction , circulatory impairment and sepsis showed significant association with the occurrence of pressure ulcers . When multiple logistic regression was performed , subjective nursing skin assessment parameters outweighed these parameters as pressure ulcer risk predictors . A risk function comprised of five skin-related and one other parameter yielded an overall correct pressure ulcer prediction proportion of 84.6 % . With receiver-operator characteristic curve analysis , the area under the curve ( AUC ) was 0.82 . Results were vali date d in 329 patients treated in the same ICU between January 2005 and May 2006 , yielding an AUC of 0.80 . CONCLUSION Nursing skin assessment is an important pressure ulcer risk stratification tool in the ICU despite the availability of a large number of objective ly measureable ICU specific parameters in these patients Background : Studies of risk factors for clinical ly significant pressure ulcers in the hospital have been limited by the small number of study subjects that develop pressure ulcers , result ing in contradictory findings regarding some risk factors . Objective : To determine if three risk factors ( low serum albumin level , fecal incontinence , and confusion ) were significant risk factors when tested in a large data set . Methods : The study design was a longitudinal cohort study using data collected as a component of a multi-site controlled clinical trial . The data were collected at 47 Veterans Affairs Hospitals . 2,771 subjects that required high levels of nursing care were identified to have mobility impairment . Their medical records were abstract ed using a st and ard form to identify a large number of potential risk factors . The subsequent development of stage 2 or greater pressure ulcers was recorded for a maximum of 14 days after admission . Results : 406 patients ( 14.7 % ) subsequently developed at least one stage 2 or greater pressure ulcer over a 2-week period . In a multivariate model , the presence of low albumin levels ( odds ratio OR = 1.40 ) and confusion ( OR = 1.45 ) were both found to be statistically significant risk factors , while fecal incontinence was not . Having a Do Not Resuscitate ( DNR ) order was also a significant risk factor ( OR = 1.55 ) . Two other known risk factors also entered the model : being malnourished ( OR = 1.69 ) and requiring a urinary catheter ( OR = 1.55 ) . Conclusions : This study confirmed confusion and low albumin as pressure ulcer risk factors , but not fecal incontinence . A DNR order was found to be a new pressure ulcer risk factor not previously described in the literature To derive a brief bedside pressure ulcer prediction tool for patients admitted to acute care hospitals , we conducted a prospect i ve study of first pressure ulcer incidence among 1,190 consecutive patients hospitalized in selected wards of a Swiss teaching hospital . Baseline predictors included patient age and items from the Norton and Braden ulcer prediction scales . During follow-up , 170 patients developed new pressure ulcers . The predictive ability of baseline assessment s decayed over time . Occurrence of first pressure ulcer in the 5 days after admission ( 129 events ) was best predicted by patient age ( 5 levels ) , mobility ( 3 levels ) , mental status ( 3 levels ) , and friction/shear ( 3 levels ) . The Fragmment score ( sum of friction , age , mobility , mental status ) was linearly related to pressure ulcer risk , and its area under the receiver operating characteristic curve ( 0.80 ) was higher than for the Norton ( 0.74 ; P = 0.006 ) and Braden ( 0.74 ; P = 0.004 ) scores . This brief pressure ulcer prediction scale performed well in an acute care setting . Use of this scale may facilitate the implementation of pressure ulcer prevention interventions OBJECTIVE To provide data needed to design an intervention trial to prevent or treat skin disorders in a high risk , incontinent nursing home population . DESIGN The incidence and prevalence of nine common skin disorders were measured prospect ively over a 60-day period using trained observers . Urinary and fecal incontinence frequency were measured over 24 hours , and mobility was measured with subjects both in and out of bed . Direct measures of skin moisture were taken with an impedance device in the presence and absence of urinary incontinence . Multiple regression analyses were used to relate the incontinence and mobility variables to the presence and development of skin disorders . SETTING Four nursing homes . PARTICIPANTS One hundred incontinent nursing home residents . MAIN OUTCOME MEASURES Prospect i ve measures of nine common skin disorders and skin moisture in four perineal regions under continent and incontinent conditions . RESULTS All subjects had at least one skin condition identified during the 60-day data collection period . The most commonly observed skin condition was blanchable erythema , which occurred in 94 % of the subjects , predominantly in the front and back regions that were closest to the urethra and rectum . Twenty-one percent of residents developed either a Stage 1 ( nonblanchable erythema ) or 2 pressure ulcer . All skin conditions were transient when measured every 3 weeks with the exception of blanchable erythema , which showed stability . Stage 3 or greater pressure ulcers and edema were not observed , and interrater reliability for the measure of papules was poor . Measures of urinary and fecal incontinence severity were correlated with blanchable erythema severity , and blanchable erythema and low bed mobility were predictive of pressure ulcer severity . Blanchable erythema severity was also predictive of Stage 1 and 2 pressure ulcers . Skin moisture levels in the back perineal farthest from the rectum ( peripheral ) were affected most by urinary incontinence . CONCLUSION A trial to detect a 50 % preventive effect on Stage 1 and 2 pressure ulcers would require that 167 subjects be monitored for 60 days . The transient nature of the skin effects require that skin be monitored at least once a week . Because blanchable erythema is so prevalent and appears to be associated with more severe skin conditions , it would make an excellent marker for beginning to assess the potential preventive effects of various interventions on the incidence of pressure ulcers and other related skin disorders in incontinent patients . It is likely that the back area peripheral to the urethra and rectum would experience the greatest benefit from an intervention trial to reduce moisture caused by incontinence The purpose of this study was to evaluate predictors of hospital acquired heel pressure ulcers . A prospect i ve cohort study of hospitalized patients was conducted ( N = 291 ) . Subjects were enrolled by one team and followed by another team that was blind to initial assessment information . Initial assessment included demographics , Braden scale , and other variables found in the first study to be statistically significant . Ongoing evaluation involved heel assessment only . Univariate analysis yielded 15 statistically significant variables . Using multivariate logistic regression , subject 's with a potential problem on the Braden Friction and Shear item ( p = 0.01 ) and who were more frequently moist on the Braden Moisture item ( p = 0.007 ) were more likely to develop heel ulcers ( chi-square 30.52 , df 3 , p = 0.00001 ) . Receiver Operator Characteristic ( ROC ) curves were plotted for the Braden scale and multiple other scoring systems . ROC curves were virtually identical using all new scoring systems as compared to the original Braden scale . No new scoring system was identified that led to a clinical ly significant improvement in sensitivity/specificity over the total Braden scale . While not perfect , the Braden scale may currently be the best predictive tool for heel pressure ulcer development BACKGROUND The pathology literature suggests three types of pressure ulcer with six possible mechanisms leading to tissue breakdown . A limitation of current evidence is the difficulty in replicating the clinical situation and in determining the point at which a tissue assault becomes irreversible and results in tissue breakdown . In particular clinical observations of alteration in darkly pigmented skin , blanching erythema , non-blanching erythema and non-blanching erythema with other skin changes including in duration , oedema , pain , warmth or discolouration have not been assessed in relation to subsequent skin/tissue loss and their pathophysiological and aetiological importance is not fully understood . OBJECTIVES To assess the validity of clinical signs of erythema as predictors of pressure ulcer development and identify variables which independently are predictive of Grade 2 pressure ulcer development . DESIGN Prospect i ve cohort study . PARTICIPANTS 109 general , vascular and orthopaedic hospital patients , aged over 55 years with an expected length of stay of 5 days were recruited . Of these 97 were pressure ulcer free at baseline and /or had complete follow-up including 59 women and 38 men with a median age of 75 years ( range 55 - 95 ) . SETTING Single centre large acute UK NHS hospital . METHODS To identify clinical signs of erythema predictive of skin loss , the odds of pressure ulcer development were examined using logistic regression . To identify variables independently predictive of Grade 2 pressure ulcer development logistic regression modeling was undertaken . RESULTS There was significantly increased odds of pressure ulcer development associated with non-blanching erythema ( 7.98 , p=0.002 ) and non-blanching erythema with other skin changes ( 9.17 , p=0.035 ) . Logistic regression modeling identified non-blanching erythema , pre-operative albumin , weight loss , and intra-operative minimum diastolic blood pressure , as independent predictors of Grade > or = 2 pressure ulcer development . CONCLUSIONS Non-blanching erythema with or without other skin changes is distinct from normal skin/blanching erythema and is associated with subsequent pressure ulcer development OBJECTIVE The aims of the present study were to ( i ) investigate the incidence of pressure ulcers in 1997 and 1999 among patients with hip fracture , ( ii ) study changes of nursing and treatment routines during the same period and ( iii ) to identify predictors of pressure ulcer development . DESIGN The present comparative study was based partly on data collected in two prospect i ve , r and omized , controlled studies conducted in 1997 and 1999 . SETTING The study was carried out in the Accident & Emergency ( A&E ) Department and the Department of Orthopaedics at the University Hospital in Uppsala , Sweden . STUDY PARTICIPANTS INCLUSION CRITERIA patient with hip fracture , > or = 65 years , admitted without pressure ulcers . Forty-five patents were included in 1997 and 101 in 1999 . INTERVENTIONS Risk assessment , pressure ulcer grading , pressure-reducing mattress and educational programme . MAIN OUTCOME MEASURES Incidence of pressure ulcers . RESULTS There was a significant reduction of the overall incidence of pressure ulcers from 55 % in 1997 to 29 % in 1999 . The nursing notes had become significantly more informative . Nursing and treatment routines for patients with hip fractures had changed both in the A&E Department and the orthopaedic ward through initiatives developed and implemented by pressure ulcer nurses . CONCLUSION In the framework of a quality improvement project , where research activities were integrated with practice -based developmental work , the incidence of pressure ulcers was reduced significantly in patients with hip fractures . The best predictor of pressure ulcer development was increased age Objective : To describe the short-term and long-term effects of a hospital-wide pressure ulcer prevention and treatment guideline on both the incidence and the time to the onset of pressure ulcers in critically ill patients . Design : Prospect i ve cohort study . Setting : Adult intensive care department of a university medical center . Patients : Critically ill patients ( n = 399 ) . Interventions : A guideline for pressure ulcer care was implemented on all intensive care units . The attention of nurses for timely transfer to a specific pressure-reducing device was an important part of this guideline . Measurements and Main Results : Patient characteristics , demographics , pressure ulcer risk profile at admission , daily pressure ulcer grading , and type of mattress were determined to describe the short-term and long-term effects 3 and 12 months after the implementation . The incidence density of pressure ulcers grade II – IV decreased from 54 per 1000 patient days at baseline to 32 per 1000 days ( p = .001 ) 12 months after the implementation . The median pressure ulcer-free time increased from 12 days to 19 days ( hazard rate ratio , 0.58 ; p = .02 ) . After adjustment for differences in risk factors in a Cox proportional hazard model , the number of preventive transfers to special mattresses was the strongest indicator for the decreased risk of pressure ulcers ( hazard rate ratio , 0.22 ; p < .001 ) . The number needed to treat to prevent one pressure ulcer during the first 9 days was six . Conclusions : The implementation of a guideline for pressure ulcer care result ed in a significant and sustained decrease in the development of grade II – IV pressure ulcers in critically ill patients . Timely transfer to a specific mattress ( i.e. , transfer before the occurrence of a pressure ulcer ) was the main indicator for a decrease in pressure ulcer development OBJECTIVE To identify risk factors associated with pressure ulcer development among adult hospitalized medical and surgical patients . DESIGN A prospect i ve comparative study including 530 adult patients from medical and surgical wards . Registered Nurses made the data collection on admission and once a week for up to 12 weeks . The risk assessment scale used was the Risk Assessment Pressure Sore ( RAPS ) scale , including the following variables ; general physical condition , activity , mobility , moisture , food intake , fluid intake , sensory perception , friction and shear , body temperature and serum albumin . RESULTS Sixty-two ( 11.7 % ) patients developed 85 pressure ulcers . The most common pressure ulcer was that of nonblanchable erythema . Patients who developed pressure ulcers were significantly older , hospitalized for a longer time , had lower scores on the total RAPS scale , had lower weight and lower diastolic blood pressure than nonpressure ulcer patients did . In the multiple logistic regression analyses using variables included in the RAPS scale immobility emerged as a strong risk factor . When adding remaining significant variables in the analyses , mobility , time of hospitalization , age , surgical treatment and weight were found to be risk factors for pressure ulcer development . CONCLUSION It is confirmed that immobility is a risk factor of major importance for pressure ulcer development among adult hospitalized patients . The results also indicate that the RAPS scale may be useful for prediction of pressure ulcer development in clinical practice Nurses caring for elderly patients often need to select support surfaces that reduce the likelihood of pressure ulcers , but there is little information about the effectiveness of different support surfaces . This r and omized trial compared two support surfaces and investigated patient attributes related to the risk of developing a pressure ulcer . Eighty-four elderly patients were nursed on a convoluted or solid foam overlay and assessed three times a week for pressure ulcers . Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer and the variables mobility and type of support surface |
10,915 | 24,728,928 | Conclusions The findings from this systematic review suggest that nutritional interventions , which provide carbohydrate , caffeine and fluid , have potential to preserve skills performed under conditions that induce soccer-specific fatigue .
The weight of current evidence supports the consumption of carbohydrate , but is less conclusive with respect to caffeine and fluid provision . | Background The use of nutritional ergogenic aids in team sports such as soccer is now commonplace .
Aligned with the primary aim of soccer , which is to score more goals than the opposition within the allotted time , the quality of performance of technical actions ( i.e. , skills ) executed during soccer-specific exercise is likely to determine success .
However , when seeking to maintain soccer skill performance , information about the efficacy of nutritional interventions is lacking and factors which might modulate the efficacy of such strategies are unclear .
Objective This review aim ed ( i ) to systematic ally evaluate the current research that examines the efficacy of nutritional interventions on soccer skills , and ( ii ) to provide a qualitative commentary on factors that have the potential to modulate the efficacy of such strategies . | INTRODUCTION Caffeine enhances performance of single bouts of endurance exercise , but its effects on repeated bouts typical of those in high-intensity team sports are unclear . PURPOSE To investigate effects of caffeine in a performance test simulating physical and skill dem and s of a rugby union game . METHODS The study was a double-blind , r and omized , crossover design in which nine competitive male rugby players ingested either caffeine ( 6 mg.kg(-1 ) body mass ) or placebo ( dextrose ) 70 min before performing a rugby test . Each test consisted of seven circuits in each of two 40-min halves with a 10-min half-time rest . Each circuit included stations for measurement of sprint time ( two straight-line and three agility sprints ) , power generation in two consecutive drives , and accuracy for passing balls rapidly . Interstitial fluid was sample d transdermally by electrosonophoresis before ingestion of caffeine or placebo and then before testing , at half-time , and immediately after testing ; sample s were assayed chromatographically for caffeine and epinephrine concentrations . RESULTS The effects of caffeine on mean performance ( + /-90 % confidence limits ) over all 14 circuits were : sprint speeds , 0.5 % ( + /-1.7 % ) through 2.9 % ( + /-1.3 % ) ; first-drive power , 5.0 % ( + /-2.5 % ) ; second-drive power , -1.2 % ( + /-6.8 % ) ; and passing accuracy , 9.6 % ( + /-6.1 % ) . The enhancements were mediated partly through a reduction of fatigue that developed throughout the test and partly by enhanced performance for some measures from the first circuit . Caffeine produced a 51 % ( + /-11 % ) increase in mean epinephrine concentration ; correlations between individual changes in epinephrine concentration and changes in performance were mostly unclear , but there were some strong positive correlations with sprint speeds and a strong negative correlation with passing accuracy . CONCLUSION Caffeine is likely to produce substantial enhancement of several aspects of high-intensity team-sport performance PURPOSE This study was design ed to examine the effect of carbohydrate ( CHO ) feedings on physical and central nervous system ( CNS ) function during intermittent high-intensity exercise with physical dem and s similar to those of team sports such as basketball . METHODS Twenty active men ( N = 10 ) and women ( N = 10 ) , with experience competing in team sports , performed three practice sessions before two experimental trials during which they were fed either a 6 % CHO solution or a flavored placebo ( PBO ) . Experimental trials consisted of four 15-min quarters of shuttle running with variable intensities ranging from walking ( 30 % VO(2max ) ) , to running ( 120 % VO(2max ) ) , to maximal sprinting , and 40 jumps at a target hanging at 80 % of their maximum vertical jump height . Subjects received 5 mL.kg(-1 ) of fluid before exercise and 3 mL.kg(-1 ) after exercise , in addition to 3 mL.kg(-1 ) over a 5-min span after the first and third quarters , and 8 mL.kg(-1 ) during a 20-min halftime . During each break , the subjects performed a battery of tests measuring peripheral and CNS function , including 20-m sprints , a 60-s maximal jumping test , internal and external mood evaluation , cognitive function , force sensation , tests of motor skills , and target-jumping accuracy . RESULTS Compared with PBO , CHO feedings during exercise result ed in faster 20-m sprint times and higher average jump height in the fourth quarter ( P < 0.05 ) . CHO feedings also reduced force sensation , enhanced motor skills , and improved mood late in exercise versus PBO ( P < 0.05 ) . CONCLUSION These results suggest that CHO feedings during intermittent high-intensity exercise similar to that of team sports benefited both peripheral and CNS function late in exercise compared with a flavored placebo BACKGROUND AND PURPOSE Prolonged wakefulness impairs sustained vigilant attention , measured with the psychomotor vigilance task ( PVT ) , and induces a compensatory increase in sleep intensity in recovery sleep , quantified by slow‐wave activity ( SWA ) in the sleep electroencephalogram ( EEG ) . These effects of sleep deprivation are counteracted by the adenosine receptor antagonist caffeine , implying involvement of the adenosine neuromodulator/receptor system . To examine a role for adenosine A2A receptors , we investigated whether variation of the A2A receptor gene ( ADORA2A ) modified effects of caffeine on PVT and SWA after sleep deprivation To examine the effects of aerobic interval training on the decline in short-passing ability caused by a short bout of high-intensity intermittent activities . For this r and omized controlled trial , 26 junior soccer players ( mean age , 17.8 + /- 0.6 years ; mean height , 178 + /- 5 cm ; mean body mass , 74.5 + /- 6.9 kg ) were recruited . After baseline measurements , subjects were r and omly allocated to 1 of 2 groups : the control group ( CG ) or the aerobic interval training group ( ITG ) . The ITG completed 4 weeks of high-intensity aerobic training , consisting of 4 bouts of running for 4 min at 90%-95 % of maximal heart rate , with 3 min of active recovery between sets , in addition to normal training . Maximum oxygen uptake , Yo-Yo Intermittent Recovery Test level 1 ( YYIRT ) , and short-passing ability ( measured using the Loughborough Soccer Passing Test ( LSPT ) ) were measured before and after a 5 min high-intensity simulation ( HIS ) , reproducing the most intense phase of a match . The ITG ( n = 11 ) , but not the CG ( n = 10 ) , showed a significant 12 % and 4 % increase in YYIRT and maximal oxygen consumption after training , respectively , and reduced the worsening in LSPT penalty time after the HIS ( p < 0.05 ) . The relative exercise intensity during HIS decreased in the ITG only ( p < 0.01 ) . Our results demonstrated that junior soccer players may benefit from aerobic training to attenuate the decline in short-passing ability caused by a short bout of intermittent activities completed at the same pretraining workload PURPOSE This study was design ed to examine the effects of carbohydrate-electrolyte ingestion on physical and mental function associated with the performance of intermittent high-intensity ( IHI ) exercise similar to many common competitive sporting events . METHODS Physically active men ( N = 5 ) and women ( N = 5 ) , experienced in competitive soccer or basketball , completed three practice sessions and two experimental trials of an IHI shuttle running protocol design ed to closely stimulate the dem and s of an actual competitive sporting event such as basketball . The experimental trials consisted of four 15-min quarters ( QTR ) of intermittent shuttle running at various percentages of .VO(2max ) ( walking , jogging , running , sprinting and jumping ) , separated by a 20-min halftime rest period ( HALF ) and followed by a shuttle run to fatigue . Various tests of physical and mental function ( shuttle run to fatigue , 20-m maximal sprint , 10-repetition maximal vertical jumping , whole body motor skill test ( MS-Test ) , profile of mood states ( POMS ) , and Stroop Color-Word Test ) were performed throughout the experimental trial . Carbohydrate-electrolyte ( CHO ) or placebo ( P ) drinks were consumed before exercise ( 5 mL.kg(-1 ) ; 6 % solution ) and at halftime ( 5 mL.kg(-1 ) ; 18 % solution ) . Smaller volumes ( 3 mL.kg(-1 ) ; 6 % solution ) were given after QTR-1 , HALF , QTR-3 , and QTR-4 . RESULTS CHO ingestion result ed in a 37 % longer run time to fatigue and faster 20-m sprint time during QTR-4 ( P < 0.05 ) . MS-Test performance was also improved during the latter stages of exercise along with self-reported perceptions of fatigue ( subscale of POMS ) ( P < 0.05 ) in CHO versus P. CONCLUSION These results suggest a beneficial role of carbohydrate-electrolyte ingestion on physical and mental function during intermittent exercise similar to that of many competitive team sports This study examined the effects of ingesting a glucose-polymer ( GP ) solution on the motor skill proficiencies of association football ( soccer ) players from two teams playing during two matches in a cool environment . Fifteen minutes before each match and at halftime , players from both teams ingested 5 ml/kg of either placebo or a 6.9 % GP solution . GP ingestion did not improve tackling , heading , dribbling , or shooting ability . On the contrary , the mean of successful tackles was lower with GP ingestion than with placebo . The success rate for heading , dribbling , and shooting also tended to be lower in the GP than in the placebo condition . In contrast , success in passing and ball control was similar in the two conditions . Improvements in passing and ball control may have been related to a decrease in the intensity of play in the second half of the game . These data indicate that there are no measurable benefits of GP ingestion for the motor skill proficiencies of soccer players during games played in a cool environment The presence of carbohydrate in the mouth can immediately improve physical performance . How this occurs is not well understood . Here we used transcranial magnetic stimulation of primary motor cortex ( M1 ) to investigate the effects of non-sweet carbohydrate on corticomotor excitability and voluntary force production . In Experiment 1 , 16 participants performed a fatiguing isometric elbow flexion exercise for 30 min , and Motor evoked potentials ( MEPs ) were recorded from the biceps brachii during maximal voluntary force ( MVF ) produced every 2 min . After 11 min participants drank a carbohydrate solution ( CHO ) or an energy-free placebo solution ( PLA ) , in a double-blind , cross-over protocol . MEP amplitude increased by 30 % , and MVF increased by 2 % , immediately after carbohydrate ingestion . There was no relationship between the facilitation of MEP amplitude and plasma glucose or magnitude of fatigue . In a control experiment , 17 participants alternately mouth-rinsed CHO and PLA , in a r and omized , double-blind protocol . MEPs were recorded from right first dorsal interosseous at rest or during isometric contraction . MEP amplitude increased by 9 % with CHO , when the muscle was voluntarily activated . In both experiments , there were no effects on silent period duration , indicating that MEP facilitation was not due to reduced inhibition within M1 . This is the first demonstration that carbohydrate in the mouth immediately increases the excitability of the corticomotor pathway , prior to its ingestion . Afference from oral receptors is integrated with descending motor output , perhaps via nuclei in the brainstem . This novel form of sensorimotor integration facilitates corticomotor output to both fatigued and fresh muscle The effects of high-intensity , short- duration , re-warm-ups on team-sport-related performance were investigated . In a r and omised , cross-over study , participants performed 2 × 26-min periods of an intermittent activity protocol ( IAP ) on a non-motorized treadmill , interspersed by 15-min of passive recovery ( CON ) ; 3-min small-sided game ( SSG ) ; or a 5RM leg-press . Measures included counter-movement jump , repeated-sprint , the Loughborough soccer passing test ( LSPT ) , blood lactate concentration , heart-rate , and perceptual measures . Data were analyzed using effect size ( 90 % confidence intervals ) , and percentage change ; determining magnitudes of effects . A 5RM re-warm-up improved flight-time to contraction-time ratio when compared to SSG ( 9.8 % , ES ; 0.5±0.3 ) and CON ( ES : 9.4 % , 0.7±0.5 ) re-warm-ups , remaining higher following the second IAP ( 8.8 % , ES ; 0.5±0.3 and 10.2 % , ES ; 0.6±0.6 , respectively ) . Relative-maximum rate-of-force development was greater in the 5RM condition following the second IAP compared to SSG ( 29.3 % , ES ; 0.7±0.5 ) and CON ( 16.2 % , ES ; 0.6±0.6 ) . Repeated-sprint ability during the second IAP improved in the 5RM re-warm-up ; peak velocity , mean velocity , and acceleration were 4 , 3 , and 18 % greater , respectively . Within groups , the SSG re-warm-up improved LSPT performance post-intervention ; 6.4 % ( ES : 0.6±0.8 ) and following the second IAP 6.2 % ( ES : 0.6±0.6 ) , compared to pre-intervention . A 5RM leg-press re-warm-up improved physical performance , while a SSG re-warm-up enhanced skill execution following st and ardized intermittent exercise OBJECTIVES To examine the effect of a high carbohydrate meal on serum caffeine concentration following caffeine intake . DESIGN R and omised , double-blind , crossover . METHODS Fourteen healthy males r and omly completed 4 trials , each separated by 5 days . Participants either remained fasted ( on 2 occasions ) or ingested a high carbohydrate meal ( 2.0gkg(-1 ) carbohydrate , 42.4±0.6kJkg(-1 ) ) prior to consuming either 6 or 9mgkg(-1 ) anhydrous caffeine . Venous blood was sample d for the analysis of serum caffeine at baseline and at 6 time-points over 4h following caffeine intake . RESULTS Peak caffeine concentration occurred 60min following ingestion for both the 6 and 9mgkg(-1 ) fasted ( p<0.001 ) trials compared to 120 and 180min following ingestion for the 6 and 9mgkg(-1 ) fed trials , respectively ( p<0.001 ) . Peak concentration was greater in the 9mgkg(-1 ) fasted trial than the corresponding fed condition ( 70±9μmolL(-1 ) and 56±6μmolL(-1 ) , respectively ) and both were greater than the 6mgkg(-1 ) conditions ( 44±8μmolL(-1 ) and 38±8μmolL(-1 ) for 6mgkg(-1 ) fasted and fed , respectively ) . Area under the caffeine curve was significantly greater ( p<0.001 ) in the 9mgkg(-1 ) fasted trial ( 3262μmolL(-1)h(-1 ) ) , whilst areas were lowest in the 6mgkg(-1 ) fed trial ( 1644μmolL(-1)h(-1 ) ) . CONCLUSIONS A high carbohydrate meal consumed prior to caffeine ingestion significantly reduced serum caffeine concentrations and delayed time to peak concentration . Differences in research findings between caffeine supplementation studies may , at least in part , be related to variations in postpr and ial timing of caffeine intake . The influence of postpr and ial timing should be considered when athletes consume caffeine with the aim of enhancing performance Objective : To examine medication use in male top-level football players prior to and during international tournaments . Design : Prospect i ve survey . Material : 2944 team physicians ’ reports on players ’ medication intake . Methods : Each team physician was asked to document all medication and nutritional supplements taken in the 72 h prior to each match . Results : A total of 10 384 substances were reported ( 1.8 substances/player/match ) ; 4450 ( 42.9 % ) of these were medicinal and 5934 ( 57.1 % ) nutritional supplements . The medications prescribed most frequently were non-steroidal anti-inflammatory agents ( n = 2092 ; 20.1 % ) ; more than half of the players took these at least once during a tournament and more than 10 % prior to every match ( 156 out of 1472 ) . β-2-Agonists were reported for 1.4 % ( n = 20 ) and inhaled corticosteroids for 1.6 % ( n = 23 ) of participating players . Injected corticosteroids were reported for 73 players . Conclusions : The high intake of medication in international football – especially of non-steroidal anti-inflammatory drugs – is alarming and should be addressed . The results raise questions as to whether the medication was taken solely for therapeutic reasons . In view of the potential side effects , more restrictive recommendations for sport need to be developed The aim of this study was to examine the effects of ingesting a carbohydrate-electrolyte solution on endurance capacity during a prolonged intermittent , high-intensity shuttle running test ( PIHSRT ) . Nine trained male games players performed two exercise trials , 7 days apart . On each occasion , they completed 75 min exercise , comprising of five 15-min periods of intermittent running , consisting of sprinting , interspersed with periods of jogging and walking ( Part A ) , followed by intermittent running to fatigue ( Part B ) . The subjects were r and omly allocated either a 6.9 % carbohydrate-electrolyte solution ( CHO ) or a non-carbohydrate placebo ( CON ) immediately prior to exercise ( 5 ml kg-1 body mass ) and every 15 min thereafter ( 2 ml kg-1 body mass ) . Venous blood sample s were obtained at rest , during and after each PIHSRT for the determination of glucose , lactate , plasma free fatty acid , glycerol , ammonia , and serum insulin and electrolyte concentrations . During Part B , the subjects were able to continue running longer when fed CHO ( CHO = 8.9 + /- 1.5 min vs CON = 6.7 + /- 1.0 min ; P < 0.05 ) ( mean + /- S.E.M. ) . These results show that drinking a carbohydrate-electrolyte solution improves endurance running capacity during prolonged intermittent exercise The aim of this study was to examine the effect of intermittent high-intensity shuttle running and fluid ingestion on the performance of a soccer skill . Nine semi-professional soccer players volunteered to participate in the study . Their mean ( + /- s(x ) ) age , body mass and maximal oxygen uptake were 20.2+/-0.4 years , 73.2+/-1.8 kg and 59.1+/-1.3 ml x kg(-1 ) min(-1 ) respectively . The players were allocated to two r and omly assigned trials : ingesting or abstaining from fluid intake during a 90 min intermittent exercise protocol ( Loughborough Intermittent Shuttle Test : LIST ) . This test was design ed to simulate the minimum physical dem and s faced by soccer players during a game . Before and immediately after performance of the test , the players completed a soccer skill test and a mental concentration test . Performance of the soccer skill test after the ' no-fluid ' trial deteriorated by 5 % ( P<0.05 ) , but was maintained during the fluid trial . Mean heart rate , perceived exertion , serum aldosterone , osmolality , sodium and cortisol responses during the test were higher ( P<0.05 ) in the ' no-fluid ' trial than in the fluid trial . The results of this study suggest that soccer players should consume fluid throughout a game to help prevent a deterioration in skill performance UNLABELLED There is little evidence regarding the benefits of caffeine ingestion on cognitive function and skillful actions during sporting performance , especially in sports that are multifaceted in their physiological , skill , and cognitive dem and s. PURPOSE To examine the influence of caffeine on performance during simulated soccer activity . METHODS Twelve male soccer players completed two 90-min soccer-specific intermittent running trials interspersed with tests of soccer skill ( LSPT ) . The trials were separated by 7 days and adhered to a r and omized crossover design . On each occasion participants ingested 6 mg/kg body mass ( BM ) of caffeine ( CAF ) or a placebo ( PLA ) in a double-blind fashion 60 min before exercise . Movement time , penalties accrued , and total time were recorded for the LSPT . Physiological and performance markers were measured throughout the protocol . Water ( 3 ml/kg BM ) was ingested every 15 min . RESULTS Participants accrued significantly less penalty time in the CAF trial ( 9.7 + /- 6.6 s vs. PLA 11.6 + /- 7.4 s ; p = .02 ) , leading to a significantly lower total time in this trial ( CAF 51.6 + /- 7.7 s vs. PLA 53.9 + /- 8.5 s ; p = .02 ) . This decrease in penalty time was probably attributable to an increased passing accuracy in the CAF trial ( p = .06 ) . Jump height was 2.7 % ( + /- 1.1 % ) higher in the CAF trial ( 57.1 + /- 5.1 cm vs. PLA 55.6 + /- 5.1 cm ; p = .01 ) . CONCLUSIONS Caffeine ingestion before simulated soccer activity improved players ' passing accuracy and jump performance without any detrimental effects on other performance parameters Abstract There is little published data in relation to the effects of caffeine upon cycling performance , speed and power in trained cyclists , especially during cycling of ∼60 s duration . To address this , eight trained cyclists performed a 1 km time-trial on an electronically braked cycle ergometer under three conditions : after ingestion of 5 mg · kg−1 caffeine , after ingestion of a placebo , or a control condition . The three time-trials were performed in a r and omized order and performance time , mean speed , mean power and peak power were determined . Caffeine ingestion result ed in improved performance time ( caffeine vs. placebo vs. control : 71.1 ± 2.0 vs. 73.4 ± 2.3 vs. 73.3 ± 2.7 s ; P = 0.02 ; mean ± s ) . This change represented a 3.1 % ( 95 % confidence interval : 0.7–5.6 ) improvement compared with the placebo condition . Mean speed was also higher in the caffeine than placebo and control conditions ( caffeine vs. placebo vs. control : 50.7 ± 1.4 vs. 49.1 ± 1.5 vs. 49.2 ± 1.7 km · h−1 ; P = 0.0005 ) . Mean power increased after caffeine ingestion ( caffeine vs. placebo vs. control : 523 ± 43 vs. 505 ± 46 vs. 504 ± 38 W ; P = 0.007 ) . Peak power also increased from 864 ± 107 W ( placebo ) and 830 ± 87 W ( control ) to 940 ± 83 W after caffeine ingestion ( P = 0.027 ) . These results provide support for previous research that found improved performance after caffeine ingestion during short- duration high-intensity exercise . The magnitude of the improvements observed in our study could be due to our use of sport-specific ergometry , a tablet form and trained participants PURPOSE This study examined the effects of caffeine ( CAF ) on vigilance , marksmanship , and run performance during 27 h of sustained wakefulness in Special Forces personnel . METHODS There were 31 soldiers ( 29.8 + /- 5.4 yr , 86.4 + /- 8.6 kg ) who were divided into placebo ( PLAC , n = 15 ) and CAF ( n = 16 ) groups . A 6.3-km control run was completed on the morning of Day 1 . In the evening of Day 2 , soldiers performed a control observation and reconnaissance vigilance task ( ORVT ) in the field . This 90-min task was repeated twice more between 02:00 and 06:00 on Day 3 during an overnight period of sleep deprivation . Marksmanship was assessed before and after the ORVT . PLAC or 200 mg of CAF gum was administered at 01:45 , 03:45 , and approximately 06:30 on Day 3 . A final 6.3-km run commenced within 30 min of receiving the final dose . RESULTS ORVT was maintained in CAF at control levels of 77 + /- 13 % during the overnight testing . However , values decreased significantly for PLAC from 77 + /- 15 % to 54 + /- 29 % and 51 + /- 31 % during the first and second overnight testing periods , respectively . CAF had no effect on marksmanship but improved 6.3-km run times by 1.2 + /- 1.8 min . Run times slowed for PLAC by 0.9 + /- 0.8 min from approximately 35 min during the control run ; the changes in performance were significant between groups . CONCLUSIONS It was concluded that CAF maintained vigilance and improved running performance during an overnight field operation for Special Forces personnel PURPOSE This investigation was conducted to study the effects on sprint performance of glucose and fructose ingestion during a 15-min rest period half way through 90 min of continuous and intermittent exercise . On three occasions , eight subjects cycled at 76 + /- 2 % VO2max for 90 min ( continuous trials : CON trials ) with a 15-min half-time break . METHODS On another three occasions , they cycled for 90 min between moderate ( 65 % VO2max ) and high ( 100 % VO2max ) intensity ( intermittent trials : INT trials ) with the same half-time . In both trials , 90-min exercise was followed by a 40-s Wingate test to evaluate remaining sprint capacity . During half-time , they consumed either 20 % glucose polymer ( G ) , 20 % fructose ( F ) or sweet placebo ( P ) . Ingestion of G maintained plasma glucose levels , carbohydrate oxidation rate and lower value of ratings of perceived exertion ( RPE ) in both trials and indicated higher sprint performance compared with P ( mean power of CON trials : 614.3 + /- 23.3 W vs 574.0 + /- 22.7 W , P < 0.001 , INT trials : 629.5 + /- 27.6 W vs 596.3 + /- 25.5 W , P < 0.01 ) . RESULTS Ingestion of F showed similar effect in CON trials ( 603.8 + /- 26.1 W vs 574.0 + /- 22.7 W , P < 0.01 ) but had no positive effect in INT trials . Additionally , mean power of G was higher than F ( 629.5 + /- 27.6 W vs 598.4 + /- 34.2 W , P < 0.01 ) in INT trials . CONCLUSIONS These results indicated that ingestion of G during half-time of 90-min exercise could maintain carbohydrate utilization and improve sprint performance in both CON and INT trials This study examined the effect of a high-carbohydrate diet on the performance of dribbling and shooting skills of recreational soccer players . Six male midfield soccer players first completed 60 minutes of intermittent treadmill exercise , followed either by a mixed or a high-carbohydrate diet for 48 hours . A modified Zelenka Functional Performance Test was then administered , followed by the intermittent treadmill exercise and another skills test . Subjects then repeated the protocol two weeks later under the alternative dietary regime . Blood sample s were obtained pre exercise and after each procedure for Hematocrit and concentrations of hemoglobin , plasma glucose and lactate . Heart rate was recorded during and after each procedure . Repeated measures MANOVA revealed ( 1 ) the skill performance was not impaired by the intermittent treadmill exercise ( p > 0.05 ) ; ( 2 ) the high-carbohydrate diet did not increase the ability of players to shoot or dribble ( p > 0.05 ) ; ( 3 ) a significant increase in heart rate during the post treadmill exercise skill test compared with that during the pre treadmill exercise test ( p < 0.05 ) ; ( 4 ) a significant order by time effect for hematocrit ( p < 0.05 ) ; ( 5 ) no significant differences in plasma glucose , plasma lactate or hemoglobin concentrations between tests ( p > 0.05 ) ; and ( 6 ) a significant decrease in body mass from pre to post dietary regime within both conditions ( p < 0.05 ) . It is speculated that either ( 1 ) muscle glycogen depletion may not impair the ability of the player to execute game skills ; ( 2 ) an alternative fatigue mechanism such as dehydration or increased lactate production may be causative factors in the reduction in skill performance ; or ( 3 ) the treadmill protocol employed failed to induce a degree of glycogen depletion or fatigue large enough to cause a significant fall in skill performance The main aim of this study was to investigate the influence of consuming a 6 % carbohydrate-electrolyte ( CHO-E ) solution on the intermittent , high-intensity endurance performance and capacity of adolescent team games players . Fifteen participants ( mean age 12.7 ± 0.8 years ) performed two trials separated by 3–7 days . In each trial , they completed 60 min of exercise composed of four 15-min periods of part A of the Loughborough Intermittent Shuttle Test , followed by an intermittent run to exhaustion ( part B ) . In a double-blind , r and omised , counterbalanced fashion participants consumed either the 6 % CHO-E solution or a non-carbohydrate ( CHO ) placebo ( 5 ml kg−1 BM ) during the 5 min pre-trial and after each 15-min period of part A ( 2 ml kg−1 BM ) . Time to fatigue was increased by 24.4 % during part B when CHO was ingested ( 5.1 ± 1.8 vs. 4.1 ± 1.6 min , P < 0.05 ) , with distance covered in part B also significantly greater in the CHO trial ( 851 ± 365 vs. 694 ± 278 m , P < 0.05 ) . No significant between-trials differences were observed for mean 15-m sprint time ( P = 0.35 ) , peak sprint time ( P = 0.77 ) , or heart rate ( P = 0.08 ) during part A. These results demonstrate , for the first time , that ingestion of a CHO-E solution significantly improves the intermittent , high-intensity endurance running capacity of adolescent team games players during an exercise protocol design ed to simulate the physiological dem and s of team games PURPOSE AND METHOD To investigate the possible role of carbohydrate ( CHO ) receptors in the mouth in influencing exercise performance , seven male and two female endurance cyclists ( VO(2max ) 63.2 + /- 2.7 ( mean + /- SE ) mL.kg*(-1).min(-1 ) ) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible ( 914 + /- 40 kJ ) . On one occasion a 6.4 % maltodextrin solution ( CHO ) was rinsed around the mouth for every 12.5 % of the trial completed . On the other occasion , water ( PLA ) was rinsed . Subjects were not allowed to swallow either the CHO solution or water , and each mouthful was spat out after a 5-s rinse . RESULTS Performance time was significantly improved with CHO compared with PLA ( 59.57 + /- 1.50 min vs 61.37 + /- 1.56 min , respectively , P = 0.011 ) . This improvement result ed in a significantly higher average power output during the CHO compared with the PLA trial ( 259 + /- 16 W and 252 + /- 16 W , respectively , P = 0.003 ) . There were no differences in heart rate or rating of perceived exertion ( RPE ) between the two trials ( P > 0.05 ) . CONCLUSION The results demonstrate that carbohydrate mouth rinse has a positive effect on 1-h time trial performance . The mechanism responsible for the improvement in high-intensity exercise performance with exogenous carbohydrate appears to involve an increase in central drive or motivation rather than having any metabolic cause . The nature and role of putative CHO receptors in the mouth warrants further investigation PURPOSE This study compared the effect of a honey-sweetened beverage with those of a commercial sports drink and a placebo on performance and inflammatory response to a 90-min soccer simulation . METHODS Ten experienced male soccer players r and omly performed 3 trials ( honey [ H ] , sports drink [ S ] , and placebo [ P ] ) , consuming the beverage before and during halftime for a total of 1.0 g/kg carbohydrate for H and S. Performance measures included 5 sets ( T1-T5 ) of a high-intensity run and agility and ball-shooting tests followed by a final progressive shuttle-run ( PSR ) test to exhaustion . Blood sample s were drawn pretest , posttest ( B2 ) , and 1 hr posttest ( B3 ) for markers of inflammation , oxygen radical absorbance capacity ( ORAC ) , and hormone response . RESULTS T2-T5 were significantly slower than T1 ( p < .05 ) , and a decrease in PSR time was observed from baseline ( -22.9 % ) for all treatments . No significant effect of the interventions was observed for any performance measures . Plasma IL-1ra levels increased posttest for all treatments ( 65.5 % S , 63.9 % P , and 25.8 % H ) , but H was significantly less than S at posttest and P at B3 . Other cytokines and ORAC increased at B2 ( 548 % IL-6 , 514 % IL-10 , 15 % ORAC ) with no difference by treatment . CONCLUSION Acute ingestion of honey and a carbohydrate sports drink before and during a soccer-simulation test did not improve performance , although honey attenuated a rise in IL-1ra . Ingestion of carbohydrate and / or antioxidant-containing beverages at frequencies typical of a regulation match may not be beneficial for trained soccer players This investigation was undertaken to determine whether consuming several small feedings of preexercise carbohydrate ( CHO ) , rather than a single bolus , would affect blood glucose and insulin responses during rest and exercise . Eight trained cyclists ingested 22.5 , 45 , or 75 total g maltodextrin and dextrose dissolved in 473 ml of water or an equal volume of placebo ( PL ) . Drinks were divided into four portions and consumed at 15-min intervals in the hour before a 120-min ride at 66 % VO2max . Serum glucose values were elevated by the CHO feedings at rest and fell significantly below baseline and PL at 15 min of exercise . However , glucose concentrations were similar in each of the CHO trials . Insulin concentrations also increased rapidly during rest , then fell sharply at the onset of exercise . The findings demonstrate that CHO consumed within an hour before exercise , even when taken in several small feedings , can produce transient hypoglycemia near the onset of exercise . Additionally , the magnitude of the response appears to be unrelated to either the amount of CHO ingested or the insulin response Abstract . The development of rebound hypoglycaemia has been reported after pre-exercise carbohydrate ( CHO ) ingestion in some studies but not in others . Differences in the experimental design and factors such as the exercise intensity are likely to be responsible for the discrepancies between these studies . Exercise intensity might be a crucial factor since it affects both insulinaemia and glucose uptake . Therefore the aim of the present study was to compare the glycaemic and insulinaemic responses to exercise at different intensities after ingestion of a st and ardized pre-exercise CHO load . Eight moderately trained subjects consumed 75 g of glucose 45 min prior to 20 min of exercise at 40 % , 65 % or 80 % maximal power output . Blood sample s were collected before glucose ingestion , at 15 min intervals at rest and 5 min intervals during exercise . During exercise , measurements of heart rate and breath-by-breath analysis of expired gas were performed continuously . The trials were performed at [ mean ( SEM ) ] 55 ( 1 ) , 77 ( 1 ) and 90 ( 1 ) percentages maximal oxygen uptake . At the onset of exercise , plasma glucose concentration returned to pre-ingestion levels , while the insulin concentration was more than three times higher than at rest [ on average 57 ( 7 ) compared to 16 ( 1 ) μU·ml–1 ) . During exercise , plasma glucose concentrations decreased during the first 5 min of exercise and then stabilized in all trials at concentrations that would not be considered to be hypoglycaemic . There were no significant differences in glucose or insulin concentrations between the three trials during exercise . These data suggest that the glycaemic response to ingestion of 75 g of CHO 45 min pre-exercise is similar during exercise of different intensities Rationale In everyday life , people are usually capable of performing two tasks simultaneously . However , in a previous study we showed that during a fatiguing motor task , cognitive performance declined progressively . There is extensive literature on the ( positive ) effects of caffeine on cognitive and motor performance . These effects are most pronounced under suboptimal conditions , for example during fatigue . However , little is known about the effects of caffeine on cognitive performance during a fatiguing motor task . Objective This study was aim ed to investigate whether a moderate dose of caffeine could attenuate the decline in cognitive performance during a fatiguing motor task . Methods The study consisted of a placebo and a caffeine ( 3 mg/kg ) session . A total of 23 subjects completed these sessions in a semi-r and omized and double-blind order . In each session , subjects performed maximal voluntary contractions of the index finger , a choice reaction time ( CRT ) task and a dual task consisting of a fatiguing motor task concomitantly with the same CRT task . After the fatiguing dual task , the CRT task was repeated . Results Caffeine improved cognitive task performance , in both the single and dual task , as shown by decreased reaction times together with unchanged accuracy . Cognitive performance in the dual task deteriorated with increasing fatigue . However , the decrease in cognitive performance in the beginning of the dual task , as observed in the placebo condition , was partly prevented by caffeine administration ( i.e. , no increase in reaction times ) . We found no effects of caffeine on motor parameters ( absolute force , endurance time or electromyographic amplitude ) . Conclusions Caffeine improved cognitive performance . This effect also extends under dem and ing situations , as was shown by the performance during the dual task , even during progressive motor fatigue Rationale The cognitive and mood effects of caffeine are well documented . However , the majority of studies in this area involve caffeine-deprived , habitual caffeine users . It is therefore unclear whether any beneficial findings are due to the positive effects of caffeine or to the alleviation of caffeine withdrawal . Objectives The present placebo-controlled , double-blind , balanced crossover study investigated the acute cognitive and mood effects of caffeine in habitual users and habitual non-users of caffeine . Method Following overnight caffeine withdrawal , 24 habitual caffeine consumers ( mean=217 mg/day ) and 24 habitual non-consumers ( 20 mg/day ) received a 150 ml drink containing either 75 or 150 mg of caffeine or a matching placebo , at intervals of ≥48 h. Cognitive and mood assessment s were undertaken at baseline and 30 min post-drink . These included the Cognitive Drug Research computerised test battery , two serial subtraction tasks , a sentence verification task and subjective visual analogue mood scales . Results There were no baseline differences between the groups ’ mood or performance . Following caffeine , there were significant improvements in simple reaction time , digit vigilance reaction time , numeric working memory reaction time and sentence verification accuracy , irrespective of group . Self-rated mental fatigue was reduced and ratings of alertness were significantly improved by caffeine independent of group . There were also group effects for rapid visual information processing false alarms and spatial memory accuracy with habitual consumers outperforming non-consumers . There was a single significant interaction of group and treatment effects on jittery ratings . Separate analyses of each groups ’ responses to caffeine revealed overlapping but differential responses to caffeine . Caffeine tended to benefit consumers ’ mood more while improving performance more in the non-consumers . Conclusions These results do not support a withdrawal alleviation model . Differences in the patterns of responses to caffeine by habitual consumers and habitual non-consumers may go some way to explaining why some individuals become caffeine consumers Previous research has shown that glucose can enhance memory in animals and humans . In humans , the facilitative effect of glucose is best observed with declarative memory tasks in older subjects . While the memory-enhancing action of glucose is well established , the underlying physiological mechanisms and the specific aspects of memory that are modulated by glucose in humans are not well understood . The present study sought to examine the effects of glucose on memory in young women using a memory paradigm sensitive to specific encoding and retrieval strategies . The glucose dose was adjusted for the weight of each participant in order to generate a dose response curve covering most doses used in previous studies . The results showed that 300 mg/kg glucose enhanced the primacy effect as defined by the recall of the first five items of the lists . However , none of the doses of glucose produced changes in the recall priority given to primacy items . The effect of glucose appears to be localized on the recall primacy effect , suggesting that glucose acts on precise memory operations . This improvement , however , is independent of the order in which subjects recalled the words . Cholinergic drugs have been shown to alter the recall of the primacy part of word lists and this observation is consistent with the hypothesis that glucose acts on memory through an interaction with brain cholinergic systems BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert chewing gum and capsule formulation . METHODS This was a double blind , parallel , r and omized , seven treatment study . The treatment groups were : 50 , 100 , and 200 mg gum , 50 , 100 , and 200 mg capsule , and a placebo . Subjects consisted of 84 ( n=12 per group ) ; healthy , non-smoking , males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were r and omly assigned to the treatment groups . Blood sample s were collected pre-dose and at 5 , 15 , 25 , 35 , 45 , 55 , 65 , 90 min and 2 , 3 , 4 , 6 , 8 , 12 , 16 and 29 h post administration . Plasma caffeine levels were analyzed by a vali date d UV-HPLC method . RESULTS Mean Tmax for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0 - 120.0 min for the capsule groups . The Tmax , for the pooled data was significantly lower ( P<0.05 ) for the gum groups as compared with the capsule groups . Differences in Tmax were significant for the 200 mg capsule versus 200 mg gum ( P<0.05 ) . The mean ka values for the gum group ranged from 3.21 to 3.96 h-1 and for the capsule groups ranged from 1.29 to 2.36 h-1 . Relative bioavailability of the gum formulation after the 50 , 100 and 200 mg dose was 64 , 74 and 77 % , respectively . When normalized to the total drug released from the gum ( 85 % ) , the relative bioavailability of the 50 , 100 and 200 mg dose were 75 , 87 , and 90 % , respectively . No statistical differences were found for Cmax and AUCinf for comparisons of the gum and capsule formulations at each dose . Within each dose level , there were no significant formulation related differences in Cmax . No significant differences were observed in the elimination of caffeine after the gum or capsule . CONCLUSIONS The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa . In addition , for the 100 and 200 mg groups , the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation . These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation , which is advantageous in situations where the rapid reversal of alertness and performance deficits result ing from sleep loss is desirable Abstract Souglis , AG , Chryssanthopoulos , CI , Travlos , AK , Zorzou , AE , Gissis , IT , Papadopoulos , CN , and Sotiropoulos , AA . The effect of high vs. low carbohydrate diets on distances covered in soccer . J Strength Cond Res 27(8 ) : 2235–2247 , 2013—The purpose of this study was to compare the distances covered during a 11-a-side soccer match after players had consumed either a high carbohydrate ( CHO ) or a low CHO diet . Twenty-two male professional soccer players formed 2 teams ( A and B ) , of similar age , body characteristics , and training experience . The 2 teams played against each other twice with a week interval between . For 3.5 days before the first match , the players of team A followed a high CHO diet that provided 8 g CHO per kg body mass ( BM ) ( HC ) , whereas team B players followed a low CHO diet that provided 3 g CHO per kg BM ( LC ) for the same time period . Before the second match the dietary treatment was reversed and followed for the same time period . Training during the study was controlled , and distances covered were measured using global positioning system technology . Every player covered a greater total distance in HC compared with the distance covered in LC ( HC : 9,380 ± 98 m vs. LC : 8,077 ± 109 m ; p < 0.01 ) . All distances covered from easy jogging ( 7.15 km·h−1 ) to sprinting ( 24.15 km·h−1 ) were also higher in HC compared with LC ( p < 0.01 ) . When players followed the HC treatment , they won the match ( team A vs. team B : 3 - 1 for the first game and 1 - 2 for the second game ) . The HC diet probably helped players to cover a greater distance compared with LC . Soccer players should avoid eating a low ( 3 g CHO per kg BM ) CHO diet 3–4 days before an important soccer match and have a high CHO intake that provides at least 8 g CHO per kg BM To determine the effect of a carbohydrate-(CHO ) enriched diet on long-term , intermittent exercise performance , seven professional soccer players ( mean maximum oxygen uptake : 60.6 ( range : 56.0 - 65.1 ) ml.min-1.kg-1 ) were tested twice . The st and ardized test consisted initially of a field part ( 6856 m ) followed by treadmill running to exhaustion . The relative work rates were 65 , 57 and 81 % of maximum oxygen uptake during the field test , and during the first and last part of the treadmill running , respectively . The players ingested a diet containing either 39 % ( C-diet ) or 65 % carbohydrate ( CHO-diet ) during the two days prior to each test . The order of the diets was assigned r and omly . Neither blood lactate nor glucose concentrations at exhaustion differed after the two diets . The total mean running distance after the CHO-diet was 17.1 km , which was 0.9 km longer ( p less than 0.05 ) than after the C-diet . Nevertheless , three subjects had a difference in running distance of less than 420 m. In contrast to the remaining players , these players had a higher RER-value during treadmill running in association with the CHO-diet . The mean CHO intake of 46 % in the normal diet of the players was below the Nordic Nutritional Recommendation . In conclusion , performance during intermittent running was enhanced following the ingestion of a CHO enriched diet for two days . However , not all players benefited from the CHO-diet perhaps because they , in contrast to the other players , responded with a higher utilization of CHO after the CHO-diet PURPOSE The purpose of this study was to examine the effects of caffeine ( CAF ) on physical , vigilance , and marksmanship tasks in soldiers during a sustained 55-h field exercise . METHODS There were 30 soldiers ( 23.6 + /- 4.5 yr , 81.8 + /- 10.3 kg ) who were divided into a placebo ( PLAC ) and a CAF group . After a period of restricted sleep of 3 h during the first night , a period of sustained wakefulness began that ended at 11:00 of the third day . PLAC or CAF doses of 100 mg , 200 mg , 100 mg , and 200 mg were administered at 21:45 , 23:45 , 01:45 , and 03:45 , respectively . At 22:00 of day 2 , subjects began two cycles of marksmanship , urban operations vigilance , and psychomotor vigilance ( PVT ) testing which ended at 06:00 of day 3 . RESULTS CAF maintained marksmanship vigilance at 85 % throughout the second night as compared with PLAC , who significantly declined to 61.4 + /- 28.2 % overnight . Marksmanship accuracy also decreased significantly in PLAC from 95.1 + /- 8.3 % to 83.3 + /- 19.2 % , but no change was observed in CAF . Urban operations vigilance decreased for both groups over the night , but the decrease was less for CAF ( 81.2 + /- 14.4 % to 63.4 + /- 24.1 % ) compared with PLAC ( 77.6 + /- 19.2 % to 44.0 + /- 30.2 % ) . Reaction time and the number of major and minor lapses with the PVT significantly increased in PLAC but were unaffected in CAF . CONCLUSIONS It was concluded that CAF was an effective strategy to sustain vigilance and psychomotor performance during military operations involving sleep deprivation PURPOSE To investigate the effect of ingesting a carbohydrate-electrolyte solution ( CHO-E ) , in subjects with reduced carbohydrate stores , during an intermittent shuttle running test ( LIST ) on soccer passing ( LSPT ) and shooting ( LSST ) performance . METHODS Sixteen healthy male university soccer players ingested either a 6.4 % CHO-E or placebo ( PLA ) solution during 90 min of the LIST ( 5 mL x kg(-1 ) BM before and 2 mL x kg(-1 ) BM every 15 min of exercise ) , in a double-blind , r and omized , crossover design , with each trial separated by at least 7 d. On the evening before the main trial ( 17:00 h ) , subjects performed the glycogen-reducing cycling exercise ( approximately 80 min at 70 % VO2max ) . They were then fed a low-carbohydrate evening meal and reported to the laboratory the following morning after a 10-h fast . Blood was collected at rest and after every 30 min of exercise ; skill tests were performed before and after the LIST . RESULTS The change in mean LSST performance from pre- to post-LIST was better in the CHO-E trial ( 11 + /- 45 vs -16 + /- 42 % ; P < 0.01 ) but not significantly different for the LSPT performance ( -1 + /- 10 % ( CHO-E ) vs -6 + /- 13 % ( PLA ) , P = 0.13 ) . Sprint performance during the LIST was quicker in the CHO-E trial ( 2.50 + /- 0.13 vs 2.53 + /- 0.13 s , P < 0.01 ) . Plasma glucose was higher in the CHO-E trial after 90 min of exercise ( 5.2 + /- 0.3 vs 3.9 + /- 0.4 mM , P < 0.01 ) . CONCLUSIONS Ingestion of a carbohydrate-electrolyte solution during exercise enabled subjects with compromised glycogen stores to better maintain skill and sprint performance than when ingesting fluid alone Caffeine has known ergogenic effects , some of which have been observed during submaximal isometric contractions . We used 15 subjects in a r and omized , double-blind , repeated- measures experiment to determine caffeine 's ergogenic effects on neuromuscular variables that would contribute to increased endurance capacity . Subjects performed repeated submaximal ( 50 % maximal voluntary contraction ) isometric contractions of the right quadriceps to the limit of endurance ( T(lim ) ) 1 h after oral caffeine administration ( 6 mg/kg ) . Time to reach T(lim ) increased by 17 + /- 5.25 % ( P < 0.02 ) after caffeine administration compared with the placebo trial . The changes in contractile properties , motor unit activation , and M-wave amplitude that occurred as the quadriceps reached T(lim ) could not account for the prolonged performance after caffeine ingestion . In a separate experiment with the same subjects , we used a constant-sensation technique to determine whether caffeine influenced force sensation during 100 s of an isometric contraction of the quadriceps . The results of this experiment showed that caffeine reduced force sensation during the first 10 - 20 s of the contraction . The rapidity of this effect suggests that caffeine exerts its effects neurally . Based on these data , the caffeine-induced increase in T(lim ) may have been caused by a willingness to maintain near-maximal activation longer because of alterations in muscle sensory processes The aim of the study was to investigate the reliability of a new test of soccer performance and evaluate the effect of carbohydrate ( CHO ) on soccer performance . Eleven university footballers were recruited and underwent 3 trials in a r and omized order . Two of the trials involved ingesting a placebo beverage , and the other , a 7.5 % maltodextrin solution . The protocol comprised a series of ten 6-min exercise blocks on an outdoor Astroturf pitch , separated by the performance of 2 of the 4 soccer-specific tests , making the protocol 90 min in duration . The intensity of the exercise was design ed to be similar to the typical activity pattern during soccer match play . Participants performed skill tests of dribbling , agility , heading , and shooting throughout the protocol . The coefficients of variation for dribbling , agility , heading , and shooting were 2.2 % , 1.2 % , 7.0 % , and 2.8 % , respectively . The mean combined placebo scores were 42.4 + /- 2.7 s , 43.1 + /- 3.7 s , 210 + /- 34 cm , and 212 + /- 17 points for agility , dribbling , heading , and kicking , respectively . CHO ingestion led to a combined agility time of 41.5 + /- 0.8 s , for dribbling 41.7 + /- 3.5 s , 213 + /- 11 cm for heading , and 220 + /- 5 points for kicking accuracy . There was a significant improvement in performance for dribbling , agility , and shooting ( p < .05 ) when CHO was ingested compared with placebo . In conclusion , the protocol is a reliable test of soccer performance , and ingesting CHO leads to an improvement in soccer performance Abstract The aim of this study was to investigate the effect of ingesting a carbohydrate-electrolyte solution , during the 90-min Loughborough Intermittent Shuttle Test , on soccer skill performance . Seventeen male soccer players ingested either a 6.4 % carbohydrate-electrolyte solution or placebo solution equivalent to 8 ml · kg−1 body mass before exercise and 3 ml · kg−1 body mass after every 15 min of exercise , in a double-blind r and omized cross-over design , with the trials separated by 7 days . The evening before the main trial , the participants performed glycogen-reducing exercise on a cycle ergometer ( 80 min at 70%[Vdot]O2max ) and were then fed a low-carbohydrate meal . After a 12-h overnight fast , they performed The Loughborough Soccer Passing Test before and after every 15 min of exercise . Analysis of the combined skill test data showed a significant time effect ( P = 0.001 ) with differences between 0–45 and 75–90 min ( P < 0.05 ) . There was a 3 % reduction in skill performance from before to after exercise in the carbohydrate-electrolyte trial , whereas in the placebo trial the decrease was 14 % ( P = 0.07 ) . In conclusion , skill performance during the simulated soccer activity appeared to deteriorate in the last 15–30 min of exercise . However , providing 52 g · h−1 carbohydrate during exercise showed a tendency to better maintain soccer skill performance than a taste-matched placebo OBJECTIVES This study investigated the influence of carbohydrate supplementation on skill performance throughout exercise that replicates soccer match-play . DESIGN Experimentation was conducted in a r and omised , double-blind and cross-over study design . METHODS After familiarization , 15 professional academy soccer players completed a soccer match simulation incorporating passing , dribbling and shooting on two separate occasions . Participants received a 6 % carbohydrate-electrolyte solution ( CHO ) or electrolyte solution ( PL ) . Precision , success rate , ball speed and an overall index ( speed-precision-success ; SPS ) were determined for all skills . Blood sample s were taken at rest , immediately before exercise , every 15 min during exercise ( first half : 15 , 30 and 45 min ; second half : 60 , 75 and 90 min ) , and 10 min into the half time ( half-time ) . RESULTS Carbohydrate supplementation influenced shooting ( time × treatment interaction : p<0.05 ) , where CHO attenuated the decline in shot speed and SPS index . Supplementation did not affect passing or dribbling . Blood glucose responses to exercise were influenced by supplementation ( time × treatment interaction : p<0.05 ) , where concentrations were higher at 45 min and during half-time in CHO compared with PL . Blood glucose concentrations reduced by 30±1 % between half-time and 60 min in CHO . CONCLUSIONS Carbohydrate supplementation attenuated decrements in shooting performance during simulated soccer match-play ; however , further research is warranted to optimise carbohydrate supplementation regimes for high-intensity intermittent sports |
10,916 | 29,952,095 | MRA treatment reduced heart failure hospitalisation ( 11 % of participants in the intervention arm versus 14 % in the control arm ; RR 0.82 ; 95 % CI 0.69 to 0.98 ; NNTB 41 ; 3714 participants ; 3 studies ; moderate- quality evidence ) however , little or no effect on all-cause and cardiovascular mortality and quality of life measures was observed .
The evidence suggested that ACEI treatment likely has little or no effect on cardiovascular mortality , all-cause mortality , heart failure hospitalisation , or quality of life .
There is evidence that MRA treatment reduces heart failure hospitalisation in heart failure with preserverd ejection fraction , however the effects on mortality related outcomes and quality of life remain unclear . | BACKGROUND Beta-blockers and inhibitors of the renin-angiotensin aldosterone system improve survival and reduce morbidity in people with heart failure with reduced left ventricular ejection fraction .
There is uncertainty whether these treatments are beneficial for people with heart failure with preserved ejection fraction and a comprehensive review of the evidence is required .
OBJECTIVES To assess the effects of beta-blockers , angiotensin converting enzyme inhibitors , angiotensin receptor blockers , angiotensin receptor neprilysin inhibitors , and mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction . | Background — Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist ( TOPCAT ) patients with heart failure and preserved left ventricular ejection fraction assigned to spironolactone did not achieve a significant reduction in the primary composite outcome ( time to cardiovascular death , aborted cardiac arrest , or hospitalization for management of heart failure ) compared with patients receiving placebo . In a post hoc analysis , an ≈4-fold difference was identified in this composite event rate between the 1678 patients r and omized from Russia and Georgia compared with the 1767 enrolled from the United States , Canada , Brazil , and Argentina ( the Americas ) . Methods and Results — To better underst and this regional difference in clinical outcomes , demographic characteristics of these population s and their responses to spironolactone were explored . Patients from Russia/Georgia were younger , had less atrial fibrillation and diabetes mellitus , but were more likely to have had prior myocardial infa rct ion or a hospitalization for heart failure . Russia/Georgia patients also had lower left ventricular ejection fraction and creatinine but higher diastolic blood pressure ( all P<0.001 ) . Hyperkalemia and doubling of creatinine were more likely and hypokalemia was less likely in patients receiving spironolactone in the Americas with no significant treatment effects in Russia/Georgia . All clinical event rates were markedly lower in Russia/Georgia , and there was no detectable impact of spironolactone on any outcomes . In contrast , in the Americas , the rates of the primary outcome , cardiovascular death , and hospitalization for heart failure were significantly reduced by spironolactone . Conclusions — This post hoc analysis demonstrated greater potassium and creatinine changes and possible clinical benefits with spironolactone in patients with heart failure and preserved ejection fraction from the Americas . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00094302 Background —The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was used in a large , multinational , r and omized , placebo-controlled trial to measure adverse effects of heart failure with preserved ejection fraction ( HF-PEF ) on patients ' lives and the effects of irbesartan . Methods and Results — Patients with symptomatic HF-PEF were r and omly assigned to irbesartan ( up to 300 mg daily ) or placebo . The MLHFQ was administered at baseline ( n=3605 ) , month 6 ( n=3137 ) , month 14 ( n=2904 ) , and the end of study ( median , 56 months , n=2205 ) . Baseline MLHFQ scores of 43±21 indicated that HF-PEF had a substantial adverse effects . Estimated retest reliability was 0.80 . Baseline MLHFQ scores were associated with other measures of the severity of heart failure including symptoms , signs of congestion , cardiac structure , and time to hospitalizations or deaths attributed to heart failure . Slight improvement in shortness of breath or fatigue was associated with significant improvement in MLHFQ scores ( −5.9 and −5.0 , P<0.0001 ) . Compared with placebo , further improvement in MLHFQ scores was not observed with irbesartan after 6 months ( mean adjusted difference , 0.4 ; 95 % confidence interval , −0.8 to 1.7 ) , 14 months ( 0.5 ; 95 % confidence interval , −0.9 to 1.8 ) , or the end of study ( 2.0 ; 95 % confidence interval , −4.1 to 0.01 ) . Conclusions —The MLHFQ scores are a reliable , valid , and sensitive measure of the adverse impact of HF-PEF on patients ' lives . Irbesartan did not substantially improve MLHFQ scores during a long period of follow-up . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00095238 Background —Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking . As aldosterone has been implicated in the genesis of myocardial fibrosis , hypertrophy , and dysfunction , we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a r and omized , double-blinded , placebo-controlled study . Methods and Results —Thirty medically treated ambulatory hypertensive patients ( 19 women , age 62±6 years ) with exertional dyspnea , ejection fraction > 50 % , and diastolic dysfunction ( E/A < 1 , E deceleration time > 250m/sec ) and without ischemia were r and omized to spironolactone 25 mg/d or placebo for 6 months . Patients were overweight ( 31±5 kg/m2 ) with reduced treadmill exercise capacity ( 6.7±2.1 METS ) . Long-axis strain rate ( SR ) , peak systolic strain , and cyclic variation of integrated backscatter ( CVIB ) were averaged from 6 walls in 3 st and ard apical views . Mean 24-hour ambulatory blood pressure at baseline ( 133±17/80±7 mm Hg ) did not change in either group . Values for SR , peak systolic strain , and CVIB were similar between groups at baseline and remained unchanged with placebo . Spironolactone therapy was associated with increases in SR ( baseline : −1.57±0.46 s−1 versus 6-months : −1.91±0.36 s−1 , P<0.01 ) , peak systolic strain ( −20.3±5.0 % versus −26.9±4.3 % , P<0.001 ) , and CVIB ( 7.4±1.7dB versus 8.6±1.7 dB , P=0.08 ) . Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months ( P=0.05 , P=0.02 , and P=0.02 , respectively ) , and the increases remained significant after adjusting for baseline differences . The increase in strain was independent of changes in blood pressure with intervention . The spironolactone group also exhibited reduction in posterior wall thickness ( P=0.04 ) and a trend to reduced left atrial area ( P=0.09 ) . Conclusions —Aldosterone antagonism improves myocardial function in hypertensive heart disease Background — Heart failure with preserved ejection fraction ( HFPEF ) is a common and increasing public health problem . Myocardial fibrosis is a key pathological feature of HFPEF . Peripheral collagen markers may reflect this excess fibrosis ; however , the relation of these markers to prognosis in patients with HFPEF has not as yet been determined . Methods and Results — This sub study of the Irbesartan in Heart Failure With Preserved Systolic Function ( I-PRESERVE ) trial measured plasma levels of procollagen type I amino-terminal peptide , procollagen type III amino-terminal peptide , and osteopontin in 334 patients with HFPEF . Measurements were performed at baseline and 6 months after r and omization to placebo or irbesartan 300 mg/day . The relation of baseline collagen markers to the I-PRESERVE primary end point ( all-cause death and hospitalization for prespecified cardiovascular causes ) was evaluated by single and multivariable analysis . Similar evaluations were performed for all-cause death alone as well as heart failure events ( death or hospitalization because of heart failure ) . Increased plasma levels of collagen markers at baseline were associated with increased frequency of the study primary end point for all collagen markers . For each 10-&mgr;g/L increase in procollagen type I amino-terminal peptide , the hazard ratio ( HR ) for the primary end point was 1.09 ( 95 % CI , 1.052 to 1.13 ; P<0.0001 ) ; for each 10-&mgr;g/L increase in procollagen type III amino-terminal peptide procollagen type I amino-terminal peptide , the HR was 2.47 ( 95 % CI , 0.97 to 6.33 ; P=0.059 ) ; and for each 10-nmol/L increase in osteopontin , the HR was 1.084 ( 95 % CI , 1.026 to 1.15 ; P=0.004 ) . No variable remained significant as an independent predictor when introduced into a multivariable model . Both treatment groups tended to reduce collagen markers , with the reduction significantly greater for placebo versus irbesartan for procollagen type III amino-terminal peptide only ( P=0.0185 ) . Conclusions — Increased peripheral collagen turnover markers were not independently associated with increased mortality and cardiovascular hospitalization in an HFPEF population on multivariable analysis but were associated on single-variable analysis . These findings provide some support to the hypothesis that pathological fibrosis in the heart , and possibly the peripheral vasculature , may be contributory to adverse clinical outcomes in patients with HFPEF . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00095238 BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors improve outcome of patients with chronic heart failure ( CHF ) . A substantial proportion of patients , however , experience no benefit from ACE inhibitors because of previous intolerance . We aim ed to find out whether c and esartan , an angiotensin-receptor blocker , could improve outcome in such patients not taking an ACE inhibitor . METHODS Between March , 1999 , and March , 2001 , we enrolled 2028 patients with symptomatic heart failure and left-ventricular ejection fraction 40 % or less who were not receiving ACE inhibitors because of previous intolerance . Patients were r and omly assigned c and esartan ( target dose 32 mg once daily ) or matching placebo . The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF . Analysis was by intention to treat . FINDINGS The most common manifestation of ACE-inhibitor intolerance was cough ( 72 % ) , followed by symptomatic hypotension ( 13 % ) and renal dysfunction ( 12 % ) . During a median follow-up of 33.7 months , 334 ( 33 % ) of 1013 patients in the c and esartan group and 406 ( 40 % ) of 1015 in the placebo group had cardiovascular death or hospital admission for CHF ( unadjusted hazard ratio 0.77 [ 95 % CI 0.67 - 0.89 ] , p=0.0004 ; covariate adjusted 0.70 [ 0.60 - 0.81 ] , p<0.0001 ) . Each component of the primary outcome was reduced , as was the total number of hospital admissions for CHF . Study -drug discontinuation rates were similar in the c and esartan ( 30 % ) and placebo ( 29 % ) groups . INTERPRETATION C and esartan was generally well tolerated and reduced cardiovascular mortality and morbidity in patients with symptomatic chronic heart failure and intolerance to ACE inhibitors OBJECTIVES The aims of this study were to explore the relationship of baseline levels of natriuretic peptides ( NPs ) with outcomes and to test for an interaction between baseline levels of NPs and the effects spironolactone . BACKGROUND Plasma NPs are considered to be helpful in the diagnosis of heart failure ( HF ) with preserved ejection fraction ( HFpEF ) , and elevated levels are associated with adverse outcomes . Levels of NPs higher than certain cutoffs are often used as inclusion criteria in clinical trials of HFpEF to increase the likelihood that patients have HF and to select patients at higher risk for events . Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear . METHODS The TOPCAT ( Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial ) trial r and omized patients with HFpEF and either prior hospitalization for HF or elevated natriuretic peptide levels ( B-type NP [ BNP ] ≥100 pg/ml or N-terminal proBNP ≥360 pg/ml ) to spironolactone or placebo . Baseline BNP ( n = 430 ) or N-terminal proBNP ( n = 257 ) levels were available in 687 patients enrolled from the Americas in the elevated-NP stratum of TOPCAT . RESULTS Higher levels of NPs were independently associated with an increased risk for TOPCAT 's primary endpoint of cardiovascular mortality , aborted cardiac arrest , or hospitalization for HF when analyzed either continuously or grouped by terciles , adjusting for region of enrollment , age , sex , atrial fibrillation , diabetes , renal function , body mass index , and heart rate . There was a significant interaction between the effect of spironolactone and baseline NP terciles for the primary outcome ( p = 0.017 ) , with greater benefit of the drug in the lower compared with higher NP terciles . CONCLUSIONS Similar to the effects of irbesartan in the I-PRESERVE ( Irbesartan in Heart Failure With Preserved Ejection Fraction ) trial , a greater benefit of spironolactone was observed in the group with lower levels of NPs and overall risk in TOPCAT . Elevated NPs in HFpEF identify patients at higher risk for events but who may be less responsive to treatment . The mechanism of this apparent interaction between disease severity and response to therapy requires further exploration . ( Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [ TOPCAT ] ; NCT00094302 ) We describe the baseline characteristics of subjects r and omised in the largest placebo‐controlled , morbidity‐mortality trial to date in patients with heart failure and preserved ejection fraction — the irbesartan in heart failure with preserved systolic function trial ( I‐PRESERVE ) Aim To determine the safety and efficacy of nebivolol in elderly heart failure ( HF ) patients with renal dysfunction . Methods and results SENIORS recruited patients aged 70 years or older with symptomatic HF , irrespective of ejection fraction , and r and omized them to nebivolol or placebo . Patients ( n = 2112 ) were divided by tertile of estimated glomerular filtration rate ( eGFR ) . Mean age of patients was 76.1 years , 35 % of patients had an ejection fraction of > 35 % , and 37 % were women result ing in a unique cohort , far more representative of clinical practice than previous trials . eGFR was strongly associated with outcomes and nebivolol was similarly efficacious across eGFR tertiles . The primary outcome rate ( all-cause mortality or cardiovascular hospital admission ) and adjusted hazard ratio for nebivolol use in those with low eGFR was 40 % and 0.84 ( 95 % CI 0.67–1.07 ) , 31 % and 0.79 ( 0.60–1.04 ) in the middle tertile , and 29 % and 0.86 ( 0.65–1.14 ) in the highest eGFR tertile . There was no interaction noted between renal function and the treatment effect ( P = 0.442 ) . Nebivolol use in patients with moderate renal impairment ( eGFR < 60 ) was not associated with major safety concerns , apart from higher rates of drug-discontinuation due to bradycardia . Conclusion Nebivolol is safe and has a similar effect in elderly HF patients with mild or moderate renal impairment BACKGROUND Half of patients with chronic heart failure ( CHF ) have preserved left-ventricular ejection fraction ( LVEF ) , but few treatments have specifically been assessed in such patients . In previous studies of patients with CHF and low LVEF or vascular disease and preserved LVEF , inhibition of the renin-angiotensin system is beneficial . We investigated the effect of addition of an angiotensin-receptor blocker to current treatments . METHODS Between March , 1999 , and July , 2000 , we r and omly assigned 3023 patients c and esartan ( n=1514 , target dose 32 mg once daily ) or matching placebo ( n=1509 ) . Patients had New York Heart Association functional class II-IV CHF and LVEF higher than 40 % . The primary outcome was cardiovascular death or admission to hospital for CHF . Analysis was done by intention to treat . FINDINGS Median follow-up was 36.6 months . 333 ( 22 % ) patients in the c and esartan and 366 ( 24 % ) in the placebo group experienced the primary outcome ( unadjusted hazard ratio 0.89 [ 95 % CI 0.77 - 1.03 ] , p=0.118 ; covariate adjusted 0.86 [ 0.74 - 1.0 ] , p=0.051 ) . Cardiovascular death did not differ between groups ( 170 vs 170 ) , but fewer patients in the c and esartan group than in the placebo group were admitted to hospital for CHF once ( 230 vs 279 , p=0.017 ) or multiple times . Composite outcomes that included non-fatal myocardial infa rct ion and non-fatal stroke showed similar results to the primary composite ( 388 vs 429 ; unadjusted 0.88 [ 0.77 - 1.01 ] , p=0.078 ; covariate adjusted 0.86 [ 0.75 - 0.99 ] , p=0.037 ) . INTERPRETATION C and esartan has a moderate impact in preventing admissions for CHF among patients who have heart failure and LVEF higher than 40 % Background —Heart failure with preserved ejection fraction is a clinical syndrome that has been associated with changes in the extracellular matrix . The purpose of this study was to determine whether profibrotic biomarkers accurately reflect the presence and severity of disease and underlying pathophysiology and modify response to therapy in patients with heart failure with preserved ejection fraction . Methods and Results —Four biomarkers , soluble form of ST2 ( an interleukin-1 receptor family member ) , galectin-3 , matrix metalloproteinase-2 , and collagen III N-terminal propeptide were measured in the Prospect i ve Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction ( PARAMOUNT ) trial at baseline , 12 and 36 weeks after r and omization to valsartan or LCZ696 . We examined the relationship between baseline biomarkers , demographic and echocardiographic characteristics , change in primary ( change in N-terminal pro B-type natriuretic peptide ) and secondary ( change in left atrial volume ) end points . The median ( interquartile range ) value for soluble form of ST2 ( 33 [ 24.6–48.1 ] ng/mL ) and galectin 3 ( 17.8 [ 14.1–22.8 ] ng/mL ) were higher , and for matrix metalloproteinase-2 ( 188 [ 155.5–230.6 ] ng/mL ) lower , than in previously published referent controls ; collagen III N-terminal propeptide ( 5.6 [ 4.3–6.9 ] ng/mL ) was similar to referent control values . All 4 biomarkers correlated with severity of disease as indicated by N-terminal pro B-type natriuretic peptide , E/E′ , and left atrial volume . Baseline biomarkers did not modify the response to LCZ696 for lowering N-terminal pro B-type natriuretic peptide ; however , left atrial volume reduction varied by baseline level of soluble form of ST2 and galectin 3 ; patients with values less than the observed median ( <33 ng/mL soluble form of ST2 and < 17.8 ng/mL galectin 3 ) had reduction in left atrial volume , those above median did not . Although LCZ696 reduced N-terminal pro B-type natriuretic peptide , levels of the other 4 biomarkers were not affected over time . Conclusions —In patients with heart failure with preserved ejection fraction , biomarkers that reflect collagen homeostasis correlated with the presence and severity of disease and underlying pathophysiology , and may modify the structural response to treatment . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00887588 Background —&bgr;-Blocking agents improve functional status and reduce morbidity in mild-to-moderate heart failure , but it is not known whether they produce such benefits in severe heart failure . Methods and Results —We r and omly assigned 2289 patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction < 25 % ( but not volume-overloaded ) to double-blind treatment with either placebo ( n=1133 ) or carvedilol ( n=1156 ) for an average of 10.4 months . Carvedilol reduced the combined risk of death or hospitalization for a cardiovascular reason by 27 % ( P = 0.00002 ) and the combined risk of death or hospitalization for heart failure by 31 % ( P = 0.000004 ) . Patients in the carvedilol group also spent 27 % fewer days in the hospital for any reason ( P = 0.0005 ) and 40 % fewer days in the hospital for heart failure ( P < 0.0001 ) . These differences were as a result of both a decrease in the number of hospitalizations and a shorter duration of each admission . More patients felt improved and fewer patients felt worse in the carvedilol group than in the placebo group after 6 months of maintenance therapy ( P = 0.0009 ) . Carvedilol-treated patients were also less likely than placebo-treated patients to experience a serious adverse event ( P = 0.002 ) , especially worsening heart failure , sudden death , cardiogenic shock , or ventricular tachycardia . Conclusion —In euvolemic patients with symptoms at rest or on minimal exertion , the addition of carvedilol to conventional therapy ameliorates the severity of heart failure and reduces the risk of clinical deterioration , hospitalization , and other serious adverse clinical events BACKGROUND Approximately 50 % of patients with heart failure have a left ventricular ejection fraction of at least 45 % , but no therapies have been shown to improve the outcome of these patients . Therefore , we studied the effects of irbesartan in patients with this syndrome . METHODS We enrolled 4128 patients who were at least 60 years of age and had New York Heart Association class II , III , or IV heart failure and an ejection fraction of at least 45 % and r and omly assigned them to receive 300 mg of irbesartan or placebo per day . The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause ( heart failure , myocardial infa rct ion , unstable angina , arrhythmia , or stroke ) . Secondary outcomes included death from heart failure or hospitalization for heart failure , death from any cause and from cardiovascular causes , and quality of life . RESULTS During a mean follow-up of 49.5 months , the primary outcome occurred in 742 patients in the irbesartan group and 763 in the placebo group . Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1000 patient-years , respectively ( hazard ratio , 0.95 ; 95 % confidence interval [ CI ] , 0.86 to 1.05 ; P=0.35 ) . Overall rates of death were 52.6 and 52.3 per 1000 patient-years , respectively ( hazard ratio , 1.00 ; 95 % CI , 0.88 to 1.14 ; P=0.98 ) . Rates of hospitalization for cardiovascular causes that contributed to the primary outcome were 70.6 and 74.3 per 1000 patient-years , respectively ( hazard ratio , 0.95 ; 95 % CI , 0.85 to 1.08 ; P=0.44 ) . There were no significant differences in the other prespecified outcomes . CONCLUSIONS Irbesartan did not improve the outcomes of patients with heart failure and a preserved left ventricular ejection fraction . ( Clinical Trials.gov number , NCT00095238 . We examined whether an additive treatment with an angiotensin receptor blocker , olmesartan , reduces the mortality and morbidity in hypertensive patients with chronic heart failure ( CHF ) treated with angiotensin-converting enzyme ( ACE ) inhibitors , β-blockers , or both . In this prospect i ve , r and omized , open-label , blinded endpoint study , a total of 1147 hypertensive patients with symptomatic CHF ( mean age 66 years , 75 % male ) were r and omized to the addition of olmesartan ( n = 578 ) to baseline therapy vs. control ( n = 569 ) . The primary endpoint was a composite of all-cause death , non-fatal acute myocardial infa rct ion , non-fatal stroke , and hospitalization for worsening heart failure . During a median follow-up of 4.4 years , the primary endpoint occurred in 192 patients ( 33.2 % ) in the olmesartan group and in 166 patients ( 29.2 % ) in the control group [ hazard ratio ( HR ) 1.18 ; 95 % confidence interval ( CI ) , 0.96–1.46 , P = 0.112 ] , while renal dysfunction developed more frequently in the olmesartan group ( 16.8 vs. 10.7 % , HR 1.64 ; 95 % CI 1.19–2.26 , P = 0.003 ) . Subgroup analysis revealed that addition of olmesartan to combination of ACE inhibitors and β-blockers was associated with increased incidence of the primary endpoint ( 38.1 vs. 28.2 % , HR 1.47 ; 95 % CI 1.11–1.95 , P = 0.006 ) , all-cause death ( 19.4 vs. 13.5 % , HR 1.50 ; 95 % CI 1.01–2.23 , P = 0.046 ) , and renal dysfunction ( 21.1 vs. 12.5 % , HR 1.85 ; 95 % CI 1.24–2.76 , P = 0.003 ) . Additive use of olmesartan did not improve clinical outcomes but worsened renal function in hypertensive CHF patients treated with evidence -based medications . Particularly , the triple combination therapy with olmesartan , ACE inhibitors and β-blockers was associated with increased adverse cardiac events . This study is registered at clinical trials.gov-NCT00417222 AIMS Large r and omized trials have shown that beta-blockers reduce mortality and hospital admissions in patients with heart failure . The effects of beta-blockers in elderly patients with a broad range of left ventricular ejection fraction are uncertain . The SENIORS study was performed to assess effects of the beta-blocker , nebivolol , in patients > /=70 years , regardless of ejection fraction . METHODS AND RESULTS We r and omly assigned 2128 patients aged > /=70 years with a history of heart failure ( hospital admission for heart failure within the previous year or known ejection fraction < /=35 % ) , 1067 to nebivolol ( titrated from 1.25 mg once daily to 10 mg once daily ) , and 1061 to placebo . The primary outcome was a composite of all cause mortality or cardiovascular hospital admission ( time to first event ) . Analysis was by intention to treat . Mean duration of follow-up was 21 months . Mean age was 76 years ( SD 4.7 ) , 37 % were female , mean ejection fraction was 36 % ( with 35 % having ejection fraction > 35 % ) , and 68 % had a prior history of coronary heart disease . The mean maintenance dose of nebivolol was 7.7 mg and of placebo 8.5 mg . The primary outcome occurred in 332 patients ( 31.1 % ) on nebivolol compared with 375 ( 35.3 % ) on placebo [ hazard ratio ( HR ) 0.86 , 95 % CI 0.74 - 0.99 ; P=0.039 ] . There was no significant influence of age , gender , or ejection fraction on the effect of nebivolol on the primary outcome . Death ( all causes ) occurred in 169 ( 15.8 % ) on nebivolol and 192 ( 18.1 % ) on placebo ( HR 0.88 , 95 % CI 0.71 - 1.08 ; P=0.21 ) . CONCLUSION Nebivolol , a beta-blocker with vasodilating properties , is an effective and well-tolerated treatment for heart failure in the elderly BACKGROUND Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure , but little is known about their effects in severe heart failure . METHODS We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion , who were clinical ly euvolemic , and who had an ejection fraction of less than 25 percent . In a double-blind fashion , we r and omly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months , during which st and ard therapy for heart failure was continued . Patients who required intensive care , had marked fluid retention , or were receiving intravenous vasodilators or positive inotropic drugs were excluded . RESULTS There were 190 deaths in the placebo group and 130 deaths in the carvedilol group . This difference reflected a 35 percent decrease in the risk of death with carvedilol ( 95 percent confidence interval , 19 to 48 percent ; P=0.00013 , unadjusted ; P=0.0014 , adjusted for interim analyses ) . A total of 507 patients died or were hospitalized in the placebo group , as compared with 425 in the carvedilol group . This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol ( 95 percent confidence interval , 13 to 33 percent ; P<0.001 ) . The favorable effects on both end points were seen consistently in all the subgroups we examined , including patients with a history of recent or recurrent cardiac decompensation . Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons ( P=0.02 ) . CONCLUSIONS The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial AIMS The SENIORS trial recently demonstrated that nebivolol reduces the composite risk of all-cause mortality and cardiovascular hospital admission in elderly patients with chronic heart failure and , importantly , that ejection fraction does not influence the clinical effects of nebivolol . An echocardiographic sub study was design ed to evaluate the effects of nebivolol on systolic and diastolic left ventricular ( LV ) function in patients stratified according to the presence or absence of systolic LV dysfunction . METHODS AND RESULTS The sub study r and omized 112 patients in 29 European centres , of whom 104 were evaluable for the study ; 43 had an ejection fraction ( EF ) < or=35 % and 61 had an EF>35 % . LV end-systolic volume ( ESV ) , EF , mitral valve E/A ratio , and E-wave deceleration time were assessed at baseline and after 12 months . Echocardiograms were su bmi tted to a core laboratory to perform quantitative analysis in blinded condition . In the group with EF</=35 % , nebivolol reduced ESV ( adjusted difference between treatments 25.8 mL , 95%CI : -46.6 ; -5.0 , P=0.016 ) and improved EF ( adjusted difference between treatments 4.6 % , 95%CI : 1.3;7.9 , P=0.008 ) ; no changes were observed in the E/A ratio or E-wave deceleration time . In EF>35 % group , no significant changes in either systolic or diastolic parameters were observed . CONCLUSION In patients with heart failure and advanced systolic LV dysfunction , nebivolol reduces ventricular size and improves EF . The absence of detectable changes with st and ard echocardiography in patients with predominant diastolic heart failure questions the mechanism of benefit on morbidity/mortality in such patients AIMS The therapeutic strategy for heart failure with preserved ejection fraction ( HFPEF ) has not been established . The Japanese Diastolic Heart Failure Study ( J-DHF ) is a multicentre , prospect i ve , r and omized , open , blinded-endpoint trial , design ed to assess the effects of carvedilol in HFPEF patients . METHODS AND RESULTS A total of 245 patients with heart failure and ejection fraction > 40 % were r and omly assigned into those treated with ( carvedilol group , n = 120 ) and without carvedilol ( control group , n = 125 ) . The primary outcome is a composite of cardiovascular death and unplanned hospitalization for heart failure . During a median follow-up of 3.2 years , the primary endpoint occurred in 29 patients in the carvedilol group and in 34 patients in the control group [ adjusted hazard ratio ( HR ) 0.902 , 95 % confidence interval ( CI ) 0.546 - 1.488 , P = 0.6854 ] . Another major composite endpoint , cardiovascular death and unplanned hospitalization for any cardiovascular causes , occurred in 38 patients of the carvedilol group and 52 patients of the control group ( HR 0.768 , 95 % CI 0.504 - 1.169 ; P = 0.2178 ) . The target dose of carvedilol was 20 mg/day , but the median prescribed dose was 7.5 mg/day . In the patients treated with st and ard doses ( carvedilol > 7.5 mg/day , n = 58 ) , this composite outcome was significantly less than in the controls ( HR 0.539 , 95 % CI 0.303 - 0.959 ; P = 0.0356 ) , whereas it was comparable with the controls in the patients treated with carvedilol ≤7.5 mg/day ( n = 62 , HR 1.070 , 95 % CI 0.650 - 1.763 ; P = 0.7893 ) . CONCLUSIONS Carvedilol did not improve prognosis of HFPEF patients overall ; however , the st and ard dose , not the low dose , prescription might be effective . This may facilitate further investigation . UMIN number : C000000318 BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure . It is unclear , however , if low doses and high doses of ACE inhibitors have similar benefits . METHODS AND RESULTS We r and omly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction < or = 30 % to double-blind treatment with either low doses ( 2.5 to 5.0 mg daily , n=1596 ) or high doses ( 32.5 to 35 mg daily , n=1568 ) of the ACE inhibitor , lisinopril , for 39 to 58 months , while background therapy for heart failure was continued . When compared with the low-dose group , patients in the high-dose group had a nonsignificant 8 % lower risk of death ( P=0.128 ) but a significant 12 % lower risk of death or hospitalization for any reason ( P=0.002 ) and 24 % fewer hospitalizations for heart failure ( P=0.002 ) . Dizziness and renal insufficiency was observed more frequently in the high-dose group , but the 2 groups were similar in the number of patients requiring discontinuation of the study medication . Conclusions -These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor ( unless these are the only doses that can be tolerated ) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor ( if any ) is likely to be very small Background The SENIORS trial demonstrated that nebivolol has beneficial effects in patients with heart failure . However , the role of beta-blocker therapy in patients with heart failure and preserved left ventricular ejection fraction ( HFPEF ) is still unsettled . Objective To assess the long-term effects of administration of nebivolol , compared to placebo , on the clinical symptoms , exercise capacity and parameters of left ventricular ( LV ) function in patients with HFPEF . Methods The Effect of Long-term Administration of Nebivolol on clinical symptoms , exercise capacity and left ventricular function in patients with Diastolic Dysfunction ( EL AND D ) study is a prospect i ve multicenter European trial in 120 patients with HFPEF r and omised to nebivolol or placebo . HFPEF is defined as symptoms or signs of heart failure , a LV ejection fraction > 45 % and evidence of diastolic LV dysfunction by Doppler echocardiography . Procedures include a baseline clinical examination , 6-min walk test ( 6MWT ) , electrocardiography , Doppler echocardiography and Minnesota QoL question naire . Nebivolol or placebo is started at 2.5 mg/day and gradually uptitrated to 10 mg/day . After initiation of the study , patients are assessed at 1 , 2 , 5 and 6 weeks ( titration phase ) and at weeks 12 and 26 . The primary endpoint is the change from baseline in the 6MWT distance with nebivolol versus placebo . Sample size calculations are based on an anticipated 15 % difference ( 70 m ) in the 6MWT distance between nebivolol and placebo-treated patients . This study will allow the collection of data regarding the possible clinical benefits and the effects on LV function of nebivolol administration in patients with HFPEF BACKGROUND It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity . We studied the effect of an angiotensin-converting -- enzyme inhibitor , enalapril , on total mortality and mortality from cardiovascular causes , the development of heart failure , and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure . METHODS Patients were r and omly assigned to receive either placebo ( n = 2117 ) or enalapril ( n = 2111 ) at doses of 2.5 to 20 mg per day in a double-blind trial . Follow-up averaged 37.4 months . RESULTS There were 334 deaths in the placebo group , as compared with 313 in the enalapril group ( reduction in risk , 8 percent by the log-rank test ; 95 percent confidence interval , -8 percent [ an increase of 8 percent ] to 21 percent ; P = 0.30 ) . The reduction in mortality from cardiovascular causes was larger but was not statistically significant ( 298 deaths in the placebo group vs. 265 in the enalapril group ; risk reduction , 12 percent ; 95 percent confidence interval , -3 to 26 percent ; P = 0.12 ) . When we combined patients in whom heart failure developed and those who died , the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group ( 630 vs. 818 ; risk reduction , 29 percent ; 95 percent confidence interval , 21 to 36 percent ; P less than 0.001 ) . In addition , fewer patients given enalapril died or were hospitalized for heart failure ( 434 in the enalapril group ; vs. 518 in the placebo group ; risk reduction , 20 percent ; 95 percent confidence interval , 9 to 30 percent ; P less than 0.001 ) . CONCLUSIONS The angiotensin-converting -- enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations , as compared with the rates in the group given placebo , among patients with asymptomatic left ventricular dysfunction . There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril AIMS Anaemia is a co-morbidity frequently seen in patients with heart failure ( HF ) and reduced left ventricular ejection fraction ( LVEF ) . Its presence carries adverse prognostic effects . The effects of anaemia have not been extensively investigated in patients with preserved or only mildly reduced LVEF . We sought to investigate prevalence and incidence of anaemia in patients with HF irrespective of whether reduced or preserved ejection fraction are present . In addition , we sought to study the effects of nebivolol on the development of anaemia . METHODS AND RESULTS We analysed data from 2069 patients r and omized to nebivolol or placebo in the SENIORS study , 391 ( 10.0 % ) of whom were anaemic . Anaemia was similarly common in patients with LVEF≤35 % and those with LVEF>35 % ( 19.0 vs. 18.7 % , P= 0.89 ) . Anaemic patients were older , had lower diastolic blood pressure , and worse kidney function ( all P < 0.05 ) . No difference was found between patients on nebivolol or placebo with regard to the presence of anaemia . A total of 348 ( 16.8 % ) patients died during follow-up . The combined primary endpoint of all-cause mortality and cardiovascular hospital admission was reached by 687 ( 33.2 % ) patients during follow-up , 164 ( 23.4 % ) of whom were anaemic . Anaemic patients had a higher risk of reaching a primary endpoint than non-anaemics [ LVEF≤35 % : hazard ratio ( HR ) 1.47 , 95 % confidence interval ( CI ) 1.18 - 1.82 , P < 0.001 ; LVEF>35 % : HR 1.47 , 95 % CI 1.09 - 2.00 , P= 0.012 ] . After multivariable adjustment , haemoglobin remained an independent predictor of the primary outcome in this cohort of patients ( HR 0.94 per 1 g/dL increase , 95 % CI 0.89 - 0.99 , P= 0.017 ) . CONCLUSIONS Anaemia is an independent predictor of death or hospitalization for cardiovascular reasons among elderly patients with chronic HF and reduced or preserved/mildly reduced LVEF . Nebivolol does not affect haemoglobin values during follow-up AIMS To investigate the prognostic significance of hospitalization for worsening heart failure ( WHF ) , myocardial infa rct ion ( MI ) , and stroke in patients with chronic heart failure ( HF ) . METHODS AND RESULTS We studied 5011 patients with HF and reduced EF ( HF-REF ) in the CORONA trial and 4128 patients with HF and preserved EF ( HF-PEF ) in the I-Preserve trial . Adjusted hazard ratios ( HRs ) for death were estimated for 0 - 30 days and ≥31 days after first post-r and omization WHF , MI , or stroke used as a time-dependent variable , compared with patients with none of these events . In CORONA , 1616 patients ( 32 % ) had post-r and omization first events ( 1223 WHF , 216 MI , 177 stroke ) , and the adjusted HR for mortality ≤30 days after an event was : WHF 7.21 [ 95 % confidence interval ( CI ) 2.05 - 25.40 ] , MI 23.08 ( 95 % CI 6.44 - 82.71 ) , and stroke 32.15 ( 95 % CI 8.93 - 115.83 ) . The HR for mortality at > 30 days was : WHF 3.62 ( 95 % CI 3.11 - 4.21 ) , MI 4.41 ( 95 % CI 3.23 - 6.02 ) , and stroke 3.19 ( 95 % CI 2.21 - 4.61 ) . In I-Preserve , 896 patients ( 22 % ) experienced a post-r and omization event ( 638 WHF , 111 MI , 147 stroke ) . The HR for mortality ≤30 days was WHF 31.77 ( 95 % CI 7.60 - 132.81 ) , MI 154.77 ( 95 % CI 34.21 - 700.17 ) , and stroke 223.30 ( 95 % CI 51.42 - 969.78 ) ; for > 30 days it was WHF 3.36 ( 95 % CI 2.79 - 4.05 ) , MI 3.29 ( 95 % CI 2.14 - 5.06 ) , and stroke 5.13 ( 95 % CI 3.61 - 7.29 ) . CONCLUSIONS In patients with both HF-REF and HF-PEF , hospitalization for WHF was associated with high early and late mortality . The early relative risk of death was not as great as following MI or stroke , but the longer term relative risk of death was similar following all three types of event . Numerically , more deaths occurred following WHF because it was a much more common event Although the benefits of carvedilol in patients with heart failure and depressed ejection fraction ( EF ) have been eluci date d , those in patients with preserved EF are not understood . We enrolled 40 patients with mild or moderate heart failure and EF > /=45 % . They were r and omly assigned to carvedilol ( n = 19 ) or conventional therapy ( n = 21 ) . After 12 months of treatment , carvedilol significantly improved all end points ( plasma concentration of B-type natriuretic peptide [ BNP ] from 175 ( 35 to 209 ) to 106 ( 52 to 160 ) pg/ml , mean ( 95 % confidence interval ) p < 0.01 ; New York Heart Association functional class from 2.37 ( 2.13 to 2.61 ) to 1.56 ( 1.21 to 1.91 ) , p < 0.01 ; exercise capacity estimated with the Specific Activity Scale from 4.75 ( 4.50 to 5.00 ) to 5.68 ( 5.22 to 6.14 ) METs , p < 0.02 ) , whereas conventional therapy did not ( plasma BNP concentration from 150 ( 114 to 186 ) to 174 ( 100 to 248 ) pg/ml ; New York Heart Association functional class from 2.29 ( 2.08 to 2.50 ) to 2.11 ( 1.73 to 2.49 ) ; exercise capacity from 4.57 ( 4.34 to 4.80 ) to 4.72 ( 4.41 to 5.03 ) METs ) . Univariate regression analyses showed that only the use of carvedilol was correlated with the decrease in plasma BNP concentration ( p < 0.03 ) . Multivariate analyses demonstrated that an ischemic cause of heart failure ( p < 0.02 ) , high plasma concentration of BNP ( p < 0.02 ) , left ventricular dilation ( p < 0.03 ) , and use of carvedilol ( p < 0.04 ) at baseline were predictive of a decrease in plasma concentration of BNP . In conclusion , carvedilol potentially decreased neurohumoral activation , decreased symptoms , and increased exercise capacity in patients with heart failure and preserved EF INTRODUCTION Chronic mitral regurgitation ( MR ) is characterized by adverse ventricular remodeling and progressive LV dysfunction leading to heart failure ( HF ) . Beta-blockers ( BB ) improve LV remodeling and prognosis in patients with HF . As chronic severe MR results in neuroendocrine activation similar to HF , it is likely that BB may also exert favorable effects in these patients . No study has assessed the role of oral BB therapy in chronic rheumatic MR . AIMS A total of 100 patients of chronic rheumatic MR ( mean age 30±13.48 years , NYHA 2.2±0.5 ) were r and omized to BB ( Metoprolol , 37±13.5 mg , n=48 ) vs no BB ( n=52 ) in addition to st and ard therapy . RESULTS Baseline BNP and echocardiographic parameters were comparable in the two groups . At 3 months , BB therapy result ed in significantly lower NYHA class ( 1.97 vs 2.35 ) , BNP ( 141 vs 207 pg/mL ) , LV end-systolic ( 35.89 vs 51.30 ) and LV end-diastolic volumes ( 101 vs 128 mL/m(2 ) ) , LV end-systolic stress ( 81.1 vs 93.3 dyn/cm(2 ) ) , LV mass ( 122 vs 154 gm/m(2 ) ) , and LV work ( 737.02 vs 952.82 mm Hg L/min , all P significant ) . Therapy with BB result ed in a -15.6 % , -10.4%,-12.1 % , and -7.3 % reduction in LV end-systolic and end-diastolic dimensions and LVESVi and LVEDVi , respectively . Following BB therapy , BNP levels , end-systolic stress , indexed LV mass , and LV work also reduced significantly by 27.3 % , 15.6 % , 8.7 % , and 28 % , respectively . The control group had no significant change . The MR grade reduced from severe to moderate in 11 % of those on BB ( controls : no change ) . At 6 months , the BB group had further improvement in all echocardiographic parameters ranging from + 9.1 to -18.2 % . CONCLUSION In this first study of BB in rheumatic MR , targeting the sympatho-adrenergic axis exerted favorable effects on NYHA class , LV volumes , LV end-systolic stress , and LV work . Further studies are required to eluci date the role of BB in rheumatic MR Background —There are few sex-specific outcome data in heart failure with preserved ejection fraction . Methods and Results —We assessed sex differences in baseline characteristics and outcomes among 4128 patients with heart failure with preserved ejection fraction in the Irbesartan in Heart Failure with Preserved Ejection Fraction ( I-PRESERVE ) trial . Women ( n=2491 ) with heart failure with preserved ejection fraction were ≈1 year older ( 72±7 years versus 71±7 years ) and more likely to be obese ( 46 % versus 35 % ) and have chronic kidney disease ( 34 % versus 26 % ) and hypertension ( 91 % versus 85 % ) than men but less likely to have an ischemic cause ( 19 % versus 34 % ) , atrial fibrillation ( 27 % versus 33 % ) , or chronic obstructive pulmonary disease ( 8 % versus 13 % ) ( all P<0.001 ) . During a mean of 49.5 months , there were 881 deaths ( 447 in women , 434 in men ; risk ratio , 0.64 ; 95 % CI , 0.56–0.74 ) and 5776 hospitalizations ( 3239 in women , 2537 in men ; risk ratio , 0.80 ; 95 % CI , 0.76–0.84 ) . Women had lower risk of all-cause events ( deaths and hospitalizations ) , even after adjusting for baseline characteristics ( adjusted hazards ratio , 0.81 ; 95 % CI , 0.73–0.89 ) . However , the sex-related difference in risk of all-cause events was modified in the presence or absence of atrial fibrillation , renal dysfunction , stable angina pectoris , or advanced New York Heart Association class symptoms . Conclusions —In patients with typical heart failure with preserved ejection fraction , there were prominent sex differences in baseline characteristics and outcomes . Women had better overall prognosis , although the presence of 4 common baseline characteristics seemed to moderate this finding . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT000095238 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 BACKGROUND Patients with heart failure and preserved ejection fraction ( HFpEF ) have a poor prognosis , and no therapies have been proven to improve outcomes . It has been proposed that heart failure , including HFpEF , represents overlapping syndromes that may have different prognoses . We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study ( I-PRESERVE ) using latent class analysis ( LCA ) with validation using the C and esartan in Heart failure : Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study to identify HFpEF subgroups . METHODS AND RESULTS In total , 4113 HFpEF patients r and omized to irbesartan or placebo were characterized according to 11 clinical features . The HFpEF subgroups were identified using LCA . Event-free survival and effect of irbesartan on the composite of all-cause mortality and cardiovascular hospitalization were determined for each subgroup . Subgroup definitions were applied to 3203 patients enrolled in CHARM-Preserved to vali date observations regarding prognosis and treatment response . Six subgroups were identified with significant differences in event-free survival ( P < 0.001 ) . Clinical profiles and prognoses of the six subgroups were similar in CHARM-Preserved . The two subgroups with the worst event-free survival in both studies were characterized by a high prevalence of obesity , hyperlipidaemia , diabetes mellitus , anaemia , and renal insufficiency ( Subgroup C ) and by female predominance , advanced age , lower body mass index , and high rates of atrial fibrillation , valvular disease , renal insufficiency , and anaemia ( Subgroup F ) . CONCLUSION Using a data -driven approach , we identified HFpEF subgroups with significantly different prognoses . Further development of this approach for characterizing HFpEF subgroups is warranted OBJECTIVES We sought to evaluate the effects of angiotensin receptor blocker ( ARB ) on cardiac sympathetic nerve activity ( CSNA ) in patients with congestive heart failure ( CHF ) with a preserved left ventricular ejection fraction ( LVEF ) . BACKGROUND Approximately 50 % of patients with CHF have preserved LVEF . It is reported that ARB therapy improves CSNA in CHF patients and reduced LVEF . However , the effect of ARB therapy on CSNA evaluated by iodine-123 meta-iodobenzylguanidine ( (123)I-MIBG ) scintigraphy has not been determined in CHF patients with preserved LVEF . METHODS We selected 50 patients with nonischemic CHF and LVEF > 40 % who were treated with st and ard therapy . Twenty-five patients were r and omized to also receive c and esartan , whereas the remaining 25 patients received placebo . The delayed heart/mediastinum count ( H/M ) ratio , delayed total defect score ( TDS ) , and washout rate ( WR ) were determined by (123)I-MIBG scintigraphy before and six months after treatment . The LV end-diastolic volume and LVEF were determined by echocardiography , and the plasma brain natriuretic peptide ( BNP ) concentration was also measured . RESULTS In patients receiving c and esartan , (123)I-MIBG scintigraphic and echocardiographic parameters were significantly improved after treatment . In contrast , there were no significant changes in these parameters in patients receiving placebo . There was a significant correlation between the changes in (123)I-MIBG scintigraphic findings and the percent change in BNP from baseline to six months in patients receiving c and esartan ( TDS : r = 0.587 , p < 0.005 ; H/M ratio : r = -0.509 , p < 0.01 ; WR : r = 0.602 , p < 0.005 ) . CONCLUSIONS Adding c and esartan to st and ard therapy can improve CSNA and LV performance in CHF patients with preserved LVEF AIM The purpose of this study was to investigate the effects of carvedilol on diastolic function ( DF ) in heart failure patients with preserved left ventricular ( LV ) systolic function and abnormal DF . PATIENTS AND METHODS We r and omised 113 patients with diastolic heart failure ( DHF ) ( symptomatic , with normal systolic LV function and abnormal DF ) into a double blind multi-centre study . The patients received either carvedilol or matching placebo in addition to conventional treatment . After uptitration , treatment was continued for 6 months . Two-dimensional and Doppler echocardiography were used for quantification of LV function at baseline and at follow-up . Four different DF variables were evaluated by Doppler echocardiography : mitral flow E : A ratio , deceleration time ( DT ) , isovolumic relaxation time ( IVRT ) and the ratio of systolic/diastolic pulmonary venous flow velocity ( pv-S/D ) . Primary endpoint was change in the integrated quantitative assessment of all four variables during the study . RESULTS Ninety-seven patients completed the study . A mitral flow pattern reflecting a relaxation abnormality was recorded in 95 patients . There was no effect on the primary endpoint , although a trend towards a better effect in carvedilol treated patients was noticed in patients with heart rates above 71 beats per minute . At the end of the study , there was a statistically significant improvement in E : A ratio in patients treated with carvedilol ( 0.72 to 0.83 ) vs. placebo ( 0.71 to 0.76 ) , P<0.05 . CONCLUSIONS Treatment with carvedilol result ed in a significant improvement in E : A ratio in patients with heart failure due to a LV relaxation abnormality . E : A ratio was found to be the most useful variable to identify diastolic dysfunction in this patient population . This effect was observed particularly in patients with higher heart rates at baseline BACKGROUND Although spironolactone has been shown to decrease morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction , its role in patients with heart failure and preserved left ventricular ejection fraction ( HFpEF ) is not well defined . In this study we investigated the mechanisms involved when elderly women with HFpEF are treated with spironolactone . METHODS AND RESULTS Forty-eight women with HFpEF were enrolled in a r and omized placebo-controlled trial and were assigned to 25 mg spironolactone daily ( n = 24 ) or placebo ( n = 24 ) for 6 months . Six-minute walk distance , clinical composite score , Doppler echocardiography , and biomarkers were determined at baseline and after 3 and 6 months of therapy . Six months of spironolactone treatment stabilized clinical symptoms , as demonstrated by significant worsening of the clinical composite score in the placebo group ( P = .02 ) . In addition , spironolactone treatment improved diastolic function by significantly increasing early diastolic tissue Doppler velocity of the lateral mitral annulus ( lateral e ' ; P = .003 ) and significantly reducing the mitral peak E velocity to lateral e ' ratio ( lateral E/e ' ; P = .0001 ) . Finally , spironolactone favorably affected remodeling through a reduction in myocardial fibrosis measured by a reduction in type III procollagen levels ( P = .035 ) . Six-minute walk distance did not significantly improve with spironolactone treatment compared with placebo . CONCLUSIONS Spironolactone stabilizes functional capacity and symptoms and improves diastolic function , possibly through its ability to suppress type III procollagen synthesis BACKGROUND Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently . We studied the effect of an angiotensin-converting-enzyme inhibitor , enalapril , on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35 . METHODS Patients receiving conventional treatment for heart failure were r and omly assigned to receive either placebo ( n = 1284 ) or enalapril ( n = 1285 ) at doses of 2.5 to 20 mg per day in a double-bind trial . Approximately 90 percent of the patients were in New York Heart Association functional classes II and III . The follow-up averaged 41.4 months . RESULTS There were 510 deaths in the placebo group ( 39.7 percent ) , as compared with 452 in the enalapril group ( 35.2 percent ) ( reduction in risk , 16 percent ; 95 percent confidence interval , 5 to 26 percent ; P = 0.0036 ) . Although reductions in mortality were observed in several categories of cardiac deaths , the largest reduction occurred among the deaths attributed to progressive heart failure ( 251 in the placebo group vs. 209 in the enalapril group ; reduction in risk , 22 percent ; 95 percent confidence interval , 6 to 35 percent ) . There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure . Fewer patients died or were hospitalized for worsening heart failure ( 736 in the placebo group and 613 in the enalapril group ; risk reduction , 26 percent ; 95 percent confidence interval , 18 to 34 percent ; P less than 0.0001 ) . CONCLUSIONS The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions BACKGROUND Although monitoring the clinical status of patients with heart failure rests at the core of clinical medicine , the ability of different techniques to reflect clinical change has not been evaluated . This study sought to describe changes in various measures of disease status associated with gradations of clinical change . METHODS A prospect i ve , 14-center cohort of 476 out patients was assessed at baseline and 6 + /- 2 weeks to compare changes in 7 heart failure measures with clinical ly observed change . Measures included health status instruments ( the Kansas City Cardiomyopathy Question naire [ KCCQ ] , Short Form-12 , and EQ-5D ) , physician-assessed functional class ( New York Heart Association [ NYHA ] ) , an exercise test ( 6-minute walk ) , patient weight , and a biomarker ( B-type natriuretic peptide ) . Cardiologists , blinded to all measures except weight and NYHA , categorized clinical change ranging from large deterioration to large improvement . RESULTS The KCCQ , NYHA , and 6-minute walk test were most sensitive to clinical change . For patients with large , moderate , and small deteriorations , the KCCQ decreased by 25 + /- 16 , 17 + /- 14 , and 5.3 + /- 11 points , respectively . For patients with small , moderate , and large improvements , the KCCQ increased by 5.7 + /- 16 , 10.5 + /- 16 , and 22.3 + /- 16 points , respectively ( P < .01 for all compared with the no change group ) . New York Heart Association and 6-minute walk distance were significantly different for those with moderate and large changes ( P < .05 ) but neither revealed a difference between those with small versus no clinical deterioration . The KCCQ had the highest c statistic for monitoring individual patients , followed by NYHA and 6-minute walk . CONCLUSION The KCCQ , followed by the NYHA and the 6-minute walk test , most accurately reflected clinical change in patients with heart failure BACKGROUND The prevalence of chronic heart failure ( CHF ) rises with increasing age , from < 1 % in those below 65 years of age to > 5 % in those over 65 years of age and is a major cause of morbidity and mortality in older people . Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure , and a lack of information on treatment for heart failure in the elderly in general . AIMS The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people , in the absence of any major left ventricular systolic dysfunction . SUBJECTS One thous and people over the age of 70 years will be recruited into this study . Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography . METHODS Once a diagnosis of chronic heart failure has been confirmed , the patient will receive either perindopril or placebo in addition to their usual treatment . Death , and unplanned heart failure related hospitalisations , are the primary outcomes . Quality of life , as measured by the Guyatt question naire will be assessed at the beginning of the study and at 1 year . Sub- studies of this trial include a 6-min walking test and more detailed evaluation of ventricular function ( as assessed by echocardiography ) . Both parameters will be measured at 8 weeks and 1 year , and analysed against baseline data . Cognitive function in this group of patients will also be evaluated at baseline and 1 year . This trial is due to report in the year 2001 BACKGROUND Heart failure with preserved ejection fraction is associated with substantial morbidity and mortality , but effective treatments are lacking . We assessed the efficacy and safety of LCZ696 , a first-in-class angiotensin receptor neprilysin inhibitor ( ARNI ) , in patients with this disorder . METHODS PARAMOUNT was a phase 2 , r and omised , parallel-group , double-blind multicentre trial in patients with New York Heart Association ( NYHA ) class II-III heart failure , left ventricular ejection fraction 45 % or higher , and NT-proBNP greater than 400 pg/mL. Participants were r and omly assigned ( 1:1 ) by central interactive voice response system to LCZ696 titrated to 200 mg twice daily or valsartan titrated to 160 mg twice daily , and treated for 36 weeks . Investigators and participants were masked to treatment assignment . The primary endpoint was change in NT-proBNP , a marker of left ventricular wall stress , from baseline to 12 weeks ; analysis included all patients r and omly assigned to treatment groups who had a baseline and at least one postbaseline assessment . This trial is registered at Clinical trials.gov , number NCT00887588 . FINDINGS 149 patients were r and omly assigned to LCZ696 and 152 to valsartan ; 134 in the LCZ696 group and 132 in the valsartan group were included in analysis of the primary endpoint . NT-proBNP was significantly reduced at 12 weeks in the LCZ696 group compared with the valsartan group ( LCZ696 : baseline , 783 pg/mL [ 95 % CI 670 - 914 ] , 12 weeks , 605 pg/mL [ 512 - 714 ] ; valsartan : baseline , 862 pg/mL [ 733 - 1012 ] , 12 weeks , 835 [ 710 - 981 ] ; ratio LCZ696/valsartan , 0·77 , 95 % CI 0·64 - 0·92 , p=0·005 ) . LCZ696 was well tolerated with adverse effects similar to those of valsartan ; 22 patients ( 15 % ) on LCZ696 and 30 ( 20 % ) on valsartan had one or more serious adverse event . INTERPRETATION In patients with heart failure with preserved ejection fraction , LCZ696 reduced NT-proBNP to a greater extent than did valsartan at 12 weeks and was well tolerated . Whether these effects would translate into improved outcomes needs to be tested prospect ively . FUNDING Novartis BACKGROUND The prognostic merit of insulin-like growth factor-binding protein 7 ( IGFBP7 ) is unknown in heart failure and preserved ejection fraction ( HFpEF ) . METHODS AND RESULTS Baseline IGFBP7 ( BL-IGFBP7 ; n = 302 ) and 6-month change ( Δ ; n = 293 ) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction ( I-PRESERVE ) trial . Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years ; secondary outcomes included HF events . Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age ( R2 = 0.13 ; P < .0001 ) , amino-terminal pro-B-type NP ( R2 = 0.22 ; P < .0001 ) , and estimated glomerular filtration rate ( eGFR ; R2 = 0.14 ; P < .0001 ) , but not with signs/symptoms of HFpEF . BL-IGFBP7 was significantly associated with the primary outcome ( hazard ratio [ HR ] = 1.007 per ng/mL ; P < .001 ) , all-cause mortality ( HR = 1.008 per ng/mL ; P < .001 ) , and HF events ( HR = 1.007 per ng/mL ; P < .001 ) . IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro-B-type NP and eGFR but not all variables in the I-PRESERVE prediction model . After 6 months , IGFBP7 did not change significantly in either treatment group . ΔIGFBP7 was significantly associated with decrease in eGFR in patients r and omized to irbesartan ( R2 = 0.09 ; P = .002 ) . ΔIGFBP7 was not independently associated with outcome . CONCLUSIONS Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events , but after multivariable adjustment this association was no longer present . Further studies of IGFBP7 are needed to eluci date its mechanism . CLINICAL TRIAL REGISTRATION www . clinical trials.gov , NCT00095238 BACKGROUND Cardiac fibrosis is a major determinant of myocardial stiffness , diastolic dysfunction , and heart failure ( HF ) . By reducing cardiac fibrosis , aldosterone antagonists have the potential to be beneficial in heart failure with preserved ejection fraction ( HFpEF ) . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled trial of 44 patients with HFpEF , we examined the effects of eplerenone , an aldosterone antagonist , on changes in 6-minute walk distance ( primary end point ) , diastolic function , and biomarkers of collagen turnover ( secondary end points ) . All patients had a history of hypertension , 61 % were diabetic , and 52 % had prior HF hospitalization . After 6 months of treatment , similar improvements in 6 minute walk distance were noted in the eplerenone and placebo groups ( P = .91 ) . However , compared with placebo , eplerenone was associated with a significant reduction in serum markers of collagen turnover ( procollagen type I aminoterminal peptide , P = .009 and carboxy-terminal telopeptide of collagen type I , P = .026 ) and improvement in echocardiographic measures of diastolic function ( E/E ' , P = .01 ) . CONCLUSIONS Although eplerenone was not associated with an improvement in exercise capacity compared to placebo , it was associated with significant reduction in markers of collagen turnover and improvement in diastolic function . Whether these favorable effects will translate into morbidity and mortality benefit in HFpEF remains to be determined BACKGROUND Mineralocorticoid antagonists improve survival among patients with chronic , severe systolic heart failure and heart failure after myocardial infa rct ion . We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms . METHODS In this r and omized , double-blind trial , we r and omly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35 % to receive eplerenone ( up to 50 mg daily ) or placebo , in addition to recommended therapy . The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure . RESULTS The trial was stopped prematurely , according to prespecified rules , after a median follow-up period of 21 months . The primary outcome occurred in 18.3 % of patients in the eplerenone group as compared with 25.9 % in the placebo group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.54 to 0.74 ; P<0.001 ) . A total of 12.5 % of patients receiving eplerenone and 15.5 % of those receiving placebo died ( hazard ratio , 0.76 ; 95 % CI , 0.62 to 0.93 ; P=0.008 ) ; 10.8 % and 13.5 % , respectively , died of cardiovascular causes ( hazard ratio , 0.76 ; 95 % CI , 0.61 to 0.94 ; P=0.01 ) . Hospitalizations for heart failure and for any cause were also reduced with eplerenone . A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8 % of patients in the eplerenone group and 7.2 % of those in the placebo group ( P<0.001 ) . CONCLUSIONS Eplerenone , as compared with placebo , reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00232180 . ) BACKGROUND Despite increasing prevalence of heart failure ( HF ) in patients with preserved ejection fraction ( PEF ) , there are no available therapies proven to reduce morbidity and mortality . Aldosterone , a potent stimulator of myocardial and vascular fibrosis , may be a key mediator of HF progression in this population and is therefore an important therapeutic target . OBJECTIVE The TOPCAT trial is design ed to evaluate the effect of spironolactone , an aldosterone antagonist , on morbidity , mortality , and quality of life in patients with HF-PEF . METHODS Up to 3,515 patients with HF-PEF will be r and omized in double-blind fashion to treatment with spironolactone ( target dose 30 mg daily ) or matching placebo . Eligible patients include those with age ≥50 years , left ventricular ejection fraction ≥45 % , symptomatic HF , and either a hospitalization for HF within the prior year or an elevated natriuretic peptide level ( B-type natriuretic peptide ≥100 pg/mL or N-terminal pro-B-type natriuretic peptide ≥360 pg/mL ) within the 60 days before r and omization . Patients with uncontrolled hypertension and those with known infiltrative or hypertrophic cardiomyopathy are excluded . The primary end point is the composite of cardiovascular death , hospitalization for HF , or aborted cardiac arrest . Key secondary end points include quality of life , nonfatal cardiovascular events , and new-onset atrial fibrillation . Ancillary studies of echocardiography , tonometry , and cardiac biomarkers will provide more insight regarding this understudied population and the effects of spironolactone therapy . CONCLUSION TOPCAT is design ed to assess definitively the role of spironolactone in the management of HF-PEF OBJECTIVES This study was design ed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure ( HFPSF ) . BACKGROUND Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction , the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown . METHODS We evaluated 44 patients with HFPSF , r and omly assigned to control ( n = 20 ) or eplerenone 25 mg daily ( n = 24 ) for 6 months , increased to 50 mg daily from 6 to 12 months . Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides , matrix metalloproteinase type-2 , interleukin-6 and -8 , and tumor necrosis factor-alpha . Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained . RESULTS The mean age of the patients was 80 + /- 7.8 years ; 46 % were male ; 64 % were receiving an angiotensin-converting enzyme inhibitor , 34 % an angiotensin-II receptor blocker , and 68 % were receiving beta-blocker therapy . Pro-collagen type-III and -I aminoterminal peptides , matrix metalloproteinase type-2 , interleukin-6 and -8 , and tumor necrosis factor-alpha increased with time in the control group . Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months ( p = 0.006 ) . Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide . CONCLUSIONS This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction . Despite high background utilization of renin-angiotensin-aldosterone modulators , eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease . ( The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure ; NCT00505336 ) BACKGROUND Worsening renal function ( WRF ) associated with renin-angiotensin-aldosterone system ( RAAS ) inhibition does not confer excess risk in heart failure patients with reduced ejection fraction ( HFrEF ) . OBJECTIVES The goal of this study was to investigate the relationship between WRF and outcomes in heart failure patients with preserved ejection fraction ( HFpEF ) and the interaction with RAAS blockade . METHODS In 3,595 patients included in the I-PRESERVE ( Irbesartan in Heart Failure With Preserved Ejection Fraction ) trial , change in estimated glomerular filtration rate ( eGFR ) and development of WRF after initiation of irbesartan or placebo were examined . We examined the association between WRF and the first occurrence of cardiovascular death or heart failure hospitalization ( primary outcome in this analysis ) and the interaction with r and omized treatment . RESULTS Estimated GFR decreased early with irbesartan treatment and remained significantly lower than in the placebo group . WRF developed in 229 ( 6.4 % ) patients and occurred more frequently with irbesartan treatment ( 8 % vs. 4 % ) . Overall , WRF was associated with an increased risk of the primary outcome ( adjusted hazard ratio [ HR ] : 1.43 ; 95 % confidence interval [ CI ] : 1.10 to 1.85 ; p = 0.008 ) . Although the risk related to WRF was greater in the irbesartan group ( HR : 1.66 ; 95 % CI : 1.21 to 2.28 ; p = 0.002 ) than with placebo ( HR : 1.09 ; 95 % CI : 0.66 to 1.79 ; p = 0.73 ) , the interaction between treatment and WRF on outcome was not significant in an adjusted analysis . CONCLUSIONS The incidence of WRF in HFpEF was similar to that previously reported in HFrEF but more frequent with irbesartan than with placebo . WRF after initiation of irbesartan treatment in HFpEF was associated with excess risk , in contrast to WRF occurring with RAAS blockade in HFrEF |
10,917 | 30,389,320 | The RCTs were from USA ( n = 3 ) , Sweden ( n = 2 ) , Belgium ( n = 2 ) , China ( n = 2 ) , Australia ( n = 2 ) , Denmark ( n = 2 ) , Northern Irel and , Norway , Canada , UK and Netherl and s. The economic studies were from UK ( n = 2 ) , Sweden ( n = 2 ) , Belgium and Netherl and s. The results showed that regular pharmacist input was most cost effective .
No evidence was found for 7-day pharmacist presence .
CONCLUSIONS Pharmacist inclusion in the ward multidisciplinary team improves patient safety and satisfaction and is cost-effective when regularly provided throughout the ward stay .
Research is needed to determine whether the provision of 7-day service is cost-effective | BACKGROUND Pharmacists play important role in ensuring timely care delivery at the ward level .
The optimal level of pharmacist input , however , is not clearly defined .
OBJECTIVE To systematic ally review the evidence that assessed the outcomes of ward pharmacist input for people admitted with acute or emergent illness . | BACKGROUND Previous studies found that medication errors result from lack of sufficient information during the prescribing step . Therefore , it is proposed that having a pharmacist available when patients are evaluated during the rounding process may reduce the likelihood of preventable adverse drug events ( ADEs ) . The objectives of this study were to evaluate the impact of having a pharmacist participate with a physician rounding team on preventable ADEs in general medicine units and to document pharmacist interventions made during the rounding process . METHODS A single-blind , st and ard care-controlled study design was used to compare patients receiving care from a rounding team including a pharmacist with patients receiving st and ard care ( no pharmacist on rounding team ) . Patients admitted to and discharged from the same general medicine unit were included in the study . The main outcome measure of this study was preventable ADEs . Patient records were r and omly selected and evaluated by a blinded process involving independent senior pharmacist specialists and a senior staff physician . Interventions made by the pharmacists in the treatment group were documented . RESULTS The rate of preventable ADEs was reduced by 78 % , from 26.5 per 1000 hospital days to 5.7 per 1000 hospital days . There were 150 documented interventions recommended during the rounding process , 147 of which were accepted by the team . The most common interventions were ( 1 ) dosing-related changes and ( 2 ) recommendations to add a drug to therapy . CONCLUSION Pharmacist participation with the medical rounding team on a general medicine unit contributes to a significant reduction in preventable ADEs Objective Heart failure patients are regularly admitted to hospital and frequently use multiple medication . Besides intentional changes in pharmacotherapy , unintentional changes may occur during hospitalisation . The aim of this study was to investigate the effect of a clinical pharmacist discharge service on medication discrepancies and prescription errors in patients with heart failure . Setting A general teaching hospital in Tilburg , the Netherl and s. Method An open r and omized intervention study was performed comparing an intervention group , with a control group receiving regular care by doctors and nurses . The clinical pharmacist discharge service consisted of review of discharge medication , communicating prescribing errors with the cardiologist , giving patients information , preparation of a written overview of the discharge medication and communication to both the community pharmacist and the general practitioner about this medication . Within 6 weeks after discharge all patients were routinely scheduled to visit the outpatient clinic and medication discrepancies were measured . Main outcome measure The primary endpoint was the frequency of prescription errors in the discharge medication and medication discrepancies after discharge combined . Results Forty-four patients were included in the control group and 41 in the intervention group . Sixty-eight percent of patients in the control group had at least one discrepancy or prescription error against 39 % in the intervention group ( RR 0.57 ( 95 % CI 0.37–0.88 ) ) . The percentage of medications with a discrepancy or prescription error in the control group was 14.6 % and in the intervention group it was 6.1 % ( RR 0.42 ( 95 % CI 0.27–0.66 ) ) . Conclusion This clinical pharmacist discharge service significantly reduces the risk of discrepancies and prescription errors in medication of patients with heart failure in the 1st month after discharge OBJECTIVES To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management ( GEM ) care on the appropriateness of prescribing . DESIGN R and omized , controlled trial , with the patient as unit of r and omization . SETTING Acute GEM unit . PARTICIPANTS Two hundred three patients aged 70 and older . INTERVENTION Pharmaceutical care provided from admission to discharge by a specialist clinical pharmacist who had direct contacts with the GEM team and patients . MEASUREMENTS Appropriateness of prescribing on admission , at discharge , and 3 months after discharge , using the Medication Appropriateness Index ( MAI ) , Beers criteria , and Assessing Care of Vulnerable Elders ( ACOVE ) underuse criteria and mortality , readmission , and emergency visits up to 12 months after discharge . RESULTS Intervention patients were significantly more likely than control patients to have an improvement in the MAI and in the ACOVE underuse criteria from admission to discharge ( odds ratio (OR)=9.1 , 95 % confidence interval (CI)=4.2 - 21.6 and OR=6.1 , 95 % CI=2.2 - 17.0 , respectively ) . The control and intervention groups had comparable improvements in the Beers criteria . CONCLUSION Pharmaceutical care provided in the context of acute GEM care improved the appropriate use of medicines during the hospital stay and after discharge . This is an important finding , because only limited data exist on the effect of various strategies to improve medication use in elderly in patients . The present approach has the potential to minimize risk and improve patient outcomes PURPOSE OF THE STUDY To determine the prevalence of delayed discharges of elderly in patients and associated costs . DESIGN AND METHODS We search ed Medline , Embase , Global Health , CAB Abstract s , Econlit , Web of Knowledge , EBSCO - CINAHL , The Cochrane Library , Health Management Information Consortium , and SCIE - Social Care Online for evidence published between 1990 and 2015 on number of days or proportion of delayed discharges for elderly in patients in acute hospitals . Descriptive and regression analyses were conducted . Data on proportions of delayed discharges were pooled using a r and om effects logistic model and the association of relevant factors was assessed . Mean costs of delayed discharge were calculated in USD adjusted for Purchasing Power Parity ( PPP ) . RESULTS Of 64 studies included , 52 ( 81.3 % ) reported delayed discharges as proportions of total hospital stay and 9 ( 14.1 % ) estimated the respective costs for these delays . Proportions of delayed discharges varied widely , from 1.6 % to 91.3 % with a weighted mean of 22.8 % . This variation was also seen in studies from the same country , for example , in the United Kingdom , they ranged between 1.6 % and 60.0 % . No factor was found to be significantly associated with delays . The mean costs of delayed discharge also varied widely ( between 142 and 31,935 USD PPP adjusted ) , reflecting the variability in mean days of delay per patient . IMPLICATION S Delayed discharges occur in most countries and the associated costs are significant . However , the variability in prevalence of delayed discharges and available data on costs limit our knowledge of the full impact of delayed discharges . A st and ardization of methods is necessary to allow comparisons to be made , and additional studies are required-preferably by disease area-to determine the postdischarge needs of specific patient groups and the estimated costs of delays Background Pharmacists may improve medication-related outcomes during transitions of care . The aim of the Iowa Continuity of Care Study was to determine if a pharmacist case manager ( PCM ) providing a faxed discharge medication care plan from a tertiary care institution to primary care could improve medication appropriateness and reduce adverse events , rehospitalization and emergency department visits . Methods Design . R and omized , controlled trial of 945 participants assigned to enhanced , minimal and usual care groups conducted 2007 to 2012 . Subjects . Participants with cardiovascular-related conditions and /or asthma or chronic obstructive pulmonary disease were recruited from the University of Iowa Hospital and Clinics following admission to general medicine , family medicine , cardiology or orthopedics . Intervention . The minimal group received admission history , medication reconciliation , patient education , discharge medication list and medication recommendations to inpatient team . The enhanced group also received a faxed medication care plan to their community physician and pharmacy and telephone call 3–5 days post-discharge . Participants were followed for 90 days post-discharge . Main Outcomes and Measures . Medication appropriateness index ( MAI ) , adverse events , adverse drug events and post-discharge healthcare utilization were compared by study group using linear and logistic regression , as models accommodating r and om effects due to pharmacists indicated little clustering . Results Study groups were similar at baseline and the intervention fidelity was high . There were no statistically significant differences by study group in medication appropriateness , adverse events or adverse drug events at discharge , 30-day and 90-day post-discharge . The average MAI per medication as 0.53 at discharge and increased to 0.75 at 90 days , and this was true across all study groups . Post-discharge , about 16 % of all participants experienced an adverse event , and this did not differ by study group ( p > 0.05 ) . Almost one-third of all participants had any type of healthcare utilization within 30 days post-discharge , where 15 % of all participants had a 30-day readmission . Healthcare utilization post-discharge was not statistically significant different at 30 or 90 days by study group . Conclusion The pharmacist case manager did not affect medication use outcomes post-discharge perhaps because quality of care measures were high in all study groups . Trial registration Clinical trials.gov registration : NCT00513903 , August 7 , 2007 BACKGROUND Adverse events related to drugs occur frequently among in patients , and many of these events are preventable . However , few data are available on adverse drug events among out patients . We conducted a study to determine the rates , types , severity , and preventability of such events among out patients and to identify preventive strategies . METHODS We performed a prospect i ve cohort study , including a survey of patients and a chart review , at four adult primary care practice s in Boston ( two hospital-based and two community-based ) , involving a total of 1202 out patients who received at least one prescription during a four-week period . Prescriptions were computerized at two of the practice s and h and written at the other two . RESULTS Of the 661 patients who responded to the survey ( response rate , 55 percent ) , 162 had adverse drug events ( 25 percent ; 95 percent confidence interval , 20 to 29 percent ) , with a total of 181 events ( 27 per 100 patients ) . Twenty-four of the events ( 13 percent ) were serious , 51 ( 28 percent ) were ameliorable , and 20 ( 11 percent ) were preventable . Of the 51 ameliorable events , 32 ( 63 percent ) were attributed to the physician 's failure to respond to medication-related symptoms and 19 ( 37 percent ) to the patient 's failure to inform the physician of the symptoms . The medication classes most frequently involved in adverse drug events were selective serotonin-reuptake inhibitors ( 10 percent ) , beta-blockers ( 9 percent ) , angiotensin-converting-enzyme inhibitors ( 8 percent ) , and nonsteroidal antiinflammatory agents ( 8 percent ) . On multivariate analysis , only the number of medications taken was significantly associated with adverse events . CONCLUSIONS Adverse events related to drugs are common in primary care , and many are preventable or ameliorable . Monitoring for and acting on symptoms are important . Improving communication between out patients and providers may help prevent adverse events related to drugs RATIONALE , AIMS AND OBJECTIVES To determine whether an increased input by clinical pharmacists at each stage of the patient 's hospital journey , from admission through discharge , result ed in an enhanced level of patient care as measured by a number of clinical and economic outcomes . METHODS This project was design ed to address medicines management issues in patients deemed at risk of drug-related problems . During the project , these latter patients at the time of admission were r and omly assigned to an integrated medicines management ( IMM ) service group ( n = 371 ) or regular hospital care group ( n = 391 ) . The IMM service involved comprehensive pharmaceutical care provided by a pharmacy team throughout each of three stages : patient admission , inpatient monitoring and counselling , and patient discharge . RESULTS Patients who received the IMM service benefited from a reduced length of hospital stay [ by 2 days ( P = 0.003 ; independent sample s t-test log(e ) ) ] . IMM patients also had a decreased rate of readmission over a 12-month follow-up period ( 40.8 % vs. 49.3 % ; p = 0.027 ; Fisher 's exact test ) and an increased time to readmission [ 20 days longer ( P = 0.0356 ; log rank test ) ] . A numbers-needed-to-treat calculation indicated that for approximately every 12 patients receiving the IMM service , one readmission to hospital , within 12 months of discharge , would be prevented . The new service was welcomed by cognate health care professionals . CONCLUSION The IMM service proved very effective and can be used as a template to support the implementation of comprehensive pharmaceutical care as a routine service across Northern Irel and and beyond Elderly patients are vulnerable to medication errors and adverse drug events due to increased morbidity , polypharmacy and inappropriate interactions . The objective of this study was to investigate whether systematic medication review and counselling performed by a clinical pharmacist and clinical pharmacologist would reduce length of in-hospital stay in elderly patients admitted to an acute ward of internal medicine . A r and omized , controlled study of 100 patients aged 70 years or older was conducted in an acute ward of internal medicine in Denmark . Intervention arm : a clinical pharmacist conducted systematic medication review s after an experienced medical physician had prescribed the patients ' medication . Information was collected from medical charts , interview with the patients and data base registration s of drug purchase . Subsequently , medication histories were conferred with a clinical pharmacologist and advisory notes recommending medication changes were completed . Physicians were not obliged to comply with the recommendations . Control arm : medication was review ed by usual routine in the ward . Primary end-point was length of in-hospital stay . In addition , readmissions , mortality , contact to primary healthcare and quality of life were measured at 3-month follow-up . In the intervention arm , the mean length of in-hospital stay was 239.9 hr ( 95 % CI : 190.2 - 289.6 ) and in the control arm : 238.6 hr ( 95 % CI : 137.6 - 339.6 ) , which was neither a statistical significant nor a clinical ly relevant difference . Moreover , no differences were observed for any of the secondary end-points . Systematic medication review and medication counselling did not show any effect on in-hospital length of stay in elderly patients when admitted to an acute ward of internal medicine Objective To evaluate the impact of pharmacist interventions on antibiotic use in in patients with respiratory tract infections in a tertiary hospital in China . Method Two independent respiratory wards were r and omized into control and intervention group . Between July 2009 and April 2010 , all in patients diagnosed with respiratory tract infections were enrolled . Pharmacist interventions were performed on the physicians in the intervention group . The total cost of hospitalization , cost of antibiotics , length of hospital stay and the scores of 6 items of inappropriate antibiotic use ( including indication , choice , dosage , dosing schedule , duration and conversion ) were analyzed . Results The total costs of hospitalization in the intervention group were significant lower compared to the control group ( $ 1442.3 ± 684.9 vs. $ 1729.6 ± 773.7 , P < 0.001 ) , as well as the cost of antibiotics ( $ 832.0 ± 373.0 vs. $ 943.9 ± 412.0 , P = 0.01 ) , and the patients required shorter length of hospital stay ( 14.2 ± 6.2 vs. 15.8 ± 6.0 days , P = 0.03 ) . The scores with respect to the 6 items of inappropriate antibiotic use were all lower in the intervention group than in the control group . Conclusions Pharmacist interventions , interacted directly with the physicians at ward level , could play an important role in optimizing antibiotic use , thus lead to the reduction in patients ’ length of hospital stay and health care cost Objective To evaluate the effects of a clinical pharmacist service on health-related quality of life ( HRQL ) and prescribing of drugs . Methods A r and omised controlled study was performed in two internal medicine wards . The intervention consisted of medication review s with feedback to the physicians , drug treatment discussion with patients at discharge and medication reports . HRQL was evaluated at inclusion and after six months by self-rated global health ( 1 : very poor ; 5 : very good ) and by the EuroQol 5-dimension question naire ( EQ-5D ) . Prescribing of drugs was analysed regarding three established drug-specific quality indicators ( intervention and control patients ) and potential drug-related problems ( DRPs ) during in-hospital care ( intervention patients ) . Results 345 patients ( 61 % female ; median age : 82 ) were analysed , 204 of whom ( 59 % ) completed the six-month HRQL follow-up . A total of 87 patients ( 53 % of the intervention patients ) received all parts of the intervention . Intention-to-treat analysis revealed no significant findings for any of the HRQL measures . Per- protocol analysis revealed significantly better HRQL in the intervention group at six-month follow-up as measured by global health ( mean : 3.14 ( SD : 0.87 ) vs 2.77 ( 0.94 ) , p=0.020 ) , but not as measured by summarised EQ-5D index ( 0.48 ( 0.36 ) vs 0.43 ( 0.37 ) , p=0.57 ) . The number of potentially inappropriate prescribings per patient according to the quality indicators ( admission vs discharge ) was 0.35 ( 0.73 ) versus 0.38 ( 0.72 ) , p=0.47 ( control patients ) , and 0.39 ( 0.83 ) versus 0.26 ( 0.56 ) , p=0.039 ( intervention patients who received the intervention ) . In the intervention group , 133 relevant potential DRPs were identified in 81 patients , 55 of which ( 41 % ) were acted upon by the attending physician . Conclusion A clinical pharmacist service during inpatient care may improve quality of prescribing and patients ' HRQL . Trial registration clinical trials.gov Identifier : NCT01016301 RATIONALE , AIMS AND OBJECTIVES This study evaluated clinical pharmacy costs against drug costs . METHOD We conducted a r and omized interventional comparative trial at the surgical intensive care unit ( ICU ) of Ghent University Hospital , Belgium ( period B : group B1 with pharmacist consultation ; control group B0 ) . We obtained before ( period A ) and after ( period C ) control groups using 1:1 propensity score matching with B1 and B0 . Mean daily ICU drug costs with st and ard error of the mean ( SEM ) were compared between B1 and B0 ( primary analysis ) and between matched pairs ( AB1 , AB0 , CB1 and CB0 ; secondary analysis ) . For B , we performed a 1000 bootstrapping ( by resampling B1 and B0 ) , calculated the benefit-cost ratio using pharmacy time ( gross salary ) as cost ( euros ) and drug cost savings as benefit . We performed sensitivity analysis with and without outlier drug costs ( i.e. twice the st and ard deviation ) . PERSPECTIVE Belgian health care payer . RESULTS In period B , 135 patients were r and omized : B0 , n = 60 ; B1 , n = 75 . Pharmacists provided recommendations in 148/706 ( 21.0 % ) therapies with 83.1 % acceptance . Mean drug cost difference between B0 ( 430.6 euros , SEM 406.0 ) and B1 ( 221.2 euros , SEM 58.7 ) ( P = 0.870 ) became significant after excluding outlier drug costs ( B0 , 184.4 euros , SEM 42.5 ; B1 , 90.5 euros , SEM 17.7 ; P < 0.001 ) . Recommendations were cost-beneficial ( break-even drug costs or savings ) in 53.8 % of patients with a benefit-cost ratio of 25:1 ( confidence interval -5:1 to 94:1 ) . In sensitivity analysis excluding outlier drug costs , B0 costs were significantly higher than both A and C , indicating high baseline expenses in B0 . CONCLUSIONS The r and omized interventional comparative trial in a small ICU patient group suggested the potential cost-benefit of clinical pharmacy on daily ICU drug costs . However , after matching , this benefit was attenuated . A final conclusion dem and s a larger r and omized trial adopting a similar design with matched controls . Future research should include clinical impact of recommendations Background Medication discrepancies may occur at transitions in care and negatively impact patient outcomes . Objective To determine if involving clinical pharmacists in hospital care , medication reconciliation and discharge medication plan communication can reduce medication discrepancies with a prospect i ve , r and omized , blinded , controlled trial . Setting A large , tertiary care , academic medical center . Method The intervention consisted of clinical pharmacist medication reconciliation , patient education and improved communication of the discharge medication plan , as devised by the hospital physician and care team , to primary care physicians and community pharmacists . Medication discrepancies were identified by blinded research pharmacists who review ed primary care physician and pharmacy records at discharge through 90 days post-discharge to create 30- and 90-day medication lists . Main outcome measure Rate of medication discrepancies compared across groups . Results A total of 592 subjects from internal medicine , family medicine , cardiology and orthopedic services were evaluated for this study . Clinical ly important medication discrepancies in the primary care physician record were different between groups 30 days after hospital discharge following a clinical pharmacist ’s intervention . The mean number of medication discrepancies per patient for the enhanced group being nearly half the number in the control group . However , this effect did not persist to 90 days post-discharge and did not extend to community pharmacy records . Conclusion The present study demonstrates the involvement of pharmacists in hospital care , medication reconciliation and discharge medication plan communication may affect the quality of the outpatient medical record Introduction Patients admitted to an intensive care unit ( ICU ) are at high risk for prescribing errors and related adverse drug events ( ADEs ) . An effective intervention to decrease this risk , based on studies conducted mainly in North America , is on-ward participation of a clinical pharmacist in an ICU team . As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established , we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm ( preventable ADEs ) in this specific setting . Methods A prospect i ve study compared a baseline period with an intervention period . During the intervention period , an ICU hospital pharmacist review ed medication orders for patients admitted to the ICU , noted issues related to prescribing , formulated recommendations and discussed those during patient review meetings with the attending ICU physicians . Prescribing issues were scored as prescribing errors when consensus was reached between the ICU hospital pharmacist and ICU physicians . Results During the 8.5-month study period , medication orders for 1,173 patients were review ed . The ICU hospital pharmacist made a total of 659 recommendations . During the intervention period , the rate of consensus between the ICU hospital pharmacist and ICU physicians was 74 % . The incidence of prescribing errors during the intervention period was significantly lower than during the baseline period : 62.5 per 1,000 monitored patient-days versus 190.5 per 1,000 monitored patient-days , respectively ( P < 0.001 ) . Preventable ADEs ( patient harm , National Coordinating Council for Medication Error Reporting and Prevention severity categories E and F ) were reduced from 4.0 per 1,000 monitored patient-days during the baseline period to 1.0 per 1,000 monitored patient-days during the intervention period ( P = 0.25 ) . Per monitored patient-day , the intervention itself cost € 3 , but might have saved € 26 to € 40 by preventing ADEs . Conclusions On-ward participation of a hospital pharmacist in a Dutch ICU was associated with significant reductions in prescribing errors and related patient harm ( preventable ADEs ) at acceptable costs per monitored patient-day . Trial registration numberIS RCT AIMS The use of medication and information discharge summaries ( MIDS ) has become a st and ard procedure in many hospitals . We have evaluated if these summaries , together with in-patient pharmaceutical counselling backed up with a simple medicine reminder card , may help with the delivery of seamless pharmaceutical care . METHODS Elderly patients prescribed more than four items discharged to their own home received the st and ard discharge policy including a recently introduced MIDS and medicine reminder card . Each patient 's GP was sent a copy on discharge . Pre-discharge a pharmacist counselled study patients about their medicines and compliance . A research pharmacist visited patients in their home approximately 2 - 3 weeks and at 3 months post-discharge to determine their drug knowledge , compliance , home medicine stocks and any healthcare related events . RESULTS Forty-three study and 40 control patients completed both visits . Their mean ( s.d . ) ages were 80.2 ( 5,7 ) and 81.1 ( 5,8 ) years and they were prescribed 7.1 ( 1.8 ) and 7.1 ( 2.3 ) items , respectively . At visit 1 knowledge ( P < 0.01 ) and compliance ( P < 0.001 ) was better in the study group . At visit 2 compliance had improved in the study group ( P < 0.001 ) . Unplanned visits to the GP and readmission to hospital amongst the study group were 19 and 5 , respectively , which were both significantly less ( P < 0.05 ) than 27 and 13 in the control group . At visit 2 for the study group the 24 unplanned GP visits and three re-admissions were significantly ( P < 0.05 ) less than the respective 32 and 15 in the control group . At visit 1 , two study group patients had altered their own medication compared with 10 control patients . At visit 2 these reduced to 0 and 4 , respectively . CONCLUSIONS In-patient pharmaceutical counselling , linked to a medication and information discharge summary and a medicine reminder card , contributed to better drug knowledge and compliance together with reduced unplanned visits to the doctor and re-admissions . A pharmaceutical domiciliary visit consoli date d the improved healthcare outcomes Objectives Physicians in acute admission units ( AAUs ) are obliged to obtain medication history and perform medication reconciliation , which is time consuming and often incomplete . Studies show that clinical pharmacists ( CPs ) can obtain accurate medication histories , but so far no studies have investigated the effect of this on time measures . Therefore , the objective of the present study was to investigate the effect of a CP intervention on length of stay ( LOS ) in an AAU . Methods The study was design ed as a prospect i ve , cluster r and omised study . Weekdays were r and omised to control or intervention . CP intervention consisted of obtaining medication history and performing medication reconciliation and review . The primary outcome was LOS in the AAU . Secondary outcomes were other time-related measures —for example , physicians ’ self-reported time spent on medication topics . Finally , the number of documented medications per patient was established . Results 232 and 216 patients , respectively , were included on control ( n=63 ) and intervention ( n=63 ) days . The mean LOS was 342 ( 95 % CI 323 to 362 ) min in the intervention group and 339 ( 95 % CI 322 to 357 ) min in the control group , which was not statistically significantly different . Physicians spent on average 4.3 ( 95 % CI 3.7 to 5.0 ) min in the intervention group and 7.5 ( 95 % CI 6.6 to 8.5 ) min in the control group , corresponding to an overall reduction of 43.0 % ( 95 % CI 30.9 % to 53.0 % , p<0.001 ) . The number of documented medications per patient was 10.0 ( intervention group ) and 8.8 ( control group ) . Conclusions This study indicates that LOS in the AAU was not affected by CP intervention ; however , physicians reported a significant reduction in time spent on medication topics . Trial registration number Clinical Trial Gov : 1 - 16 - 02 - 379 - 13 |
10,918 | 30,798,316 | Compared with other teaching methods , HFPS revealed higher effects sizes on nursing students ' knowledge and performance . | OBJECTIVE The purpose was to analyse the effectiveness of high-fidelity patient simulation ( HFPS ) based on life-threatening clinical condition scenarios on undergraduate and postgraduate nursing students ' learning outcomes . | This study evaluated the effects of brief monthly refresher training on CPR skill retention , confidence , and satisfaction with CPR skill level of 606 nursing students from ten different US schools . Students were r and omized to course type , HeartCode ™ Basic Life Support ( BLS ) or an instructor-led ( IL ) course , and then r and omized to a practice group , six minutes of monthly practice or no further practice . End-of- study survey results were compiled and reported as percentages . Short answer data were grouped by category for reporting . Fewer HeartCode ™ BLS students were satisfied with their CPR training compared to the IL students . Students who practice d CPR monthly were more confident than students who did not practice . Monthly practice improved CPR confidence , but initial course type did not . Students were most satisfied when they participated in the IL courses and frequent practice of CPR skills BACKGROUND The use of simulation to reproduce the experience of health care setting s and its use as a strategy in the teaching of nurses has grown at an unprecedented rate . There is little scientific evidence to examine the differences in satisfaction and gains perceived by the students with the use of medium and high fidelity . OBJECTIVES To analyse and benchmark gains and satisfaction perceived by nursing students , according to their participation in medium- and high-fidelity simulated practice . DESIGN R and omized control trial post-test only design with control group . SETTING AND PARTICIPANTS Students of the 4th year of the Bachelor 's Degree in Nursing who performed medium and high-fidelity simulated practice in a Simulation Centre environment . METHODS A satisfaction scale and a scale of perceived gains from the simulation were applied to the students who underwent simulated practice in a medium-fidelity environment ( control group ) and high-fidelity environment ( experimental group ) . Statistical analysis was performed and a significance level of p<0.05 was established . RESULTS Of the 85 students who participated in the study , the majority were female ( 92.94 % ) , with an average age of 21.89years ( SD=2.81years ) . Satisfaction is statistically significant in the realism dimension and overall satisfaction . In the gains perceived with the simulation there is a statistically significant difference in the dimension recognition/decision . CONCLUSION Students are very satisfied with the realism of high-fidelity simulated practice and consider that this helps them more with recognition and decision compared with the medium-fidelity simulation INTRODUCTION One of the newest teaching modalities in health education is the use of human patient simulators ( HPS ) . A simulation scenario creates a software program vignette in which nursing , medical , and other students interact with a manikin to practice caring for patients in a risk-free environment . Although used extensively in schools of nursing , there is little research that examines if these expensive simulators improve the clinical decision-making ability of nursing students . The purpose of this quasi-experimental differentiated treatment study was to assess if HPS technology leads to greater clinical decision-making ability and clinical performance compared to the teaching modality of a paper and pencil case study . METHODS Students ( n = 133 ) learning about the care of a patient with a myocardial infa rct ion at four licensed practical nursing programs ( LPN ) in Pennysylvania , USA were r and omly assigned to one of two groups at each site : an HPS simulation group or a paper and pencil case study group . One-tailed , independent t-tests were used to compare learning gains measured by differences in pre- and post clinical decision-making exam scores and clinical performance . RESULTS Results indicated that students in the simulation groups were significantly more likely to score higher on the clinical decision-making exams and to respond clinical ly by performing CPR more quickly on the manikin than students in the case study groups . On the 100-point exam , the simulation groups had a 20-point gain , while the case study groups had a 12-point gain ( P < 0.001 ) . Students in the simulation groups provided CPR to a manikin 30 seconds faster , on an average ( P < 0.001 ) . DISCUSSION Results vali date the use of HPS technology in nursing education . Ultimately patients may benefit from increased knowledge and speed of care from practical nurses whose training was improved through the use of HPS technology BACKGROUND Clinical simulations can provide students with realistic clinical learning environments to increase their knowledge , self-confidence , and decrease their anxiety prior to entering clinical practice setting s. OBJECTIVE To compare the effectiveness of two maternal newborn clinical simulation scenarios ; virtual clinical simulation and face-to-face high fidelity manikin simulation . DESIGN R and omized pretest-posttest design . SETTING A public research university in Canada . PARTICIPANTS Fifty-six third year Bachelor of Science in Nursing students . METHODS Participants were r and omized to either face-to-face or virtual clinical simulation and then to dyads for completion of two clinical simulations . Measures included : ( 1 ) Nursing Anxiety and Self-Confidence with Clinical Decision Making Scale ( NASC-CDM ) ( White , 2011 ) , ( 2 ) knowledge pretest and post-test related to preeclampsia and group B strep , and ( 3 ) Simulation Completion Question naire . Before and after each simulation students completed a knowledge test and the NASC-CDM and the Simulation Completion Question naire at study completion . RESULTS There were no statistically significant differences in student knowledge and self-confidence between face-to-face and virtual clinical simulations . Anxiety scores were higher for students in the virtual clinical simulation than for those in the face-to-face simulation . Students ' self-reported preference was face-to-face citing the similarities to practicing in a ' real ' situation and the immediate debrief . Students not liking the virtual clinical simulation most often cited technological issues as their rationale . CONCLUSIONS Given the equivalency of knowledge and self-confidence when undergraduate nursing students participate in either maternal newborn clinical scenarios of face-to-face or virtual clinical simulation identified in this trial , it is important to take into the consideration costs and benefits /risks of simulation implementation BACKGROUND There is a gap in the literature regarding learning outcomes linked to the use of high-fidelity simulators compared to that of traditional teaching methods . AIM To examine the effect of using high-fidelity simulators on knowledge and skills acquisition and retention with university students . METHODS A r and omized two-arm trial using two different educational approaches on 90 nursing students assigned r and omly to two groups was used at two points of time . FINDINGS The results showed significant differences in favor of the participants in the high-fidelity simulator group on both the acquisition and retention of knowledge and skills over time . However , a significant loss of cardiopulmonary resuscitation knowledge and skills occurred at 3 months after training in both groups . CONCLUSIONS The findings of this study may assist educators in integrating high-fidelity simulators in education and training . In addition , the findings may help nursing educators to arrange additional cardiopulmonary resuscitation training sessions in order to improve cardiac arrested patients ' outcomes . LINKING EVIDENCE TO ACTION High-fidelity simulation ( HFS ) provides students with interactive learning experiences in a safe controlled environment . HFS enables teachers to implement critical clinical scenarios , such as cardiac arrest , without risk to patients . Integrating the simulation training into nursing curricula will help to overcome the challenges that face many courses , specifically the shortage of clinical areas for training and the increase in numbers of nursing students PURPOSE To investigate occupational exposures to biological material potentially infected by blood-borne viruses in nursing student population during the course years . DESIGN AND METHODS An observational retrospective study was design ed . Data were collected in May 2007 . Two-thous and -two-hundred-fifteen nursing students from the 3 years of degree course were enrolled in the four Italian universities . A structured question naire was constructed and was given out unannounced to nursing students in four universities on a r and omly chosen day . The likelihood of association between nursing student exposure and certain assumed risk factors was measured . FINDINGS The exposure risk is associated with each study year of nursing students . Specifically , the probability of accidental exposure is reduced significantly with the increase of clinical skills during the training period . The risk for exposure in the 1st year students appears significantly higher than in those of the next years ( odds ratio [ OR ] 1.465 ; 95 % confidence interval [ CI ] 1.105 - 1.943 ) . Data highlighted a gradual increase of bio-safety knowledge in nursing students from the 1st to the 3rd years of study . However , a statistically significant association exists only between awareness of a correct use of gloves and exposure risk ( OR 0.435 ; 95%CI 0.227 - 0.834 ) . Mucocutaneous exposures are more frequent than percutaneous exposures ( 62.2 % ) , and the hollow-bore needle is the device most often involved . In 42.5 % of cases , accidental exposures occurred when nursing students are working alone in a medical ward or surgery area . CONCLUSIONS During their clinical training , nursing students can encounter a real risk for percutaneous and mucocutaneous exposures to blood potentially infected with blood-borne viruses . However , this risk is reduced with an increase in clinical skills . CLINICAL RELEVANCE Results show that some new strategies are necessary for exposure risk reduction such as development of simulation laboratories for nursing practice and the adequate presence of tutors in clinical training education Epidemiological evidence about the accuracy of diagnostic tests , the power of prognostic markers , and the efficacy and safety of interventions is the cornerstone of evidence -based health care.1 Practitioners of evidence -based health care require critical appraisal skills to judge the validity of this evidence . The Evidence -Based Medicine ( EBM ) Working Group members are international leaders in teaching critical appraisal skills , and their users ’ guides for appraising the validity of the healthcare literature 2 have long been the basis of teaching programmes worldwide . However , we found that many of our students took a reductionist “ paint by numbers ” approach when using the Working Group ’s guides . Students could answer individual appraisal questions correctly but would have difficulty assessing overall study quality . We believe this is due to a poor underst and ing of epidemiological study design . So over the past 15 years of teaching critical appraisal we have modified the EBM Working Group approach and developed the Graphic Appraisal Tool for Epidemiological studies ( GATE ) frame to help our students conceptualise the whole study as well as its component parts . GATE is a visual framework that illustrates the generic design of all epidemiological studies ( figure 1 ) . We now teach critical appraisal by “ hanging ” studies and the EBM Working Group ’s appraisal questions on the GATE frame . Figure 1 The GATE frame . This editorial outlines the GATE approach to critical appraisal , illustrated throughout using the Heart and Estrogen/progestin Replacement Study ( HERS ) , a r and omised , double blind , placebo controlled trial of the effect of daily oestrogen plus progestin on coronary heart disease ( CHD ) death in postmenopausal women.3 A detailed critical appraisal of HERS using a GATE-based checklist is available online.4 The GATE frame incorporates a triangle , circle , square , and arrow ( figure 1 ) , labelled with the acronym PECOT ( or PICOT ) . The triangle ( figure 2 ) represents the population studied : “ P ” for population or BACKGROUND An undergraduate nursing health assessment course provided three experiential modalities for practicing health assessment skills : high-fidelity human simulators ( HFS ) , st and ardized patients ( SP ) and community volunteers ( CV ) . Previous research has examined the impact of each distinct modality on learning outcomes . However , few studies have compared these learning strategies . This study investigates learners ' satisfaction , self-efficacy and performance behaviors among three learning approaches . METHOD Forty-four undergraduate nursing students were r and omly assigned to perform focused respiratory assessment s on a HFS , SP or CV . Participants completed the Health Assessment Educational Modality Evaluation ( HAEME ) survey to assess self-efficacy and modality satisfaction . A performance checklist evaluated assessment skills . RESULTS Performance behaviors were significantly greater with HFS , but learners were significantly less satisfied with this modality . Significant differences in students ' self-efficacy were not found across the three modalities . CONCLUSIONS Significantly lower satisfaction with HFS may reflect learners ' perceived lack of realism . However , HFS may provide a low-stress opportunity for novice learners to practice skills . Results support the integration of distinct experiential learning modalities in an undergraduate nursing health assessment course Patient simulation is increasingly used in the education of healthcare providers , yet few studies have compared simulation to other teaching modalities . The purpose of this study was to determine differences in knowledge acquisition and student satisfaction between two methods of teaching the principles of mechanical ventilation to advanced practice nursing ( APN ) students : high-fidelity patient simulation ( including face-to-face instruction ) versus an online , narrated PowerPoint presentation . Twenty APN students were r and omized to either the simulation or online teaching method in this pre/posttest study . Measures included a 12-item knowledge question naire and a 5-item satisfaction survey . Both groups had significant improvement in knowledge scores from pretest to posttest , but knowledge scores were not significantly different at posttest between groups . Student satisfaction with their learning method was significantly higher in the simulation group . Students choosing to participate in the alternative teaching method after study completion preferred the simulation to the online method Nursing actively engages various technologies to enhance education and training with increased learner confidence and patient safety . Simulation is a key technology to address the strain on the current nursing education system . The purpose of this study was to determine the effect of simulation-enhanced orientation on pediatric acute care examination scores and pediatric clinical course grade s among junior-level baccalaureate nursing students . No significant difference between groups ( p < 0.05 ) was detected for the students ' examination scores . Clinical grade s of the intervention group ( mean = 3.7 ) were significantly higher ( t[75.3 ] = 5.2 , p < 0.001 ) than those of the control group ( mean = 3.4 ) . These results support the expansion of simulation in the curriculum and prompt the proposal of simulation as an appropriate substitution for portions of pediatric clinical experience . Given the strain on the current nursing education system , simulation will be a critical component of nursing education in the future The purpose of this study was to compare the effectiveness of static simulation to high-fidelity simulation when teaching advanced cardiac life support guidelines . Using a quasi-experimental design , 49 BSN students were r and omly assigned to 2 groups of either static or high-fidelity simulation . There were no significant differences between the static and high-fidelity simulation groups on the written examination . The high-fidelity simulation group outperformed the static simulation group on megacode performance The study was design ed to compare the efficacy of controlled simulation mannequin ( SM ) assisted learning and case study presentation on knowledge and confidence of nurse practitioner ( NP ) students in managing a cardiac event . Twenty-three volunteer students were r and omly assigned to the experimental ( simulation ) or control ( case study presentation ) group . All participants were instructed on atrial arrhythmias , were pre- and post-tested on knowledge and confidence , and completed an evaluation of the experience . There were no statistically significant differences in knowledge test scores , although the control group scored significantly higher on post- test confidence ( p=.040 ) . Both groups rated their experience as valuable . The simulation and case study presentation had similar outcomes . Additional research is needed to determine the effectiveness of this teaching modality ABSTRACT This study examined and compared the effectiveness of videotape training versus h and s‐on instruction in preparing senior nursing students to respond to emergency clinical situations . Fourth year nursing students ( n = 27 ) were r and omly assigned to one of three groups ; one group received videotaped instruction , one group engaged in a h and s‐on experience , and one group , a control , received no instruction . Students were evaluated using a three‐station objective structured clinical examination that involved high‐fidelity simulations . Differences between the control and the two instructional groups were significant ( p = .007 ) ; however , there was no significant difference between the two types of instruction . It was concluded that instruction on crisis management with a high‐fidelity simulator , using either video or h and s‐on instruction , can result in a significant improvement in performance BACKGROUND Existing research literature indicates that the use of various simulation techniques in the training of physical examination skills develops students ' cognitive and psychomotor abilities in a realistic learning environment while improving patient safety . OBJECTIVES The study aim ed to compare the effects of the use of a high-fidelity simulator and st and ardized patients on the knowledge and skills of students conducting thorax-lungs and cardiac examinations , and to explore the students ' views and learning experiences . DESIGN A mixed- method explanatory sequential design . SETTING S The study was conducted in the Simulation Laboratory of a Nursing School , the Training Center at the Faculty of Medicine , and in the inpatient clinics of the Education and Research Hospital . PARTICIPANTS Fifty-two fourth-year nursing students . METHODS Students were r and omly assigned to Group I and Group II . The students in Group 1 attended the thorax-lungs and cardiac examination training using a high-fidelity simulator , while the students in Group 2 using st and ardized patients . After the training sessions , all students practice d their skills on real patients in the clinical setting under the supervision of the investigator . RESULTS Knowledge and performance scores of all students increased following the simulation activities ; however , the students that worked with st and ardized patients achieved significantly higher knowledge scores than those that worked with the high-fidelity simulator ; however , there was no significant difference in performance scores between the groups . The mean performance scores of students on real patients were significantly higher compared to the post-simulation assessment scores ( p<0.001 ) . CONCLUSIONS Results of this study revealed that use of st and ardized patients was more effective than the use of a high-fidelity simulator in increasing the knowledge scores of students on thorax-lungs and cardiac examinations ; however , practice on real patients increased performance scores of all students without any significant difference in two groups The realistic and practical environment that simulation provides is an extremely useful part of the teaching process . Simulation is widely used in health and nursing education today . This study aims to evaluate the effect of simulation-based teaching on the acquisition and retention of arrhythmia-related knowledge among nursing students . A r and omized controlled design involving a pretest – posttest was used . Nursing students were allocated r and omly either to the experimental group ( n = 47 ) , who attended simulation scenarios on cardiac arrhythmia , or to the control group ( n = 44 ) who received a traditional lecture on the same topic . A paired t test showed that the mean knowledge score at the posttest was significantly higher than at the pretest for both groups . However , participants in the experimental group demonstrated significantly increased knowledge of cardiac arrhythmia in the first and the second posttest compared with those in the control group . Thus , simulation is superior and significantly improves students ’ arrhythmia knowledge CONTEXT A principal justification for the use of high-fidelity ( HF ) simulation is that , because it is closer to reality , students will be more motivated to learn and , consequently , will be better able to transfer their learning to real patients . However , the increased authenticity is accompanied by greater complexity , which may reduce learning , and variability in the presentation of a condition on an HF simulator is typically restricted . OBJECTIVES This study was conducted to explore the effectiveness of HF and low-fidelity ( LF ) simulation for learning within the clinical education and practice domains of cardiac and respiratory auscultation and physical assessment skills . METHODS Senior-level nursing students were r and omised to HF and LF instruction groups or to a control group . Primary outcome measures included LF ( digital sounds on a computer ) and HF ( human patient simulator ) auscultation tests of cardiac and respiratory sounds , as well as observer-rated performances in simulated clinical scenarios . RESULTS On the LF auscultation test , the LF group consistently demonstrated performance comparable or superior to that of the HF group , and both were superior to the performance of the control group . For both HF outcome measures , there was no significant difference in performance between the HF and LF instruction groups . CONCLUSIONS The results from this study suggest that highly context ualised learning environments may not be uniformly advantageous for instruction and may lead to ineffective learning by increasing extraneous cognitive load in novice learners OBJECTIVES This study is involved in design ing high-fidelity simulations reflecting the Korean nursing education environment . In addition , it evaluated the simulations by nursing students ' learning outcomes and perceptions of the simulation design features . DESIGN A quantitative design was used in two separate phases . SETTING S AND PARTICIPANTS For the first phase , five nursing experts participated in verifying the appropriateness of two simulation scenarios that reflected the intended learning objectives . For the second phase , 69 nursing students in the third year of a bachelor 's degree at a nursing school participated in evaluating the simulations and were r and omized according to their previous course grade s. METHODS The first phase verified the two simulation scenarios using a question naire . The second phase evaluated students ' perceptions of the simulation design , self-confidence , and critical thinking skills using a quasi-experimental post-test design . ANCOVA was used to compare the experimental and control groups , and correlation coefficient analysis was used to determine the correlation among them . RESULTS We created 2 simulation scenarios to integrate cognitive and psychomotor skills according to the learning objectives and clinical environment in Korea . The experimental group had significantly higher scores on self-confidence in the first scenario . The positive correlations between perceptions of the simulation design features , self-confidence , and critical thinking skill scores were statistically significant . CONCLUSIONS Students with a more positive perception of the design features of the simulations had better learning outcomes . Based on this result , simulations need to be design ed and implemented with more differentiation in order to be perceived more appropriately by students |
10,919 | 31,104,484 | In addition , resistance training showed no significant association with cancer mortality .
Conclusion Resistance training is associated with lower mortality and appears to have an additive effect when combined with aerobic exercise .
There are insufficient data to determine the potential beneficial effect of resistance training on non-fatal events or the effect of substituting aerobic exercise with resistance training | Background The benefits of aerobic exercise are well-studied ; there is no consensus on the association between resistance training and major adverse cardiovascular outcomes .
This systematic review and meta- analysis aim ed to address this issue . | BACKGROUND The role of weight training in the primary prevention of type 2 diabetes mellitus ( T2DM ) is largely unknown . METHODS To examine the association of weight training with risk of T2DM in US men and to assess the influence of combining weight training and aerobic exercise , we performed a prospect i ve cohort study of 32 002 men from the Health Professionals Follow-up Study observed from 1990 to 2008 . Weekly time spent on weight training and aerobic exercise ( including brisk walking , jogging , running , bicycling , swimming , tennis , squash , and calisthenics/rowing ) was obtained from question naires at baseline and biennially during follow-up . RESULTS During 508 332 person-years of follow-up ( 18 years ) , we documented 2278 new cases of T2DM . In multivariable-adjusted models , we observed a dose-response relationship between an increasing amount of time spent on weight training or aerobic exercise and lower risk of T2DM ( P < .001 for trend ) . Engaging in weight training or aerobic exercise for at least 150 minutes per week was independently associated with a lower risk of T2DM of 34 % ( 95 % CI , 7%-54 % ) and 52 % ( 95 % CI , 45%-58 % ) , respectively . Men who engaged in aerobic exercise and weight training for at least 150 minutes per week had the greatest reduction in T2DM risk ( 59 % ; 95 % CI , 39%-73 % ) . CONCLUSIONS Weight training was associated with a significantly lower risk of T2DM , independent of aerobic exercise . Combined weight training and aerobic exercise conferred a greater benefit Background Increased exercise capacity favourably influences clinical outcomes after transcatheter aortic valve implantation . In our SPORT : TAVI r and omised pilot trial , eight weeks of endurance and resistance training ( training group , TG ) shortly after transcatheter aortic valve implantation result ed in significantly improved exercise capacity , muscular strength and quality of life compared to usual care ( UC ) . However , the long-term clinical benefits of such an intervention are unknown . Design A r and omised controlled trial . Methods SPORT : TAVI participants underwent re assessment of trial endpoints 24 ± 6 months after baseline : maximal oxygen uptake ( VO2peak ) and anaerobic threshold ( VO2AT ) were assessed with cardiopulmonary exercise testing , muscular strength with one-repetition maximum testing , quality of life with the Kansas City cardiomyopathy and medical outcomes study 12-item short-form health survey question naires , and prosthetic aortic valve function with echocardiography . Results Of 27 original participants ( TG 13 ; UC 14 ; age 81 ± 6 years ) , more patients had died during follow-up in UC ( n = 5 ) than in TG ( n = 2 ; P = 0.165 ) ; three further patients ( TG 1 ; UC 2 ) were unavailable for other reasons . In the remaining patients ( TG 10 ; UC 7 ) , a significant between-group difference in favour of TG was observed for change in VO2AT from baseline ( 2.7 ml/min/kg ( 95 % confidence interval 0.8–4.6 ) ; P = 0.008 ) , but not for change in VO2peak ( 2.1 ml/min/kg ( –1.1–5.4 ) ; P = 0.178 ) . Changes in muscular strength and quality of life did not differ between groups over time . Overall , prosthetic valve function remained intact in both groups . Conclusions Eight weeks of exercise training shortly after transcatheter aortic valve implantation result ed in preserved long-term improvements in VO2AT , but not VO2peak , muscular strength or quality of life compared to usual care . The findings emphasise the importance of ongoing exercise interventions following transcatheter aortic valve implantation to maintain initial improvements long term . Clinical Trial Registration ( original trial ) : Clinical trials.gov NCT01935297 BACKGROUND Exercise has been reported to decrease cancer-related fatigue and to increase quality of life ( QoL ) in various breast cancer ( BC ) population s. However , studies investigating exercise during radiotherapy or resistance training are scarce . We conducted a r and omized , controlled trial ( BEST study ) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention . PATIENTS AND METHODS One hundred sixty patients with BC stage 0-III were r and omly assigned to a 12-week progressive resistance training ( 2 times/week ) or a 12-week relaxation control ( RC , 2 times/week ) . Both interventions were group-based . The primary end point fatigue was assessed with a 20-item multidimensional question naire , QoL with EORTC question naires . Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13 . RESULTS Adherence to the intervention program as well as the completion rate ( 97 % ) for the primary outcome variable fatigue was high . In intention-to-treat analyses for the N = 155 patients , significant between-group mean differences ( MD ) favoring the exercise group ( EX ) were observed for general fatigue ( P = 0.044 ) , especially for the subscale physical fatigue [ MD = -0.8 ; 95 % confidence interval -1.5 to -0.2 , P = 0.013 ] , but not for affective ( P = 0.91 ) or cognitive fatigue ( P = 0.65 ) . For QoL , significantly larger improvements regarding the role function ( P = 0.035 ) and pain ( P = 0.040 ) were noted among exercisers compared with RCs . Future perspective improved significantly stronger in the RC group compared with the EX group ( P = 0.047 ) . CONCLUSIONS The 12-week resistance training program was a safe , feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy . As exercise was compared with another group-based intervention , results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits , and that the clinical ly relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher . TRIAL REGISTRATION Clinical Trials.gov NCT01468766 Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background : Resistance training ( RT ) improves muscular strength , physical functioning and quality of life in prostate cancer survivors , but the optimal frequency of RT is unknown . We conducted a pilot r and omized controlled trial to compare the effects of 3 versus 2 days per week of RT in prostate cancer survivors diagnosed within the past 2 years . Methods : Prostate cancer survivors ( N=30 ) were r and omized to 12 weeks of supervised RT performed either 3 days per week ( n=16 ) or 2 days per week ( n=14 ) . The primary outcome was muscular strength assessed by a multiple repetition maximum test at baseline and postintervention . Secondary outcomes were objective physical functioning , quality of life and psychosocial functioning . Results : A trend ( P<0.10 ) and /or potentially meaningful effects ( st and ardized effect size d⩾0.20 ) were found favoring 3 days per week over 2 days per week for the primary outcome of lower body strength ( mean difference=27.8 kg ; 95 % confidence interval=−0.9 to 56.5 ; P=0.057 ; d=0.72 ) and for the secondary outcomes of 30-s chair st and ( d=0.29 ; P=0.31 ) , sit and reach ( d=0.24 ; P=0.33 ) , 6 -min walk ( d=0.21 ; P=0.42 ) and the physical component summary ( d=0.21 ; P=0.41 ) . Conversely , a trend and /or potentially meaningful effects were found favoring 2 days per week over 3 days per week for the mental component summary ( d=−0.38 ; P=0.10 ) , mental health ( d=−0.44 ; P=0.11 ) , vitality ( d=−0.31 ; P=0.28 ) , role-emotional ( d=−0.23 ; P=0.43 ) , anxiety ( d=0.32 ; P=0.29 ) , happiness ( d=−0.31 ; P=0.36 ) and perceived stress ( d=0.23 ; P=0.39 ) . Conclusions : This pilot r and omized dose – comparison trial provides preliminary data to suggest that RT 3 days per week compared with 2 days per week may improve the strength and physical functioning in prostate cancer survivors , but may also blunt improvements in psychosocial functioning . Larger and more targeted phase II and III trials are needed to confirm the potentially complex effects of RT frequency in prostate cancer survivors BACKGROUND Resistance training has been introduced in cardiac rehabilitation to give more benefit than traditional training . Haemodynamic evaluation of cardiac patients to resistance training has generally consisted of continuous HR monitoring and discontinuous blood pressure measurements . DESIGN AND METHODS Blood pressure ( BP ) and heart rate ( HR ) responses to resistance training were evaluated using continuous monitoring ( Finapres ) during low ( four sets of 17 repetitions at 40 % of the one-repetition maximum strength [ 1-RM ] ) and high intensity resistance training ( four sets of 10 repetitions at 70 % of 1-RM ) on a leg extension machine in 14 patients who participated in a rehabilitation programme . Work volume was identical in the low- and high-level resistance training . RESULTS The HR and systolic blood pressure ( SBP ) during low intensity resistance training were always larger than during high intensity ( P<0.001 ) . Peak SBP increased from set 1 to set 3 and 4 during both low and high intensity resistance training ( P<0.05 ) . Peak HR was larger in set 4 ( 95+/-11 bpm ) than in set 1 only during low intensity resistance training ( 91+/-12 bpm ) ( P<0.05 ) . One-minute recovery periods did not allow a return to baseline HR and SBP during both low and high intensity modalities . CONCLUSIONS The SBP and HR responses to resistance training are related to the duration of exercise . Sets with < or = 10 repetitions of high intensity should be preferred to longer sets with low intensity . Pauses between exercise sets should exceed 1 min . Blood pressure should be measured during the last repetitions of the exercise set OBJECTIVE To examine the individual , combined , and isolated effects of movement-based behaviors ( MBBs ) on all-cause mortality and CVD-specific mortality . METHODS The present prospect i ve study included data from the 1999 - 2004 National Health & Nutrition Examination Survey , with follow-up data through December 31 , 2006 ( N=12,321 U.S. adults ) . Measures included self-report engagement in 4 MBBs ( moderate-intensity exercise , vigorous-intensity exercise , muscular strength activities , and active transport ) , with all-cause mortality and CVD-specific mortality as the outcome measures . RESULTS Regarding all-cause mortality , the hazard ratio for those with 1 ( vs. 0 ) , 2 ( vs. 0 ) , and 3 - 4 ( vs. 0 ) MBBs , respectively , was 0.61 ( 95 % CI : 0.49 - 0.76 ) , 0.49 ( 95 % CI : 0.36 - 0.66 ) , and 0.24 ( 95 % CI : 0.16 - 0.37 ) . The only MBBs independently associated with all-cause-mortality were vigorous exercise ( HR=0.56 ; 95 % CI : 0.41 - 0.76 ) and moderate-intensity exercise ( HR=0.58 ; 95 % CI : 0.45 - 0.74 ) . When examining the isolation/exclusivity effects of the MBBs , the only MBB performed in isolation that was statistically significantly associated with all-cause mortality was " Only VPA " ( HR=0.45 ; 95 % CI : 0.23 - 0.86 ) . CVD-specific mortality results were similar to the all-cause mortality results . CONCLUSIONS There was little evidence of a MBB isolation effect on mortality risk , but individuals engaging in more MBBs had a lower risk of all-cause mortality and CVD-specific mortality . These findings suggest that , in addition to promoting greater engagement in overall physical activity , recommendations for adults to engage in multiple MBBs may be advisable Background Exercise training is effective for improving physical fitness and physical function in people with type 2 diabetes . However , limited research has been conducted on the optimal exercise training intensity for this population . Objective The primary study objective was to investigate the effects of moderate- versus high-intensity exercise training on physical fitness and physical function in people with type 2 diabetes . Design This was a r and omized clinical trial . Setting The setting was a university campus . Participants Twenty-one people with type 2 diabetes were r and omly allocated to receive either moderate-intensity training ( MOD group ) or high-intensity training ( HIGH group ) . Intervention The MOD group performed resistance training at an intensity of 75 % of the 8-repetition maximum ( 8-RM ) and aerobic training at an intensity of 30 % to 45 % of the heart rate reserve ( HRR ) . The HIGH group performed resistance training at an intensity of 100 % of the 8-RM and aerobic training at an intensity of 50 % to 65 % of the HRR . Measurements Muscle strength ( peak torque [ newton-meters ] ) , exercise capacity ( grade d exercise test duration [ minutes ] ) , and physical function ( Patient-Specific Functional Scale question naire ) were measured at baseline and 3 months later . Acute exercise-induced changes in glucose levels were assessed immediately before exercise , immediately after exercise , and 1 hour after exercise during the first exercise training session . Results Although both groups showed improvements in physical fitness and physical function , the between-group effect sizes were not statistically significant ( exercise capacity estimated marginal mean [ EMM ] difference=2.1 , 95 % confidence interval [ 95 % CI]=−0.2 , 4.5 ; muscle strength EMM difference=20.8 , 95 % CI=−23.3 , 65.0 ; and physical function EMM difference=0.1 , 95 % CI=−0.6 , 0.9 ) . Mean percent changes in glucose levels measured immediately before exercise and immediately after exercise , immediately after exercise and 1 hour after exercise , and immediately before exercise and 1 hour after exercise for the MOD group were −11.4 % , −5.0 % , and −15.8 % , respectively ; those for the HIGH group were −21.5 % , 7.9 % , and −15.3 % , respectively . Limitations Sample size , lack of outcome assessor masking , and physical function measurement subjectivity were limitations . Conclusions Moderate- and high-intensity exercise training , as defined in this study , may lead to similar improvements in physical fitness and physical function in people with type 2 diabetes UNLABELLED Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease ( NAFLD ) , which is extremely common in people with type 2 diabetes , no intervention studies have compared the effects of aerobic ( AER ) or resistance ( RES ) training on hepatic fat content in type 2 diabetic subjects with NAFLD . In this r and omized controlled trial , we compared the 4-month effects of either AER or RES training on insulin sensitivity ( by hyperinsulinemic euglycemic clamp ) , body composition ( by dual-energy X-ray absorptiometry ) , as well as hepatic fat content and visceral ( VAT ) , superficial ( SSAT ) , and deep ( DSAT ) subcutaneous abdominal adipose tissue ( all quantified by an in-opposed-phase magnetic resonance imaging technique ) in 31 sedentary adults with type 2 diabetes and NAFLD . After training , hepatic fat content was markedly reduced ( P < 0.001 ) , to a similar extent , in both the AER and the RES training groups ( mean relative reduction from baseline [ 95 % confidence interval ] -32.8 % [ -58.20 to -7.52 ] versus -25.9 % [ -50.92 to -0.94 ] , respectively ) . Additionally , hepatic steatosis ( defined as hepatic fat content > 5.56 % ) disappeared in about one-quarter of the patients in each intervention group ( 23.1 % in the AER group and 23.5 % in the RES group ) . Insulin sensitivity during euglycemic clamp was increased , whereas total body fat mass , VAT , SSAT , and hemoglobin A1c were reduced comparably in both intervention groups . CONCLUSION This is the first r and omized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD AIM To compare different volumes and intensities of resistance training ( RT ) combined with aerobic training ( AT ) for improvements in glycemic control and cardiovascular health for persons with type 2 diabetes ( T2DM ) . METHODS Participants with T2DM were stratified by HbA1c and r and omized : " usual care " ( RT1 ) , which consisted of moderate intensity ( 50 % 1-repetition maximum [ 1-RM ] ) , low volumeRT ( initiated half-way through program ) ; higher intensity ( 75 % 1-RM ) and higher volume ( initiated at program onset ) RT ( RT2 ) ; or moderate intensity but higher volume RT ( RT3 ) . RT sets and repetitions were adjusted to maintain similar work and volume between RT2 and RT3 . Walking or cycling ( 60 - 80 % aerobic capacity)was prescribed 5 times/week , and RT was prescribed 2 times/week . An ANCOVA , adjusted for baseline and gender , assessed changes post-6months in glycemic control ( HbA1c- primary outcome ) , aerobic capacity and anthropometrics . RESULTS Sixty-two participants ( 52.3±1.2years , 48 % female ) were r and omized ( RT1 , n=20 ; RT2 , n=20 ; RT3 , n=22 ) . Only post-training fasting glucose , without significant HbA1c change , was different between groups ( RT1-RT3=-1.7mmol/L , p=0.046 ) . Pre-post differences were found in pooled HbA1c ( 7.4±0.2%[57±2.2mmol/mol ] vs. 6.7±0.2%[50±2.2mmol/mol ] , p<0.001 ) , aerobic capacity ( 21.5±0.8vs . 25.2±0.8ml/kg/min , p<0.001 ) , body mass ( 84.0±2.7vs . 83.0±2.7 kg , p=0.022[DXA ] ) , body mass index ( 30.8±0.9vs . 30.3±0.8kg/m2 , p=0.02 ) and body fat ( 32.3±1.1vs . 31.3±1.2 % , p<0.001 ) . The trial was discontinued early ; no HbA1c advantage was found with either RT2 or RT3 over RT1 . CONCLUSIONS Combined AT+RT exercise improved glycemic control , cardiovascular risk factors and body composition after 6months for participants with T2DM , but differential effects between the prescribed intensities and volumes of RT were not found to effect HbA1c Abstract Aims It is unknown whether different training modalities exert differential cellular effects . Telomeres and telomere-associated proteins play a major role in cellular aging with implication s for global health . This prospect i ve training study examines the effects of endurance training , interval training ( IT ) , and resistance training ( RT ) on telomerase activity and telomere length ( TL ) . Methods and results One hundred and twenty-four healthy previously inactive individuals completed the 6 months study . Participants were r and omized to three different interventions or the control condition ( no change in lifestyle ) : aerobic endurance training ( AET , continuous running ) , high-intensive IT ( 4 × 4 method ) , or RT ( circle training on 8 devices ) , each intervention consisting of three 45 min training sessions per week . Maximum oxygen uptake ( VO2max ) was increased by all three training modalities . Telomerase activity in blood mononuclear cells was up-regulated by two- to three-fold in both endurance exercise groups ( AET , IT ) , but not with RT . In parallel , lymphocyte , granulocyte , and leucocyte TL increased in the endurance-trained groups but not in the RT group . Magnet-activated cell sorting with telomerase repeat-ampliflication protocol ( MACS-TRAP ) assays revealed that a single bout of endurance training — but not RT — acutely increased telomerase activity in CD14 + and in CD34 + leucocytes . Conclusion This r and omized controlled trial shows that endurance training , IT , and RT protocol s induce specific cellular pathways in circulating leucocytes . Endurance training and IT , but not RT , increased telomerase activity and TL which are important for cellular senescence , regenerative capacity , and thus , healthy aging UNLABELLED Observational studies suggest that physical activity after a breast cancer diagnosis is associated with improved cancer outcomes ; however , no r and omized data are available . Here , we report an exploratory follow-up of cancer outcomes from the Supervised Trial of Aerobic versus Resistance Training ( START ) . METHODS The START was a Canadian multicenter trial that r and omized 242 breast cancer patients between 2003 and 2005 to usual care ( n = 82 ) , supervised aerobic ( n = 78 ) , or resistance ( n = 82 ) exercise during chemotherapy . The primary end point for this exploratory analysis was disease-free survival ( DFS ) . Secondary end points were overall survival , distant DFS , and recurrence-free interval . The two exercise arms were combined for analysis ( n = 160 ) , and selected subgroups were explored . RESULTS After a median follow-up of 89 months , there were 25/160 ( 15.6 % ) DFS events in the exercise groups and 18/82 ( 22.0 % ) in the control group . Eight-year DFS was 82.7 % for the exercise groups compared with 75.6 % for the control group ( HR , 0.68 ; 95 % confidence interval ( CI ) , 0.37 - 1.24 ; log-rank , P = 0.21 ) . Slightly stronger effects were observed for overall survival ( HR , 0.60 ; 95 % CI , 0.27 - 1.33 ; log-rank , P = 0.21 ) , distant DFS ( HR , 0.62 ; 95 % CI , 0.32 - 1.19 ; log-rank , P = 0.15 ) , and recurrence-free interval ( HR , 0.58 ; 95 % CI , 0.30 - 1.11 ; Gray test , P = 0.095 ) . Subgroup analyses suggested potentially stronger exercise effects on DFS for women who were overweight/obese ( HR , 0.59 ; 95 % CI , 0.27 - 1.27 ) , had stage II/III cancer ( HR , 0.61 ; 95 % CI , 0.31 - 1.20 ) , estrogen receptor-positive tumors ( HR , 0.58 ; 95 % CI , 0.26 - 1.29 ) , human epidermal growth factor receptor 2-positive tumors ( HR , 0.21 ; 95 % CI , 0.04 - 1.02 ) , received taxane-based chemotherapies ( HR , 0.46 ; 95 % CI , 0.19 - 1.15 ) , and ≥85 % of their planned chemotherapy ( HR , 0.50 ; 95 % CI , 0.25 - 1.01 ) . CONCLUSIONS This exploratory follow-up of the START provides the first r and omized data to suggest that adding exercise to st and ard chemotherapy may improve breast cancer outcomes . A definitive phase III trial is warranted |
10,920 | 24,105,424 | Participants receiving BDP/LABA also had a statistically significant increased rate of exacerbations leading to hospitalisation ( risk ratio ( RR ) 1.84 , 95 % CI 1.17 to 2.90 , P = 0.008 ) ( moderate quality ) , although this finding is debatable as this study 's post hoc analysis showed no statistically significant difference when accounting for country-specific differences in hospitalisation policies . | BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is a chronic obstructive lung condition , diagnosed in patients with dyspnoea , chronic cough or sputum production and /or a history of risk factor exposure , if their postbronchodilator forced expiratory lung volume in 1 second (FEV1)/forced vital lung capacity ( FVC ) ratio is less than 0.70 , according to the international GOLD ( Global Initiative for Obstructive Lung Disease ) criteria .Inhaled corticosteroid ( ICS ) medications are now recommended for COPD only in combination treatment with long-acting beta2-agonists ( LABAs ) , and only for patients of GOLD stage 3 and stage 4 severity , for both GOLD groups C and D.ICS are expensive and how effective they are is a topic of controversy , particularly in relation to their adverse effects ( pneumonia ) , which may be linked to more potent ICS .
It is unclear whether beclometasone dipropionate ( BDP ) , an unlicensed but widely used inhaled steroid , is a safe and effective alternative to other ICS .
OBJECTIVES To determine the effectiveness and safety in COPD of inhaled beclometasone alone compared with placebo , and of inhaled beclometasone in combination with LABAs compared with LABAs alone . | Small airways disease plays an important role in the pathogenesis of asthma , but assessment of small airways impairment is not easy in everyday clinical practice . The small airways can be examined by several invasive and noninvasive methods , most of which can at present be used only in the experimental setting . Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways . Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation , ie , on dysfunction in both the central and distal airways in asthmatics , and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes , including nocturnal asthma , severe steroid-dependent or difficult-to-treat asthma , asthma complicated by smoking , elderly asthmatic patients and /or patients with fixed airflow obstruction , and asthmatic children . The relevant r and omized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints , but there are certain clinical ly important endpoints for which the extrafine formulations show additional benefits Purpose : Results of r and omized controlled trials may not predict effectiveness of inhaled corticosteroids ( ICS ) in real-world clinical practice , where inhaler technique and device characteristics can influence effectiveness . We compared asthma outcomes for ICS delivered via three different inhaler devices : pressurized metered-dose inhaler ( pMDI ) , breath-actuated MDI ( BAI ) , and dry powder inhaler ( DPI ) . Patients and methods : This retrospective data base study evaluated 1-year outcomes for primary care patients with asthma aged 5–60 years prescribed their first ICS ( initiation population ) by pMDI ( n = 39,746 ) , BAI ( n = 9809 ) , or DPI ( n = 6792 ) , or their first ICS dose increase ( step-up population ) by pMDI ( n = 6245 ) , BAI ( n = 1388 ) , or DPI ( n = 1536 ) . Co- primary outcome measures were composite proxy measures of asthma control ( no hospital attendance for asthma , oral corticosteroids , or antibiotics for lower respiratory infection ) and severe exacerbations ( unscheduled hospital admission , emergency room attendance , or oral corticosteroids ) . Outcomes were adjusted for potential confounding factors identified during a baseline year . Results : In the initiation population , adjusted odds ratios ( 95 % confidence intervals [ CI ] ) for asthma control , as compared with pMDIs , were significantly better for BAIs ( 1.08 [ 1.02–1.14 ] ) and DPIs ( 1.13 [ 1.06–1.21 ] ) , while adjusted exacerbation rate ratios ( 95 % CI ) were 1.00 ( 0.93–1.08 ) and 0.88 ( 0.81–0.95 ) , respectively . In the step-up population , adjusted odds of asthma control were 1.21 ( 1.05–1.39 ) for BAIs and 1.13 ( 0.99–1.29 ) for DPIs ; adjusted exacerbation rate ratios were 0.83 ( 0.71–0.98 ) for BAIs and 0.85 ( 0.74–0.98 ) for DPIs , compared with pMDIs . Conclusion : Inhaler device selection may have a bearing on clinical outcomes . Differences in real-world effectiveness among these devices require closer evaluation in well- design ed prospect i ve trials Chronic bronchitis is associated with airways obstruction and inflammation . In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction , subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage ( BAL ) before and after receiving 6 wk of therapy ( five puffs four times a day ) with either aerosolized beclomethasone ( n = 20 ) or placebo ( n = 10 ) in a double-blinded , r and omized fashion . All subjects received aerosolized albuterol before each use of the study medications . Before BAL , the airways were visually assessed for the appearance of inflammation and assigned a score , the bronchitis index . BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a " bronchial sample . " The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis . The fluid was prepared for cytologic examination by cytocentrifugation . Albumin ( as a measure of epithelium permeability ) and lactoferrin and lysozyme ( as measures of serous cell activity ) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay , and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution . After treatment , the beclomethasone group , but not the placebo group , showed improvement in FVC ( p = 0.02 ) , FEV1 ( p = 0.002 ) , and 25 to 75 % forced expiratory flow ( p = 0.006 ) . Associated with the improvement in spirometry , the bronchitis index fell ( 13.5 + /- 1.0 versus 10.75 + /- 1.1 , p = 0.02 ) in the beclomethasone-treated group , but not the placebo-treated group . ( ABSTRACT TRUNCATED AT 250 WORDS Bone mass and biochemical bone markers were prospect ively studied in 33 patients with chronic obstructive pulmonary disease treated for 1 year with inhaled beclomethasone 200 micrograms/q.i.d . ( group A , 8 men and 4 women ) , inhaled budesonide 200 micrograms/q.i.d . ( group B , 6 men and 5 women ) , or not requiring steroids ( group C , 6 men and 4 women ) . Both inhaled corticosteroids decreased serum concentrations of the osteoblastic markers , osteocalcin and carboxy-terminal propeptide of type I collagen ( PICP ) . The osteoclastic marker cross-linked carboxy-terminal telopeptide of type I collagen ( ICTP ) increased significantly more in patients on beclomethasone than in those on budesonide . The decrease in bone mineral density was more pronounced in patients treated with beclomethasone ( 1.1 % in the spine 1.7 % in the hip P < 0.05 ) compared to those treated with budesonide ( 0.6 % in both spine and hip ) or in the control group . Inhaled corticosteroids affect biochemical bone markers and bone mineral density , but there is a different effect for the two corticosteroids evaluated in the present study One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a r and omised , double blind , placebo controlled , crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day , both given for two weeks . One hundred and seven patients completed the study . Response was assessed as change in FEV1 and FVC measured on the last treatment day , and as change in mean peak expiratory flow ( PEF ) over the final seven days of treatment from home PEF recordings performed five times daily . A full response to treatment was defined as an increase in FEV or FVC , or an increase in mean daily PEF over the final seven days of treatment , of at least 20 % from baseline values . An improvement in one measurement of at least 15 % , or of 10 % in any two measurements , was defined as a partial treatment response . Response to placebo showed a significant order effect , suggesting a carry over effect of active treatment of at least three weeks . Response to active treatment was therefore related to initial baseline values , and compared with placebo by considering responses in the first treatment phase only . A full response to oral prednisolone ( 16/38 ) was significantly more common than to placebo ( 3/35 ) . The number of full responses to inhaled beclomethasone ( 8/34 ) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase , though full and partial responses to inhaled beclomethasone ( 12/34 ) were significantly more common than those to placebo ( 4/35 ) . When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment , a response to prednisolone ( 39 ) occurring more frequently than to inhaled beclomethasone ( 26 ) . Only 21 of the 44 responders showed a response to both forms of treatment . Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day , but better than placebo , in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction . It was , however , an effective alternative in over half of those showing a response to prednisolone BACKGROUND --High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma . Although effective , they may cause systemic side effects . Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses . METHODS --Fluticasone propionate , 1.5 mg per day , was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma ; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate . The study was multicentre , double blind and of a parallel design . For the first three months patients attended the clinic every four weeks and completed daily diary cards . For the next nine months they were only seen at three monthly intervals in the clinic . RESULTS --During the first three months diary card peak expiratory flow ( PEF ) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate ( difference in morning PEF 15 l/min ( 95 % CI 6 to 25 ) ) , and these differences were apparent at the end of the first week . The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8 % compared with those receiving beclomethasone dipropionate . No significant differences between the two groups were observed in morning plasma cortisol levels , urinary free cortisol levels , or response to synthetic ACTH stimulation . In addition , both the rates of withdrawal and of adverse events were low , and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate . CONCLUSIONS --This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate , with no increase in systemic or other side effects BACKGROUND : In a previous single dosing comparison between fluticasone propionate and budesonide differences in cortisol levels measured at 08.00 hours were observed at doses in excess of 1000 micrograms . The aim of this study was to compare the adrenal suppression caused by chronic twice daily dosing with inhaled fluticasone propionate ( FP ) and budesonide ( B ) given on a microgram equivalent basis by metered dose inhaler to asthmatic patients . METHODS : Twelve stable asthmatic patients of mean age 29.7 years with forced expiratory volume in one second ( FEV1 ) 89.0 % predicted and mid forced expiratory flow ( FEF25 - 75 ) 58.9 % predicted , on 400 micrograms/day or less of inhaled corticosteroid , were studied in a double blind , placebo controlled , crossover design comparing inhaled budesonide and fluticasone propionate in doses of 250 micrograms , 500 micrograms , and 1000 micrograms twice daily . Each dose was given at 08.00 hours and 22.00 hours for four days by metered dose inhaler with mouth rinsing . Measurements were made of overnight urinary cortisol excretion and plasma cortisol levels at 08.00 hours , 10 hours after the eighth dose . RESULTS : The plasma cortisol levels ( nmol/ l ) at 08.00 hours showed that fluticasone propionate produced lower cortisol levels than budesonide at all three dose levels : F500 333.8 , B500 415.2 ( 95 % CI 28.9 to 134.0 ) ; F1000 308.3 , B1000 380.3 ( 95 % CI 10.5 to 133.5 ) ; F2000 207.3 , B2000 318.5 ( 95 % CI 5.8 to 216.7 ) ; placebo 399.9 . Fluticasone produced greater effects than budesonide on the overnight urinary cortisol/creatinine ratio ( nmol/mmol ) at all three dose levels : F500 3.12 , B500 5.55 ( 95 % CI 0.16 to 3.79 ) ; F1000 2.54 , B1000 6.12 ( 95 % CI 1.25 to 5.91 ) ; F2000 2.07 , B2000 6.09 ( 95 % CI 0.88 to 7.18 ) ; placebo 5.23 . CONCLUSIONS : With repeated dosing across a dose range of 250 - 1000 micrograms twice daily , fluticasone propionate produced significantly greater adrenal suppression than budesonide for both plasma and urinary cortisol . It was therefore possible to demonstrate differences between fluticasone and budesonide at lower doses with chronic dosing from those previously found with single dosing when given on a microgram equivalent basis in asthmatic patients . Factors contributing to the systemic adverse activity profile of fluticasone comprise enhanced receptor potency , prolonged receptor residency time , greater tissue retention , and a longer elimination half life OBJECTIVE There is less unanimity about the effects of inhaled corticosteroid in patients with non-asthmatic chronic obstructive pulmonary disease ( COPD ) . The aim of this study is to determine whether patients with non-asthmatic COPD have favorable responses to inhaled corticosteroid ( ICS ) . METHOD A r and omized , placebo-controlled , single-blind trial of inhaled beclomethasone dipropionate(BDP 1000 micrograms daily for 6 weeks ) was carried out in 61 patients with stable non-asthmatic COPD . Before and after the therapy , the scores of clinical symptoms and the scores of quality of life were recorded , and the pulmonary function and plasma level of endothelin-1 ( ET-1 ) were measured . RESULT 58 patients finished the study . Compared with the placebo-group , after receiving 6 weeks of ICS therapy , the BDP group showed significant improvement in clinical symptoms ( P < 0.05 ) , but not in the quality of life ( P > 0.05 ) . There was also an improvement in FEV1(P < 0.001 ) , but not in MMEF ( P > 0.05 ) . The plasma concentration of ET-1 was not changed significantly in both groups . CONCLUSION The study suggested that the therapy of ICS ( 1000 micrograms daily for 6 weeks ) can improve clinical symptoms and pulmonary function in patients with stable non-asthmatic COPD , but can not affect the quality of life and the plasma concentration of ET-1 Background Chronic obstructive pulmonary disease ( COPD ) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation . Objectives The present study was design ed to evaluate whether an extra-fine combination of beclomethasone and formoterol ( BDP/F ) was effective in reducing air trapping in COPD patients with hyperinflation . Fluticasone salmeterol ( FP/S ) combination treatment was the active control . Methods COPD patients with forced expiratory volume in one second < 65 % and plethysmographic functional residual capacity ≥120 % of predicted were r and omized to a doubleblind , double-dummy , 12-week , parallel group , treatment with either BDP/F 400/24 μg/day or FP/S 500/100 μg/day . Lung volumes were measured with full body plethysmography , and dyspnea was measured with transition dyspnea index . Results Eighteen patients were evaluable for intention to treat . A significant reduction in air trapping and clinical ly meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group . Functional residual capacity , residual volume ( RV ) and total lung capacity significantly improved from baseline in the BDP/F group only . With regard to group comparison , a significantly greater reduction in RV was observed with BDP/F versus FP/S. Conclusion BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation The present study was design ed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite ® ( Chiesi Farmaceutici , Parma , Italy ) pressurised metered-dose inhaler ( pMDI ) , with a combination of budesonide and formoterol administered via a Turbuhaler ® ( AstraZeneca , Lund , Sweden ) dry powder inhaler ( DPI ) . This was a phase III , multinational , multicentre , double-blind , double-dummy , r and omised , two-arm parallel groups , controlled study design . After a 2-week run-in period , 219 patients with moderate-to-severe asthma were r and omised to a 12-week treatment with beclomethasone 200 μg plus formoterol 12 μg b.i.d . delivered via a pMDI or budesonide 400 μg plus formoterol 12 μg b.i.d . delivered via a DPI . The analysis of noninferiority on primary outcome , morning peak expiratory flow in the last 2 weeks of treatment , showed no difference between groups . A statistically significant improvement from baseline in lung function , symptoms and rescue medication use was observed in both groups at all time-points . No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events . The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite ® pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile BACKGROUND Chronic obstructive pulmonary disease ( COPD ) is characterized by an incompletely reversible limitation in airflow . A physiological variable -- the forced expiratory volume in one second (FEV1)--is often used to grade the severity of COPD . However , patients with COPD have systemic manifestations that are not reflected by the FEV1 . We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients . METHODS We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort : the body-mass index ( B ) , the degree of airflow obstruction ( O ) and dyspnea ( D ) , and exercise capacity ( E ) , measured by the six-minute-walk test . We used these variables to construct the BODE index , a multidimensional 10-point scale in which higher scores indicate a higher risk of death . We then prospect ively vali date d the index in a cohort of 625 patients , with death from any cause and from respiratory causes as the outcome variables . RESULTS There were 25 deaths among the first 207 patients and 162 deaths ( 26 percent ) in the validation cohort . Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency , 14 percent to myocardial infa rct ion , 12 percent to lung cancer , and 13 percent to other causes . Patients with higher BODE scores were at higher risk for death ; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 ( 95 percent confidence interval , 1.26 to 1.42 ; P<0.001 ) , and the hazard ratio for death from respiratory causes was 1.62 ( 95 percent confidence interval , 1.48 to 1.77 ; P<0.001 ) . The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV1 ( 0.74 vs. 0.65 ) . CONCLUSIONS The BODE index , a simple multidimensional grading system , is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects ( microgram dose producing equal systemic cortisol suppression ) of inhaled corticosteroids ( ICS ) . Steroid naive asthma subjects ( n = 156 ) were enrolled at six centers . A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses . Systemic effect was evaluated by hourly plasma cortisol concentrations ( 8 P.M. to 8 A.M. ) , 12- and 24-hour urine cortisol concentrations , and a morning blood osteocalcin . The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect . For the six ICS and matching placebos ( beclomethasone-chlorofluorocarbon [ CFC ] , budesonide dry powder inhaler [ DPI ] , fluticasone DPI , fluticasone-CFC metered dose inhaler [ MDI ] , flunisolide-CFC , and triamcinolone-CFC ) , only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect . Thus microgram comparison of all ICS could only be performed at a 10 % cortisol suppression : flunisolide-CFC - 936 ; triamcinolone-CFC - 787 ; beclomethasone-CFC - 548 ; fluticasone DPI - 445 ; budesonide DPI - 268 ; fluticasone-CFC MDI - 111 . This study represents the first step in evaluation of ICS efficacy based on equisystemic ( cortisol suppression ) effects of a given ICS , rather than doses judged arbitrarily to be comparable on a microgram basis BACKGROUND AND OBJECTIVE To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction , compare the estimate of treatment effect derived from these methods , and compare the time requirements for these methods . METHODS Review ers were r and omized to the role of data extractor or data verifier , and were blind to the study hypothesis . The frequency of errors associated with each method of data extraction was compared using the McNemar test . The data set for each method was used to calculate an efficacy estimate by each method , using st and ard meta-analytic techniques . The time requirement for each method was compared using a paired t-test . RESULTS Single data extraction result ed in more errors than double data extraction ( relative difference : 21.7 % , P = .019 ) . There was no substantial difference between methods in effect estimates for most outcomes . The average time spent for single data extraction was less than the average time for double data extraction ( relative difference : 36.1 % , P = .003 ) . CONCLUSION In the case that single data extraction is used in systematic review s , review ers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates Relatively little is known about the influence of inhaled corticosteroids on general well-being ( quality of life ) in patients with asthma or COPD . In a 4-year prospect i ve controlled study , we examined the influence of beclomethasone dipropionate ( BDP ) , 400 micrograms , two times daily , on quality of life in 56 patients with asthma or COPD in comparison with the effects of BDP on symptoms and lung function . During the first 2 years , patients received only bronchodilator therapy with salbutamol or ipratropium bromide . During the third and fourth years , additional treatment with BDP was given . Fifty-six patients ( 28 with asthma , 28 with COPD ) with an annual decline in the forced expiratory volume in 1 s ( FEV1 ) of at least 80 mL/yr in combination with at least two exacerbations per year during bronchodilator therapy alone participated . Quality of life was assessed at the start and after 2 and 4 years by means of the Inventory of Subjective Health ( ISH ) and the Nottingham Health Profile ( NHP ) . Although BDP significantly improved the course of lung function (FEV1)(p < 0.0001 ) , it did not improve the ISH score or the six dimensions of the NHP neither in asthma nor in COPD . Beclomethasone dipropionate temporarily decreased respiratory symptoms during months 4 to 6 of BDP treatment in patients with asthma ( p < 0.01 ) and during months 7 to 12 in patients with COPD ( p < 0.05 ) . A weak correlation was found both cross-sectionally and longitudinally between ( change in ) symptoms and quality of life on the one h and , and the ( change in ) FEV1 on the other . It was concluded that BDP did not improve the general well-being of patients with asthma or COPD as measured by these generic health instruments . However , BDP significantly improved the course of lung function and temporarily decreased the severity of symptoms . It seems probable that changes in quality of life would have been better detected by use of a disease-specific health instrument . Such an instrument was not available at the start of the study . Another possible explanation for these observations is that patients soon get used to different levels of lung function and learn to live with their disease . It is advised that disease-specific health instruments are used in future intervention studies and that quality of life is measured frequently during the early phase of the intervention , eg , once every month BACKGROUND --The effect of treatment with inhaled corticosteroids in patients with non-asthmatic chronic airflow obstruction is still disputed . Whether any physiological improvements seen are accompanied by changes in bronchial responsiveness and symptoms and quality of life is also still unclear . METHODS --A sequential placebo controlled , blinded parallel group study investigating the effect of three weeks of treatment with inhaled beclomethasone dipropionate ( BDP ) , 750 micrograms or 1500 micrograms twice daily , and oral prednisolone , 40 mg per day , was carried out in 105 patients with severe non-asthmatic chronic airflow obstruction ( mean age 66 years , mean forced expiratory volume in one second ( FEV1 ) 1.05 litres [ 40 % predicted ] , geometric mean PD20 0.52 mumol ) . End points assessed were FEV1 , forced vital capacity ( FVC ) , and peak expiratory flow ( PEF ) , bronchial responsiveness to inhaled histamine , and quality of life as measured by a formal quality of life question naire . RESULTS --Both doses of BDP produced equivalent , small , but significant improvements in FEV1 ( mean 48 ml ) , FVC ( mean 120 ml ) , and PEF ( mean 12.4 l/min ) . The addition of oral prednisolone to the treatment regime in two thirds of the patients did not produce any further improvement in these parameters . Inhaled BDP produced a treatment response in individual patients ( defined as an improvement in FEV1 , FVC , or mean PEF of at least 20 % compared with baseline values ) more commonly than placebo ( 34 % v 15 % ) . The two doses of BDP were equally effective in this respect and again no further benefit of treatment with oral prednisolone was noted . Treatment with BDP for up to six weeks did not affect bronchial responsiveness to histamine . Small but significant improvements were seen in dyspnoea during daily activities , and the feeling of mastery over the disease . CONCLUSIONS --High dose inhaled BDP is an effective treatment for patients with chronic airflow obstruction not caused by asthma . Both objective and subjective measures show improvement . Unlike asthma , no improvement in bronchial responsiveness was detected after six weeks of treatment Treatment of chronic obstructive pulmonary disease ( COPD ) with inhaled and oral corticosteroids is common , although their exact role is unclear . Previous studies suggest these drugs may reduce decline in lung function in this group of patients . We report a study investigating the effect of inhaled beclomethasone diproprionate ( BDP ) on lung function and symptoms in a group of patients with COPD . Treatment was given for 2 years , and the decline in FEV1 in individual patients calculated over this period . Ninety‐eight patients were r and omized for the study , 59 completing 2 years of treatment . Patients withdrawn had more severe airflow obstruction . Decline in FEV1 , measured both prior to and after bronchodilator , was less in patients receiving inhaled BDP , although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction . Exacerbation rates were also reduced by inhaled BDP , but again the differences failed to reach conventional levels of statistical significance . The results of this study are consistent with previous published work , but further insight into the long‐term role of corticosteroids in COPD await the publication of large studies which have recently been completed . Although the changes seen in this study and others are numerically small , the rate of decline in FEV1 returned to normal levels expected from age‐related decline , and hence such treatment combined with other strategies may well have a significant role in the long‐term treatment of this condition Since the relationships between pulmonary function , exercise capacity , and functional state or quality of life are generally weak , a self report question naire has been developed to determine the effect of treatment on quality of life in clinical trials . One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness , and how important their symptoms and limitations were . The most frequent and important items were used to construct a question naire evaluating four dimensions : dyspnoea , fatigue , emotional function , and the patient 's feeling of control over the disease ( mastery ) . Reproducibility , tested by repeated administration to patients in a stable condition , was excellent : the coefficient of variation was less than 12 % for all four dimensions . Responsiveness ( sensitivity to change ) was tested by administering the question naire to 13 patients before and after optimisation of their drug treatment and to another 28 before and after participation in a respiratory rehabilitation programme . In both cases large , statistically significant improvements in all four dimensions were noted . Changes in question naire score were correlated with changes in spirometric values , exercise capacity , and patients ' and physicians ' global ratings . Thus it has been shown that the question naire is precise , valid , and responsive . It can therefore serve as a useful disease specific measure of quality of life for clinical trials Inhaled corticosteroids have been used in the treatment of chronic obstructive pulmonary disease ( COPD ) for many years . However the adverse effects of corticosteroids on bone formation may require special consideration in these patients . This study was undertaken to investigate the effects of long-term inhaled beclomethasone dipropionate treatment on the biochemical markers of bone formation . For this purpose , serum osteocalcin , alkaline phosphatase , free calcium , and inorganic phosphate levels were measured in 65 male COPD patients . Patients in the control group ( n = 30 ) had not taken oral or inhaled corticosteroids for at least 1 year . Only those patients using beclomethasone with metered-dose inhalers were included in the treatment group ( n = 35 ) . The mean age of the control group was 61.63 + /- 1.84 ( mean + /- SEM ) . In the treatment group , the mean age was 59.10 + /- 2.29 and patients in this group had taken beclomethasone for an average time of 23.94 + /- 2.72 months ( for at least 12 months ) at an average concentration of 1,142.0 + /- 79.64 microg/d . The mean serum osteocalcin levels in the control group and treatment group were 7.03 + /- 0.19 ng/mL and 3.74 + /- 0.12 ng/mL , respectively . Comparison of values between groups indicates that serum osteocalcin levels in patients using beclomethasone were significantly lower than that of patients in the control group . Serum alkaline phosphatase levels were 167.96 + /- 1.49 U/L and 168.17 + /- 1.60 U/L for the control and treatment groups , respectively . There was no statistically significant difference among these values ( Student 's t test ; P > .05 ) . The mean values of total serum calcium and inorganic phosphate were not statistically different between the groups ( P > .05 ) . These results indicate that long-term inhaled beclomethasone treatment in COPD patients may induce significant changes in osteocalcin levels and require close monitoring for osteoporotic changes OBJECTIVES To compare the systemic bioavailability ( assessed by cortisol suppression ) of high-dose budesonide when given by four inhaler devices and orally . Also studied are the relative systemic potencies of three inhaled steroids ( budesonide , fluticasone propionate , and beclomethasone dipropionate ) when given by metered-dose inhaler ( MDI ) with a large volume spacer . DESIGN Double-blind , crossover , placebo-controlled trial . PARTICIPANTS Sixteen healthy , steroid-naive adult volunteers . METHODS On separate occasions , each subjects took 4 mg of budesonide through the following devices : MDI alone , MDI with 750-mL. spacer , dry-powder inhaler and nebulizer ; 4 mg of budesonide was also taken orally to assess the effects of GI absorption . For the drug comparison , each subject took 4 mg of budesonide , fluticasone , and beclomethasone , and 2 mg of budesonide and fluticasone by MDI and spacer . RESULTS Greatest percent suppression ( 95 % confidence interval ) of 9:00 AM cortisol with budesonide was observed with MDI alone ( 73 % [ 57 to 90 ] ) and turbohaler ( 72 % [ 58 to 86 ] ) compared with MDI spacer ( 42 % [ 22 to 64 ] ) and oral administration ( 14 % [ + 6- to -34 ] ) . Nebulized budesonide produced an insignificant rise in 9:00 AM cortisol level . The most suppressive drug ( given by MDI spacer ) was fluticasone at 4 mg ( 86 % [ 82 to 91 ] ) and at 2 mg ( 72 % [ 59 to 85 ] ) . The least suppressive drug was budesonide at 4 mg ( 43 % [ 22 to 64 ] ) and at 2 mg ( 25 % [ 3 to 47 ] ) . The effects of 4 mg of beclomethasone were intermediate ( 66 % [ 49 to 82 % ] ) . CONCLUSIONS The choice of delivery device for administration of budesonide can lead to important differences in systemic bioavailability . Fluticasone has greater systemic potency than budesonide or beclomethasone when given at microgram equivalent dosage . The systemic potency ratio of fluticasone propionate to budesonide in normal human volunteers in the present study is similar to the therapeutic potency ratio of the drug in asthmatic patients ( approximately 2:1 ) AIMS The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid . METHODS The study was a r and omised , double blind , placebo controlled , crossover investigation in 18 patients . The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler . At the end of each treatment period , patients received oral prednisone 30 mg/day for ten days . The two treatment phases were separated by a one month washout interval . Peak flow rates , symptom scores and " rescue " bronchodilator use were recorded twice daily . Lung function ( FEV1 , FVC and lung volumes ) and bronchial hyperresponsiveness ( PC20 methacholine ) were measured at monthly visits . The number of exacerbations requiring intervention therapy were also recorded . RESULTS There were no consistent benefits attributable to beclomethasone . Lung function was not significantly better as a result of active treatment . Sputum production improved but other symptom scores were similar during active and placebo therapy . Three patients exhibited an increase in FEV1 of 15 % or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment . A further three patients showed an improvement in FEV1 of 15 % or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone . The predictive value of the " trial of steroid " was 0 % and 81.3 % for positive and negative outcomes respectively . CONCLUSIONS Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms . The response to a " trial of steroid " using oral prednisone is not clinical ly helpful in selecting the small number of patients who may subsequently benefit from this form of therapy BACKGROUND Long-acting beta-agonists and inhaled corticosteroids are used to treat chronic obstructive pulmonary disease ( COPD ) , but their effect on survival is unknown . METHODS We conducted a r and omized , double-blind trial comparing salmeterol at a dose of 50 microg plus fluticasone propionate at a dose of 500 microg twice daily ( combination regimen ) , administered with a single inhaler , with placebo , salmeterol alone , or fluticasone propionate alone for a period of 3 years . The primary outcome was death from any cause for the comparison between the combination regimen and placebo ; the frequency of exacerbations , health status , and spirometric values were also assessed . RESULTS Of 6112 patients in the efficacy population , 875 died within 3 years after the start of the study treatment . All-cause mortality rates were 12.6 % in the combination-therapy group , 15.2 % in the placebo group , 13.5 % in the salmeterol group , and 16.0 % in the fluticasone group . The hazard ratio for death in the combination-therapy group , as compared with the placebo group , was 0.825 ( 95 % confidence interval [ CI ] , 0.681 to 1.002 ; P=0.052 , adjusted for the interim analyses ) , corresponding to a difference of 2.6 percentage points or a reduction in the risk of death of 17.5 % . The mortality rate for salmeterol alone or fluticasone propionate alone did not differ significantly from that for placebo . As compared with placebo , the combination regimen reduced the annual rate of exacerbations from 1.13 to 0.85 and improved health status and spirometric values ( P<0.001 for all comparisons with placebo ) . There was no difference in the incidence of ocular or bone side effects . The probability of having pneumonia reported as an adverse event was higher among patients receiving medications containing fluticasone propionate ( 19.6 % in the combination-therapy group and 18.3 % in the fluticasone group ) than in the placebo group ( 12.3 % , P<0.001 for comparisons between these treatments and placebo ) . CONCLUSIONS The reduction in death from all causes among patients with COPD in the combination-therapy group did not reach the predetermined level of statistical significance . There were significant benefits in all other outcomes among these patients . ( Clinical Trials.gov number , NCT00268216 [ Clinical Trials.gov ] . ) Abstract Objective : This study aim ed to compare the clinical efficacy of two anti-inflammatory medications ( fenspiride and inhaled beclomethasone [ beclomethasone dipropionate ] ) in patients with stable chronic obstructive pulmonary disease ( COPD ) over 6 months . Design , methods and patients : This was a r and omised comparison of 58 patients with COPD , divided into five treatment groups : fenspiride ( stages 1 and 2 ) , beclomethasone ( stage 2 ) , and two control groups ( stages 1 and 2 ) . In addition , 64 patients with exacerbations of COPD were evaluated over a 2-week treatment period during which they received either fenspiride or prednisolone . Clinical signs and symptoms of COPD were evaluated every 2 months ( aggregated numerical index of signs and symptoms ) , as were lung function tests ( forced vital capacity [ FVC ] , forced expiratory volume in 1 second [ FEV1 ] , FEV1/FVC ) and a 6-minute walking test . Results : Statistically significant reductions in all evaluated COPD signs and symptoms were achieved with fenspiride in stage 1 COPD . Fenspiride therapy significantly reduced the indices of sputum parameters ( 8-fold decrease ) , incidence of dry rales ( 6-fold decrease ) , dyspnoea ( 4-fold decrease ) and cough ( 2.5-fold decrease ) . In comparison with beclomethasone , fenspiride was superior in stage 2 COPD . In patients with stage 2 COPD , reductions were less marked , but remained significantly superior in the fenspiride group in comparison with the beclomethasone group and the control groups . In patients with exacerbations of COPD , fenspiride had equivalent efficacy to that of systemic corticosteroids . Conclusion : Anti-inflammatory therapy with fenspiride in addition to bronchodilators significantly improved clinical signs and symptoms , external respiratory function tests and physical activity tests in patients with stage 1 COPD . Adjunctive fenspiride therapy was superior to inhaled beclomethasone in stage 2 COPD . Anti-inflammatory therapy in COPD may be more effective at an early stage of this disease OBJECTIVES To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol ( non-inferiority ) and versus formoterol ( superiority ) in patients with severe stable chronic obstructive pulmonary disease ( COPD ) . METHODS A double-blind , double-dummy , r and omised , active-controlled , parallel-group study . After 4 weeks run-in with ipratropium/salbutamol ( 40/200 μg , three times daily ) patients were r and omised to receive beclomethasone/formoterol ( 200/12 μg pressurised metered dose inhaler ) , budesonide/formoterol ( 400/12 μg dry powder inhaler ) or formoterol ( 12 μg dry powder inhaler ) twice daily for 48 weeks . Co- primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1 s ( FEV(1 ) ) and mean rate of COPD exacerbations . RESULTS Of 718 patients r and omised , 703 ( 232 beclomethasone/formoterol , 238 budesonide/formoterol , 233 formoterol ) were in the ITT analysis . Improvement in pre-dose morning FEV(1 ) was 0.077 L , 0.080 L and 0.026 L for beclomethasone/formoterol , budesonide/formoterol and formoterol respectively ( LS mean from the ANCOVA model ) . Beclomethasone/formoterol was not inferior to budesonide/formoterol ( 95 % CI of the difference -0.052 , 0.048 ) and superior to formoterol ( p = 0.046 ) . The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments ( beclomethasone/formoterol 0.414 , budesonide/formoterol 0.423 and formoterol 0.431 ) . Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased . Safety profiles were as expected and treatments well-tolerated . CONCLUSIONS Beclomethasone/formoterol ( 400/24 μg ) treatment for 48 weeks improved pulmonary function , reduced symptoms compared to formoterol , was safe and well-tolerated in patients with severe stable COPD . Neither of the long-acting β2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population Fluticasone propionate pressurized metered dose inhalers ( pMDIs ) containing the hydrofluoroalkane ( HFA ) propellant , HFA 134a , are being developed to replace existing chlorofluorocarbon ( CFC ) pMDIs . This is part of the ongoing worldwide project to limit the damage to the earth 's ozone layer . The in vivo performance and dose proportionality of fluticasone propionate HFA 134a pMDIs was examined for fluticasone propionate doses of 400 , 1000 and 2000 microg using the 50 , 125 and 250 microg strength pMDIs , respectively . The 125 and 250 microg strength HFA 134a pMDIs were compared with corresponding fluticasone propionate CFC pMDIs . Twenty-three healthy subjects participated in this single dose , r and omized , five-way , cross-over study . Serial blood sample s were collected 24 h post-dose to measure fluticasone propionate plasma concentrations . Twenty-four hour urinary-free cortisol was also measured before and after dosing . A dose-proportional increase in plasma fluticasone propionate concentrations was observed with increasing dose for the HFA 134a pMDIs . This was associated with a dose-related decrease in urinary cortisol excretion . Similar or lower fluticasone propionate systemic exposure was observed with the HFA 134a pMDIs compared to the corresponding CFC inhalers . The differences in systemic exposure observed for the HFA 134a and CFC pMDIs were too small to produce a differential effect on urinary cortisol excretion . Since fluticasone propionate has negligible oral bioavailability , the systemic exposure , which arises only from pulmonary absorption , is a measure of lung deposition . There was a good correlation between the in vitro fine particle mass produced by the different strengths and types of pMDI and the systemic exposure to fluticasone propionate . Therefore , the fluticasone propionate HFA 134a pMDI is an acceptable pharmaceutical alternative to the current CFC pMDI , producing similar lung deposition and no increase in systemic exposure at microgram equivalent doses |
10,921 | 29,673,837 | Exergaming does encourage individuals to st and up ( 3 ) , lean while st and ing ( 4 ) , move upper limbs and turn heads ( 6 ) and dual-task while st and ing ( 9 ) , to some extent move the body forwards , backwards and sideways ( 1 ) , and coordinate movements ( 2 ) but hardly at all to kick , hop , jump or walk ( 7 ) , or to force a postural reaction from a physical force to the individual ( 5 ) and it does not mimic actual changes in sensory context ( 8) .
Some elements of PC are too unsafe to be trained using exergames , such as restricting sensory inputs or applying physical perturbations to an individual to elicit postural responses | One in three older adults fall annually , in part due to impairments in the physiological systems that make up the postural control ( PC ) system .
Exercise , particularly balance training , helps to prevent deterioration and even to improve outcomes in the PC system .
Exergaming ( exercise-gaming ) is interactive computer gaming whereby an individual moves the body in response to onscreen cues in a playful format .
Exergaming is an alternative method to st and ard practice for improving PC outcomes , which has been shown to reduce the risk of falling .
Exergaming has received research attention , yet the intervention is still in its infancy .
This is the first review , to our knowledge , that synthesis es the literature on movements trained in exergaming interventions with respect to an established theoretical framework for PC . | Abstract Background : Falls and fall-related injuries are symptomatic of an aging population . This study aim ed to design , develop , and deliver a novel method of balance training , using an interactive game-based system to promote engagement , with the inclusion of older adults at both high and low risk of experiencing a fall . Study Design : Eighty-two older adults ( 65 years of age and older ) were recruited from sheltered accommodation and local activity groups . Forty volunteers were r and omly selected and received 5 weeks of balance game training ( 5 males , 35 females ; mean , 77.18 ± 6.59 years ) , whereas the remaining control participants recorded levels of physical activity ( 20 males , 22 females ; mean , 76.62 ± 7.28 years ) . The effect of balance game training was measured on levels of functional balance and balance confidence in individuals with and without quantifiable balance impairments . Results : Balance game training had a significant effect on levels of functional balance and balance confidence ( P < 0.05 ) . This was further demonstrated in participants who were deemed at high risk of falls . The overall pattern of results suggests the training program is effective and suitable for individuals at all levels of ability and may therefore play a role in reducing the risk of falls . Conclusions : Commercial hardware can be modified to deliver engaging methods of effective balance assessment and training for the older population BACKGROUND the study compares the effects of a Nintendo Wii exercise programme and a st and ard Gym-based exercise intervention on fear of falling , knee strength , physical function and falls rate in older adults . METHODS eighty community-dwelling adults aged 60 years and above with short physical performance battery score of 5 - 9 points and modified falls efficacy scale ( MFES ) score of ≤9 points participated in the parallel-group r and omised trial . Each intervention arm involved an hour of intervention per week , totalling 12 sessions over 12 weeks . Besides 1-year fall incidence , the participants were evaluated on MFES , knee extensor strength ( KES ) , timed-up- and -go test , gait speed , 6-minute walk test and narrow corridor walk test at weeks 13 and 24 . RESULTS at week 13 , between interventions , the effect of MFES changes did not reach statistical significance ( difference = -0.07 point , 95 % CI -0.56 to 0.42 , P = 0.78 ) ; at week 24 , the Wii group showed statistically significant effects over the Gym group ( difference = 0.8 point , 95 % CI 0.27 to 1.29 , P < 0.01 ) . For KES , the two groups did not differ statistically at week 13 ( difference = -2.0 % , 95 % CI -5.6 to -1.7 , P = 0.29 ) ; at week 24 , the Gym group had greater strength gains than the Wii group ( difference = -5.1 % , 95 % CI -8.7 to -1.5 , P < 0.01 ) . No between-group differences were observed for other outcome measures . CONCLUSION on completion of a 12-week Nintendo Wii exercise programme , there was no significant benefit seen on fear of falling when compared to a st and ard Gym-based exercise intervention ; however , post-intervention there was an apparent reduction in fear of falling in the group allocated to Wii training , despite knee strength apparently improving more in those allocated to the Gym . It is possible that long-term gains after using the Wii might be due to a carry-over effect . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry , ACTRN12610000576022 BACKGROUND Many issues prevent elderly individuals from exercising in daily life . There is a need for a system that allows elderly individuals to engage in exercise regularly at a low cost . We developed an exergame that uses a Kinect ( ® ) sensor ( Microsoft Corp. , Redmond , WA ) and conducted a r and omized controlled trial of the effects of using this exergame on muscle strength and balance in healthy elderly individuals . SUBJECTS AND METHODS We enrolled 57 healthy elderly individuals and r and omly divided them into an intervention group ( n=29 ) and a control group ( n=28 ) using a table of r and om numbers . All participants underwent gait analyses and were examined using the Berg Balance Scale ( BBS ) , Functional Reach Test ( FRT ) , and the 30-second chair-st and ( CS-30 ) test before the intervention . Participants in the intervention group played the exergame once or twice a week , up to a total of 24 times . The tests were repeated after intervention , and the scores were compared with those obtained before intervention . RESULTS Our results indicated that walking , muscle strength , and motor function improved in participants in the intervention group . Decreased double st and ing time ( P=0.03 ) , minimum foot clearance ( P=0.04 ) , BBS scores ( P<0.01 ) , CS-30 scores ( P<0.01 ) , and FRT scores ( P<0.01 ) significantly improved in the intervention group compared with values in the control group . CONCLUSIONS The Kinect-based exergame developed in this study was found to be effective in improving walking , muscular strength , and balance in elderly people Background Falls are a leading cause of injury and death for old adults , with one risk factor for falls being balance deficits . The low cost ( < 400 USD ) , wide availability , and ability to incorporate multiple training paradigms make gaming systems appealing as possible balance intervention tools . Aims To investigate the feasibility of using the Xbox Kinect for training to improve clinical measures of balance in old adults and retain improvements after a period of time . Methods Thirteen healthy old adults ( aged 70 + years ) were r and omly divided into two groups . The experimental group completed Kinect training three times a week for 3 weeks while the control group continued with normal activities . Four clinical measures of balance were assessed before training , 1 week and 1 month after training : Berg balance scale ( BBS ) , Fullerton advanced balance ( FAB ) scale , functional reach ( FR ) , and timed up and go ( TUG ) . Results The ability to implement the training program was successful . The experimental group significantly increased their BBS and FAB after training while the control group did not . There was no significant change for either groups with FR and TUG . Conclusion A training program using the Kinect with commercially available games was feasible with old adults . Kinect training may be an inexpensive way for old adults to receive helpful feedback encouraging them to continue with balance training program in their home [ Purpose ] The aim of this study was to examine the effects of ball exercise as a general exercise on the balance abilities of elderly individuals by comparing ball exercise with virtual reality exercise . [ Subjects and Methods ] Thirty elderly individuals residing in communities were r and omly divided into a virtual reality game group and a ball exercise group and conducted exercise for 30 min 3 times a week for 8 weeks . [ Results ] Step length increased significantly , and the average sway speed and Timed Up and Go time significantly decreased in both groups . A comparison of sway length after the intervention between the two groups revealed that the virtual reality game exercise result ed in a reduction than the ball exercise . [ Conclusion ] The results of this study indicated that the virtual reality game exercise may improve balance and gait of elderly individuals in communities Frequent or recurrent fallers are more likely to have chronic medical conditions and physiological impairments , exhibit functional decline and have poor outcomes , than single fallers [ 1 ] . Fractures are also more common in recurrent fallers than single fallers [ 2 ] . Modern surgery for hip fracture can no longer improve on its outcomes [ 3 ] and therefore , effective prevention of falls [ 4 , 5 ] is the key to preventing disability and death . There is still no published evidence that a single intervention ( tailored group exercise ) can prevent falls or injuries in a high risk group of frequent fallers . This r and omised controlled trial ( RCT ) aim ed to investigate the impact of a 36 week individualised and tailored group and home exercise intervention , compared with a control intervention , in reducing falls and injuries in communitydwelling , independent-living , frequent falling women aged 65 years and over . Preliminary results have been published in abstract form [ 6 ] . The primary outcome was falls and fallrelated injuries . The secondary outcome was the number of frequent fallers who had died , had moved into residential care or were in hospital compared with the group they were in Background The use of exergaming is a potential alternative to traditional methods of balance training , which can be repetitive and somewhat monotonous . The purpose of this study was to assess the effects of exergaming using XBOX Kinect ™ versus traditional gym-based exercise with no virtual stimuli ( TGB ) on postural control , technology acceptance , flow experience and exercise intensity , in young healthy adults . Methods Fifty healthy active adults ( age : 33.8 ± 12.7 years , height : 172.9 ± 11.9 cm , weight : 75 ± 15.8 kg ) were recruited ; 44 completed both baseline and post-intervention data collection . Participants were r and omised ( blind card ) allocation to one of two groups : ( 1 ) received balance training using the XBOX Kinect ™ and ( 2 ) performed traditional gym-based exercise . Exercises were matched for intensity , duration and movement patterns across groups . All participants completed three , 30-minute , exercise sessions a week for four weeks . Postural sway was measured using a Kistler ™ Force platform during unipedal st and ing . Mean heart rate ( HR ) and rate of perceived exertion ( RPE ) were collected during each exercise session to determine and verify that intensity of exercise was matched between groups . Technology acceptance was measured with the Unified Theory of Acceptance and Use of Technology ( UTAUT ) and flow experience with the Flow State Scale ( FSS ) . Results Heart rate was matched between groups and BORG RPE was significantly lower in the Kinect ™ group . There were significant between-group differences in postural sway in the medial-lateral direction and CoP. There were also significant differences in technology acceptance between groups for performance expectancy , social influence and behavioral intention , with higher values in the Kinect exercise group . The flow state scale showed significant differences between the groups on several dimensions , with higher values in the Kinect exercise group . Conclusion Objective physiological dem and of exercise ( HR ) was matched across groups , but the exergaming group perceived it as being less dem and ing and of lower intensity . This suggests that exergaming may offer an alternative method of rehabilitation exercise through improved concordance . Balance training in healthy adults using the Kinect is both accepted and intrinsically motivating . Trial registration Retrospectively registered on 27th July 2016 . Trial number NCT02851017 Background / Objectives . Balance problems are well-established modifiable risk factors for falls , which are common in older adults . The objective of this study was to establish the efficacy of a Wii-Fit interactive video-game-led physical exercise program to improve balance in older Veterans . Methods . A prospect i ve r and omized controlled parallel-group trial was conducted at Veterans Affairs Medical Center . Thirty community dwelling Veterans aged 68 ( ±6.7 ) years were r and omized to either the exercise or control groups . The exercise group performed Wii-Fit program while the control group performed a computer-based cognitive program for 45 minutes , three days per week for 8-weeks . The primary ( Berg Balance Scale ( BBS ) ) and secondary outcomes ( fear of falling , physical activity enjoyment , and quality of life ) were measured at baseline , 4 weeks , and 8 weeks . Results . Of 30 r and omized subjects , 27 completed all aspects of the study protocol . There were no study -related adverse events . Intent-to-treat analysis showed a significantly greater improvement in BBS in the exercise group ( 6.0 ; 95 % CI , 5.1–6.9 ) compared to the control group ( 0.5 ; 95 % CI , −0.3–1.3 ) at 8 weeks ( average intergroup difference ( 95 % CI ) , 5.5 ( 4.3–6.7 ) , p < 0.001 ) after adjusting for baseline . Conclusion . This study establishes that the Wii-Fit exercise program is efficacious in improving balance in community dwelling older Veterans . This trial is registered with Clinical Trials.gov Identifier NCT02190045 Objective : To compare the effectiveness of three protocol s ( Adapted Physical Activities , Wii Fit ® , Adapted Physical Activities + Wii Fit ® ) on the balance of independent senior subjects . Design : Case comparison study . Setting s : Healthy elderly subjects living in independent community dwellings . Subjects : Thirty-six subjects , average age 75.09 ± 10.26 years , took part in this study , and were r and omly assigned to one of the four experimental groups : G1 followed an Adapted Physical Activities training programme , while the second group ( G2 ) participated in Wii Fit ® training and the third one ( G3 ) combined both methods . There was no training for the fourth group ( G4 ) . All subjects trained once a week ( 1 hour ) for 20 weeks and were assessed before and after treatment . Main measures : The Tinetti test , unipedal tests and the Wii Fit ® tests . Results : After training , the scores in the Tinetti test decreased significantly ( P < 0.05 ) for G1 , G2 and G3 respectively in static conditions and for G1 and G3 in dynamic conditions . After training , the performance in the unipedal tests decreased significantly ( P < 0.05 ) for G1 and G3 . The position of the centre of gravity was modified significantly ( P < 0.05 ) for G2 and G3 . Conclusion : After 20 training sessions , G1 ( Adapted Physical Activities ) , G2 ( Wii Fit ® ) and G3 ( Adapted Physical Activities and Wii Fit ® ) improved their balance . In addition , G1 and G3 increased their dynamic balance . The findings suggest that Adapted Physical Activities training limits the decline in sensorial functions in the elderly ABSTRACT Objective The prospect i ve pre – post control study was design ed to evaluate the effect of introducing balance-focused interactive virtual-reality games to community-dwelling older women to improve their agility , balance and functional mobility . Method The study was set in a senior citizens ’ club in Cheras , Kuala Lumpur , Malaysia . The participants were 36 community-dwelling older women . Participants were r and omly divided into either a group undertaking balance-focused virtual-reality games or a group doing therapeutic balance exercises . The program lasted 6 weeks and was conducted twice a week for 40 min during each session . As the main outcome measures , the results of the Ten Step Test ( TST ) , postural sway ( overall performance index , OPI ) and the Timed Up and Go test ( TUG ) were measured pre- and post-intervention to evaluate agility , balance and functional mobility , respectively . Results Although both groups improved in OPI ( F = 4.63 , p < 0.001 ) , TST ( F = 46.15 , p < 0.001 ) and TUG ( F = 52.57 , p = 0.03 ) , combined time and group interaction only improved in the TUG ( F = 4.54 , p < 0.05 ) . No significant differences between the two groups were found in terms of TST ( F = 0.02 , p = 0.86 ) , OPI ( F = 0.66 , p = 0.42 ) , and TUG ( F = 0.11 , p = 0.74 ) . Conclusion Older people could improve their agility , balance and functional mobility by complementing therapeutic balance exercises with active participation in interactive virtual-reality games at home or in the community BACKGROUND AND PURPOSE This prospect i ve clinical investigation examined the effects of a multidimensional exercise program on balance , mobility , and risk for falls in community-dwelling older adults with a history of falling . Factors used to predict adherence and a successful response to exercise were identified . SUBJECTS A total of 105 community-dwelling older adults ( > or = 65 years of age ) with a history of two or more falls in the previous 6 months ( no neurologic diagnosis ) participated . They were classified into ( 1 ) a control group of fallers ( n = 21 ) , ( 2 ) a fully adherent exercise group ( n = 52 ) , and ( 3 ) a partially adherent exercise group ( n = 32 ) . METHODS Following evaluation , each patient received an individualized exercise program addressing the impairments and functional disabilities identified during the assessment . The control group received no intervention . Changes in performance on five clinical tests of balance and mobility and fall risk were compared among groups . RESULTS Both exercise groups scored better than the control group on all measures of balance and mobility . Although both exercise groups showed a reduction in fall risk compared with the control group , the greatest reduction was found in the fully adherent exercise group . Factors associated with successful response to exercise included degree of adherence to exercise program and pretest score on the Tinetti Mobility Assessment . CONCLUSION AND DISCUSSION Exercise can improve balance and mobility function and reduce the likelihood for falls among community-dwelling older adults with a history of falling . The amount of exercise needed to achieve these results , however , could not be determined from this study To study risk factors for falling , we conducted a one-year prospect i ve investigation , using a sample of 336 persons at least 75 years of age who were living in the community . All subjects underwent detailed clinical evaluation , including st and ardized measures of mental status , strength , reflexes , balance , and gait ; in addition , we inspected their homes for environmental hazards . Falls and their circumstances were identified during bimonthly telephone calls . During one year of follow-up , 108 subjects ( 32 percent ) fell at least once ; 24 percent of those who fell had serious injuries and 6 percent had fractures . Predisposing factors for falls were identified in linear-logistic models . The adjusted odds ratio for sedative use was 28.3 ; for cognitive impairment , 5.0 ; for disability of the lower extremities , 3.8 ; for palmomental reflex , 3.0 ; for abnormalities of balance and gait , 1.9 ; and for foot problems , 1.8 ; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables . The risk of falling increased linearly with the number of risk factors , from 8 percent with none to 78 percent with four or more risk factors ( P less than 0.0001 ) . About 10 percent of the falls occurred during acute illness , 5 percent during hazardous activity , and 44 percent in the presence of environmental hazards . We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling OBJECTIVE To compare the impacts of Tai Chi , a st and ard balance exercise program , and a video game balance board program on postural control and perceived falls risk . DESIGN R and omized controlled trial . SETTING Research laboratory . PARTICIPANTS Independent seniors ( N=40 ; 72.5±8.40 ) began the training , 27 completed . INTERVENTIONS Tai Chi , a st and ard balance exercise program , and a video game balance board program . MAIN OUTCOME MEASURES The following were used as measures : Timed Up & Go , One-Leg Stance , functional reach , Tinetti Performance Oriented Mobility Assessment , force plate center of pressure ( COP ) and time to boundary , dynamic posturography ( DP ) , Falls Risk for Older People-Community Setting , and Falls Efficacy Scale . RESULTS No significant differences were seen between groups for any outcome measures at baseline , nor were significant time or group × time differences for any field test or question naire . No group × time differences were seen for any COP measures ; however , significant time differences were seen for total COP , 3 of 4 anterior/posterior displacement and both velocity , and 1 displacement and 1 velocity medial/lateral measure across time for the entire sample . For DP , significant improvements in the overall score ( dynamic movement analysis score ) , and in 2 of the 3 linear and angular measures were seen for the sample . CONCLUSIONS The video game balance board program , which can be performed at home , was as effective as Tai Chi and the st and ard balance exercise program in improving postural control and balance dictated by the force plate postural sway and DP measures . This finding may have implication s for exercise adherence because the at-home nature of the intervention eliminates many obstacles to exercise training |
10,922 | 21,127,279 | Dose titration was shown to influence both the change in arterial blood pressure and heart rate .
: This review suggests that titration of esmolol to a hemodynamic end point can be safe and effective . | BACKGROUND : Although & bgr ; blockers have been found to decrease perioperative myocardial infa rct ion ( MI ) , & bgr;-blocker-mediated hypotension is associated with postoperative stroke and mortality .
In this systematic review we assessed the safety and efficacy of the & bgr;1-specific , adrenergic receptor antagonist esmolol in noncardiac surgery .
Safety was assessed by analyzing the incidence of postoperative hypotension and bradycardia , and efficacy was assessed by analyzing the incidence of myocardial ischemia . | OBJECTIVES The purpose of this research was to perform a feasibility study of prophylactic coronary revascularization in patients with preoperative extensive stress-induced ischemia . BACKGROUND Prophylactic coronary revascularization in vascular surgery patients with coronary artery disease does not improve postoperative outcome . If a beneficial effect is to be expected , then at least those with extensive coronary artery disease should benefit from this strategy . METHODS One thous and eight hundred eighty patients were screened , and those with > or =3 risk factors underwent cardiac testing using dobutamine echocardiography ( 17-segment model ) or stress nuclear imaging ( 6-wall model ) . Those with extensive stress-induced ischemia ( > or = 5 segments or > or =3 walls ) were r and omly assigned for additional revascularization . All received beta-blockers aim ing at a heart rate of 60 to 65 beats/min , and antiplatelet therapy was continued during surgery . The end points were the composite of all-cause death or myocardial infa rct ion at 30 days and during 1-year follow-up . RESULTS Of 430 high-risk patients , 101 ( 23 % ) showed extensive ischemia and were r and omly assigned to revascularization ( n = 49 ) or no revascularization . Coronary angiography showed 2-vessel disease in 12 ( 24 % ) , 3-vessel disease in 33 ( 67 % ) , and left main in 4 ( 8 % ) . Two patients died after revascularization , but before operation , because of a ruptured aneurysm . Revascularization did not improve 30-day outcome ; the incidence of the composite end point was 43 % versus 33 % ( odds ratio 1.4 , 95 % confidence interval 0.7 to 2.8 ; p = 0.30 ) . Also , no benefit during 1-year follow-up was observed after coronary revascularization ( 49 % vs. 44 % , odds ratio 1.2 , 95 % confidence interval 0.7 to 2.3 ; p = 0.48 ) . CONCLUSIONS In this r and omized pilot study , design ed to obtain efficacy and safety estimates , preoperative coronary revascularization in high-risk patients was not associated with an improved outcome Forty-five patients of ASA physical status 1 and II undergoing a variety of non-cardiac surgical procedures were studied to determine the effect of bolus administration of esmolol , a new short-acting beta blocking drug , on heart rate and blood pressure responses to induction of anaesthesia and tracheal intubation . Subjects were allocated r and omly to receive placebo , 100 mg or 200 mg of esmolol IV as part of an anaesthetic induction technique . The differences in heart rate between the placebo group and both the 100 mg and 200 mg groups were significant prior to intubation ( 95 ± 7.9 , 82 ± 9.7 , 80 ± 7.3 beats per min respectively ) , and also at 0.5 min and 1.5 min following intubation for the 200 mg group . In the 200 mg group there was a significant decrease , compared with placebo , in systolic blood pressure at 0.5 min ( 144 ± 32.1 vs 165 ± 18.7 mmHg ) and 1.5 min ( 154 ± 25.0 vs 170 ± 19.5 mmHg ) after intubation . In this study , adequate haemodynamic control was obtained following administration of 200 mg of esmolol . RésuméQuarante-cinq patients ASA classe I et II devant subir une variété de procédures chirurgicales non-cardiaques ont été étudiés afin de déterminer l’effet de l’administration de l’esmolol en bolus sur la fréquence cardiaque et la tension artérielle lors de l’induction de l’anesthesie et l’intubation endotrachéale . Les sujets ont été r and omisés afin de recevoir soit du placebo , soit 100 mg ou 200 mg d’esmolol lors de l’induction . Les différences dans la fréquence cardiaque entre le groupe placebo et les deux groupes de 100 mg et 200 mg etaient significatives avant l’intubation ( 95 ± 7,9 , 82 ± 9,7 , 80 ± 7,3 battlminute respectivement ) , et aussi à 0,5 minutes et 1,5 minutes après l ’ intubation pour le groupe de 200 mg . Pour le groupe 200 mg , il y avait une diminution significative ( comparativement au placebo ) dans la pression artérielle systolique à 0,5 minutes ( 144 ± 32,1 versus 165 ± 18,7 mmHg ) et à 1,5 minutes ( 154 ± 25,0 versus 170 ± 19,5 mmHg ) après intubation . Dans cette etude , un contrôle hémodynamique adéquat était obtenu aprés administration de 200 mg d’esmolol Background : Carbon dioxide ( CO2 ) pneumoperitoneum for laparoscopic surgery increases arterial pressures , systemic vascular resistance and heart rate and decreases urine output The goal of this study was to compare the efficacy of esmolol and sodium nitroprusside ( SNP ) as primary drugs for producing controlled hypotension and limiting blood loss during orthognathic surgery . Thirty ASA physical status I and II patients ( mean age 22 yr ) undergoing LeFort I maxillary osteotomies were r and omly assigned to receive either esmolol ( n = 15 ) or SNP ( n = 15 ) as the primary drug to induce hypotension . All patients received a balanced anesthetic technique including isoflurane , with controlled hypotension during the down fracture of the maxilla . Patients assigned to the esmolol treatment group received boluses of 500 μg/kg of esmolol , followed by a continuous infusion of 100–300 μkg−1 · min−1 , and the SNP treatment group received a continuous infusion of SNP at 0.25 - -4.00 μkg−1 · min−1 ; both infusions were nitrated to obtain a mean arterial blood pressure within the target range of 55 - -65 mm Hg . The mean arterial blood pressure during the hypotensive period was 58.7 ±0.7 ( mean ± SEM ) and 61.8 ± 0.4 mm Hg for esmolol and SNP , respectively ( P < 0.001 ) . In addition , 40 % ± 4 % of the observed values in the esmolol group and 53 % ± 3 % in the SNP group were outside the target range for mean arterial blood pressure ( difference significant at P < 0.05 ) , and a greater proportion of the deviations were above 65 mm Hg in the SNP group than in the esmolol group ( 0.64 vs 0.46 , respectively , P < 0.05 ) . The mean heart rate was 70 Rekha 3 beats/min ( esmolol ) and 100 ± 3 beats/min ( SNP ) ( P < 0.001 ) , and the mean blood loss was 436 ± 65 mL ( esmolol ) and 895 ± 101 mL ( SNP ) ( P < 0.001 ) . The surgical field was judged to be drier with esmolol than with SNP ( P < 0.05 ) . Plasma renin activity decreased slightly in the esmolol group , whereas in the SNP group it increased 267 % ( P < 0.001 ) . The absence of the renin release may have facilitated the stability of controlled hypotension with esmolol . The advantages of esmolol over SNP for controlled hypotension during orthognathic surgery include greater control of blood pressure , reduction in blood loss , and a drier surgical field . These advantages must be weighed against the possibility of significant myocardial depression produced by intense β1-adrenergic blockade BACKGROUND Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol In a double‐blind study the effect of esmolol and alfentanil on the QT interval of the ECG corrected by the heart rate ( QTc ) , heart rate and arterial pressure during anaesthetic induction was studied in 59 oxycodone‐ and atropine‐premedicated ASA class I‐(II ) patients with a mean age of 26 yr ( range 15–50 yr ) . The patients were r and omly allocated to one of the four groups : saline , esmolol 2 mg · kg‐1 , esmolol 3 mg · kg‐1 or alfentanil 0.03 mg·kg‐1 . Both doses of esmolol prevented the prolongation of the QTc interval after thiopental and suxamethonium , but not after laryngoscopy and intubation . Alfentanil prevented the prolongation of the QTc interval following thiopental , suxamethonium and laryngoscopy but not after intubation . Esmolol did not prevent the increase in the heart rate and arterial pressure in response to laryngoscopy and intubation . No cardiovascular responses to laryngoscopy and intubation occurred in the patients treated with alfentanil . No cardiac arrhythmias occurred in the esmolol 3 mg·kg‐1 group , whereas the frequency of ventricular ectopic beats was 40 % in the saline group and 13–20 % m the other groups BACKGROUND Beta-adrenergic agonists enhance behavioural and electroencephalographic arousal reactions . We explored whether adding esmolol , a short-acting beta(1)-adrenoceptor antagonist , to propofol anaesthesia modified the bispectral index ( BIS ) during induction of anaesthesia and orotracheal intubation . METHODS Fifty patients were r and omly allocated , in a double-blind fashion , to receive esmolol 1 mg kg(-1 ) followed by 250 micro g kg(-1 ) min(-1 ) or saline ( control ) . Esmolol or saline was started 6 min after a target-controlled infusion ( TCI ) of propofol ( effect-site concentration 4 micro g ml(-1 ) ) . After loss of consciousness , and before administration of vecuronium 0.1 mg kg(-1 ) , a tourniquet was applied to one arm and inflated to 150 mm Hg greater than systolic pressure . Eleven minutes after the TCI began , the trachea was intubated ; gross movement within the first min after orotracheal intubation was recorded . BIS was recorded at 10-s intervals . Mean arterial pressure ( MAP ) and heart rate were measured non-invasively every min . RESULTS There were no intergroup differences in BIS , heart rate or MAP before laryngoscopy . BIS increased significantly after orotracheal intubation ( compared with the pre-laryngoscopy values ) in the control group only , with a maximum increase of 40 ( SD 18)% vs 8 (11)% in the esmolol group ( P<0.01 ) . Maximum changes in heart rate [ 45 (19)% vs 23 (14)% ] and MAP [ 62 (24)% vs 45 (23)% ] with orotracheal intubation were also significantly greater in the control group than in the esmolol group . More patients in the control than in the esmolol group moved after orotracheal intubation ( 23 vs 12 , P<0.01 ) . CONCLUSION Esmolol not only attenuated haemodynamic and somatic responses to laryngoscopy and orotracheal intubation , but also prevented BIS arousal reactions in patients anaesthetized with propofol Background and objective : This r and omized , double-blinded , prospect i ve study compared the effects of clonidine , esmolol or alfentanil on the level of hypnosis and haemodynamic responses to intravenous induction of anaesthesia and endotracheal intubation . Methods : Forty-five patients scheduled for elective surgery were allotted to one of three groups . They were given either alfentanil 3 μg kg−1 min−1 ( n = 15 ) ; esmolol 1 mg kg−1 min−1 ( n = 16 ) or clonidine 3 μg kg−1 ( n = 14 ) as a 10 min infusion . The infusions of alfentanil and esmolol , but not of clonidine , were maintained during endotracheal intubation . Anaesthesia was induced with midazolam ( 2 mg ) and thiopental as required to suppress the eyelash reflex . Atracurium ( 0.5 mg kg−1 ) was given to produce neuromuscular block . Mean arterial pressure , heart rate , and bispectral index were recorded on arrival ( baseline ) , after study drug infusion , after injecting midazolam and thiopental , as well as after endotracheal intubation . ANOVA and χ2-test were used for analysis . Results : Blood pressure , heart rate and the bispectral index were unaltered by the study drugs , but thiopental requirements were reduced by alfentanil and clonidine ( P < 0.014 ) . Mean arterial pressure values ( mean ± st and ard error of mean ) in the alfentanil , esmolol and clonidine groups were : baseline : 107.8 ± 3.8 ; 106.6 ± 3.9 ; 103.4 ± 3.7 mmHg ; after thiopental : 74.0 ± 4.2 ; 85.6 ± 4.3 ; 94.2 ± 4.1 mmHg and after endotracheal intubation : 91.7 ± 5.3 ; 114.1 ± 6.9 ; 123.6 ± 5.6 mmHg , respectively ( two-way ANOVA , P < 0.001 ) . Mean arterial pressure changed significantly after intubation from baseline ( P < 0.001 ) after alfentanil ( − 15 % ) and clonidine ( + 20 % ) but not after esmolol ( + 7 % ) , while the changes between pre- and postintubation values were similar in all groups ( 24 - 33 % increase ) . The bispectral index indicated that all patients had an adequate level of hypnosis , but the variability was higher in the esmolol group ( P < 0.002 ) . Conclusions : None of the study drugs blocked the increase in mean arterial pressure induced by endotracheal intubation , but esmolol provided better overall haemodynamic stability . All groups had an adequate level of hypnosis BACKGROUND Perioperative use of beta-blockers has been advocated as a strategy to prevent cardiac sequelae . This study evaluated the influence of perioperative esmolol administration upon anaesthesia and postoperative pain management amongst patients undergoing hysterectomy . METHODS Ninety-seven ASA I-II patients , undergoing abdominal total hysterectomy , were r and omly divided into one of two groups . Patients in the Esmolol group received an i.v . loading dose of esmolol 0.5 mg kg(-1 ) followed by infusion of 0.05 mg kg(-1 ) min(-1 ) before anaesthesia induction . The infusion was documented at the completion of surgery . The Control group received a volume of normal saline . After surgery , all patients were treated with patient-controlled i.v . analgesia ( PCA ) , which was programmed to deliver 1 mg of morphine on dem and for 3 consecutive days . Pain intensity on movement and at rest , sedation score , and side effects were recorded . RESULTS The two groups were comparable with respect to their characteristics . Patients in the esmolol group received significantly lower end-tidal isoflurane concentrations ( 1.0 ( 0.3 ) vs 1.4 (0.5)% , respectively ; P<0.001 ) and fentanyl ( 0.9 ( 0.2 ) vs 1.2 ( 0.5 ) microg kg(-1 ) , respectively ; P=0.006 ) during anaesthesia . They also showed a reduced heart rate and arterial pressure response to tracheal intubation , skin incision , and tracheal extubation . The Esmolol group consumed less PCA morphine in 3 days ( 37.3 ( 8.4 ) vs 54.7 ( 11.2 ) mg , respectively ; P=0.005 ) . Pain intensity and medication side effects were similar in the two groups . CONCLUSION The results suggest that perioperative esmolol administration during anaesthesia reduces the intraoperative use of inhalation anaesthetic and fentanyl , decreases haemodynamic responses , and reduced morphine consumption for the first 3 postoperative days Purpose To compare the ability of different bolus doses of esmolol to blunt the haemodynamic effects of laryngoscopy and tracheal intubation in treated hypertensive patients . Methods In this r and omised , doubleblind placebo controlled study , 45 ASA II patients , treated for essential hypertension with drugs other than beta blockers , were divided into three groups of 15 patients each . Patients in different groups either received 20 ml normal saline ( Group P ) , or 100 mg esmolol ( Group E100 ) or 200 mg esmolol ( Group E200 ) as a single bolus intravenous dose before laryngoscopy and intubation . Systolic , diastolic and mean arterial pressure and heart rate were monitored for up to 10 min following intubation and were compared with respective basal readings as well as across groups . Results Esmolol alone reduced systolic arterial pressure ( P < 0.01 in Group E100 and P < 0.001 in Group E200 ) and heart rate ( P < 0.001 ) . Though there was an increase in arterial pressure and heart rate in the control group , esmolol 100 mg maintained arterial pressure and heart rate at levels comparable to basal values throughout the study ( P > 0.05 ) . Patients receiving esmolol 200 mg had lower values ( P < 0.001 ) than their basal readings during most of the postintubation study period . Conclusion Esmolol 100 mg given as bolus , is effective as well as safe in blunting the haemodynamic responses to laryngoscopy and tracheal intubation in treated hypertensive patients .RésuméObjectifComparer l’efficacité de différentes doses d’esmolol administrées pour atténuer les effets hémodynamiques de la laryngoscopie et de l’intubation de la trachée chez des hypertendus traités . MéthodesDans cette étude contrôlée aléatoire , à double aveugle avec placebo , 45 patients ASA II , traités pour hypertension essentielle avec des médicaments autres que des βbloquants ont été répartis en trois groupes de 15 patients . Ils ont reçu soit 20 ml de sol . physiologique ( groupe P ) , soit 100 mg d’esmolol ( groupe E100 ) , soit 200 mg d’esmolol ( groupe E200 ) en un seul bolus intraveineux avant la laryngoscopie et l’intubation . Les pressions systolique , diastolique et moyenne ainsi que la fréquence cardiaque ont été monitorés pendant 10 min après l’intubation et comparées aux mesures initiales et entre les groupes . RésultatsSeul l’esmolol a diminué la pression artérielle systolique ( P < 0,01 dans le groupe E100 et P < 0,001 dans le groupe E200 ) et la fréquence cardiaque ( P < 0,001 ) . Alors qu ’ on notait une augmentation de ta pression artérielle et de la fréquence cardiaque dans le groupe contrôle , l’esmolol 100 mg maintenait la pression artérielle et la fréquence cardiaque à des niveaux comparables aux valeurs initiales ( P < 0,05 ) . Les patients recevant esmolol 200 mg avaient des valeurs inférieures ( P < 0,001 ) aux valeurs initiales pendant la majeure partie de la période étudiée . Conclusion L’esmolol 100 mg administré en bolus est efficace et sans danger pour atténuer tes réponses hémodynamiques de la laryngoscopie et de l’intubation chez des hypertendus traités OBJECTIVE To assess the effect of esmolol vs lidocaine to attenuate the detrimental rise in heart rate and blood pressure during intubation of patients with isolated head trauma . METHODS This was a prospect i ve , double-blind , r and omized study , performed at an urban , county teaching emergency department . Participants were 30 patients with isolated head trauma . Each underwent a st and ardized intubation protocol including esmolol or lidocaine , both at 2 mg/kg . RESULTS Esmolol was used in 16 patients and lidocaine in 14 . Mechanisms of injury included 12 assaults , 6 motor vehicle collisions , 6 falls , 4 auto-vs-pedestrian crashes , and 2 bicycle incidents . Mean ethanol level was 0.116+/-0.133 SD ( range 0 - 0.482 ) . Mean Glasgow Coma Scale ( GCS ) score was 7.9+/-4.0 SD . Cranial computed tomography ( CT ) hemorrhagic findings included 9 subdural/epidural hematomas , 6 cortex hemorrhages , and 2 multi-hemorrhages . Eleven patients received surgical intervention : 9 patients received a craniotomy , and 2 a ventricular catheter . The 2-minute time interval around intubation was used to assess each drug 's efficacy . The mean difference change between groups for heart rate was 4.0 beats/min ( 95 % CI = -17.7 to 9.7 beats/min ) , for systolic blood pressure was 1.3 mm Hg ( 95 % CI = -27.8 to 30.4 mm Hg ) , and for diastolic blood pressure was 2.6 mm Hg ( 95 % CI = -27.1 to 21.9 mm Hg ) . The power of this study was 90 % to detect a 20-beat/min difference in heart rate , a 35-mm Hg difference in systolic blood pressure , and a 20-mm Hg difference in diastolic blood pressure . CONCLUSIONS Esmolol and lidocaine have similar efficacies to attenuate moderate hemodynamic response to intubation of patients with isolated head trauma UNLABELLED A r and omized , double-blind , parallel , placebo-controlled study was conducted to determine the safety and efficacy of intravenous ( IV ) bolus administration of esmolol in treating intraoperative tachycardia in patients undergoing noncardiac general surgery . Forty-eight ASA II-IV patients were r and omized into three equal groups to receive either placebo , esmolol 50 mg , or esmolol 100 mg . Premedication ( lorazepam ) and anesthetic induction techniques ( thiopental sodium and succinylcholine ) were identical between groups . Approximately 20 minutes after intubation , during isoflurane/N2O/O2 maintenance anesthesia , patients with systolic pressure ( SBP ) greater than or equal to 110 mmHg were advanced into a 10-minute study drug period if one of two conditions were met : ( 1 ) heart rate ( HR ) was greater than or equal to 95 beats/minute , or ( 2 ) an increase in HR of greater than 20 % above preinduction baseline occurred . After two consecutive recordings of HR and blood pressure ( BP ) , the study drug ( or placebo ) was injected . HR was recorded every 30 seconds and BP was recorded every minute during the ensuing 10-minute period . Compared to placebo responses , HR was significantly reduced with both doses of esmolol within 1 minute of bolus injection and remained below placebo levels for 5 minutes after 50 mg of esmolol and for 9.5 minutes after 100 mg of esmolol . There were , however , only minor differences among groups with respect to SBP , diastolic blood pressure ( DBP ) , and mean blood pressure ( MBP ) changes . CONCLUSION Bolus administration of esmolol can produce a rapid reduction of HR with relatively few adverse effects in an unhealthy surgical population . ( ABSTRACT TRUNCATED AT 250 WORDS Esmolol attenuates hemodynamic responses to tracheal intubation and extubation in young patients , but has less well documented pharmacokinetics and efficacy in older patients . Following cataract surgery , application of pressure on the eye during eye b and aging may have vasomotor effects . The present study of older patients having cataract surgery investigated 1 ) the effects of normal saline 1.0 ml . 10kg(-1 ) or esmolol 4.0 mg.kg(-1 ) IV given 90 secs prior to tracheal intubation and of normal saline 0.5 ml.10 kg(-1 ) or esmolol 2.0 mg.kg(-1 ) IV given 60 sec prior to each of eye b and aging and tracheal extubation ; 2 ) the time to onset and duration of action of esmolol ; 3 ) the cardiovascular effects of eye b and aging . Esmolol attenuated the cardiovascular effects of tracheal intubation , eye b and aging and tracheal extubation , but caused relative bradycardia and hypotension after induction and hypotension after extubation . Its effect occurred within 60 - 90 secs and lasted about 6 mins . Pressure on the eye during b and aging in those not given esmolol caused hypertension without tachycardia Esmolol , an ultra-short-acting cardioselective betaadrenergic blocker , was investigated in a double-blind prospect i ve protocol for its ability to control haemodynamic responses associated with tracheal intubation after thiopentone and succinylcholine . Thirty ASA physical status I patients received a 12-minute infusion of esmolol ( 500 µg·kg-1·min-1 for four minutes , then 300 µg·kg-1 min-1 for 8 mnutes ) or saline . Five minutes after the start of the drug/placebo infusion , anaesthesia was induced with 4 mg·kg-1 thiopentone followed by succinylcholine for tracheal intubation . Prior to induction esmolol produced significant decreases in heart rate ( HR ) ( 9.3 ± 1.8 per cent ) and rate-pressure product ( RPP ) ( 13.1 ± 1.8 per cent ) , systolic blood pressure ( SAP ) ( 4.3 ± 1.5 per cent ) and mean arterial blood pressure ( MAP ) ( 1.7 ± 2.0 per cent ) . Increases in HR , SAP and RPP after intubation were approximately 50 per cent less in patients given esmolol compared to patients given placebo . There were highly significant differences in HR ( p < 0.0001 ) , and RPP ( p < 0.0005 ) and significant differences in SAP ( p < 0.05 ) when the maximal esmolol post-intubation response was compared to the maximal placebo response . Infusion of esmolol in the dose utilized in this study significantly attenuated but did not completely eliminate cardiovascular responses to intubation . RésuméL’esmolol , un bloquer bêta-adrénergique cardiosélectif de courte durée d’action a été investigué dans une étude prospect i ve à double insu pour sa capacité de contrôler les réponses hémodynamiques associées à l’intubation trachéale après thiopentone et succinylcholine . Trente patients ASA I ont requ une perfusion de 12 minutes d’esmolol ( 500 µg · kg-1 · min-1 pour quatre minutes , puis 300 µg · kg-1 pour huit minutes ) ou du salin . Cinq minutes après le début de la perfusion du médicament ou du placebo , l ’ anesthésie était induite avec 4 mg·kg-1 de thiopentone suivi de succinylcholine pour l’intubation trachéale . Avant l’induction l’esmolol a produit une diminution significative de la fréquence cardiaque ( HR ) ( 9.3 ± 1.8 pour cent ) et du produit fréquence-pression ( RPP ) ( 13.1 ±1.8 pour cent ) , de la tension artérielle systolique ( SAP ) ( 4.3 ± 1.5 pour cent ) et de la pression artérielle mopenne ( MAP ) ( 1.7 ± 2.0 pour cent ) . Après l’intubation , l’augmentation dans la fréquence cardiaque , la pression artérielle systolique et la produit fréquence-pression était approximativement 50 pour cent moindre chez les patients ayant reçu de l’esmolol que chez les patients ayant regu du placebo . Il y avait une difference hautement significative dans la frequence cardiaque ( p < 0.0001 ) et dans le produit fréquencepression ( p < 0.0005 ) ainsi qu’une difference significative dans la pression artérielle systolique ( p < 0.05 ) qu and la réponse maximale post-intubation à l’esmolol a été comparée à la réponse maximale au placebo . La perfusion d’esmolol aux doses utilisées dans cette étude atténue significativement mais n’élimine pas complètement les réponses cardiovasculaires à l’intubation OBJECTIVE The purpose of this study was to compare the effectiveness of intravenous ( IV ) nicardipine versus esmolol in controlling heart rate ( HR ) and blood pressure ( BP ) responses to emergence and extubation . DESIGN Prospect i ve , r and omized , double blind . SETTING University hospital , single institution . PARTICIPANTS Twenty-two American Society of Anesthesiologists physical class 1 to 3 adult in patients scheduled for general anesthesia . INTERVENTIONS General endotracheal anesthesia with oxygen/isoflurane and muscle relaxation . At end of surgery , with at least 2 twitches by nerve stimulator and end-tidal isoflurane < 0.4 % , muscle relaxant reversal was accomplished with neostigmine and glycopyrrolate . Two minutes postreversal , the IV study drug nicardipine , 0.03 mg/kg , or esmolol , 1.5 mg/kg , was administered . HR and BP were measured every minute up to 10 minutes and at minute 15 postreversal . MEASUREMENTS AND MAIN RESULTS There were no significant differences between groups in age , weight , gender , American Society of Anesthesiologists physical class or preoperative hemodynamics ( HR , BP , mean arterial pressure [ MAP ] ) . Compared with nicardipine , 0.03 mg/kg IV , esmolol , 1.5 mg/kg IV , significantly ( p < 0.05 ) attenuated HR more than nicardipine for the 15-minute time period post study drug . Compared with esmolol , nicardipine was significantly ( p < 0.05 ) more effective in controlling MAP and systolic BP for the 1- to 3-minute and diastolic BP for the 1- to 2-minute time periods post study drug . There were no episodes of hypotension or adverse events . CONCLUSIONS Although esmolol , 1.5 mg/kg , IV was more effective than nicardipine , 0.03 mg/kg , IV for attenuating the HR response to extubation , nicardipine was more effective in controlling the BP response A new cardioselective and rapidly metabolized beta-blocker , esmolol ( E ) , was given to prevent post-intubation tachycardia in 40 ASA Class PS I-II patients induced with thiopental , succinylcholine , N2O : O2 and enflurane sequence . The control group ( A , n = 10 ) received 5 % D/W. Three study groups received E loading doses of 500 micrograms/kg/min for 1 min ( B , n = 8) , 2 min ( C , n = 10 ) and 4 min ( D , n = 12 ) ; the continuous i.v . maintenance doses were 100 , 200 and 300 micrograms/kg/min for a total of 10 min , respectively . The pre-esmolol heart rates were 85 + /- 4 in group A , 80 + /- 5 in B , 77 + /- 5 in C , 83 + /- 5 in D ; at anesthetic induction and at 4 min after E-infusion , heart rates were 93 + /- 5 , 65 + /- 4 , 71 + /- 4 , 70 + /- 5 , respectively ; three min post-intubation heart rates were in the control group 111 + /- 4 and 82 + /- 5 , 93 + /- 5 , 85 + /- 4 , respectively , in the E-treated groups . Group A showed marked tachycardia ( p less than or equal to 0.001 ) not observed in the treated groups B , C , D. A significant blockade of HR increases at all infusion rates of E ( p less than or equal to 0.05 ) was found . E at all doses reduced the significant increase in BP observed in Group A. Catecholamine increases were identical and not significantly different among the groups . No adverse effects e.g. bradycardia , arrhythmias and hypotension caused by E or intubation were seen . ( ABSTRACT TRUNCATED AT 250 WORDS Cerebral hyperemia has been demonstrated during emergence from anesthesia in neurosurgical patients , but its mechanism is speculative . We performed this study to test the hypothesis that this could be attributed to sympathetic overactivity . Thirty neurosurgical patients were included in a prospect i ve , r and omized , double-blinded study comparing esmolol , a short-acting & bgr;-blocker , and a placebo . Esmolol ( 0.3 mg · kg−1 · min−1 ) was infused from the end of anesthesia to 15 min after extubation . Cerebral blood flow velocity ( CBFV ) , mean arterial blood pressure , and heart rate were recorded before anesthesia , during anesthesia after surgery , at extubation , and 5–60 min after extubation . Cardiac output ( COe ) was estimated by using an esophageal Doppler from anesthesia to 60 min after extubation . CBFV , COe , and heart rate were significantly lower in the esmolol group . Mean arterial blood pressure was comparable between the groups . There was no correlation between CBFV and COe at any time point during the study . In conclusion , esmolol blunted the CBFV increase during emergence , confirming that sympathetic overactivity contributes to cerebral hyperemia during neurosurgical recovery Activation of the peripheral nerve system by endotracheal intubation is accompanied by an increase in bispectral index ( BIS ) . Esmolol produces a dose-dependent attenuation of the adrenergic response to endotracheal intubation . Desflurane increases sympathetic nerve activity and plasma norepinephrine relative to sevoflurane . The authors hypothesized that esmolol might blunt the BIS response to endotracheal intubation more during sevoflurane anesthesia than desflurane anesthesia . In this double blind , r and omized study , after the induction of anesthesia , patients were mask-ventilated with either sevoflurane or desflurane ( end-tidal 1 minimum alveolar concentration ) and received normal saline or esmolol ( 0.5 mg/kg ) 1 minute before intubation ( sevoflurane-control , sevoflurane-esmolol , desflurane-control , and desflurane-esmolol groups , n=20/group ) . BIS , mean arterial pressure , and heart rate were measured before the induction of anesthesia ( awake ) , before esmolol injection ( time point -1 ) , immediately before intubation ( time point 0 ) , and every minute for 5 minutes after tracheal intubation ( time point 1 to 5 ) . Compared with preintubation , esmolol attenuated the increase in BIS at 1 minute after intubation during sevoflurane anesthesia ( 5.1 % for esmolol and 31.7 % for control ) but not during desflurane anesthesia ( 28.6 % for esmolol and 30.8 % for control ) . Mean arterial pressure and heart rate increased after intubation in all groups but the changes were greater in the control groups than the esmolol groups . In conclusion , a single dose of esmolol blunted the increase in BIS to tracheal intubation during sevoflurane but not desflurane anesthesia The purpose of this r and omized , double-blind study was to compare the ability of a combination of fentanyl and esmolol to blunt the haemodynamic effects of intubation with that of either agent alone . Patients received fentanyl or saline four minutes before , and esmolol or saline two minutes before rapid-sequence induction of anaesthesia . The F2 group ( n = 24 ) received fentanyl 2 μg · kg−1 , the E2 group ( n = 24 ) received esmolol 2 mg · kg−1 , the F2/E2 group ( n = 25 ) received a combination of fentanyl 2 μg · kg−1 and esmolol 2 mg · kg−1 , and the F5 group ( n = 26 ) received fentanyl 5 μg · kg−1 . Following tracheal intubation , the maximum percent change from baseline heart rate was less in the F2/E2 and F5 groups ( 12 % and 16 % respectively ) than in the E2 group (34%)(P < 0.05 ) . The maximum percent changes from baseline systolic blood pressure in the F2/E2 and F5 groups ( 15 % and 6 % respectively ) were less than in the F2 and E2 groups ( 24 % and 33 % respectively ) ( P < 0.05 ) . The combination of a low dose of fentanyl and esmolol provides an alternative to a higher dose of fentanyl for blunting the haemodynamic responses to laryngoscopy and tracheal intubation during rapidsequence induction in healthy patients .RésuméCette étude r and omisée , à double insu , compare la capacité de blocage de la réponse hémodynamique à l’intubation de l’association fentanyl/esmolol avec celle des deux agents utilisés séparément . Les patients reçoivent soit du fentanyl ou du soluté physiologique , soit de l’esmolol ou du soluté physiologique , respectivement à quatre minutes et à deux minutes de l’induction d’une anesthésie à séquence rapide . Le groupe F2 ( n = 24 ) reçoit fentanyl 2 μg · kg−1 , le groupe E2 ( n = 24 ) reçoit esmolol 2 mg · kg−1 , le groupe F2/E2 ( n = 25 ) reçoit une association de 2 μg · kg−1 de fentanyl et d’esmolol 2 mg · kg−1 et le groupe F5 ( n = 26 ) reçoit fentanyl 5 μg · kg−1 . Après l’intubation endotrachéale , le pourcentage maximal de variation de la fréquence cardiaque initiale est moindre pour les groupes F2/E2 et F5 ( respectivement 15 % et 16 % ) que pour le groupe E2 ( 34 % ) ( P < 0,05 ) . Le pourcentage maximal de variation de la tension systolique initiale pour les groupes F2/E2 et F5 ( respectivement 15 % et 6 % ) est moindre que pour les groupes F2 et E2 ( respectivement 24 % et 33 % ) ( P < 0,05 ) . L’association d’une faible dose de fentanyl et d’esmolol constitue une alternative valable aux doses élevées de fentanyl pour atténuer les effets hémodynamiques de la laryngoscopie directe et de l’intubation endotrachéale lors de l’induction à sequence rapide de l’anesthésie chez des sujets en bonne santé In addition to laryngoscopy , endotracheal intubation , and other stressful intraoperative phases , hypertension occurs during recovery from anaesthesia , provoking post-operative complications like bleeding and increased intracranial or intraocular pressure . Furthermore , these hypertensive reactions result in life-threatening complications , especially in patients with pre-existing cardiovascular diseases . In this study , the effect of the new , short-acting beta-blocker esmolol given as a single bolus for preventing the increases in blood pressure and heart rate during recovery from anaesthesia and extubation in patients with hypertension was investigated . PATIENTS AND METHODS . Sixty-three patients with a history of hypertension over a period of more than 6 months and blood pressure ( BP ) more than 150/90 mm Hg undergoing intervertebral-disc , otolaryngologic , or eye surgery were included in the study . The operations were performed during thiopentone-induced isoflurane anaesthesia with relaxation by atracurium . The patients were assigned to three groups after giving witnessed oral informed consent . During the study period they received the study drug twice : ( A ) 30 - 90 s before turning off the nitrous oxide ; and ( B ) 20 - 90 s before extubation . Group I ( placebo ) received placebo each time , group II ( 100 mg esmolol ) placebo at A and 100 mg esmolol i.v . at B , and group III ( 200 mg esmolol ) 100 mg esmolol i.v . each time . After each medication the cardiovascular parameters were measured noninvasively over a period of 10 min every minute and in the following 2 h every 15 min . RESULTS . After the first medication systolic and diastolic BP , heart rate ( HR ) , and rate-pressure product ( RPP ) were lower in patients receiving 100 mg esmolol ( Group III ) than in groups I and II . After the second injection the blood pressure was lower in the two groups receiving 100 mg esmolol , than the placebo group ( I : 180.1 + /- 7.4/100.7 + /- 3.6 ; II : 152.8 + /- 5.8/87.9 + /- 3.4 ; III : 157.9 + /- 5.3/91.5 + /- 3.6 mm Hg [ mean 2 min + /- SEM ] ) . The changes in HR ( I : 88.2 + /- 3.8 ; II : 75.6 + /- 2.6 ; III : 72 + /- 3.1 min-1 ) and RPP ( I : 15,800 + /- 900 ; II : 11,700 + /- 700 ; III : 11,400 + /- 600 ) were similar . In 8 of the 20 patients in group III the HR dropped below 60.min-1 , but in none of these patients did the BP become instable . CONCLUSIONS . The sympathoadrenergic reaction during recovery from anaesthesia and extubation can be treated by beta-blocking agents , but such therapy is not without risk because of the long half-life and effects of the therapy on other factors such as postoperative loss of intravascular volume . Esmolol is a new , short-acting , cardioselective beta-blocker with a very short plasma distribution time and a elimination half-life of 9.2 min . Thus , the potential risks of beta-blockers due to half-life are minimised . The results of this study show that a dangerous increase in BP and HR with increased myocardial oxygen consumption can be prevented by a single bolus , and better by a double bolus of 100 mg esmolol . Although bradycardia with HR below 50.min-1 in 8 patients might indicate a risk of cardiac instability , the systolic BP did not fall below 100 mm Hg , and the episode of bradycardia was so short that there was no risk to the patients BACKGROUND We sought to assess the intra- and postoperative haemodynamic effects of continuous perioperative beta-adrenergic blockade combined with phosphodiesterase ( PDE ) III inhibition and its potential benefits in limiting perioperative myocardial ischaemia in high-risk vascular surgery patients . METHODS Seventy-five patients were r and omly assigned to receive tight heart rate ( HR ) control by a continuous infusion of : esmolol in combination with the PDE III inhibitor enoximone ( esmolol+enoximone group ) , esmolol infusion alone ( esmolol group ) , or st and ard therapy ( control group ) for a period of 48 h. Myocardial ischaemia and dysfunction were detected by serial plasma Troponin T ( TnT ) and B-type natriuretic peptide ( BNP ) measurements . RESULTS Cardiac index ( CI ) increased significantly only in esmolol+enoximone-treated patients [ CI : from 2.4 ( 0.2 ) litre min(-1 ) m(-2 ) at baseline to 3.2 ( 0.2 ) litre min(-1 ) m(-2 ) at 24 h after surgery ; P=0.001 ] and was significantly higher than in the esmolol [ CI : from 2.5 ( 0.2 ) litre min(-1 ) m(-2 ) at baseline to 2.6 ( 0.2 ) litre min(-1 ) m(-2 ) at 24 h ; P=0.18 ] and the control groups [ CI : from 2.4 ( 0.2 ) litre min(-1 ) m(-2 ) at baseline to 2.7 ( 0.2 ) litre min(-1 ) m(-2 ) at 24 h ; P=0.13 ] . A significant postoperative release of TnT was detected only in control patients . Plasma BNP levels increased towards the end of surgery in all patients . Peak plasma BNP concentrations were significantly higher in control patients [ 293 ( 98 ) pg ml(-1 ) ] than in esmolol [ 118 ( 71 ) pg ml(-1 ) ] and in esmolol+enoximone-treated patients [ 78 ( 21 ) pg ml(-1 ) ] . CONCLUSIONS Inotropic therapy with the PDE III inhibitor enoximone combined with tight HR control by a continuous infusion of esmolol improved cardiac function and reduced myocardial ischaemia in high-risk vascular surgery patients . CLINICAL TRIAL REGISTRATION INFORMATION-URL : http://www . clinical trials.gov . Unique identifier : NCT00348101 Tachycardia and hypertension usually accompany laryngoscopy and tracheal intubation . This response is undesirable , especially in patients with cardiovascular or intracranial diseases . Esmolol is a cardioselective , ultrashort-acting beta adrenergic blocking agent with a very short half-life . The efficacy of bolus dose of esmolol in blunting hemodynamic responses during laryngoscopy and tracheal intubation was evaluated . 45 patients ( 15 in each group ) of ASA physical status I and II scheduled for elective non-cardiac surgery were included in this r and omized , placebo-controlled study . At time zero , the study preparation ( placebo , 100 or 200 mg of esmolol ) was administered intravenously , followed by thiopentone 5 mg/kg and succinylcholine 1.5 mg/kg for induction . Tracheal intubation was performed 2 minutes after time zero . Anesthesia was maintained with 50 % nitrous oxide and 1.0 MAC halothane in oxygen , and vecuronium 0.08 mg/kg . Heart rate ( HR ) and systolic blood pressure ( SBP ) were recorded every minute for 10 minutes . To compare with the placebo group , there was a significant decrease in either HR or SBP in 200 mg group in the 8 minutes course after intubation ( p < 0.05 ) . There was a significant decrease in HR in the 100 mg group at the 3rd , 4th , and 5th minutes when compared with the placebo group ( p < 0.05 ) . The differences in SBP between the 100 mg group and placebo group were significant at the 3rd and 4th minutes ( p < 0.05 ) . Both bolus dosages of esmolol could effectively attenuate the tachycardia and hypertension produced by laryngoscopy and tracheal intubation . Furthermore , esmolol 200 mg presented a better hemodynamic stability than esmolol 100 mg during induction of anesthesia Laryngomicroscopy is a short-lasting procedure , which causes considerable hemodynamic and ECG changes . Therefore it sets specific dem and s on anesthetic care . In this double-blind r and omized work , we studied hemodynamic and ECG changes in patients during laryngomicroscopy in jet ventilation under propofol-alfentanil anesthesia with and without esmolol , a short-acting beta1-adrenergic receptor blocking agent . Forty ASA class I-II patients were allocated to receive either esmolol 1 mg.kg-1 + 200 micrograms.kg-1.min-1 ( the esmolol group ) or saline ( the control group ) ( mean age + /- SD 36 + /- 12 yrs in the esmolol group and 39 + /- 9 yrs in the control group ) . The heart rate and arterial pressure were measured non-invasively and ECG was analyzed with the aid of a microcomputer . In the control group , neither the heart rate nor the QTc interval of the ECG did change significantly when compared with the baseline values . In the presence of esmolol , the heart rate decreased and the QTc interval shortened during the procedure . Arterial pressure increased in the control group , but not in the esmolol group , when compared with the baseline values . No cardiac arrhythmias occurred in either of the groups . On the basis of the present study , propofol-alfentanil anesthesia combined with esmolol is a satisfactory method to meet specific dem and s of laryngomicroscopy in young and middle-aged ASA I-II patients . However , a combination of propofol and esmolol showed a tendency to decrease both the heart rate and arterial pressure and a caution is necessary when the combination were used in elderly patients BACKGROUND Laryngoscopy and tracheal intubation are known to increase sympathetic activity that may be detrimental to patients with pre-existing ischemic or hypertensive heart diseases . In order to alter the hyperdynamic consequences result ing from intubation during induction of general anesthesia , we chose esmolol , an ultra-short acting cardioselective beta-adrenergic blocker , to attenuate the cardiovascular responses during tracheal intubation in patients undergoing elective surgery . The efficacy of esmolol in this regard was carefully evaluated . METHODS Eighty ASA physical status class I or II patients undergoing elective , non-cardiac procedures were included in a r and omized , single-blinded study consisting of 4 groups with each group receiving a design ated drug : group A received normal saline as control , while group B , group C and group D received lidocaine 2 mg/kg , fentanyl 3 micrograms/kg and esmolol 2 mg/kg , respectively . Monitoring included EKG , pulse oximetry , capnometry and arterial pressure . All patients were premedicated with diazepam 0.1 mg/kg 30 min before induction of general anesthesia . Each design ated drug was given upon induction of anesthesia ( time zero ) . Anesthesia was induced with thiopental 5 mg/kg and succinylcholine 1.5 mg/kg , and maintained with N2O , 1 % isoflurane in 50 % O2 and vecuronium . Intubation was carried out 3 min after the design ated drug was given . Heart rate ( HR ) and systolic arterial blood pressure ( SBP ) were obtained every min for 10 min after induction . Either chi-square test or analysis of variances ( ANOVA ) was used for statistical comparison . A p value less than 0.05 was considered statistically significant . RESULTS There was no difference in the demographic data among the four groups . After intubation , the incidence of tachycardia ( HR > 100/min ) was found in 3 of 20 ( 15 % ) patients in esmolol group , significantly lower than 17 of 20 ( 85 % ) patients in the control group , 15 of 20 ( 75 % ) patients in lidocaine group , and 11 of 20 ( 55 % ) patients in fentanyl group , respectively ( p < 0.05 ) . The incidence of hypertension ( SBP > 180 mmHg ) was found in 4 of 20 ( 20 % ) patients in esmolol group , significantly lower than 16 of 20 ( 80 % ) patients in control group and 14 of 20 ( 70 % ) patients in lidocaine group , respectively ( p < 0.05 ) , but not in 8 of 20 ( 40 % ) patients in fentanyl group . Besides , the incidence of hypertension in fentanyl group ( 40 % ) was significantly lower than control group ( 80 % ; p < 0.05 ) , but not in lidocaine group ( 70 % ) . CONCLUSIONS Results of this study showed that only esmolol could reliably offer protection against the increase in both HR and SBP , low dose of fentanyl ( 3 micrograms/kg ) prevented hypertension but not tachycardia , and 2 mg/kg lidocaine had no effect to blunt adverse hemodynamic responses during laryngoscopy and tracheal intubation Background : Laryngomicroscopy causes considerable haemo‐dynamic and ECG changes and therefore requires high doses of anaesthetic agents , which prolong recovery . In this double‐blind r and omized work , we studied the effect of esmolol , a short‐acting beta‐adrenergic receptor‐blocking agent , on haemodyn‐amic and ECG changes during laryngomicroscopy under thio‐pental‐alfentanil‐isoflurane‐suxamethonium anaesthesia The purpose of this study was to compare surgical conditions for functional endoscopic sinus surgery ( FESS ) under general anaesthesia during controlled induced hypotension , using either sodium nitroprusside ( SNP ) or esmolol . Twenty patients , assigned to receive either of the drugs as the primary hypotensive agent , were studied . The same surgeon , blinded to the hypotensive agent used and the haemodynamic variables , performed all the operations . The surgeon used a category scale ( 0–5 ) to assess surgical conditions — a value of 2–3 being ideal . Patients were positioned in 5 ° reverse Trendelenburg position and the mean arterialblood pressure ( MABP ) was reduced in steps of 5 mmHg . The anaesthetist prompted category scale estimations by the surgeon following a change in any of the haemodynamic variables . Average category scale ( ACS ) values were compared between the two groups for four data groups , i.e. , MABP > 65 mmHg ( mild ) , 60–64 mmHg , 55–59 mmHg and 50–54 mmHg . Pre-treatment MABP was 79.8 ± 10.4 mmHg in the SNP group and 76.1 ± 6.8 mmHg in the esmolol group . At mild SNP-induced hypotension , surgical conditions were poor ( ACS = 3.63 ± 0.22 ; mean ± SEM ) , while in the esmolol group , ideal surgical conditions ( ACS = 2.94 ± 0.34 ) were recorded at MABP > 65 mmHg . The combined effects of increased venous drainage due to the reverse Trendelenburg position , hypotension as well as capillary vasoconstriction due to unopposed alpha-adrenergic effect on the mucous membrane vasculature in the esmolol group ( as opposed to vasodilatation in the SNP group ) probably caused the superior surgical conditions . RésuméCette étude vise à comparer pendant la chirurgie endoscopique fonctionnelle des sinus sous anesthésie générale , les conditions chirurgicales obtenues avec l’hypotension délibérée réalisée soit avec du nitroprussiate de soude ( SNP ) , soit avec de l’esmolol . Vingt patients sont assignés à recevoir l’un ou l’autre des agents hypotenseurs . Un seul chirurgien , ignorant l’agent utilisé et les paramètres hémodynamiques , effectue toutes les interventions . Le chirurgien cote les conditions chirurgicales sur une échellle de catégories de 0 à 5 , les valeurs 2 et 3 étant jugées idéales . Les patients sont placés en Trendélenbourg renversé a 5 ° et la pression artérielle moyenne ( PAM ) est réduite par paliers de 5 mmHg . L’anesthésiste dem and e au chirurgien son évaluation sur l’échelle de catégorie à chaque changement de paramètre hémodynamique . Les valeurs moyennes de l’échelle de catégorie ( ECM ) sont comparées entre les deux groupes pour quatre sous-groupes de données , c-à-d , PAM > 65 mmHg ( légère ) , 60–64 mmHg , 55–59 mmHg et 50–54 mmHg . Avant la perfusion , la PAM est 79,8 ± 10,4 mmHg dans le groupe SNP et 76,1 ± 6,8 mmHg dans le groupe esmolol . En l’hypotension légère au SNP , les conditions chirurgicales sont pauvres ( ECM = 3,63 ± 0,22 , moyenne ± SEM ) , alors que dans le groupe esmolol , les conditions chirurgicales idéales ( ECM = 2,94 ± 0,34 ) surviennent avec une PAM > 65 mmHg . Les effets associés du drainage veinewc en position de Trendélenbourg renversé , l’hypotension ainsi que la vasoconstriction capillaire causée par l’action alpha-adrénergique de l’esmolol sur les vaisseaux de la muqueuse dans ce groupe ( contrairement à la vasodilatation dans le groupe SNP ) sont , selon toutes probabilités , les causes des meilleures conditions chirurgicales The circulatory response to a 30-second laryngoscopy followed by orotracheal intubation was recorded in 60 patients of ASA physical status III or TV undergoing a variety of non-cardiac surgical procedures . Patients were r and omly allocated to either the placebo , esmolol ( 500μg·kg−1·min− 1 × 6 minutes , followed by 300 μg · kg− 1 · min− 1 × 9 minutes ) , or fentanyl ( 0.8μg·kg− 1.min− 1 × 10 minutes ) group , and the observer was blinded to the infusion administered . Esmolol blunted the heart rate ( HR ) response , while fentanyl decreased it below the baseline and maintained it there , in spite of laryngoscopy . Similarly , fentanyl decreased the systolic ( SBP ) , mean ( MBP ) and diaslolic blood pressures ( DBP ) significantly below the baseline , while these pressures were either retained at or elevated slightly above control in the esmolol group . In these doses , the HR response to laryngoscopy was more effectively blocked by fentanyl , while esmolol better retained perfusion pressure . There were no complications or ischaemic electrocardiographic changes in any patient . RésuméNous avons mesuré la riponse hemodynamique à une laryngoscopie de 30 secondes suivie d ’ une intubation orotrachéale chez 60 patients de classe ASA III ou IV devant subir diverses interventions chirurgicales autres que cardiaques . Le hasard determinant si la manoeuvre allait être précédée d ’ un placebo , desmolol ( 500μg·kg− 1·min− 1 × 6 minutes , puis 300 μg·kg− 1 · min− 1 × 9 minutes ) , ou de fentanyl ( 0.8 μg·kg− 1·min− 1 × 10 minutes ) et ce , à l’insu d’un observateur neutre . L’esmolol limitait l’accélération dupouls t and is que le fentanyl ralentissait le coeur avant , pendant et apris la laryngoscopie . Avec le fentanyl , on a vu s’abaisser significativement les pressions artérielles systoliques , moyennes et diastoliques alors qu’elles se maintenaient ou s’élevaient légèrement avec l’esmolol . Ainsi , aux doses employées , le fentanyl prévient mieux la réponse chronotrope à la laryngoscopie alors que l’esmolol maintient la pression de perfusion . Nous n’avons noté aucune complication ni aucun signe électrocardiographique d’ischémie pendant cette etude OBJECTIVE To compare the effectiveness of single bolus dose of esmolol or fentanyl in attenuating the haemodynamic responses during laryngoscopy and endotracheal intubation . DESIGN R and omized , placebo controlled , double blind study . PLACE AND DURATION OF STUDY Department of Anaesthesia and Surgical Intensive Care Unit , Civil Hospital , Karachi , from December 1998 to November 1999 . PATIENTS AND METHODS Sixty adult ASA-I and ASA-II patients undergoing elective surgery were included in the study . The patients were r and omly divided into three groups i.e. , A , B and C. Heart rate , systolic , diastolic and mean blood pressures were recorded as 0= baseline and after administration of study drug , laryngoscopy and endotracheal intubation and 10 minutes thereafter . Study agent was injected 30 seconds before the induction of anaesthesia . Group ' A ' ( control ) received 10 ml saline , group ' B ' and group ' C ' received fentanyl 2 mg/kg and esmolol 2 mg/kg respectively diluted to make a total volume of 10 ml in normal saline . RESULTS Readings of heart rate , systolic , diastolic and mean arterial pressures were compared with baseline and among each group . The rise in heart rate was minimal in esmolol group and was statistically significant . Following intubation , blood pressure was increased in all groups but was least in group C. CONCLUSION Bolus injection of fentanyl 2 mg/kg 2 minutes prior to laryngoscopy and intubation failed to protect against elevation of both the heart rate and systolic blood pressure , whereas esmolol at 2 mg/kg provided consistent and reliable protection against the increase of heart rate but not arterial blood pressure BACKGROUND : The use of opioids during ambulatory surgery can delay hospital discharge or cause unexpected hospital admission . Preliminary studies using an intraoperative continuous infusion of esmolol in place of an opioid have inconsistently reported a postoperative opioid-sparing effect . In this study , we compared esmolol versus either intermittent fentanyl or continuous remifentanil on postoperative opioid-sparing , side effects , and time of discharge . METHODS : Ninety patients ( consisting of three groups ) were enrolled in this prospect i ve , r and omized , and observer-blinded study . The control group ( n = 30 ) received intermittent doses of fentanyl , the esmolol group ( n = 30 ) received a continuous infusion of esmolol ( 5–15 & mgr;g · kg−1 · min−1 ) and no supplemental opioids during surgery , and the remifentanil group ( n = 30 ) received a continuous infusion of remifentanil ( 0.1–0.5 & mgr;g · kg−1 · min−1 ) . General anesthesia was st and ardized , and adjuvant medications included acetaminophen , ketorolac , local anesthetics in the skin incisions , dexamethasone , and droperidol . Postoperative analgesia included fentanyl . RESULTS : The amount of fentanyl in the postanesthesia care unit was significantly less in the esmolol group , 91.5 ± 42.7 & mgr;g , compared with the other two groups , remifentanil , 237.8 ± 54.7 & mgr;g , control , 168.1 ± 96.8 & mgr;g ( P < 0.0001 ) . The incidence of nausea was more frequent in the control ( 66.7 % ) and remifentanil ( 67.9 % ) groups compared with the esmolol group ( 30 % ) ( P < 0.01 ) . The esmolol group reached the White-Song score of 12 of 14 faster than the remifentanil group ( P < 0.01 ) , and left the hospital 45–60 min earlier ( P < 0.004 ) . CONCLUSIONS : Intraoperative IV infusion of esmolol contributes to a significant decrease in postoperative administration of fentanyl and ondansetron and facilitates earlier discharge Summary We examined the effect of different combinations of esmolol and nicardipine upon the circulatory response to tracheal intubation . One hundred patients were r and omly allocated into five groups of twenty to receive pretreatments of saline or different combinations of esmolol ( 0.5 or 1.0 mg.kg−1 ) and nicardipine ( 15 or 30 µg.kg−1 ) . Significant tachycardia persisted over a 5‐min period after intubation in all five groups compared with baseline levels ( p < 0.05 ) . Patients receiving esmolol 1.0 mg.kg−1 and nicardipine 30 μg.kg−1 showed no significant change in systolic blood pressure after tracheal intubation compared with baseline and significant lower peak systolic blood pressure than those receiving saline ( p = 0.023 ) The effectiveness of esmolol , an ultra short-acting cardioselective β blocker , in the prevention and treatment of post-intubation haemodynamic perturbations , was investigated . Forty-eight ASA physical status I and II patients undergoing hysterectomy were r and omly assigned to receive a single intravenous bolus of placebo , esmolol 100 mg , or esmolol 200 mg in a double-blind fashion . This was administered over 15 sec , and immediately followed by thiopentone 3–5 mg · kg- 1 , succinylcholine 1.5 mg · kg- 1 , and tracheal intubation 90 sec later . The heart rate following induction of anaesthesia was lower in the esmolol 200 mg group ( P < 0.01 ) ; following intubation , the increase in heart rate in the placebo group was greater than in the esmolol groups ( P < 0.05 ) . The systolic blood pressure post-induction was lower in the esmolol 200 mg group ( P < 0.05 ) ; following intubation , however , no significant differences were seen among groups in systolic , diastolic , or mean blood pressures . Following tracheal intubation , the incidence of ventricular arrythmias was lower in the esmolol groups ( P < 0.05 ) . In summary , esmolol in 100 mg and 200 mg doses was effective in mitigating the haemodynamic response following tracheal intubation . RésuméL’efficacité de l’esmolol , dans la prevention et le traitement des variations hémodynamiques lors de l’intubation a été investiguee . Quarante-huit patientes ASA I et II devant subir une hystérectomie étaient r and omisées afin de recevoir soit un bolus de placebo , soit 100 mg ou 200 mg d’esmolol à double insu . L’administration intraveineuse s’est faite sur 15 secondes immediatement après du thiopentone 3–5 mg · kg- 1 , succinylcholine 1,5 mg · kg- 1 et intubation trachéale 90 sec. plus tard . Lafréquence cardiaque après induction de l’anesthésie ’ etait plus basse dans le groupe esmolol 200 mg ( P < 0,01 ) ; après l’intubation , l’augmentation de lafréquence cardiaque dans le groupe placebo était plus gr and e que celle des groupes esmolol ( P < 0,05 ) . La pression artérielle systolique après l’induction était plus basse dans le groupe esmolol 200 mg ( P < 0,05 ) ; après l’intubation , cependant , il n’y avail aucune différence significative entre le groupe dans la pression artérielle systolique , diastolique ou la pression artérielle moyenne . Après intubation trachéale , l’incidence d’arythmie ventriculaire était plus basse dans les groupes esmolol ( P < 0,05 ) . En résumé , des doses desmolol de 100 mg et 200 mg étaient efficaces pour atténuer la réponse hémodynamique après intubation endotrachéale & NA ; We evaluated the clinical effectiveness of esmolol , an ultra‐short‐acting , cardioselective beta‐adrenergic receptor blocker , in controlling sinus tachycardia and increased systolic blood pressure occurring perioperatively in 30 ASA physical status II or III patients having elective , non‐cardiac surgery . Esmolol 80 mg I.V. bolus ( N = 15 ) or placebo ( N = 15 ) followed by 12 mg/min or placebo were infused in 30 isoflurane‐anesthetized patients using a r and omized double‐blind study design . The bolus plus infusions were given when surgical stimuli caused heart rate to exceed 95 bpm or systolic blood pressure 140 mm Hg . Esmolol significantly decreased heart rate ( 107 ± 4 , mean ± SEM to 99 ± 4 , mean ± SEM bpm ) within 45 sec after starting the bolus plus infusion ; the placebo had no effect , heart rate being 105 ± 4 before and 106 ± 3 bpm after the bolus plus infusion . Patients given esmolol continued to have heart rates significantly lower than patients given placebo injections throughout a six min infusion ( Ex . , at 5 min 81 ± 3 vs 91 ± 4 bpm ) . The study demonstrated no apparent effect of esmolol on blood pressure but that esmolol is effective in treating perioperative sinus tachycardia In this r and omized , double-blind , controlled study , we tested the hypothesis that the short-acting & bgr;1-adrenoceptor antagonists esmolol and l and iolol suppress hemodynamic changes and bispectral index ( BIS ) increases , both of which are induced by tracheal intubation under general anesthesia with sevoflurane alone . Forty-five patients were r and omly assigned to the control , esmolol , and l and iolol groups ( n = 15 each ) . Anesthesia was induced with sevoflurane in oxygen , with an end-tidal concentration maintained at 1 minimum alveolar anesthetic concentration ( MAC ) . Infusion of saline ( control group ) , esmolol ( bolus of 1 mg/kg and then 0.25 mg · kg−1 · min−1 ; esmolol group ) , or l and iolol ( bolus of 0.125 mg/kg and then 0.04 mg · kg−1 · min−1 ; l and iolol group ) was started 5 min after the induction of anesthesia and was continued throughout the study . Tracheal intubation was performed 12 min after anesthesia induction . There were no differences in overall changes of mean arterial blood pressure among the three groups , whereas , at 1–5 min after tracheal intubation , heart rate increased in all groups but was significantly slower in the esmolol and l and iolol groups than in the control group ( P < 0.05 ) . BIS was between 96 and 98 for all patients at baseline and decreased during the induction of anesthesia . There were no differences in BIS among the three groups before laryngoscopy ( 39 ± 5 , 39 ± 5 , and 38 ± 4 in the control , esmolol , and l and iolol groups , respectively ) . BIS increased significantly in the control group ( 54 ± 10 ; P < 0.05 ) 1 min after intubation , whereas it remained unchanged in the esmolol and l and iolol groups ( 45 ± 10 and 41 ± 6 , respectively ) . In conclusion , the increase in both heart rate and BIS after tracheal intubation under 1 MAC sevoflurane anesthesia was suppressed by the concomitant administration of either esmolol or l and iolol The administration of esmolol decreases the propofol blood concentration , preventing movement after skin incision during propofol/morphine/nitrous oxide anesthesia . However , interaction with esmolol has not been tested when propofol is infused alone . Accordingly , we tested the hypothesis that esmolol decreases the propofol blood concentration , preventing response to comm and ( CP50-awake ) when propofol is infused alone in healthy patients presenting for minor surgery . With approval and consent , we studied 30 healthy patients , who were r and omized to esmolol bolus ( 1 mg/kg ) and then infusion ( 250 & mgr;g · kg−1 · min−1 ) or placebo . Five minutes later , a target-controlled infusion of propofol was commenced . Ten minutes later , responsiveness was assessed by a blinded observer . Oxygen saturation , heart rate , and noninvasive arterial blood pressure were recorded every 2 min . Arterial blood sample s were taken at 5 and 10 min of propofol infusion for propofol assay . Results were analyzed with a generalized linear regression model : P < 0.05 was considered statistically significant . The probability of response to comm and decreased with increasing propofol blood concentration ( CP50-awake = 3.42 & mgr;g/mL ) . Esmolol did not alter the relative risk of response to comm and . We conclude that the previously observed effect of esmolol on propofol CP50 was not caused by an interaction between these two drugs This study was performed to investigate the efficacy of esmolol , an agent used in hypotensive anesthesia for middle ear surgery . We compared 20 ASA I-II patients to 20 controls in whom we administered routine anesthesia . All patients were premedicated with intramuscular 0.05 mg/kg atropine , 1 mg/kg pethidine and 25 mg promethazine . Anesthesia was induced with 0.004 mg/kg fentanyl and 5 mg/kg thiopental sodium . Succinylcholine 1.5 mg/kg was administered to facilitate intubation . Isoflurane , nitrous oxide , oxygen , 0.08 mg/kg vecuronium bromide and controlled ventilation were used for anesthetic maintenance . Before the controlled hypotensive period , nitrous oxide was discontinued and an esmolol infusion started . We registered hemodynamic values ( via noninvasive and invasive radial artery cannulation ) , central venous pressure , electrocardiography , body temperature , end-tidal carbon dioxide levels , periferal oxygen saturation , and arterial blood gas analysis . Mean infusion rate of esmolol was 330 + /- 10 micrograms/kg/min . We found significant decreases in systolic blood pressure ( 28.7 % ) , mean blood pressure ( 26.5 % ) and diastolic blood pressure ( 33.4 % ) . The operative field was virtually bloodless . Hemodynamic values recovered to normal or to within -12.45 % of normal at the end of intravenous esmolol infusion . During the postoperative period , no side effects were observed . In conclusion , esmolol is an appropriate hypotensive agent for patients undergoing middle ear surgery under hypotensive anesthesia because it yields no side effects , it is easy to control administration and it provides the desired degree of hypotension without complications INTRODUCTION Emergence from general anaesthesia and extubation are often accompanied by significant surges in heart rate and blood pressure . To document these changes and the efficacy of low-dose beta-blocker infusions in ameliorating these rises , we undertook a descriptive dose-ranging study comparing the use of esmolol to placebo in patients emerging from neuro-anaesthesia . MATERIAL S AND METHODS Thirty-six patients undergoing intracranial surgery were r and omised to receive saline , esmolol 100 micrograms/kg/min or 200 micrograms/kg/min infusions . The number of patients developing severe hypertension or tachycardia in each group was compared using Fisher 's exact test . RESULTS Systolic blood pressure ( SBP ) and heart rate ( HR ) increased in all 3 groups during emergence and peaked at extubation . The proportion of patients with severe tachycardia or hypertension was reduced from 92 % in the placebo group to 40 % ( P = 0.02 ) and 8 % ( P = 0.001 ) in the low and intermediate dose esmolol groups , respectively . Results were better in the intermediate dose group but the difference was not statistically significant . Two patients from the esmolol infusion groups required supplemental medication for bradycardia . CONCLUSION Severe hypertension or tachycardia occurs in 92 % of patients during extubation following neuro-anaesthesia and warrants the consideration of routine prophylaxis . Prophylactic esmolol infusion for the control of haemodynamic disturbances during extubation is feasible and safe . A modest level of obtundation is evident at 100 micrograms/kg/min but a rate of 200 micrograms/kg/min may prove to be more effective A multicentre trial was design ed to determine the dose-response and side-effects of esmolol when administered as a single iv bolus prior to induction of anaesthesia for controlling the haemodynamic response to tracheal intubation . Five hundred and forty-eight patients from 12 university-affiliated centres across Canada were r and omized prospect ively to receive either placebo ( PLAC ) or esmolol ( E ) in a dose of 100 mg ( E100 ) or 200 mg ( E200 ) . Study medication was given immediately before induction of anaesthesia with thiopentone 3–5 mg·kg−1 and succinylcholine 1.5 mg·kg−1 . Low-dose narcotic ( fentanyl 2–3 μg·kg−1 or sufentanil 0.3 μg·kg−1 ) or moderate dose narcotic ( fentanyl 4–7 μg·kg−1 ) was also given at five of the participating centres , whereas patients in the remaining seven centres received no narcotic . Patients who received PLAC and no narcotic had greater HR and SBP values after tracheal intubation than patients who received either E100 or E200 ( P<0.005 ) . The proportion of patients whose maximum HR exceeded 110 min−1 was also greater in the PLAC group ( 22/180 ) than in either the E100 ( 10/187 ) or E200 ( 9/181 ) groups ( P<0.05 ) , but was not different when comparing E100 with E200 . Esmolol was less effective in controlling blood pressure , but , in combination with low-dose narcotic , esmolol suppressed the SBP response to tracheal intubation . In the presence of moderatedose narcotic , however , a decrease in SBP occurred in all three groups following induction of anaesthesia ( P<0.003 ) , with the largest decrease ( 17±4 % ) occurring in patients who had received E200 . The overall incidence of hypotension ( SBP<90 mmHg ) was greater in the E200 group ( 33 % ) than either the E100 ( 25 % ) or PLAC ( 16 % ) groups ( P<0.05 ) . Other side-effects , such as bradycardia , bronchospasm or pain on injection , occurred no more frequently in either esmolol group than with placebo . It is concluded that a 100 mg bolus of esmolol is safe and effective for controlling the haemodynamic response to tracheal intubation . This dose of esmolol combined with a low dose of narcotic ( fentanyl 2–3 μg·kg−1 or equivalent ) results in effective control of both heart rate and blood pressure , while avoiding important side-effects . RésuméUne étude multicentrique fut conçue afin de déterminer la dose-réponse et les effets secondaires de l’esmolol lorsqu’ad-ministré en un bolus intraveineux unique avant l’induction de l’anesthésie pour contrôler la réponse hémodynamique à l’intubation trachéale . Cinq cent quarante-huit patients de 12 centres affiliés à l’université à travers le Canada furent r and omisés d’une façon prospect i ve afin de recevoir soit du placebo ( PLAC ) ou de l’esmolol ( E ) à des doses de 100 mg ( E100 ) ou 200 ( E200 ) . Le médicament à l’étude fut administré immédiatement avant l’induction de l’anesthésie avec du thiopentone 3–5 mg·kg−1 et du succinylcholine 1,5 mg·kg−1 . Des faibles doses de narcotiques ( fentanyl 2–3 μg·kg−1 ou du sufentanil 0,3 μg·kg−1 ) ou une dose modérée de narcotique ( fentanyl 4–7 μg·kg−1 ) a été administrée à cinq des centres participants , alors que les patients dans les sept autres centres n’ont reçu aucun narcotique . Les patients avant reçu du PLAC et aucun narcotique ont présenté des fréquences cardiaques et une pression systolique artérielle lors de l’intubation plus élevées que les patients avant reçu soit E100 ou E200 ( P<0,005 ) . La proportion des patients chez qui la fréquence cardiaque maximale exéda 110 min−1 fut encore supérieure dans le groupe PLAC ( 22/180 ) que ceux des groupes E100 ( 10/187 ) ou E200 ( 9/181 ) ( P<0,05 ) , mais ne fut pas différente lorsqu’on compare E100 avec E200 . L’esmolol était moins efficace pour contrôler la pression artérielle mais en combinaison avec des narcotiques à faible dose , l’esmolol a aboli la réponse hypertensive lors de l’intubation trachéale . En présence de doses modérées de narcotiques , cependant , une diminution de la pression systolique est survenue chez tous les trois groupes après induction de l’anesthésie ( P<0,001 ) , et la plus gr and e diminution ( 17±4 % ) est survenue chez les patients ayant reçu E200 mg d’esmolol . L’incidence générale d’hypotension ( SBP<90 mmHg ) fut plus gr and e chez le groupe E200 ( 33 % ) que ceux du groupe E100 ( 25 % ) ou PLAC ( 16 % ) ( P<0,05 ) . Les autres effets secondaires , tels que bradycardie , bronchospasme ou douleur au site d’injection , sont survenus à égale fréquence dans le groupe esmolol et groupe placebo . On conclut que 100 mg d’esmolol en bolus est sécuritaire et efficace pour contrôler la réponse hémodynamique à l’intubation trachéale . Cette dose d’esmolol combinée avec de faibles doses de narcotiques ( fentanyl 2–3 μg·kg−1 ou équivalent ) a amené un contrôle efficace de la fréquence cardiaque et de la pression artérielle , tout en évitant des effets secondaires importants Background : Drug‐induced controlled hypotension ( CH ) combined with acute normovolemic hemodilution ( ANH ) is being widely used for blood conservation in surgical patients . The purpose of this study was to investigate the efficacy and safety of esmolol‐induced CH combined with ANH ( hematocrit down to 28 % ) This is an open r and omized study comparing the efficacy and safety of iv esmolol and labetalol in the treatment of perioperative hypertension in ambulatory surgery . Twenty-two elderly patients undergoing cataract surgery under local anaesthesia were studied . The main inclusion criteria were development of systolic blood pressure > 200 mmHg or diastolic > 100 mmHg . Esmolol was given as a bolus 500 μg · kg−1 iv followed by a maintenance infusion ( 150–300 μg · kg−1 · min−1 ) . Labetalol was given as a bolus of 5 mg iv followed by 5 mg increments as needed up to a maximum of 1 mg · kg−1 . Esmolol and labetalol both produced reductions in systolic and diastolic blood pressure ( P < 0.05 ) within ten minutes of administration which lasted for at least two hours . Reduction of blood pressure by esmolol was accompanied by a decrease in HR ( P < 0.05 ) . Two patients developed extreme bradycardia ( HR < 50 beats · min−1 ) and esmolol had to be discontinued . Labetalol , in contrast , induced only a moderate decrease in HR . None of the patients treated with labetalol experienced any prolonged side effects such as orthostatic hypotension . In conclusion , esmolol may produce considerable bradycardia in elderly patients when hypertension is not accompanied by tachycardia . Labetalol was easier to administer in the ambulatory setting and one-tenth the cost of esmolol . RésuméIl s’agit d’une étude r and omisée comparant l’efficacité et la sécurité du traitement avec esmolol et labétalol iv de l’hypertension peropératoire lors de la chirurgie ambulatoire . Nous avons étudié 22 patients âgés subissant une chirurgie pour cataracte sous anesthésie locale . Les critères d ’ inclusion principaux étaient l’apparition d’une tension artérielle systolique plus gr and e que 200 mmHg ou diastolique plus gr and e que 100 mmHg . Le traitement à l’esmolol comprenait un bolus de 500 μg · kg−1 iv suivi d’une perfusion de 150 a 300 μg · kg−1 · min−1 . Le traitement au labétalol comprenait un bolus de 5 mg iv suivi d’une dose de 5 mg selon les besoins jusqu’à un maximum de 1 mg · kg−1 . L’esmolol et le labétalol ont diminué les tensions artérielle systoliques et diastoliques ( P < 0,05 ) en dedans de dix minutes après leur administration , effet qui a persisté pour au moins deux heures . La diminution de la tension artérielle par l’esmolol était accompagnée par une diminution de la fréquence cardiaque ( P < 0,05 ) . Deux patients ont présenté une bradycardie sévère ( fréquence cardiaque < 50 battements · min−1 ) et l’esmolol a du être cessé . Le labétalol ne causait qu’une diminution modérée de la fréquence cardiaque . Aucun des patients traités avec labétalol n’a montré d’effets secondaires prolongés importants tel que l’hypotension orthostatique . En conclusion , l’esmolol peut causer une bradycardie importante chez les patients âgés lorsque Vhypertension n’est pas accompagnée de tachycardie . Le labétalol est plus facile à administrer dans le context e ambulatoire , et ce à un coût dix fois moins important que l’esmolol We sought to evaluate the effectiveness of esmolol vs placebo in 40 patients emerging from general anesthesia for neurosurgery . Efficacy was defined as a decrease in systolic blood pressure to within 20 % above average ward pressure . The need for additional antihypertensive agents to control blood pressure was also used to define efficacy . During the infusion period 20 of 21 ( 95 % ) of the esmolol‐treated patients and two of 19 ( 11 % ) of the patients receiving placebo had return of systolic blood pressure to within 20 % of average ward pressure ( p < 0.001 ) . One out of 21 ( 5 % ) esmolol‐treated patients and 14 of 19 ( 74 % ) of the placebo group required intervention with additional antihypertensive medications ( p < 0.001 ) . Esmolol was found to be effective in controlling hypertension that develops on emergence from general anesthesia in patients undergoing neurosurgery Laryngoscopy and tracheal intubation ( LTI ) often provoke an undesirable increase in blood pressure ( BP ) and /or heart rate ( HR ) . We tested the premise that nicardipine ( NIC ) and esmolol ( ESM ) in combination ( COMB ) would oppose both . Adult surgical patients received pretreatment ( r and omized ) with IV bolus NIC 30 & mgr;g/kg ( n = 31 ) , ESM 1.0 mg/kg ( n = 34 ) , or COMB ( one-half dose each , n = 32 ) . Peak BP and HR after LTI were compared with controls ( CONT;n = 35 ) with no pretreatment . Anesthetic induction was st and ardized : IV thiopental ( 5–7 mg/kg ) , fentanyl ( 1–2 & mgr;g/kg ) , and succinylcholine ( 1.5 mg/kg ) . Systolic ( S ) , diastolic ( D ) , and mean ( M ) BP and HR awake before pretreatment ( baseline ) were similar in all test groups . No patient was treated for hypotension , bradycardia , or tachycardia after pretreatment or anesthetic induction . Peak HR after LTI was increased versus baseline in CONT and all test groups , but did not differ from CONT among the test groups . Peak SBP and DBP increased versus baseline in CONT , and with ESM and NIC , but not COMB . Peak SBP , DBP , and MBP were increased with ESM versus COMB , and peak DBP with ESM versus NIC . Compared with no pretreatment before the IV induction of general anesthesia , the peak increase in BP after LTI is best blunted by the combination of nicardipine and ESM , compared with either drug alone . No single drug or combination in the doses tested opposed increased HR . Implication s Compared with no pretreatment before the IV induction of general anesthesia , the peak increase in blood pressure after laryngoscopy and tracheal intubation is best blunted by the combination of nicardipine and esmolol , compared with either drug alone . No single drug or combination in the doses tested opposed increased heart rate The cardiovascular responses to double lumen endobronchial intubation and the effect of esmolol were examined in two groups of 10 ASA 2 & 3 patients undergoing pulmonary surgery in a double blind , placebo‐controlled study . Endobronchial intubation was associated with a significant increase in arterial pressure and heart rate ( p = 0.004 ) , and a significant increase in plasma noradrenaline concentrations ( p < 0.01 ) in the control group . The haemodynamic changes were smaller ( p < 0.001 ) in the patients who received esmolol compared with the changes in the the control group . The increase in plasma noradrenaline concentrations was significantly greater ( p < 0.05 ) in the esmolol group . The pressor response to endobronchial intubation in this study was of a similar magnitude to that known to occur in response to tracheal intubation Background Although beta blockers have been used primarily to decrease unwanted perioperative hemodynamic responses , the sedative properties of these compounds might decrease anesthetic requirements . This study was design ed to determine whether esmolol , a short‐acting beta1 ‐receptor antagonist , could reduce the propofol concentration required to prevent movement at skin incision . Methods Sixty consenting patients were premedicated with morphine , and then propofol was delivered by computer‐assisted continuous infusion along with 60 % nitrous oxide . Patients were r and omly divided into three groups , propofol alone , propofol plus low‐dose esmolol ( bolus of 0.5 mg/kg , then 50 micro gram [ center dot ] kg‐1 min‐1 ) , and propofol plus high‐dose esmolol ( bolus of 1 mg/kg , then 250 micro gram [ center dot ] kg ( ‐1 ) min‐1 ) . Two venous blood sample s were drawn at equilibrium . The serum propofol concentration that prevented movement to incision in 50 % of patients ( Cp50 ) was calculated by logistic regression . Results The propofol Cp50 with nitrous oxide was 3.85 micro gram/ml . High‐dose esmolol infusion was associated with a significant reduction in the Cp50 to 2.80 micro gram/ml ( P < 0.04 ) . Propofol computer‐assisted continuous infusion produced stable serum concentrations with a slight positive bias . Esmolol did not alter the serum propofol concentration . No intergroup differences in heart rate or blood pressure response to intubation or incision were found . Conclusions Esmolol significantly decreased the anesthetic requirement for skin incision . The components and mechanism of this interaction remain unclear . A simple pharmacokinetic interaction between esmolol and propofol does not explain the Cp50 reduction . These results demonstrate an anesthetic‐sparing effect of a beta‐adrenergic antagonist in humans under clinical ly relevant conditions This prospect i ve study was design ed to compare the effectiveness of esmolol ( either 100 mg or 200 mg ) with a placebo in blunting the haemodynamic response to laryngoscopy and intubation . Seventy-five patients of ASA I or II scheduled for routine-surgery were selected and entered into a placebo-controlled study . Patients were r and omly allocated to receive placebo , 100 mg or 200 mg of esmolol IV as part of an anaesthetic induction technique . There were no significant differences in the demographic distribution of the patients in the study . There was no statistical difference in the baseline heart rate ( HR ) and systolic blood pressure ( SBP ) between the three groups . One minute after the administration of the drug ( prior to intubation ) the differences in HR between the placebo group and both the 100 mg and 200 mg groups were significant ( p < 0.05 ) , and also at 1 min and 2 min following intubation for the 200 mg group ( p < 0.05 ) . In the 200 mg group there was a significant decrease , compared with placebo , in SBP at 1 min ( p < 0.05 ) and at 2 min ( p < 0.05 ) after intubation . In this study , adequate haemodynamic control following was obtained with the administration of 200 mg of esmolol Laryngoscopy and intubation cause an adrenergic response manifested by tachycardia and hypertension . Various pharmacological agents , including fentanyl , have been administered prior to induction in an attempt to attenuate the adrenergic response but they all have limitations . Esmolol , an ultrashort-acting cardioselective beta blocker , has been administered by infusion to successfully protect surgical patients from the stresses of intubation . The objective of our study was to determine if esmolol would be equally effective when administered in a bolus with and without fentanyl . Forty-four ASA I and II females undergoing elective surgery were r and omly divided into four groups and received the following agents prior to intubation : Group 1-esmolol 1 mg/kg and fentanyl 2 micrograms/kg , Group 2-placebo ( normal saline ) , Group 3-esmolol 1 mg/kg and Group 4-fentanyl 3.5 micrograms/kg . Groups 1 and 4 , which received fentanyl , demonstrated significantly less elevation in blood pressure . Esmolol appeared to attenuate increases in heart rate . Esmolol has a tissue distribution time of 2 minutes and an elimination half-life of 9 minutes . The window of its availability to the tissues is narrow , and timing of bolus administration is more critical than in administration by infusion . Doses in excess of 1 mg/kg appear to be necessary for effective control of heart rate . However , when used with fentanyl , esmolol provides effective protection against the adrenergic response to laryngoscopy and intubation Background Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia . They are metabolized by cytochrome P450 3A ( CYP3A ) enzymes . These isozymes are inhibited by concurrent medications , including the calcium channel antagonist diltiazem , which may have an effect on recovery from anesthesia . Methods Thirty patients having coronary artery bypass grafting were r and omly assigned to receive either diltiazem ( 60 mg orally 2 h before induction of anesthesia and an infusion of 0.1 mg [ centered dot ] kg sup -1 [ centered dot ] h sup -1 started at induction and continued for 23 h ) or placebo in a double-blind study . Anesthesia was induced with 0.1 mg/kg midazolam , 50 micro gram/kg alfentanil , and 20 to 80 mg propofol and maintained with infusions of 1 micro gram [ centered dot ] kg sup -1 [ centered dot ] min sup -1 of both midazolam and alfentanil supplemented with isoflurane . Plasma midazolam and alfentanil concentrations and areas under the plasma concentration-time curves were determined . The terminal half-life and the time for the drug plasma level to decrease 50 % after cessation of the infusion ( t50 ) were calculated for midazolam and alfentanil . Separation from mechanical ventilation and tracheal extubation were performed according to the study protocol . Results Diltiazem increased the mean concentration-time curves ( from end of anesthesia until 23 h ) of midazolam by 24 % ( P < 0.05 ) and that of alfentanil by 40 % ( P < 0.05 ) . The mean half-life of midazolam was 43 % ( P < 0.05 ) and that of alfentanil was 50 % ( P < 0.05 ) longer in patients receiving diltiazem . The mean t50 of alfentanil was 40 % longer ( P < 0.05 ) in patients receiving diltiazem , but the change in the mean t50 of midazolam ( 25 % ) was not statistically significant . In patients receiving diltiazem , tracheal extubation was performed on average 2.5 h later ( P = 0.054 ) than in those receiving placebo . Conclusions Diltiazem slows elimination of midazolam and alfentanil and may delay tracheal extubation after large doses of these anesthetic adjuncts . CYP3A-mediated drug interactions should be considered as confounders when recovery from anesthesia with midazolam and alfentanil infusions is assessed STUDY OBJECTIVE To compare the safety and efficacy of lidocaine , esmolol , and nitroglycerin in modifying the hemodynamic response to laryngoscopy and intubation . DESIGN R and omized , placebo-controlled , double-blind study . SETTING University-affiliated VA medical center . PATIENTS 40 ASA physical status I and II patients undergoing electric surgery with general endotracheal anesthesia . INTERVENTIONS Anesthesia was induced with thiopental sodium 5 mg/kg , and intubation was facilitated with vecuronium 0.15 mg/kg . Isoflurane ( 0.5 % to 1 % ) and 50 % nitrous oxide in oxygen were used for maintenance of anesthesia . In addition , patients received one of the following four study drugs intravenously ( i.v . ) prior to laryngoscopy : Group 1 ( control ) = saline 5 ml ; Group 2 = lidocaine 1.5 mg/kg ; Group 3 = esmolol 1.4 mg/kg ; Group 4 = nitroglycerin 2 micrograms/kg . MEASUREMENTS AND MAIN RESULTS Mean arterial pressure ( MAP ) and heart rate ( HR ) were recorded every minute for 20 minutes following induction of anesthesia . Following laryngoscopy and intubation , MAP increased significantly in all four treatment groups ( control 49 % + /- 19 % , lidocaine 55 % + /- 26 % , esmolol 25 % + /- 11 % , nitroglycerin 45 % + /- 21 % ) compared with preinduction baseline values . In the esmolol-pretreated patients , the increase in HR was significantly lower ( 20 % + /- 3 % ) compared with the nitroglycerin ( 37 % + /- 8 % ) , lidocaine ( 52 % + /- 8 % ) , and control ( 29 % + /- 4 % ) groups . CONCLUSIONS Lidocaine 1.5 mg/kg i.v . and nitroglycerin 2 micrograms/kg i.v . were ineffective in controlling the acute hemodynamic response following laryngoscopy and intubation . Esmolol 1.4 mg/kg i.v . was significantly more effective than either lidocaine or nitroglycerin in controlling the HR response to laryngoscopy and intubation ( p < 0.05 ) . Esmolol also was significantly more effective than lidocaine in minimizing the increase in MAP ( 25 % vs. 55 % ) Many research ers have studied esmolol and its effects on heart rate and blood pressure . All studied relatively large doses of esmolol . Therefore , the purpose of the present study was to determine whether small doses of esmolol would blunt the transient increases in blood pressure and heart rate caused by laryngoscopy . This double-blind , prospect i ve , r and omized study included 61 subjects . The subjects were r and omized to 1 of 3 groups : group 1 received esmolol , 0.2 mg/kg ; group 2 received esmolol , 0.4 mg/kg ; and group 3 received saline placebo . Groups 1 and 2 had smaller increases in heart rate than group 3 . We also found that the 0.4 mg/kg dose significantly blunted the increase in mean arterial pressure seen in group 3 . This study shows that small doses of esmolol may block the increases in heart rate and blood pressure result ing from laryngoscopy and intubation The efficacy of a single bolus dose of esmolol in the prevention of intubation-induced tachycardia and hypertension was studied in a double-blind manner . Thirty patients from the Ambulatory Surgery Unit at Rush-Presbyterian-St . Luke 's Medical Center were prospect ively r and omized to receive a placebo , 100 mg of esmolol , or 200 mg of esmolol immediately prior to induction ( 2.5 to 3.0 minutes before intubation ) . The groups were similar in demographic characteristics and with regard to preoperative blood pressure ( BP ) and heart rate ( HR ) . Anesthetic management was st and ardized for all patients . Esmolol 100 mg ( 1.4 + /- 0.3 mg/kg ) and 200 mg ( 2.6 + /- 0.7 mg/kg ) significantly ( p less than 0.05 ) blunted the maximum increases in HR and BP following intubation . The average maximum HR increase in the placebo group was 40 % as opposed to 16 % in the esmolol 100 mg group and 14 % in the esmolol 200 mg group . Both esmolol groups blunted the tachycardic response over a 4-minute postintubation time period . The average maximum BP increase was 47 % in the placebo group versus 22 % and 19 % in the esmolol 100 mg and esmolol 200 mg groups , respectively . There were no significant differences between the two esmolol groups . This study demonstrates the efficacy of a single bolus dose of esmolol in blunting the tachycardic and hypertensive responses to laryngoscopy and intubation in an ambulatory surgery setting 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 Eighty patients , ASA physical status II-IV , scheduled for noncardiac surgery , were r and omly assigned in a double‐blind , placebo‐controlled manner to receive a preintubation dose of either placebo , 200 mg lidocaine , 200 pg fentanyl , or 150 mg esmolol . Induction of anesthesia was accomplished with 4–6 mg/kg thiopental IV followed immediately by the study drug ; 1–1.5 mg/kg succinylcholine was given at minute I. Laryngoscopy and intubation were performed at minute 2 with anesthesia thereafter maintained with 1 MAC ( ±10 % ) isoflurane in 60 % nitrous oxide in oxygen at a 5 L/min flow for 10 min . Heart rate was recorded every 15 s and blood pressure every minute from induction until 10 min after intubation . Maximum percent increases in heart rate ( mean ± SE ) during and after intubation were similar in the placebo ( 44 % ± 6 % ) , lidocaine ( 51 % ± 10 % ) , and fentanyl ( 37 % ± 5 % ) groups , but lower in the esmolol ( 18 % ± 5 % ) group ( P<0.05 ) . Maximum systolic blood pressure percent increases were lower in the lidocaine ( 20 % ± 6 % ) , fentanyl ( 12 % ± 3 % ) , and esmolol ( 19 % ± 4 % ) groups than in the placebo ( 36 % ± 5 % ) group ( P<0.05 ) , but not different from each other ( P>0.05 ) . Only esmolol provided consistent and reliable protection against increases in both heart rate and systolic blood pressure accompanying laryngoscopy and intubation A double‐blind , r and omised study was conducted to examine the efficacy of a single bolus dose of esmolol in treating surgically‐induced tachycardia . Anaesthetic technique was identical in all patients , and consisted of premedication with midazolam and glycopyrronium , induction with thiopentone followed by suxamethonium , tracheal intubation , and maintenance with isoflurane 0.6 % ( end‐tidal ) and 60 % nitrous oxide in oxygen . Forty‐eight patients developed a heart rate of greater than 95 beats/minute or 20 % more than pre‐induction values at an average time of 34 minutes after tracheal intubation and received placebo ( 15 patients ) , esmolol 50 mg ( 16 patients ) , or esmolol 100 mg ( 17 patients ) . Controlled intervention was instituted if heart rate or blood pressure was not adequate . Both 50 and 100 mg of esmolol result ed in lower heart rates compared to placebo ( p < 0.05 ) , with no difference between the two esmolol groups ( p > 0.05 ) . Patients who received placebo had more episodes of medical intervention than those given esmolol ( p < 0.05 ) . No adverse effects occurred in any patient We compared the effect of alfentanil 10 µg.kg−1 and esmolol 1.5 mg.kg−1 on the cardiovascular responses to laryngoscopy and double‐lumen endobronchial intubation in two groups of 20 ASA 2–3 patients undergoing pulmonary surgery , in a r and omised double‐blind study . Arterial pressure and heart rate decreased after induction of anaesthesia and increased after intubation in both groups ( p < 0.05 ) but remained at or below baseline values , and changes were comparable in both groups . Plasma catecholamine concentrations decreased after induction of anaesthesia in both groups ( p < 0.05 ) . Epinephrine concentrations increased in the esmolol group after intubation ( p < 0.05 ) but remained below baseline in the alfentanil group ( p < 0.05 ) . Norepinephrine concentrations increased significantly in both groups after intubation but were higher in the esmolol group ( p < 0.05 ) . Although both esmolol 1.5 mg.kg−1 and alfentanil 10 µg.kg−1 similarly attenuated the arterial pressure and heart rate response to endobronchial intubation , plasma catecholamine concentrations increased in the esmolol group to values greater than previously reported after tracheal intubation Objectives : Cigarette smokers constitute a group of patients with an increased hemodynamic response to tracheal intubation . We studied the dose-response and side effects of bolus administration of esmolol hydrochloride in cigarette smokers undergoing elective microlaryngeal surgery , when esmolol was used for reducing the intense hemodynamic response to laryngoscopy and tracheal intubation . Methods : We r and omly allocated 165 patients ( American Society of Anesthesiologists physical status classes I to III ) to receive placebo ( Eplac ) or esmolol 1 mg/kg ( E1 ) or 2 mg/kg ( E2 ) . The esmolol was given 2 minutes before laryngoscopy and tracheal intubation . The same anesthetic technique was used in all patients . Cardiovascular parameters were recorded every minute for the first 5 minutes and thereafter every 3 minutes . Bronchospasm , other side effects , and rescue esmolol treatment were noted during anesthesia . Results : In group Eplac , significant increases ( p < .05 ) in arterial blood pressure and heart rate were observed in the first 3 minutes after tracheal intubation . In group E1 , significant increases ( p < .05 ) in diastolic blood pressure were observed in the first 2 minutes after intubation . In group E2 , no significant fluctuations were recorded in cardiovascular parameters after intubation . During surgery , 17 % of the patients in group Eplac showed an increase in blood pressure and tachycardia . Conclusions : We conclude that esmolol administration of 2 mg/kg during induction of anesthesia in smokers provides hemodynamic stability after laryngoscopy and tracheal intubation with no severe side effects There is controversy regarding the optimal technique for maintaining hemodynamic stability during anesthesia . We design ed this prospect i ve , r and omized , double-blinded study to test the hypothesis that the technique used for maintaining hemodynamic stability during general anesthesia can influence recovery after ambulatory surgery . Forty-five healthy consenting women undergoing gynecologic laparoscopy procedures were r and omly assigned to 1 of 3 treatment groups : Group 1 ( control , n = 15 ) received normal saline 5 mL and 1 mL , followed by a saline infusion at a rate of 0.005 mL · kg−1 · min−1 ; Group 2 ( n = 15 ) received esmolol 50 mg and saline 1 mL , followed by an esmolol infusion 5 & mgr;g · kg−1 · min−1 ; and Group 3 ( n = 15 ) received esmolol 50 mg and nicardipine 1 mg , followed by an esmolol infusion 5 & mgr;g · kg−1 · min−1 . The study drugs were administered after the induction of anesthesia with fentanyl 1.5 & mgr;g/kg , and propofol 2 mg/kg IV . Tracheal intubation was facilitated with vecuronium 0.12 mg/kg IV . Anesthesia was initially maintained with desflurane 2 % end-tidal and N2O 67 % in oxygen in all 3 groups . During surgery , the mean arterial blood pressure ( MAP ) was maintained within ±15 % of the baseline value by varying the study drug infusion rate and the inspired concentration of desflurane . In addition to MAP and heart rate values , electroencephalogram bispectral index values were recorded throughout the perioperative period . Recovery times and postoperative side effects were assessed . Compared with the control group , adjunctive use of esmolol and nicardipine attenuated the increase in heart rate ( in Group 2 ) and MAP ( in Group 3 ) after tracheal intubation . Furthermore , the use of an esmolol infusion as an adjunct to desflurane to control the acute autonomic responses during the maintenance period significantly decreased emergence times ( 4 ± 2 versus 7 ± 4 min ) , decreased the need for postoperative opioid analgesics ( 43 % versus 80 % ) , and reduced the time to discharge ( 209 ± 89 versus 269 ± 100 min ) . We conclude that the adjunctive use of esmolol alone or in combination with nicardipine during the induction of anesthesia reduced the hemodynamic response to tracheal intubation . Furthermore , use of an esmolol infusion as an adjuvant to desflurane-N2O anesthesia for controlling the acute hemodynamic responses during the maintenance period improved the recovery profile after outpatient laparoscopic surgery Perioperative myocardial ischemia ( MI ) is associated with postoperative cardiac morbidity . Postoperative sympatholysis may reduce the incidence of MI . This study evaluated such a reduction postoperatively with the administration of prophylactic & bgr;-blockers in patients undergoing elective total knee arthroplasty with epidural anesthesia and postoperative epidural analgesia . One hundred seven patients were preoperatively r and omized into two groups , control and & bgr;-blockers , who received postoperative esmolol infusions on the day of surgery and metoprolol for the next 48 h to maintain a heart rate less than 80 bpm . Patients were followed for ST segment depression by using a Holter monitor and adverse cardiac outcomes . Postoperative electrocardiographic ischemia was significantly more prevalent in the control group compared with the & bgr;-blocker group during esmolol blockade ( 0 of 52 vs 4 of 55;P = 0.04 ) and tended to be more common in the control group the next two days ( 8 of 55 vs 3 of 52;P = 0.135 ) . In addition , the number of ischemic events ( control , 50 ; & bgr;-blockers , 16 ) and total ischemic time ( control , 709 min ; & bgr;-blocker , 236 min ) were also significantly different from the control group . Myocardial infa rct ions and cardiac events were more common in the control group , but these differences were not significant . Our results suggest that the use of prophylactic & bgr;-blocker therapy may reduce the incidence of postoperative MI . Implication s Prophylactic & bgr ; adrenergic blockade administered after elective total knee arthroplasty was associated with a reduced prevalence and duration of postoperative myocardial ischemia detected with Holter monitoring Background : A rapid increase In the end-tidal concentration of desflurane to greater than 1 MAC transiently increases heart rate , arterial blood pressure , and circulating epinephrine and vasopressin concentrations . We hypothesized that drugs that block sympathetic activity or decrease sympathetic outflow ( an oploid , a β-adrenergic antagonist , and an α2-adrenergic agonist ) would blunt these responses . Methods : After induction of anesthesia with intravenous propofol 2 mg/kg in ten healthy male volunteers age 25 ± 1 yr ( mean ± st and ard error ) , anesthesia was maintained with 4 % end-tidal desflurane in oxygen ( 0.55 MAC ) via an endotracheal tube for 32 min . Controlled ventilation provided normocapnia . We then increased the end-tidal desflurane concentration within 1 min to 8 % ( 1.1 MAC ) and maintained this concentration for 10 min . On separate days , five of these volunteers were similarly anesthetized except that 5 min before the increase to 8 % desflurane , we administered intravenous fentanyl 1.5 µg/kg and on another day 4.5 µg/kg ( dose r and omly assigned ) . On 2 separate days , intravenous esmolol 0.75 mg/kg was given to five volunteers 1.5 min before , or clonidine 4.3 µg/kg by mouth to four volunteers 90 min before , the increase from 4 % to 8 % desflurane . Results : Without pretreatment , the increase to 8 % desflurane increased heart rate ( from 57 ± 2 to 118 ± 6 beats/ min at peak , mean ± st and ard error ) and mean arterial blood pressure ( from 66 ± 2 to 118 ± 5 mmHg ) . At the time of peak hemodynamic changes ( within 1 - 2 min of the increase in desflurane concentration ) , plasma epinephrine and norepinephrine concentrations increased ( from 22 ± 6 to 339 ± 83 pg/ml and from 205 ± 19 to 283 ± 30 pg/ml , respectively ) . Fentanyl 1.5 and 4.5 µg/kg attenuated the heart rate increase by 61 ± 14 % and 70 ± 7 % and the mean arterial blood pressure Increase by 31 ± 16 % and 46 ± 11 % but did not alter the epinephrine or norepinephrine response at the time of peak cardiovascular changes . Esmolol attenuated the heart rate response but no other response . Clonidine attenuated all responses except that of norepinephrine and also caused postanesthesia sedation . Conclusions : Fentanyl , esmolol , and clonidine blunt the transient cardiovascular response to a rapid increase in desflurane concentration . Fentanyl may be the most clinical ly useful of these drugs because it blunts the increase in heart rate and blood pressure , has minimal cardiovascular depressant effects , and imposes little postanesthetlc sedation OBJECTIVES To determine ( 1 ) if perioperative use of esmolol in major vascular surgery patients provides strict heart rate ( HR ) control , ( 2 ) what doses of esmolol are required to do this , and ( 3 ) does this control influence myocardial ischemia or result in adverse consequences . DESIGN Prospect i ve study of 40 patients r and omized to two groups : The HR was controlled to either less than 80 beats/min ( group 80 ) or less than 110 beats/min ( group 110 ) using esmolol . Patients were monitored continuously for electrocardiographic changes perioperatively . HR control began after induction of anesthesia and continued for 48 hours thereafter . SETTING Operating room and intensive care unit . PATIENTS Patients undergoing abdominal vascular surgery involving aortic cross-clamping . INTERVENTIONS Esmolol was titrated until the target HR was met . MEASUREMENTS AND RESULTS Only one patient demonstrated an adverse effect . The median infusion rates were 100 and 12.5 microg/kg/min for groups 80 and 110 . Target HR was met less in group 80 than in group 110 , primarily in the postoperative period . Ischemia patterns were not significantly different between groups . CONCLUSION Using esmolol for HR control in the intraoperative period for abdominal vascular surgery patients is effective and safe . HR control was much less effective in the postoperative period , but esmolol is safe when used at recommended doses . Further study with a larger number of patients is necessary to determine whether strict HR control with esmolol affects the incidence of myocardial ischemia or infa rct ion in this patient population We compared esmolol and remifentanil infusions with respect to their effect on intraoperative hemodynamic stability and early recovery after outpatient laparoscopic surgery when administered as IV adjuvants during desflurane anesthesia . After premedication with midazolam 2 mg IV , anesthesia was induced with propofol 2 mg · kg−1 IV in combination with either esmolol 1 mg · kg−1 IV ( n = 27 ) or remifentanil 1 & mgr;g · kg−1 IV ( n = 26 ) and succinylcholine 1 mg · kg−1 IV according to a r and omized , double-blinded protocol . Anesthesia was initially maintained with des- flurane 2.5 % ( subsequently titrated to maintain an electroencephalogram-bispectral index value of 60 ) and nitrous oxide 65 % in oxygen . Before skin incision , an infusion of either esmolol ( 5 & mgr;g · kg−1 · min−1 ) or remifentanil ( 0.05 & mgr;g · kg−1 · min−1 ) was started and titrated to maintain the heart rate within 25 % of the baseline value . Mivacurium , 0.04 mg/kg IV , bolus doses were administered to maintain a stable peak inspiratory pressure . Esmolol ( 12.8 ± 13.1 & mgr;g · kg−1 · min−1 ) and remifentanil ( 0.04 ± 0.02 & mgr;g · kg−1 · min−1 ) infusions were equally effective in maintaining a stable heart rate during these laparoscopic procedures . Although the mivacurium requirement was larger in the Esmolol group ( 7 ± 5 vs 3 ± 4 mg ) , the Esmolol group reported a smaller incidence of postoperative nausea and vomiting ( 4 % vs 35 % ) . Both drugs were associated with frequent “ postanesthesia care unit bypass ” rates ( 78–81 % ) , short times to “ home readiness ” ( 119–120 min ) , excellent patient satisfaction ( 81–85 % ) , and rapid resumption of normal activities ( 2.6–3.2 d ) . Fast-tracked patients were ready for discharge home significantly earlier ( 112 ± 46 vs 151 ± 50 min ) . We concluded that esmolol infusion is an acceptable alternative to remifentanil infusion for maintaining hemodynamic stability during desflurane-based fast-track anesthesia for outpatient gynecologic laparoscopic surgery . Implication s Adjunctive use of a variable-rate infusion of esmolol during outpatient anesthesia with desflurane-nitrous oxide was associated with less postoperative nausea and vomiting than a remifentanil infusion . However , both adjuvants facilitated fast-tracking and lead to early discharge after laparoscopic tubal ligation surgery BACKGROUND Adverse cardiac events are common after vascular surgery . We hypothesized that perioperative statin therapy would improve postoperative outcomes . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned patients who had not previously been treated with a statin to receive , in addition to a beta-blocker , either 80 mg of extended-release fluvastatin or placebo once daily before undergoing vascular surgery . Lipid , interleukin-6 , and C-reactive protein levels were measured at the time of r and omization and before surgery . The primary end point was the occurrence of myocardial ischemia , defined as transient electrocardiographic abnormalities , release of troponin T , or both , within 30 days after surgery . The secondary end point was the composite of death from cardiovascular causes and myocardial infa rct ion . RESULTS A total of 250 patients were assigned to fluvastatin , and 247 to placebo , a median of 37 days before vascular surgery . Levels of total cholesterol , low-density lipoprotein cholesterol , interleukin-6 , and C-reactive protein were significantly decreased in the fluvastatin group but were unchanged in the placebo group . Postoperative myocardial ischemia occurred in 27 patients ( 10.8 % ) in the fluvastatin group and in 47 ( 19.0 % ) in the placebo group ( hazard ratio , 0.55 ; 95 % confidence interval [ CI ] , 0.34 to 0.88 ; P=0.01 ) . Death from cardiovascular causes or myocardial infa rct ion occurred in 12 patients ( 4.8 % ) in the fluvastatin group and 25 patients ( 10.1 % ) in the placebo group ( hazard ratio , 0.47 ; 95 % CI , 0.24 to 0.94 ; P=0.03 ) . Fluvastatin therapy was not associated with a significant increase in the rate of adverse events . CONCLUSIONS In patients undergoing vascular surgery , perioperative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome . ( Current Controlled Trials number , IS RCT N83738615 . |
10,923 | 31,789,698 | Conclusions : Transfusion was not associated with a decrease in mean cardiac output or mean heart rate .
The increase in mean oxygen delivery following transfusion was associated with an increase in mean oxygen consumption after transfusion , especially in patients with sepsis | Objectives : RBC transfusions can increase oxygen availability to the tissues , but studies have provided conflicting results .
The objectives of this study were , therefore , to evaluate , using systematic review and meta- analysis , the effects of transfusion on hemodynamic/oxygenation variables in patients without acute bleeding . | Objective To evaluate the immediate effects of red blood cell transfusion on central venous oxygen saturation and lactate levels in septic shock patients with different transfusion triggers . Methods We included patients with a diagnosis of septic shock within the last 48 hours and hemoglobin levels below 9.0g/dL Patients were r and omized for immediate transfusion with hemoglobin concentrations maintained above 9.0g/dL ( Group Hb9 ) or to withhold transfusion unless hemoglobin felt bellow 7.0g/dL ( Group Hb7 ) . Hemoglobin , lactate , central venous oxygen saturation levels were determined before and one hour after each transfusion . Results We included 46 patients and 74 transfusions . Patients in Group Hb7 had a significant reduction in median lactate from 2.44 ( 2.00 - 3.22 ) mMol/L to 2.21 ( 1.80 - 2.79 ) mMol/L , p = 0.005 , which was not observed in Group Hb9 [ 1.90 ( 1.80 - 2.65 ) mMol/L to 2.00 ( 1.70 - 2.41 ) mMol/L , p = 0.23 ] . Central venous oxygen saturation levels increased in Group Hb7 [ 68.0 ( 64.0 - 72.0)% to 72.0 ( 69.0 - 75.0)% , p < 0.0001 ] but not in Group Hb9 [ 72.0 ( 69.0 - 74.0)% to 72.0 ( 71.0 - 73.0)% , p = 0.98 ] . Patients with elevated lactate or central venous oxygen saturation < 70 % at baseline had a significant increase in these variables , regardless of baseline hemoglobin levels . Patients with normal values did not show a decrease in either group . Conclusion Red blood cell transfusion increased central venous oxygen saturation and decreased lactate levels in patients with hypoperfusion regardless of their baseline hemoglobin levels . Transfusion did not appear to impair these variables in patients without hypoperfusion . Clinical Trials.gov Introduction The aim of this study was to evaluate the effects of red blood cell ( RBC ) transfusions on muscle tissue oxygenation , oxygen metabolism and microvascular reactivity in critically ill patients using near-infrared spectroscopy ( NIRS ) technology . Methods This prospect i ve , observational study included 44 consecutive patients hospitalized in the 31-bed , medical-surgical intensive care unit of a university hospital with anemia requiring red blood cell transfusion . Thenar tissue oxygen saturation ( StO2 ) and muscle tissue hemoglobin index ( THI ) were measured using a tissue spectrometer ( InSpectra ™ Model 325 ; Hutchinson Technology Inc. , Hutchinson , MN , USA ) . A vaso-occlusive test was performed before and 1 hour after RBC transfusion by rapid inflation of a pneumatic cuff around the upper arm . The following variables were recorded : THI , the StO2 desaturation slope during the occlusion ( % /minute ) and the StO2 upslope of the reperfusion phase following the ischemic period ( % /second ) . Muscle oxygen consumption ( NIR VO2 ; arbitrary units ) was calculated as the product of the inverse StO2 desaturation slope and the mean THI over the first minute of arterial occlusion . Results Blood transfusion result ed in increases in hemoglobin ( from 7.1 ( 6.7 to 7.7 ) to 8.4 ( 7.1 to 9 ) g/dl ; P < 0.01 ) and in oxygen delivery ( from 306 ( 259 to 337 ) to 356 ( 332 to 422 ) ml/minute/m2 ; P < 0.001 ) . However , systemic VO2 was unchanged . RBC transfusion did not globally affect NIRS-derived variables , but there was considerable interindividual variation . Changes in the StO2 upslope of the reperfusion phase after transfusion were negatively correlated with baseline StO2 upslope of the reperfusion phase ( r2 = 0.42 ; P < 0.0001 ) . Changes in NIR VO2 after transfusion were also negatively correlated with baseline NIR VO2 ( r2 = 0.48 ; P = 0.0015 ) . There were no correlations between RBC storage time and changes in StO2 slope or NIR VO2 . Conclusions Muscle tissue oxygenation , oxygen consumption and microvascular reactivity are globally unaltered by RBC transfusion in critically ill patients . However , muscle oxygen consumption and microvascular reactivity can improve following transfusion in patients with alterations of these variables at baseline Background Red blood cell ( RBC ) transfusion is commonly used to increase oxygen transport in patients with sepsis . However it does not consistently increase oxygen uptake at either the whole-body level , as calculated by the Fick method , or within individual organs , as assessed by gastric intra-mucosal pH. Aim This study evaluates the hemodynamic and oxygen utilization effects of hemoglobin infusion on critically ill septic patients . Methods Fifteen septic patients undergoing mechanical ventilation whose hemoglobin was < 10 g% were eligible . Ten patients ( APACHE II : 25.5 ± 7.6 ) received an infusion of 1 unit of packed RBC over 1 h while se date d and paralyzed . The remaining five control patients ( APACHE II : 24.3 ± 6.0 ) received a 5 % albumin solution ( 500 ml ) over 1 h. Hemodynamic data , gastric tonometry and calorimetry were obtained prior to and immediately after RBC transfusion or 5 % albumin infusion . Results Transfusion of RBC was associated with an improvement in left ventricular systolic work index ( 38.6 ± 12.6 to 41.1 ± 13.0 g/min/m2 ; P = 0.04 ) . In the control group there was no significant change in the left ventricular systolic work index ( 37.2 ± 14.3 to 42.2 ± 18.9 g/min/m2 ) . An increase in pulmonary vascular resistance index ( 203 ± 58 to 238 ± 49 dyne/cm5/m2 ; P = 0.04 ) was also observed , while no change was produced by colloid infusion ( 237 ± 87.8 to 226.4 ± 57.8 dyne/cm5/m2 ) . Oxygen utilization did not increase either by Fick equation or by indirect calorimetry in either group . Gastric intramucosal pH increased only in the control group but did not reach statistical significance . Conclusion Hemoglobin increase does not improve either global or regional oxygen utilization in anemic septic patients . Furthermore , RBC transfusion may hamper right ventricular ejection by increasing the pulmonary vascular resistance index Background Although the optimum hemoglobin ( H ) concentration for patients with septic shock ( SS ) has not been specifically investigated , current guidelines suggest that H of 7 - 9 g/dL , compared with 10 - 12 g/dL , was not associated with increased mortality in critically ill adults . This contrasts with early goal -directed resuscitation protocol s that use a target hematocrit of 30 % in patients with low central venous oxygen saturation ( ScvO2 ) during the first 6 hours of resuscitation of SS . Methods Data elements were prospect ively collected on all patients with SS patients ( lactic acid ( LA ) > 4 mmol/L , or hypotension ) . Out of a total of 396 SS patients , 46 patients received red blood cell ( RBC ) transfusion for ScvO2 < 70 % ( RBC group ) . We then matched 71 SS patients that did not receive RBC transfusion ( NRBC group ) on the following goals ( G ) : LA obtained within 6 hours ( G1 ) , antibiotics given within 3 hours ( G2 ) , 20 mL/kg fluid bolus followed by vasopressors ( VP ) if needed to keep mean arterial pressure > 65 mm Hg ( G3 ) , central venous pressure > 8 mm Hg within 6 hours ( G4 ) and ScvO2 > 70 % within 6 hours ( G5 ) . Results In the RBC group , after one unit of RBC transfusion , ScvO2 improved from average of 63 % ( ± 12 % ) to 68 % ( ± 10 % ) ( P = 0.02 ) . Sixteen patients required another unit of RBC , and this result ed in increase of ScvO2 to 78 % ( ± 11 % ) ( P < 0.01 ) . The RBC and NRBC groups were matched on sequential organ failure assessment ( SOFA ) scores and all five goals . There was no difference in mortality between the two groups : 41 % vs. 39.4 % ( OR : 0.8 , 95 % CI : 0.4 - 1.7 , P = 0.6 ) . Conclusions In our study , transfusion of RBC was not associated with decreased mortality in SS patients BACKGROUND AND OBJECTIVES Haemoglobin threshold for transfusion has been significantly decreased , but haemoglobin plasma concentration may not be sufficient to assess the need of red-blood-cell ( RBC ) transfusion . Central venous oxygen saturation ( ScvO2 ) is a clue of metabolic matching between O2 transport and consumption , which could help to assess when transfusion is appropriate once anaemia has been diagnosed in ICU patients . MATERIAL S AND METHODS Adult patients admitted consecutively to a cardiothoracic and vascular ICU were included in a prospect i ve , observational and single-centre study over a 6-month period ( September 2014 to February 2015 ) , provided they were transfused with RBC . Patients with active bleeding or in unstable condition were excluded . Haemoglobin and ScvO2 were collected through a central venous catheter before and after transfusion . In order to identify a ScvO2 threshold , analysis of ScvO2 changes after transfusion was performed . RESULTS Fifty-three patients received 100 RBC transfusions . Haemoglobin at the time of transfusion was 7·2 g/dl [ 6·8 - 7·7 ] , while ScvO2 was 66·9 % [ 60 - 73 ] . A 5 % increase in ScvO2 after transfusion has the best specificity and positive predictive values , with a ScvO2 threshold of 65 % . After transfusion ( RBC units , 2 [ 1 - 2 ] ) , ScvO2 increased only in patients with ScvO2 ≤65 % , from 58 % [ 53 - 62 ] to 69 % [ 64 - 73 ] ( P < 0·001 ) . CONCLUSION In anaemic patients , RBC transfusion induced a significant increase in ScvO2 , provided it was low before transfusion . A 65 % cut-off value of ScvO2 before transfusion showed good specificity and good positive predictive value for a 5 % increase after transfusion BACKGROUND Red blood cell transfusion is commonly used to augment systemic oxygen delivery to supranormal levels in patients with sepsis . However , clinical studies have not consistently demonstrated that this therapeutic maneuver is accompanied by an increase in oxygen utilization at either the whole-body level or within individual organs . STUDY OBJECTIVES To determine the effect of red blood cell transfusion on gastrointestinal and whole-body oxygen uptake . DESIGN Prospect i ve , controlled , interventional study . SETTING Multidisciplinary intensive care unit of a tertiary care teaching hospital . PATIENTS Twenty-three critically ill patients with sepsis undergoing mechanical ventilation . MEASUREMENTS AND MAIN RESULTS Systemic oxygen uptake was measured by indirect calorimetry and calculated by the Fick method . Gastric intramucosal pH as measured by tonometry was used to assess changes in splanchnic oxygen availability . Measurements were made prior to transfusion of 3 U of packed red blood cells . These were then repeated immediately following transfusion , as well as 3 and 6 hours later . There was no increase in systemic oxygen uptake measured by indirect calorimetry in any of the patients studied for up to 6 hours posttransfusion ( including those patients with an elevated arterial lactate concentration ) . However , the calculated systemic oxygen uptake increased in parallel with the oxygen delivery in all the patients . More importantly , we found an inverse association between the change in gastric intramucosal pH and the age of the transfused blood ( r = -.71 ; P < .001 ) . In those patients receiving blood that had been stored for more than 15 days , the gastric intramucosal pH consistently decreased following the red blood cell transfusion . CONCLUSION We failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis . Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia . We postulate that the poorly deformable transfused red blood cells cause micro-circulatory occlusion in some organs , which may lead to tissue ischemia in some organs The role of isolated blood transfusion as a means toward improving oxygen transport was evaluated in 19 critically ill patients having sepsis syndrome as defined by st and ard criteria . ICU therapies were unchanged during transfusion and hemodynamic profiles with serum lactate levels were obtained before and after packed red blood cells were given . Blood transfusions in these patients did not cause a change in hemodynamic status . Arterial lactate determination was normal before and after transfusion was administered . Oxygen uptake failed to increase with transfusion , corresponding to increased arterial and mixed venous oxygen content . In the presence of sepsis , patients having oxygen delivery and uptake above normal without evidence of ischemia ( normal lactate ) will not increase oxygen consumption by raising the hemoglobin Background Microcirculation plays a vital role in the development of multiple organ failure in severe sepsis . The effects of red blood cell ( RBC ) transfusions on these tissue oxygenation and microcirculation variables in early severe sepsis are not well defined . Methods This is a prospect i ve , observational study of patients with severe sepsis requiring RBC transfusions of one to two units of non-leukoreduced RBCs for a hemoglobin < 7.0 , or for a hemoglobin between 7.0 and 9.0 with lactic acidosis or central venous oxygen saturation < 70 % . This study took place in a 54-bed , medical-surgical intensive care unit of a university-affiliated hospital . Thenar tissue oxygen saturation was measured by using a tissue spectrometer on 21 patients , and a vaso-occlusive test was performed before and 1 hour after transfusion . The sublingual microcirculation was assessed with a Sidestream Dark Field device concomitantly on 11 of them . Results RBC transfusion result ed in increase in hemoglobin ( 7.23 ( ± 0.87 ) to 8.75 ( ± 1.06 ) g/dl ; p < 0.001 ) . RBC transfusion did not globally affect near-infrared spectrometry (NIRS)-derived variables . However , percent change in muscle oxygen consumption was negatively correlated with baseline ( r = - 0.679 , p = 0.001 ) . There was no statistically significant correlation between percent change in vascular reactivity and baseline ( p = 0.275 ) . There was a positive correlation between percent change in oxygen consumption and percent change in vascular reactivity ( r = 0.442 , p = 0.045 ) . In the 11 patients , RBC transfusion did not globally affect NIRS-derived variables or SDF-derived variables . There was no statistically significant correlation between percent change in small vessel perfusion and baseline perfusion ( r = -0.474 , p = 0.141 ) , between percent change in small vessel flow and baseline flow ( r = -0.418 , p = 0.201 ) , or between percent change in small vessel perfusion and percent change in small vessel flow ( r = 0.435 , p = 0.182 ) . Conclusions In a small sample population , muscle tissue oxygen consumption , microvascular reactivity and sublingual microcirculation were globally unaltered by RBC transfusion in severe septic patients . However , muscle oxygen consumption improved in patients with low baseline and deteriorated in patients with preserved baseline . Future research with larger sample s is needed to further examine the association between RBC transfusion and outcomes of patients resuscitated early in severe sepsis , with an emphasis on elucidating the potential contribution of microvascular factors Objective To evaluate the use of serum lactic acid values to predict flow-dependent increases in oxygen consumption ( & OV0616;o2 ) in response to increasing oxygen delivery ( & U1E0A;o2 ) after blood transfusion in surgical sepsis . Design Prospect i ve study . Setting Tertiary care , trauma center . Patients Twenty-one patients , postsurgical or posttrauma , judged septic by defined criteria . Interventions Serum lactic acid concentrations , & U1E0A;o2 , and & OV0616;o2 were measured before and after transfusion therapy . Measurements and Main Results Overall , the & U1E0A;o2 increased from 532 ± 146 to 634 ± 225 ( sd ) mL/min.m2 ( p < .001 ) , and the & OV0616;o2 increased from 145 ± 39 to 160 ± 56 mL/min.m2 ( p = .02 ) . These changes occurred with an Hgb increase from 9.3 ± 1.1 to 10.7 ± 1.5 g/dL ( p < .001 ) . The patients were grouped by their pretransfusion serum lactic acid values . In those patients with normal ( < 1.6 mmol/dL ) serum lactic acid ( n = 10 ) , & U1E0A;o2 increased from 560 ± 113 to 676 ± 178 mL/min.m2 ( p < .02 ) , and & OV0616;o2 increased from 150 ± 25 to 183 ± 46 mL/min.m2 ( p < .02 ) . However , in the increased serum lactic acid group ( n = 17 ) , & OV0616;o2 was not significantly changed after transfusion ( 143 ± 46 to 146 ± 58 mL/min.m2 ) despite increased & OV0616;o2 ( 515 ± 163 to 609 & U1E0A;251 mL/min.m2 , p < .01 ) . Conclusions Blood transfusion can be used to augment & OV0616;o2 and & U1E0A;o2 in septic surgical patients . Increased serum lactic acid values do not predict patients who will respond . The absence of lactic acidosis should not be used in this patient population to justify withholding blood transfusions to improve flow-dependent & OV0616;o2 . Patients who have increased lactate concentrations may have a peripheral oxygen utilization defect that prevents improvement in & OV0616;o2 with increasing & U1E0A;o2 . ( Crit Care Med 1991 ; 19:512 BACKGROUND Although central venous oxygen saturation ( ScvO2 ) is used to decide on red blood cell ( RBC ) transfusion , whether its improvement is associated with parallel improvement in cerebral oxygenation is not adequately studied . This study looked at changes in regional cerebral tissue oxygen saturation ( rSO2 ) following RBC transfusion in neuro-intensive care unit ( ICU ) patients . METHODS In this prospect i ve observational pilot study , rSO2 was measured in adult neuro-ICU patients before RBC transfusion , at the end and at 6 , 12 , 18 and 24 h after RBC transfusion . rSO2 measurements were taken using cerebral oximetry on both sides of the hemicraniums . Haemoglobin , central venous pressure , ScvO2 and temperature were recorded during the study period . Arterial oxygen content , central venous oxygen content and cerebral fractional oxygen extraction were calculated . Mann Whitney U test was used to study the changes in variables at baseline and at 24 h following RBC transfusion . Friedman 's test was used to study changes in parameters from baseline to 24 h post-transfusion . A P value of < 0·05 was considered to be significant . RESULTS The data from 13 subjects were analysed . rSO2 increased significantly following RBC transfusion on both sides of the brain ( P = 0·002 , P = 0·007 ) , with a corresponding decrease in cerebral fractional oxygen extraction ( P = 0·001 , P = 0·007 ) . CONCLUSIONS RBC transfusion increased rSO2 significantly on both sides of the brain . As patients ' outcomes were not studied , whether this increase in regional cerebral oxygen saturation is beneficial or if it is because of excess DO2 is still unclear . Further studies are required to clarify this issue OBJECTIVE The aim of this study was to assess the value of central venous oxygen saturation ( ScvO(2 ) ) for the decision of blood transfusion in comparison with the criteria of the French guidelines for blood transfusion ( 2003 ) . STUDY DESIGN Prospect i ve , observational . PATIENTS AND METHODS Sixty patients , haemodynamically stable , for whom a blood transfusion ( BT ) was discussed in the postoperative course of general surgery , were included . ScvO(2 ) ( % ) and haemoglobin ( g/dl ) were measured before and after BT . Patients were retrospectively divided into two groups according to ScvO(2 ) measured before BT ( < or > or=70 % ) . Results are expressed as median . RESULTS The ScvO(2 ) before transfusion was greater or equal to 70 % in 25 ( 47.2 % ) patients . Following BT , the ScvO(2 ) increased significantly ( from 57.8 to 68.5 % ) in the group with initial ScvO(2 ) less than 70 % whereas it was unchanged in patients with initial ScvO(2 ) greater or equal 70 % ( from 76.8 to 76.5 % ) . Twenty patients ( 37.7 % ) did not meet the French guidelines for BT criteria . Eighteen patients out of 33 that met the criteria had ScvO(2 ) greater or equal 70 % before BT while 13 patients with ScvO(2 ) less than 70 % were not detected by these same criteria . CONCLUSION ScvO(2 ) could be a relevant biological parameter to complete the current guidelines for BT in stable patient with a central venous catheter during the postoperative period BACKGROUND Literature suggests poorer outcomes during anaemia as well as following red blood cell transfusion ( BT ) in brain injured patients . Recently , central venous oxygen saturation ( ScvO2 ) has been proposed as a physiological trigger to guide red BT . In this study , we looked at ScvO2 changes following BT in patients admitted to a neurointensive care unit ( NICU ) . STUDY DESIGN In this prospect i ve , observational study , adult , acutely ill neurological patients of > 18 years were recruited . The following parameters were measured before and immediately after transfusion and then at 6 , 12 , 18 and 24 h after transfusion : haemoglobin ( Hb ) , ScvO2 and central venous oxygen partial pressure ( PcvO2 ) ( blood sample d from central venous catheter ) . Simultaneously , hemodynamic parameters [ central venous pressure ( CVP ) , heart rate ( HR ) , mean arterial pressure ( MAP ) and systolic blood pressure ( SBP ) ] were also noted . RESULTS Data from 70 adult patients were analysed . Following BT , significant improvement was noted in Hb , ScvO2 and all hemodynamic parameters . The ScvO2 changes correlated significantly with the number of units of BT ( P = 0·039 ) , pre-transfusion Hb ( P = 0·010 ) , ScvO2 ( P = 0·001 ) and PcvO2 ( P = 0·001 ) . When receiver operating characteristic ( ROC ) curves were drawn , optimum cut-off values of baseline ScvO2 and Hb to predict the need for transfusion in terms of oxygen delivery were 70 % and 8·6 gm dL-1 respectively . DISCUSSION Baseline ScvO2 < 70 % appears to be a useful physiological trigger for deciding the need for BT in brain injured patients . Whether improvement in ScvO2 leads to improvement in regional brain oxygenation needs to be studied Objective To quantify the incidence of anemia and red blood cell ( RBC ) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes . Design Prospect i ve , multiple center , observational cohort study of intensive care unit ( ICU ) patients in the United States . Enrollment period was from August 2000 to April 2001 . Patients were enrolled within 48 hrs of ICU admission . Patient follow-up was for 30 days , hospital discharge , or death , whichever occurred first . Setting A total of 284 ICUs ( medical , surgical , or medical-surgical ) in 213 hospitals participated in the study . Patients A total of 4,892 patients were enrolled in the study . Measurements and Main Results The mean hemoglobin level at baseline was 11.0 ± 2.4 g/dL. Hemoglobin level decreased throughout the duration of the study . Overall , 44 % of patients received one or more RBC units while in the ICU ( mean , 4.6 ± 4.9 units ) . The mean pretransfusion hemoglobin was 8.6 ± 1.7 g/dL. The mean time to first ICU transfusion was 2.3 ± 3.7 days . More RBC transfusions were given in study week 1 ; however , in subsequent weeks , subjects received one to two RBC units per week while in the ICU . The number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality . Patients who received transfusions also had more total complications and were more likely to experience a complication . Baseline hemoglobin was related to the number of RBC transfusions , but it was not an independent predictor of length of stay or mortality . However , a nadir hemoglobin level of < 9 g/dL was a predictor of increased mortality and length of stay . Conclusions Anemia is common in the critically ill and results in a large number of RBC transfusions . Transfusion practice has changed little during the past decade . The number of RBC units transfused is an independent predictor of worse clinical outcome STUDY OBJECTIVES During isovolemic hemodilution , healthy individuals maintain oxygen consumption VO2 by identical increases in cardiac index ( CI ) and oxygen extraction ratio ( O(2)ER ) . In critically ill patients , the relationship between CI and O(2)ER may be different . Patients with an altered cardiac function may have a decreased CI/O(2)ER ratio , whereas patients with sepsis may have an increased CI/O(2)ER ratio . We hypothesized that the analysis of the CI-O(2)ER relationship could help us to assess the adequacy of cardiac function in critically ill patients with anemia . DESIGN Prospect i ve , observational study . SETTING Thirty-one-bed medicosurgical ICU of a university hospital . PATIENTS Sixty patients equipped with arterial and Swan-Ganz catheters presenting with anemia , which was defined as a hemoglobin level < or = 10 g/dL in the absence of active bleeding . Patients were classified into those with compromised cardiac function ( group 1 ; n = 40 ) , and those with normal cardiac function ( group 2 ; n = 20 ) . MEASUREMENTS AND RESULTS In addition to the pertinent clinical data , initial hemodynamic measurements , including pulmonary artery occlusion pressure ( PAOP ) , CI , and O(2)ER , were collected in all patients at the onset of anemia . As anticipated , group 1 patients ( n = 40 ) had lower CIs , higher O(2)ER levels , and lower CI/O(2)ER ratios than group 2 patients . However , there was no significant difference in PAOP values between the groups . The CI/O(2)ER ratio was < 10 in 27 of 40 group 1 patients but only in 4 of 20 group 2 patients . Of these latter four patients , three were found to be hypovolemic , and one patient with sepsis had severe myocardial depression . There was no statistically significant difference in PAOP in group 2 patients with or without hypovolemia ( [ mean + /- SD ] 12.3+/-2.1 mm Hg ) vs 13.7+/-4.3 mm Hg ; p = 0.21 ) . In group 1 , survivors had a higher CI and CI/O(2)ER ratio than nonsurvivors . In group 2 , however , such a relationship did not reach statistical significance . CONCLUSIONS The relationship between CI and O(2)ER level can help interpret the CI in anemic patients . In anemic patients with no cardiac history , a low CI/O(2)ER ratio ( < 10 ) suggests hypovolemia even when CI is not depressed Fifty-four patients with systemic sepsis and signs of circulatory shock were prospect ively investigated immediately before and after 1 of 3 therapeutic interventions chosen to increase systemic oxygen delivery ( DO2 ) : colloidal fluid loading ( Group I , n = 20 ) , blood transfusion ( Group II , n = 17 ) , or catecholamine infusion ( dopamine or dobutamine , Group III , n = 17 ) . Patients in Groups I and II with normal blood lactate concentrations ( less than 2.2 mmol/L ) exhibited no significant increases in systemic oxygen consumption ( VO2 ) in response to the increases in DO2 . However , significant increases in VO2 were noted in patients in Groups I and II with elevated lactate concentrations ( greater than 2.2 mmol/L ) . In contrast to patients in Groups I and II , patients in Group III with and without lactic acidosis exhibited significant increases in VO2 after catecholamine administration . Lactic acidosis , a clinical marker of anaerobic metabolism or oxygen debt , appears to predict increases in VO2 in response to increases in DO2 in septic patients receiving fluid and catecholamines increase VO2 without regard for the presence or absence of anaerobic metabolism . The results of this clinical trial therefore suggest that catecholamines may exert a direct effect on oxidative metabolism Objective To investigate whether increasing oxygen delivery ( Do2 ) by increasing hematocrit results in increases in oxygen uptake ( Vo2 ) in septic patients with an abnormal Do2/Vo2 relationship . Design Prospect i ve , r and omized , interventional crossover study . Setting Tertiary care hospital . Patients A consecutive sample of 16 patients admitted to the intensive care unit , who were diagnosed as having severe sepsis by defined criteria and who had a hemoglobin concentration of<10 g/dL. Interventions Patients received , in r and om order , an infusion of dobutamine ( 10 μg/kg/min ) and a blood transfusion ( 800 mL of packed red blood cells in 90 mins ) . Hemodynamic and oxygen transport variables were determined before and after each treatment , allowing at least 20 mins during the infusion of dobutamine to achieve the steady state . Measurements and Main Results Changes in Do2 and Vo2 induced by each intervention were measured . Dobutamine significantly increased Do2 ( 48.5 ± 6.9 % ; p = .0001 ) and Vo2 ( 21.7 ± 3.3 % ; p = .0001 ) . Blood transfusion increased Do2 ( 21.4 ± 4.3 % ; p = .005 ) but Vo2 did not change significantly ( 2.2 ± 4.1 % ) . Correlation coefficients for the percent changes of Do2 and Vo2 ( r2 = .67 p = .001 for dobutamine ; and r2 = 21 , p = .07 for blood transfusion ) were significantly different for each treatment ( p = .0001 ) . Conclusions In patients with an abnormal Do2-dependent Vo2 , as shown by increases in Vo2 brought about by an infusion of dobutamine , blood transfusion does not significantly increase Vo2 , despite significant changes in Do2 . The Vo2 in some critically ill patients , depends more on blood flow than on global Do2 . ( Crit Care Med 1993 ; 21:1312–1318 Objectives : Microvascular alterations may play a role in the development of multiple organ failure in severe sepsis . The effects of red blood cell transfusions on microvascular perfusion are not well defined . We investigated the effects of red blood cell transfusion on sublingual microvascular perfusion in patients with sepsis . Design : Prospect i ve , observational study . Setting : A 31-bed , medical-surgical intensive care unit of a university hospital . Patients : Thirty-five patients with severe sepsis requiring red blood cell transfusions . Interventions : Transfusion of one to two units of leukocyte-reduced red blood cells . Measurements and Main Results : The sublingual microcirculation was assessed with an Orthogonal Polarization Spectral device before and 1 hr after red blood cell transfusion . Red blood cell transfusions increased hemoglobin concentration from 7.1 ( 25th–75th percentile , 6.7–7.6 ) to 8.1 ( 7.5–8.6 ) g/dL ( p < .01 ) , mean arterial pressure from 75 ( 69–89 ) to 82 ( 75–90 ) mm Hg ( p < .01 ) , and oxygen delivery from 349 ( 278–392 ) to 391 ( 273–473 ) mL/min·M2 ( p < .001 ) . Microvascular perfusion was not significantly altered by transfusion , but there was considerable interindividual variation . The change in capillary perfusion after transfusion correlated with baseline capillary perfusion ( Spearman-rho = −.49 ; p = .003 ) . Capillary perfusion was significantly lower at baseline in patients who increased their capillary perfusion by > 8 % compared with those who did not ( 57 [ 52–64 ] vs. 75 [ 70–79 ] ; p < .01 ) , while hemodynamic and global oxygen transport variables were similar in the two groups . Red blood cell storage time had no influence on the microvascular response to red blood cell transfusion . Conclusions : The sublingual microcirculation is globally unaltered by red blood cell transfusion in septic patients ; however , it can improve in patients with altered capillary perfusion at baseline PURPOSE Whether transfusions of packed red blood cells ( PRBCs ) affect tissue oxygenation in stable critically ill patients is still matter of discussion . The microvascular capacity for tissue oxygenation can be determined noninvasively by measuring transcutaneous oxygen tension ( tcpO2 ) . The aim of this study was to assess tissue oxygenation by measuring tcpO2 in stable critically ill patients receiving PRBC transfusions . METHODS Nineteen stable critically ill patients , who received 2 units of PRBC , were prospect ively included into this pilot study . Transcutaneous oxygen tension was measured continuously during PRBC transfusions using Clark 's electrodes . In addition , whole blood viscosity and global hemodynamics were determined . RESULTS Reliable measurement signals during continuous tcpO2 monitoring were observed in 17 of 19 included patients . Transcutaneous oxygen tension was related to the global oxygen consumption ( r=-0.78 ; P=.003 ) , the arterio-venous oxygen content difference ( r=-0.65 ; P=.005 ) , and the extraction rate ( r=-0.71 ; P=.02 ) . The transfusion-induced increase of the hemoglobin concentration was paralleled by an increase of the whole blood viscosity ( P<.001 ) . Microvascular tissue oxygenation by means of tcpO2 was not affected by PRBC transfusions ( P=.46 ) . Packed red blood cell transfusions result ed in an increase of global oxygen delivery ( P=.02 ) and central venous oxygen saturation ( P=.01 ) , whereas oxygen consumption remained unchanged ( P=.72 ) . CONCLUSIONS In stable critically ill patients , microvascular tissue oxygenation can be continuously monitored by Clark 's tcpO2 electrodes . According to continuous tcpO2 measurements , the microvascular tissue oxygenation is not affected by PRBC transfusions |
10,924 | 32,270,406 | Exercise-based CR improves the post-exercise parasympathetic function , with greater effects in younger CAD patients and in those who were revascularised with percutaneous intervention .
The effects on resting parasympathetic function are more controversial due to method ological inconsistencies in measuring HRV , with the use of RMSSD recommended instead of HF because its results show higher consistency . | The effects of exercise-based cardiac rehabilitation ( CR ) on parasympathetic modulation are controversial .
This systematic review and meta- analysis aims to ( a ) determine the effect of exercise-based CR on heart-rate-derived indices associated with cardiac parasympathetic modulation in resting and post-exercise conditions in coronary artery disease ( CAD ) patients and ( b ) identify the possible moderator variables of the effect of exercise-based CR on parasympathetic modulation .
We search ed CENTRAL and Web of Science up to November 2018 for the following terms : adult CAD patients , controlled exercise-based CR interventions and parasympathetic modulation measured in resting ( vagal-related heart rate variability [ HRV ] indices of the root mean square of the differences in successive in RR interval [ RMSSD ] and high frequency [ HF ] ) and post-exercise ( heart rate recovery [ HRR ] ) pre- and post-intervention . | BACKGROUND High-mobility group box-1 ( HMGB1 ) is a novel predictor of adverse postinfa rct ion clinical outcomes , playing a crucial role in the appropriate postinfa rct ion healing process . METHODS AND RESULTS Seventy-five postinfa rct ion patients were enrolled in a single-center r and omized study ( clinical trial.gov identifier : NCT00755131 ) . Group T patients ( training , n = 37 ) underwent 6-month exercise-based cardiac rehabilitation ( CR ) program , whereas group C patients ( controls , n = 38 ) were discharged with generic instructions for maintaining physical activity and a correct lifestyle . After 6 months , HMGB1 levels were significantly reduced in the total population ( 26.1 ± 23.5 vs. 16.2 ± 12.9 ng/mL ; P = .0006 ) . After adjusting for several confounders , linear regression analysis showed that the inclusion in the training group ( β = -10.54 , P = .043 ) was associated with marked reduction of HMGB1 levels . After 6 months , HMGB1 levels were significantly lower in trained patients compared to controls ( 11.7 ± 7.0 vs. 20.5 ± 15.6 ng/mL , P = .0027 , respectively ) . In trained patients , decreased HMGB1 levels were significantly associated with the improvement in peak oxygen consumption ( β = -3.879 , P = .003 ) and heart rate recovery ( β = -2.492 , P = .002 ) , and with reduced left ventricular end-diastolic volume ( β = 1.412 , P = .001 ) and wall motion score index ( β = 1.138 , P = .002 ) . CONCLUSIONS The decrease in HMGB1 levels after anterior myocardial infa rct ion was associated with exercise training and with the improvement of cardiopulmonary and autonomic function , and with favorable cardiac remodeling Wu S-K , Lin Y-W , Chen C-L , Tsai S-W : Cardiac rehabilitation vs. home exercise after coronary artery bypass graft surgery : a comparison of heart rate recovery . Am J Phys Med Rehabil 2006;85:711–717 . Objective : The autonomic dysfunction is known to adversely affect clinical outcome in patients with cardiovascular disease , and exercise training has been shown to modify the sympathovagal control of heart rate . The purpose s of this study were to investigate the effect of cardiac rehabilitation on heart rate recovery in patients who received coronary artery bypass grafting ( CABG ) and compare the effect with that of a home-based exercise program . Design : Fifty-four male patients having undergone CABG were r and omly assigned to a cardiac rehabilitation exercise program ( n = 18 ) , a home-based exercise program ( n = 18 ) , and a control group ( n = 18 ) for 12 wks to evaluate the differences in heart rate recovery among groups . Results : Patients in the cardiac rehabilitation group had significant increases in heart rate recovery ( 19.1 ± 6.2 vs. 14.0 ± 5.4 beats/min , P = 0.022 ) compared with those in the control group . There were no significant differences in heart rate recovery between cardiac rehabilitation and home-based exercise groups ( 16.2 ± 4.8 beats/min ) or between home-based exercise and control groups . All three groups had significantly improved heart rate recovery compared with their baseline data ( P < 0.001 , < 0.001 , and 0.007 ) . Conclusion : Our results point out that a cardiac rehabilitation exercise program has a positive effect on heart rate recovery in patients having undergone CABG and is consistent with the autonomic improvement . Although the home-based exercise group did not reveal statistical significance s over those in the control group , it had comparable efficacy to that demonstrated in the cardiac rehabilitation group Heart rate variability ( HRV ) reflects the autonomic tone of the heart , and QT dispersion reflects the regional inhomogeneity of ventricular repolarization . The purpose of the present study was to determine the effects of early exercise training on HRV and QT dispersion in patients with acute myocardial infa rct ion ( AMI ) . Forty patients ( mean age : 59 years ) with AMI were r and omized to training rehabilitation ( group Tr , n=20 ) or conventional rehabilitation ( group C , n=20 ) . Two weeks after AMI , group Tr underwent 10 min of exercise using a bicycle ergometer ( 80 % of anaerobic threshold ) twice a day . At the end of the second and fourth weeks , 12-lead and 24-h Holter ECGs were recorded . QT intervals were measured and corrected using Bazett 's formula ( QTc ) , and QTc dispersion ( QTcd ) was defined as the difference between maximum and minimum QTc . HRV was accessed by the high-frequency component ( HF : 0.15 - 0.40 Hz ) of the HRV power spectrum ( parasympathetic activity ) and the ratio of low frequency ( 0.04 - 0.15 Hz ) to HF ( L/H ratio : sympathetic activity ) . In group Tr , HF increased ( 82.5 to 131.1 ms2 ) , the L/H ratio decreased ( 3.9 to 2.6 ) , and QTcd decreased ( 77.2 to 57.2 ms ) . In group C , none of the indices changed . It was concluded that early exercise training improves sympathovagal balance and decreases QTcd , and may reduce the arrhythmogenic substrate following AMI INTRODUCTION Heart rate recovery , defined as the fall in heart rate during the first minute after exercise , is an indicator of autonomic function , and has been found to be an independent predictor of mortality after acute myocardial infa rct ion . Exercise training has several well-known benefits in terms of cardiorespiratory fitness , modifiable cardiovascular risk factors and prognosis after acute coronary events . However , there are no r and omized controlled studies in the literature evaluating the effects of exercise training per se , controlling for changes in medication and diet , on heart rate recovery . Thus , this study aims to assess the effects of exercise training on autonomic function in coronary artery disease patients recovering from acute myocardial infa rct ion . METHODS Thirty-eight patients following a first acute myocardial infa rct ion participated in this prospect i ve r and omized clinical trial . Patients were r and omized into two groups : exercise training or control . The exercise group participated in an 8-week aerobic exercise program , while the control received st and ard medical care and follow-up . Changes in hemodynamics at rest and at peak exercise ( heart rate , systolic and diastolic blood pressure , and rate pressure product ) , dietary intake , cardiorespiratory fitness , and heart rate recovery were assessed . RESULTS Medication and diet remained unchanged in both groups during the study period . The exercise-training group improved resting hemodynamics , particularly resting heart rate ( from 68.0 ± 9.2 to 62.6 ± 8.7 bpm , p=0.030 ) and systolic blood pressure ( from 135 ± 7.1 to 125.6 ± 11.3 mm Hg , p=0.012 ) , cardiorespiratory fitness ( from 30.8 ± 7.8 to 33.9 ± 8.3 ml/min/kg , p=0.016 ) , and heart rate recovery ( from 20 ± 6 to 24 ± 5 bpm , p=0.007 ) . No significant changes were observed in the control group . CONCLUSIONS Exercise training improved autonomic function , assessed by heart rate recovery , resting heart rate and systolic blood pressure , in the absence of changes in diet or medication OBJECTIVES The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease . BACKGROUND Although there is good evidence that clinical depression is associated with poor prognosis , optimal therapeutic strategies are currently not well defined . METHODS One hundred one out patients with coronary heart disease and elevated depressive symptoms underwent assessment of depression , including a psychiatric interview and the Hamilton Rating Scale for Depression . Participants were r and omized to 4 months of aerobic exercise ( 3 times/week ) , sertraline ( 50 - 200 mg/day ) , or placebo . Additional assessment s of cardiovascular biomarkers included measures of heart rate variability , endothelial function , baroreflex sensitivity , inflammation , and platelet function . RESULTS After 16 weeks , all groups showed improvement on Hamilton Rating Scale for Depression scores . Participants in both the aerobic exercise ( mean -7.5 ; 95 % confidence interval : -9.8 to -5.0 ) and sertraline ( mean -6.1 ; 95 % confidence interval : -8.4 to -3.9 ) groups achieved larger reductions in depressive symptoms compared with those receiving placebo ( mean -4.5 ; 95 % confidence interval : -7.6 to -1.5 ; p = 0.034 ) ; exercise and sertraline were equally effective at reducing depressive symptoms ( p = 0.607 ) . Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo ( p = 0.052 ) ; exercise tended to result in greater improvements in heart rate variability compared with sertraline ( p = 0.093 ) . CONCLUSIONS Both exercise and sertraline result ed in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease . Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life . ( Exercise to Treat Depression in Individuals With Coronary Heart Disease ; NCT00302068 ) The aim of this study was to evaluate the influence of cardiac rehabilitation ( CR ) on heart rate variability ( HRV ) indices in men with coronary artery disease ( CAD ) treated with percutaneous coronary intervention ( PCI ) or coronary artery bypass graft surgery ( CABG ) . The study population consisted of 131 male patients with CAD prospect ively and consecutively admitted to CR after PCI n = 72 , or CABG n = 59 . Participants performed cycle ergometer interval training for 45 min three times a week for 8 weeks . At baseline and after 8 weeks , all patients underwent the HRV assessment . HRV indices in CAGB survivals were significantly lower in comparison to PCI patients at baseline . Significant increases were seen for SDNN , rMSSD , and HF in the CABG group and only in HF component in PCI group after 8 weeks of CR . Eight weeks of CR seems to be more effective in CABG patients than patients after PCI CONTEXT Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality , but the effects of behavioral interventions on psychosocial and medical end points remain uncertain . OBJECTIVE To determine the effect of 2 behavioral programs , aerobic exercise training and stress management training , with routine medical care on psychosocial functioning and markers of cardiovascular risk . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 134 patients ( 92 male and 42 female ; aged 40 - 84 years ) with stable ischemic heart disease ( IHD ) and exercise-induced myocardial ischemia . Conducted from January 1999 to February 2003 . INTERVENTIONS Routine medical care ( usual care ) ; usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks ; usual care plus weekly 1.5-hour stress management training for 16 weeks . MAIN OUTCOME MEASURES Self-reported measures of general distress ( General Health Question naire [ GHQ ] ) and depression ( Beck Depression Inventory [ BDI ] ) ; left ventricular ejection fraction ( LVEF ) and wall motion abnormalities ( WMA ) ; flow-mediated dilation ; and cardiac autonomic control ( heart rate variability during deep breathing and baroreflex sensitivity ) . RESULTS Patients in the exercise and stress management groups had lower mean ( SE ) BDI scores ( exercise : 8.2 [ 0.6 ] ; stress management : 8.2 [ 0.6 ] ) vs usual care ( 10.1 [ 0.6 ] ; P = .02 ) ; reduced distress by GHQ scores ( exercise : 56.3 [ 0.9 ] ; stress management : 56.8 [ 0.9 ] ) vs usual care ( 53.6 [ 0.9 ] ; P = .02 ) ; and smaller reductions in LVEF during mental stress testing ( exercise : -0.54 % [ 0.44 % ] ; stress management : -0.34 % [ 0.45 % ] ) vs usual care ( -1.69 % [ 0.46 % ] ; P = .03 ) . Exercise and stress management were associated with lower mean ( SE ) WMA rating scores ( exercise : 0.20 [ 0.07 ] ; stress management : 0.10 [ 0.07 ] ) in a subset of patients with significant stress-induced WMA at baseline vs usual care ( 0.36 [ 0.07 ] ; P = .02 ) . Patients in the exercise and stress management groups had greater mean ( SE ) improvements in flow-mediated dilation ( exercise : mean [ SD ] , 5.6 % [ 0.45 % ] ; stress management : 5.2 % [ 0.47 % ] ) vs usual care patients ( 4.1 % [ 0.48 % ] ; P = .03 ) . In a subgroup , those receiving stress management showed improved mean ( SE ) baroreflex sensitivity ( 8.2 [ 0.8 ] ms/mm Hg ) vs usual care ( 5.1 [ 0.9 ] ms/mm Hg ; P = .02 ) and significant increases in heart rate variability ( 193.7 [ 19.6 ] ms ) vs usual care ( 132.1 [ 21.5 ] ms ; P = .04 ) . CONCLUSION For patients with stable IHD , exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone Objective : To evaluate the effects of cardiac rehabilitation on the recovery of heart rate over 1 min after peak exercise of patients who received coronary artery bypass graft ( CABG ) surgery . Design : Thirty subjects who received CABG surgery were r and omly assigned to enter or not enter a cardiac rehabilitation exercise programme ( cardiac rehabilitation n=15 ; control group n=15 ) . Setting : Outpatient cardiac rehabilitation centre in a national medical hospital . Interventions : Patients assigned to the cardiac rehabilitation group received 36 sessions of the exercise programme , three times a week , with the intensity design ed to achieve an individual 60 - 85 % peak heart rate in cardiopulmonary exercise test . Patients assigned to the control group did not get further advice about a specific exercise programme . Main outcome measures : Resting heart rate and recovery of heart rate over 1 min after a peak exercise test at discharge and three months later were collected . The heart rates were analysed with computer-recorded electrocardiogram . Results : At follow-up , the 15 patients in the cardiac rehabilitation group had a significantly lower resting heart rate ( 77.469± 9.49 versus 92.319± 10.18 bpm ; p B± 0.001 ) and a significantly higher recovery of heart rate over 1 min ( 16.389± 6.32 versus 11.389± 4.81 bpm ; p ± 0.03 ) compared with the control group . There were also significant reductions in resting heart rates ( cardiac rehabilitation p ± 0.001 ; control p=0.05 ) and improvements in recovery on heart rate over 1 min ( cardiac rehabilitation p ± 0.001 ; control p= 0.001 ) compared with baseline measurements in both the cardiac rehabilitation and control groups . Conclusion : Cardiac rehabilitation had a positive effect on the improvement of recovery on heart rate over 1 min in patients with coronary artery disease who received CABG surgery Heart rate variability and postexercise heart rate recovery are used to assess cardiac parasympathetic tone in human studies , but in some cases these indexes appear to yield discordant information . We utilized pyridostigmine , an acetylcholinesterase inhibitor that selectively augments the parasympathetic efferent signal , to further characterize parasympathetic regulation of rest and postexercise heart rate . We measured time- and frequency-domain indexes of resting heart rate variability and postexercise heart rate recovery in 10 sedentary adults and 10 aerobically trained athletes after a single oral dose of pyridostigmine ( 30 mg ) and matching placebo in r and omized , double-blind , crossover trial . In sedentary adults , pyridostigmine decreased resting heart rate [ from 66.7 ( SD 12.6 ) to 58.1 beats/min ( SD 7.6 ) , P = 0.005 vs. placebo ] and increased postexercise heart rate recovery at 1 min [ from 40.7 ( SD 10.9 ) to 45.1 beats/min ( SD 8.8 ) , P = 0.02 vs. placebo ] . In trained athletes , pyridostigmine did not change resting heart rate or postexercise heart rate recovery when compared with placebo . Time- and frequency-domain indexes of resting heart rate variability did not differ after pyridostigmine versus placebo in either cohort and were not significantly associated with postexercise heart rate recovery in either cohort . The divergent effects of pyridostigmine on resting and postexercise measures of cardiac parasympathetic function in sedentary subjects confirm that these measures characterize distinct aspects of cardiac parasympathetic regulation . The lesser effect of pyridostigmine on either measure of cardiac parasympathetic tone in the trained athletes indicates that the enhanced parasympathetic tone associated with exercise training is at least partially attributable to adaptations in the efferent parasympathetic pathway Twenty-two male and female patients who had recently suffered a myocardial infa rct ion were r and omly assigned to a treatment group who participated in a 10-week exercise-based cardiac rehabilitation programme or a routine care group who did not participate in the rehabilitation programme . Physiological and psychological function were assessed before the programme started and after it finished . Results indicated that the treatment group did not improve physiological functioning more than the control group but they did evidence statistically significant improved psychological functioning . This investigation appears to be the first attempt to assess the potential benefits of an exercise-based cardiac rehabilitation programme in Glasgow and supports the suggestion that exercise-based cardiac rehabilitation has psychological benefits BACKGROUND Cardiovascular diseases are the leading cause of death globally and sedentary lifestyle is one of the main risk factors . Home-based cardiac rehabilitation ( CR ) programs appear to be effective to improve exercise tolerance . The aim of the study , therefore , was to evaluate the effects of a phase IV ( maintenance ) home-based CR program on cardiorespiratory fitness and daily physical activity of patients recovering from an acute myocardial infa rct ion . METHODS This pilot study , with a sub-group r and omised controlled trial , included 32 individuals recovering from a myocardial infa rct ion , r and omly divided into the experimental group ( EG , n=16 ) and the control group ( CG , n=16 ) . The EG performed an exercise program , three times per week , at home during eight weeks . The two groups received health education sessions . Baseline and final assessment s included cardiorespiratory fitness , resting and peak heart rate , blood pressure and rate pressure , heart rate recovery and daily physical activity . ( Clinical Trials.gov : NCT01887080 ) . RESULTS At baseline no significant differences were observed between groups . After eight weeks of exercise , the EG significantly increased peak oxygen uptake ( p=0.02 ) , test duration ( p=0.019 ) , peak rate pressure ( p=0.003 ) , peak heart rate ( p=0.003 ) and heart rate recovery ( 0.025 ) when compared to the CG . No changes were observed on daily physical activity in both groups . CONCLUSION This specific phase IV home-based exercise program seems to improve cardiorespiratory fitness , haemodynamics at peak exercise and heart rate recovery , an indicator of cardiac autonomic function The aims of the present study are twofold : 1 ) to investigate whether heart rate recovery ( HRR ) after a cycle ergometry test is affected by exercise training and 2 ) to test the ability of HRR to replicate the baroreflex sensitivity ( BRS ) changes that occur in response to an exercise training program in coronary artery patients . We r and omized 82 coronary artery patients undergoing a residential cardiac rehabilitation program to an exercise training group ( TR ; n = 43 ) and an untrained group ( UTR ; n = 39 ) . All of the patients underwent an exercise test before and after the rehabilitation program . HRR was recorded at the end of the 1st and 2nd min after exercise . BRS was determined at rest before and after treatment . HRR after the 2nd min was significantly improved in TR patients ( -21.4 + /- 0.9 beats/min ) compared with UTR patients ( -17.8 + /- 1.2 beats/min ) at the end of the training program . Improvement in HRR paralleled that in BRS in TR patients ( from 3.2 + /- 0.3 to 5.3 + /- 0.8 ms/mmHg ; P < 0.001 ) , whereas no significant change was evident in UTR patients ( from 3.5 + /- 0 to 4.0 + /- 0.4 ms/mmHg ; P = 0.230 ) . Our data show that HRR in the 2nd min after the cessation of a cycle ergometer exercise test increased in coronary artery patients after an exercise training period . This result confirms the positive effect induced by exercise training on HRR and extends the conclusions of previous studies to different modalities of exercise ( i.e. , cycle ergometer ) . HRR might provide an additional simple marker of the effectiveness of physical training programs in cardiac patients 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 AIMS Reduced heart rate variability is associated with an unfavourable prognosis in patients with ischaemic heart disease . Whether physical training can modify this risk factor is not definitely proven . Our hypothesis was that training might increase both physical capacity and heart rate variability in elderly patients recovering from an acute coronary event , i.e. acute myocardial infa rct ion ( n=38 ) or an episode of unstable angina ( n=27 ) . METHODS AND RESULTS 24 h ambulatory ECG recordings were obtained from 65 patients r and omized to either a 3 months supervised outpatient group training programme 50 min three times a week ( n=29 ) or to a control group ( n=36 ) . The two groups were well balanced as regards demographic data and pharmacological treatment at the time of r and omization . Body mass index and pharmacological therapy remained unchanged during the study . Heart rate variability was analysed in the time and frequency domains . At the 3 month follow-up , exercise tolerance had increased from 103 to 120 W in the training group ( P<0.001 ) , and from 102 to 106 W in the control group ( ns ) . The time-domain heart rate variability measures SDNN ( st and ard deviation of all filtered RR intervals over the analysed time period ) and SDANN ( st and ard deviation of the means of all filtered RR intervals for all 5 min epochs of the analysed time period ) increased significantly during the daytime in the training group ( P<0.01 and P<0.05 , respectively ) , but not in the control group . A significant improvement in night-time heart rate variability was observed among controls . There was a statistically significant correlation ( P<0.05 ) between changes in 24 h overall power ( frequency domain measure ) and changes in maximal exercise capacity in the training group . CONCLUSION A regular aerobic group training programme after an acute coronary event can significantly improve exercise capacity and modify heart rate variability in a prognostically favourable direction in elderly low-to-intermediate risk patients , recovering from an acute coronary event BACKGROUND AND PURPOSE Cardiac autonomic dysfunction is associated with risk of restenosis and cardiovascular mortality in patients after percutaneous transluminal coronary angioplasty ( PTCA ) . Analysis of heart rate variability ( HRV ) is an important , widely used method for assessing cardiac autonomic regulation . The purpose of this study was to investigate the effect of exercise training on HRV in subjects after PTCA . SUBJECTS AND METHODS A total of 84 subjects who had undergone PTCA were recruited for this study . The subjects ( age [mean+/-SD]=57.0+/-9.3 years ) were r and omly assigned to either an exercise group to undergo an 8-week outpatient exercise program or a control group to undergo usual care . Heart rate variability was measured for 5 minutes in the supine resting position at baseline and at the end of 8 weeks . RESULTS The parasympathetically modulated HRV of the subjects in the exercise group increased significantly compared with the HRV of subjects in the control group . The effects of training on HRV were independent of angioplasty type ( balloon or stent ) and were unrelated to whether the subjects had received previous PTCA . DISCUSSION AND CONCLUSION Exercise training can increase parasympathetic modulation of cardiac function in people after they have undergone successful PTCA . Our results suggest that analysis of HRV can be extended to assess the effect of exercise training on cardiac autonomic dysfunction in people after coronary angioplasty To investigate the effects of physical training on neurovegetative profile of patients with previous anterior myocardial infa rct ion ( MI ) , we studied 38 patients out of the EAMI study at 4 to 6 weeks after anterior MI ( test 1 ) , who were then assigned r and omly to a training group ( n = 22 ) or to a control group ( n = 16 ) and studied again 6 months later ( test 2 ) . Neurovegetative function was assessed by analyzing the heart rate variability ( HRV ) of 24 h , from ambulatory ECG recording , both in time domain , as st and ard deviation of sinus rhythm RR intervals ( sdRR ) and percentage of differences greater than 50 ms for successive sinus rhythm R-R intervals ( pNN50 ) , and in frequency domain , as low frequency ( LF ) and high frequency ( HF ) components of RR variability power spectrum . At test 1 , HRV was almost in normal range or slightly decreased in few subjects . HRV increased on average at test 2 : sdRR augmented significantly ( p less than 0.05 ) without significant differences between training group and control group ; mean LF/HF ratio increased slightly ( p less than 0.05 ) at test 2 . This might suggest a shift of neurovegetative balance toward a sympathetic rule , but the difference is too small and the patient population limited to reach firm conclusions . Analysis of 24-h dynamics of HRV in single patients showed different patterns and different adaptations during the time course of 6 months after anterior MI Analysis of heart rate variability ( HRV ) can identify patients at risk of sudden cardiac death after myocardial infa rct ion . The present study examined the effect of 2 weeks of supervised aerobic exercise training on the recovery of the autonomic nervous activity , exercise capacity , and cardiac output ( CO ) after coronary artery bypass grafting ( CABG ) . Twenty-eight patients were r and omly divided into the training group or the control group and performed exercise tests at 1 week , 3 weeks , 3 months , 6 months and 1 year after CABG . The HRV was measured , and the high-frequency component of HRV was used as an index of parasympathetic nerve activity ( PNA ) ; the plasma norepinephrine concentration ( NE ) was used as an index of sympathetic nervous activity . Cardiac output was also measured . In the training group , peak VO2 , peak CO and PNA during exercise had improved at 3 weeks , but there was no improvement in these indices in the control group . NE decreased 1 week after CABG in both groups . These results indicate that physical training soon after CABG improves not only the exercise capacity , but also PNA PURPOSE The purpose of this study is to evaluate the effects of an 8-week exercise-based cardiac rehabilitation program on traditional and nonlinear heart rate variability ( HRV ) indexes , assessing the potential confounding influences of habitual physical activity ( PA ) and dietary intake . METHODS In this parallel-group trial , 96 patients ( 56 ± 10 years old ) were r and omized to the exercise group ( EG ) or to the control group ( CG ) 4 weeks after an acute myocardial infa rct ion . Exercise-based cardiac rehabilitation program consisted of aerobic exercise at 70 % to 85 % of maximal heart rate for 3 sessions per week plus usual care . The CG received only usual care . The baseline and final assessment s comprised resting short-term HRV ( primary outcome ) by a Polar R-R recorder under controlled breathing ( 12 breaths per minute ) , habitual PA by accelerometers , and dietary intake by a 4-day food diary . RESULTS Two patients in each group dropped out and were not included in the intention-to-treat analysis . In the remaining 92 patients ( EG = 47 and CG = 45 ) , at baseline , only a difference in the proportion of nitrate medication use was significant between groups . After 8 weeks , no significant changes were found between groups on traditional and nonlinear HRV indexes ( eg , ln HF , EG from 5.7 ± 1.5 to 5.9 ± 1.3 and CG from 5.5 ± 1.6 to 5.5 ± 1.5 ) , habitual PA , and dietary intake . CONCLUSION Eight weeks of exercise-based cardiac rehabilitation program is an insufficient stimulus to improve cardiac autonomic function in post-myocardial infa rct ion patients under optimal medication and with high levels of traditional and nonlinear HRV indexes at baseline Cardiopulmonary exercise training is beneficial to people with coronary artery disease ( CAD ) . Nevertheless , the correlation between aerobic capacity , and functional mobility and quality of life in elderly CAD patients is less addressed . The purpose of the current study is to investigate the beneficial effects of exercise training in elderly people with CAD , integrating exercise stress testing , functional mobility , h and grip strength , and health-related quality of life . Elderly people with CAD were enrolled from the outpatient clinic of a cardiac rehabilitation unit in a medical center . Participants were assigned to the exercise training group ( N = 21 ) or the usual care group ( N = 15 ) . A total of 36 sessions of exercise training , completed in 12 weeks , was prescribed . Echocardiography , exercise stress testing , the 6-minute walking test , Timed Up and Go test , and h and grip strength testing were performed , and the Short-Form 36 question naire ( SF-36 ) was administered at baseline and at 12-week follow-up . Peak oxygen consumption improved significantly after training . The heart rate recovery improved from 13.90/minute to 16.62/minute after exercise training . Functional mobility and h and grip strength also improved after training . Significant improvements were found in SF-36 physical function , social function , role limitation due to emotional problems , and mental health domains . A significant correlation between dynamic cardiopulmonary exercise testing parameters , the 6-minute walking test , Timed Up and Go test , h and grip strength , and SF-36 physical function and general health domains was also detected . Twelve-week , 36-session exercise training , including moderate-intensity cardiopulmonary exercise training , strengthening exercise , and balance training , is beneficial to elderly patients with CAD , and cardiopulmonary exercise testing parameters correlate well with balance and quality of life BACKGROUND The aim of this study was to verify the changes in the autonomic balance by means of heart rate variability assessment in patients with myocardial infa rct ion referred for cardiac rehabilitation . METHODS We studied 122 patients ( 79 males , 43 females , mean age 56 + /- 5 years ) , with a first uncomplicated myocardial infa rct ion ( anterior 48 , thrombolysis 72 ) , Killip class 1 , preserved left ventricular function ( ejection fraction 49 + /- 6 % ) . All patients were free of inducible residual ischemia . Four weeks after myocardial infa rct ion , patients were r and omized into two groups ; Group 1 ( n = 58 ) referred for an 8 week cardiac rehabilitation program ( scheduled : 24 sessions ) ; Group 2 ( n = 64 ) : normal daily physical activity . During a 24-hour Holter ECG monitoring the following parameters were calculated in pharmacological wash-out at r and omization ( T0 ) and at the end of cardiac rehabilitation/control period ( T1 ) : mean value of RR intervals ( RR ) , its st and ard deviation ( SDNN ) , pNN50 , rMSSD in the time domain ; low frequency ( LF ) and high frequency ( HF ) value and the LF/HF ratio in the frequency domain . T1-T0 changes in percent values ( delta % ) were considered and compared between the two groups . RESULTS Thirty-one patients were excluded from the study either for insufficient adhesion to the cardiac rehabilitation program ( < 13 sessions , 22 patients ) or recurrent ischemia ( 3 Group 1 patients and 3 Group 2 patients ) and non-assessable 24-hour Holter ECG monitoring ( 3 patients ) . Thirty-one Group 1 patients and 60 Group 2 patients completed the study with a first and a second 24-hour Holter ECG monitoring performed at 30 + /- 3 days and 60 + /- 4 days respectively . At the same time an ergospirometric test was performed to evaluate cardiopulmonary function by means of exercise time , maximum oxygen consumption , anaerobic threshold , exercise time at the anaerobic threshold , and maximum oxygen consumption at the anaerobic threshold . Twenty-eight Group 1 patients and 44 Group 2 patients completed the study with a first and a second ergospirometric test . Baseline heart rate variability parameters were comparable in the two groups . During the observation period only in Group 1 patients heart rate variability parameters changed significantly : RR ( Group 1 = + 18.3 + /- 21.3 ; Group 2 = + 4.2 + /- 5.2 , p = 0.000 ) , pNN50 ( Group 1 = 45.0 + /- 38.9 ; Group 2 = + 24.2 + /- 34.7 , p = 0.011 ) , HF ( Group 1 = + 81.6 + /- 124 ; Group 2 = -28.7 + /- 75.4 , p = 0.014 ) and LF/HF ratio ( Group 1 = -26.0 + /- 16.1 ; Group 2 = -4.9 + /- 6.1 , p = 0.062 ) . There were no significant differences in SDNN , rMSSD and LF . A linear correlation between delta LF/HF ratio and baseline LF/HF ratio values was found in Group 1 ( r = 0.489 , p = 0.006 ) , whereas no correlation was found between this parameter and age , ejection fraction , creatine phosphokinase , and infa rct localization . Group 1 patients had a significant improvement in exercise tolerance compared to Group 2 patients . CONCLUSIONS A cardiac rehabilitation program positively modifies the sympatho-vagal balance in patients with uncomplicated myocardial infa rct ion , increasing the parasympathetic tone and exercise tolerance BACKGROUND Experimental evidence suggests that autonomic markers such as heart-rate variability and baroreflex sensitivity ( BRS ) may contribute to postinfa rct ion risk stratification . There are clinical data to support this concept for heart-rate variability . The main objective of the ATRAMI study was to provide prospect i ve data on the additional and independent prognostic value for cardiac mortality of heart-rate variability and BRS in patients after myocardial infa rct ion in whom left-ventricular ejection fraction ( LVEF ) and ventricular arrhythmias were known . METHODS This multicentre international prospect i ve study enrolled 1284 patients with a recent ( < 28 days ) myocardial infa rct ion . 24 h Holter recording was done to quantify heart-rate variability ( measured as st and ard deviation of normal to normal RR intervals [ SDNN ] ) and ventricular arrhythmias . BRS was calculated from measurement of the rate-pressure response to intravenous phenylephrine . FINDINGS During 21 ( SD 8) months of follow-up , the primary endpoint , cardiac mortality , included 44 cardiac deaths and five non-fatal cardiac arrests . Low values of either heart-rate variability ( SDNN < 70 ms ) or BRS ( < 3.0 ms per mm Hg ) carried a significant multivariate risk of cardiac mortality ( 3.2 [ 95 % CI 1.42 - 7.36 ] and 2.8 [ 1.24 - 6.16 ] , respectively ) . The association of low SDNN and BRS further increased risk ; the 2-year mortality was 17 % when both were below the cut-offs and 2 % ( p<0.0001 ) when both were well preserved ( SDNN > 105 ms , BRS > 6.1 ms per mm Hg ) . The association of low SDNN or BRS with LVEF below 35 % carried a relative risk of 6.7 ( 3.1 - 14.6 ) or 8.7 ( 4.3 - 17.6 ) , respectively , compared with patients with LVEF above 35 % and less compromised SDNN ( > or = 70 ms ) and BRS ( > or = 3 ms per mm Hg ) . INTERPRETATION ATRAMI provides clinical evidence that after myocardial infa rct ion the analysis of vagal reflexes has significant prognostic value independently of LVEF and of ventricular arrhythmias and that it significantly adds to the prognostic value of heart-rate variability In medical research , continuous variables are often converted into categorical variables by grouping values into two or more categories . We consider in detail issues pertaining to creating just two groups , a common approach in clinical research . We argue that the simplicity achieved is gained at a cost ; dichotomization may create rather than avoid problems , notably a considerable loss of power and residual confounding . In addition , the use of a data -derived ' optimal ' cutpoint leads to serious bias . We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a r and omized trial in primary biliary cirrhosis . Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models OBJECTIVE To study the effects of 6 months exercise training on ventricular remodelling and autonomic tone in patients with acute myocardial infa rct ion and percutaneous coronary intervention . DESIGN Single-blinded r and omized control trial . PARTICIPANTS Sixty patients with acute myocardial infa rct ion who had undergone percutaneous coronary intervention . METHODS The exercise group followed a 6-month supervised exercise programme , while the control group received routine recommendations . All patients underwent an incremental cardiopulmonary exercise test and Doppler echocardiography at baseline and after 6 months . RESULTS Three patients in the exercise group did not complete the programme . At 6 months follow-up , an improvement was seen in the exercise group compared with the control group regarding peak VO2 ( p<0.01 ) , Powermax ( p<0.05 ) , VO2 at anaerobic threshold ( p<0.01 ) , time to reach anaerobic threshold ( p<0.05 ) , heart rate recovery ( p<0.01 ) , left ventricular end-diastolic diameter ( p<0.01 ) and left ventricular ejection fraction ( p<0.05 ) . CONCLUSION Six months exercise training in patients with acute myocardial infa rct ion and percutaneous coronary intervention with mild ventricular systolic dysfunction could prevent ventricular remodelling to a certain extent , and favourable modulating sympatho-vagal balance may be an important mechanism Objective . Coronary artery bypass grafting ( CABG ) is accompanied by severe impairment of cardiac autonomous regulation ( CAR ) . This study aim ed to determine whether a short-term physiotherapy exercise protocol post-CABG , during inpatient cardiac rehabilitation ( CR ) , might improve CAR . Design . Seventy-four patients eligible for CABG were recruited and r and omised into physiotherapy exercise group ( EG ) or physiotherapy usual care group ( UCG ) . EG patients underwent a short-term supervised inpatient physiotherapy exercise protocol consisting of an early mobilisation with progressive exercises plus usual care ( respiratory exercises ) . UCG only received respiratory exercises . Forty-seven patients ( 24 EG and 23 UGC ) completed the study . Outcome measures of CAR included linear and non-linear measures of heart rate variability ( HRV ) assessed before discharge . Results . By hospital discharge , EG presented significantly higher parasympathetic HRV values [ rMSSD , high frequency ( HF ) , SD1 ) ] , global power ( STD RR , SD2 ) , non-linear HRV indexes [ detrended fluctuation analysis (DFA)α1 , DFAα2 , approximate entropy ( ApEn ) ] and mean RR compared to UCG ( p < 0.05 ) . Conversely , higher values of mean HR , low frequency ( LF ) ( sympathetic activity ) and the LF/HF ( global sympatho-vagal balance ) were found in the UCG . Conclusions . A short-term supervised physiotherapy exercise protocol during inpatient CR improves CAR at the time of discharge . Thus , exercise-based inpatient CR might be an effective non-pharmacological tool to improve autonomic cardiac tone in patient 's post-CABG Exercise training elicits an improvement in work capacity and in left-ventricular function in patients with coronary artery disease . An improvement in myocardial oxygen supply accounts for these effects . The aim of this study was to test the hypothesis that exercise training could favorably influence diastolic perfusion time , a major determinant of subendocardial perfusion . Twenty-two male patients with coronary artery disease were r and omized to a training or control group . At the study entry and after one year , all patients underwent an exercise stress test . After one year , rest heart rate was lower and diastolic perfusion time was higher in the training group but not in the control group . At peak of exercise , diastolic perfusion time increased and ST-segment depression decreased significantly in the training group but not in the control group . A significant relation was found between the R-R interval and the diastolic perfusion time either before or after training , with a difference in the intercepts of two regressions . Training shifted updown-line regression , effecting a higher value of diastolic perfusion time for a given value of heart rate . Thus , training increases diastolic perfusion time , independently from the effect on heart rate . This mechanism may contribute to the improvement of myocardial perfusion The effects of early physical training on heart rate variability and autonomic nerve activity in acute myocardial infa rct ion were studied in 20 patients ( men , mean age 57 + /- 11 years ) successfully treated by direct coronary angioplasty . Patients were r and omly divided into the physical training group ( training group : 10 patients ) and conventional rehabilitation group ( non-training group : 10 patients ) . Exercise tolerance ( VO2 peak and anaerobic threshold : AT ) , heart rate variability indices , serum levels of catecholamines , and 24-hour urinary excretion of catecholamines were measured on the 14th and 28th days . The conventional cardiac rehabilitation program was followed by each group , and the training group patients were also instructed to follow a training program using the bicycle ergometer ( 80 % AT , 10 min , 2 times a day ) for 2 weeks from the 15th day . Autonomic nerve activity was assessed by non-spectral ( 24-hour averaged normal RR intervals : mean NN , st and ard deviation of normal RR intervals over 24 hours : SDNN and st and ard deviation of the mean RR intervals for each 5 min periods over 24 hours : SDANN ) and spectral [ high frequency power ( HF ) 0.15 - 0.40 Hz ; represents parasympathetic activity , and the low/high frequency power ( L/H ratio ) ; represents sympathetic activity ] indices of heart rate variability . There were no cardiac events during physical training . Comparison of the 14th and 28th day in the training group showed that the VO2 peak and VO2 AT significantly increased , SDNN and SDANN significantly increased , HF ( 82.5 + /- 56.2 to 131.1 + /- 99.8 msec2 ) increased and the L/H ratio ( 3.9 + /- 2.2 to 2.6 + /- 1.3 ) decreased significantly during the night-time , and serum noradrenalin concentration ( 0.47 + /- 0.11 to 0.35 + /- 0.13 ng/ml ) and urinary noradrenalin excretion ( 195.6 + /- 130.7 to 139.6 + /- 73.3 micrograms/day ) significantly decreased . In contrast , the non-training group showed no significant changes . These results suggest early physical training may be safe and improves the autonomic nerve balance and exercise tolerance in patients with acute myocardial infa rct ion BACKGROUND The COPE-ICD ( Copenhagen Outpatient ProgrammE-implantable cardioverter defibrillator ) trial studied comprehensive cardiac rehabilitation for patients with ICDs . The purpose of this paper was to explore : ( 1 ) gender differences in self-rated health and quality of life ( QoL ) at hospital discharge after ICD implantation , ( 2 ) gender differences in effect of cardiac rehabilitation , and ( 3 ) predictors of effect of cardiac rehabilitation . METHODS Patients with first-time ICD implantation were r and omized to comprehensive cardiac rehabilitation versus usual care . Gender differences in self-rated health and QoL and effect of rehabilitation were tested using t-tests . Predictors of effect of rehabilitation were tested using logistic regression . RESULTS A total of 196 patients ( mean age 58 ± 13 years ; 155 men , 41 women ) were included . At hospital discharge , significant differences were found in physical component scale , mental component scale , social functioning , physical functioning , bodily pain , vitality , mental health , and QoL with men having higher scores . Among men only , significant differences were found in VO2 ( rehabilitation : 20.9 mL/min/kg [ st and ard deviation ( SD ) 8.1 ] vs 23.4 mL/min/kg [ SD 9.5 ] and usual care : 22.1 mL/min/kg [ SD 8.1 ] vs 21.8 mL/min/kg [ SD 8.3 ] , P = 0.01 ) , total exercise time ( rehabilitation : 587.0 seconds [ SD 249.6 ] vs 650.7 seconds [ SD 279.8 ] and usual care : 613.8 seconds [ SD 264.7 ] vs 606.1 seconds [ SD 277.3 ] , P = 0.01 ) , and the mental component scale ( rehabilitation : 47.7 points [ SD 10.1 ] vs 54.8 points [ 7.1 ] and usual care : 48.1 points [ SD 10.9 ] vs 51.9 points [ SD 9.6 ] , P = 0.05 ) . CONCLUSIONS After ICD implantation , significant gender differences were found in physical health , mental health , and QoL. Effects of rehabilitation were found among men only and gender predicted effect of rehabilitation on the mental component scale Autonomic dysfunction , including baroreceptor attenuation and sympathetic activation , has been reported in patients with myocardial infa rct ion ( MI ) and has been associated with increased mortality . We tested the hypotheses that exercise training ( ET ) in post-MI patients would normalize arterial baroreflex sensitivity ( BRS ) and muscle sympathetic nerve activity ( MSNA ) , and long-term ET would maintain the benefits in BRS and MSNA . Twenty-eight patients after 1 month of uncomplicated MI were r and omly assigned to 2 groups , ET ( MI-ET ) and untrained . A normal control group was also studied . ET consisted of three 60-minute exercise sessions per week for 6 months . We evaluated MSNA ( microneurography ) , blood pressure ( automatic oscillometric method ) , heart rate ( ECG ) , and spectral analysis of RR interval , systolic arterial pressure ( SAP ) , and MSNA . Baroreflex gain of SAP-RR interval and SAP-MSNA were calculated using the & agr;-index . At 3 to 5 days and 1 month after MI , MSNA and low-frequency SAP were significantly higher and BRS significantly lower in MI patients when compared with the normal control group . ET significantly decreased MSNA ( bursts per 100 heartbeats ) and the low-frequency component of SAP and significantly increased the low-frequency component of MSNA and BRS of the RR interval and MSNA . These changes were so marked that the differences between patients with MI and the normal control group were no longer observed after ET . MSNA and BRS in the MI-untrained group did not change from baseline over the same time period . ET normalizes BRS , low-frequency SAP , and MSNA in patients with MI . These improvements in autonomic control are maintained by long-term ET . These findings highlight the clinical importance of this nonpharmacological therapy based on ET in the long-term treatment of patients with MI Signs of sympathetic hyperactivity and low parasympathetic activity have been found during the acute and recovery phases of myocardial infa rct ion and have been associated with an increased risk of cardiac mortality . Beneficial effects of physical training have been recently reported in post-myocardial infa rct ion patients . We tested the hypothesis that physical training would be effective in improving the autonomic balance by study ing 22 patients with a first and recent myocardial infa rct ion who were r and omly assigned to enter or not enter a 4-week in-hospital physical training program . Spectral indices of heart rate variability were analyzed at rest and during 70 degrees head-up tilt before and after the index training , not training period . As expected , physical training induced a significant increase in exercise duration ( 13.7 + /- 0.8 vs 17.1 + /- 0.1 min , p less than 0.001 ) and in the anaerobic threshold ( 9.5 + /- 0.7 vs 12.0 + /- 1.0 min , p less than 0.02 ) in trained patients , while no changes were observed in the untrained group . At entry , in both groups , spectral profile of heart rate variability was characterized by a predominant LF component and a smaller HF component with no further modification after head-up tilt . After 4 weeks , in resting conditions , no significant changes in spectral components were observed in both trained and untrained patients . After physical training , head-up tilt produced significant modifications in spectral profile with an increase in the LF component ( 84 + /- 3 vs 69 + /- 5 nu , p less than 0.01 ) and a decrease in the HF component ( 7 + /- 1 vs 19 + /- 4 nu , p less than 0.05 ) in trained patients , while no changes were observed in the untrained patients . Our data suggest that in postmyocardial infa rct ion patients , 4 weeks of physical training may induce an improvement in the autonomic balance with a restoration toward normal in the reflex activity of the system BACKGROUND Heart rate recovery ( HRR ) , defined as the fall in HR during the first minute after exercise , is a marker of vagal tone , which is a powerful predictor of mortality in patients with coronary artery disease and in older patients . Whether exercise training ( ET ) modifies HRR in elderly patients recovering from acute myocardial infa rct ion ( AMI ) is still unknown . Therefore , this study aims at evaluating the effect of ET on HRR in elderly AMI patients . METHODS This was a prospect i ve observational study including 268 older patients after AMI ( 217 men , 51 women ) , subdivided in two groups : Group A ( n = 104 ) , enrolled in an ET program ; Group B ( n = 164 ) , discharged with generic instructions to continue physical activity . At baseline and at 3-month follow-up , all Group A and 54/164 Group B patients underwent a cardiopulmonary exercise stress test , whereas 110/164 Group B patients underwent an exercise stress test . RESULTS After completion of the ET program , in Group A we observed an improvement in oxygen consumption at peak exercise ( VO2peak ; from 14.7 + /- 1.3 to 17.6 + /- 1.9 mL/kg/min , p < .001 ) , in the rate of increase of ventilation per unit of increase of carbon dioxide production ( VE/VCO2slope ; from 34.2 + /- 3.8 to 30.4 + /- 3.0 , p < .001 ) , and in HRR ( from 13.5 + /- 3.7 to 18.7 + /- 3.5 beats/min , p < .001 ) . The changes in VO2peak and in VE/VCO2slope after ET were correlated with the improvement of HRR ( r = -0.865 , p < .01 ; r = -0.594 , p < .01 , respectively ) . No changes in these parameters were observed in Group B patients . CONCLUSIONS In older AMI patients , ET results in HRR improvement , which was correlated to the improvement in cardiopulmonary parameters . These findings may shed additional light on the possible mechanisms of the beneficial prognostic effects of ET in this patient population Aims : To determine whether a home-based exercise program is able to increase functional capacity ( FC ) and reduce heart rate variability ( HRV ) in postmenopausal women with coronary heart disease . Background : Regular exercise training has been shown to improve both FC and HRV . However , those studies were conducted within institutional training programs , and few have included women . Methods : Thirty-two postmenopausal women were r and omly assigned to either an experimental or control group with 16 participants in each group . Those in the experimental group underwent home-based exercise training , 3 times a week for 8 weeks . On the first and final week , each participant 's HRV was measured , and their FC was evaluated using a 6-minute walking test . Findings : After 8 weeks , the FC of those who had undergone the home-based exercise program showed a significant improvement compared with subjects in the control group ( P = .001 ) . The total power ( ms2 ) , high-frequency ( ms2 ) , and low-frequency ( ms2 ) indexes of HRV were also significantly improved over control values . Conclusion : In postmenopausal women with coronary heart disease , a home-based exercise program appears able to improve FC and HRV CONTEXT Both attenuated heart rate recovery following exercise and the Duke treadmill exercise score have been demonstrated to be independent predictors of mortality , but their prognostic value relative to each other has not been studied . OBJECTIVE To assess the associations among abnormal heart rate recovery , treadmill exercise score , and death in patients referred specifically for exercise electrocardiography . DESIGN AND SETTING Prospect i ve cohort study conducted in an academic medical center between September 1990 and December 1997 , with a median follow-up of 5.2 years . PATIENTS A total of 9454 consecutive patients ( mean [ SD ] age , 53 [ 11 ] years ; 78 % male ) who underwent symptom-limited exercise electrocardiographic testing . Exclusion criteria included age younger than 30 years , history of heart failure or valvular disease , pacemaker implantation , and uninterpretable electrocardiograms . MAIN OUTCOME MEASURES All-cause mortality , as predicted by abnormal heart rate recovery , defined as failure of heart rate to decrease by more than 12/min during the first minute after peak exercise , and by treadmill exercise score , defined as ( exercise time ) - ( 5 x maximum ST-segment deviation ) - ( 4 x treadmill angina index ) . RESULTS Three hundred twelve deaths occurred in the cohort . Abnormal heart rate recovery and intermediate- or high-risk treadmill exercise score were present in 20 % ( n = 1852 ) and 21 % ( n = 1996 ) of patients , respectively . In univariate analyses , death was predicted by both abnormal heart rate recovery ( 8 % vs 2 % in patients with normal heart rate recovery ; hazard ratio [ HR ] , 4.16 ; 95 % confidence interval [ CI ] , 3.33 - 5.19 ; chi(2 ) = 158 ; P<.001 ) and intermediate- or high-risk treadmill exercise score ( 8 % vs 2 % in patients with low-risk scores ; HR , 4.28 ; 95 % CI , 3.43 - 5.35 ; chi(2 ) = 164 ; P<.001 ) . After adjusting for age , sex , st and ard cardiovascular risk factors , medication use , and other potential confounders , abnormal heart rate recovery remained predictive of death ( among the 8549 patients not taking beta-blockers , adjusted HR , 2.13 ; 95 % CI , 1.63 - 2.78 ; P<.001 ) , as did intermediate- or high-risk treadmill exercise score ( adjusted HR , 1 . 49 ; 95 % CI , 1.15 - 1.92 ; P = .002 ) . There was no interaction between these 2 predictors . CONCLUSIONS In this cohort of patients referred specifically for exercise electrocardiography , both abnormal heart rate recovery and treadmill exercise score were independent predictors of mortality . Heart rate recovery appears to provide additional prognostic information to the established treadmill exercise score and should be considered for routine incorporation into exercise test interpretation . JAMA . 2000;284:1392 - 1398 METHODS Twenty patients with uncomplicated myocardial infa rct ion r and omized in two groups ( group 1 and 2 ) of ten patients were investigated . Only group 1 trained four months according to a protocol of rehabilitation , whereas patients of group 2 followed their usual activity ( control group ) . The autonomic cardiovascular function was estimated by Ewing 's tests , that evaluate the variations of heart rate and blood pressure during deep breathing . RESULTS Our data showed an increase of parasympathetic tone in group 1 ( Valsalva ratio 1.55 + /- 0.28 vs 1.36 + /- 0.28 , p < 0.01 ; variation in heart rate during deep breathing 17.3 + /- 4.6 vs 13.3 + /- 4.2 ) . The sympathetic activity tests showed no significant difference after training . On the other h and , group 2 showed no significant difference in sympathetic and parasympathetic activity . CONCLUSIONS In patients with uncomplicated myocardial infa rct ion physical training increases the parasympathetic activity ; as shown in the literature , such an increase can have clinical and prognostic importance , since improves cardiac performance and reduces the risk of sudden death from arrhythmic events OBJECTIVES This study sought to determine whether a moderate intensity supervised exercise training program , performed immediately after an uncomplicated acute myocardial infa rct ion , improves recovery in cardiac autonomic function compared with st and ard advice about activity at home . BACKGROUND Exercise training has beneficial effects on cardiac autonomic function and may improve prognosis after acute myocardial infa rct ion . METHODS Thirty-nine male and 10 female patients , mean ( + /-SE ) age 57 + /- 1 years , with an uncomplicated acute myocardial infa rct ion were r and omized to either a 6-week moderate intensity supervised hospital-based exercise training program ( exercise group ) or to an unsupervised low intensity home walking program ( control group ) . Outcome measures included changes in baroreflex sensitivity ( phenylephrine bolus method ) and heart rate variability ( 24-h Holter monitoring ) and the endurance time at 85 % of peak oxygen consumption . RESULTS At baseline , there were no significant differences in left ventricular ejection fraction ( 57 + /- 2 % vs. 53 + /- 2 % ) , frequency of anterior infa rct ion ( 27 % vs. 18 % ) and peak creatine kinase ( 1,256 + /- 170 vs. 2,599 + /- 295 IU ) between the exercise and control groups . Baroreflex sensitivity ( 10.5 + /- 1.0 vs. 8.4 + /- 1.2 ms/mm Hg ) and time domain measures of heart rate variability were also similar . After completion of the program , the exercise group exercised for a median of 15 min ( interquartile range 12 to 25 ) at a workload of 104 + /- 7 W compared with 7 min ( interquartile range 3.5 to 12 ) at a workload of 89 + /- 8 W in the control group ( p < 0.01 ) . There were significant ( p < 0.001 ) improvements in baroreflex sensitivity and heart rate variability for the 49 patients combined but no differences between the exercise and control groups . Baroreflex sensitivity improved by 3.4 + /- 1.0 and 1.7 + /- 1.0 ms/mm Hg and the st and ard deviation of 24-h RR intervals by 36 + /- 6 and 40 + /- 10 ms , respectively ( p > 0.1 ) . CONCLUSIONS A hospital-based exercise training program increased endurance capacity but did not improve recovery of cardiovascular antonomic function after uncomplicated acute myocardial infa rct ion This study investigated the effects of aerobic exercise training on the early phase of the recovery process following acute myocardial infa rct ion ( AMI ) in terms of the autonomic nervous system , cardiac function and exercise capacity . Twenty-eight patients in the first week after the onset of AMI were assigned r and omly to either a training group or a control group . The training group performed aerobic exercise for 2 weeks . Cardiopulmonary exercise testing was performed 3 times during the 3 months after the onset . Heart rate variability , plasma norepinephrine ( NE ) levels , and cardiac index ( CI ) during exercise were measured . In the training group , plasma NE level and deltaCI ( peak CI-rest CI ) were significantly improved from 1 to 3 weeks after the onset , and the high frequency of heart rate variability and peak oxygen uptake were significantly increased up to 3 months after the onset . In the control group , the plasma NE level and the deltaCI during the 1 - 3 weeks post-AMI , the high frequency of heart rate variability and the peak oxygen uptake showed a tendency to improve up to 3 months after the onset . These results indicate that sympathetic nervous activity improves soon after the onset of AMI , in conjunction with improvement in cardiac function , and that this improvement is not affected by exercise training . In contrast , the recovery of parasympathetic nervous activity requires a longer period , along with the recovery of exercise capacity , which is facilitated by even short-term aerobic exercise training BACKGROUND Resistance exercise ( RE ) is an important part of cardiac rehabilitation . However , it is not known about the low intensity of RE training that could modify the heart rate variability ( HRV ) , muscular strength and endurance in patients with coronary artery disease ( CAD ) . AIM To investigate the effects of high repetition/low load resistance training ( HR/LL-RT ) program on HRV and muscular strength and endurance in CAD patients . DESIGN R and omized and controlled trial . SETTING Patients seen at the Cardiopulmonary Physical Therapy Laboratory between May 2011 and November 2013 . POPULATION Twenty male patients with CAD were r and omized to a training group ( 61.3±5.2 years ) or control group ( 61±4.4 years ) . METHODS 1 repetition maximum ( 1-RM ) maneuver , discontinuous exercise test on the leg press ( DET-L ) , and resting HRV were performed before and after 8 weeks of HR/LL-RT on a 45 ° leg press . RMSSD , SD1 , mean HR and ApEn indices were calculated . The HR/LL-RT program consisted of a lower limb exercise using a 45 ° leg press ; 3 sets of 20 repetitions , two times a week . The initial load was set at 30 % of the 1-RM load and the duration of the HR/LL-RT program was performed for 8 weeks . RESULTS After 8 weeks of HR/LL-RT there were significant increases of RMSSD and SD1 indices in the training group only ( P<0.05 ) . There was a significant decrease in mean HR after HR/LL-RT in the training group ( P<0.05 ) . There was a significantly higher ApEn after in the training group ( P<0.05 ) . There were significantly higher values in the training group in contrast to the control group ( P<0.05 ) . CONCLUSION These results show positive improvements on HRV , as well as muscle strength and endurance in CAD patients . CLINICAL REHABILITATION IMPACT Eight weeks of HR/LL-RT is an effective sufficient to beneficially modify important outcomes as HRV , muscle strength and endurance in CAD patients BACKGROUND Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability ( HRV ) toward parasympathetic dominance in patients after acute myocardial infa rct ion ( MI ) . However , its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown . We aim ed to investigate the effects of 8 weeks of supervised , high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population . METHODS AND RESULTS Twenty-five men with an acute MI and a low ejection fraction were r and omly assigned to enter or not to enter a training program in a regional rehabilitation center . HRV was evaluated before and after 1 and 2 months of training and at 12 months . Maximal exercise testing with respiratory gas exchange was performed at baseline and after training . Resting heart rate decreased ( P < . 01 ) and the percentage of R-R intervals differing > 50 ms from the preceding one ( pNN50 ) increased ( P < .05 ) after training . The st and ard deviation of R-R intervals ( SDRR ) tended to increase , but frequency-domain indexes remained unchanged . There was a significant decrease in SDRR ( P < .05 ) and high-frequency power ( P < .01 ) at 12 months in untrained patients . Exercise time increased by 38 % and maximal oxygen uptake increased by 29 % in the training group ( P < . 01 ) . CONCLUSIONS Despite beneficial effects on clinical variables , exercise training did not markedly alter HRV indexes . A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction OBJECTIVE Impairment of the baroreceptor reflex activity reflects an alteration of the autonomous regulation of the cardiovascular system and has proven to predict fatal outcome in patients after acute myocardial infa rct ion . The following study was performed to analyse the baroreceptor sensitivity , heart rate variability and blood pressure variability in patients early after coronary surgery . METHODS Twenty-five male patients undergoing coronary artery bypass were examined in a prospect i ve study ; normal values were obtained from healthy volunteers . Arterial pressure signals were recorded from a radial artery catheter for 30 min preoperatively and in short intervals after surgery . Mechanical manipulations and pharmacological interventions were avoided during the sampling periods . Baroreflex function was calculated according to the dual sequence method , heart rate variability and blood pressure variability were calculated including nonlinear methods . RESULTS Initial values of the patients did not differ from healthy volunteers . The strength of baroreflex sensitivity ( increase in blood pressure causing a synchronous decrease of heart rate ) is low 2 h postoperatively . The number of delayed tachycardic changes of heart rate , which are caused by sympathetic activation , is only moderately reduced as compared to values obtained from healthy volunteers . Heart rate variability is widely unchanged as compared to preoperative values ; blood pressure variability showed an increase of low-frequency components , again indicating sympathetic predominance . Nonlinear analyses revealed reduced system complexity at the beginning of the postoperative course . CONCLUSION Obviously , there is a vagal suppression 20 h after surgery , while the sympathetic tonus works in a normal range . This unbalanced interaction of the autonomous systems is similar to findings in patients after myocardial infa rct ion . The predictive value of these markers has to be eluci date d in further clinical studies BACKGROUND Exercise-based cardiac rehabilitation increases peak oxygen uptake ( peak VO₂ ) , which is an important predictor of mortality in cardiac patients . However , it remains unclear which exercise characteristics are most effective for improving peak VO₂ in coronary artery disease ( CAD ) patients . Proof of concept papers comparing Aerobic Interval Training ( AIT ) and Moderate Continuous Training ( MCT ) were conducted in small sample sizes and findings were inconsistent and heterogeneous . Therefore , we aim ed to compare the effects of AIT and Aerobic Continuous Training ( ACT ) on peak VO₂ , peripheral endothelial function , cardiovascular risk factors , quality of life and safety , in a large multicentre study . METHODS Two-hundred CAD patients ( LVEF > 40 % , 90 % men , mean age 58.4 ± 9.1 years ) were r and omized to a supervised 12-week cardiac rehabilitation programme of three weekly sessions of either AIT ( 90 - 95 % of peak heart rate ( HR ) ) or ACT ( 70 - 75 % of peak HR ) on a bicycle . Primary outcome was peak VO₂ ; secondary outcomes were peripheral endothelial function , cardiovascular risk factors , quality of life and safety . RESULTS Peak VO₂ ( ml/kg/min ) increased significantly in both groups ( AIT 22.7 ± 17.6 % versus ACT 20.3 ± 15.3 % ; p-time<0.001 ) . In addition , flow-mediated dilation ( AIT+34.1 % ( range -69.8 to 646 % ) versus ACT+7.14 % ( range -66.7 to 503 % ) ; p-time<0.001 ) quality of life and some other cardiovascular risk factors including resting diastolic blood pressure and HDL-C improved significantly after training . Improvements were equal for both training interventions . CONCLUSIONS Contrary to earlier smaller trials , we observed similar improvements in exercise capacity and peripheral endothelial function following AIT and ACT in a large population of CAD patients Background : Heart rate recovery ( HRR ) after exercise cessation is thought to reflect the rate of reestablishment of parasympathetic tone . Relatively little research has focused on improved HRR in women after completing cardiac rehabilitation ( CR ) exercise training . Objective : We examined the influence of exercise training on HRR in women completing a traditional CR program and in women completing a CR program tailored for women . Methods : A 2-group r and omized clinical trial compared HRR between 99 women completing a traditional 12-week CR program and 137 women completing a tailored CR program . Immediately upon completion of a symptom-limited grade d exercise test , HRR was measured at 1 through 6 minutes . Results : Compared with baseline , improvement in 1-minute HRR ( HRR1 ) was similar ( P = 0.777 ) between the tailored ( mean [ SD ] , 17.5 [ 11 ] to 19.1 [ 12 ] ) and the traditional CR program ( 15.7 [ 9.0 ] to 16.9 [ 9.5 ] ) . The amount of change in the 2-minute HRR ( HRR2 ) for the tailored ( 30 [ 13 ] to 32.8 [ 14.6 ] ) and traditional programs ( 28.3 [ 12.8 ] to 31.2 [ 13.7 ] ) also was not different ( P = 0.391 ) . Similar results were observed for HRR at 3 through 6 minutes . Given these comparable improvements of the 2 programs , in the full cohort , the factors independently predictive of post-CR HRR1 , in rank order , were baseline HRR1 ( part correlation , 0.35 ; P < 0.001 ) ; peak exercise capacity , estimated as metabolic equivalents ( METs ; 0.24 , P < 0.001 ) ; anxiety ( −0.17 , P = 0.001 ) ; and age ( −0.13 , P = 0.016 ) . The factors independently associated with post-CR HRR2 were baseline HRR2 ( 0.44 , P < 0.001 ) , peak METs ( 0.21 , P < 0.001 ) , and insulin use ( −0.10 , P = 0.041 ) . Conclusions : One to 6 minutes after exercise cessation , HRR was significantly improved among the women completing both CR programs . The modifiable factors positively associated with HRR1 included peak METs and lower anxiety , whereas HRR2 was associated with insulin administration and peak METs . Additional research on HRR after exercise training in women is warranted Objective : Heart rate recovery ( HRR ) is a recognised marker used in clinical practice for assessing the risk of sudden cardiac death . Physical exercise leads to an improvement in HRR and has a proven beneficial effect on erection quality ( EQ ) related to the activity of the autonomic nervous system in men with ischaemic heart disease ( IHD ) . This paper evaluates the relationship between HRR and EQ in patients with IHD and erectile dysfunction ( ED ) who underwent cardiac rehabilitation . Methods : The main analysis was based on the Mann – Whitney U test , Wilcoxon signed-rank test , Spearman correlation coefficient , Pearson ’s chi-square test , chi-square test , with the Yates correction and ( if possible ) parametric tests were used . This prospect i ve , non-r and omised intervention study included 124 men with IHD and ED [ International Index of Erectile Function ( IIEF-5 ) scores of ≤21 ] . Of these , 89 patients underwent a 6-month cardiac rehabilitation phase III programme , whereas 35 did not . The results of the participants ’ total IIEF-5 scores and their HRR , demographic and clinical data were analysed . Results : The results of the 89 rehabilitated patients ( mean age : 60.44±9.29 years ) and 35 controls ( mean age : 61.43±8.81 years ) were analysed . In the rehabilitated patients , the mean baseline IIEF-5 score was 13.15±5.76 ( 95 % CI : 11.93–14.36 ) and HRR was 16.49±7.68/min ( 95 % CI : 14.88–18.11 ) . After cardiac rehabilitation , the parameters of ED and HRR improved significantly and were significantly higher than those of the controls ; the mean IIEF-5 score of the rehabilitated group increased to 15.36±6.51 ( 95 % CI : 13.99–16.73 ) , while HRR increased to 21.40±7.25/min ( 95 % CI : 19.88–22.93 ) . A significant correlation was found between ∆HRR and ∆EQ ( r=0.409791 ) as a result of the 6-month cardiac training programme Conclusion : Cardiac rehabilitation assessed by HRR has a sizable effect on autonomic balance in patients with IHD and ED , which plays a significant role in the mechanism of erection improvement |
10,925 | 11,699,981 | There is good evidence that sealants can be used efficaciously and effectively in high-risk children as long as the sealant is retained .
Sealants are more effective in preventing further caries and providing cost savings in a shorter time span if placed in children who have high rather than low caries risk | This paper examines the evidence demonstrating the effectiveness of sealants in high-caries-risk children and discusses the Research Triangle Institute/University of North Carolina 's ( RTI/UNC ) systematic review . | Results are reported of a double-blind trial to assess the accuracy with which three examiners identified an opaque and a clear fissure sealant . The combined identification error rate for opaque resin was only 1.4 % , whilst for clear resin it was 22.8 % . The difference was highly significant ( P less than 0.0001 ) . Significant differences were also found in the accuracy with which the three dentists identified each type of resin . The most common error was to identify the presence of clear resin on an untreated PURPOSE To evaluate the clinical performance of Helioseal-F , a fluoride-containing fissure sealant , in school children at caries risk . MATERIAL S AND METHODS A caries risk assessment based on past caries experience , saliva microbial tests , buffer capacity and frequency of sugar intake was carried out in 204 healthy children , 6 - 7 years of age . Children exhibiting one or more risk factors were considered at caries risk ( n = 121 ) and their permanent molars were sealed with a fluoride-containing fissure sealant , thus forming a fissure sealant group ( FSG ) . The remaining 83 children with low caries risk received no fissure sealants and constituted a reference group ( RG ) . Both groups were followed for 2 years . From 15 children of both groups , unstimulated whole saliva was collected 1 month after sealant placement in order to determine fluoride levels . In another 20 children , a split-mouth study design was utilized to compare the colonization of mutans streptococci adjacent to and on F-containing sealants and conventional controls . The sealants were placed by dental hygienists according to the manufacturers ' instructions . RESULTS A total of 431 fissure sealants were placed at baseline . Complete retention was found in 76.6 % during the study period while 22.0 % were partially lost . Six sealants ( 1.4 % ) were completely lost . The enamel caries incidence was 45 % lower ( P < 0.05 ) in the permanent molars of the caries risk FSG compared with the low risk RG . There was no significant increase in saliva fluoride concentration following placement of the sealants and the proportion of mutans streptococci in relation to total viable counts was unaffected by type of material . The levels of salivary mutans streptococci were mainly unchanged in both groups during the study period , while the levels of salivary lactobacilli decreased in the FSG PURPOSE The effect of sealants on S. mutans presence in situ was investigated . METHODS Four intact , fully erupted first permanent molars in each of 74 children , aged 6 - 8 years were required for inclusion in the study . Baseline examination included deft and plaque index . S. mutans presence on occlusal surfaces of the molars was evaluated , using a microbial replica method . Immediately after sealing the first permanent molars on one side , S. mutans presence in situ was re-evaluated , as well as three and six months thereafter . Three months after the initiation of the study , S. mutans presence was evaluated on the molars of the unsealed side , which were consequently sealed and re-evaluated immediately , and three months later . RESULTS Positive correlation was found between deft scores , plaque indices and microbial replica values , at baseline . Sealing caused a significant reduction in S. mutans levels on the treated occlusal surfaces , in vivo ( P < 0.001 ) , which lasted , in most cases , up to six months . CONCLUSIONS The data suggest that sealants enable a prolonged reduction of S. mutans presence in situ , indicating an additional prevention effect , by reducing one source of dissemination This study evaluated the outcome of a targeted dental sealant program by comparing the survival probabilities of sealed high-risk first molar tooth sites to unsealed low-risk tooth sites in 1,122 children enrolled in a school-based sealant program . A comparison of the survival probabilities between low-risk first molar teeth that did not receive sealants and the sealed high-risk first molar teeth did not show significant differences . The results suggest that the protocol used by the program provides a satisfactory method for identification of children who could best benefit from sealants in a school-based situation Recent in vitro work and a short clinical study suggest that adding a bonding agent layer between sealant and saliva-contaminated enamel allows for adequate bond strength and retention of resin sealants and may improve success of all sealant applications . This five-year clinical study scored 617 occlusal and 441 buccal/lingual molar sealants , with use of a split-mouth design , with half receiving sealant alone and half bonding agent plus sealant . Treatment effects and potential risk factors for sealant failure were tested by means of a Cox regression model . Three bonding agent groups were analyzed for treatment effect : Tenure primer , Scotchbond Multi- Purpose , and 3 single-bottle dentin bonding agents as a third group . The single-bottle group was successful in reducing risk of sealant failure , with a hazard ratio ( HR ) of 0.53 ( p = 0.014 ) for occlusal and 0.35 ( p = 0.006 ) for buccal/lingual sealants . Scotchbond was detrimental to occlusal sealant success , with a HR of 2.96 ( p = 0.0003 ) . Tenure primer was neutral , showing HRs close to 1.0 . Variables that affected success differed between occlusal and buccal/lingual sealants , suggesting that failures on these two surfaces may be dependent upon differing factors . Early eruption stage was a significant risk factor for both surfaces ( HR = 2.91 , p = 0.00001 , occlusal ; and HR = 1.52 , p = 0.015 , buccal/lingual ) . Behavior ( HR = 1.96 , p = 0.0007 ) , salivary problems ( HR = 1.73 , p = 0.002 ) , and visually apparent variations in enamel ( HR = 1.51 , p = 0.018 ) were significant risk factors for occlusal sealants only . In addition to completing detailed analyses of risk factors for sealant survival , this study shows that single-bottle bonding agents protect sealant survival , yielding half the usual risk of failure for occlusal sealants and one-third the risk of failure for buccal/lingual sealants Following a single application of a chemically polymerized fissure sealant ( Concise Enamel Bond System ) 60 % of the sealants were present after 2 years of examination . The effectiveness of the treatment was highly significant and the caries reduction , irrespective of the sealant status , was found to be about 50 % . The caries reduction was 98 % in sealed pairs where the material was fully retained The half-mouth technique was used to determine the treatment effect of an application of an ultraviolet-light-polymerized sealant . The side of the mouth to be treated with the sealant was r and omly selected . At the one-year examination , a statistically significant reduction in occlusal caries was found for teeth coated with the sealant . Practically no color change or marginal discoloration was evident and retention of the sealant was excellent |
10,926 | 27,237,747 | These results indicate that the WBV may improve the knee extension muscle strength .
However , the WBV does not show a meaningful improvement of functional mobility in MS patients | OBJECTIVES This review aim ed to confirm the effects of the whole body vibration ( WBV ) on muscle performance and functional mobility in multiple sclerosis ( MS ) patients . | OBJECTIVE To investigate the acute effects of long-term whole-body vibration on leg muscle performance and functional capacity in persons with multiple sclerosis . DESIGN A r and omized controlled trial . SUBJECTS Twenty-five patients with multiple sclerosis ( mean age 47.9 ± 1.9 years ; Exp and ed Disability Status Scale 4.3 ± 0.2 ) were assigned r and omly to whole-body vibration training ( n = 11 ) or to a control group ( n = 14 ) . METHODS The whole-body vibration group performed static and dynamic leg squats and lunges on a vibration platform ( 25 - 45 Hz , 2.5 mm amplitude ) during a 20-week training period ( 5 training sessions per 2-week cycle ) , and the control group maintained their usual lifestyle . PRE- , MID- ( 10 weeks ) and POST- ( 20 weeks ) knee-muscle maximal isometric and dynamic strength , strength endurance and speed of movement were measured using isokinetic dynamometry . Function was determined through the Berg Balance Scale , Timed Up and Go , Two-minute Walk Test and the Timed 25-Foot Walk Test . RESULTS Leg muscle performance and functional capacity were not altered following 10 or 20 weeks of whole-body vibration . CONCLUSION Under the conditions of the present study , the applied 20-week whole-body vibration exercise protocol did not improve leg muscle performance or functional capacity in mild- to moderately impaired persons with multiple sclerosis during and immediately after the training programme The effects of hard squatting exercise with ( VbX+ ) and without ( VbX− ) vibration on neuromuscular function were tested in 19 healthy young volunteers . Before and after the exercise , three different tests were performed : maximum serial jumping for 30 s , electromyography during isometric knee extension at 70 % of the maximum voluntary torque , and the quantitative analysis of the patellar tendon reflex . Between VbX+ and VbX− values , there was no difference found under baseline conditions . Time to exhaustion was significantly shorter in VbX+ than in VbX− ( 349 ± 338 s versus 515 ± 338 s ) , but blood lactate ( 5·49 ± 2·73 mmol l−1 versus 5·00 ± 2·26 mmol l−1 ) and subjectively perceived exertion ( rate of perceived exertion values 18·1 ± 1·2 versus 18·6 ± 1·6 ) at the termination of exercise indicate comparable levels of fatigue . After the exercise , comparable effects were observed on jump height , ground contact time , and isometric torque . The vastus lateralis mean frequency during isometric torque , however , was higher after VbX+ than after VbX−. Likewise , the tendon reflex amplitude was significantly greater after VbX+ than after VbX− ( 4·34 ± 3·63 Nm versus 1·68 ± 1·32 Nm ) . It is followed that in exercise unto comparable degrees of exhaustion and muscular fatigue , superimposed 26 Hz vibration appears to elicit an alteration in neuromuscular recruitment patterns , which apparently enhance neuromuscular excitability . Possibly , this effect may be exploited for the design of future training regimes Objective : To examine whether a whole-body vibration ( mechanical oscillations ) in comparison to a placebo administration leads to better postural control , mobility and balance in patients with multiple sclerosis . Design : Double-blind , r and omized controlled trial . Setting : Outpatient clinic of a university department of physical medicine and rehabilitation . Subjects : Twelve multiple sclerosis patients with moderate disability ( Kurtzke 's Exp and ed Disability Status Scale 2.5 - 5 ) were allocated either to the intervention group or to the placebo group . Interventions : In the intervention group a whole-body vibration at low frequency ( 2.0 - 4.4 Hz oscillations at 3-mm amplitude ) in five series of 1 min each with a 1-min break between the series was applied . In the placebo group a Burst-transcutaneous electrical nerve stimulation ( TENS ) application on the nondominant forearm in five series of 1 min each with a 1-min break between the series was applied as well . Main outcome measures : Posturographic assessment using the Sensory Organization Test , the Timed Get Up and Go Test and the Functional Reach Test immediately preceding the application , 15 min , one week and two weeks after the application . The statistical analysis was applied to the change score from preapplication values to values 15 min , one week and two weeks post intervention . Results : Compared with the placebo group the intervention group showed advantages in terms of the Sensory Organization Test and the Timed Get Up and Go Test at each time point of measurement after the application . The effects were strongest one week after the intervention , where significant differences for the change score ( p=0.041 ) were found for the Timed Get Up and Go Test with the mean score reducing from 9.2 s ( preapplication ) to 8.2 s one week after whole-body vibration and increasing from 9.5 s ( preapplication ) to 10.2 s one week after placebo application . The mean values of the posturographic assessment increased from 70.5 points ( preapplication ) to 77.5 points one week after whole body vibration and increased only from 67.2 points ( preapplication ) to 67.5 points one week after the placebo application . No differences were found for the Functional Reach Test . Conclusion : The results of this pilot study indicated that whole-body vibration may positively influence the postural control and mobility in multiple sclerosis patients PURPOSE The aim of this study was to investigate and to compare the effect of a 12-wk period of whole-body vibration training and resistance training on human knee-extensor strength . METHODS Sixty-seven untrained females ( 21.4 + /- 1.8 yr ) participated in the study . The whole-body vibration group ( WBV , N = 18 ) and the placebo group ( PL , N = 19 ) performed static and dynamic knee-extensor exercises on a vibration platform . The acceleration of the vibration platform was between 2.28 g and 5.09 g , whereas only 0.4 g for the PL condition . Vibration ( 35 - 40 Hz ) result ed in increased EMG activity , but the EMG signal remained unchanged in the PL condition . The resistance-training group ( RES , N = 18 ) trained knee extensors by dynamic leg-press and leg-extension exercises ( 10 - 20 RM ) . All training groups exercised 3x wk-1 . The control group ( CO , N = 12 ) did not participate in any training . Pre- and postisometric , dynamic , and ballistic knee-extensor strength were measured by means of a motor-driven dynamometer . Explosive strength was determined by means of a counter-movement jump . RESULTS Isometric and dynamic knee-extensor strength increased significantly ( P < 0.001 ) in both the WBV group ( 16.6 + /- 10.8 % ; 9.0 + /- 3.2 % ) and the RES group ( 14.4 + /- 5.3 % ; 7.0 + /- 6.2 % ) , respectively , whereas the PL and CO group showed no significant ( P > 0.05 ) increase . Counter-movement jump height enhanced significantly ( P < 0.001 ) in the WBV group ( 7.6 + /- 4.3 % ) only . There was no effect of any of the interventions on maximal speed of movement , as measured by means of ballistic tests . CONCLUSIONS WBV , and the reflexive muscle contraction it provokes , has the potential to induce strength gain in knee extensors of previously untrained females to the same extent as resistance training at moderate intensity . It was clearly shown that strength increases after WBV training are not attributable to a placebo effect The aim of this study was to investigate the effects of vibration exercise on postural steadiness performance in a healthy , older population . Forty-three healthy , older participants ( 23 men and 20 women , aged 73.5+/-4.5 yr ) were r and omly assigned to either a vibration group ( VIB ) , an exercise without vibration group ( EX ) or a control group ( CONT ) . The VIB and EX groups undertook static and dynamic bodyweight exercises three times per week for eight weeks . Static balance was assessed using a one-legged postural steadiness ( OLPS ) test . This test was performed prior to and immediately after the training period . OLPS improved significantly for the VIB intervention after eight weeks training ( p<0.05 ) compared to the EX and CONT groups . The improvements in OLPS were significantly affected by the baseline values , with the largest changes evident for VIB participants with a poorer initial score ( p<0.01 ) . Vibration exercise can contribute to improved static one-legged balance in a healthy , older population . As improvements in OLPS were related to baseline values , vibration exercise as an intervention would appear to serve the most benefit for those that exhibit diminished postural control OBJECTIVE To investigate the effects of whole body vibration ( WBV ) training on gait function in persons with mild multiple sclerosis ( MS ) . DESIGN A r and omized controlled trial . SUBJECTS 18 patients with MS were assigned r and omly to WBV ( intervention group ) or to placebo WBV . METHODS Both groups performed a 3-week training period under static conditions on a vibration platform . In the placebo group , the vibration platform was covered and therefore vibrations could not operate . Gait function ( gait velocity , stride length , double support phase , single-step variability left and right ) was assessed at baseline , after 3-weeks of WBV intervention or sham WBV , 4-weeks after baseline , and 5-weeks after baseline using a mobile plantar food pressure system and the " Timed Up and Go " test under four different gait conditions ( comfortable overground gait , comfortable gait on treadmill , -20 % comfortable gait velocity on treadmill and + 20 % comfortable gait velocity on treadmill ) . RESULTS None of the outcome measures of gait function showed statistically significant alterations following 3-weeks of intervention/placebo WBV . CONCLUSION The applied protocol of WBV does not show a meaningful improvement of gait function in mildly affected MS patients |
10,927 | 25,451,790 | Conclusion : This systematic review and meta- analysis of ACL and knee injury prevention program studies found a statistically significant reduction in injury risk for knee injuries but did not find a statistically significant reduction of ACL injuries | Background : Soccer has one of the highest incidences of anterior cruciate ligament ( ACL ) injuries for both males and females .
Several injury prevention programs have been developed to address this concern .
However , an analysis of the pooled effect has yet to be elicited .
Purpose : To conduct a systematic review and meta- analysis of ACL and knee injury prevention programs for soccer players , assess the heterogeneity among the studies , and evaluate the reported effectiveness of the prevention programs . | Objective To assess the effect of a neuromuscular training program on the incidence of anterior cruciate ligament injuries in female team h and ball players . Design Prospect i ve intervention study . Setting Female team h and ball : Division I – III in Norway . Participants Players from the three top divisions : control season ( 1998–1999 ) , 60 teams ( 942 players ) ; first intervention season ( 1999–2000 ) , 58 teams ( 855 players ) ; second intervention season ( 2000–2001 ) , 52 teams ( 850 players ) . InterventionA five-phase program ( duration , 15 min ) with three different balance exercises focusing on neuromuscular control and planting/l and ing skills was developed and introduced to the players in the autumn of 1999 and revised before the start of the season in 2000 . The teams were instructed in the program and supplied with an instructional video , poster , six balance mats , and six wobble boards . Additionally , a physical therapist was attached to each team to follow up with the intervention program during the second intervention period . Main Outcome Measures The number of anterior cruciate ligament injuries during the three seasons and compliance with the program . Results There were 29 anterior cruciate ligament injuries during the control season , 23 injuries during the first intervention season ( OR , 0.87 ; CI , 0.50–1.52 ; p = 0.62 ) , and 17 injuries during the second intervention season ( OR , 0.64 ; CI , 0.35–1.18 ; p = 0.15 ) . In the elite division , there were 13 injuries during the control season , six injuries during the first intervention season ( OR , 0.51 ; CI , 0.19–1.35 ; p = 0.17 ) , and five injuries in the second intervention season ( OR , 0.37 ; CI , 0.13–1.05 ; p = 0.06 ) . For the entire cohort , there was no difference in injury rates during the second intervention season between those who complied and those who did not comply ( OR , 0.52 ; CI , 0.15–1.82 ; p = 0.31 ) . In the elite division , the risk of injury was reduced among those who completed the anterior cruciate ligament injury prevention program ( OR , 0.06 ; CI , 0.01–0.54 ; p = 0.01 ) compared with those who did not . Conclusions This study shows that it is possible to prevent anterior cruciate ligament injuries with specific neuromuscular training Background This study was conducted to investigate whether the most common injuries in soccer could be prevented , and to determine if a simple question naire could identify players at increased risk . Hypothesis Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle , knee , hamstring , or groin will prevent injuries . Study Design R and omized controlled trial ; Level of evidence , 2 . Methods A total of 508 players representing 31 teams were included in the study . A question naire indicating previous injury and /or reduced function as inclusion criteria was used to divide the players into high-risk ( HR ) ( 76 % ) and low-risk ( LR ) groups . The HR players were r and omized individually into an HR intervention group or HR control group . Results A total of 505 injuries were reported , sustained by 56 % of the players . The total injury incidence was a mean of 3.2 ( 95 % confidence interval [ CI ] , 2.5–3.9 ) in the LR control group , 5.3 ( 95 % Cl , 4.6–6.0 ) in the HR control group ( P = .0001 vs the LR control group ) , and 4.9 ( 95 % Cl , 4.3–5.6 ) in the HR intervention group ( P = .50 vs the HR control group ) . For the main outcome measure , the sum of injuries to the ankle , knee , hamstring , and groin , there was also a significantly lower injury risk in the LR control group compared with the 2 other groups , but no difference between the HR intervention group and the HR control group . Compliance with the training programs in the HR intervention group was poor , with only 27.5 % in the ankle group , 29.2 % in the knee group , 21.1 % in the hamstring group , and 19.4 % in the groin defined as having carried out the minimum recommended training volume . Conclusion The players with a significantly increased risk of injury were able to be identified through the use of a question naire , but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected To study the efficacy of an injury prevention program in a r and omized trial , 12 teams ( 180 players ) in a male senior soccer division were followed up for 6 months . The 12 teams were allocated at r and om to two groups of six teams , one being given a prophylactic program and the other serving as control . The program was based on previous studies of injury mechanisms . It comprised ( 1 ) correction of training , ( 2 ) provision of optimum equipment ; ( 3 ) prophylactic ankle taping ; ( 4 ) controlled rehabilitation ; ( 5 ) exclusion of players with grave knee instability ; ( 6 ) information about the impor tance of disciplined play and the increased risk of injury at training camps ; and ( 7 ) correction and supervision by doctor(s ) and physiotherapist(s ) . The injuries in the test teams were 75 % fewer than in the controls . The most common types of soccer injuries , sprains and strains to ankles and knees , were all significantly reduced . It is concluded that the pro posed prophylactic program , including close supervi sion and correction by doctors and physiotherapists , significantly reduces soccer injuries Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group Background The incidence rate of soccer injuries is among the highest in sports , particularly for adult male soccer players . Purpose To investigate the effect of the ‘ The11 ’ injury prevention programme on injury incidence and injury severity in adult male amateur soccer players . Study design Cluster-r and omised controlled trial . Methods Teams from two high-level amateur soccer competitions were r and omly assigned to an intervention ( n=11 teams , 223 players ) or control group ( n=12 teams , 233 players ) . The intervention group was instructed to perform The11 in each practice session during one soccer season . The11 focuses on core stability , eccentric training of thigh muscles , proprioceptive training , dynamic stabilisation and plyometrics with straight leg alignment . All participants of the control group continued their practice sessions as usual . Results In total , 427 injuries were recorded , affecting 274 of 456 players ( 60.1 % ) . Compliance with the intervention programme was good ( team compliance=73 % , player compliance=71 % ) . Contrary to the hypothesis , injury incidences were almost equal between the two study groups : 9.6 per 1000 sports hours ( 8.4–11.0 ) for the intervention group and 9.7 ( 8.5–11.1 ) for the control group . No significant differences were found in injury severity , but a significant difference was observed in the location of the injuries : players in the intervention group sustained significantly less knee injuries . Conclusions This study did not find significant differences in the overall injury incidence or injury severity between the intervention and control group of adult male soccer players . More research is recommended , focusing on injury aetiology and risk factors in adult male amateur soccer players To prospect ively evaluate the effect of neuromuscular training on the incidence of knee injury in female athletes , we monitored two groups of female athletes , one trained before sports participation and the other not trained , and a group of untrained male athletes throughout the high school soccer , volleyball , and basketball seasons . Weekly reports included the number of practice and competition exposures and mechanism of injury . There were 14 serious knee injuries in the 1263 athletes tracked through the study . Ten of 463 untrained female athletes sustained serious knee injuries ( 8 noncontact ) , 2 of 366 trained female athletes sustained serious knee injuries ( 0 noncontact ) , and 2 of 434 male athletes sustained serious knee injuries ( 1 noncontact ) . The knee injury incidence per 1000 athlete-exposures was 0.43 in untrained female athletes , 0.12 in trained female athletes , and 0.09 in male athletes ( P 0.02 , chi-square analysis ) . Untrained female athletes had a 3.6 times higher incidence of knee injury than trained female athletes ( P 0.05 ) and 4.8 times higher than male athletes ( P 0.03 ) . The incidence of knee injury in trained female athletes was not significantly different from that in untrained male athletes ( P 0.86 ) . The difference in the incidence of noncontact injuries between the female groups was also significant ( P 0.01 ) . This prospect i ve study demonstrated a decreased incidence of knee injury in female athletes after a specific plyometric training program Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction Abstract Objective To investigate the effect of a structured warm-up programme design ed to reduce the incidence of knee and ankle injuries in young people participating in sports . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 120 team h and ball clubs from central and eastern Norway ( 61 clubs in the intervention group , 59 in the control group ) followed for one league season ( eight months ) . Participants 1837 players aged 15 - 17 years ; 958 players ( 808 female and 150 male ) in the intervention group ; 879 players ( 778 female and 101 male ) in the control group . Intervention A structured warm-up programme to improve running , cutting , and l and ing technique as well as neuromuscular control , balance , and strength . Main outcome measure The rate of acute injuries to the knee or ankle . Results During the season , 129 acute knee or ankle injuries occurred , 81 injuries in the control group ( 0.9 ( SE 0.09 ) injuries per 1000 player hours ; 0.3 ( SE 0.17 ) in training v 5.3 ( SE 0.06 ) during matches ) and 48 injuries in the intervention group ( 0.5 ( SE 0.11 ) injuries per 1000 player hours ; 0.2 ( SE 0.18 ) in training v 2.5 ( SE 0.06 ) during matches ) . Fewer injured players were in the intervention group than in the control group ( 46 ( 4.8 % ) v ( 76 ( 8.6 % ) ; relative risk intervention group v control group 0.53 , 95 % confidence interval 0.35 to 0.81 ) . Conclusion A structured programme of warm-up exercises can prevent knee and ankle injuries in young people playing sports . Preventive training should therefore be introduced as an integral part of youth sports programmes Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports . It can also improve rehabilitation after anterior cruciate ligament ( ACL ) injuries whether treated operatively or nonoperatively . Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability , it is essential to try to prevent them . In a prospect i ve controlled study of 600 soccer players in 40 semiprofessional or amateur teams , we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons . Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty . The first phase consisted of balance training without any balance board ; phase 2 of training on a rectangular balance board ; phase 3 of training on a round board ; phase 4 of training on a combined round and rectangular board ; phase 5 of training on a so-called BABS board . A control group of 300 players from other , comparable teams trained “ normally ” and received no special balance training . Both groups were observed for three whole soccer seasons , and possible ACL lesions were diagnosed by clinical examination , KT-1000 measurements , magnetic resonance imaging or computed tomography , and arthroscopy . We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group ( P<0.001 ) . Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players Background : Risk factors for soccer injuries and possibilities for prevention have been discussed by several authors , but only a few have investigated the effectiveness of preventive interventions . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of soccer injuries in male youth amateur players . Study Design : Prospect i ve controlled intervention study . Methods : Seven soccer teams took part in a prevention program that focused on education and supervision of coaches and players , while seven other teams were instructed to train and play soccer as usual . Over 1 year all injuries were documented weekly by physicians . Complete weekly injury reports were available for 194 players . Results : The incidence of injury per 1000 hours of training and playing soccer was 6.7 in the intervention group and 8.5 in the control group , which equates to 21 % fewer injuries in the intervention group . The greatest effects were observed for mild injuries , overuse injuries , and injuries incurred during training . The prevention program had greater effects in low-skill than in high-skill teams . Conclusions : The incidence of soccer injuries can be reduced by preventive interventions , especially in low skill level youth teams . Coaches and players need better education regarding injury prevention strategies and should include such interventions as part of their regular training A set of exercises -- the " 11"--have been selected to prevent football injuries . The purpose of this cluster-r and omized controlled trial was to investigate the effect of the " 11 " on injury risk in female youth football . Teams were r and omized to an intervention ( n=59 teams , 1091 players ) or a control group ( n=54 teams , 1001 players ) . The intervention group was taught the " 11 , " exercises for core stability , lower extremity strength , neuromuscular control and agility , to be used as a 15-min warm-up program for football training over an 8-month season . A total of 396 players ( 20 % ) sustained 483 injuries . No difference was observed in the overall injury rate between the intervention ( 3.6 injuries/1000 h , confidence interval ( CI ) 3.2 - 4.1 ) and control group ( 3.7 , CI 3.2 - 4.1 ; RR=1.0 , CI 0.8 - 1.2 ; P=0.94 ) nor in the incidence for any type of injury . During the first 4 months of the season , the training program was used during 60 % of the football training sessions , but only 14 out of 58 intervention teams completed more than 20 prevention training sessions . In conclusion , we observed no effect of the injury prevention program on the injury rate , most likely because the compliance with the program was low OBJECTIVE To determine the numbers needed to treat ( NNT ) and relative risk reduction ( RRR ) associated with neuromuscular training programs aim ed at preventing noncontact anterior cruciate ligament ( ACL ) injuries in female athletes . DATA SOURCES We search ed PubMed , MEDLINE , SPORT Discus , CINAHL , and Web of Science from 1966 through 2005 using the terms knee , injury , anterior cruciate ligament , ACL , prevention , plyometric , and neuromuscular training . STUDY SELECTION Selected articles were from peer- review ed journals written in English that described original research studies comparing neuromuscular training programs with control programs to determine the number of noncontact ACL injuries per event exposure or hours of playing time . Five studies met the inclusion criteria and were independently rated by 3 review ers using the Physiotherapy Evidence Data base ( PEDro ) scale . Consensus PEDro scores ranged from 4 to 7 out of 10 . DATA EXTRACTION We used numbers of subjects , ACL injuries , and injury exposure rates to calculate NNT and RRR for each study . The NNT calculations from all studies were based on the number of players across 1 competitive season and were described as NNT benefit or NNT harm . DATA SYNTHESIS All 5 studies demonstrated a prophylactic effect due to the neuromuscular training programs . The pooled NNT estimates showed that 89 individuals ( 95 % confidence interval : 66 to 136 ) would need to participate in the prophylactic training program to prevent 1 ACL injury over the course of 1 competitive season . Pooled RRR was 70 % ( 95 % confidence interval : 54 % to 80 % ) among individuals who participated in the intervention program . One high- quality r and omized control trial and 4 medium- quality prospect i ve cohort studies showed mostly consistent findings . Thus , a Strength of Recommendation Taxonomy level of evidence of 1 with a grade B recommendation supports the use of neuromuscular training programs in the prevention of noncontact ACL injuries in female athletes Background Neuromuscular and proprioceptive training programs can decrease noncontact anterior cruciate ligament injuries ; however , they may be difficult to implement within an entire team or the community at large . Hypothesis A simple on-field alternative warm-up program can reduce noncontact ACL injuries . Study Design R and omized controlled trial ( clustered ) ; Level of evidence , 1 . Methods Participating National Collegiate Athletic Association Division I women 's soccer teams were assigned r and omly to intervention or control groups . Intervention teams were asked to perform the program 3 times per week during the fall 2002 season . All teams reported athletes ’ participation in games and practice s and any knee injuries . Injury rates were calculated based on athlete exposures , expressed as rate per 1000 athlete exposures . A z statistic was used for rate ratio comparisons . Results Sixty-one teams with 1435 athletes completed the study ( 852 control athletes ; 583 intervention ) . The overall anterior cruciate ligament injury rate among intervention athletes was 1.7 times less than in control athletes ( 0.199 vs 0.340 ; P = .198 ; 41 % decrease ) . Noncontact anterior cruciate ligament injury rate among intervention athletes was 3.3 times less than in control athletes ( 0.057 vs 0.189 ; P = .066 ; 70 % decrease ) . No anterior cruciate ligament injuries occurred among intervention athletes during practice versus 6 among control athletes ( P = .014 ) . Game-related noncontact anterior cruciate ligament injury rates in intervention athletes were reduced by more than half ( 0.233 vs 0.564 ; P = .218 ) . Intervention athletes with a history of anterior cruciate ligament injury were significantly less likely to suffer another anterior cruciate ligament injury compared with control athletes with a similar history ( P = .046 for noncontact injuries ) . Conclusion This program , which focuses on neuromuscular control , appears to reduce the risk of anterior cruciate ligament injuries in collegiate female soccer players , especially those with a history of anterior cruciate ligament injury Subgroup analyses can pose serious multiplicity concerns . By testing enough subgroups , a false-positive result will probably emerge by chance alone . Investigators might undertake many analyses but only report the significant effects , distorting the medical literature . In general , we discourage subgroup analyses . However , if they are necessary , research ers should do statistical tests of interaction , rather than analyse every separate subgroup . Investigators can not avoid interim analyses when data monitoring is indicated . However , repeatedly testing at every interim raises multiplicity concerns , and not accounting for multiplicity escalates the false-positive error . Statistical stopping methods must be used . The O'Brien-Fleming and Peto group sequential stopping methods are easily implemented and preserve the intended alpha level and power . Both adopt stringent criteria ( low nominal p values ) during the interim analyses . Implementing a trial under these stopping rules resembles a conventional trial , with the exception that it can be terminated early should a treatment prove greatly superior . Investigators and readers , however , need to grasp that the estimated treatment effects are prone to exaggeration , a r and om high , with early stopping The incidence of severe anterior cruciate ligament sprains was once only a third the current rate . This fact led the authors to believe a means to help reduce the risk of anterior cruciate ligament injury among skiers might be found . Using videotapes of the occurrences of anterior cruciate ligament sprains in alpine skiers and the data associated with more than 1400 anterior cru ciate ligament injuries observed in a 22-year study , the authors identified two common mechanisms of anterior cruciate ligament injury . From this information , a study was design ed to determine if training could help reduce the risk of anterior cruciate ligament sprains . During the 1993 to 1994 season , the on-slope staff from 20 ski areas participated in a training program involving view ing videotaped scenes where knee injuries occurred . Data from 22 ski areas , where staff were not exposed to the training , were assembled to form a control group . Data concerning anterior cruciate ligament injuries were collected from both groups for the three seasons 1991 to 1994 . A total of 179 serious knee sprains were evalu ated . Serious knee sprains declined by 62 % among trained patrollers and instructors compared with the two previous seasons , but no decline occurred in the control group Blinding in medical research possesses a rich history spanning a couple of centuries ( 1 ) . Most research ers and readers grasp its meaning . Unfortunately , beyond that general underst and ing lies confusion . In addition to terms such as single blind and double blind meaning different things to different people , some steadfastly refuse to use the term blinding and insist instead on the term masking . Others confuse blinding with other method ologic pre caution s , such as concealment of allocation during the process of creating comparison groups . Still others consider that r and omization is of little use unless accompanied by double-blinding , thus revealing that they have not understood that these separate aspects of methodology address separate sources of bias . A recent survey addressed whether the process historically termed blinding should be termed masking ( 2 ) . The survey revealed a lack of accord on that question and inconsistencies concerning other blinding terminology . Although many re sources address the lexicon of blinding , including clinical trial textbooks ( 3 - 5 ) , clinical trial dictionaries ( 6 , 7 ) , and a recently released epidemiology dictionary ( 8) , these sources do not entirely clear the lexicographic fog . Indeed , a recent study found that investigators , textbooks , and published articles all varied greatly in their interpretations of single- , double- , and triple-blinding ( 9 ) . In other words , terminologic tangles abound with blinding . We delve into the l and scape and lexicon of blinding in r and omized trials in the hope of untangling some of that terminology . Synopsis of the History of Blinding Scientists sometimes portray blinding as a recent method ologic achievement , but research ers have used blinding for more than 200 years . Lavoisier and Franklin introduced blinding in the late 18th century to test therapeutic cl aims made for Mesmerisma therapy founded on the notion that magnetism had healing properties ( 1 , 10 ) . Toward the middle of the 19th century , many homeopaths used blinding in their provings and in comparisons of homeopathy with mainstream medicine ( 11 ) . By the late 19th century , psychological research ers began to use blinding for traditional questions , more to minimize bias than to expose fraud ( 1 ) . The beginning of the 20th century found some physiologists and pharmacologists , particularly in Germany , using blind assessment . That use became more frequent in Germany by the 1930s . Research ers in Britain and the United States developed interest in blind assessment , but a different rationale motivated their interest . The rationale in Germany for blinding centered on the elimination of bias . In contrast , the interest in Britain and the United States initially centered on preventing attrition problems ( 1 ) . Without blinding and a placebo intervention , recruiting and retaining participants for a no-intervention control group became daunting . For Anglo-American clinical research ers , the initial adoption of a placebo sham in an experiment was an architectural device to create a viable and camouflaged concurrent no-treatment arm in a clinical trial ( 1 ) . Toward the end of the 1930s , British and U.S. research ers also began to acknowledge the benefits of blinding in avoiding bias . The evolution of the r and omized , controlled trial during the first half of the 20th century promoted greater use of blinding . Properly concealed r and om allocation to comparison groups abolished selection bias at entry to a trial , and clinical investigators began to appreciate fully the biases that could affect studies after participants had entered a trial . That realization transferred greater credibility to blinding arguments ( 1 ) . We recommend Kaptchuk ( 1 ) for a historical account . Background Blinding is intended to reduce bias in medical research . Although blinding is often associated in people 's minds with r and omized , controlled trials , it can be used in a variety of study design s to reduce observer biases ( 12 ) . For example , investigators can assess outcome measures blinded to exposure status in nonr and omized cohort studies or exposure status blinded to case or control status in casecontrol studies . Indeed , when investigators first used blinding in the 18th century , they assessed the effects of Mesmerism in nonr and omized experiments ( 1 , 10 ) . Having noted this , however , we focus on blinding in the context of r and omized comparisons of interventions . Blinding is widely recognized as reducing differential assessment of outcomes of interest ( known as ascertainment bias , information bias , or observer bias ) , prompted by knowledge of the group assignment of individuals being observed ( 3 - 5 ) . Blinding is less frequently recognized as also operationally improving compliance and retention of trial participants and reducing biased supplemental care or treatment ( sometimes called co-intervention ) ( 3 , 5 ) . We provide glimpses of the potential disadvantages of participants ' , investigators ' , and outcome assessors ' knowing the intervention group to which the participants have been assigned . In many cases , the biases that result might well be subconscious , but they are biases nonetheless . Possible Consequences of Participants ' Knowing Psychological effects could arise from participants ' knowing that they have received a promising new treatment , a thoroughly tested st and ard treatment , an untested new treatment , or a disappointing st and ard treatment . In other words , how the treatment options are perceived may influence the way in which they are evaluated . Despite evidence suggesting that new treatments are as likely to be inferior as they are to be superior to st and ard treatments ( 13 ) , we have the impression that participants generally assume that new treatments will be better than st and ard treatments . In any case , knowledge of the intervention received can affect the psychological or physical responses of the participants ( 3 - 5 ) . Furthermore , knowledge of the intervention could influence participants ' cooperation . For example , if participants believe that they were assigned to what they perceive as an inferior intervention , they may not comply well with the regimen . Moreover , they may not adhere to follow-up procedures , leading to a potentially biased loss to follow-up . Possible Consequences of Investigators ' Knowing We define investigators in an aggregate sense to include a broad trial teamfor example , trial design ers , participant enrollers , r and omization executors , health care providers , intervention counselors , and routine- data collectors . Investigators particularly pertinent to blinding include health care providers ( such as an attending physician or nurse ) and intervention counselors ( for example , someone delivering a behavioral prevention message ) who interact with the participants throughout the trial . The inclinations of investigators for or against the interventions can be directly transferred to participants by their attitudes ( 14 ) . Their inclinations may also be manifested in , for example , differential use of ancillary interventions of supplemental care or treatment ( co- interventions ) . Of note , the implementer could also encourage or discourage continuation in the trial on the basis of knowledge of the intervention group assignment . Possible Consequences of Outcome Assessors ' Knowing When they know the intervention group assignment of the participants whom they are assessing , outcome assessors with inclinations for or against any of the interventions being compared may make biased assessment s. For example , if they believe the new intervention is superior , then they could register more generous responses to that intervention . Obviously , more subjective outcomes present greater opportunities for bias . Pain scores assessed by participants are a good example of a subjective outcome . Even some outcomes considered objective can be fraught with subjectivityfor example , pelvic inflammatory disease and myocardial infa rct ion . In general , blinding becomes less important to reduce observer bias as the outcomes become less subjective . Hard outcomes leave little room for bias . For example , knowledge of the intervention would have little effect on measuring a hard outcome , such as death ( but still could influence the attributed cause of death ) . Of importance , even when participants and investigators have not been blinded , blinding of outcome assessors is often possible and advisable ( 12 ) . Placebos and Blinding Blinding frequently leads to the use of placebos . Placebos may or may not have effects mediated through psychological mechanisms , but they are administered to participants in a trial because they are otherwise inactive . An active placebo is a placebo with properties that mimic the symptoms or side effects ( for example , dry mouth , sweating ) that might otherwise reveal the identity of the ( pharmacologically ) active test treatment . The effect , in practice , of using placebos is contentious ( 15 ) , but the widespread view remains that placebos should be administered , whenever possible , to participants in control groups when assessing the effects of proposed new treatments for a condition for which no effective treatment already exists ( 3 , 4 ) . Placebos are generally used in trials of drugs , vaccines , and other medicinal interventions but can sometimes also be used in trials of procedures , such as ultrasonography , acupuncture , and , occasionally , surgery . For example , perhaps when placebo treatments are inappropriate , some closely analogous approach , such as placebo wound dressings , may suffice in a trial of laparoscopic versus open appendicectomy ( 16 ) . When an effective st and ard treatment exists , it is frequently used in the control group for comparison against a new treatment . Thus , investigators might compare two active treatment groups without a placebo group . Even then , however , investigators frequently attempt to achieve blinding by using the double-dummy method in essence , two placebos ( 12 , 17 ) . For example , in comparing two agents , one in a blue capsule BACKGROUND Studies have suggested that exercise programs can reduce the incidence of noncontact injuries of the anterior cruciate ligament in female athletes . We conducted a two-year prospect i ve study to assess the effects of a knee ligament injury prevention exercise program on the incidence of noncontact anterior cruciate ligament injuries in high-school female athletes . METHODS A prospect i ve cohort design was used to study high-school female athletes ( playing soccer , basketball , and volleyball ) from fifteen schools ( 112 teams ) for two consecutive seasons . The schools were divided into treatment and control groups . The treatment group participated in a plyometric-based exercise program twice a week throughout the season . Practice and game exposures and compliance with the exercise program were recorded on a weekly basis . Suspected noncontact anterior cruciate ligament injuries were confirmed on the basis of the history as well as at the time of surgery and /or with magnetic resonance imaging . RESULTS A total of 1439 athletes ( 862 in the control group and 577 in the treatment group ) were monitored . There were six confirmed noncontact anterior cruciate ligament injuries : three in the treatment group , and three in the control group . The incidence of noncontact anterior cruciate ligament injuries per 1000 exposures was 0.167 in the treatment group and 0.078 in the control group , yielding an odds ratio of 2.05 , which was not significant ( p > 0.05 ) . CONCLUSIONS Our results suggest that a twenty-minute plyometric-based exercise program that focuses on the mechanics of l and ing from a jump and deceleration when running performed twice a week throughout the season will not reduce the rate of noncontact anterior cruciate ligament injuries in high-school female athletes Background Soccer is a leading sport for participation and injury in youth . Objective To examine the effectiveness of a neuromuscular prevention strategy in reducing injury in youth soccer players . Design Cluster-r and omised controlled trial . Setting Calgary soccer clubs ( male or female , U13–U18 , tier 1–2 , indoor soccer ) . Participants Eighty-two soccer teams were approached for recruitment . Players from 60 teams completed the study ( 32 training ( n=380 ) , 28 control ( n=364 ) ) . Intervention The training programme was a soccer-specific neuromuscular training programme including dynamic stretching , eccentric strength , agility , jumping and balance ( including a home-based balance training programme using a wobble board ) . The control programme was a st and ardised warm-up ( static and dynamic stretching and aerobic components ) and a home-based stretching programme . Main outcome measures Previously vali date d injury surveillance included injury assessment by a study therapist . The injury definition was soccer injury result ing in medical attention and /or removal from a session and /or time loss . Results The injury rate in the training group was 2.08 injuries/1000 player-hours , and in the control group 3.35 injuries/1000 player-hours . Based on Poisson regression analysis , adjusted for clustering by team and covariates , the incidence rate ratios ( IRR ) for all injuries and acute onset injury were 0.62 ( 95 % CI 0.39 to 0.99 ) and 0.57 ( 95 % CI 0.35 to 0.91 ) . Point estimates also suggest protection of lower extremity , ankle and knee sprain injuries ( IRR=0.68 ( 95 % CI 0.42 to 1.11 ) , IRR=0.5 ( 95 % CI 0.24 to 1.04 ) and IRR=0.38 ( 95 % CI 0.08 to 1.75 ) ) . Conclusions A neuromuscular training programme is protective of all injuries and acute onset injury in youth soccer players 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 |
10,928 | 23,596,162 | Inorganic nitrate and beetroot juice supplementation was associated with a significant reduction in systolic BP . | Diets including food products rich in inorganic nitrate are associated with lower blood pressure ( BP ) .
The evidence for the BP-lowering effects of inorganic nitrate and beetroot in r and omized clinical trials has not been systematic ally assessed .
The objective was to conduct a systematic review and meta- analysis of r and omized clinical trials that examined the effects of inorganic nitrate and beetroot supplementation on BP . | A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria , and further to vasoprotective NO endogenously . In the present study , two separate r and omly controlled , single-blind , cross-over , postpr and ial studies were performed in normotensive volunteers . Ambulatory blood pressure ( BP ) was measured over a 24 h period following consumption of either four doses of beetroot juice ( BJ ) , 0 , 100 , 250 and 500 g ( n 18 ) , or three bread products , control bread ( 0 g beetroot ) , red beetroot- and white beetroot-enriched breads ( n 14 ) . Total urinary nitrate/nitrite ( NO(x ) ) was measured at baseline , and at 2 , 4 and 24 h post-ingestion . BJ consumption significantly , and in a near dose-dependent manner , lowered systolic BP ( SBP , P < 0·01 ) and diastolic BP ( DBP , P < 0·001 ) over a period of 24 h , compared with water control . Furthermore , bread products enriched with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h ( red beetroot-enriched bread , P < 0·05 ) , with no statistical differences between the varieties . Total urinary NO(x ) significantly increased following the consumption of 100 g ( P < 0·01 ) , 250 g ( P < 0·001 ) and 500 g BJ ( P < 0·001 ) and after red beetroot-enriched bread ingestion ( P < 0·05 ) , but did not reach significance for white beetroot-enriched bread compared with the no-beetroot condition . These studies demonstrated significant hypotensive effects of a low dose ( 100 g ) of beetroot which was unaffected by processing or the presence of betacyanins . These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables Background The consumption of beetroot juice on a low nitrate diet may lower blood pressure ( BP ) and therefore reduce the risk of cardiovascular events . However , it is unknown if its inclusion as part of a normal diet has a similar effect on BP . The aim of the study was to conduct a r and omized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP . Method Fifteen women and fifteen men participated in a double-blind , r and omized , placebo-controlled , crossover study . Volunteers were r and omized to receive 500 g of beetroot and apple juice ( BJ ) or a placebo juice ( PL ) . Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor ( ABPM ) . Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities . The identical procedure was repeated 2-wk later with the drink ( BJ or PL ) not consumed on the first visit . Results Overall , there was a trend ( P=0.064 ) to lower systolic blood pressure ( SBP ) at 6-h after drinking BJ relative to PL . Analysis in men only ( n=13 ) after adjustment for baseline differences demonstrated a significant ( P<0.05 ) reduction in SBP of 4 – 5 mmHg at 6-h after drinking BJ . Conclusions Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults . Trial registration anzctr.org.au Use of the DASH ( Dietary Approaches to Stop Hypertension ) diet , which is rich in fruits , vegetables , and low-fat dairy foods , significantly lowers blood pressure . Among the 459 participants in the DASH Trial , 72 had stage 1 isolated systolic hypertension ( ISH ) ( systolic blood pressure , 140 to 159 mm Hg ; diastolic blood pressure , < 90 mm Hg ) . We examined the blood pressure response in these 72 participants to determine whether the DASH diet is an effective treatment for stage 1 ISH . After a 3-week run-in period on a typical American ( control ) diet , participants were r and omly assigned for 8 weeks to 1 of 3 diets : a continuation of the control diet ( n=25 ) , a diet rich in fruits and vegetables ( n=24 ) , or the DASH diet ( n=23 ) . Sodium content was the same in the 3 diets , and caloric intake was adjusted during the trial to prevent weight change . Blood pressure was measured at baseline and at the end of the 8-week intervention period with st and ard sphygmomanometry . Use of the DASH diet significantly lowered systolic blood pressure compared with the control diet ( −11.2 mm Hg ; 95 % confidence interval , −6.1 to −16.2 mm Hg;P < 0.001 ) and the fruits/vegetables diet ( −8.0 mm Hg ; 95 % confidence interval , −2.5 to −13.4 mm Hg;P < 0.01 ) . Overall , blood pressure in the DASH group fell from 146/85 to 134/82 mm Hg . Similar results were observed with 24-hour ambulatory blood pressure measurements . In the DASH diet group , 18 of 23 participants ( 78 % ) reduced their systolic blood pressure to < 140 mm Hg , compared with 24 % and 50 % in the control and fruits/vegetables groups , respectively . Our results indicate that the DASH diet , which is rich in fruits , vegetables , and low-fat dairy foods , is effective as first-line therapy in stage 1 ISH The mechanism underlying blood pressure ( BP ) reduction in the high fruits and vegetables arm of the Dietary Approaches to Stop Hypertension ( DASH ) study is unknown but may include potassium , magnesium and fibre . This study was design ed to separate minerals and fibre from other components of DASH on BP in abdominally obese individuals with metabolic syndrome with pre-hypertension to stage 1 hypertension ( obese hypertensives ) . A total of 15 obese hypertensives and 15 lean normotensives were studied on a st and ardized usual diet , r and omized to DASH or usual diet supplemented with potassium , magnesium and fibre to match DASH , then crossed over to the complementary diet . All diets were 3 weeks long , isocaloric and matched for sodium and calcium . In obese hypertensives , BP was lower after 3 weeks on DASH than usual diet ( −7.6±1.4/−5.3±1.4 mm Hg , P<0.001/0.02 ) and usual diet supplemented ( −6.2±1.4/−3.7±1.4 P<0.005/0.06 ) , whereas BP was not significantly different on usual and supplemented diets . BP values were not different among the three diets in lean normotensives . Small artery elasticity was lower in obese hypertensives than in lean normotensives on the usual and supplemented diets ( P<0.02 ) . This index of endothelial function improved in obese hypertensives ( P<0.02 ) but not lean normotensives on DASH , and was no longer different from values in lean normotensives ( P>0.50 ) . DASH is more effective than potassium , magnesium and fibre supplements for lowering BP in obese hypertensives , which suggest that high fruits and vegetables DASH lowers BP and improves endothelial function in this group by nutritional factors in addition to potassium , magnesium and fibre 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 The anion nitrate-abundant in our diet-has recently emerged as a major pool of nitric oxide ( NO ) synthase-independent NO production . Nitrate is reduced stepwise in vivo to nitrite and then NO and possibly other bioactive nitrogen oxides . This reductive pathway is enhanced during low oxygen tension and acidosis . A recent study shows a reduction in oxygen consumption during submaximal exercise attributable to dietary nitrate . We went on to study the effects of dietary nitrate on various physiological and biochemical parameters during maximal exercise . Nine healthy , nonsmoking volunteers ( age 30+/-2.3 years , VO(2max ) 3.72+/-0.33 L/min ) participated in this study , which had a r and omized , double-blind crossover design . Subjects received dietary supplementation with sodium nitrate ( 0.1 mmol/kg/day ) or placebo ( NaCl ) for 2 days before the test . This dose corresponds to the amount found in 100 - 300 g of a nitrate-rich vegetable such as spinach or beetroot . The maximal exercise tests consisted of an incremental exercise to exhaustion with combined arm and leg cranking on two separate ergometers . Dietary nitrate reduced VO(2max ) from 3.72+/-0.33 to 3.62+/-0.31 L/min , P<0.05 . Despite the reduction in VO(2max ) the time to exhaustion trended to an increase after nitrate supplementation ( 524+/-31 vs 563+/-30 s , P=0.13 ) . There was a correlation between the change in time to exhaustion and the change in VO(2max ) ( R(2)=0.47 , P=0.04 ) . A moderate dietary dose of nitrate significantly reduces VO(2max ) during maximal exercise using a large active muscle mass . This reduction occurred with a trend toward increased time to exhaustion implying that two separate mechanisms are involved : one that reduces VO(2max ) and another that improves the energetic function of the working muscles Six days of dietary nitrate supplementation in the form of beetroot juice ( ~0.5 L/d ) has been reported to reduce pulmonary oxygen uptake ( VO₂ ) during submaximal exercise and increase tolerance of high-intensity work rates , suggesting that nitrate can be a potent ergogenic aid . Limited data are available regarding the effect of nitrate ingestion on athletic performance , and no study has investigated the potential ergogenic effects of a small-volume , concentrated dose of beetroot juice . The authors tested the hypothesis that 6 d of nitrate ingestion would improve time-trial performance in trained cyclists . Using a double-blind , repeated- measures crossover design , 12 male cyclists ( 31±3 yr , VO2peak=58±2 ml·kg⁻¹·min⁻¹ , maximal power [Wmax]=342±10 W ) ingested 140 ml/d of concentrated beetroot ( ~8 mmol/d nitrate ) juice ( BEET ) or a placebo ( nitrate-depleted beetroot juice ; PLAC ) for 6 d , separated by a 14-d washout . After supplementation on Day 6 , subjects performed 60 min of submaximal cycling ( 2 × 30 min at 45 % and 65 % Wmax , respectively ) , followed by a 10-km time trial . Time-trial performance ( 953±18 vs. 965±18 s , p<.005 ) and power output ( 294±12 vs. 288±12 W , p<.05 ) improved after BEET compared with PLAC supplementation . Submaximal VO₂ was lower after BEET ( 45 % Wmax=1.92±0.06 vs. 2.02±0.09 L/min , 65 % Wmax 2.94±0.12 vs. 3.11±0.12 L/min ) than with PLAC ( main effect , p<.05 ) . Whole-body fuel selection and plasma lactate , glucose , and insulin concentrations did not differ between treatments . Six days of nitrate supplementation reduced VO₂ during submaximal exercise and improved time-trial performance in trained cyclists PURPOSE Dietary nitrate supplementation has been shown to reduce the O2 cost of submaximal exercise and to improve high-intensity exercise tolerance . However , it is presently unknown whether it may enhance performance during simulated competition . The present study investigated the effects of acute dietary nitrate supplementation on power output ( PO ) , VO2 , and performance during 4- and 16.1-km cycling time trials ( TT ) . METHODS After familiarization , nine club-level competitive male cyclists were assigned in a r and omized , crossover design to consume 0.5 L of beetroot juice ( BR ; containing ∼ 6.2 mmol of nitrate ) or 0.5 L of nitrate-depleted BR ( placebo , PL ; containing ∼ 0.0047 mmol of nitrate ) , ∼ 2.5 h before the completion of a 4- and a 16.1-km TT . RESULTS BR supplementation elevated plasma [ nitrite ] ( PL = 241 ± 125 vs BR = 575 ± 199 nM , P < 0.05 ) . The VO2 values during the TT were not significantly different between the BR and PL conditions at any elapsed distance ( P > 0.05 ) , but BR significantly increased mean PO during the 4-km ( PL = 279 ± 51 vs BR = 292 ± 44 W , P < 0.05 ) and 16.1-km TT ( PL = 233 ± 43 vs BR = 247 ± 44 W , P < 0.01 ) . Consequently , BR improved 4-km performance by 2.8 % ( PL = 6.45 ± 0.42 vs BR = 6.27 ± 0.35 min , P < 0.05 ) and 16.1-km performance by 2.7 % ( PL = 27.7 ± 2.1 vs BR = 26.9 ± 1.8 min , P < 0.01 ) . CONCLUSIONS These results suggest that acute dietary nitrate supplementation with 0.5 L of BR improves cycling economy , as demonstrated by a higher PO for the same VO2 and enhances both 4- and 16.1-km cycling TT performance BACKGROUND It is known that obesity , sodium intake , and alcohol consumption factors influence blood pressure . In this clinical trial , Dietary Approaches to Stop Hypertension , we assessed the effects of dietary patterns on blood pressure . METHODS We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg . For three weeks , the subjects were fed a control diet that was low in fruits , vegetables , and dairy products , with a fat content typical of the average diet in the United States . They were then r and omly assigned to receive for eight weeks the control diet , a diet rich in fruits and vegetables , or a " combination " diet rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat . Sodium intake and body weight were maintained at constant levels . RESULTS At base line , the mean ( + /-SD ) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg , respectively . The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; the fruits- and -vegetables diet reduced systolic blood pressure by 2.8 mm Hg more ( P<0.001 ) and diastolic blood pressure by 1.1 mm Hg more than the control diet ( P=0.07 ) . Among the 133 subjects with hypertension ( systolic pressure , > or = 140 mm Hg ; diastolic pressure , > or = 90 mm Hg ; or both ) , the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; among the 326 subjects without hypertension , the corresponding reductions were 3.5 mm Hg ( P<0.001 ) and 2.1 mm Hg ( P=0.003 ) . CONCLUSIONS A diet rich in fruits , vegetables , and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure . This diet offers an additional nutritional approach to preventing and treating hypertension Ingestion of dietary ( inorganic ) nitrate elevates circulating and tissue levels of nitrite via bioconversion in the entero-salivary circulation . In addition , nitrite is a potent vasodilator in humans , an effect thought to underlie the blood pressure – lowering effects of dietary nitrate ( in the form of beetroot juice ) ingestion . Whether inorganic nitrate underlies these effects and whether the effects of either naturally occurring dietary nitrate or inorganic nitrate supplementation are dose dependent remain uncertain . Using a r and omized crossover study design , we show that nitrate supplementation ( KNO3 capsules : 4 versus 12 mmol [ n=6 ] or 24 mmol of KNO3 ( 1488 mg of nitrate ) versus 24 mmol of KCl [ n=20 ] ) or vegetable intake ( 250 mL of beetroot juice [ 5.5 mmol nitrate ] versus 250 mL of water [ n=9 ] ) causes dose-dependent elevation in plasma nitrite concentration and elevation of cGMP concentration with a consequent decrease in blood pressure in healthy volunteers . In addition , post hoc analysis demonstrates a sex difference in sensitivity to nitrate supplementation dependent on resting baseline blood pressure and plasma nitrite concentration , whereby blood pressure is decreased in male volunteers , with higher baseline blood pressure and lower plasma nitrite concentration but not in female volunteers . Our findings demonstrate dose-dependent decreases in blood pressure and vasoprotection after inorganic nitrate ingestion in the form of either supplementation or by dietary elevation . In addition , our post hoc analyses intimate sex differences in nitrate processing involving the entero-salivary circulation that are likely to be major contributing factors to the lower blood pressures and the vasoprotective phenotype of premenopausal women Diets rich in green , leafy vegetables have been shown to lower blood pressure ( BP ) and reduce the risk of cardiovascular disease . Green , leafy vegetables and beetroot are particularly rich in inorganic nitrate . Dietary nitrate supplementation , via sequential reduction to nitrite and NO , has previously been shown to lower BP and improve endothelial function in healthy humans . We sought to determine if supplementing dietary nitrate with beetroot juice , a rich source of nitrate , will lower BP and improve endothelial function and insulin sensitivity in individuals with type 2 diabetes ( T2DM ) . Twenty-seven patients , age 67.2±4.9 years ( 18 male ) , were recruited for a double-blind , r and omized , placebo-controlled crossover trial . Participants were r and omized to begin , in either order , a 2-week period of supplementation with 250ml beetroot juice daily ( active ) or 250ml nitrate-depleted beetroot juice ( placebo ) . At the conclusion of each intervention period 24-h ambulatory blood pressure monitoring , tests of macro- and microvascular endothelial function , and a hyperinsulinemic isoglycemic clamp were performed . After 2 weeks administration of beetroot juice mean ambulatory systolic BP was unchanged : 134.6±8.4mmHg versus 135.1±7.8mmHg ( mean±SD ) , placebo vs active-mean difference of -0.5mmHg ( placebo-active ) , p=0.737 ( 95 % CI -3.9 to 2.8 ) . There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity . Supplementation of the diet with 7.5mmol of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration , but did not lower BP , improve endothelial function , or improve insulin sensitivity in individuals with T2DM Dietary supplementation with beetroot juice ( BR ) has been shown to reduce resting blood pressure and the O(2 ) cost of submaximal exercise and to increase tolerance to high-intensity cycling . We tested the hypothesis that the physiological effects of BR were consequent to its high NO(3)(- ) content per se , and not the presence of other potentially bioactive compounds . We investigated changes in blood pressure , mitochondrial oxidative capacity ( Q(max ) ) , and physiological responses to walking and moderate- and severe-intensity running following dietary supplementation with BR and NO(3)(-)-depleted BR [ placebo ( PL ) ] . After control ( nonsupplemented ) tests , nine healthy , physically active male subjects were assigned in a r and omized , double-blind , crossover design to receive BR ( 0.5 l/day , containing ∼6.2 mmol of NO(3)(- ) ) and PL ( 0.5 l/day , containing ∼0.003 mmol of NO(3)(- ) ) for 6 days . Subjects completed treadmill exercise tests on days 4 and 5 and knee-extension exercise tests for estimation of Q(max ) ( using (31)P-magnetic resonance spectroscopy ) on day 6 of the supplementation periods . Relative to PL , BR elevated plasma NO(2)(- ) concentration ( 183 ± 119 vs. 373 ± 211 nM , P < 0.05 ) and reduced systolic blood pressure ( 129 ± 9 vs. 124 ± 10 mmHg , P < 0.01 ) . Q(max ) was not different between PL and BR ( 0.93 ± 0.05 and 1.05 ± 0.22 mM/s , respectively ) . The O(2 ) cost of walking ( 0.87 ± 0.12 and 0.70 ± 0.10 l/min in PL and BR , respectively , P < 0.01 ) , moderate-intensity running ( 2.26 ± 0.27 and 2.10 ± 0.28 l/min in PL and BR , respectively , P < 0.01 ) , and severe-intensity running ( end-exercise O(2 ) uptake = 3.77 ± 0.57 and 3.50 ± 0.62 l/min in PL and BL , respectively , P < 0.01 ) was reduced by BR , and time to exhaustion during severe-intensity running was increased by 15 % ( 7.6 ± 1.5 and 8.7 ± 1.8 min in PL and BR , respectively , P < 0.01 ) . In contrast , relative to control , PL supplementation did not alter plasma NO(2)(- ) concentration , blood pressure , or the physiological responses to exercise . These results indicate that the positive effects of 6 days of BR supplementation on the physiological responses to exercise can be ascribed to the high NO(3)(- ) content per se The purpose of this study was to eluci date the mechanistic bases for the reported reduction in the O(2 ) cost of exercise following short-term dietary nitrate ( NO(3)(- ) ) supplementation . In a r and omized , double-blind , crossover study , seven men ( aged 19 - 38 yr ) consumed 500 ml/day of either nitrate-rich beet root juice ( BR , 5.1 mmol of NO(3)(-)/day ) or placebo ( PL , with negligible nitrate content ) for 6 consecutive days , and completed a series of low-intensity and high-intensity " step " exercise tests on the last 3 days for the determination of the muscle metabolic ( using (31)P-MRS ) and pulmonary oxygen uptake ( Vo(2 ) ) responses to exercise . On days 4 - 6 , BR result ed in a significant increase in plasma [ nitrite ] ( mean + /- SE , PL 231 + /- 76 vs. BR 547 + /- 55 nM ; P < 0.05 ) . During low-intensity exercise , BR attenuated the reduction in muscle phosphocreatine concentration ( [ PCr ] ; PL 8.1 + /- 1.2 vs. BR 5.2 + /- 0.8 mM ; P < 0.05 ) and the increase in Vo(2 ) ( PL 484 + /- 41 vs. BR 362 + /- 30 ml/min ; P < 0.05 ) . During high-intensity exercise , BR reduced the amplitudes of the [ PCr ] ( PL 3.9 + /- 1.1 vs. BR 1.6 + /- 0.7 mM ; P < 0.05 ) and Vo(2 ) ( PL 209 + /- 30 vs. BR 100 + /- 26 ml/min ; P < 0.05 ) slow components and improved time to exhaustion ( PL 586 + /- 80 vs. BR 734 + /- 109 s ; P < 0.01 ) . The total ATP turnover rate was estimated to be less for both low-intensity ( PL 296 + /- 58 vs. BR 192 + /- 38 microM/s ; P < 0.05 ) and high-intensity ( PL 607 + /- 65 vs. BR 436 + /- 43 microM/s ; P < 0.05 ) exercise . Thus the reduced O(2 ) cost of exercise following dietary NO(3)(- ) supplementation appears to be due to a reduced ATP cost of muscle force production . The reduced muscle metabolic perturbation with NO(3)(- ) supplementation allowed high-intensity exercise to be tolerated for a greater period of time Dietary nitrate ( NO(3)(- ) ) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults . We investigated whether these effects might also be evident in older adults . In a double-blind , r and omized , crossover study , 12 healthy , older ( 60 - 70 yr ) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice ( BR ; 2 × 70 ml/day , ∼9.6 mmol/day NO(3)(- ) ) or a nitrate-depleted beetroot juice placebo ( PL ; 2 × 70 ml/day , ∼0.01 mmol/day NO(3)(- ) ) . Before and after the intervention periods , resting blood pressure and plasma [ nitrite ] were measured , and subjects completed a battery of physiological and cognitive tests . Nitrate supplementation significantly increased plasma [ nitrite ] and reduced resting systolic ( BR : 115 ± 9 vs. PL : 120 ± 6 mmHg ; P < 0.05 ) and diastolic ( BR : 70 ± 5 vs. PL : 73 ± 5 mmHg ; P < 0.05 ) blood pressure . Nitrate supplementation result ed in a speeding of the Vo(2 ) mean response time ( BR : 25 ± 7 vs. PL : 28 ± 7 s ; P < 0.05 ) in the transition from st and ing rest to treadmill walking , although in contrast to our hypothesis , the O(2 ) cost of exercise remained unchanged . Functional capacity ( 6-min walk test ) , the muscle metabolic response to low-intensity exercise , brain metabolite concentrations , and cognitive function were also not altered . Dietary nitrate supplementation reduced resting blood pressure and improved Vo(2 ) kinetics during treadmill walking in healthy older adults but did not improve walking or cognitive performance . These results may have implication s for the enhancement of cardiovascular health in older age |
10,929 | 24,480,951 | Subgroup analyses performed in NSLBP trials have been severely underpowered , are only able to provide exploratory or insufficient findings , and have rather poor quality of reporting . | OBJECTIVE To evaluate the quality , conduct , and reporting of subgroup analyses performed in r and omized controlled trials of therapist-delivered interventions for nonspecific low back pain ( NSLBP ) .
SUMMARY OF BACKGROUND DATA R and omized controlled trials of therapist-delivered interventions for NSLBP to date have , at best , shown small to moderate positive effects .
Identifying subgroups is an important research priority .
This review evaluates the quality , conduct , and reporting of subgroup analyses performed in the NSLBP literature . | Abstract Objective To estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months This study examined the supplemental value of a cognitive coping skills training when added to an operant-behavioral treatment for chronic low-back pain patients . The complete treatment package ( OPCO ) was compared with an operant program + group discussion ( OPDI ) and a waiting-list control ( WLC ) . After the WL period , the WLC patients received a less protocol ized operant program usually provided in Dutch rehabilitation centers ( OPUS ) . Regression analyses showed that , compared with WLC , both OPCO and OPDI led to less negative affect , higher activity tolerance , less pain behavior , and higher pain coping and pain control . At posttreatment , OPCO led to better pain coping and pain control than OPDI . Calculation of improvement rates revealed that OPCO and OPDI had significantly more improved patients than OPUS on all the dependent variables . The discussion includes findings regarding treatment credibility , compliance , and contamination bias Study Design . A prospect i ve clinical trial was conducted that involved six groups of patients with chronic low back pain selected from a large cohort ( N = 816 ) . Objectives . To correlate pretreatment baseline variables with outcome parameters after treatment in a functional restoration program or in control programs , to identify possible factors predictive of the need for functional restoration . Summary of Background Data . Since the functional restoration program was first described , research has focused on identifying patients who will or will not benefit from such a program . The value of previous studies is limited , however , because predictive factors from a control group were not " subtracted . " Methods . Eight hundred sixteen patients with chronic low back disability were included . All had a structured medical examination , including various physical tests before participation in either a functional restoration program ( n = 621 ) or shorter " control " outpatient programs ( n = 144 ) . A smaller group of the cohort ( n = 51 ) had no treatment and served as a pure control group . Six groups were selected from the cohort : Three underwent an identical functional restoration program and three underwent different outpatient control programs . Several baseline demographic , physical , and socioeconomic variables were correlated to 1‐year outcome parameters . Results . Age , days of sick leave , connection to the work force , and back pain intensity , were significantly correlated to success 1 year after entry into the study in all groups , no matter what kind of treatment was administered . Back muscle endurance , sports activity , activity of daily living scores , and vibrations were of importance in some outcome parameters for success after functional restoration . Smoking was positively correlated to disability pension . Days of sick leave and , in functional restoration , ability to work were the only factors that were correlative with statistics for people who withdrew . Conclusions . Different factors can be identified as predictive of outcome in a functional restoration program , but most of these factors were also shown to predict success for shorter control outpatient programs or of no treatment Introduction The Multinational Musculoskeletal Inception Cohort Study ( MMICS ) Statement is a consensus statement aim ed at improving the quality of prospect i ve investigations into the transition from early stages of low back pain ( LBP ) to persistent problems . The statement aims to help improve the quality of such studies by recommending an agreed minimal list of measures for inclusion in baseline data collection . The MMICS Statement is primarily aim ed at research ers who want to investigate prognosis in LBP , and this will allow data from cohorts to be pooled and will facilitate comparisons between different health care systems . One approach to preventing acute new episodes of LBP ( up to 3 weeks from onset ) from developing into persistent disabling pain is to identify those individuals with LBP who are most likely to progress to chronic disability . Targeting interventions at those at highest risk could reduce the population burden of chronic LBP . A wide range of baseline parameters have been associated with poor outcome in inception cohort studies ( 1–6 ) . Few existing studies have been of sufficient size and method ologic rigor to produce conclusive findings . Even in method ologically robust studies , baseline factors only account for a small proportion of the variance in outcome ( 7 ) , typically around 30 % . Systematic review s of the literature could not pool data because studies used different measurements ( 1–3 ) . Despite some information on physical , psychosocial , and work-related risk factors , it has not been possible to adequately estimate the comparative impact of individual psychosocial and societal factors on the transition from acute to persistent disabling LBP . How to address this problem was one focus of the VI International Forum for Primary Care Research in Low Back Pain held in April 2003 . A steering group for the collaboration was appointed , and 8 national team leaders volunteered to recruit teams of national experts . Three additional team leaders were recruited by the steering group ( Australia , France , and Germany ) . Independent experts were invited to advise on the quality of the MMICS process . The MMICS steering group , located in the UK , met regularly and included expert research ers in clinical and outcome factors in back pain ( AB ) , work-related issues in back pain ( AKB ) , psychosocial aspects of back pain ( TP and RS ) , and general practice aspects of back pain ( MU ) . The MMICS Statement set out to include 1 ) a minimal but comprehensive number of predictor factors based on current evidence and theory ; 2 ) appropriate measurement instruments for agreed predictor factors based on their clinometric properties , availability , and practical characteristics ; and 3 ) a minimum set of followup measures , including recommendations about measurement and timing Objective To determine the effectiveness of lessons in the Alex and er technique , massage therapy , and advice from a doctor to take exercise ( exercise prescription ) along with nurse delivered behavioural counselling for patients with chronic or recurrent back pain . Design Factorial r and omised trial . Setting 64 general practice s in Engl and . Participants 579 patients with chronic or recurrent low back pain ; 144 were r and omised to normal care , 147 to massage , 144 to six Alex and er technique lessons , and 144 to 24 Alex and er technique lessons ; half of each of these groups were r and omised to exercise prescription . Interventions Normal care ( control ) , six sessions of massage , six or 24 lessons on the Alex and er technique , and prescription for exercise from a doctor with nurse delivered behavioural counselling . Main outcome measures Rol and Morris disability score ( number of activities impaired by pain ) and number of days in pain . Results Exercise and lessons in the Alex and er technique , but not massage , remained effective at one year ( compared with control Rol and disability score 8.1 : massage −0.58 , 95 % confidence interval −1.94 to 0.77 , six lessons −1.40 , −2.77 to −0.03 , 24 lessons −3.4 , −4.76 to −2.03 , and exercise −1.29 , −2.25 to −0.34 ) . Exercise after six lessons achieved 72 % of the effect of 24 lessons alone ( Rol and disability score −2.98 and −4.14 , respectively ) . Number of days with back pain in the past four weeks was lower after lessons ( compared with control median 21 days : 24 lessons −18 , six lessons −10 , massage −7 ) and quality of life improved significantly . No significant harms were reported . Conclusions One to one lessons in the Alex and er technique from registered teachers have long term benefits for patients with chronic back pain . Six lessons followed by exercise prescription were nearly as effective as 24 lessons . Trial registration National Research Register N0028108728 . How does the Alex and er Technique work ? What are the authors findings about the clinical and cost effectiveness of the treatment ? Watch this video to find out ( 12 mins ) . Many manual therapists assess and treat spinal stiffness of people with low back pain . The objectives of this study were to investigate : ( i ) whether spinal stiffness changes after treatment ; ( ii ) the relationship between pre-treatment spinal stiffness and change in stiffness with treatment ; ( iii ) the relationship between spinal stiffness , pain , disability and global perceived effect of treatment ; ( iv ) whether spinal stiffness predicts outcome of treatment or response to treatment in chronic low back pain patients . One hundred and ninety-one subjects with chronic low back pain were r and omly allocated to groups that received either spinal manipulative therapy , motor control exercise , or a general exercise program . Spinal stiffness was assessed before and after intervention . All three groups showed a significant decrease in stiffness following treatment ( p<0.001 ) . No difference between groups was observed . There was a significant negative correlation between pre-treatment stiffness and change in stiffness ( r=-0.61 ; p<0.001 ) . There was a significant but weak correlation ( r=0.18 ; p=0.02 ) between change in stiffness and change in global perceived effect of treatment , and a significant but weak correlation between change in stiffness and change in function for subjects in the spinal manipulative therapy group ( r=-0.28 ; p=0.02 ) . No significant association was observed between initial stiffness score and any of the final outcome measures following treatment . Initial stiffness did not predict response to any treatment . In conclusion , spinal stiffness decreases over the course of an episode of treatment , more so in those with the stiffest spines , but the decrease is not dependent on treatment and is not generally related to outcome 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 The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found Intensive group training using principles of grade d activity has been proven to be effective in occupational care for workers with chronic low back pain . Objective of the study was to compare the effects of an intensive group training protocol aim ed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain . The study was design ed as pragmatic r and omised controlled trial with a setup of 105 primary care physiotherapists in 49 practice s and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study . In the intensive group training protocol exercise therapy , back school and operant-conditioning behavioural principles are combined . Patients were treated during 10 individual sessions along 20 group sessions . Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain . Main outcome measures were functional disability ( Rol and Morris disability question naire ) , pain intensity , perceived recovery and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 and 52 weeks . Both an intention-to-treat analysis and a per- protocol analysis were performed . Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period , with one exception . After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group , but this difference was absent after 52 weeks . We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain OBJECTIVES To identify characteristics of r and omized controlled trial participants which predict greater benefits from physical treatments for low back pain . If successful , this would allow more appropriate selection of patients for different treatments . METHODS We did a secondary analysis of the UK Back pain Exercise And Manipulation trial ( UK BEAM n = 1334 ) data set to identify baseline characteristics predicting response to manipulation , exercise and manipulation followed by exercise ( combined treatment ) . Rather than simply identifying factors associated with overall outcome , we tested for the statistical significance of the interaction between treatment allocation , baseline characteristics and outcome to identify factors that predicted response to treatment . We also did a post-hoc subgroup analysis to present separate results for trial participants with subacute and chronic low back pain to inform future evidence synthesis . RESULTS Age , work status , age of leaving school , ' pain and disability ' , ' quality of life ' and ' beliefs ' at baseline all predicted overall outcome . None of these predicted response to treatment . In those allocated to combined treatment , there was a suggestion that expecting treatment to be helpful might improve outcome at 1 yr . Episode length at study entry did not predict response to treatment . CONCLUSION Baseline participant characteristics did not predict response to the UK BEAM treatment packages . Using recognized prognostic variables to select patients for different treatment packages , without first demonstrating that these factors affect response to treatment , may be inappropriate . In particular , this analysis suggests that the distinction between subacute and chronic low back pain may not be useful when considering treatment choices Background Although many clinicians believe there are clinical ly important subgroups of persons with " non-specific " low back pain , such subgroups have not yet been clearly identified . As part of a large trial evaluating acupuncture for chronic low back pain , we sought to identify subgroups of participants that were particularly responsive to acupuncture . Methods We performed a secondary analysis of data for the 638 participants in our clinical trial comparing different types of acupuncture to usual care to identify baseline characteristics that predicted responses to individualized , st and ardized , or simulated acupuncture treatments . After identifying factors that predicted improvements in back-related function or symptoms , we determined if these factors were more likely to predict improvement for those receiving the acupuncture treatments than for those receiving usual care . This was accomplished by testing for an interaction between the prognostic factors and treatment group in four models : functional outcomes ( measured by the Rol and -Morris Disability Scale ) at 8 and 52 weeks post-r and omization and symptom outcomes ( measured with a numerical rating scale ) at 8 and 52 weeks . Results Overall , the strongest predictors of improvement in back function and symptoms were higher baseline levels of these measures , receipt of an acupuncture treatment , and non-use of narcotic analgesics . Benefit from acupuncture compared to usual care was greater with worse pre-treatment levels of back dysfunction ( interaction p < 0.004 for the functional outcome , Rol and Morris Disability Scale at 8 weeks ) . No other consistent interactions were observed . Conclusion This secondary analysis found little evidence for the existence of subgroups of patients with chronic back pain that would be especially likely to benefit from acupuncture . However , persons with chronic low back pain who had more severe baseline dysfunction had the most short-term benefit from acupuncture In a r and omized controlled trial plus a nonr and omized cohort , the authors investigated the effectiveness and costs of acupuncture in addition to routine care in the treatment of chronic low back pain and assessed whether the effects of acupuncture differed in r and omized and nonr and omized patients . In 2001 , German patients with chronic low back pain were allocated to an acupuncture group or a no-acupuncture control group . Persons who did not consent to r and omization were included in a nonr and omized acupuncture group . All patients were allowed to receive routine medical care in addition to study treatment . Back function ( Hannover Functional Ability Question naire ) , pain , and quality of life were assessed at baseline and after 3 and 6 months , and cost-effectiveness was analyzed . Of 11,630 patients ( mean age=52.9 years ( st and ard deviation , 13.7 ) ; 59 % female ) , 1,549 were r and omized to the acupuncture group and 1,544 to the control group ; 8,537 were included in the nonr and omized acupuncture group . At 3 months , back function improved by 12.1 ( st and ard error ( SE ) , 0.4 ) to 74.5 ( SE , 0.4 ) points in the acupuncture group and by 2.7 ( SE , 0.4 ) to 65.1 ( SE , 0.4 ) points among controls ( difference=9.4 points ( 95 % confidence interval 8.3 , 10.5 ) ; p<0.001 ) . Nonr and omized patients had more severe symptoms at baseline and showed improvements in back function similar to those seen in r and omized patients . The incremental cost-effectiveness ratio was euro10,526 ( euros ) per quality -adjusted life year . Acupuncture plus routine care was associated with marked clinical improvements in these patients and was relatively cost-effective BACKGROUND Acupuncture is a popular complementary and alternative treatment for chronic back pain . Recent European trials suggest similar short-term benefits from real and sham acupuncture needling . This trial addresses the importance of needle placement and skin penetration in eliciting acupuncture effects for patients with chronic low back pain . METHODS A total of 638 adults with chronic mechanical low back pain were r and omized to individualized acupuncture , st and ardized acupuncture , simulated acupuncture , or usual care . Ten treatments were provided over 7 weeks by experienced acupuncturists . The primary outcomes were back-related dysfunction ( Rol and -Morris Disability Question naire score ; range , 0 - 23 ) and symptom bothersomeness ( 0 - 10 scale ) . Outcomes were assessed at baseline and after 8 , 26 , and 52 weeks . RESULTS At 8 weeks , mean dysfunction scores for the individualized , st and ardized , and simulated acupuncture groups improved by 4.4 , 4.5 , and 4.4 points , respectively , compared with 2.1 points for those receiving usual care ( P < .001 ) . Participants receiving real or simulated acupuncture were more likely than those receiving usual care to experience clinical ly meaningful improvements on the dysfunction scale ( 60 % vs 39 % ; P < .001 ) . Symptoms improved by 1.6 to 1.9 points in the treatment groups compared with 0.7 points in the usual care group ( P < .001 ) . After 1 year , participants in the treatment groups were more likely than those receiving usual care to experience clinical ly meaningful improvements in dysfunction ( 59 % to 65 % vs 50 % , respectively ; P = .02 ) but not in symptoms ( P > .05 ) . CONCLUSIONS Although acupuncture was found effective for chronic low back pain , tailoring needling sites to each patient and penetration of the skin appear to be unimportant in eliciting therapeutic benefits . These findings raise questions about acupuncture 's purported mechanisms of action . It remains unclear whether acupuncture or our simulated method of acupuncture provide physiologically important stimulation or represent placebo or nonspecific effects Abstract Objective To determine whether a short course of traditional acupuncture improves longer term outcomes for patients with persistent non-specific low back pain in primary care . Design Pragmatic , open , r and omised controlled trial . Setting Three private acupuncture clinics and 18 general practice s in York , Engl and . Participants 241 adults aged 18 - 65 with non-specific low back pain of 4 - 52 weeks ' duration . Interventions 10 individualised acupuncture treatments from one of six qualified acupuncturists ( 160 patients ) or usual care only ( 81 patients ) . Main outcome measures The primary outcome was SF-36 bodily pain , measured at 12 and 24 months . Other outcomes included reported use of analgesics , scores on the Oswestry pain disability index , safety , and patient satisfaction . Results 39 general practitioners referred 289 patients of whom 241 were r and omised . At 12 months average SF-36 pain scores increased by 33.2 to 64.0 in the acupuncture group and by 27.9 to 58.3 in the control group . Adjusting for baseline score and for any clustering by acupuncturist , the estimated intervention effect was 5.6 points ( 95 % confidence interval −0.2 to 11.4 ) at 12 months ( n = 213 ) and 8.0 points ( 2.8 to 13.2 ) at 24 months ( n = 182 ) . The magnitude of the difference between the groups was about 10%-15 % of the final pain score in the control group . Functional disability was not improved . No serious or life threatening events were reported . Conclusions Weak evidence was found of an effect of acupuncture on persistent non-specific low back pain at 12 months , but stronger evidence of a small benefit at 24 months . Referral to a qualified traditional acupuncturist for a short course of treatment seems safe and acceptable to patients with low back pain . Trial registration IS RCT N80764175 [ controlled-trials.com ] BACKGROUND Although acupressure has been reported to be effective in managing various types of pain , its efficacy in relieving pain associated with low back pain ( LBP ) remains unclear . The aim of this study is to compare the efficacy of acupressure with that of physical therapy in reducing low back pain . METHODS A r and omized controlled clinical trial in an orthopedic referral hospital in Taiwan was conducted between December 20 , 2000 , and March 2 , 2001 . A total of 146 participants with chronic low back pain were r and omly assigned to the acupressure group ( 69 ) or the physical therapy group ( 77 ) , each with a different treatment technique . Self-appraised pain scores were obtained before treatment as baseline and after treatment as outcomes using the Chinese version of Short-Form Pain Question naire ( SF-PQ ) . RESULTS There were no significant differences in baseline characteristics among patients r and omized into the two groups . The mean of posttreatment pain score after a 4-week treatment ( 2.28 , SD = 2.62 ) in the acupressure group was significantly lower than that in the physical therapy group ( 5.05 , SD = 5.11 ) ( P = 0.0002 ) . At the 6-month follow-up assessment , the mean of pain score in the acupressure group ( 1.08 , SD = 1.43 ) was still significantly lower than that in the physical therapy group ( 3.15 , SD = 3.62 ) ( P = 0.0004 ) . CONCLUSIONS Our results suggest that acupressure is another effective alternative medicine in reducing low back pain , although the st and ard operating procedures involved with acupressure treatment should be carefully assessed in the future Study Design . A r and omized controlled trial . Objectives . To determine 1 ) whether , among patients with persistent disabling low back pain ( LBP ) , a group program of exercise and education using a cognitive behavioral therapy ( CBT ) approach , reduces pain and disability over a subsequent 12-month period ; 2 ) the cost-effectiveness of the intervention ; and 3 ) whether a priori preference for type of treatment influences outcome . Summary of Background Data . There is evidence that both exercise and CBT delivered in specialist setting s is effective in improving LBP . There is a lack of evidence on whether such interventions , delivered by trained individuals in primary care , result in improved outcomes . Methods . The study was conducted in nine family medical practice s in East Cheshire , UK . Patients 18 to 65 years of age , consulting with LBP , were recruited ; those still reporting LBP 3 months after the initial consultation were r and omized between the two trial arms . The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach . Both arms received an educational booklet and audio-cassette . The primary outcome measures were pain ( 0–100 Visual Analogue Scale ) and disability ( Rol and and Morris Disability Scale ; score 0–24 ) . Results . A total of 196 subjects ( 84 % ) completed follow-up 12 months after the completion of the intervention program . The intervention showed only a small and nonsignificant effect at reducing pain ( −3.6 mm ; 95 % confidence interval , −8.5 , 1.2 mm ) and disability ( −0.6 score ; 95 % confidence interval , −1.6 , 0.4 ) . The cost of the intervention was low with an incremental cost-effectiveness ratio of £ 5000 ( U.S. $ 8650 ) per quality adjusted life year . In addition , patients allocated to the intervention that had expressed a preference for it had clinical ly important reductions in pain and disability . Conclusions . This intervention program produces only modest effects in reducing LBP and disability over a 1-year period . The observation that patient preference for treatment influences outcome warrants further investigation BACKGROUND Because the value of popular forms of alternative care for chronic back pain remains uncertain , we compared the effectiveness of acupuncture , therapeutic massage , and self-care education for persistent back pain . METHODS We r and omized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture ( n = 94 ) , therapeutic massage ( n = 78 ) , or self-care educational material s ( n = 90 ) . Up to 10 massage or acupuncture visits were permitted over 10 weeks . Symptoms ( 0 - 10 scale ) and dysfunction ( 0 - 23 scale ) were assessed by telephone interviewers masked to treatment group . Follow-up was available for 95 % of patients after 4 , 10 , and 52 weeks , and none withdrew for adverse effects . RESULTS Treatment groups were compared after adjustment for prer and omization covariates using an intent-to-treat analysis . At 10 weeks , massage was superior to self-care on the symptom scale ( 3.41 vs 4.71 , respectively ; P = .01 ) and the disability scale ( 5.88 vs 8.92 , respectively ; P<.001 ) . Massage was also superior to acupuncture on the disability scale ( 5.89 vs 8.25 , respectively ; P = .01 ) . After 1 year , massage was not better than self-care but was better than acupuncture ( symptom scale : 3.08 vs 4.74 , respectively ; P = .002 ; dysfunction scale : 6.29 vs 8.21 , respectively ; P = .05 ) . The massage group used the least medications ( P<.05 ) and had the lowest costs of subsequent care . CONCLUSIONS Therapeutic massage was effective for persistent low back pain , apparently providing long-lasting benefits . Traditional Chinese Medical acupuncture was relatively ineffective . Massage might be an effective alternative to conventional medical care for persistent back pain Inpatient and outpatient treatments were compared with a control intervention in 288 men and 168 women , aged 35 - 54 , who were at work , but suffered from chronic or recurrent low back pain . Physical measurements and back pain assessment s were carried out before the intervention and at a 3-month follow-up . Physical fitness improved most in the in patients , but the out patients did not differ from the controls . Correlations between back pain and physical measurements indicated that increase of lumbar and hip mobility was more important than increase of trunk strength for subjective progress in these patients . Increased trunk extension strength correlated significantly with subjective progress in women , who also had higher correlations between improved physical fitness and progress than men Objective : To determine whether treatment with spinal manipulative therapy ( SMT ) administered in addition to st and ard care is associated with clinical ly relevant early reductions in pain and analgesic consumption . Methods : 104 patients with acute low back pain were r and omly assigned to SMT in addition to st and ard care ( n = 52 ) or st and ard care alone ( n = 52 ) . St and ard care consisted of general advice and paracetamol , diclofenac or dihydrocodeine as required . Other analgesic drugs or non-pharmacological treatments were not allowed . Primary outcomes were pain intensity assessed on the 11-point box scale ( BS-11 ) and analgesic use based on diclofenac equivalence doses during days 1–14 . An extended follow-up was performed at 6 months . Results : Pain reductions were similar in experimental and control groups , with the lower limit of the 95 % CI excluding a relevant benefit of SMT ( difference 0.5 on the BS-11 , 95 % CI −0.2 to 1.2 , p = 0.13 ) . Analgesic consumptions were also similar ( difference −18 mg diclofenac equivalents , 95 % CI −43 mg to 7 mg , p = 0.17 ) , with small initial differences diminishing over time . There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups . The extended follow-up showed similar patterns . Conclusions : SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain BACKGROUND Few studies have evaluated the association between patient expectations for recovery and clinical outcomes , and no study has evaluated whether asking patients to choose their therapy modifies such an association . OBJECTIVE To evaluate the association between patients ’ expectations and functional recovery in patients with acute low back pain ( LBP ) , and to determine whether that association is affected by giving patients choice of therapy . DESIGN AND PARTICIPANTS A secondary analysis of a r and omized controlled trial comparing usual care alone to usual care plus choice of chiropractic , acupuncture , or massage in 444 adults with acute LBP , lasting less than 21 days . MEASUREMENTS AND MAIN RESULTS Primary outcome was functional disability ( Rol and score ) at 5 and 12 weeks . Patients ’ general expectations for improvement were associated with improvement in functional status ( β = 0.96 , 95 % CI = 0.56 , 1.36 ) . A 1-point increase in general expectations was associated with a 0.96-point improvement in Rol and score . The association of expectation with outcome was 2–3 times greater in the usual care group than the choice group . However , these differences did not reach statistical significance . CONCLUSIONS In patients with acute LBP , higher expectations for recovery are associated with greater functional improvement . Eliciting patient expectations for improvement may be a simple way to identify patients with the highest ( or lowest ) likelihood of experiencing functional improvement . Incorporating questions about patient expectations in future trials may clarify the role of this important correlate of clinical outcomes OBJECTIVE To compare the short-term outcomes of active individual therapy ( AIT ) with those of a functional restoration program ( FRP ) . DESIGN Prospect i ve r and omized controlled study . SETTING Two rehabilitation centers and private ambulatory physiotherapy facilities . PARTICIPANTS One hundred thirty-two adults with chronic low back pain . Fifty-one percent of patients on sick leave or out of work ( mean duration , 180d in the 2y before treatment ) . INTERVENTIONS For 5 weeks , FRP ( at 25h/wk ) or AIT ( at 3h/wk ) . MAIN OUTCOME MEASURES Trunk flexibility , back flexor , and extensor endurance ( Ito and Sorensen tests ) , general endurance , pain intensity , Dallas Pain Question naire ( DPQ ) scores , daily activities , anxiety depression , social interest , and work and leisure activities , and self-reported improvement ( work ability , resumption of sport and leisure activities ) . RESULTS All outcome measures improved after treatment except endurance in AIT . There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores . Better results were observed in FRP for all other outcome measures . There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction ; a significant effect of treatment and initial value on the gains of Ito , endurance , and DPQ social interest and anxiety depression scores , with no treatment or initial value interaction ; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores . CONCLUSIONS Low-cost ambulatory AIT is effective . The main advantage of FRP is improved endurance . We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities Many clinical trials on chiropractic management of low back pain have neglected to include specific forms of care . This study compared two well-defined treatment protocol s. The objective was to compare the outcome of flexion – distraction ( FD ) procedures performed by chiropractors with an active trunk exercise protocol ( ATEP ) performed by physical therapists . A r and omized clinical trial study design was used . Subjects , 18 years of age and older , with a primary complaint of low back pain ( > 3 months ) were recruited . A 100 mm visual analogue scale ( VAS ) for perceived pain , the Rol and Morris ( RM ) Question naire for low back function , and the SF-36 for overall health status served as primary outcome measures . Subjects were r and omly allocated to receive either FD or ATEP . The FD intervention consisted of the application of flexion and traction applied to specific regions in the low back , with the aid of a specially design ed manipulation table . The ATEP intervention included stabilizing and flexibility exercises , the use of modalities , and cardiovascular training . A total of 235 subjects met the inclusion /exclusion criteria and signed the informed consent . Of these , 123 were r and omly allocated to FD and 112 to the ATEP . Study patients perceived significantly less pain and better function after intervention , regardless of which group they were allocated to ( P<0.01 ) . Subjects r and omly allocated to the flexion – distraction group had significantly greater relief from pain than those allocated to the exercise program ( P=0.01 ) . Subgroup analysis indicated that subjects categorized as chronic , with moderate to severe symptoms , improved most with the flexion – distraction protocol . Subjects categorized with recurrent pain and moderate to severe symptoms improved most with the exercise program . Patients with radiculopathy did significantly better with FD . There were no significant differences between groups on the Rol and Morris and SF-36 outcome measures . Overall , flexion – distraction provided more pain relief than active exercise ; however , these results varied based on stratification of patients with and without radiculopathy and with and without recurrent symptoms . The subgroup analysis provides a possible explanation for contrasting results among r and omized clinical trials of chronic low back pain treatments and these results also provide guidance for future work in the treatment of chronic low back pain In a r and omized , observer-blind trial , 150 men and women , aged 21 - 64 years , with chronic/subchronic low-back pain , followed one of these three treatment regimens : 1 ) intensive , dynamic back-muscle exercises ; 2 ) conventional physiotherapy , including isometric exercises for the trunk and leg muscles ; and 3 ) placebo-control treatment involving semihot packs and light traction . Eight treatment sessions were given during the course of 4 weeks , each session lasting 1 hour . The short-term effect was evaluated at the end of the treatment period and 1 month later , and the long-term effect at 6 and 12 months . The evaluations included recording of changes in pain level and assessment of overall treatment effect , which were indicated on visual interval scales . Subgroups of patients could be identified according to their treatment responses : physiotherapy was the superior treatment for the male participants , whereas the intensive back exercises appeared to be most efficient for the female participants . Patients with moderate or hard physical occupations tended toward a better response with physiotherapy , whereas intensive back exercises seemed most effective for those with sedentary/light job functions & NA ; Psychosocial factors have been shown to play an important role in the development of chronic low back pain ( LBP ) . In our recently completed cluster‐r and omized trial we found , however , no evidence of an effect of our minimal intervention strategy ( MIS ) aim ed at psychosocial factors , over usual care ( UC ) in patients with (sub)acute LBP . To explore the reasons why , this paper presents an evaluation of the processes presumably underlying the effectiveness of MIS . General practitioner ( GP ) attitude was evaluated by the Pain Attitudes and Beliefs Scale and two additional questions . GP behaviour was evaluated by analysing treatment registration forms and patients ' responses to items regarding treatment content . Patients also scored items on satisfaction and compliance . Modification of psychosocial measures was evaluated by analysing changes after 6 and 52 weeks on the Fear Avoidance and Beliefs Question naire , the Coping Strategies Question naire and the 4‐Dimensional Symptom Question naire . A total of 60 GPs and 314 patients participated in the study . GPs in the MIS‐group adopted a less biomedical orientated attitude than in the UC‐group , but were only moderately successful in identification of psychosocial factors . Treatment contents as perceived by the patient and patient satisfaction differed significantly between both groups . Changes on psychosocial measures , however , did not differ between groups . The suboptimal identification of psychosocial factors in the MIS‐group and the absence of a relevant impact on psychosocial factors may explain why MIS was not more effective than UC Purpose To evaluate whether patients ’ treatment preferences , characteristics , or symptomatic response to assessment moderated the effect of the McKenzie method for acute low back pain ( LBP ) . Methods This study involved a secondary analysis of a previous RCT on the effect of adding the McKenzie method to the recommended first-line care for patients with acute non-specific LBP . 148 patients were r and omized to the First-line Care Group ( recommended first-line care alone ) or the McKenzie Group ( McKenzie method in addition to the first-line care ) for a 3-week course of treatment . The primary outcome was pain intensity at 3 weeks . The ability of six patient characteristics to identify those who respond best to McKenzie method was assessed using interaction terms in linear regression models . Results The six investigated potential effect modifiers for response to the McKenzie method did not predict a more favorable response to this treatment . None of the point estimates for effect modification met our pre-specified criterion of clinical importance of a 1 point greater improvement in pain . For five of the six predictors , the 95 % CI did not include our criterion for meaningful clinical improvement . Conclusion We were unable to find any clinical ly useful effect modifiers for patients with acute LBP receiving the McKenzie method Study Design . A subgroup analysis of patient outcomes from a r and omized controlled trial comparing a Back to Fitness program with usual general practitioner care . Objectives . To test whether patients with high scores on measures of fear-avoidance and distress/depression benefit the most . Summary of Background Data . A fitness program , ongoing since the 1980s , was developed for use in the community and has been shown to be effective in reducing disability . Detailed analyses are needed to identify patient groups who benefit . Recent evidence points to the potentially important role of fear , distress , and depression . Method . Data from 98 patients allocated to normal general practitioner care and 89 patients allocated to a group exercise program were analyzed after categorizing baseline scores on fear-avoidance beliefs ( high/low ) and distress/depression ( at risk/normal ) . The main outcome measure was the Rol and Disability Question naire . Outcomes were compared between the intervention and control groups at 6 weeks , 6 months , and 12 months . Results . High fear-avoiders fared significantly better in the exercise program than in usual general practitioner care at 6 weeks and at 1 year . Low fear-avoiders did not . Patients who were distressed or depressed were significantly better off at 6 weeks , but the benefits were not maintained long-term . Conclusion . Patients with high levels of fear-avoidance beliefs could significantly benefit from the Back to Fitness program . The benefits of the exercise program for patients with high levels of distress/depression appear to be short-term only . Average attendance was only 4 to 5 classes , which may not be sufficient for more recalcitrant cases . Further research is indicated Objective : To investigate the effects of a multidisciplinary back school programme ( Roessingh Back Rehabilitation Programme , RRP ) compared with usual care , as well as differences in treatment outcome between subgroups defined using two multiaxial assessment instruments : the Multidimensional Pain Inventory ( MPI-DLV ) and lumbar dynamometry . Design : R and omized controlled trial . Setting : Rehabilitation . Subjects : One hundred and sixty-three patients with chronic , aspecific low back pain . Intervention : All subjects were r and omly assigned either to a multidisciplinary , physically oriented group treatment or to their usual care . Main outcome measures : The Rol and Disability Question naire and health-related quality of life ( EuroQol , EQ5-D ) were measured as primary outcomes before r and omization and after eight weeks and six months follow-up . Result : Only 30 - 50 % of the patients in the RRP group showed improvement and this number is not significantly different from the control group . Subgroup analyses give some first indications that multiaxial measurement instruments can be used to identify subgroups with differences in treatment effects . Conclusion : The overall effect of a multidisciplinary treatment is disappointing , however multiaxial assessment before admission might be valuable in clinical practice , result ing in more effective treatments for patients with chronic low back pain Objectives ( 1 ) To determine if treatment outcome in chronic low back pain can be predicted by a predefined multivariate prognostic model based on consistent predictors from the literature and ( 2 ) to explore the value of potentially prognostic factors further . Methods Data were derived from a r and omized controlled trial on the effect of a multidisciplinary rehabilitation program for chronic low back pain compared with usual care . The primary outcome measure was the Rol and and Morris Disability Question naire and secondary outcomes were the Physical and Mental Component Summary Scales , derived from the Short Form Health Survey . Outcomes were expressed as the differences between baseline and follow-up ( 8 wk and 6 mo ) values . A confirmatory and an exploratory model were defined . Baseline predictors included in the confirmatory model were pain intensity , work status , and Multidimensional Pain Inventory subgroup membership . The exploratory model included sick leave , compensation , depression , and fear-avoidance beliefs . Statistical analysis was performed using multiple linear regression analysis . Results One hundred and sixty-three patients participated in the study . More pain was prognostic for more improvement in the rehabilitation group . No value was found for work status or the Multidimensional Pain Inventory subgroups . For the exploratory model , more depression and fear-avoidance beliefs predicted more improvement after rehabilitation . The explained variance ranged from 18.5 % to 43.8 % depending on the length of follow-up evaluation , the treatment group , and the outcome variable of interest . Discussion The results of this study do not support the construction of a clinical prediction model . Future confirmative studies of homogeneous rehabilitation treatments and outcome measures are needed to shed more light on relevant prognostic factors Abstract We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme , an intensive training programme , or a general practitioner programme , the latter serving as the control group . Patients aged 19–64 years on sick leave for low-back pain with or without sciatica were included in a prospect i ve r and omised study evaluating outcomes such as impairment , pain , functional disability , socio-economic disability and satisfaction with the treatment or explanations . Evaluation by unbiased observers was performed at 1 , 3 and 12 months . The three treatment groups were comparable at baseline . With regard to satisfaction , the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups . With regard to the explanations of current low-back pain episodes , the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups . The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up . However , no differences were revealed between the groups with respect to outcomes on measures of impairment , pain , functional disability or socio-economic disability . All three study groups showed rapid improvement . After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study . Within the limitations discussed in our study , it is concluded that ( 1 ) patients sick listed with acute low-back pain , with or without sciatica , will be significantly improved after 1 month regardless of conservative treatment programme ; ( 2 ) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme ; ( 3 ) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups , especially the manual treatment group ; ( 4 ) they will not show any other differences with respect to subjective and objective variables , either at short-term or at long-term follow-ups Study Design . Cluster r and omized controlled trial . Objective . To improve quality of care for patients with low back pain ( LBP ) a multifaceted general practitioner education alone and in combination with motivational counseling by practice nurses has been implemented in German general practice s. We studied effects on functional capacity ( main outcome ) , days in pain , physical activity , quality of life , or days of sick leave ( secondary outcomes ) compared with no intervention . Summary of Background Data . International research has lead to the development of the German LBP guideline for general practitioners . However , there is still doubt about the most effective implementation strategy . Although effects on process of care have been observed frequently , changes in patient outcomes are rarely seen . Methods . We recruited 1378 patients with LBP in 118 general practice s , which were r and omized to 1 of 3 study arms : a multifaceted guideline implementation ( GI ) , GI plus training of practice nurses in motivational counseling ( MC ) , and the postal dissemination of the guideline ( controls , C ) . Data were collected ( question naires and patient interviews ) at baseline and after 6 and 12 months . Multilevel mixed effects modeling was used to adjust for clustering of data and potential confounders . Results . After 6 months , functional capacity was higher in the intervention groups with a cluster adjusted mean difference of 3.650 between the MC group and controls ( 95 % CI = 0.320–6.979 , P = 0.032 ) and 2.652 between the GI group and controls ( 95 % CI = −0.704 to 6.007 , P = 0.120 ) . Intervention effects were more pronounced regarding days in pain per year with an average reduction of 16 ( GI ) to 17 days ( MC ) after 6 months ( 12 and 9 days after 12 months ) compared with controls . Conclusion . Active implementation of the German LBP guideline results in slightly better outcomes during 6 months follow-up than its postal dissemination . Results are more distinct when practice nurses are trained in motivational counseling BACKGROUND Recent studies on chronic low back pain ( cLBP ) rehabilitation suggest that predictors of treatment outcome may be differ according to the considered conservative treatment . AIM To identify predictors of response to back school ( BS ) , individual physiotherapy ( IP ) or spinal manipulation ( SM ) for cLBP . POPULATION out patients with cLBP . SETTING Outpatient rehabilitation department . DESIGN Retrospective analysis from a r and omized trial . METHODS Two hundred and ten patients with cLBP were r and omly assigned to either BS , IP or SM ; the Rol and Morris Disability Question naire ( RM ) was assessed before and after treatment : those who decreased their RM score < 2.5 were considered non-responders . Baseline potential predictors of outcome included demographics , general and cLBP history , life satisfaction . RESULTS Of the 205 patients who completed treatment ( 140/205 women , age 58 + 14 years ) , non-responders were 72 ( 34.2 % ) . SM showed the highest functional improvement and the lowest non-response rate . In a multivariable logistic regression , lower baseline RM score ( OR 0.82 , 95 % CI 0.76 - 0.89 , P<0.001 ) and received treatment ( OR 0.32 , 95 % CI 0.21 - 0.50 , P<0.001 ) were independent predictors of non-response . Being in the lowest tertile of baseline RM score ( < 6 ) predicted non response to treatment for BS and IP , but not for SM ( same risk for all tertiles ) . CONCLUSIONS In our patients with cLBP lower baseline pain-related disability predicted non-response to physiotherapy , but not to spinal manipulation . CLINICAL REHABILITATION IMPACT Our results suggest that , independent form other characteristics , patients with cLBP and low pain-related disability should first consider spinal manipulation as a conservative treatment Previous trials to assess the efficacy of lumbar traction for back pain have been method ologically flawed . To avoid these shortcomings , we conducted a r and omised controlled trial in which high-dose traction was compared with sham traction . The sham traction was given with a specially developed brace that tightens in the back during traction . To the patient , the experience is that of traction . The patients and outcome assessor were blinded for the assigned treatment . 151 patients with at least six weeks of non-specific low back pain were r and omised . Intention to treat analysis showed no differences between the groups on all outcome measures ( patients ' global perceived effect , severity of main complaints , functional status and pain ) ; all 95 % confidence intervals included the value zero . The number of withdrawals from treatment , loss to follow-up , and protocol deviations was low . Consequently , the per- protocol analysis showed results similar to the intention to treat analysis . Subgroup analyses did not show any group for which traction might seem promising . Our data do not support the cl aim that traction is effective for patients with low back pain Study Design . R and omized controlled trial . Objectives . To Investigate the long-term effectiveness , costs , and effect modifiers of a mini-intervention , provided in addition to the usual care , and the incremental effect of a worksite visit for patients with subacute disabling low back pain ( LBP ) . Summary of Background Data . A mini-intervention was earlier proved to be an effective treatment for subacute LBP . Whether the beneficial effect is sustained is not known . Furthermore , modifiers of a treatment effect are largely unknown . Methods . A total of 164 patients with subacute LBP r and omized into a mini-intervention ( A , n = 56 ) , a mini-intervention plus a worksite visit ( B , n = 51 ) , or the usual care ( C , n = 57 ) . Mini-intervention consisted of a detailed assessment of the patients ’ history , beliefs , and physical findings by a physician and a physiotherapist , followed by recommendations and advice . The usual care patients received the conventional care . Pain , disability , health-related quality of life , satisfaction with care , days on sick leave , and health care consumption and costs were measured during a 24-month follow-up . Thirteen c and i date modifiers were tested for each outcome . Results . There were no differences between the three treatment arms regarding the intensity of pain , the perceived disability , or the health-related quality of life . However , mini-intervention decreased occurrence of daily ( A vs. , C , P = 0.01 ) and bothersome ( A vs. C , P < 0.05 ) pain and increased treatment satisfaction . Costs result ing from LBP were lower in the intervention groups ( A 4670 Euros , B 5990 Euros ) than in C ( C 9510 Euros ) ( A vs. C , P = 0.04 ; and B vs. C , not significant ) . The average number of days on sick leave was 30 in A , 45 in B , and 62 in C ( A vs. C , P = 0.03 ; B vs. C , not significant ) . The perceived risk for not recovering was the strongest modifier of treatment effect . Mental and mental-physical workers in A and B were less often on sick leave than those in C. Conclusions . Mini-intervention is an effective treatment for subacute LBP . Despite lack of a significant effect on intensity of low back pain and perceived disability , mini-intervention , including proper recommendations and advice , according to the “ active approach , ” is able to reduce LBP-related costs . The perceived risk of not recovering was the strongest modifier of treatment effect . In alleviating pain , the intervention was most effective among the patients with a high perceived risk of not recovering Study Design . A sub analysis of data derived from a r and omized clinical trial was performed . Objective . To evaluate the association of a patient ’s expectation for benefit from a specific treatment with improved functional outcome . Summary of Background Data . Psychosocial factors , ambiguous diagnoses , and lack of a clearly superior treatment have complicated the management of patients with chronic low back pain . The authors hypothesized that patient expectation for benefit from a specific treatment is associated with improved functional outcomes when that treatment is administered . Methods . In a r and omized trial , 135 patients with chronic low back pain who received acupuncture or massage were studied . Before r and omization , study participants were asked to describe their expectations regarding the helpfulness of each treatment on a scale of 0 to 10 . The primary outcome was level of function at 10 weeks as measured by the modified Rol and Disability scale . Results . After adjustment for baseline characteristics , improved function was observed for 86 % of the participants with higher expectations for the treatment they received , as compared with 68 % of those with lower expectations ( P = 0.01 ) . Furthermore , patients who expected greater benefit from massage than from acupuncture were more likely to experience better outcomes with massage than with acupuncture , and vice versa ( P = 0.03 ) . Conclusions . The results of this study suggest that patient expectations may influence clinical outcome independently of the treatment itself . In contrast , general optimism about treatment , divorced from a specific treatment , is not strongly associated with outcome . These results may have important implication s for clinical trial design and recruitment , and may help to explain the apparent success of some conventional and alternative therapies in trials that do not control for patient expectations . The findings also may be important for therapy choices made in the clinical setting Purpose . To compare a group exercise programme known as the Back to Fitness programme with individual physiotherapy for patients with non-specific low back pain from a material ly deprived area . Method . This was a r and omized controlled trial including 237 physiotherapy patients with back pain lasting more than six weeks . Participants were allocated to either the Back to Fitness programme or to individual physiotherapy , and followed up at three months and 12 months after r and omization . The main outcome measure was the Rol and Disability Question naire . Secondary measures were : SF12 , EQ5D , Pain Self-Efficacy Scale . Health care diaries recording patients ' use of health care re sources were also collected over a 12-month period . Results . There were no statistically significant differences in change scores between groups on the primary outcome measure at three months ( CI − 2.24 to 0.49 ) and at 12 months ( CI − 1.68 to 1.39 ) . Only minor improvements in disability scores were observed in the Back to Fitness group at three months and 12 months respectively ( mean change scores ; − 0.89 , − 0.77 ) and in the individual physiotherapy arm ( mean change scores ; − 0.02 , − 0.63 ) . Further analysis showed that patients from the most severely deprived areas were marginally worse at three month follow-up whereas those from more affluent areas tended to improve ( CI 0.43 to 3.15 ) BACKGROUND Low-back pain is a common and costly problem . We estimated the effectiveness of a group cognitive behavioural intervention in addition to best practice advice in people with low-back pain in primary care . METHODS In this pragmatic , multicentre , r and omised controlled trial with parallel cost-effectiveness analysis undertaken in Engl and , 701 adults with troublesome subacute or chronic low-back pain were recruited from 56 general practice s and received an active management advisory consultation . Participants were r and omly assigned by computer-generated block r and omisation to receive an additional assessment and up to six sessions of a group cognitive behavioural intervention ( n=468 ) or no further intervention ( control ; n=233 ) . Primary outcomes were the change from baseline in Rol and Morris disability question naire and modified Von Korff scores at 12 months . Assessment of outcomes was blinded and followed the intention-to-treat principle , including all r and omised participants who provided follow-up data . This study is registered , number IS RCT N54717854 . FINDINGS 399 ( 85 % ) participants in the cognitive behavioural intervention group and 199 ( 85 % ) participants in the control group were included in the primary analysis at 12 months . The most frequent reason for participant withdrawal was unwillingness to complete question naires . At 12 months , mean change from baseline in the Rol and Morris question naire score was 1.1 points ( 95 % CI 0.39 - 1.72 ) in the control group and 2.4 points ( 1.89 - 2.84 ) in the cognitive behavioural intervention group ( difference between groups 1.3 points , 0.56 - 2.06 ; p=0.0008 ) . The modified Von Korff disability score changed by 5.4 % ( 1.99 - 8.90 ) and 13.8 % ( 11.39 - 16.28 ) , respectively ( difference between groups 8.4 % , 4.47 - 12.32 ; p<0.0001 ) . The modified Von Korff pain score changed by 6.4 % ( 3.14 - 9.66 ) and 13.4 % ( 10.77 - 15.96 ) , respectively ( difference between groups 7.0 % , 3.12 - 10.81 ; p<0.0001 ) . The additional quality -adjusted life-year ( QALY ) gained from cognitive behavioural intervention was 0.099 ; the incremental cost per QALY was 1786 pound sterling , and the probability of cost-effectiveness was greater than 90 % at a threshold of 3000 pound sterling per QALY . There were no serious adverse events attributable to either treatment . INTERPRETATION Over 1 year , the cognitive behavioural intervention had a sustained effect on troublesome subacute and chronic low-back pain at a low cost to the health-care provider . FUNDING National Institute for Health Research Health Technology Assessment Programme OBJECTIVES To estimate the clinical effectiveness of active management ( AM ) in general practice versus AM plus a group-based , professionally led cognitive behavioural approach ( CBA ) for subacute and chronic low back pain ( LBP ) and to measure the cost of each strategy over a period of 12 months and estimate cost-effectiveness . DESIGN Pragmatic multicentred r and omised controlled trial with investigator-blinded assessment of outcomes . SETTING Fifty-six general practice s from seven English regions . PARTICIPANTS People with subacute and chronic LBP who were experiencing symptoms that were at least moderately troublesome . INTERVENTIONS Participants were r and omised ( in a ratio of 2:1 ) to receive either AM+CBA or AM alone . MAIN OUTCOME MEASURES Primary outcomes were the Rol and Morris Disability Question naire ( RMQ ) and the Modified Von Korff Scale ( MVK ) , which measure LBP and disability . Secondary outcomes included mental and physical health-related quality of life ( Short Form 12-item health survey ) , health status , fear avoidance beliefs and pain self-efficacy . Cost-utility of CBA was considered from both the UK NHS perspective and a broader health-care perspective , including both NHS costs and costs of privately purchased goods and services related to LBP . Quality -adjusted life-years ( QALYs ) were calculated from the five-item EuroQoL. RESULTS Between April 2005 and April 2007 , 701 participants were r and omised : 233 to AM and 468 to AM+CBA . Of these , 420 were female . The mean age of participants was 54 years and mean baseline RMQ was 8.7 . Outcome data were obtained for 85 % of participants at 12 months . Benefits were seen across a range of outcome measures in favour of CBA with no evidence of group or therapist effects . CBA result ed in at least twice as much improvement as AM . Mean additional improvement in the CBA arm was 1.1 [ 95 % confidence interval ( CI ) 0.4 to 1.7 ] , 1.4 ( 95 % CI 0.7 to 2.1 ) and 1.3 ( 95 % CI 0.6 to 2.1 ) change points in the RMQ at 3 , 6 and 12 months respectively . Additional improvement in MVK pain was 6.8 ( 95 % CI 3.5 to 10.2 ) , 8.0 ( 95 % CI 4.3 to 11.7 ) and 7.0 ( 95 % CI 3.2 to 10.7 ) points , and in MVK disability was 4.3 ( 95 % CI 0.4 to 8.2 ) , 8.1 ( 95 % CI 4.1 to 12.0 ) and 8.4 ( 95 % CI 4.4 to 12.4 ) points at 3 , 6 and 12 months respectively . At 12 months , 60 % of the AM+CBA arm and 31 % of the AM arm reported some or complete recovery . Mean cost of attending a CBA course was 187 pounds per participant with an additional benefit in QALYs of 0.099 and an additional cost of 178.06 pounds . Incremental cost-effectiveness ratio was 1786.00 pounds . Probability of CBA being cost-effective reached 90 % at about 3000 pounds and remained at that level or above ; at a cost-effectiveness threshold of 20,000 pounds the CBA group had an almost 100 % probability of being considered cost-effective . User perspectives on the acceptability of group treatments were sought through semi-structured interviews . Most were familiar with key messages of AM ; most who had attended any group sessions had retained key messages from the sessions and two-thirds talked about a reduction in fear avoidance and changes in their behaviour . Group sessions appeared to provide reassurance , lessen isolation and enable participants to learn strategies from each other . CONCLUSIONS Long-term effectiveness and cost-effectiveness of CBA in treating subacute and chronic LBP was shown , making this intervention attractive to patients , clinicians and purchasers . Short-term ( 3-month ) clinical effects were similar to those found in high- quality studies of other therapies and benefits were maintained and increased over the long term ( 12 months ) . Cost per QALY was about half that of competing interventions for LBP and because the intervention can be delivered by existing NHS staff following brief training , the back skills training programme could be implemented within the NHS with relative ease . TRIAL REGISTRATION Current Controlled Trials IS RCT N37807450 . FUNDING The National Institute for Health Research Health Technology Assessment programme BACKGROUND Recommendations for the management of low back pain in primary care emphasise the importance of recognising and addressing psychosocial factors at an early stage . We compared the effectiveness of a brief pain-management programme with physiotherapy incorporating manual therapy for the reduction of disability at 12 months in patients consulting primary care with subacute low back pain . METHODS For this pragmatic , multicentre , r and omised clinical trial , eligible participants consulted primary care with non-specific low back pain of less than 12 weeks ' duration . They were r and omly assigned either a programme of pain management ( n=201 ) or manual therapy ( n=201 ) . The primary outcome was change in the score on the Rol and and Morris disability question naire at 12 months . Analysis was by intention to treat . FINDINGS Of 544 patients assessed for eligibility , 402 were recruited ( mean age 40.6 years ) and 329 ( 82 % ) reached 12-month follow-up . Mean disability scores were 13.8 ( SD 4.8 ) for the pain-management group and 13.3 ( 4.9 ) for the manual-therapy group . The mean decreases in disability scores were 8.8 ( 6.4 ) and 8.8 ( 6.1 ) at 12 months ( difference 0 [ 95 % CI -1.3 to 1.4 ] , p=0.99 ) , and median numbers of physiotherapy visits per patient were three ( IQR one to five ) and four ( two to five ) , respectively ( p=0.001 ) . One adverse reaction ( an exacerbation of pain after the initial assessment ) was recorded . INTERPRETATION Brief pain management techniques delivered by appropriately trained clinicians offer an alternative to physiotherapy incorporating manual therapy and could provide a more efficient first-line approach for management of non-specific subacute low back pain in primary care BACKGROUND AND METHODS There are few data on the relative effectiveness and costs of treatments for low back pain . We r and omly assigned 321 adults with low back pain that persisted for seven days after a primary care visit to the McKenzie method of physical therapy , chiropractic manipulation , or a minimal intervention ( provision of an educational booklet ) . Patients with sciatica were excluded . Physical therapy or chiropractic manipulation was provided for one month ( the number of visits was determined by the practitioner but was limited to a maximum of nine ) ; patients were followed for a total of two years . The bothersomeness of symptoms was measured on an 11-point scale , and the level of dysfunction was measured on the 24-point Rol and Disability Scale . RESULTS After adjustment for base-line differences , the chiropractic group had less severe symptoms than the booklet group at four weeks ( P=0.02 ) , and there was a trend toward less severe symptoms in the physical therapy group ( P=0.06 ) . However , these differences were small and not significant after transformations of the data to adjust for their non-normal distribution . Differences in the extent of dysfunction among the groups were small and approached significance only at one year , with greater dysfunction in the booklet group than in the other two groups ( P=0.05 ) . For all outcomes , there were no significant differences between the physical-therapy and chiropractic groups and no significant differences among the groups in the numbers of days of reduced activity or missed work or in recurrences of back pain . About 75 percent of the subjects in the therapy groups rated their care as very good or excellent , as compared with about 30 percent of the subjects in the booklet group ( P<0.001 ) . Over a two-year period , the mean costs of care were $ 437 for the physical-therapy group , $ 429 for the chiropractic group , and $ 153 for the booklet group . CONCLUSIONS For patients with low back pain , the McKenzie method of physical therapy and chiropractic manipulation had similar effects and costs , and patients receiving these treatments had only marginally better outcomes than those receiving the minimal intervention of an educational booklet . Whether the limited benefits of these treatments are worth the additional costs is open to question |
10,930 | 24,384,441 | The pooled relative risks for both studies reporting the risk estimates by IL-10 categories and studies reporting the risk estimates by unit IL-10 indicated an association between high IL-10 levels and adverse events .
Sensitivity and subgroup analysis indicated that the results obtained in IL-10 categories were not stable .
Data from our meta- analysis supported the existence of a relationship between high serum IL-10 levels and adverse events in patients with ACS . | BACKGROUND Several studies investigating the prognostic utility of interleukin-10 ( IL-10 ) in patients with acute coronary syndrome ( ACS ) have provided conflicting findings .
The aim of the study was to assess the existing evidence regarding association between serum IL-10 levels and adverse events . | IL-10 is considered a potent antiinflammatory cytokine that strongly inhibits the production of proinflammatory cytokines . Recent studies have suggested that IL-10 also has immunostimulatory properties on CD4 + , CD8 + T cells , and /or NK cells , result ing in increased IFN-γ production . To determine the effect of IL-10 on IFN-γ production and related inflammatory responses in humans , 16 healthy subjects received a bolus i.v . injection of LPS ( 4 ng/kg ) in combination with either placebo or recombinant human IL-10 ( 25 μg/kg ) , administered just before or 1 h after LPS . IL-10 treatment , particularly when administered after LPS , enhanced LPS-induced IFN-γ release , as well as the release of the IFN-γ-dependent chemokines IFN-γ-inducible protein-10 and monokine induced by IFN-γ , while inhibiting or not influencing the production of IFN-γ-inducing cytokines . In addition , IL-10 treatment enhanced activation of CTLs and NK cells after LPS injection , as reflected by increased levels of soluble granzymes . These data indicate that high-dose IL-10 treatment in patients with inflammatory disorders can be associated with undesired proinflammatory effects Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective —The goal of this study was to examine the association of the antiinflammatory interleukin-10 ( IL-10 ) with risk of cardiovascular disease ( CVD ) . Methods and Results —In the PROSPER ( PROspect i ve Study of Pravastatin in the Elderly at Risk ) cohort , we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control ( n=1618 ) study of 3.2 years of follow-up . Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein . IL-10 was positively associated with risk of CVD events ( odds ratio [ OR ] 1.17 , 95 % CI 1.05 to 1.31 per unit increase in log IL-10 ) after adjusting for classical risk factors and C-reactive protein . Furthermore , IL-10 was associated more strongly with CVD risk among those with no previous history of CVD ( OR 1.42 , 95 % CI 1.18 to 1.70 ) , compared with those with previous CVD ( OR 1.04 , 95 % CI 0.90 to 1.19 ; P=0.018 ) . Overall , IL-10 showed a modest ability to add discrimination to classical risk factors ( C-statistic + 0.005 , P=0.002 ) . Conclusion —Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events , although the association is less evident in those with a history of CVD . Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted OBJECTIVES The goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A ( PAPP-A ) in patients with acute coronary syndromes ( ACS ) . BACKGROUND Pregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization . METHODS In 547 patients with angiographically vali date d ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain , respectively , PAPP-A as well as markers of myocardial necrosis ( troponin T [ TnT ] ) , ischemia ( vascular endothelial growth factor [ VEGF ] ) , inflammation ( high-sensitivity C-reactive protein [ hsCRP ] ) , anti-inflammatory activity ( interleukin [IL]-10 ) , and platelet activation ( soluble CD40 lig and [ sCD40L ] ) were determined . Patients were followed for the occurrence of death or myocardial infa rct ion . RESULTS In patients with ACS , elevated PAPP-A levels ( > 12.6 mIU/l ) indicated an increased risk ( odds ratio 2.44 [ 95 % confidence interval ( CI ) 1.43 to 4.15 ] ; p = 0.001 ) . When the analysis was restricted to TnT-negative patients , PAPP-A still identified a subgroup of high-risk patients ( odds ratio [ OR ] 2.72 [ 95 % confidence interval ( CI ) 1.25 to 5.89 ] ; p = 0.009 ) . In a multivariable model , PAPP-A ( OR 2.01 ; p = 0.015 ) , sCD40L ( OR 2.37 ; p = 0.003 ) , IL-10 ( OR 0.43 ; p = 0.003 ) , and VEGF ( OR 2.19 ; p = 0.018 ) were independent predictors . Prospect i ve validation in patients with chest pain confirmed that PAPP-A levels reliably identify high-risk patients ( adjusted OR 2.32 [ 95 % CI 1.32 to 4.26 ] ; p = 0.008 ) . Patients negative for all three markers ( TnT , sCD40L , and PAPP-A ) were at very low cardiac risk ( 30 days : 3.0 % event rate ; no death ) . CONCLUSIONS The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS . Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS Objectives : To re-evaluate the relation between plasma interleukin-10 ( IL-10 ) concentration at hospital admission and outcome and to investigate the impact of single nucleotide polymorphisms ( SNP ) in the IL-10 gene in patients with non-ST elevation acute coronary syndrome ( ACS ) . Design : Determination of IL-10 plasma concentrations and genotyping of SNPs in the IL-10 gene in a prospect i ve trial of patients with ACS and in a group of healthy controls . Patients : 3179 patients in the Fragmin and fast revascularisation during InStability in Coronary artery disease II ( FRISC II ) trial and 393 healthy controls . Main outcome measures : Mortality and incidence of myocardial infa rct ion ( MI ) at 12 months . Results : The median and interquartile ranges of IL-10 were 0.8 ( 0.5–1.0 ) pg/ml in healthy controls and 1.1 ( 0.7–1.9 ) pg/ml in patients ( p<0.001 ) . In patients , IL-10 predicted a crude risk increase of death/MI , with the highest risk observed in the fourth quartile ( adjusted odds ratio 1.7 ( 95 % confidence interval 1.2 to 2.3 ) ) . Adjustment for common risk indicators , including C-reactive protein and interleukin-6 , weakened the association to a non-significant level . The 1170 CC genotype weakly predicted increased plasma concentrations of IL-10 in patients ( p = 0.04 ) and in controls ( p = 0.03 ) , which was consistent with the modest association of this variant with coronary disease ( p = 0.01 ) . Conclusion : In contrast with some previous reports , we conclude that IL-10 reflects a proinflammatory state in patients with ACS and we therefore suggest that IL-10 is as effective a biomarker for the risk prediction of future cardiovascular events as other markers of systemic inflammation BACKGROUND The prognostic value of interleukin (IL)-10 in patients with ST-segment elevation acute myocardial infa rct ion ( ST-se AMI ) is currently unclear . The purpose of this study was to test whether the serum IL-10 level can predict 30-day mortality in patients with ST-se AMI undergoing primary percutaneous coronary intervention ( PCI ) . METHODS AND RESULTS The study design was a prospect i ve cohort study of 250 consecutive patients with ST-se AMI of onset < 12 h who were undergoing primary PCI . Blood sample s for serum IL-10 levels were collected in the catheterization laboratory following vascular puncture . The serum IL-10 level was also evaluated in 20 healthy and 30 at-risk control subjects . The mean serum level of IL-10 was significantly higher in the AMI patients than in either group of controls ( all values of p<0.0001 ) . Patients with a high serum IL-10 level ( > or = 30 pg/ml ) had a significantly lower left ventricular ejection fraction ( LVEF ) ( defined as < 50 % ) , significantly higher incidence of cardiogenic shock , higher white blood cell ( WBC ) count , more advanced congestive heart failure ( defined as New York Heart Association function classification of > or = 3 ) , and increased 30-day mortality than those patients with a low serum IL-10 level ( < 30 pg/ml ) ( all values of p<0.0001 ) . Multiple stepwise logistic regression analysis demonstrated that a high serum IL-10 level , together with low LVEF , high WBC count and unsuccessful reperfusion , was independently predictive of increased 30-day mortality ( all values of p<0.005 ) . CONCLUSION In patients with ST-se AMI , the serum IL-10 level is a major independent predictor of 30-day mortality and should be used for early risk stratification following acute myocardial infa rct ion UNLABELLED Interleukin-10 ( IL-10 ) is a cytokine with pleiotropic properties . Limited biochemical and clinical evidence suggest a link between IL-10 and coronary heart disease ( CHD ) . However , more data are needed to clarify the relationship between IL-10 and risk for CHD events . METHODS The present study was a secondary analysis of the estrogen replacement and atherosclerosis ( ERA ) trial , a r and omized clinical trial that examined the effects of hormone replacement therapy on post-menopausal women with known coronary atherosclerosis . IL-10 concentration , measured at baseline , was treated as both a continuous and categorical variable . Cox proportional hazards models were used to compute hazard ratios as estimates of relative risk for CHD events . RESULTS There were 71 events over an average 3.2 year follow-up . Incident rates were higher for individuals with IL-10 concentrations equal to or greater than the median level ( 1.04 pg/mL ) compared to those individuals below the median level ( 30 % versus 18.5 % , p=0.02 ) . The cumulative incidence of CHD events was significantly greater in individuals with IL-10 concentrations > or=1.04 pg/mL ( p=0.01 ) . A one st and ard deviation increase in baseline IL-10 concentration was associated with a 34 % greater risk of a CHD event ( HR 1.34 [ 1.06 - 1.68 ] , p=0.01 ) . This elevated risk was not altered by interleukin-6 , C-reactive protein , or additional cardiovascular risk factors . IL-10 concentration and risk for CHD events was most pronounced in diabetics ( HR 2.4 [ 1.46 - 3.83 ] , p=0.0005 ) . CONCLUSION In the ERA trial , elevated IL-10 concentration was associated with an increased risk for future cardiovascular events in post-menopausal women with established coronary atherosclerosis . Further study of the relationship between IL-10 and the pathogenesis and progression of atherosclerosis and cardiovascular events is warranted OBJECTIVE To evaluate the safety and clinical efficacy of administering an anti-interleukin-10 ( anti-IL-10 ) monoclonal antibody ( mAb ) to systemic lupus erythematosus ( SLE ) patients with active and steroid-dependent disease . In addition , we sought to assess the effects of in vivo IL-10 neutralization on biologic markers of SLE . METHODS Treatment consisted of 20 mg/day intravenous administration of an anti-IL-10 murine mAb ( B-N10 ) for 21 consecutive days , with a followup period of 6 months . Six patients were studied . RESULTS Treatment was safe and well tolerated . All patients developed antibodies against B-N10 . Cutaneous lesions and joint symptoms improved in all patients beginning during B-N10 administration and continuing to month 6 . The SLE Disease Activity Index decreased from a mean + /- SEM of 8.83+/-0.91 on day 1 to 3.67+/-0.67 on day 21 ( P = 0.001 ) , 1.50+/-0.84 at month 2 , and 1.33+/-0.80 at month 6 ( P<0.001 ) . At the end of followup , the disease was clinical ly inactive in 5 of the 6 patients . Prednisone administration was decreased from a mean + /- SEM of 27.9+/-5.7 mg/day on day 1 to 9.6+/-2.0 mg/day at month 6 ( P<0.005 ) . Activity of immune and endothelial cells rapidly decreased , as assessed by the early evolution of several biologic markers . CONCLUSION This is the first report of IL-10 antagonist administration to humans . The study shows the involvement of IL-10 in the pathogenesis of SLE , and indicates that the use of IL-10 antagonists may be beneficial in the management of refractory SLE Overexpression of proinflammatory , type 1 cytokines has been demonstrated in psoriasis and is believed to be of pathophysiological importance . IL-10 is a type 2 cytokine with major impact on immunoregulation , since it inhibits type 1/proinflammatory cytokine formation . Therefore , we investigated its role in psoriasis . We found a relative deficiency in cutaneous IL-10 mRNA expression compared with other inflammatory dermatoses . Interestingly , patients during established antipsoriatic therapy showed higher IL-10 mRNA expression of peripheral blood mononuclear cells than patients before therapy . This suggested that IL-10 may have antipsoriatic capacity . Therefore , we performed a phase 2 pilot trial with subcutaneous IL-10 administration ( 8 microg/kg/d ) over 24 d in three patients . Clinical efficiency measured by objective and subjective parameters was found . Immunosuppressive effects ( depressed monocytic HLA-DR expression , TNF-alpha and IL-12 secretion capacity , IL-12 plasma levels , and responsiveness to recall antigens ) as well as a shift toward a type 2 cytokine pattern ( increasing proportion of IL-4 , IL-5 , and IL-10 producing T cells , selective increase in IgE serum levels ) were observed . Remarkably , IL-10 administration also enhanced the intracutaneous IL-10 mRNA expression . Our investigations demonstrate the major importance of IL-10 in psoriasis and show that IL-10 administration represents a new therapeutic approach . This is the first report on IL-10 therapy for cutaneous disorders Atherosclerosis is currently considered a chronic inflammatory disease of the vessel wall . Systemic markers of inflammation have been shown to be of significant prognostic relevance for assessing the risk of atherosclerotic disease progression (1)(2)(3)(4 ) . Previous data showed that proinflammatory markers , such as C-reactive protein ( CRP ) , play an important role in acute coronary events (5)(6)(7 ) and that decreased plasma concentrations of antiinflammatory cytokines , for example , interleukin-10 ( IL-10 ) were also associated with acute coronary syndrome ( ACS ) (8)(9)(10 ) . Statins , 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors , represent a well-established class of drugs that effectively lower serum cholesterol concentrations and are widely used for the treatment of cardiovascular disease (11)(12)(13 ) . In addition to their cholesterol-lowering activity , statins have been demonstrated to possess pleiotropic effects , including antiinflammatory effects (14)(15)(16)(17 ) . Results obtained in numerous investigations have suggested that administration of statins could modify concentrations of CRP and other proinflammatory cytokines with a concurrent decrease in cardiovascular events . However , the potential influence of statins on the antiinflammatory cytokine IL-10 in patients with ACS has not been investigated . In the present study , 42 patients with unstable angina ( UA ) were r and omly assigned immediately after admission to st and ard therapy plus either 20 mg/day atorvastatin or placebo . The st and ard therapy included aspirin , beta-blockers , heparin/low – molecular-weight heparin , angiotensin-converting enzyme inhibitors , and oral nitrates . The protocol s of the study were approved by the Ethics Review Board of the Hospital , and all patients gave written , informed consent . The patients with UA presented with ischemic chest pain at rest in the absence of extracardiac cause with ST-segment depression ≥0.1 mV in 2 or more contiguous leads on 12-lead electrocardiograms at administration . Echocardiography was performed in all patients to exclude patients with an impaired left UNLABELLED PURPOSE OR BACKGROUND : Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by a variety of cell types , such as macrophages and activated monocytes . IL-10 possesses numerous anti-inflammatory , anti-thrombotic and anti-atherosclerotic properties . Furthermore , patients with acute coronary syndrome have been demonstrated to have reduced levels of IL-10 compared to their stable counterparts . For these reasons , it has been proposed that IL-10 plays a protective role in both atherogenesis and plaque vulnerability . However , 2 short-term studies on the prognostic utility of IL-10 in patients with acute coronary syndrome have provided conflicting results , with one study showing that reduced levels of IL-10 were predictors of adverse outcomes and another showing that elevated levels predicted poor outcomes . The objective of the present study was to investigate the long-term prognostic significance of baseline IL-10 levels in patients with acute coronary syndrome . METHODS Baseline plasma IL-10 levels were measured in 193 well-characterized male patients with acute coronary syndrome who were referred for coronary angiography and followed prospect ively for 5 years for the development of major adverse cardiovascular events . RESULTS After controlling for a variety of baseline variables ( including established biomarkers such as high-sensitivity C-reactive protein and N-terminal-pro-B-type natriuretic peptide ) , plasma IL-10 levels ( whether analyzed as a continuous variable or as a categorical variable using receiver operating characteristic-derived cut point ) were a strong and independent predictor of the composite outcome of death or non-fatal myocardial infa rct ion when using a Cox proportional hazards model . CONCLUSIONS These data demonstrate that , despite biologic plausibility for IL-10 as being a cardioprotective cytokine , elevated baseline plasma levels of IL-10 are a strong and independent predictor of long-term adverse cardiovascular outcomes in patients with acute coronary syndrome |
10,931 | 26,321,038 | RESULTS The evaluated studies show that patients treated with OXY-TDS experience a significant reduction in urinary incontinence episodes compared with placebo , which is comparable to that observed in patients treated with oral oxybutynin or with tolterodine .
The clinical practice study also showed improved quality of life , achieving benefits in numerous patient profiles , with an efficacy independent of previous treatments .
The safety of the drug was demonstrated in the various patient profiles .
OXY-TDS represents an effective alternative for the symptomatic treatment of adult patients with OAB , which , thanks to its pharmacokinetic profile , better tolerability , different administration method and dosage , could represent an added value in treating special population | CONTEXT There is currently a broad therapeutic arsenal of drugs for treating overactive bladder syndrome ( OAB ) .
However , there is still a need for new compounds and for improving known drugs in terms of efficacy , compliance and tolerability .
OBJECTIVE To report the scientific evidence on the safety and efficacy of transdermal oxybutynin ( OXY-TDS ) for treating OAB . | The safety and efficacy of oxybutynin transdermal delivery system ( oxybutynin-TDS ) versus placebo in adults with urge and mixed urinary incontinence was investigated using combined results from double-blind stages of 2 phase3 clinical trials . Study 1 : placebo-controlled , parallel-group comparison of 3 oxybutynin – TDS doses in 12-week double-blind and open-label periods , followed by a 28-week open-label extension . Study 2 was a 12-week r and omized , double-blind , placebo-controlled comparison of oxybutynin-TDS versus long-acting tolterodine and placebo , followed by a 52-week open-label extension . Efficacy analysis included 241 patients receiving oxybutynin-TDS , 244 receiving placebo . Most participants were Caucasian women ( 92 % ) . Approximately 60 % received prior anticholinergic therapy . Primary outcome was determined by changes from baseline to end of treatment in frequency of incontinence episodes , frequency of urination , and void volume . Oxybutynin-TDS was significantly more effective than placebo in reducing median daily incontinence episodes ( −3.0 vs placebo −2.0 ; P=.00004 ) and daily urinary frequency ( −2.0 vs −1.0 ; P=.0023 ) , and in increasing void volume ( 25 mL vs 5.5 mL ; P<.00001 ) . Overall rates of anticholinergic adverse events ( AEs ) were 12.8 % for oxybutynin-TDS and 11.0 % for placebo ( P=0.5421 ) . The most common systemic anticholinergic AEs were dry mouth ( 7.0 % for oxybutynin-TDS vs 5.3 % for placebo ) and constipation ( 2.1 % vs 2.0 % ) . Application site erythema occurred in 7.0 % of participants who received oxybutynin-TDS ( 3.7 % discontinuation rate ) ; pruritus occurred in 16.1 % ( 3.3 % discontinuation rate ) . Transdermal oxybutynin was shown to be efficacious , with a proven safety profile . It may be utilized for patients with overactive bladder as a treatment option that could enhance compliance OBJECTIVES To compare the efficacy and safety of an oxybutynin transdermal delivery system ( OXY-TDS ) and oral , long-acting tolterodine ( TOL-LA ) with placebo in previously treated patients with urge or mixed urinary incontinence . METHODS After withdrawal of their current antimuscarinic therapy , 361 adult patients were r and omized to 12 weeks of double-blind , double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day , daily TOL-LA 4 mg , or placebo . Evaluations included change from baseline in patient urinary diary symptoms , incontinence-specific quality of life , and safety . RESULTS OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes ( median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo ; P < 0.05 ) , increased the average void volume ( median change 24 and 29 mL versus 5.5 mL , P < 0.01 ) , and improved quality of life ( incontinence impact question naire [ IIQ ] total score , P < 0.05 ; Urogenital Distress Inventory Irritative Symptom subscale , P < 0.05 ) compared with placebo . The most common adverse event for OXY-TDS was localized application site pruritus ( 14 % versus 4 % placebo ) accompanied by a low incidence of systemic side effects ( eg , dry mouth 4.1 % ) . Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment ( dry mouth 7.3 % versus 1.7 % placebo , P < 0.05 ) . CONCLUSIONS OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence . OXY-TDS improves systemic safety with regard to anticholinergic side effects . Local skin irritation occurs in some OXY-TDS patients OBJECTIVE The objective of the study was to determine the impact of overactive bladder on sexual function from a preliminary analysis of the Multicenter Assessment of Transdermal Therapy in Overactive Bladder with Oxybutynin study . STUDY DESIGN The Multicenter Assessment of Transdermal Therapy in Overactive Bladder with Oxybutynin study was an open-label , prospect i ve trial of 2878 subjects with overactive bladder , treated with transdermal oxybutynin for 6 months or less . The impact of overactive bladder on sexual function before and after treatment was assessed via item responses from the King 's Health Question naire and Beck Depression Inventory-II ( kappa-test ) . RESULTS At baseline , 586 ( 23.1 % ) reported that overactive bladder had an impact on their sex life . Coital incontinence in 569 ( 22.8 % ) decreased after treatment to 438 ( 19.3 % ) . Effects of overactive bladder on subjects ' sex lives improved in 19.1 % ( worsened in 11.2 % ) , and the effect on relationships with partners improved in 19.6 % ( worsened in 11.9 % ) . Reduced interest in sex , reported by 52.1 % at baseline , improved significantly . ( all P < .0001 ) . CONCLUSION Overactive bladder negatively affects sexual function . Treatment with transdermal oxybutynin improved sexual function and marital relationships PURPOSE We evaluated the efficacy and safety of an oxybutynin transdermal delivery system ( TDS ) in a general population of patients with overactive bladder and urge or mixed urinary incontinence . MATERIAL S AND METHODS Following symptom stabilization or treatment withdrawal 520 adult patients were r and omized to 12 weeks of double-blind daily treatment with 1.3 , 2.6 or 3.9 mg . oxybutynin TDS or placebo administered twice weekly , followed by a 12-week open-label , dose titration period to assess efficacy and safety further . Evaluations included patient urinary diaries , incontinence specific quality of life and safety . RESULTS A dose of 3.9 mg . daily oxybutynin TDS significantly reduced the number of weekly incontinence episodes ( median change -19.0 versus -14.5 , p = 0.0165 ) , reduced average daily urinary frequency ( mean change -2.3 versus -1.7 , p = 0.0457 ) , increased average voided volume ( median change 24 versus 6 ml . , p = 0.0063 ) and significantly improved quality of life ( Incontinence Impact Question naire total score , p = 0.0327 ) compared with placebo . Average voided volume increased in the daily 2.6 mg . group ( 19 ml . , p = 0.0157 ) but there were no other significant differences between 1.3 and 2.6 mg . oxybutynin TDS and placebo . The most common adverse event was application site pruritus ( oxybutynin TDS 10.8 % to 16.8 % , placebo 6.1 % ) . Dry mouth incidence was similar in both groups ( 7.0 % versus 8.3 % , p not significant ) . In the open-label period a sustained reduction of nearly 3 incontinence episodes per day was reported for all groups . CONCLUSIONS Doses of 2.6 and 3.9 mg . oxybutynin TDS daily improve overactive bladder symptoms and quality of life , and are well tolerated . Transdermal oxybutynin is an innovative new treatment for overactive bladder BACKGROUND AND OBJECTIVE Oxybutynin is a common antimuscarinic therapy for overactive bladder . Transdermally administered oxybutynin chloride topical gel 10 % ( OTG ) has a low propensity for anticholinergic adverse effects and possibly also a low risk of cognitive impairment . A r and omized , double-blind , placebo- and active-controlled study evaluated the effects of OTG on cognitive and psychomotor functions in older healthy adults . METHODS Healthy adults aged 60 - 79 years were assigned r and omly ( 1:1:1 ) to 1-week 's treatment with OTG ( 1 g [ 100 mg oxybutynin ] applied once daily on rotating sites of upper arms/shoulders , abdomen or thighs ) plus oral placebo , immediate-release oxybutynin ( OXB-IR ; 5 mg capsule three times/day ) plus placebo gel , or double placebo . Delayed recall Name-Face Association Test ( NFAT ) score was the primary end point . Treatments were compared by analysis of covariance . RESULTS Of 152 participants ( mean age , 68 years ) , 49 received OTG , 52 OXB-IR and 51 placebo . NFAT Delayed Recall tests revealed no significant treatment differences ( overall , p = 0.2733 ; OTG vs placebo , p = 0.1551 ; OXB-IR vs placebo , p = 0.1767 ) . However , a significant effect ( p = 0.0294 ) was noted for the Misplaced Objects Test , with scores declining only for OXB-IR . Approximately twice as many participants receiving OXB-IR ( n = 10 ) as those receiving OTG ( n = 5 ) or placebo ( n = 6 ) showed a significant decline ( ≥6 points ) in Total Recall score for the Hopkins Verbal Learning Test-Revised . No significant effects on psychomotor reaction time were observed . The most common adverse event , dry mouth , occurred in 6.1 % , 73.1 % and 7.8 % of participants receiving OTG , OXB-IR and placebo , respectively . CONCLUSIONS OTG applied for 1 week had no clinical ly meaningful effect on recent memory or other cognitive functions in healthy , older adults . CLINICAL TRIAL REGISTRATION Registered as NCT00752141 at www . clinical trials.gov PURPOSE We compared the short-term efficacy , safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence . MATERIAL S AND METHODS Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study . Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent r and omization to transdermal or oral treatment . Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily . Dose titration was based on anticholinergic symptoms . Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary , a visual analog scale for efficacy and anticholinergic symptoms reported on a question naire . Safety monitoring included adverse events and skin tolerability of the transdermal system . RESULTS A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment . Mean age in the transdermal and oral groups was 64 and 63 years , and 87 % and 97 % were female , respectively . Daily incontinent episodes decreased in the transdermal and oral groups ( 7.3 to 2.4 [ 66 % ] and 7.4 to 2.6 [ 72 % ] , respectively , p = 0.39 ) . The visual analog scale reduction in urinary leakage improved from washout in both groups ( p < 0.0001 ) with no difference between them ( p = 0.9 ) . Dry mouth occurred in significantly fewer patients in the transdermal ( 38 % ) compared with those in the oral group ( 94 % , p < 0.001 ) . Of the patients in the transdermal group 67 % noticed a reduction in dry mouth severity compared with previous oral treatment , and 90 % had none or mild skin erythema . CONCLUSIONS Transdermal delivery of oxybutynin result ed in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence |
10,932 | 12,535,413 | REVIEW ER 'S CONCLUSIONS The use of mesh during laparoscopic hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30 - 50 % .
However , there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair .
The data suggests less persisting pain and numbness following laparoscopic repair .
Return to usual activities is faster .
However , operation times are longer and there appears to be a higher risk of serious complication rate in respect of visceral ( especially bladder ) and vascular injuries | BACKGROUND Inguinal hernia repair is the most frequently performed operation in general surgery .
The st and ard method for inguinal hernia repair had changed little over a hundred years until the introduction of synthetic mesh .
This mesh can be placed by either using an open approach or by using a minimal access laparoscopic technique .
Although many studies have explored the relative merits and potential risks of laparoscopic surgery for the repair of inguinal hernia , most individual trials have been too small to show clear benefits of one type of surgical repair over another .
OBJECTIVES The objective of this review was to compare minimal access laparoscopic mesh techniques with open techniques .
Comparisons of open mesh techniques versus open non-mesh techniques have been considered in a separate Cochrane review . | Abstract Background : Giant prosthetic reinforcement of the visceral sac ( GPRVS ) , an open preperitoneal mesh repair , is a very effective groin hernia repair . Laparoscopic transabdominal preperitoneal repair ( TAPP ) , based on the same principle , is expected to combine low recurrence rates with minimal postoperation morbidity . Methods : Seventy-nine patients with 93 recurrent and 15 concomitant primary inguinal hernias were r and omized between GPRVS ( 37 patients ) and TAPP ( 42 patients ) . Operating time , complications , pain , analgesia use , disability period , and recurrences were recorded . Results : Mean operating time was 56 min with GPRVS versus 79 min with TAPP ( p < 0.001 ) . Most complications were minor , except for a pulmonary embolus and an ileus , both after GPRVS . Patients experienced less pain after a laparoscopic repair . Average disability period was 23 days with GPRVS versus 13 days with TAPP ( p= 0.03 ) for work , and 29 versus 21 days , respectively ( p= 0.07 ) for physical activities . Recurrence rates at a mean follow-up of 34 months were 1 in 52 ( 1.9 % ) for GPRVS versus 7 in 56 ( 12.5 % ) for TAPP ( p= 0.04 ) . Hospital costs in U.S. dollars were comparable , with GPRVS at $ 1,150 and TAPP at $ 1,179 . Conclusions : Laparoscopic repair of recurrent inguinal hernia has a lower morbidity than GPRVS . However , laparoscopic repair is a difficult operation , and the potential technical failure rate is higher . With regard to recurrence rates , the open preperitoneal prosthetic mesh repair remains the best repair OBJECTIVE To compare outcome and costs between laparoscopic and open hernia repair . DESIGN Prospect i ve r and omised study . SETTING One university and two district hospitals in Sweden . SUBJECTS 200 men aged 25 - 75 years . MAIN OUTCOME MEASURES Operating time , hospital stay , complications , and time to recovery . A cost-minimisation- analysis was used in which the total costs were calculated for a defined period of time for each option . RESULT The one year follow-up rate was 98 % . Mean ( SD ) operation times in the laparoscopic and open groups were 72 ( 30 ) and 62 ( 25 ) minutes , respectively ( p = 0.009 ) . Hospital stay and complication rates did not differ between the groups . Among employees the mean ( SD ) periods off work in the laparoscopic and open groups were 10 ( 8) and 23 ( 21 ) days , respectively ( p = 0.0001 ) . The mean direct costs of the laparoscopic operation were increased by SEK 4037 ( US$ 483 ) but the savings in indirect costs result ing from earlier return to work were SEK 11392 ( US$ 1364 ) . CONCLUSIONS Laparoscopic hernia repair gave the employed patients faster recovery and return to work , and was the most cost-effective strategy provided that both direct and indirect costs were included BACKGROUND Benefits of laparoscopic herniorrhaphy ( LH ) over open hernia repair ( OH ) remain unproved . METHODS Interim analysis of a prospect i ve r and omized controlled trial compared OH with LH where study outcomes were measured by third-party evaluators through patient interviews . RESULTS Both groups were well matched for all baseline parameters , although LH patients anticipated a quicker postoperative recovery than OH ( p = 0.014 ) . No significant difference was noted in operating time or surgeon operative satisfaction . The median duration of hospital stay was 1 day in both groups ; LH patients made use of significantly less postoperative narcotics than OH ( p = 0.02 ) . No difference was observed in the duration s of convalescence ( LH , 9.6 + /- 7.6 days ; OH , 10.9 + /- 7.4 days ) . Greater improvements in quality of life were exhibited in LH patients than OH patients 1 month after operation ( p = 0.035 ) , with one of the two measures used . A greater percentage of LH patients seemed " very satisfied with their operation " ( p = 0.07 ) . Complication rates were similar , and a single recurrence , in a patient in the OH group , has been observed after a median follow-up of 14 months . CONCLUSIONS Direct cost measurements showed LH to be 40 % more expensive than OH in the context of a Canadian-type health care system . To date , benefits in postoperative pain and possibly quality of life have been detected in the LH group Abstract Background : In February 1993 a prospect i ve r and omized multicenter trial was initiated to compare laparoscopic transabdominal preperitoneal hernioplasty to Shouldice herniorrhaphy as performed by surgeons of nonspecialized clinics . Methods : Until January 1994 , 87 patients with 108 hernias took part in the trial ( 43 Shouldice and 44 laparoscopic repairs ) . Results : The laparoscopic procedure took significantly longer than did the open operation but caused less pain as measured by pain analogue score and consumption of paracetamol and narcotics . The postoperative complication rate was 26 % in the open and 16 % in the laparoscopic group . The patients in the laparoscopic group were discharged earlier and their convalescence was shorter than after open hernia repair . There has been one early recurrence in the laparoscopic and two in the open group to date with a mean follow-up of 201 days . Conclusions : Laparoscopic hernia repair causes less pain than the conventional operation and enables the patient to return to full work and usual activities earlier . The recurrence rate will not be known for 5 years Abstract Background : Laparoscopic herniorrhaphy is controversial and deserves critical evaluation . Methods : In a r and omized prospect i ve study transabdominal preperitoneal laparoscopic herniorrhaphy ( n= 24 ) was compared in patients to the tension-free Lichtenstein repair ( n= 29 ) utilizing vali date d and reliable pain and activity assessment tools . The Sickness Impact Profile ( SIP ) was used to compare preoperative normal activity to postoperative activity . A Pain-O-Meter ( visual analogue scale plus affective and sensory pain descriptors ) assessed intensity of pain . The total pain assessment score and SIP were compared across time ( postoperative day 1–42 ) . Analgesic medication was used as a covariate . Results : The total pain score was less for laparoscopic herniorrhaphy but this did not reach statistical significance . Similarly , the SIP showed modest improvement for laparoscopic herniorrhaphy . No differences between groups were noted for morphine equivalents of administered analgesics or length of hospitalization . Conclusion : Further investigation of laparoscopic herniorrhaphy is warranted A prospect i ve study of 242 patients with inguinal hernia who underwent tension‐free mesh repair by the laparoscopic transperitoneal ( n = 121 ) or the open Lichtenstein ( n = 121 ) technique was performed . There was no significant difference in operation time between the laparoscopic ( median ( range ) 35 ( 20–90 ) min ) and Lichtenstein ( 40 ( 20–90 ) min ) procedures . Discharge within 24 h of operation was more common after laparoscopic surgery ( 89·3 per cent versus 48·7 per cent ) . Consequently , hospital stay was reduced with this approach ( median ( range ) 1 ( 1–7 ) days versus 2 ( 1–10 ) days for patients who had a Lichtenstein repair ) . There was no significant difference in parenteral analgesia requirements or visual analogue pain scores between the two groups . Although use of oral analgesia in hospital was greater in patients who underwent Lichtenstein hernioplasty , this may reflect their longer stay . Rehabilitation to normal activity and return to work was shorter in patients receiving laparoscopic repair ( median 7 and 10 days , respectively ) than Lichtenstein repair ( 14 and 21 days ) ( P < 0·001 ) . Initial results suggest that laparoscopic procedures may be associated with more rapid rehabilitation compared with that of open tension‐free mesh surgery . Most patients with inguinal hernia undergoing tension‐free mesh repair by either technique would be suitable for day‐case surgery To evaluate the merits of laparoscopic inguinal hernia repair ( LHR ) compared to conventional open hernia repair ( OHR ) a r and omized study has been conducted . All patients were day surgical cases , of which 44 were r and omized to a st and ardized OHR under local anesthetic ( LA ) and 42 to an LHR under general anesthesia ( GA ) . Fifteen LHR patients had bilateral repairs . Operative time for OHR was 30.5 min , for unilateral LHR 35 min , and for bilateral LHR 60 min . OHR patients were discharged after a median of 134.5 min , which was significantly shorter than LHR patients , whose median discharge was 225 min ( P<0.01 ) . Pain scores , activity levels , analgesia requirements , and time taken to return to work were not significantly different following surgery in either group ( P<0.05 ) . There have been two recurrent hernias and one small bowel obstruction in the LHR group . We conclude that both repairs can be successfully performed as day surgical procedures . The added cost of LHR at this stage does not warrant its widespread use in unilateral hernia repairs . Which procedure is adopted should be individualized ; however , patients with bilateral hernias on presentation can be successfully managed as day cases , obviating the need for hospitalization or two operations In a prospect i ve r and omized study postoperative pain , analgesic consumption , return to physical activity and work , cosmetic result and experience with the type of operation were assessed in 86 patients undergoing inguinal hernia repair by means of either the Shouldice technique ( n = 34 ) , the laparoscopic transabdominal preperitoneal ( TAPP ) ( n = 28 ) or total preperitoneal ( TPP ) ( n = 24 ) repair . Patients having TAPP repair had decreased visual analogue scale scores for pain on the day of operation compared with those undergoing TPP and Shouldice repair ( 4.8 versus 6.5 and 6.2 respectively , P = 0.02 ) and on the first postoperative day compared with TPP ( 4.0 versus 6.0 , P = 0.01 ) . There was no difference between the three groups for days 2 , 3 , 4 , 5 and 30 after operation . Patient satisfaction with the operation , analgesic consumption , return to physical activity such as walking , driving , climbing stairs , running , bicycling and sexual intercourse , as well as return to work , was comparable in the three groups . There was a better cosmetic result after TAPP and TPP repair . This study failed to demonstrate significant benefits from laparoscopic hernia repair over the Shouldice technique Laparoscopic hernia operations have been criticized in regard to their high hospital costs . This study was design ed to compare the costs and some outcome features of totally extraperitoneal endoscopic hernia operation ( TEP ) and Lichtenstein mesh repair ( OPN ) among 45 r and omized employed patients . The medians of operative time in the TEP and OPN groups were 67.5 and 53 min , respectively . Return to normal life was 14 days in the TEP group and 20 days in the OPN group . The hospital costs per patient were $ 1,239 ( all costs are in US dollars ) in the TEP group and $ 782 in the OPN group . The median total costs were $ 3,912 and $ 4,661 in the TEP and OPN groups , respectively . The Lichtenstein operation is cheaper for the hospital . The total costs for working patients are lower with the endoscopic technique because fewer working days are lost BACKGROUND Inguinal hernias can be repaired by laparoscopic techniques , which have had better results than open surgery in several small studies . METHODS We performed a r and omized , multicenter trial in which 487 patients with inguinal hernias were treated by extraperitoneal laparoscopic repair and 507 patients were treated by conventional anterior repair . We recorded information about postoperative recovery and complications and examined the patients for recurrences one and six weeks , six months , and one and two years after surgery . RESULTS Six patients in the open-surgery group but none in the laparoscopic-surgery group had wound abscesses ( P=0.03 ) , and the patients in the laparoscopic-surgery group had a more rapid recovery ( median time to the resumption of normal daily activity , 6 vs. 10 days ; time to the return to work , 14 vs. 21 days ; and time to the resumption of athletic activities , 24 vs. 36 days ; P<0.001 for all comparisons ) . With a median follow-up of 607 days , 31 patients ( 6 percent ) in the open-surgery group had recurrences , as compared with 17 patients ( 3 percent ) in the laparoscopic-surgery group ( P=0.05 ) . All but three of the recurrences in the latter group were within one year after surgery and were caused by surgeon-related errors . In the open-surgery group , 15 patients had recurrences during the first year , and 16 during the second year . Follow-up was complete for 97 percent of the patients . CONCLUSIONS Patients with inguinal hernias who undergo laparoscopic repair recover more rapidly and have fewer recurrences than those who undergo open surgical repair Abstract Objective : To compare tension-free open mesh hernioplasty under local anaesthetic with transabdominal preperitoneal laparoscopic hernia repair under general anaesthetic . Design : A r and omised controlled trial of 403 patients with inguinal hernias . Setting : Two acute general hospitals in London between May 1995 and December 1996 . Subjects : 400 patients with a diagnosis of groin hernia , 200 in each group . Main outcome measures : Time until discharge , postoperative pain , and complications ; patients ' perceived health ( SF-36 ) , duration of convalescence , and patients ' satisfaction with surgery ; and health service costs . Results : More patients in the open group ( 96 % ) than in the laparoscopic group ( 89 % ) were discharged on the same day as the operation ( χ2=6.7 ; 1 df ; P=0.01 ) . Although pain scores were lower in the open group while the effect of the local anaesthetic persisted ( proportional odds ratio at 2 hours 3.5 ( 2.3 to 5.1 ) ) , scores after open repair were significantly higher for each day of the first week ( 0.5 ( 0.3 to 0.7 ) on day 7 ) and during the second week ( 0.7 ( 0.5 to 0.9 ) ) . At 1 month there was a greater improvement ( or less deterioration ) in mean SF-36 scores over baseline in the laparoscopic group compared with the open group on seven of eight dimensions , reaching significance on five . For every activity considered the median time until return to normal was significantly shorter for the laparoscopic group . Patients r and omised to laparoscopic repair were more satisfied with surgery at 1 month and 3 months after surgery . The mean cost per patient of laparoscopic repair was £ 335 ( 95 % confidence interval £ 228 to £ 441 ) more than the cost of open repair . Conclusion : This study confirms that laparoscopic hernia repair has considerable short term clinical advantages after discharge compared with open mesh hernioplasty , although it was more expensive . Key messages In the 4 hours after surgery laparoscopic hernia repair with general anaesthesia causes more pain than open repair with local anaesthesia ( mainly because of the anaesthesia used ) and necessitates longer stay in hospital . Laparoscopic hernia repair , however , causes less pain than open hernia repair during the first 2 weeks after discharge Laparoscopic hernia repair results in fewer episodes of wound infection , persistent local pain , genital swelling , numbness , and constipation than open repair . Urinary disturbances are more common after laparoscopic than after open repair Patients ' perception of health 1 month after the operation ( assessed with the SF-36 ) and satisfaction with treatment is superior for laparoscopic patients who also have a shorter period of convalescence after surgery The health service cost of day case laparoscopic repair is £ 335 more than the cost of open mesh hernioplasty performed on a day case Abstract Background : The aim of this prospect i ve , r and omized , controlled clinical study was to compare laparoscopic transabdominal preperitoneal ( TAPP ) hernia repair with a st and ard tension-free open mesh repair ( open ) . Methods : A total of 108 low-risk patients with unilateral ( primary or recurrent ) or bilateral hernias were r and omized to TAPP ( group 1 = 52 cases ) or open ( group 2 = 56 cases ) . The outcome measures included operating time , complications , postoperative pain , return to normal activity , operating theater costs , and recurrences . Results : The mean operative time was longer for the TAPP than for the open group only in unilateral primary hernias . At rest , the median Visual Analog Scale ( VAS ) score was higher for group 1 than group 2 at 48 h postoperatively . Mild to discomforting pain in the inguinal region after 7 days , night pain after 30 days , and inguinal hardening after 3 months were more frequent in group 2 than group 1 . No significant differences were observed in return to normal activities between the groups . One hernia recurrence was observed after 1 month in group 1 . TAPP was significantly more expensive than open . Conclusions : TAPP was associated with less postoperative pain than open . The increase in operating theater costs , however , was dramatic and was not compensated by shorter time away from work . TAPP should not be adopted routinely unless its costs can be drastically reduced Abstract . The aim of the study was prospect ively to compare the early results and outcome in 105 patients r and omly allocated to undergo tension-free laparoscopic hernia repair ( LHR ) with transabdominal preperitoneal technique ( 53 patients ) or open hernia repair ( OHR ) with mesh apposition ( 52 patients ) . The mean ( SD ) operation time was longer in the LHR group than in the OHR group : 49.6 ( 5.4 ) versus 33.9 ( 6.2 ) minutes ; p < 0.001 . One laparoscopic case was converted to open repair to deal with a hemorrhage from an aberrant obturatory artery at the level of Cooper 's ligament . Groin discomfort or pain was the most common complication after both procedures . The patients requiring none , one , two , or more than two doses of intramuscular diclofenac were , respectively , 40.4 % , 40.4 % , 15.4 % , and 3.8 % after LHR and 50.0 % , 30.8 % , 17.3 % , and 1.9 % after OHR ( p= 0.69 ; NS ) . The mean ± SEM ( range ) postoperative visual analog scale score , ranging from 0 ( no pain ) to 10 ( worst pain imaginable ) , was 3.1 ± 0.2 ( 1–7 ) in the LHR subset and 2.7 ± 0.2 ( 1–5 ) in the OHR group ( p= 0.14 ; NS ) ; on the second postoperative day the score was 2.3 ± 0.2 ( 1–6 ) and 1.8 ± 0.1 ( 1–4 ) , respectively ( p < 0.03 ) . The time ± SEM ( range ) of resumption of pain-free normal activities and work was faster in OHR group : 6.1 ± 0.2 ( 4–8 ) weeks versus 6.5 ± 0.1 ( 4–8 ) weeks ; p < 0.03 . Our results showed that tension-free open hernia repair is superior to LHR in terms of postoperative pain with no important differences in recovery BACKGROUND The rapid and widespread introduction of minimal access surgery has major implication s for the National Health Service . It can not be assumed that replacing an open procedure with a minimal access alternative will be cost-effective . Laparoscopic inguinal hernia repair is a procedure for which the potential economic benefits are particularly unclear . It is currently being adopted in many centres , although limited evidence on its clinical and cost-effectiveness exists . METHODS This economic comparison of laparoscopic versus open hernia repair was undertaken on data collected on 104 patients undergoing surgery on a day case basis , in the context of a r and omized controlled trial . RESULTS The mean total health service cost of laparoscopic repair was 1074 pounds versus 489 pounds for open repair [ mean difference in total health service costs 583 pounds ; 95 percent confidence interval ( CI ) 265 pounds-904 pounds ] . This difference was largely accounted for by the difference in theatre costs . Laparoscopic repair remained significantly more expensive for most but not all of the scenarios explored in the sensitivity analysis . The direction of the cost-effectiveness ratio was not sensitive to assumptions about long-term recurrence . Neither was it sensitive to halving the operating time in the laparoscopic arm of the trial . When both operating time and the costs of consumables were reduced , laparoscopic repair remained more expensive , but results for this scenario did not achieve statistical significance on this sample size . CONCLUSIONS Laparoscopic hernia repair appears an expensive option in most plausible situations . Furthermore , many uncertainties still exist about long-term outcome after the procedure and about the conditions necessary to maximize cost-effectiveness . Large-scale r and omized studies to evaluate laparoscopic hernia repair are currently under way to address these issues . We suggest that further evidence is awaited before this technology is further diffused OBJECTIVE To determine whether transabdominal preperitoneal laparoscopic hernia repair can equal or surpass an established open method at an acceptable cost . DESIGN A r and omized , prospect i ve comparison with a follow-up of 7 to 18 months ( median , 10 months ; planned , 5 years ) . SETTING Health maintenance organization hospital . PATIENTS One hundred patients between 20 and 70 years of age were r and omized . No patient withdrew from the study after r and omization . INTERVENTIONS Transabdominal preperitoneal laparoscopic and open tension-free repairs using a polypropylene mesh . MAIN OUTCOME MEASURES Operative and discharge times , costs , recovery , and morbidity . " Return to work " was supplemented by a performance assessment using a panel of exercises . RESULTS Operative and hospitalization times were not significantly different between the two types of repair . Patients with laparoscopic unilateral repairs returned to work faster ( 9 vs 17 days ) . At 1 week postoperatively , performance of straight-leg raises correlated well with time to return to work for patients with strenuous jobs . The laparoscopic repair was more expensive than the open approach ( $ 3093 vs $ 2494 ) . CONCLUSIONS Laparoscopic transabdominal preperitoneal hernia repair can be accomplished with operative and hospitalization times and a short-term recurrence rate similar to those of an established open technique . Perioperative exercise testing may be an important adjunct to return to work in the comparison of methods We previously showed that patients undergoing transabdominal preperitoneal laparoscopic inguinal herniorrhaphy ( TAPP ) returned to activity twice as fast as open herniorrhaphy without mesh but that TAPP was twice as expensive . However , it was not clear if the immediate postoperative benefits offered by TAPP result ed from smaller incisions and less tissue dissection or from the requisite tension-free placement of mesh . We have therefore completed a prospect i ve outcome and cost analysis comparing TAPP ( n=59 ) to open preperitoneal mesh herniorrhaphy ( PPO ) ( n=40 ) to determine the differences between the two different surgical techniques . When comparing unilateral repairs , there was no difference in hernia type . PPO patients were older ( P<0.05 ) and their operations were shorter ( P<0.01 ) . Comparison of outcome parameters of pill days , out-of-house activity , and intial day to full activity revealed no difference . Cost analysis showed that total costs , disposable equipment costs , and operating room time costs were significantly less for PPO ( P<0.01 ) . There were two major complications ( 3 % ) and twelve minor complications ( 20 % ) in the TAPP group while PPO exhibited no major and five minor complications ( 12 % ) . Follow-up data revealed one recurrence in the TAPP group . There were no recurrences in the PPO group at only 7 months average follow-up . We conclude that since both procedures had similar outcomes in the immediate postoperative period , the increased cost of TAPP and increased potential for both major and minor complications make it difficult to justify its routine use Laparoscopic surgery benefits patients because it reduces pain and enables earlier mobilisation . There is concern that laparoscopic hernia repair may enter surgical practice without proper evaluation . We have done a r and omised , prospect i ve study comparing laparoscopic and open inguinal hernia repair performed under day-case general anaesthesia . 150 patients were r and omised to have laparoscopic ( group L ) or open ( group O ) herniorrhaphy . Group L underwent transabdominal stapling of preperitoneal Prolene mesh . Group O underwent open repair , with a tension-free nylon darn . Postoperatively patients completed pain analogue scales eight times over 7 days , and use of analgesia was recorded . Time of return to normal domestic activity and to work was assessed . The groups were similar in age , sex , and body surface area . Self-administered co-proxamol was a median of 18 tablets ( 1 tablet = 325 mg ) in group O ( n = 75 ) and 6 in group L ( n = 75 , p < 0.001 ) . Overall mean pain analogue score was 3.1 ( SD 1.8 , n = 70 ) in group O and 1.8 ( SD 1.1 , n = 71 ) in group L ( p < 0.0001 ) . Return to normal domestic activity was a median of 7 days in group O ( n = 72 ) and 3 days in group L ( n = 73 ) ( p < 0.001 ) . Return to work was a median of 28 days in group O ( n = 39 ) and 14 days in group L ( n = 40 ) ( p < 0.002 ) . These data suggest that laparoscopic hernia repair induces less pain than open hernia repair , and enables patients to return to normal activity and work more quickly Inguinal hernias can be repaired by traditional methods , tension-free , mesh-plug hernioplasty , and the less conventional laparoscopic techniques that have the added advantage of quicker recovery . Between September 1994 and September 1997 , a prospect i ve r and omized controlled trial was performed on 292 patients with a total of 315 hernias . Of these , 150 patients with 169 hernias underwent the extraperitoneal laparoscopic repair ( TEP ) and 142 patients with 146 hernias were treated with mesh-plug hernioplasty . Patients were examined at 1 week after surgery and every 4 months thereafter for 3 years . Operative results , postoperative recovery , complications , and recurrences were recorded . Follow-up was complete for 89 % of the patients . The average operative time was 31.5 minutes for the TEP and 30.5 minutes for the mesh-plug hernioplasty . The average operative time for the last 75 laparoscopic cases was 20 minutes , 10 minutes shorter than the open-surgery group . The overall recurrence rate was ( 2.5 % ) for the TEP and ( 3 % ) for the mesh-plug hernioplasty . Patients undergoing the laparoscopic repair consumed less narcotic analgesic and returned to their normal activity 1 week sooner than the open-surgery group . A median of 8 days vs. 15 days was required for patients to return to work , respectively , in the TEP and open-surgery group ( p<0.01 ) . Intraoperative complications occurred in two patients ( 1.3 % ) in the TEP repair . Both had peritoneal tear that m and ated conversion to the TAPP repair . There were no major postoperative complications . A total of 20 ( 13 % ) minor postoperative complications occurred in the TEP . Thirty-three ( 23 % ) minor complications occurred in the open-surgery group ( p<0.01 ) . Ninety-eight percent of the patients were discharged the same day in the open-surgery group compared to 100 % in the laparoscopy group . Patients with inguinal hernias who undergo extraperitoneal laparoscopic repair have the same recurrences and hospital stay but recover more rapidly , consume less analgesic , and have fewer minor complications than those who undergo the mesh-plug hernioplasty In a prospect i ve , r and omized study , laparoscopic ( n = 20 ) and Lichtenstein ( n = 18 ) inguinal hernia repairs were compared in relation to operative time , operative costs , hospital stay , postoperative pain , return to work , patient satisfaction , complications , and total costs . All the operations were performed with the patient under general anesthesia . The median operative times in the laparoscopic and Lichtenstein groups were 71.5 ( range , 43 - 140 ) and 45 ( 16 - 83 ) min , respectively ( p < 0.001 ) . Postoperative pain and use of analgesics was less in the laparoscopic group . The median time to return to work was 14 ( 8 - 26 ) days in the laparoscopic group and 19 ( 5 - 40 ) days in the Lichtenstein group . More complications occurred in the Lichtenstein group . The median of the operative costs , in U.S. dollars , was $ 1,395 and $ 878 , respectively , and the median total costs ( including community expenses result ing from lost workdays ) were $ 4,796 in the laparoscopic and $ 5,320 in the Lichtenstein groups OBJECTIVE To compare postoperative pain after laparoscopic hernia repair and conventional open hernia repair . DESIGN Prospect i ve , r and omized study . SETTING Veterans Affairs Medical Center . PATIENTS Sixty-two patients scheduled for elective inguinal hernia repair . INTERVENTIONS Patients were r and omized in the operating room to have a laparoscopic hernia repair ( 30 patients ) or a conventional open hernia repair ( 32 patients ) . All operations were performed while the patient was under general anesthesia to avoid anesthesia as a confounding variable . MEASURES Postoperative pain following laparoscopic hernia repair and open hernia repair were compared using the McGill Pain Score , the McGill Visual Analogue Pain Scale score , and the number of acetaminophen with 30-mg codeine sulfate ( Tylenol 3 ) tablets needed for pain during the first and second 24-hour periods postoperatively . All of the patients were interviewed and the postoperative pain was evaluated by a special study nurse ( P.M.L. ) who was blinded to the repair technique . RESULTS At 24 hours , the patients with laparoscopic hernia repair had 26 % less pain by the McGill Pain Score ( P = .02 ) and 31 % less pain by the McGill Visual Analogue Scale ( P = .006 ) than those who underwent an open hernia repair . At 48 hours the patients who underwent laparoscopic hernia repair had 28 % less pain by the McGill Pain Score ( P = .03 ) , 42 % less pain by the McGill Visual Analogue Scale ( P = .002 ) , and used 42 % fewer analgesic tablets ( P = .004 ) . CONCLUSION Patients with a laparoscopic hernia repair had significantly less pain postoperatively than those with st and ard open hernia repairs OBJECTIVE To compare results and outcomes following laparoscopic and tension-free open inguinal herniorrhaphy . DESIGN A prospect i ve , nonr and omized trial of a single surgeon 's experience . SETTING A large university hospital . PATIENTS The study included 100 patients with 116 hernias . Patients were offered open hernia repair or , if medically suitable for general anesthesia , a laparoscopic hernia repair . Fifty-seven patients underwent open repair and 43 patients underwent laparoscopic repair . INTERVENTION Laparoscopic repair was performed using a transabdominal preperitoneal mesh technique . Open hernia repair was performed using a mesh-plug technique in which the hernia sac was reduced and held in place by a cone of mesh . The floor was covered with a second piece of mesh that encircled the cord and was sutured at the internal ring ; it was held in place under the external oblique without sutures . RESULTS Patients undergoing open repair were older than those undergoing laparoscopic repair . The distribution of hernia types was similar . The laparoscopic operation took longer than the open operation ( mean [ + /- SD ] , 1.9 + /- 0.4 hours vs 1.6 + /- 0.4 hours ; P < .05 ) , was more expensive ( $ 4165 + /- $ 1154 vs $ 2985 + /- $ 1682 ; P < .05 ) , and required more postoperative admissions ( 28 % vs 3.5 % ) . There were three recurrences in the laparoscopic group and none in the open group . Patients undergoing laparoscopic repair consumed the same amount of narcotic analgesics as did the group undergoing open repair and had discomfort for the same amount of time . Patients undergoing laparoscopic repair returned to work sooner than did patients undergoing open repair ( 5.6 days vs 10.3 days ; P < .05 ) . CONCLUSIONS Laparoscopic hernia repair returns patients to the workplace faster than open hernia repair despite a similar analgesic requirement . The laparoscopic repair costs more and has a higher recurrence rate than open repair . Laparoscopic repair is most suitable for bilateral hernias . Further investigation of this technique is required before its wide-scale application can be recommended Between October 1992 and September 1994 , 70 patients presenting with primary unilateral hernia were r and omly assigned to either a transabdominal preperitoneal laparoscopic ( group L ) repair ( n = 35 ) with a 3 x 5 inch polypropylene mesh or a conventional Shouldice repair ( group S ) ( n = 35 ) . The series consisted of 60 men and 10 women , with a median age of 56 years and a BMI of 24 . We used the Nyhus classification ; there were 25 type 2 , 24 type 3a and 21 type 3b hernias . Preoperative characteristics of both groups were equivalent . When comparing group L to group S , we noted a similar operative time ( 65 + /- 20 min ) and a similar postoperative hospital stay ( 3.8 + /- 1.3 days ) . The postoperative pain that was evaluated on a visual analogue scale ( score from 0 to 10 ) was lower in group L. On the first and third postoperative day , the mean score was 3.4 + /- 1.5 and 1.3 + /- 1.4 in ( group L compared ) to 5.3 + /- 1.9 ( p < 0.001 ) and 2.8 + /- 1.8 ( p < 0.005 ) in group S. Significant morbidity occurred in 7 patients of group L : 3 seromas and 4 cases of orchitis , and in 5 patients of group S : 1 wound abcess , 2 cases of chronic neuralgia and 2 cases of orchitis . We recorded a quicker return to home activities in group L : 6 + /- 2 versus 10 + /- 4 days ( p < 0.05 ) in group S but time off work was similar in both groups ( 30 + /- 9 days ) . All patients were evaluated in April 1996 : the median follow-up was 30 months ( range : 19 - 42 months ) . We recorded 1 recurrence in group L and 3 in group S. Statistical analysis revealed that the recurrence rate , for patients older than 50 and presenting with type 3 hernia , was higher in group S ( 3/14 = 21 % ) than in group L ( 0/13 = 0 % ) . In conclusion , compared to Shouldice repair , laparoscopic herniorrhaphy is associated with less postoperative pain , a quicker return to everyday activities and an equivalent postoperative morbidity . In our series , the recurrence rate was even lower for patients older than 50 with type 3 hernia OBJECTIVE To compare the effectiveness of open and laparoscopic primary inguinal hernia repair . DESIGN R and omised controlled trial . SETTING University hospital , The Netherl and s. SUBJECTS 87 patients had 103 open repairs and 88 patients had 114 laparoscopic repairs between November 1993 and July 1995 . INTERVENTIONS Laparoscopic repair by the transabdominal preperitoneal ( TAPP ) technique and open repair by the Bassini technique . MAIN OUTCOME MEASURES Recurrence , morbidity , pain , and duration of convalescence . RESULTS Operating time was longer for laparoscopy ( mean ( SD ) : 82 ( 28 ) compared with 45 ( 15 ) minutes p < 0.001 ) . Patients in the Bassini group had higher postoperative pain scores ( mean (SD)VAS : 2.9 ( 1.6 ) compared with 2.0 ( 1.6 ) p=0.002 ) , used more analgesics ( median total intake : 2 ( 0 - 54 ) compared with 0 tablets ( 0 - 42 ) p=0.008 ) , and needed a longer convalescence time ( mean ( SD ) time to return to work : 22 ( 12.6 ) compared with 14 ( 10.1 ) days p < 0.001 ; mean ( SD ) time to return to physical activities : 27 ( 12.6 ) compared with 17 ( 12.2 ) days p < 0.001 ) . Mean follow up was 24 months . Recurrence rates were 21 % ( 22/ 103 ) after Bassini and 6 % ( 7/114 ) after laparoscopic repair ( p=0.001 ) . CONCLUSION Laparoscopic hernia repair is a safe operation , which has obvious advantages over the Bassini repair in terms of pain , use of analgesic drugs , resumption of activities , and recurrence . A disadvantage of the laparoscopic repair is the longer operating time BACKGROUND AND AIMS Before choosing between open and laparoscopic preperitoneal tension-free repair , a study comparing their safety and short-term outcome was needed . No r and omised studies comparing the two hernia repair techniques have hitherto been published . MATERIAL AND METHODS A prospect i ve r and omised study was carried out comparing laparoscopic transabdominal preperitoneal mesh herniorrhaphy ( n = 24 ) to open preperitoneal mesh herniorrhaphy ( n = 25 ) . RESULTS When comparing unilateral repairs , the mean operation time was significantly ( P < 0.01 ) shorter in the open group ( 55 min ) than in the laparoscopic group ( 66 min ) . Pain on movement ( P < 0.05 ) and pain on coughing ( P < 0.01 ) receded more rapidly in the laparoscopic group . The median time before return to work or normal activity was 7 days ( range 1 - 60 ) in laparoscopic and 5 days ( 1 - 30 ) in open repair . There were five ( 21 % ) complications associated with the laparoscopic procedure , while the open procedure result ed in two ( 8 % ) complications . After a median follow-up of 18 months the recurrence rate in the laparoscopic group was 13 % and in the open group 8 % . CONCLUSIONS In this study the open method was associated with fewer complications and recurrences than the laparoscopic technique . Despite the decreased postoperative discomfort after laparoscopic repair , there was no significant difference in median time before return to work or normal activity . These results together with the higher cost of the laparoscopic procedure suggest that the open method is more suitable at least for unilateral hernias In this study , laparoscopic transabdominal preperitoneal inguinal hernia repair and traditional open inguinal hernia repair were compared in relation to operative time , hospital stay , pain medication use , recovery time , complications , and costs . Elective hernia repairs , 126 in 106 patients , were prospect ively followed from January 1991 through September 1993 . Seventy-five procedures were performed by laparoscopy and 51 by traditional open approach . Time off work , pain medication use , surgical complications , and hospital stay were all significantly less ( p < 0.001 ) with the laparoscopic approach . Patients in the laparoscopic group returned to work on average 5.5 weeks earlier than patients who underwent traditional herniorrhaphy . The difference in operative times was not statistically significant ; however , the difference in the cost of the operations was . In conclusion , laparoscopic inguinal hernia repair offers significantly decreased postoperative pain , shorter hospital stays , faster return to work , fewer complications , and comparable operative times , but at an increased expense for the cost of laparoscopic instrumentation and technology OBJECTIVE To determine the cost-effectiveness of laparoscopic inguinal hernia repair . SUMMARY BACKGROUND DATA Laparoscopic inguinal hernia repair seems superior to open techniques with respect to short-term results . An issue yet to be studied in depth remains the cost-effectiveness of the procedure . As part of a multicenter r and omized study in which > 1000 patients were included , a cost-effectiveness analysis from a societal point of view was performed . METHODS After informed consent , all re source costs , both in and outside the hospital , for patients between August 1994 and July 1995 were recorded prospect ively . Actual costs were calculated in a st and ardized fashion according to international guidelines . The main measures used for the evaluation of inguinal hernia repair were the number of averted recurrences and quality of life measured with the Short Form 36 question naire . RESULTS Re source costs were recorded for 273 patients , 139 in the open and 134 in the laparoscopic group . Both groups were comparable at baseline . Average total hospital costs were Dfl 1384.91 ( st and ard deviation : Dfl 440.15 ) for the open repair group and Dfl 2417.24 ( st and ard deviation : Dfl 577.10 ) for laparoscopic repair , including a disposable kit of Dfl 676 . Societal costs , including costs for days of sick leave , were lower for the laparoscopic repair and offset the hospital costs by Dfl 780.83 ( 75.6 % ) , leaving the laparoscopic repair Dfl 251.50 more expensive ( Dfl 4665 versus Dfl 4916.50 ) . At present , the recurrence rate is 2.6 % lower after laparoscopic repair . Thus , 38 laparoscopic repairs , costing an additional Dfl 9,557 , prevent the occurrence of one recurrent hernia . Quality of life was better after laparoscopic repair . CONCLUSION A better quality of life in the recovery period and the possibility of replacing parts of the disposable kit with reusable instruments may result in the laparoscopic repair becoming dominantly better -- that is , less expensive and more effective from a societal perspective BACKGROUND The use of minimal access surgery for repair of groin hernias is controversial . The aim of this study was to compare endoscopic tension-free hernia repair with open tension-free hernia repair within a r and omized clinical trial . METHODS One hundred twenty patients were r and omized by four surgeons during a 1-year period . Early outcome measures were then analyzed by intention to treat . RESULTS Median postoperative pain scores ( 63 [ interquartile range ( IQR ) , 23 to 81 ] versus 35 [ IQR , 17 to 62 ] ; p = 0.004 ) and analgesia requirements ( 2.5 [ IQR , 2 to 4 ] doses verus 2.0 [ IQR , 1 to 3 ] doses ; p = 0.0008 ) were significantly less for patients undergoing endoscopic hernia repair . Hospital stay ( 1 [ IQR , 0 to 1 ] day versus 2 [ IQR , 1 to 2 ] days ; p < 0.0001 ) was also significantly reduced for the endoscopic group . Wound complications occurred significantly more frequently in the open group . No difference in pulmonary function or metabolic response to trauma ( interleukin-6 , C-reactive protein , glucose , albumin ) was observed between the groups . CONCLUSIONS This study shows significant short-term advantages for endoscopic tension-free repair over open tension-free repair . However , larger studies with a longer follow-up period are required to establish the relative merits of both procedures in the management of patients with groin hernias Background Return to normal activity after laparoscopic inguinal hernia repair has been reported to occur sooner than after conventional repair Several studies have suggested that better results are obtained after laparoscopic repair of inguinal hernia than after conventional operation . This is most obvious for bilateral and recurrent hernias but less accepted for primary unilateral hernias This study compared the sensitivity to change of comparable dimensions of a multi-item multi-dimensional health status measure ( the SF-36 ) with the equivalent single item domains on the Dartmouth COOP charts . One hundred and twenty nine patients were r and omized to either day case laparoscopic surgery ( n=60 ) or open inguinal hernia repair ( n=69 ) . Respondents completed the SF-36 and COOP charts at baseline ( prior to surgery ) and at follow up at 10 days and 6 weeks . Equivalent dimensions of physical functioning , mental health/emotional condition , social activities , pain and overall condition/general health on the two question naires were compared . Despite slightly different pictures of change provided by the physical functioning and ‘ overall condition/general health ’ dimensions the general picture of change provided by the two instruments was similar . At 10 days , patients who underwent open surgery reported far greater levels of dysfunction than those who underwent laparoscopic surgery on both question naires . At 6 weeks the pain dimension of both question naires indicated a large improvement from baseline , whilst no other domain on either question naire for either group indicated such improvement . The general picture of change provided by the two measures was similar . The results suggest that both the SF-36 and the COOP charts may prove suitable for the assessment of health perception outcomes in surgical clinical trials . Differences on certain domains were caused in large measure by the nature of the questions posed . The study once again highlights the importance of checking item content to determine the suitability of any particular measure for a given study Inguinal hernia repair is one of the most common surgical procedures undertaken in the NHS . Despite this , no previous work has examined quality of life in this patient group . This study examines quality of life preoperatively and at 3 and 6 months postoperatively in 140 patients undergoing inguinal hernia repair in the context of a r and omised controlled trial of laparoscopic versus open hernia repair . Surgery was undertaken on a day case basis , and quality of life was assessed using the Short Form 36 ( SF36 ) . In the initial phase of the study , 57 % of those screened for suitability met the study inclusion criteria and were r and omised . No significant differences were found between laparoscopic and open hernia repair in terms of quality of life at 3 and 6 months postoperatively . No difference was found between 3 and 6 month scores , suggesting that patients had already made a good recovery by 3 months . A significant improvement was found between preoperative and postoperative scores , with the greatest change arising on dimensions assessing pain , physical function , and role limitation owing to physical restriction . After st and ardising for age , sex , and social class , a comparison of the hernia patients to population norms for the SF36 was consistent with improvement from preoperative to postoperative assessment . This study has demonstrated the improvement in quality of life in patients undergoing elective inguinal hernia repair by experienced surgeons on a day case basis . It has also demonstrated the feasibility of assessing quality of life using generic measures in this patient group . Further work in this area is required . Ultimately , the priority given to elective inguinal hernia repair will depend on how the demonstrated benefits compare with those derived from other elective surgical procedures Over a 2-year period 157 inguinal hernias in 151 patients were consecutively entered in this descriptive , observational study to determine any difference in outcome between a laparoscopic inguinal hernia repair versus an open inguinal hernia repair in a community hospital setting . The laparoscopic transabdominal preperitoneal technique was utilized in 50 cases . A conventional open repair was used in 107 cases . There were statistically significant differences when the laparoscopic and open groups were compared for the number of days until driving a car ( p < 0.01 ) , the number of days until getting in and out of bed comfortably ( p = 0.01 ) , the number of days until working on a limited basis ( p = 0.01 ) , and the number of days until working on a full-time basis ( p < 0.05 ) , although these differences may be due to confounding factors in this nonr and omized study . The average length of operating time was 72.2 min laparoscopic versus 51.6 min open ( p < 0.001 ) . We have shown that laparoscopic inguinal hernia repairs may have benefits over conventional hernia repairs . This may make its use more widespread than it has already become Abstract Objective : To establish the safety , short term outcome , and theatre costs of transabdominal laparoscopic repair of inguinal hernia performed as day surgery . Design : R and omised controlled trial . The control operation was the two layer modified Maloney darn . Setting : Teaching hospital and district general hospital . Subjects : 125 men r and omised to laparoscopic or open repair of inguinal hernia . Outcome measures : Morbidity , postoperative pain and use of analgesics , quality of life , and theatre costs . Outcome was assessed by question naires administered to patients daily for 10 days and at six weeks postoperatively and by outpatient review at six weeks . Return to normal activity was assessed by question naire at three months . Results : One vascular complication ( 2 % ) occurred in the group that had open repair . Seven complications ( 12 % ) including vessel injury and early recurrence arose in the group that had laparoscopic repair ( difference in complication rate 10 % ( 95 % confidence interval 4 % to 18 % ; P=0.02 ) . Pain scores and quality of life assessed by the short form 36 showed a significant benefit to the group that had laparoscopic repair in the early postoperative period . Return to normal activity was not significantly different between the two groups . Total theatre costs were higher in the group that had laparoscopic repair ( mean cost for laparoscopic repair pounds sterling850 ( pounds sterling622 to pounds sterling1078 ) ; mean cost for open repair pounds sterling268 ( pounds sterling245 to pounds sterling292 ) ) . Conclusions : Because of the greater complication rate and higher theatre costs forlaparoscopic repair and the patient outcome preferences expressed , the results of larger trials of clinical and cost effectiveness using recurrence as the primary outcome measure should be known before laparoscopic herniorrhaphy is widely adopted OBJECTIVE To evaluate the influence of the laparoscopic technique in hernia repair regarding time to full recovery and return to work , complications , recurrence rate , and economic aspects . SUMMARY BACKGROUND DATA Several studies have shown advantages in terms of less pain and faster recovery after laparoscopic hernia repair , whereas others have not , and the cost-effectiveness has been question ed . The laparoscopic technique must be thoroughly compared with the open procedures before its true place in hernia surgery can be defined . METHODS Six hundred thirteen male patients aged 40 to 75 years were r and omized to the conventional procedure , preperitoneal mesh placed by the open technique , or laparoscopic preperitoneal mesh ( TAPP ) . Follow-up was after 7 days , 8 weeks , and 1 year . RESULTS Of 613 patients undergoing surgery , 604 ( 98.5 % ) were followed for 1 year . Patients who underwent TAPP gained full recovery after 18.4 days , compared with 24.2 days for open mesh ( p < 0.001 ) and 26.4 days for the conventional procedure ( p < 0.001 ) . Patients who underwent TAPP returned to work after 14.7 days , compared with 17.7 days for open mesh ( p = 0.05 ) and 17.9 days for the conventional procedure ( p = 0.04 ) . They also had significantly less restriction in physical activities after 7 days . The TAPP procedure was more expensive , mainly as a result of longer surgical time and equipment costs , even after compensation for earlier return to work . Complications were more common in the TAPP group , with a varying pattern between the groups . Four recurrences in the conventional , 11 in the open mesh , and 4 in the TAPP group were recorded after 1 year ( p = n.s . ) . CONCLUSION The laparoscopic technique results in both shorter time to full recovery and shorter time to return to work , at the price of substantially increased costs Abstract Background : A r and omized controlled trial was conducted in a day surgery setting comparing a st and ardized variant of the Shouldice hernioplasty with extraperitoneal laparoscopic herniorrhaphy . Methods : The laparoscopic repair was technically challenging , evidence d by conversion from extraperitoneal to transabdominal repairs in 6.25 % of patients . It was free from the inherent dangers of intraperitoneal laparoscopy . Surgical morbidity was low and comparable to that for patients r and omized to the open repair . Results : Outcome following laparoscopic extraperitoneal herniorrhaphy varied depending on the parameter measured . It was comparable to the open repair with respect to postoperative activity levels and the number of days required for return to work but inferior to the open repair in terms of operation time and time to hospital discharge . The extraperitoneal approach was superior to the open repair with respect to postoperative pain levels and analgesic requirements . No attempt was made to compare recurrence rates due to the short follow-up period . Conclusions : Laparoscopic extraperitoneal herniorrhaphy should not supercede conventional hernia repair until subjected to further trials with the aid of larger study population s and greater technical expertise ; the results of long-term recurrence rates are awaited From 5/93 up to 12/93 a prospect i ve r and omized trial was performed . 102 patients with unilateral primary inguinal hernias were included . In 48 patients a Shouldice repair and in 54 patients a laparoscopic TAPP procedure was performed . The laparoscopic method is described . There were significantly less pain and quicker mobility in the laparoscopic group . In addition a shorter period of disability of work was seen ( 21 vs. 38 days ) in the same group . The morbidity of the procedures was as low in the Shouldice as in the laparoscopic group . There was a regular control of all patients . The current follow-up period is 16 months ( 13 - 21 ) in median . In both groups there were no recurrences up to now . The efficiency of laparoscopic hernia repair is discussed In a prospect i ve controlled trial comparing postoperative course , laparoscopic hernia repair totally pre-peritoneal approach appears significatively painless and more comfortable than Shouldice operation . Three criterions were used : pain question naire , visual scale , and antalgic use , during three days . These results partially explain a shorter delay to return to work ( 12 vs 31 days ) after " laparoscopic treatment " |
10,933 | 20,091,602 | Based on this review , the included studies showed that ss-interferon treatment was not associated with reduced disability progression in PPMS patients .
However , the trial population was too small to allow definitive conclusions on the efficacy of ss-interferon therapy in PPMS patients . | DOI : 10.1002/14651858.CD006643.pub2).Therapeutic trials with ss-interferon in Multiple Sclerosis ( MS ) have mainly focused on remitting-relapsing multiple sclerosis ( RRMS ) , demonstrating a reduction in relapse rate .
However , there is not enough evidence about their efficacy in patients with primary progressive multiple sclerosis ( PPMS ) .
OBJECTIVES Identify and summarize the evidence that ss-interferon is beneficial and safe in patients with PPMS . | We performed yearly MRI analyses on 327 of the total 372 patients in a multicenter , r and omized , double-blind , placebo-controlled trial of interferon beta-1b ( IFNB ) . Clinical results are presented in the preceding companion paper . Baseline MRI characteristics were the same in all treatment groups . Fifty-two patients at one center formed a cohort for frequent MRIs ( one every 6 weeks ) for analysis of disease activity . The MRI results support the clinical results in showing a significant reduction in disease activity as measured by numbers of active scans ( median 80 % reduction , p = 0.0082 ) and appearance of new lesions . In addition , there was an equally significant reduction in MRI-detected burden of disease in the treatment as compared with placebo groups ( mean group difference of 23 % , p = 0.001 ) . These results demonstrate that IFNB has made a significant impact on the natural history of MS in these patients Objective : Interferon ( IFN ) beta has repeatedly shown benefit in multiple sclerosis ( MS ) in reducing the rate of relapse , the disease activity as shown with magnetic resonance imaging and , to some degree , the progression of disability ; however , it is unknown how much the therapeutic response depends on the dose , the subgroup involved , and the disease stage . This multicentre , double blind , placebo controlled study explored the dose−response curve by examining the clinical benefit of low dose IFN beta-1a ( Rebif ® ) , 22 μg subcutaneously once weekly , in patients with secondary progressive MS . Methods : A total of 371 patients with clinical ly definite SPMS were r and omised to receive either placebo or subcutaneous IFN beta-1a , 22 μg once weekly , for 3 years . Clinical assessment s were performed every 6 months . The primary outcome was time to sustained disability , as defined by time to first confirmed 1.0 point increase on the Exp and ed Disability Status Scale ( EDSS ) . Secondary outcomes included a sensitive disability measure and relapse rate . Results : Treatment had no beneficial effect on time to confirmed progression on either the EDSS ( hazard ratio ( HR ) = 1.13 ; 95 % confidence interval ( CI ) 0.82 to 1.57 ; p = 0.45 for 22 μg v placebo ) or the Regional Functional Status Scale ( HR = 0.93 ; 95 % CI 0.68 to 1.28 ; p = 0.67 ) . Other disability measures were also not significantly affected by treatment . Annual relapse rate was 0.27 with placebo and 0.25 with IFN ( rate ratio = 0.90 ; 95 % CI 0.64 to 1.27 ; p = 0.55 ) . The drug was well tolerated with no new safety concerns identified . No significant gender differences were noted . Conclusions : This patient population was less clinical ly active than SPMS population s studied in other trials . Treatment with low dose , IFN beta-1a ( Rebif ® ) once weekly did not show any benefit in this study for either disability or relapse outcomes , including a subgroup with preceding relapses . These results add a point at one extreme of the dose−response spectrum of IFN beta therapy in MS , indicating that relapses in this phase may need treatment with higher doses than in the initial phases Objective : To evaluate the efficacy and safety of interferon beta-1b ( IFNβ-1b ) in subjects with secondary progressive multiple sclerosis ( SPMS ) . Methods : This 3-year , multicenter , double-blind , placebo-controlled , r and omized trial of IFNβ-1b included 939 subjects from the United States and Canada with SPMS and Exp and ed Disability Status Scale ( EDSS ) scores ranging from 3.0 to 6.5 . Subjects were r and omly assigned to receive either placebo or IFNβ-1b ( 250 μg or 160 μg/m2 body surface area ) , administered subcutaneously every other day . The primary outcome was time to progression by ≥1.0 EDSS point ( 0.5 point if EDSS score was 6.0 to 6.5 at entry ) confirmed at 6 months . Secondary outcomes included mean change in EDSS score from baseline , relapse-related measures , MRI activity , and a st and ardized neuropsychological function test . Results : There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNβ-1b treatment groups . However , IFNβ-1b treatment result ed in improvement on secondary outcome measures involving clinical relapses , newly active MRI lesions , and accumulated burden of disease on T2-weighted MRI . Effects were similar for both IFNβ-1b treatment groups . Neutralizing antibodies to IFNβ-1b were detected in 23 % of 250-μg and 32 % of 160-μg/m2 recipients , but their presence did not consistently affect clinical or MRI outcomes . IFNβ-1b was also well tolerated at both doses . Conclusions : Although no treatment benefit was seen on the time to confirmed progression of disability , relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested , a result consistent with the outcomes of earlier clinical trials Background Interferon & bgr;-1a ( IFN&bgr;-1a , Avonex ) is efficacious in relapsing forms of MS . Studies of other IFN&bgr ; preparations in secondary progressive MS ( SPMS ) yielded conflicting results . This study was undertaken to determine whether IFN&bgr;-1a slowed disease progression in SP-MS . Methods A total of 436 subjects with SPMS and Exp and ed Disability Status Scale ( EDSS ) score 3.5 to 6.5 were r and omized to receive IFN&bgr;-1a ( 60 & mgr;g ) or placebo by weekly intramuscular injection for 2 years . The primary outcome measure , used for the first time in a large-scale MS trial , was baseline to month 24 change in the MS Functional Composite ( MSFC ) , comprising quantitative tests of ambulation ( Timed 25-Foot Walk ) , arm function ( Nine-Hole Peg Test [ 9HPT ] ) , and cognition ( Paced Auditory Serial Addition Test [ PASAT ] ) . Results Median MSFC Z-score change was reduced 40.4 % in IFN&bgr;-1a subjects ( −0.096 vs −0.161 in placebo subjects , p = 0.033 ) , an effect driven mainly by the 9HPT and PASAT . There was no discernible benefit on the EDSS , which in this range principally reflects walking ability . IFN&bgr;-1a subjects had 33 % fewer relapses ( p = 0.008 ) . There was significant benefit on eight of 11 MS Quality of Life Inventory subscales . New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 ( both p < 0.001 ) . IFN&bgr;-1a was well tolerated by the majority of subjects . Neutralizing antibodies developed in 3.3 % of IFN&bgr;-1a – treated subjects . Conclusions IFN&bgr;-1a demonstrated benefit on MSFC progression , relapses , quality of life , and MRI activity in SPMS The accepted st and ard treatment of relapsing multiple sclerosis consists of medications for disease symptoms , including treatment for acute exacerbations . However , currently there is no therapy that alters the progression of physical disability associated with this disease . The purpose of this study was to determine whether interferon beta‐1a could slow the progressive , irreversible , neurological disability of relapsing multiple sclerosis . Three hundred one patients with relapsing multiple sclerosis were r and omized into a double‐blinded , placebo‐controlled , multicenter phase I11 trial of interferon beta‐la . Interferon beta‐la , 6.0 million units ( 30 μg ) , was administered by intramuscular injection weekly . The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Exp and ed Disability Status Scale ( EDSS ) . Interferon beta‐la treatment produced a significant delay in time to sustained EDSS progression ( p equals ; 0.02 ) . The Kaplan‐Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9 % in the placebo group and 21.9 % in the interferon beta‐la‐treated group . Patients treated with interferon beta‐la also had significantly fewer exacerbations ( p = 0.03 ) and a significantly lower number and volume of gadolinium‐enhanced brain lesions on magnetic resonance images ( pvalues ranging between 0.02 and 0.05 ) . Over 2 years , the annual exacerbation rate was 0.90 in placebo‐treated patients versus 0.61 in interferon beta‐la‐treated patients . There were no major adverse events related to treatment . Interferon beta‐ la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability , exacerbation frequency , and disease activity measured by gadolinium‐enhanced lesions on brain magnetic resonance images . This treatment may alter the hndamen‐ tal course of relapsing multiple sclerosis There is currently no disease-modifying treatment proven to be of efficacy in primary progressive multiple sclerosis ( PPMS ) . However , a number of therapeutic trials have recently been specifically design ed for this group . These include a r and omised controlled trial of interferon beta-1a which is discussed here . It is hoped that therapeutics in primary progressive multiple sclerosis will continue to exp and and effective therapeutic agents will be developed The unique clinical characteristics of primary progressive multiple sclerosis ( PPMS ) pose particular diagnostic difficulties , both in excluding other causes of progressive syndromes and in confirming the diagnosis of MS , which is not adequately addressed by current diagnostic criteria . This article presents new diagnostic criteria developed by a group of investigators on the basis of a review of their considerable experience with PPMS . ( We conclude that at least 1 year of clinical progression must be documented before a diagnosis of PPMS is made . ) Three levels of diagnostic certainty have been defined — definite , probable , and possible — based on clinical findings , abnormal cerebrospinal fluid , abnormalities on magnetic resonance imaging ( MRI ) of the brain and spinal cord , and evoked potentials . In definite PPMS , evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is required : ( 1 ) nine brain lesions , ( 2 ) two spinal cord lesions , or ( 3 ) four to eight brain lesions and one spinal cord lesion . Preliminary testing of these criteria was carried out on a cohort of 156 patients participating in a European natural history study of PPMS : 64 % fulfilled the criteria for definite PPMS , 35 % for probable PPMS , and only 1 % for possible PPMS . These criteria now require prospect i ve validation in a cohort of newly diagnosed patients and by postmortem examination . Ann Neurol |
10,934 | 30,670,040 | From the studies included the overall QoL seemed inversely related to the organ-specific impairment from sexual and urinary symptoms and increased with decreasing organ-specific symptoms for long term survivors > 6 months after treatment . | Background Previous quality of life ( QoL ) literature in bladder cancer ( BC ) patients has focused on finding the preferred urinary diversion while little is known about the QoL of patients in medical oncological treatment ( MOT ) .
We performed a systematic review to assess the existing literature on QoL in patients with muscle-invasive BC ( MIBC ) undergoing MOT . | Purpose Bladder cancer ( BC ) is one of the most common cancers worldwide . BC diagnosis and surveillance is based on cystoscopy ( CS ) . CS impact on patient ’s depression , anxiety , and sexual satisfaction ( SS ) is not sufficiently studied . There are no data on patient ’s comfort with flexible or rigid CS . Methods We prospect ively evaluated pain perception ( PP ) , depression , anxiety , and SS of 100 male patients who previously underwent at least one rigid CS in our department as surveillance after TURB procedure due to non-muscle-invasive BC and were scheduled for the next CS examination . The patients were r and omized for flexible or rigid CS . Before CS , patients described their recalled rigid CS-related pain by NRS and fulfilled HADS and SS question naires . After CS , PP was re-evaluated immediately and HADS and SS within 7–10 days following the CS . Results The baseline scores include 5.2 ± 2.6 points for rigid CS recalled pain , 7.2 ± 3.0 points for HADS anxiety , 5.8 ± 3.5 for depression , and 27.8 ± 5.1 for SS . The flexible CS-related pain was approximately three times lower than the recalled pain level and also than the current rigid CS related ( p < 0.001 ) . Mean SS score was two points lowered after rigid CS ( p < 0.001 ) . One point decrease in anxiety level was observed after flexible CS ( p < 0.001 ) . Multivariate analysis supported the hypothesis of patients benefiting from flexible CS in terms of pain perception , anxiety symptoms , and SS . Conclusions Our study demonstrates the superiority of flexible CS in terms of pain alleviation , and shifts in SS and anxiety levels To test the feasibility of a r and omised trial in muscle‐invasive bladder cancer ( MIBC ) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy ( RC ) or selective bladder preservation ( SBP ) , where definitive treatment [ RC or radiotherapy ( RT ) ] is determined by response to chemotherapy Background The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and re source utilization outcomes . It remains an open question whether the overall survival ( OS ) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging . Methods Advanced-stage lung cancer patients without evidence of disease progression after or during initial treatment were r and omly assigned in a multicenter phase III trial to compare a web-mediated follow-up algorithm ( experimental arm ) , based on weekly self-scored patient symptoms , with routine follow-up with CT scans scheduled every three to six months according to the disease stage ( control arm ) . In the experimental arm , an alert email was automatically sent to the oncologist when self-scored symptoms matched predefined criteria . The primary outcome was OS . Results From June 2014 to January 2016 , 133 patients were enrolled and 121 were retained in the intent-to-treat analysis ; 12 deemed ineligible after r and om assignment were not subsequently followed . Most of the patients ( 95.1 % ) had stage III or IV disease . The median follow-up was nine months . The median OS was 19.0 months ( 95 % confidence interval [ CI ] = 12.5 to noncalculable ) in the experimental and 12.0 months ( 95 % CI = 8.6 to 16.4 ) in the control arm ( one-sided P = .001 ) ( hazard ratio = 0.32 , 95 % CI = 0.15 to 0.67 , one-sided P = .002 ) . The performance status at first detected relapse was 0 to 1 for 75.9 % of the patients in the experimental arm and for 32.5 % of those in the control arm ( two-sided P < .001 ) . Optimal treatment was initiated in 72.4 % of the patients in the experimental arm and in 32.5 % of those in the control arm ( two-sided P < .001 ) . Conclusions A web-mediated follow-up algorithm based on self-reported symptoms improved OS due to early relapse detection and better performance status at relapse Purpose To examine quality of life ( QoL ) , health status , sexual function , and anxiety in patients with primary hematuria who later appear to have bladder cancer ( BC ) and patients with other diagnoses . Methods From July 2007 to July 2010 , 598 patients with primary hematuria were enrolled in this prospect i ve , multicenter study . Question naires ( WHOQOL-BREF , SF-12 , IIEF , STAI-10-item Trait ) were completed before cystoscopy . Diagnosis was subsequently derived from medical files . BC patients were compared with patients with other causes of hematuria . Results Cancer was diagnosed in 131 patients ( 21.9 % ) , including 102 patients ( 17.1 % ) with BC . No differences were found in the WHOQOL-BREF versus SF-12 psychological or physical health domains . The erectile function was significantly worse in the BC group ( 9.3 vs. 14.6 for OC , p = 0.02 ) . Patients with muscle-invasive BC ( MIBC ) had the lowest percentage anxious personalities of all BC patients ( p = 0.04 ) . Conclusions Cancer was found in 21.9 % of the patients with hematuria . Pre-diagnosis patients with BC have comparable QoL and HS to patients with OC . Erectile dysfunction was highest in patients with BC . MIBC patients had the lowest percentage anxious personalities of the patients with BC PURPOSE There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes , but evidence of impact on clinical outcomes is limited . METHODS We r and omly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians . Those with home computers received weekly e-mail prompts to report between visits . Treating physicians received symptom printouts at visits , and nurses received e-mail alerts when participants reported severe or worsening symptoms . The primary outcome was change in health-related quality of life ( HRQL ) at 6 months compared with baseline , measured by the EuroQol EQ-5D Index . Secondary endpoints included emergency room ( ER ) visits , hospitalizations , and survival . RESULTS Among 766 patients allocated , HRQL improved among more participants in the intervention group than usual care ( 34 % v 18 % ) and worsened among fewer ( 38 % v 53 % ; P < .001 ) . Overall , mean HRQL declined by less in the intervention group than usual care ( 1.4- v 7.1-point drop ; P < .001 ) . Patients receiving intervention were less frequently admitted to the ER ( 34 % v 41 % ; P = .02 ) or hospitalized ( 45 % v 49 % ; P = .08 ) and remained on chemotherapy longer ( mean , 8.2 v 6.3 months ; P = .002 ) . Although 75 % of the intervention group was alive at 1 year , 69 % with usual care survived the year ( P = .05 ) , with differences also seen in quality -adjusted survival ( mean of 8.7 v. 8.0 months ; P = .004 ) . Benefits were greater for participants lacking prior computer experience . Most patients receiving intervention ( 63 % ) reported severe symptoms during the study . Nurses frequently initiated clinical actions in response to e-mail alerts . CONCLUSION Clinical benefits were associated with symptom self-reporting during cancer care Objectives : i ) To evaluate objective response , toxicity , and quality of life ( QoL ) of gemcitabine monotherapy as second-line treatment in patients with cisplatin-refractory , metastatic transitional cell carcinoma ( TCC ) . ii ) To assess prognostic parameters for response to treatment and for improvement of QoL parameters . Patients and Methods : 30 patients were prospect ively enrolled in this open-label , nonr and omized multicenter phase II trial . Patients received up to 6 courses of gemcitabine monotherapy ( 1,250 mg/m2 on day 1 and 8 of a 21-day course ) . 28 of 30 patients were available for response evaluation . Results : Objective response ( OR ) was seen in 3/28 ( 11 % ) of patients ( 2 complete remissions , 1 partial remission ) . The mean time to progression ( TTP ) was 4.9 ± 3.5 months and mean disease-specific survival time was 8.7 ± 4.7 months . 13 of 28 patients did not progress ( OR + 10 stable diseases ) , and TTP ( 8.0 ± 2.7 months , p < 0.001 ) as well as survival time ( 10.2 ± 3.8 months , p < 0.05 ) differed significantly from those who showed progressive disease within 18 weeks of treatment . Pain values significantly improved in the group of responders from 4.3 ± 1.9 to 5.8 ± 1.3 points ( p < 0.05 ) . Response to cisplatin pretreatment was the best prognosticator for the response to gemcitabine . Conclusions : Gemcitabine monotherapy as second-line treatment is justified in patients with metastatic TCC who are refractory to cisplatin treatment . Patients with initially OR to cisplatin benefit most from second-line treatment . QoL remains stable during treatment , and pain improves especially in patients with bone metastases OBJECTIVES To explore the effects of cancer on psychosocial aspects of Pakistani patients and their families , assessing the need for interventions to improve their quality of life . METHODS A prospect i ve , Cross-sectional study was performed on 200 patients visiting the oncology outpatient facility of AKUH from December 2010 to May 2011 through an interview . Responses were recorded on pre- design ed question naires including FACT-G QOL ( Functional Assessment of Cancer Therapy-General Quality Of Life ) component . RESULTS Out of the 200 patients 52 ( 26 % ) were males and 148 ( 74 % ) were females . Mean age was 51.8 + /- 14.2 years . Breast cancer accounted for the commonest cancer in females 116 ( 58 % ) and lung in males 30 ( 15 % ) , 100 ( 50 % ) patients were currently undergoing chemotherapy . In all 148 ( 74 % ) patients were well aware of their diagnosis and were able to cope better and 142 ( 71 % ) were well supported by families ( majority being financially stable ) . Major financial impact was found in 42 ( 21 % ) cases . Religious/spiritual help was sought by 138 ( 69 % ) patients predominantly females- 113 ( 76 % ) and 22 ( 11 % ) patients consulted a psychiatrist ; 20 ( 94 % ) subjects of this group felt this intervention was helpful . Responses regarding effect on the patient 's sexual life were poor and 126 ( 63 % ) denied answering the question . CONCLUSION In our study one third of cancer patients were found to be depressed mainly affecting those who were receiving multimodality treatment or facing financial issues . Religious help was the main coping strategy for them BACKGROUND Radical radiotherapy for muscle-invasive urinary bladder cancer can sterilize the tumour with preserved organ function . Here we studied symptoms , symptom distress and trade-off among long-term survivors and compared figures to those of population controls and patients who had undergone cystectomy . MATERIAL S AND METHODS We identified 71 patients who had had urinary bladder cancer treated with radical radiotherapy before 1995 . For comparison , 325 patients treated with radical cystectomy and urostomy , continent or non-continent , during the same period and 460 individuals r and omly selected from the general population were included . Information was collected by means of an anonymously answered postal question naire to avoid investigator-related bias . RESULTS Answers were obtained from 58 ( 82 % ) radiated patients , 251 ( 85 % ) cystectomized patients and 310 ( 71 % ) population controls . Of the radiated patients , 74 % reported little or no distress from symptoms from the urinary tract , 38 % had had intercourse the previous month and 57 % ( men ) reported they had ejaculated . Among the cystectomized patients , 13 % had had intercourse and 0 % ( men ) had ejaculated . Moderate or much distress from symptoms from the gastrointestinal tract was reported by 32 % of the radiated patients , 24 % of the cystectomized patients and 9 % of the population controls . After radical radiotherapy , 46 % of the patients were willing to accept some risk of decreased survival to become symptom-free . CONCLUSIONS About 3/4 of these long-term survivors after radical radiotherapy for bladder cancer had a functioning urinary bladder with little or no distress from the urinary tract . The prevalence of sexual dysfunction was lower than after cystectomy and the prevalence of distress from the gastrointestinal tract was comparable OBJECTIVES The aim of the population -based study presented here was to evaluate quality of life ( QOL ) among bladder cancer survivors at least five years after diagnosis , ascertain the long term effects of treatments , and investigate important pathological and sociodemographic factors influencing the QOL of such survivors . METHODS A Functional Assessment of Cancer Therapy ( FACT ) question naire with a bladder-specific option ( FACT-Bl ) , was sent by mail to patients r and omly selected from the data base of the Isère and Tarn cancer registries in France . Ninety-five valid completed question naires were returned by 78 males and 17 females , with a median age of 72 years ( range , 33 - 90 ) . The pathological information contained in the completed question naires was examined . RESULTS Of the 95 patients ( 76 with a superficial tumor , 17 with an invasive tumor ) , 20 had undergone total cystectomy . Total cystectomy clearly deteriorates the autonomy of survivors ( ECOG-PSR ) , as well as their scores on the bladder cancer-specific sub-scale in sexuality-related questions . Survivors cl aim ed impotency and loss of sexual interest after the cystectomy . In contrast , neither the type of treatment nor the time from the most recent major treatment were score-modifying factors . Negative psychological effects of treatments in the long-term were not observed . Rather , patients ' QOL was affected by their autonomy in daily life and by old age . In addition , familial situation had a critical impact on emotional and Familial/Social Well-being . CONCLUSION The present study showed the long-term negative effect of total cystectomy on survivors . Survivor autonomy and other sociodemographic background s were also determinants of their QOL . The maintenance of good health , sexual function and active family relationships should be promoted so that patients can lead full lives after treatment PURPOSE Health-related quality of life ( QOL ) has not been well-studied in survivors of muscle-invasive bladder cancer ( MIBC ) . The present study compared long-term QOL in MIBC patients treated with radical cystectomy ( RC ) versus bladder-sparing trimodality therapy ( TMT ) . METHODS AND MATERIAL S This cross-sectional bi-institutional study identified 226 patients with nonmetastatic cT2-cT4 MIBC , diagnosed in 1990 to 2011 , who were eligible for RC and were disease free for ≥2 years . Six vali date d QOL instruments were administered : EuroQOL EQ-5D , European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Core Question naire and EORTC MIBC module , Exp and ed Prostate Cancer Index Composite bowel scale , Cancer Treatment and Perception Scale , and Impact of Cancer , version 2 . Multivariable analyses of the mean QOL scores were conducted using propensity score matching . RESULTS The response rate was 77 % ( n=173 ) . The median follow-up period was 5.6 years . Of the 173 patients , 64 received TMT and 109 , RC . The median interval from diagnosis to question naire completion was 9 years after TMT and 7 years after RC ( P=.009 ) . No significant differences were found in age , gender , comorbidities , tobacco history , performance status , or tumor stage . On multivariable analysis , patients who received TMT had better general QOL by 9.7 points of 100 compared with those who had received RC ( P=.001 ) and higher physical , role , social , emotional , and cognitive functioning by 6.6 to 9.9 points ( P≤.04 ) . TMT was associated with better bowel function by 4.5 points ( P=.02 ) and fewer bowel symptoms by 2.7 to 7.1 points ( P≤.05 ) . The urinary symptom scores were similar . TMT was associated with better sexual function by 8.7 to 32.1 points ( P≤.02 ) and body image by 14.8 points ( P<.001 ) . The patients who underwent TMT reported greater informed decision-making scores by 13.6 points ( P=.01 ) and less concern about the negative effect of cancer by 6.8 points ( P=.006 ) . The study limitations included missing baseline QOL data and different follow-up times . CONCLUSIONS Both TMT and RC result in good long-term QOL outcomes in MIBC survivors , supporting TMT as a good alternative to RC for selected patients . Whether TMT leads to superior QOL requires prospect i ve validation OBJECTIVES To assess , in a Phase I study , whether bladder preservation with concurrent gemcitabine and radiotherapy ( RT ) influenced patient-reported quality of life ( QOL ) as determined by the Functional Assessment of Cancer Therapy-Bladder ( FACT-BL ) . METHODS Between January 1998 and March 2002 , 24 patients with urothelial carcinoma of the bladder were enrolled , and 23 patients underwent transuretheral resection of bladder tumor , followed by twice-weekly gemcitabine with concurrent RT . The initial dose was 10 mg/m2 given twice weekly and increased as tolerated . To assess treatment-related QOL , patients completed the FACT-BL question naire . RESULTS Of the 24 patients enrolled , 23 ( 96 % ) were assessed for toxicity and response . The FACT-generic ( G ) QOL assessment was obtained from 22 ( 92 % ) of 23 patients . No statistically significant difference was found in the FACT-G or FACT-BL or the combination before , during , or after treatment . The FACT-BL values were lower in patients who received higher doses of gemcitabine ( greater than 20 mg/m2 versus 20 mg/m2 or less ) . At least one dose-limiting toxicity ( DLT ) was experienced by 5 ( 23 % ) of 22 patients . The FACT-G values were lower for those patients who experienced DLT ( difference of -13.1 , P = 0.07 ) . The physical well-being scores for patients who experienced DLT were lower after treatment ( difference of -5.2 , P = 0.03 ) compared with those without DLT . CONCLUSIONS Concurrent RT and gemcitabine failed to statistically influence patient-reported QOL , although patients who received higher doses reported lower FACT-BL scores . The results of this study suggest that concurrent gemcitabine with conformal RT is a tolerable treatment regimen for bladder preservation , as demonstrated by the excellent treatment compliance and similar FACT measurements Purpose To prospect ively assess anxiety and depression in patients undergoing diagnostic cystoscopy . Methods Patients presenting for outpatient diagnostic cystoscopy were recruited from four European urological departments . Anxiety and depression were assessed with the ‘ Hospital Anxiety and Depression Scale ’ ( HADS ) before cystoscopy and after 1 week . Statistical analyses , including the Chi-square test , univariate , and multivariate logistic regression analyses , were carried out with SPSS v. 21 ( IBM Corp. , Armonk , NY ) . Results Prior to cystoscopy , 30.2 % of patients were anxious and 24.8 % depressive ( n = 442 ) . In the post-examination period , anxiety declined to 24.5 % , while depression was unchanged ( 24.4 % ) . Pre-cystoscopy anxiety was significantly more common in women ( 41.8 vs. 24.5 % , p < 0.0001 ) , patients aged < 65 years ( 34.9 vs. 25.9 % , p = 0.04 ) , and in those being examined with rigid cystoscopes ( 35.7 vs. 23.9 % , p = 0.007 ) . In multivariate regression analyses , female gender ( OR 2.6 , p < 0.0001 ) , < 65 years of age ( OR 1.7 , p = 0.03 ) , and coexistence of depression ( OR 7.8 , p < 0.0001 ) were independently associated with elevated pre-cystoscopy anxiety . Anxious ( OR 2.1 , p = 0.03 ) and depressive ( OR 2.1 , p = 0.01 ) patients had higher odds of experiencing moderate or severe pain during cystoscopy . Bladder cancer diagnosis did not significantly change patient ’s anxiety ( p = 0.23 ) or depression ( p = 0.7 ) during the 1 week of follow-up . Conclusions Women , patients aged < 65 years , depressive patients and those being examined with rigid devices had higher rates of anxiety prior to cystoscopy . Anxious and depressive patients experienced more pain during cystoscopy . Bladder cancer diagnosis seems to have a minor effect on anxiety and depression during the first week after diagnosis PURPOSE To evaluate bladder preservation and functional quality after concurrent chemoradiotherapy for muscle-invasive cancer in 53 patients included in a Phase II trial . PATIENT AND METHODS Pelvic irradiation delivered 45 Gy , followed by an 18-Gy boost . Concurrent chemotherapy with cisplatin and 5-fluorouracil by continuous infusion was performed at Weeks 1 , 4 , and 7 during radiotherapy . Patients initially suitable for surgery were evaluated with macroscopically complete transurethral resection after 45 Gy , followed by radical cystectomy in case of incomplete response . The European Organization for Research and Treatment of Cancer quality of life question naire QLQ-C30 , specific items on bladder function , and the Late Effects in Normal Tissues-Subjective , Objective , Management , and Analytic ( LENT-SOMA ) symptoms scale were used to evaluate quality of life before treatment and 6 , 12 , 24 , and 36 months after treatment . RESULTS Median age was 68 years for 51 evaluable patients . Thirty-two percent of patients had T2a tumors , 46 % T2b , 16 % T3 , and 6 % T4 . A visibly complete transurethral resection was possible in 66 % . Median follow-up was 8 years . Bladder was preserved in 67 % ( 95 % confidence interval , 52 - 79 % ) of patients . Overall survival was 36 % ( 95 % confidence interval , 23 - 49 % ) at 8 years for all patients , and 45 % ( 28 - 61 % ) for the 36 patients suitable for surgery . Satisfactory bladder function , according to LENT-SOMA , was reported for 100 % of patients with preserved bladder and locally controlled disease 6 - 36 months after the beginning of treatment . Satisfactory bladder function was reported for 35 % of patients before treatment and for 43 % , 57 % , and 29 % , respectively , at 6 , 18 , and 36 months . CONCLUSIONS Concurrent chemoradiation therapy allowed bladder preservation with tumor control for 67 % patients at 8 years . Quality of life and quality of bladder function were satisfactory for 67 % of patients OBJECTIVE Rehabilitation programmes are intended to help cancer patients achieve optimal functioning and live independently . We evaluated whether a psychosocial rehabilitation course was effective in relieving cancer patients ' distress and improving their well-being . METHODS Patients with breast , prostate or colorectal cancer diagnosed within 2 years who had finished primary treatment were r and omised to usual care or a 6-day residential course of lectures , discussion s and peer groups on issues related to treatment and living with cancer . Changes in self-reported distress ( POMS-Sf ) and quality of life ( EORTC QLQ-C30 ) from baseline to 1 and 6 months ' follow-up were measured . Analyses were adjusted for baseline scores of outcome , cancer site , time since diagnosis , gender , age and education . RESULTS Of 507 patients , 452 were included in the analyses , 404 completed the 1-month and 394 the 6-month assessment . Patients in the control group showed greater decreases in total mood disturbance and subscales of the POMS-Sf and showed more improvement in emotional , cognitive and social functioning at both 1 and 6 months and in role functioning at 6 months than the intervention group . A similar pattern was observed in analyses of breast cancer patients only . CONCLUSION A 6-day residential rehabilitation course did not relieve cancer patients ' distress or improve their well-being PURPOSE This is the first r and omized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ( " unfit " ) for cisplatin chemotherapy . PATIENTS AND METHODS The primary objective of the phase III part of this study was to compare the overall survival ( OS ) of chemotherapy-naive patients with measurable disease and an impaired renal function ( glomerular filtration rate < 60 but > 30 mL/min ) and /or performance score of 2 who were r and omly assigned to receive either gemcitabine/carboplatin ( GC ) or methotrexate/carboplatin/vinblastine ( M-CAVI ) . To detect an increase of 50 % in median survival with GC compared with M-CAVI ( 13.5 v 9 months ) based on a two-sided log-rank test at error rates α = .05 and β = .20 , 225 patients were required . Secondary end points were overall response rate ( ORR ) , progression-free survival ( PFS ) , toxicity , and quality of life . RESULTS In all , 238 patients were r and omly assigned by 29 institutions over a period of 7 years . The median follow-up was 4.5 years . Best ORRs were 41.2 % ( 36.1 % confirmed response ) for patients receiving GC versus 30.3 % ( 21.0 % confirmed response ) for patients receiving M-CAVI ( P = .08 ) . Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm ( P = .64 ) . There was no difference in PFS ( P = .78 ) between the two arms . Severe acute toxicity ( death , grade 4 thrombocytopenia with bleeding , grade 3 or 4 renal toxicity , neutropenic fever , or mucositis ) was observed in 9.3 % of patients receiving GC and 21.2 % of patients receiving M-CAVI . CONCLUSION There were no significant differences in efficacy between the two treatment groups . The incidence of severe acute toxicities was higher for those receiving M-CAVI BACKGROUND There is no st and ard second-line chemotherapy for patients who relapse with advanced urothelial carcinoma . A GETUG phase II clinical trial was design ed to evaluate the response rate and the palliative clinical benefit of weekly paclitaxel . PATIENTS AND METHODS Paclitaxel ( 80 mg/m2 , 1 hour ) was administered on day 1 , 8 , and 15 ( 28-day course ) to 45 patients . The primary endpoint was disease control rate ( objective response and stable disease ) . Response rate was evaluated using Response Evaluation Criteria in Solid Tumors ( RECIST ) criteria ; quality of life ( QOL ) assessment used FACT-B1 and FACT-Taxane question naires . RESULTS Characteristics of the patients were : M/F , 36/9 ; mean age , 64 years ; performance status ( PS ) 0 - 1 , 82 % ; metastatic disease , 93 % ; gemcitabine/platinum first-line chemotherapy , 89 % ; median number of cycles , 2 . Grade 3/4 toxicity was uncommon . The disease control rate was 47 % . One patient achieved a complete response , 3 a partial response ( objective response , 9 % ) and 17 ( 38 % ) a stable disease . Median time to progression or death were 3 and 7 months . Among the 21 patients with controlled disease , 10 % displayed QOL improvement , and 14 % decreased their analgesic consumption . CONCLUSION Weekly paclitaxel is associated with limited objective response but a high rate of stabilization ; QOL assessment indicates that a small group of patients might experience a clinical benefit To evaluate how an increasing burden of symptoms influences well‐being , anxiety and depression at different intervals after a radical cystectomy with urostomy for bladder cancer , as this therapy can induce long‐term distressful symptoms |
10,935 | 30,931,717 | Conclusion : The best available evidence indicates that breastfeeding up to 2 y of age does not increase ECC risk .
Providing access to fluori date d water and educating caregivers are justified approaches to ECC prevention . | Introduction : A systematic review of evidence on the impact of modifiable risk factors on early childhood caries ( ECC ) was conducted to inform recommendations in a World Health Organization manual on ECC prevention .
Objectives : To systematic ally review published evidence pertaining to the effect of modifiable risk factors on ECC . | Background This survey was intended to investigate prevalence and severity of early childhood caries ( ECC ) in a sample of children in Southern Italy and to identify factors that may be related to this condition . Methods The study was design ed as a cross-sectional survey . The study population ( children aged 36–71 months ) attending thirteen kindergartens was r and omly selected through a two-stage cluster sampling procedure . Parents/guardians of all eligible children were invited to participate filling out a structured self-administered question naire , and after having returned the informed consent form an oral examination of the child was performed at school . The question naire included information on : socio-demographics about parents/guardians and child , pregnancy and newborn characteristics , oral hygiene habits of child , eating habits particularly on consumption of sweets , access to dental services , and infant feeding practice s. The WHO caries diagnostic criteria for deciduous decayed , missing and filled teeth ( dmft ) and surfaces ( dmfs ) were used to record ECC and severe-ECC ( S-ECC ) . Univariate and multiple logistic regression analyses were conducted to evaluate statistical associations of social demographics , infant feeding practice s , oral hygiene habits , and access to dental services to ECC , S-ECC , dmft and dmfs . Results 515 children participated in the study . 19 % had experienced ECC , and 2.7 % S-ECC , with a mean dmft and dmfs scores of 0.51 and 0.99 , respectively . Mean dmft was 2.68 in ECC subjects , and 6.86 in S-ECC subjects . Statistical analysis showed that prevalence of ECC significantly increased with age ( OR = 1.95 ; 95 % CI = 1.3 - 2.91 ) and duration of breastfeeding ( OR = 1.26 ; 95 % CI = 1.01 - 1.57 ) , whereas it was significantly lower in children of more educated mothers ( OR = 0.64 ; 95 % CI = 0.42 - 0.96 ) , and higher in those who had been visited by a dentist in the previous year ( OR = 3.29 ; 95 % CI = 1.72 - 6.33 ) . Conclusions Results of our study demonstrate that even in Western countries ECC and S-ECC represent a significant burden in preschool children , particularly in those disadvantaged , and that most of the known modifiable associated factors regarding feeding practice s and oral hygiene are still very spread in the population OBJECTIVE To demonstrate the effectiveness of a dental caries prevention program on the primary dentition of Chilean rural children , using fluori date d powdered milk and milk derivatives . METHODS Fluori date d milk and milk-cereal was given to about 1000 preschool children in Codegua , a rural community located in the 6th Region of Chile , using the st and ard National Complementary Feeding Program ( PNAC ) . The daily fluoride dose from fluori date d powdered milk was estimated at 0.25 mg for infants ( 0 - 2 years old ) , 0.5 mg for children aged 2 - 3 years and 0.75 for children aged 3 - 6 years . Cross-sectional sample s of children aged 3 - 6 years were taken from Codegua ( study community ) from 1994 to 1999 and from La Punta ( control community ) from 1997 and 1999 . RESULTS Significant reductions ( 72 % ) were observed in the dmfs indices in the 3 - 6-year-old groups in Codegua , when comparing 1999 with 1994 data . In 1999 , children in the study community showed significantly lower dmfs than children in the control community ( 41 % ) . The proportion of caries-free children in the study community increased after 4 years of program implementation ( from 22.0 % to 48.4 % ) . CONCLUSION Under Chilean rural conditions , fluoridation of powdered milk distributed through the PNAC is an effective caries prevention alternative for areas where water fluoridation might not be feasible Objectives The purpose of this study is to investigate the contribution of selected variables to the occurrence of severe early childhood caries ( S-ECC ) in 3- to 5-year-old kindergarten children . Methods A cross-sectional study was conducted in 2010 in 30 r and omly selected kindergartens in the German Rhein-Neckar district . After informed consent , parents were asked to complete a question naire . The oral examinations took place in the selected kindergartens and the WHO methods as well as the criteria proposed by the American Academy of Pediatric Dentistry were followed . Logistic regression was applied to explore the main factors contributing to S-ECC in a multivariate model . Results In all , 1,007 children aged 3 to 5 years with an average age of 4.1 ( SD = 0.8 ) years were examined . Five variables were associated significantly with the occurrence of S-ECC : breastfeeding for more than 12 months ( OR = 3.27 ) , use of the nursing bottle in bed ( OR = 3.08 ) , start of tooth brushing after the first anniversary ( OR = 2.42 ) , regular visits at the dentists ( OR = 0.14 ) and mother with immigration background ( OR = 4.05 ) . Prevalence rate of S-ECC was 9.5 % . The mean d3 + 4mft values were 5.69 ( S-ECC group ) and 0.23 ( non-S-ECC group ) . Conclusion These results show that occurrence of S-ECC is a complex interaction between socioeconomic , psychological and behavioural factors of parents . New and specific ways to provide preventive dental care for toddlers and infants of caries risk groups have to be developed . Clinical relevance Parents of newborn children have to receive information about timely start of tooth brushing and adequate use of nursing bottles The purpose of this study was to describe the dietary habits of infants and toddlers living in Sweden with special reference to caries prevalence at 2 and 3 years of age and to immigrant status . The study was design ed as a prospect i ve , longitudinal study starting with 671 children aged 1 year . At 3 years , all children were invited to a further examination . A total of 298 individuals , r and omly selected from the original group , were also examined at 2 years . The accompanying parent was interviewed about the child 's dietary habits . Children with caries at 2 and 3 years of age and immigrant children had , when they were 1 year old , consumed caries-risk products and been given nocturnal meals and sweetened liquid in a feeding bottle more often than caries-free 2- and 3-year-olds and non-immigrant children . Although a great variation in dietary habits was found in infants and toddlers , the use of sugar-containing products is widespread in Sweden even in early childhood OBJECTIVES To evaluate the significance of variables such as oral hygiene , dietary habits , socio-economic status and medical history of a child in assessing the level of caries risk and to generate a caries prediction model for pre-school Saudi children . DESIGN Cross-sectional study of pre-school children . SETTING Clinics and schools in Riyadh , Saudi Arabia . SAMPLE AND METHODS A sample of 446 Saudi pre-school children , 199 males and 247 females , with a mean age of 4.13 years , were selected at r and om from clinics and schools . Selection was limited to subjects who either had no caries ( dmft = 0 ) or who had high caries experience ( dmft > 8) . Each child was examined for caries experience and oral hygiene status . Their mothers were interviewed through a st and ardized question naire for information about oral hygiene habits of the children , diet history , childhood illness and socio-economic status . RESULTS There was a highly significant difference between the two groups in : debris index ( P < 0.0001 ) , aged child started tooth brushing , ( P < 0.0001 ) , age breastfeeding was stopped ( P < 0.005 ) , nocturnal bottle feeding with milk formula ( P < 0.001 ) , use of sweetened milk ( P < 0.0001 ) , frequency of use of soft drinks ( P < 0.0005 ) , frequency of consumption of sweets ( P < 0.0001 ) , and age at first dental visit ( P < 0.0001 ) . A caries prediction model developed through stepwise multivariate Logistic Regression ( LR ) analyses showed debris index , use of sweetened milk in bottle , frequency of consumption of soft drinks , frequency of intake of sweets and child 's age at the first dental visit to be significant . Predictive probability of the model was 86.31 % with a sensitivity of 90.1 % and a specificity of 80.6 % . CONCLUSIONS Risk factors for dental caries have been identified and a caries prediction model has been developed for Saudi pre-school children . The prediction model , if verified , may provide with guidance in identifying high caries risk Saudi preschool children as targets for preventive programmes OBJECTIVE Despite a marked improvement in oral health of Australian children over the last 30 years , severe early childhood caries ( S-ECC ) affects up to 17 % of 2- to 3-year-old children with some requiring hospitalization and invasive treatment . This provided a compelling rationale to develop and test an oral health promotion programme which aim ed to reduce this unnecessary suffering . The purpose of this study was to test the efficacy of an oral health promotion programme for the parents of infants , starting during the pregnancy , using a r and omized controlled trial . METHODS A programme was developed around the provision of anticipatory guidance to nulliparous women ( women expecting their first child ) in Adelaide . Mothers in the test group received oral health promotion information during pregnancy , and later when the child reached 6 and 12 months of age . After the second round of information the test group mothers were r and omized again . The information was reinforced in one of the test subgroups through a telephone consultation . There was no contact with mothers in the control group after enrolment . At the age of 20 + /- 2.5 months all test and control group children were examined by a dentist . The case definition of an incidence of S-ECC was one or more upper incisor teeth being carious at the level of a cavitated or noncavitated lesion . The differences in S-ECC incidence between the test and control groups , and the test subgroups were analysed . RESULTS Of 649 women enroled in the programme ( test group 327 , control group 322 ) , 441 had their child examined at follow-up . The incidence of S-ECC in the test group was 1.7 % and in the control group 9.6 % ( P < 0.001 ) . CONCLUSION An oral health promotion programme based on repeated rounds of anticipatory guidance initiated during the mother 's pregnancy was successful in reducing the incidence of S-ECC in these very young children PURPOSE The purpose s of this r and omized controlled trial were to : ( 1 ) test motivational interviewing ( MI ) to prevent early childhood caries ; and ( 2 ) use Poisson regression for data analysis . METHODS A total of 240 South Asian children 6 to 18 months old were enrolled and r and omly assigned to either the MI or control condition . Children had a dental exam , and their mothers completed pretested instruments at baseline and 1 and 2 years postintervention . Other covariates that might explain outcomes over and above treatment differences were modeled using Poisson regression . Hazard ratios were produced . RESULTS Analyses included all participants whenever possible . Poisson regression supported a protective effect of MI ( hazard ratio [HR]=0.54 (95%CI=035 - 0.84)-that is , the M/ group had about a 46 % lower rate of dmfs at 2 years than did control children . Similar treatment effect estimates were obtained from models that included , as alternative outcomes , ds , dms , and dmfs , including " white spot lesions . " Exploratory analyses revealed that rates of dmfs were higher in children whose mothers had : ( 1 ) prechewed their food ; ( 2 ) been raised in a rural environment ; and ( 3 ) a higher family income ( P<.05 ) . CONCLUSIONS A motivational interviewing-style intervention shows promise to promote preventive behaviors in mothers of young children at high risk for caries Fluori date d milk reduced caries increment by about 70 % OBJECTIVES Assess the effectiveness of home visits for advising mothers about breast feeding and weaning on early childhood caries ( ECC ) at the age of 12 months . METHODS A r and omized field trial was conducted in mothers who gave birth within the public health system in the Brazilian city of Sao Leopoldo ( intervention group = 200 ; controls = 300 ) . The intervention group received the advice 10 days after the child 's birth , monthly up to 6 months , at 8 , 10 and 12 months , based on the ' Ten Steps for Healthy Feeding ' , a Brazilian national health policy for primary care , based on WHO guidelines . Both groups had research assessment at 6 and 12 months , with dental caries investigated in this last assessment ; 122 children were lost in the 1-year follow-up ; 378 were assessed for caries : two predentulous children were excluded from the analysis . Mann-Whitney U was used to test if the average number of decayed surfaces ( DS ; white spots and cavities ) differed between the intervention and control groups , and logistic regression to estimate the effects of the intervention on the odds of ECC . Chi-square test was used to test for differences between the intervention and control groups in the distribution of feeding behaviours tackled by the dietary intervention . RESULTS 10.2 % of the children in the intervention group and 18.3 % of the controls had caries . The odds of caries was 48 % lower for the intervention group , adjusted for number of teeth ( OR = 0.52 , 95 % CI = 0.27 - 0.97 ) . Mean DS were lower for the intervention group ( 0.37 ) when compared with the control group ( 0.63 ) , ( Mann-Whitney U , P = 0.03 ) . The intervention group had significantly longer duration of exclusive breast feeding ( P = 0.000 ) , later introduction of sugar ( P = 0.005 ) , and smaller probability of ever having eaten biscuits ( P = 0.000 ) , honey ( P = 0.003 ) , soft drinks ( P = 0.02 ) , fromage-frais ( P = 0.001 ) , chocolate and sweets ( P = 0.001 ) . CONCLUSIONS ECC is a public health problem in that population . The home visits for dietary advice appear to help reducing dental caries in infants . Greater efforts are needed to tackle cariogenic dietary behaviours even further , as a relevant proportion of children of the intervention group were shown to present with dental caries . Further studies should examine the effect of the intervention in the longer term A study was undertaken to compare the prevalence of dental caries and developmental defects of enamel between 3-year-old children who were lifelong residents of fluori date d areas of Huddersfield ( 1 ppm F ) and non-fluori date d Dewsbury ( less than 0.3 ppm F ) . An interview was also conducted with the parents of the children to provide information regarding previous dental experiences . The study population s were identified using the national child health system . The mean dmft was 0.30 in Huddersfield and 0.74 in Dewsbury . The percentage of children who had experienced dental caries and the percentage with carious teeth were significantly lower in the fluori date d area . The Dewsbury children had suffered more toothache . There was a significantly higher number of children in Huddersfield with diffuse enamel defects on their upper and lower first molars . This study has also demonstrated that the national child health system provides a method for obtaining a r and om sample of pre-school children from the general population , thus avoiding the problems associated with studies using selected population s. Fluoridation in Huddersfield ceased in October 1989 and it is hoped that this decision will be reversed as soon as possible The aim of this study was to investigate the anticaries effect of fluori date d salt in a communal feeding program for preschool children . In the Gambian city of Brikama , drinking water had a low fluoride content ( 0.1 mg F-/L ) and young children did not use toothpaste for oral hygiene . Its 2 preschools served as clusters for the trial . R and om allocation of the kindergartens was performed by one person not involved in the study , and the clinical examinations were carried out using the envelope method . Meals were prepared with fluori date d salt ( 250 mg F-/kg salt ) in the intervention group but not in the control group . According to the inclusion criteria ( complete primary dentition and informed consent from legal guardian ) , 441 children aged 3 - 5 years were enrolled . The children were examined by calibrated persons according to WHO criteria , allowing the calculation of d3mft scores . The primary end point was the mean difference in the incidence of caries cavities ( Δd3/4mft ) after 12 months . After 12 months , the mean caries incidence per person was 1.29 d3/4mf teeth ( 95 % CI : 0.96 ; 1.62 ) in the test group ( n = 304 children ) and 3.83 d3/4mf teeth ( 95 % CI : 2.94 ; 4.72 ) in the control group ( n = 137 children ) . Thus , the caries-prevented fraction was 66.3 % . No signs of harm due to the intervention were observed . The use of fluori date d salt in a communal feeding program and in an environment with negligible availability of fluoride from other sources yields a considerable caries-preventive effect PURPOSE The purpose of this study was to prospect ively investigate the association between infant feeding practice s and the development of early childhood caries ( ECC ) . METHODS Subjects were 315 children . Information about the variables under study and potential confounding factors were obtained by question naire during pregnancy and when the children were two to nine , 16 to 24 , 29 to 39 , and 41 to 49 months old . Outcome data were collected at 41 to 50 months old . Children were classified as having ECC if one or more primary teeth had decayed or been filled . RESULTS Compared with breast-feeding for six months or fewer , breast-feeding for 18 months or longer tended to be positively associated with a risk of ECC , and a U-shaped relationship was observed . Use of a bottle to drink sweetened liquids other than milk and the introduction of solid foods at six months old or later were positively associated with a risk of ECC . There was no significant association between bottle-feeding while falling asleep at night and the risk of ECC . CONCLUSION Prolonged breast-feeding , bottle use for sweetened liquids other than milk , and the introduction of solid foods at six months old or later might be risk factors for the development of dental caries Early childhood caries ( ECC ) remains a serious problem in several developing and developed countries . This cluster r and omised trial evaluated the impact of a 6-month educational intervention on ECC . The trial targeted 12- to 15-month-old children ( n = 242 ) and their mothers in Tehran , Iran , visiting 18 public health centres , r and omly selected and assigned to two intervention groups and one control group . At baseline , each mother was interviewed and each child underwent a dental examination of all teeth for the number of decayed teeth ( dt ) and of upper central incisors for the number of teeth with enamel caries ( de ) . All mothers in the two intervention groups ( A and B ) received oral health instructions from the vaccination staff . In addition , group A received extra reminders . The outcome was defined as increments in the number of teeth with dt or de , as percentages of children developing new dt or de , and as the number needed to treat ( NNT ) . No new de appeared in group A , the mean de increment in group B was 0.2 ( SD = 0.6 ) , and in the controls , it was 0.4 ( SD = 0.7 ) ( p < 0.05 ) . The percentages of children developing new de were 0 , 14 , and 26 % , respectively . No differences in dt increments were found . Regarding de , NNT for group A was 4 and for B 9 ; the figures for dt were 13 and 17 , respectively . In conclusion , oral health education given to mothers by general health staff is a valuable tool to prevent caries in infants and toddlers OBJECTIVES To investigate the effectiveness of h and s-on training in parental toothbrushing , with or without semi-annual applications of 5 % sodium fluoride varnish in preventing ECC . METHODS Study was conducted in Hong Kong where water is optimally fluori date d. Children aged 8 - 23 months were recruited and r and omly allocated to one of three groups : Gp 1 - control , one-off oral health education talk to parents ; Gp 2 - oral health education talk and parental toothbrushing training , reinforced every 6 months ; Gp 3 - semi-annual application of fluoride varnish onto child 's teeth in addition to the intervention provided to Gp 2 . Clinical examinations of the children and interviews were conducted at baseline and after 24 months to assess the children 's dental caries status and toothbrushing behaviour . RESULTS Out of the 450 child-parent dyads recruited at baseline , 415 ( 92 % ) remained after 24 months . At baseline , 2 % of the children had non-cavitated enamel caries lesions and the mean dmft score was 0.03 ± 0.24 . Most of the children did not have daily parental toothbrushing ( 65 - 73 % ) and self toothbrushing ( 86 - 90 % ) . At 24-month follow-up , including both non-cavitated and cavitated carious lesions , the incidences of ECC in Gp 1 to Gp 3 were 11.9 % , 11.8 % , and 17.5 % , respectively ( p>0.05 ) ; and the mean new dmft scores in Gp 1 to Gp 3 were 0.3 , 0.2 , and 0.3 , respectively ( p>0.05 ) . Proportions of parents who practice d parental toothbrushing twice daily were 62.7 % , 60.4 % , and 65.7 % in Gp 1 to Gp 3 , respectively ( p>0.05 ) . CONCLUSIONS In a water fluori date d area , h and s-on training in parental toothbrushing , with or without semi-annual application of 5 % sodium fluoride varnish may not have additional effect on preventing ECC in young children with low risk of dental caries compared to provision of oral health education to parents . CLINICAL SIGNIFICANCE In a water fluori date d area , provision of individual oral health education to parents may be sufficient for preventing ECC in young children below age 3 . Supplemental training in parental toothbrushing and semi-annual applications of fluoride varnish may not have additional caries prevention effect in young children with low risk of dental caries |
10,936 | 18,504,686 | The vast majority of studies reported positive intervention effects .
It appears easier to improve knowledge or to change misconceptions of mental disorders than to reduce the tendency to distance oneself from people with mental illness .
When directly comparing the effect of interventions based exclusively on education with those combining education with facilitating contact with people with mental disorders , the latter proved more effective .
A remarkable number of targeted interventions aim ed at reducing the stigma attached to mental illness have been carried out . | OBJECTIVE To provide a systematic review of target-group oriented interventions aim ed at reducing the stigma surrounding mental illness . | This study examines the personal and attitudinal variables that are associated with helping behavior in a hypothetical general practice setting . We explored the effect of an antistigma seminar during a psychiatric clerkship on medical students ’ attitudes toward the mentally ill . We r and omly assigned three rotations of students ( 81 students ) to receive the seminar and three rotations ( 85 students ) as controls . The students expressed views about patients with schizophrenia or depressive disorder portrayed in video vignettes . How dangerous the students perceived target individuals to be was the major determinant of helping behavior . The students ’ gender , religious affiliation , affective reaction , skill assessment , and controllability attribution were less consistent in predicting behavior . Exposure to the seminar and clerkship experience significantly improved attitudes , but attributes of responsibility and readiness to provide medical care for psychiatric patients were the most resistant to change . We identified certain issues that should be highlighted in future antistigma programs This study explores the effect of classroom theory and contact with mentally ill patients on the attitudes of student nurses . The independent variables were ( a ) pre-class stage , ( b ) post-class stage , and ( c ) post- clinical placement stage . A total of 72 students took part in the study . While there were two significant changes in responses to specific attitudes at the post-class stage , there were three significant changes in responses to specific attitudes at the post- clinical stage on patients ' characteristics . However , when responses to all attitudes pertaining towards patients ' characteristics were grouped , there was no overall significant change at the post- clinical experience stage . Also , for attitudes towards patients ' treatment , there were significant changes in responses to two specific attitudes at the post-class stage and to three specific attitudes at the post- clinical experience stage . Furthermore , the highly significant positive change in attitudes towards patients ' treatment in the post-class stage remained highly significant at the post- clinical experience stage . This confirms that classroom theory , prior to clinical experience , can effect students ' attitudes towards patients treatment . In addition , students ' evaluative comments , while being critical of some aspects of their clinical placements , did not necessarily affect their attitudes towards the characteristics or treatment of the mentally ill Rreliminary evidence suggests that mental health consumers can successfully serve as peer companions , case management aides , case managers , job coaches , and drop-in center staff . However , few empirical investigations have addressed the use of consumers to train mental health professionals . This project employed a r and omized design to test the effects of using consumers as trainers for mental health service providers . Fifty-seven state mental health professionals participated in a two-day training design ed to acquaint trainees with the attitudes and knowledge necessary for delivering assertive case management services . Participants were r and omly assigned to one of two conditions : one in which they received the second day of training from a consumer and the other involving training by a nonconsumer . Analyses revealed that post-training attitudes were significantly more positive for those participants trained by the consumer . Subjective evaluations also reflected positive reactions to the use of consumers as trainers . Implication s for further use of mental health consumers as trainers are explored BACKGROUND A school mental-health programme has been developed as a component of the community mental-health programme in Rawalpindi , Pakistan . It has the objective of improving the underst and ing of disorders of mental health in the rural community . We aim ed to assess the impact of a school mental-health programme on the awareness of schoolchildren , their parents , friends who were not attending school , and neighbours . METHODS We chose two secondary schools for boys and two for girls that were similar in terms of size , staff-pupil ratio , and drop-out rates . 100 children aged 12 - 16 years ( 25 girls and 25 boys in each of the study and control groups ) , 100 parents ( one for each child ) , 100 friends who did not attend school ( one for each child ) , and 100 neighbours ( one for each child ) were given a 19-item question naire before and after the study group had had a 4-month programme of mental-health education . The maximum score for the question naire was 16 points . FINDINGS Before the school mental-health programme the awareness of mental-health issues was poor ( mean score 5.7 - 7.6 ) in the four groups of participants . In the study group there was a significant improvement in the mean scores after the school programme in the schoolchildren ( mean improvement 7.6 [ 95 % CI 6.7 - 8.5 ] , p<0.01 ) , their parents ( 5.3 [ 4.5 - 6.1 ] , p<0.01 ) , friends ( 5.1 [ 4.1 - 6.1 ] , p<0.01 ) , and neighbours ( 3.4 [ 2.6 - 4.2 ] , p<0.01 ) . In the control group the difference in awareness was significant only in schoolchildren ( 1.5 [ 0.5 - 2.3 ] , p=0.01 ) and their friends ( 0.8 [ 0.3 - 1.3 ] , p<0.01 ) . INTERPRETATION The school programme succeeded in improving awareness of mental health in schoolchildren and the community . The schoolchildren were receptive to the programme , and shared their new underst and ing with family , friends , and neighbours . Mental-health planners who wish to improve community awareness of mental health , particularly in areas with low literacy rates , should consider setting up school mental-health programmes This study evaluated the effectiveness of a cognitive behaviour therapy Internet program ( MoodGYM ) for depressive symptoms , attributional style , self‐esteem and beliefs about depression , and on depression and depression‐vulnerable status in male youth . A total of 78 boys age 15 and 16 years were allocated to either undertake MoodGYM or to st and ard personal development activities . Outcomes were measured before commencement , post‐program and 16 weeks post‐program . There were no significant between‐group differences in change scores pre‐ to post‐ or pre‐ to follow‐up using the intention to treat sample or for participants with post‐ and /or follow‐up data . For boys completing 3 or more modules there were small relative benefits of MoodGYM for depressive symptoms ( Effect Size , ES = 0.34 ) , attributional style ( ES = 0.17 ) and self‐esteem ( ES = 0.16 ) at post‐program , although only the effect for self‐esteem was sustained at follow‐up . Both groups showed improvement in their beliefs about depression at follow‐up , with the control group showing a moderate relative benefit ( ES = 0.40 ) . While the numbers are small , there was a reduction in the risk of being depressed in the MoodGYM group of 9 % at post‐treatment compared with a slightly increased risk for the control group . The risk of being classified as vulnerable to depression reduced by 17 % in the MoodGYM group at post‐treatment compared with no change in risk for the control group . These reductions in risk for the MoodGYM group were not sustained at follow‐up . The limitations of the study highlight several important challenges for MoodGYM and other self‐directed Internet cognitive behaviour therapy programs . These include how to ensure enough of the program is received and that people who could potentially benefit access the program and continue to remain engaged with it , and how to enhance the sustainability of any benefits Trauma risk management ( TRiM ) is an intensive posttraumatic stress disorder ( PTSD ) psychoeducational management strategy based on peer-group risk assessment developed by the UK Royal Navy ( RN ) . TRiM seeks to modify attitudes about PTSD , stress , and help-seeking and trains military personnel to identify at-risk individuals and refer them for early intervention . This quasiexperimental study found that TRiM training significantly improved attitudes about PTSD , stress , and help-seeking from TRiM-trained personnel . There was a nonsignificant effect on attitudes to seeking help from normal military support networks and on general health . Within both the military and civilian population s , stigma is a serious issue preventing help-seeking and reducing quality of life . The results suggest that TRiM is a promising antistigma program within organizational setting The effects of three strategies for changing stigmatizing attitudes -- education ( which replaces myths about mental illness with accurate conceptions ) , contact ( which challenges public attitudes about mental illness through direct interactions with persons who have these disorders ) , and protest ( which seeks to suppress stigmatizing attitudes about mental illness)--were examined on attributions about schizophrenia and other severe mental illnesses . One hundred and fifty-two students at a community college were r and omly assigned to one of the three strategies or a control condition . They completed a question naire about attributions toward six groups -- depression , psychosis , cocaine addiction , mental retardation , cancer , and AIDS -- prior to and after completing the assigned condition . As expected , results showed that education had no effect on attributions about physical disabilities but led to improved attributions in all four psychiatric groups . Contact produced positive changes that exceeded education effects in attributions about targeted psychiatric disabilities : depression and psychosis . Protest yielded no significant changes in attributions about any group . This study also examined the effects of these strategies on processing information about mental illness |
10,937 | 28,535,157 | Conclusions : Determination of CXCL12 expression has the potential to be of use as a cancer biomarker and adds prognostic information in various cancer types . | Background : CXCL12 ( SDF1 ) is reported to promote cancer progression in several pre clinical models and this is corroborated by the analysis of human tissue specimens .
However , the relationship between CXCL12 expression and cancer survival has not been systematic ally assessed . | The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative . The aim of this study was to investigate the prognostic role of circulating VEGF , PDGF , SDF-1 , osteopontin and CEA in patients r and omly assigned to three bevacizumab-based regimens . Plasma sample s from 50 patients treated at a single Institution were analysed using the multiplex assay BioPlex ™ 2200 ( Bio-Rad Laboratories , Inc , Berkeley , CA , USA ) at baseline , before first three cycles and subsequently every three cycles until disease progression . Prognostic analyses of baseline values were performed using multivariable Cox models , including disease extension > 10 cm or ≤10 cm ( measured as the sum of the diameters for all target lesions ) as adjustment factor . The association between progression-free and overall survival and biomarkers modulation during treatment was studied using multivariable Cox models , which included summary statistics synthesizing during-treatment modulation together with disease extension . The biomarkers significantly associated with disease extension were baseline CEA ( p = 0.012 ) and SDF-1 ( p = 0.030 ) . High values of VEGF and SDF-1 tended to be associated with worse prognosis , especially in terms of overall survival . The negative prognostic trend was more marked for baseline CEA as compared to other biomarkers ; increasing values during treatment was significantly related to worse prognosis independently of disease extension ( p = 0.007 and 0.016 for progression-free and overall survival , respectively ) . VEGF is related to bevacizumab pharmacodynamics and is associated to other angiogenic cytokines ; some of the proposed biomarkers such as SDF-1 and CEA should be further vali date d for prognosis assessment and monitoring of bevacizumab-based treatment of advanced colorectal cancer Introduction : We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment . In this study , we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma . Methods : We review ed surgically resected , solitary lung squamous cell carcinoma patients ( n = 485 ; 1999–2009 ) who were r and omly split into a training cohort ( n = 331 ) and validation cohort ( n = 154 ) . We constructed tissue microarrays and performed immunostaining for CD3 , CD45RO , CD8 , CD4 , FoxP3 , CD20 , CD68 , CXCL12 , CXCR4 , CCR7 , interleukin-7 receptor , and interleukin-12 receptor & bgr;2 . Overall survival ( OS ) was analyzed using the log-rank test and the Cox proportional hazards model . Results : Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10 + neutrophils were associated with worse prognoses in the training cohort ( p = 0.021 ) . Analysis of biologically relevant immune cell combinations identified that patients with high CD10 + neutrophil and low CD20 + lymphocyte had a significantly worse OS ( 5-year OS , 42 % ) than those with other combinations of CD10 and CD20 ( 5-year OS , 62 % ; p < 0.001 ) ; this was confirmed in the validation cohort ( p = 0.032 ) . For the multivariate analysis , high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort ( hazard ratio = 1.61 , p = 0.006 ) and the validation cohort ( hazard ratio = 1.75 ; p = 0.043 ) . Conclusion : High CD10+/low CD20 + immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma . Immunomodulatory therapy of tumor-specific neutrophil and B-lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma PURPOSE To evaluate the safety , efficacy and biomarkers of short-course proton beam radiation and capecitabine , followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma ( PDAC ) patients . METHODS AND MATERIAL S Patients with radiographically resectable , biopsy-proven PDAC were treated with neoadjuvant short-course ( 2-week ) proton-based radiation with capecitabine , followed by surgery and adjuvant gemcitabine . The primary objective was to demonstrate a rate of toxicity grade ≥ 3 of < 20 % . Exploratory biomarker studies were performed using surgical specimen tissues and peripheral blood . RESULTS The phase 2 dose was established at 5 daily doses of 5 GyE. Fifty patients were enrolled , of whom 35 patients were treated in the phase 2 portion . There were no grade 4 or 5 toxicities , and only 2 of 35 patients ( 4.1 % ) experienced a grade 3 toxicity event ( chest wall pain grade 1 , colitis grade 1 ) . Of 48 patients eligible for analysis , 37 underwent pancreaticoduodenectomy . Thirty of 37 ( 81 % ) had positive nodes . Locoregional failure occurred in 6 of 37 resected patients ( 16.2 % ) , and distant recurrence occurred in 35 of 48 patients ( 72.9 % ) . With median follow-up of 38 months , the median progression-free survival for the entire group was 10 months , and overall survival was 17 months . Biomarker studies showed significant associations between worse survival outcomes and the KRAS point mutation change from glycine to aspartic acid at position 12 , stromal CXCR7 expression , and circulating biomarkers CEA , CA19 - 9 , and HGF ( all , P<.05 ) . CONCLUSIONS This study met the primary endpoint by showing a rate of 4.1 % grade 3 toxicity for neoadjuvant short-course proton-based chemoradiation . Treatment was associated with favorable local control . In exploratory analyses , KRAS(G12D ) status and high CXCR7 expression and circulating CEA , CA19 - 9 , and HGF levels were associated with poor survival Background CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread . In epithelial ovarian cancer ( EOC ) , CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network . However , its prognostic significance remains unclear . We thus compared CXCL12 status in healthy and malignant ovaries , to assess its prognostic value . Methods Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts , including the ovaries and fallopian tubes , of healthy women , in benign and borderline epithelial tumors , and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospect i ve clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy ( GINECO study ) . Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables . Kaplan-Meier methods were used to generate progression-free and overall survival curves . Results Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12 , whereas the follicles within the ovary did not . Epithelial cells in benign , borderline and malignant tumors also expressed CXCL12 . In EOC specimens , CXCL12 immunoreactivity was observed mostly in epithelial tumor cells . The intensity of the signal obtained ranged from strong in 86 cases ( 47 % ) to absent in 18 cases ( < 10 % ) . This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC . CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status . They also had no impact on progression-free or overall survival . Conclusion Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes , indicating that EOC may originate from either of these epithelia . We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself . Trial Registration Clinical Trials.gov : The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies |
10,938 | 21,975,783 | Hospital admissions also demonstrated wide variation between trials with significant changes in some trials in both directions .
Quality of life improved in both education and control groups over time .
We found inconsistent evidence for home-based asthma educational interventions compared to st and ard care , education delivered outside of the home or a less intensive educational intervention delivered at home . | BACKGROUND While guidelines recommend that children with asthma should receive asthma education , it is not known if education delivered in the home is superior to usual care or the same education delivered elsewhere .
The home setting allows educators to reach population s ( such as the economically disadvantaged ) that may experience barriers to care ( such as lack of transportation ) within a familiar environment .
OBJECTIVES To perform a systematic review on educational interventions for asthma delivered in the home to children , caregivers or both , and to determine the effects of such interventions on asthma-related health outcomes .
We also planned to make the education interventions accessible to readers by summarising the content and components . | Asthma self-management programmes have been shown to increase children 's knowledge about asthma and improve their management practice s and health status . However , existing programmes have rarely addressed the unique learning needs of very young children . This study aim ed to develop and assess the effectiveness of a video tape and picture book design ed to teach children about the prevention and management of acute episodes of asthma . The information content of the educational re sources was determined by analysis of relevant medical information and asthma management skills . Social Learning Theory and consideration of the developmental stage of the target population informed the format and style of presentation of the re sources . Eighty children aged between 2 and 5 years who had been diagnosed with asthma by their medical practitioner and who required daily asthma medication participated in a controlled experimental study . The study evaluated the impact of the asthma education re sources on children 's knowledge about asthma , compliance with medication regimens and health status . Children were r and omly allocated to one of three experimental groups . Children in these groups were exposed to either the video tape alone , the book alone or both the video tape and book , or to a control group who viewed material s unrelated to asthma . The results for the three experimental groups were compared with the control group who did not receive exposure to any of the asthma education re sources . The results showed that children in each experimental group had significantly greater gains in asthma-related knowledge than children in the control group and children exposed to both re sources showed the greatest increases in knowledge . Children in each of the three experimental groups also had better compliance and health than children in the control group . These findings indicate that carefully design ed asthma education re sources are useful for providing even the youngest children with information about asthma and its management OBJECTIVE To test the validity and short-term responsiveness to change of a pediatric , asthma-specific , health-related quality -of-life ( HRQL ) instrument . METHODS Children 2 years and older treated in the emergency department ( ED ) for acute asthma were eligible for this prospect i ve cohort study . A 10-item instrument , the Integrated Therapeutics Group Child Asthma Short Form ( ITG-CASF ) , was administered at the time of the ED visit and again 14 days later ( via telephone ) . At the follow-up call , parents were also asked about the child 's current overall asthma status , missed school or limited activities , and persistence of asthma symptoms . RESULTS A total of 121 children were enrolled ( mean age , 7.9 years ) , and follow-up was complete for 96 ( 79 % ) . Mean + /- SD ITG-CASF scores at follow-up were significantly higher among children reported to have improved overall ( 61.8 + /- 19.6 ) than those not improved ( 41.9 + /- 21.2 ) , and there was a significant correlation between ITG-CASF score at follow-up and the number of days of school missed or limited activities ( r = -0.45 ; 95 % confidence interval [ CI ] , -0.24 to -0.66 ) . There was also a significant difference in improvement in ITG-CASF score from ED visit to follow-up among those improved ( 13.7-point improvement ) compared with those not improved ( 3.3-point improvement ; difference = 10.4 ; 95 % CI , 1.2 to 19.5 ) . The effect size was 0.68 , indicating a large responsiveness to change . CONCLUSIONS The ITG-CASF is a valid and responsive measure of HRQL in children with acute asthma and may be a useful outcome measure in evaluating ED treatment BACKGROUND Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes . Reductions in these triggers of asthma have been difficult to achieve and have seldom been associated with decreased morbidity from asthma . The objective of this study was to determine whether an environmental intervention tailored to each child 's allergic sensitization and environmental risk factors could improve asthma-related outcomes . METHODS We enrolled 937 children with atopic asthma ( age , 5 to 11 years ) in seven major U.S. cities in a r and omized , controlled trial of an environmental intervention that lasted one year ( intervention year ) and included education and remediation for exposure to both allergens and environmental tobacco smoke . Home environmental exposures were assessed every six months , and asthma-related complications were assessed every two months during the intervention and for one year after the intervention . RESULTS For every 2-week period , the intervention group had fewer days with symptoms than did the control group both during the intervention year ( 3.39 vs. 4.20 days , P<0.001 ) and the year afterward ( 2.62 vs. 3.21 days , P<0.001 ) , as well as greater declines in the levels of allergens at home , such as Dermatophagoides farinae ( Der f1 ) allergen in the bed ( P<0.001 ) and on the bedroom floor ( P=0.004 ) , D. pteronyssinus in the bed ( P=0.007 ) , and cockroach allergen on the bedroom floor ( P<0.001 ) . Reductions in the levels of cockroach allergen and dust-mite allergen ( Der f1 ) on the bedroom floor were significantly correlated with reduced complications of asthma ( P<0.001 ) . CONCLUSIONS Among inner-city children with atopic asthma , an individualized , home-based , comprehensive environmental intervention decreases exposure to indoor allergens , including cockroach and dust-mite allergens , result ing in reduced asthma-associated morbidity BACKGROUND Asthma continues to be a substantial cause of morbidity in pediatric population s. New strategies are needed to provide cost-effective educational interventions for children with asthma , particularly those in the inner city . OBJECTIVE To assess the effectiveness of a multimedia educational software program about asthma . SETTING A hospital-based primary care clinic and an affiliated neighborhood health center . DESIGN R and omized , controlled trial . POPULATION Children 3 to 12 years old with physician-diagnosed asthma . INTERVENTION An interactive educational computer program , Asthma Control , design ed to teach children about asthma and its management . Using a graphic display of a child going through simulated daily events , the game emphasizes : 1 ) monitoring ; 2 ) allergen identification ; 3 ) use of medications ; 4 ) use of health services ; and 5 ) maintenance of normal activity . Control group participants review ed printed educational material s with a research assistant . OUTCOMES Acute health care use ( emergency department and outpatient ) was the primary outcome . Secondary outcome measures included maternal report of asthma symptom severity , child functional status and school absences , satisfaction with care , and parental and child knowledge of asthma . RESULTS A total of 137 families were enrolled in the study ( 76 intervention , 61 control ) . Both intervention and control groups showed substantial improvement in all outcomes during the 12-month follow-up period . Aside from improvement in knowledge after use of the computer program , no differences were demonstrated between the 2 groups in primary or secondary outcome measures . Children reported enjoyment of program use . CONCLUSIONS This trial of an educational software program found that it did not produce greater improvement than occurred with review of traditional written material s. Because both groups showed substantial improvement over baseline , computer-based education may be more cost-effective . Alternatively , improvements in illness severity over time may overshadow the effects of such interventions . Rigorous comprehensive evaluations such as this are necessary to assess new interventions intended to improve management and outcomes of asthma Background : The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze . Methods : A prospect i ve , r and omised , partially blinded , controlled trial was design ed at two secondary care centres . Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children 's ward or attendance at an accident and emergency department or children 's ( emergency ) assessment unit ( A&E/CAU ) with a primary diagnosis of acute severe asthma or wheezing were recruited . 101 children were r and omised into the control group and received usual care and 99 were assigned to the intervention group and received : ( 1 ) a pre-school asthma booklet ; ( 2 ) a written guided self-management plan ; and ( 3 ) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s ) and child . Subjects were assessed at 3 , 6 , and 12 months . The main outcomes were GP consultation rates , hospital re-admissions , and attendances at A&E/CAU . Secondary outcomes included disability score , caregivers ' quality of life , and parental knowledge of asthma . Results : There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures . Conclusions : These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months Background : In clinical trials of asthma , the outcomes are often good , but when the same treatment regimens are implemented in primary care , equally good results are not obtained . Objective : To investigate if addition of structured patient information and monitoring by an asthma diary in primary care improves asthma control . Methods : 141 patients from 19 primary care centres were studied . The centres were r and omised to a st and ard care group or to an intervention group . The intervention group received structured written and oral information about asthma and asthma medication , and were instructed to keep an asthma diary . The primary outcome was asthma control as assessed by the Asthma Control Question naire . Secondary outcomes were costs of asthma medication , the Mini Asthma Quality of Life Question naire score and lung function . Results : Asthma Control Question naire score changes differed between the study groups ( p < 0.05 ) . In the intervention group , these changes ( M = –0.45 ) in asthma control were close to clinical significance ( minimal important difference ≈0.5 ) . Both groups improved in disease-specific quality of life scores . For the intervention group , which changed the most ( p < 0.05 ) , the change exceeded the threshold for the minimal important difference ( 0.5 ) . The costs of medications increased significantly in the intervention group , where adjustments of medication were made more often than in controls . Conclusion : Disease-specific quality of life of asthma patients could be improved by adding structured information and monitoring by diary to st and ard care This study was conducted to test the efficacy of AIR WISE , an individually administered asthma self-management program . Subjects were paired and r and omly assigned to either an experimental group ( N = 7 ) or a control group ( N = 7 ) . The frequency of experimental group emergency visits , analyzed over a 12-month posttreatment period , was substantially less than those of the control group , supporting the hypothesis that AIR WISE is effective in high-utilizer children through improved self-management The effects on self management of asthma of a specially prepared book and audiocassette tape with similar contents were observed in a controlled study of 177 patients with asthma in general practice . After a run in period of six months patients were r and omly given the book , the tape , both the book and tape , or neither . Patients ' knowledge of the use of drugs , perceptions of their disability , skill in using an inhaler , consumption of drugs , consultations with their general practitioners , morbidity ( from patients ' entries on diary cards ) , and use of the educational material were measured . Knowledge about the use of drugs was significantly increased in the groups who received the material after three months and persisted after 12 months . Patients who had been given the tape or the book and tape increased their scores of knowledge of drugs more than patients given the book alone . Patients in all groups given the material considered that their disability was reduced . There were no other significant changes . Patients given both the book and the tape preferred the book . Patients with asthma can obtain useful information from such material . The paradoxical result whereby patients learnt more from the tape but preferred the book suggests that a distinction can be made between information that patients need , which may be acquired better from an audiocassette , and information that they want , which may be acquired better from a book A r and omized , controlled trial was conducted to assess the effectiveness of Blue Angel for Asthma Kids , an Internet-based interactive asthma educational and monitoring program , used in the management of asthmatic children . One hundred sixty-four ( n = 164 ) pediatric patients with persistent asthma were enrolled and r and omized into two study groups for a 12-week controlled trial . The intervention group had 88 participants who were taught to monitor their peak expiratory flows ( PEF ) and asthma symptoms daily on the Internet . They also received an interactive response consisting of a self-management plan from the Blue Angel monitoring program . The control group had 76 participants who received a traditional asthma care plan consisting of a written asthma diary supplemented with instructions for self-management . Disease control was assessed by weekly averaged PEF values , symptom scores , and asthma control tests . Adherence measures were assessed by therapeutic and diagnostic monitoring . Outcome was assessed by examining quality of life and retention of asthma knowledge . The data were analyzed by comparing results before and after the trial . At the end of trial , the intervention group decreased nighttime ( -0.08 + /- 0.33 vs. 0.00 + /- 0.20 , p = 0.028 ) and daytime symptoms ( -0.08 + /- 0.33 vs. 0.01 + /- 0.18 , p = 0.009 ) ; improved morning ( 241.9 + /- 81.4 vs. 223.1 + /- 55.5 , p = 0.017 ) and night PEF ( 255.6 + /- 86.7 vs. 232.5 + /- 55.3 , p = 0.010 ) ; increased adherence rates ( p < 0.05 ) ; improved well-controlled rates ( 70.4 % vs. 55.3 % , p < 0.05 ) ; improved knowledge regarding self-management ( 93.2 % vs. 70.3 % , p < 0.05 ) ; and improved quality of life ( 6.5 + /- 0.5 vs. 4.3 + /- 1.2 on a 7-point scale , p < 0.05 ) when compared with conventional management . The Internet-based asthma telemonitoring program increases selfmanagement skills , improves asthma outcomes , and appears to be an effective and well-accepted technology for the care of children with asthma and their caregivers Objective Home dampness and the presence of mold and allergens have been associated with asthma morbidity . We examined changes in asthma morbidity in children as a result of home remediation aim ed at moisture sources . Design In this prospect i ve , r and omized controlled trial , symptomatic , asthmatic children ( n = 62 ) , 2–17 years of age , living in a home with indoor mold , received an asthma intervention including an action plan , education , and individualized problem solving . The remediation group also received household repairs , including reduction of water infiltration , removal of water-damaged building material s , and heating/ventilation/air-conditioning alterations . The control group received only home cleaning information . We measured children ’s total and allergen-specific serum immuno-globulin E , peripheral blood eosinophil counts , and urinary cotinine . Environmental dust sample s were analyzed for dust mite , cockroach , rodent urinary protein , endotoxin , and fungi . The follow-up period was 1 year . Results Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study . The remediation group had a significant decrease in symptom days ( p = 0.003 , as r and omized ; p = 0.004 , intent to treat ) after remodeling , whereas these parameters in the control group did not significantly change . In the postremediation period , the remediation group had a lower rate of exacerbations compared with control asthmatics ( as treated : 1 of 29 vs. 11 of 33 , respectively , p = 0 . 003 ; intent to treat : 28.1 % and 10.0 % , respectively , p = 0.11 ) . Conclusion Construction remediation aim ed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem OBJECTIVE To test a quality improvement intervention , a learning collaborative based on the Institute for Healthcare Improvement 's Breakthrough Series methodology , specifically intended to improve care and outcomes for patients with childhood asthma . DESIGN R and omized trial in primary care practice s. SETTING Practice s in greater Boston , Mass , and greater Detroit , Mich. PARTICIPANTS Forty-three practice s , with 13 878 pediatric patients with asthma , r and omized to intervention and control groups . Intervention Participation in a learning collaborative project based on the Breakthrough Series methodology of continuous quality improvement . MAIN OUTCOME MEASURES Change from baseline in the proportion of children with persistent asthma who received appropriate medication therapy for asthma , and in the proportion of children whose parent received a written management plan for their child 's asthma , as determined by telephone interviews with parents of 631 children . RESULTS After adjusting for state , practice size , child age , sex , and within- practice clustering , no overall effect of the intervention was found . CONCLUSIONS This method ologically rigorous assessment of a widely used quality improvement technique did not demonstrate a significant effect on processes or outcomes of care for children with asthma . Potential deficiencies in program implementation , project duration , sample selection , and data sources preclude making the general inference that this type of improvement program is ineffective . Additional rigorous studies should be undertaken under more optimal setting s to assess the efficacy of this method for improving care PURPOSE Studies suggest peer-led self-management training improves chronic illness outcomes by enhancing illness management self-efficacy . Limitations of most studies , however , include use of multiple outcome measures without pre design ated primary outcomes and lack of r and omized follow-up beyond 6 months . We conducted a 1-year r and omized controlled trial of Homing in on Health ( HIOH ) , a Chronic Disease Self-Management Program variant , addressing these limitations . METHODS We r and omized out patients ( N = 415 ) aged 40 years and older and who had 1 or more of 6 common chronic illnesses , plus functional impairment , to HIOH delivered in homes or by telephone for 6 weeks or to usual care . Primary outcomes were the Medical Outcomes Study 36-ltem short-form health survey‘s physical component ( PCS-36 ) and mental component ( MCS-36 ) summary scores . Secondary outcomes included the EuroQol EQ-5D and visual analog scale ( EQ VAS ) , hospitalizations , and health care expenditures . RESULTS Compared with usual care , HIOH delivered in the home led to significantly higher illness management self-efficacy at 6 weeks ( effect size = 0.27 ; 95 % CI , 0.10–0.43 ) and at 6 months ( 0.17 ; 95 % CI , 0.01–0.33 ) , but not at 1 year . In-home HIOH had no significant effects on PCS-36 or MCS-36 scores and led to improvement in only 1 secondary outcome , the EQ VAS ( 1-year effect size = 0.40 ; CI , 0.14–0.66 ) . HIOH delivered by telephone had no significant effects on any outcomes . CONCLUSIONS Despite leading to improvements in self-efficacy comparable to those in other CDSMP studies , in-home HIOH had a limited sustained effect on only 1 secondary health status measure and no effect on utilization . These findings question the cost-effectiveness of peer-led illness self-management training from the health system perspective OBJECTIVES To test the hypothesis that reinforcement of the advice given at the time of discharge from the emergency department by telephone consultation would improve asthma outcomes . METHODS A r and omized controlled trial of the parents of 310 children who had been discharged from the emergency department with asthma was undertaken . The parents were r and omized to receive either st and ard care ( 155 children ) or st and ard care plus education by telephone ( 155 children ) from a trained asthma educator . Symptoms , parental asthma knowledge , parental quality of life and use of asthma action plans and preventer therapy were collected at baseline and 6 months later . The primary measure was days of wheeze in last 3 months ; intermediate measures were regular use of preventer medications , possession and use of written asthma action plan , parental asthma knowledge scores and parental quality of life scores . RESULTS A total of 266 parents ( 136 intervention ) completed the follow-up question naires after 6 months . Both groups showed similar symptoms and process measures at baseline , apart from more regular use of preventer medication in the control children . At follow up , the intervention group children were significantly more likely than controls to possess ( 87.5 % vs 72.3 % ; P = 0.002 ) a written asthma action plan . Possession of action plans increased from baseline in the intervention group but tended to decrease in the control group . Use of action plans was greater in the intervention group but decreased from baseline in both groups . Both intervention and control groups showed significant decreases in asthma symptoms . CONCLUSIONS Reinforcement by telephone consultation did not improve the primary outcome of wheeze in the last 3 months . However , it increased the possession and regular use of written asthma action plans in the intervention group OBJECTIVE To assess the outcomes of an education intervention for childhood asthma conducted by Australian Indigenous health care workers ( IHCWs ) . DESIGN AND SETTING R and omised controlled trial in a primary health care setting on Thursday Isl and and Horn Isl and , and in Bamaga , Torres Strait region of northern Australia , April 2005 to March 2007 . PARTICIPANTS 88 children , aged 1 - 17 years , with asthma diagnosed by a respiratory physician ( intervention group , 35 ; control group , 53 ; 98 % Indigenous children ) . INTERVENTIONS Children were r and omly allocated to : ( i ) three additional asthma education sessions with a trained IHCW , or ( ii ) no additional asthma education . Both groups were re-assessed at 12 months . MAIN OUTCOME MEASURES Primary endpoint : number of unscheduled visits to hospital or a doctor caused by asthma exacerbation . SECONDARY OUTCOMES measures of quality of life ( QoL ) and functional severity index ; asthma knowledge and underst and ing of asthma action plans ( AAPs ) ; and school days missed because of wheezing . RESULTS The groups were comparable at baseline ( except for asthma severity , which was adjusted for in the analysis ) . There were no significant differences in the primary outcome ( number of unscheduled medical visits for asthma ) . School children in the intervention group missed fewer school days because of wheezing ( 100 % < 7 days v 21 % of those in the control group missed 7 - 14 days ) . Significantly more carers in the intervention group could answer questions about asthma medication , knew where their AAP was kept ( 84 % v 56 % ) , and were able to describe the plan ( 67 % v 40 % ) . In both the intervention and control groups ( before- and -after comparison ) , there was a significantly reduced frequency of asthma exacerbations , as well as an improved QoL score and functional severity index , with no significant differences between the groups . CONCLUSIONS A community-based asthma education program conducted by trained IHCWs improves some important asthma outcomes in Indigenous children with asthma . TRIAL REGISTRATION Australian Clinical Trials Registry ACTRN012605000718640 Twenty children with severe asthma using continual oral beta 2 agonists were r and omized equally into either a behavioral intervention group or a control group . The behavioral intervention consisted of : symptom discrimination of asthma signals , self-management techniques of breathlessness , and contingency management of asthma-related behavior . The purpose of the study was to evaluate the effects of the behavioral treatment when superimposed on a regular medical treatment . The design consisted of a four-week baseline period , a four-week intervention period , and a four-week follow-up period . Results showed that the group receiving the behavioral intervention significantly reduced their use of beta 2 agonist spray doses and days of school absenteeism without increasing the number of asthma symptoms compared with the control group . It was concluded that children with severe asthma may benefit substantially from a behavioral program in addition to their regular medical treatment & NA ; The issue of whether nursing instruction efforts could improve asthma knowledge and quality of life among schoolchildren was investigated using a quasi-experimental design . The key instruments were the Asthmatic Knowledge Question naire and the Childhood Asthma Question naire-Form B. Asthmatic knowledge increased among children who received instruction from nurses ( Mean pre/post= 22.20/31.87 , p < .05 ) . These children also experienced significant improvements in their active quality of life ( Mean pre/post = 27.53/30.20 , p < .05 ) , and decreased distress ( Mean pre/post= 24.04/10.86 , p < .05 ) and asthma severity ( Mean pre/post= 13.27/8.3 , p < .05 ) . This study finds nursing instruction helpful in improving asthma knowledge . However , in terms of quality of life , elevated knowledge has a marked ( negative ) correlation only with levels of distress and severity . It shows no detectable relationship with active or passive life quality . Therefore , though nursing instruction can improve schoolchildren 's knowledge about asthma , the improvement in knowledge only relates to reducing distress and severity and thus improving quality of life . This result can provide guidance for nursing personnel in developing nursing instruction to improve active quality of life in child patients OBJECTIVE To determine the effectiveness of a home-based asthma education intervention in increasing appropriate nebulizer use and reducing symptom frequency , emergency department ( ED ) visits , and hospitalizations over 12 months . DESIGN A r and omized clinical trial . Setting s Pediatric primary care , pulmonary/allergy , and ED practice s associated with the University of Maryl and Medical System and The Johns Hopkins Hospital , Baltimore . PARTICIPANTS Children with persistent asthma , aged 2 to 9 years , with regular nebulizer use and an ED visit or hospitalization within the past 12 months . Children were r and omized into the intervention ( n = 110 ) or control ( n = 111 ) group . Follow-up data were available for 95 intervention and 86 control children . INTERVENTION Home-based asthma education , including symptom recognition , home treatment of acute symptoms , appropriate asthma medication , and nebulizer practice . MAIN OUTCOME MEASURES Estimates of mean differences in asthma symptom frequency , number of ED visits and hospitalizations and appropriate quick relief , controller medication , and nebulizer practice over 12 months . RESULTS Of the 221 children , 181 ( 81.9 % ) completed the study . There were no significant differences in home nebulizer practice , asthma morbidity , ED visits , or hospitalizations between groups ( P range , .11-.79 ) . Although most children received appropriate nonurgent asthma care ( mean , 2 visits per 6 months ) , more than one third of all children received at least 6 quick-relief medication prescriptions during 12 months , with no difference by group . CONCLUSIONS A nebulizer education intervention had no effect on asthma severity or health care use . Of concern is the high quick-relief and low controller medication use in young children with asthma seen nearly every 3 months for nonurgent care This study describes a self-treatment program for parents of children with asthma . The aim was to prevent asthma exacerbations by learning to recognise prodromal signs and acting upon them by increasing inhaled corticosteroids ( ICS ) . The study questions were : ( 1 ) can we teach parents and children to recognise prodromal signs ? ( 2 ) are instructions to increase inhalation medication followed ? ( 3 ) will frequency and severity of asthma attacks diminish subsequently ? Due to physicians ' changed attitude towards prescription of ICS , fewer children could be recruited who were " ICS-naive " than expected . Twenty-nine children of the age of 4 - 11 years with moderate asthma , participated in a one year prospect i ve r and omised study . Structured information was given to all patients on asthma , symptoms and medication . The experimental group received additional information on recognising prodromal signs and doubling ICS during one week . Only in 25 % of the patients who recognised prodromal signs the dose of ICS was doubled ( as prescribed ) , in 75 % inadequately or not at all . Recognition of prodromal signs was poor as well as compliance to increase as-needed medication . No significant decrease of asthma symptoms occurred in the experimental group . Clinical implication s are important for self-treatment instructions : an individually tailored and multi-component program should be offered by health care providers in order to help the patient to recognise early alarm symptoms , comply to self-treatment instructions and to make adaptations for continuous self-regulation OBJECTIVE To evaluate Watch , Discover , Think and Act ( WDTA ) , a theory-based application of CD-ROM educational technology for pediatric asthma self-management education . DESIGN A prospect i ve pretest posttest r and omized intervention trial was used to assess the motivational appeal of the computer-assisted instructional program and evaluate the impact of the program in eliciting change in knowledge , self-efficacy , and attributions of children with asthma . Subjects were recruited from large urban asthma clinics , community clinics , and schools . Seventy-six children 9 to 13 years old were recruited for the evaluation . RESULTS Repeated- measures analysis of covariance showed that knowledge scores increased significantly for both groups , but no between-group differences were found ( P : = 0.55 ) ; children using the program scored significantly higher ( P : < 0.01 ) on questions about steps of self-regulation , prevention strategies , and treatment strategies . These children also demonstrated greater self-efficacy ( P : < 0.05 ) and more efficacy building attribution classification of asthma self-management behaviors ( P : < 0.05 ) than those children who did not use the program . CONCLUSION The WDTA is an intrinsically motivating educational program that has the ability to effect determinants of asthma self-management behavior in 9- to 13-year-old children with asthma . This , coupled with its reported effectiveness in enhancing patient outcomes in clinical setting s , indicates that this program has application in pediatric asthma education Care of asthmatic children is often episodic and more therapeutic than preventive . A 2-year r and omized , controlled trial involving 95 children measured the impact of a comprehensive home and ambulatory program for pediatric asthma management using objective outcome measures . Interventions for the study group during the first year included 3-month clinic visits , education , and home visits by a specially trained research nurse . Control subjects continued to receive regular care from a family physician or pediatrician . Eight-nine subjects ( 93 % ) completed the study . Study subjects had less school absenteeism than control subjects ( 10.7 vs. 16.0 days , P = .04 ) and showed significantly better small airway function after 1 year . Asthma severity improved in 13 study subjects and worsened in 5 . The reverse was true for control subjects . Study subjects exhibited better metered aerosol technique than control subjects ( P = .0005 ) . Fewer days were spent in hospital by the study subjects admitted compared with control subjects ( 3.67 vs 11.2 days , P = .02 ) . After 1 year , more study than control families ( 72.1 % vs 33.1 % , P = .006 ) reported that their asthmatic child took responsibility for the asthma management . The intervention failed to reduce exposure to secondh and smoke or to household pets . There were no significant differences in medical visits , theophylline levels , or records of asthma symptoms . One year after discontinuing the intervention , a marked " washout " effect was observed . Comprehensive ambulatory programs of childhood asthma management can improve objective measures of illness severity but must be sustained A r and omised controlled study of an educational programme for children with asthma and their families was carried out by community child health nurses . Three hundred and sixty eight children aged 2 to 14 years were enrolled in the study after admission to hospital for asthma . The intervention group was visited monthly by a nurse for six months . The subjects were assessed six months later by a postal , self administered question naire . European children in the intervention group were taking significantly more drugs for the treatment of asthma six months after the index admission to hospital than those in the control group ( mean ( SD ) intake 2.7 ( 1.1 ) v 2.1 ( 1.0 ) , respectively ) . In particular , they were using more theophylline ( 56.6 % v 37.0 % ) and inhaled steroids ( 34.9 % v 21.0 % ) . There was no difference between the groups for parental reports of improvement , of missed schooling , and in severe attacks of asthma of not responding to the usual treatment at home . European children in the intervention group used the hospital services for severe attacks of asthma more than controls ( 34.2 % v 10.5 % ) . There were more re-admissions in the European intervention group in the subsequent six months after the index admission than in the control group ( mean ( SD ) 0.51 ( 0.97 ) v 0.29 ( 0.65 ) . Re-admission continued to be higher in the 12 months after the nurse had stopped visiting ( 0.81 ( 1.65 ) v 0.25 ( 0.65 ] . There was no difference in the duration of hospital stay between the intervention and control groups . For Polynesian children there was no difference between the groups for any outcome measures OBJECTIVE To present an interim analysis of the effect of a home-based intervention with low-income caregivers of wheezing infants at risk for childhood asthma on mediating variables . METHOD Infants aged 9 to 24 months with 3 or more physician-documented wheezing episodes were r and omly assigned to environmental support intervention ( ES ) ( n = 90 ) or control ( n = 91 ) groups . Nurse home visitors intervened for 1 year to decrease allergen and environmental tobacco smoke exposure and improve symptom perception and management . Assessment s at baseline and 12 months included allergens in house dust , infant urinary cotinine levels , caregivers ' symptom reports , quality of life , illness management , and quality of caregiving . Medical records were coded for hospitalizations , emergency department visits , and corticosteroid bursts . RESULTS Within the ES group , cockroach allergen levels were significantly reduced and there was a trend toward reduction in dog d and er levels . Among infants with detectable urinary cotinine , levels were significantly reduced in the ES group . Caregiver psychological re sources modified the impact , and low-re source ES caregivers were the most strongly affected . Asthma knowledge and provider collaboration improved significantly in the ES group . Neither reports of infant symptoms nor emergency department visits or hospitalizations showed positive intervention effects . Number of corticosteroid bursts for infants was significantly higher for the ES group . CONCLUSIONS The Childhood Asthma Prevention Study intervention was effective in reducing several environmental exposures and improving illness management . However , even with an intensive home-based intervention , we failed to reduce respiratory symptoms or medical use in the ES group relative to the control group , illustrating the difficulty of changing the course of early asthma development among low-income infants The effectiveness of community health workers ( CHWs ) assisting families in reducing exposure to indoor asthma triggers has not been studied . In all , 274 low-income asthmatic children were r and omly assigned to high- or low-intensity groups . CHWs visited all homes to assess exposures , develop action plans and provide bedding encasements . The higher-intensity group also received cleaning equipment and five to nine visits over a year focusing on asthma trigger reduction . The asthma trigger composite score decreased from 1.56 to 1.19 ( Δ=−0.37 , 95 % CI 0.13 , 0.61 ) in the higher-intensity group and from 1.63 to 1.43 in the low-intensity group ( Δ=−0.20 , 95 % CI 0.004 , 0.4 ) . The difference in this measure due to the intervention was significant at the P=0.096 level . The higher-intensity group also showed improvement during the intervention year in measurements of condensation , roaches , moisture , cleaning behavior , dust weight , dust mite antigen , and total antigens above a cut point , effects not demonstrated in the low-intensity group . CHWs are effective in reducing asthma trigger exposure in low-income children . Further research is needed to determine the effectiveness of specific interventions and structural improvements on asthma trigger exposure and health BACKGROUND H and held electronic spirometers provide the opportunity for more comprehensive monitoring of lung function at home than has hitherto been available . The aim of this study was to assess the quality of spirometric data collected at home by 90 asthmatic schoolchildren aged 7 - 14 years . METHODS After training , children carried out twice daily recordings at home for four consecutive periods of 4 weeks using a data storage spirometer ( Vitalograph ) , encouraged by 4-weekly visits from a research nurse . Compliance ( proportion of blows recorded at correct time of day ) , technical quality ( by machine criteria ) , and valid data recorded ( the multiple of compliance and technical ability ) were assessed . RESULTS Mean compliance declined from 81.4 % to 70.4 % ( p<0.001 ) between the first and last month , although the technical quality of the manoeuvres ( 81.9 % and 80.1 % , respectively ) did not change significantly ( p=0.48 ) . CONCLUSIONS There was a steady reduction of valid data over the four periods ( from 73.6 % to 64.3 % , 59.7 % , and 57.6 % ) with wide individual differences . Even under ideal conditions , home spirometry provides an incomplete ( and therefore potentially biased ) picture of long term changes in pulmonary function Asthma educational programs have been shown to reduce the use of emergency room , frequency of severe asthma attacks and hospitalization . However , its effectiveness in other morbidity parameters and on quality of life has yet to be fully understood . This prospect i ve r and omized control trial evaluated the effectiveness of a patient education program in 77 asthmatics according to " Teach Your Patients About Asthma : A Clinicians Guide " ( 1992 ) . Forty asthmatic patients were r and omly allocated to Group A ( usual treatment ) and 37 to Group B ( usual treatment plus a patient education program ) . The effectiveness of the educational program was evaluated by comparing morbidity outcomes at baseline and 3 months after initial evaluation . At enrolment , the two groups were not different with regard to age , sex , smoking , asthma severity atopy , FEV1 , symptom-free days , use of rescue salbutamol and quality of life . Three months later , subjects in Group B showed a significant improvement in the overall quality of life ( p < 0.01 ) and in the " Symptoms"domain ( p < 0.01 ) . None of the other parameters ( use of rescue salbutamol , symptom-free days , days absent from work or school , FEV1 ) showed any significant change . After stratification for asthma severity , only subjects with moderate-to-severe asthma showed a significant improvement inthe overall quality of life ( p < 0.05 ) and in the " Symptoms " ( p < 0.01 ) and ' Activities " ( < 0.05 ) domains . Moreover , in subjects with moderate-to-severe asthma FEV1 value at the 3rd month of follow-up was higher in Group B than in Group A ( p < 0.05 ) . In conclusion , the educational program improved the quality of life in asthratic subjects , mainly in patients with moderate-to-severe asthma Allergens in house dust are risk factors for asthma causation and exacerbation , and asthma interventions often focus on exposure reduction using methods that may not be sustainable over time in low-income communities . A r and omized controlled trial with up to six home visits was used to evaluate the effectiveness of two interventions focused on reducing dust loading and allergen concentrations in 47 low-income inner-city households in Minneapolis , MN . The interventions , which included education and relatively inexpensive cleaning procedures , were developed using a community-based participatory consultation process with focus groups held in English , Somali , and Spanish to incorporate community feedback from participants into protocol s and study design decisions . Change in levels of cat , cockroach , dust mite , and culturable fungi as well as overall dust loading were evaluated by measuring the difference in concentrations before and after the cleaning intervention , and mixed models were used to assess the effect of education and cleaning on baseline allergen levels during the final three home visits . The cleaning intervention significantly lowered dust loading in all households and culturable fungi levels in single family homes , reduced cat allergen concentrations in homes with cats , but had no significant effect on cockroach allergen levels . The cleaning intervention also modestly decreased the frequency of observed allergen concentrations above suggested health benchmarks for cat , cockroach , and fungi . The cleaning and education interventions had similar effects on baseline allergen levels measured during subsequent home visits ; both interventions significantly reduced baseline levels of cat and fungal allergens observed in pre-cleaning sample s , but had no significant effect on cockroach allergen levels . Overall , the cleaning intervention modestly reduced potential exposure to risk factors associated with asthma mortality and morbidity in a way that can be implemented by most homeowners or renters , independent of education , income , or the ability to speak English Optimal home self-management in young children with asthma includes accurate symptom identification followed by timely and appropriate treatment . The objective of this study was to evaluate a home-based asthma educational intervention targeting symptom identification for parents of children with asthma . Two hundred twenty-one children with asthma were enrolled into an ongoing home-based clinical trial and r and omized into either a st and ard asthma education ( SAE ) or a symptom/nebulizer education intervention ( SNEI ) . Data included home visit records and parent 's self-report on question naires . Symptom identification and self-management skills significantly improved from preintervention to postintervention for parents in both groups with the exception of checking medications for expiration date s and the frequency of cleaning nebulizer device and equipment . However , significantly more parents of children in the SNEI group reported treating cough symptoms as compared with the SAE group ( p = 0.05 ) . Of concern is that only 38 % of all parents reported having an asthma action plan in the home . A targeted home-based asthma education intervention can be effective for improving symptom identification and appropriate use of medications in children with asthma . Home asthma educational programs should address accurate symptom identification and a demonstration of asthma medication delivery devices Children with asthma are at special risk for problems in psychological functioning , as are children with other chronic illnesses . We conducted a controlled trial of a combined education and stress management program among children ages 6 to 14 years with asthma . Eighty-one children were r and omly assigned to an intervention or a control group ; 56 children completed data collection , 29 intervention and 27 control . Psychological status was assessed by the Child Behavior Checklist ( CBCL ) before and after the intervention , as were children 's knowledge of asthma , stress ( as measured by children 's life events ) , and functional status ( as indicated by such activities as school attendance , time playing with friends , and daily chore performance ) . Children in the intervention group had a significant improvement in the total Behavior Problems score ( p < .04 ) and Internalizing scale ( p < .01 ) on the CBCL and a significant increase in daily chores ( p < .04 ) compared with the control group . Before intervention , the two groups had statistically significant positive relationships between negative life events and behavior problem scores . After intervention , children in the control group still demonstrated a significant relationship between negative life events and total and Internalizing Behavior Problem scores , although participation in the intervention group negated that relationship . Children in the intervention group whose knowledge of asthma increased were more likely to report an increase in daily chores ( p < .02 ) . We conclude that the intervention had a beneficial effect on psychological status and on children 's daily activities . The effect may have occurred in part by decreasing the likelihood that perceived stress from negative life events led to poorer adjustment The Childhood Asthma Management Program ( CAMP ) , a multicenter clinical trial sponsored by the Division of Lung Diseases of the National Heart , Lung , and Blood Institute ( NHLBI ) , is the largest outcome study of mild to moderate asthma in children to be undertaken , with eight clinical centers in the United States and Canada participating . The initial recruitment goal was 960 children within an 18-month recruitment period . Recruitment was extended to 23 months , with 1041 children r and omized from late December , 1993 , to early September , 1995 . In this time interval each of the eight centers met the recruitment goal of 120 using a variety of self-selected recruitment strategies . The goal for minority recruiting was 33 % , or 320 of the planned 960 children to be recruited . CAMP achieved the overall goal for the number of minorities , with 330 patients . Three centers recruited at or above the expected rate from the beginning . The other five centers had significant delays in recruitment . Examination of the recruitment experiences of the centers with and without delays did not indicate any single recruitment strategy that was certain to be successful . The most commonly cited factors for success were a cohesive staff , endorsement of participation by the child 's primary care provider , and ability of the staff to be flexible and honest in assessing progress and the value of recruiting methods being used OBJECTIVE : Because asthma disproportionately affects minorities , we evaluated the effects of parent mentors ( PMs ) on asthma outcomes in minority children . METHODS : This r and omized , controlled trial allocated minority asthmatic children to the PM intervention or traditional asthma care . Intervention families were assigned PMs ( experienced parents of asthmatic children who received specialized training ) . PMs met monthly with children and families at community sites , phoned parents monthly , and made home visits . Ten asthma outcomes and costs were monitored for 1 year . Outcomes were examined by using both intention-to-treat analyses and stratified analyses for high participants ( attending ≥25 % of community meetings and completing ≥50 % of PM phone interactions ) . RESULTS : Patients were r and omly assigned to PMs ( n = 112 ) or the control group ( n = 108 ) . In intention-to-treat analyses , intervention but not control children experienced significantly reduced rapid-breathing episodes , asthma exacerbations , and emergency department ( ED ) visits . High participants ( but not controls or low participants ) experienced significantly reduced wheezing , asthma exacerbations , and ED visits and improved parental efficacy in knowing when breathing problems are controllable at home . Mean reductions in missed parental work days were greater for high participants than controls . The average monthly cost per patient for the PM program was $ 60.42 , and net savings of $ 46.16 for high participants . CONCLUSIONS : For asthmatic minority children , PMs can reduce wheezing , asthma exacerbations , ED visits , and missed parental work days while improving parental self-efficacy . These outcomes are achieved at a reasonable cost and with net cost savings for high participants . PMs may be a promising , cost-effective means for reducing childhood asthma disparities To evaluate a health education program to improve family management of asthma , 310 children with asthma and their 290 parents were r and omly assigned to a program or control group . Program families participated in health education design ed to resolve specific management problems and build self-confidence in the ability to manage asthma . Following education , program parents scored better on an asthma self-management index than parents in the control group ( + 1.57 versus -0.83 , P less than 0.0001 ) . Program parents also scored better on two subindices of the self-management index : attack management ( + 0.87 vs. + 0.42 , P less than 0.05 ) and preventive measures ( + 0.42 vs. -0.35 , P less than 0.05 ) . Also , program parents reported significantly more use of guidelines to determine appropriate levels of physical activity for children . Following education , program children reported more use of three management steps than control children : productive cough or postural drainage ( 59 % vs. 35 % , P less than 0.004 ) , breathing and relaxation exercises ( 80 % vs. 65 % , P less than 0.05 ) , and attempts to stay calm ( 12 % vs. 2 % , P less than 0.05 ) . Program children reported significantly less worry than control children about the limitations asthma imposes and about making mistakes at school OBJECTIVE To conduct a controlled trial of a home-based education program for low-income caregivers of young children with asthma . METHODS Participants were r and omized to treatment-eight weekly asthma education sessions adapted from the Wee Wheezers program ( n = 49)-or usual care ( n = 46 ) . Baseline and 3- and 12-month follow-up data were gathered from caregivers and from children 's medical records . RESULTS Treatment was associated with less bother from asthma symptoms , more symptom-free days , and better caregiver quality of life at follow-up for children 1 - 3 , but not those 4 - 6 , years of age . Treatment and control groups did not differ in caregiver asthma management behavior or children 's acute care utilization . CONCLUSIONS This home-based asthma education program was most effective with younger children ; perhaps their caregivers were more motivated to learn about asthma management . Targeting psychosocial factors associated with asthma morbidity might also enhance the efficacy of asthma education for these families BACKGROUND The goal of disease management ( DM ) is to improve health outcomes and reduce cost through decreasing health care utilization . Although some studies have shown that DM improves asthma outcomes , these interventions have not been examined in a large r and omized controlled trial . OBJECTIVE To compare the effectiveness of 2 previously successful DM programs with that of traditional care . METHODS Nine hundred two individuals with asthma ( 429 adults ; 473 children ) were r and omly assigned to telephonic DM , augmented DM ( ADM ; DM plus in-home visits by a respiratory therapist ) , or traditional care . Data were collected at enrollment and at 6 and 12 months . Primary outcomes were time to first asthma-related event , quality of life ( QOL ) , and rates of asthma-related health care utilization . Secondary outcomes included rate of controller medication initiation , number of oral corticosteroid bursts , asthma symptom scores , and number of school days missed . RESULTS There were no significant differences between groups in time to first asthma-related event or health care utilization . Adult participants in the ADM group had greater improvement in QOL ( P = .04 ) and a decrease in asthma symptoms ( P = .001 ) compared with other groups . Of children not receiving controller medications at enrollment ( 13 % ) , those in the intervention groups were more likely to have controller medications initiated than the control group ( P = .01 ) . Otherwise , there were no differences in outcomes . CONCLUSIONS Overall , participation in asthma DM did not result in significant differences in utilization or clinical outcomes . The only significant impact was a higher rate of controllermedication initiation in children and improvement in asthma symptoms and QOL in adults who received ADM OBJECTIVES To test the efficacy of problem-solving skill training ( PST ) in improving health-related quality of life ( HRQOL ) of children with persistent asthma from predominantly lower socioeconomic status ( SES ) Spanish-speaking Hispanic families . METHODS R and omized controlled trial comparing st and ard care waitlist ( SC ) control , home-visiting asthma education/care coordination ( CC ) , and combined intervention ( CC + PST ) at baseline , after intervention , and 6-month follow-up . The primary outcome was parent proxy-report child HRQOL ( PedsQL ) . RESULTS Participants ( n = 252 ) were 83.3 % Hispanic and 56.3 % monolingual Spanish speakers , and 72.6 % of mothers had not graduated high school . We found a significant ( P = 0.05 ) intervention effect for parent proxy-reported child generic ( but not asthma-specific ) HRQOL , with CC + PST superior to SC [ 83.8 vs 79.8 ; adjusted mean difference of 4.05 points ( 95 % confidence interval 0.63 - 7.4 ] , but no difference between the CC and SC groups . CONCLUSIONS In this sample of vulnerable families of children with persistent asthma , a CC + PST intervention was efficacious in improving children 's generic HRQOL This article describes the design of an outcomes model incorporating adjustment for patients ' risks for various outcomes of care . A community-based educational self-management program for children with asthma is proposed for testing the model . Measures of model components : clinical factors ; non clinical factors ; psychological , cognitive , and psychosocial functioning ; and patient and client satisfaction are described . Testing this model has implication s for guiding the development of individualized culturally sensitive nursing interventions for children with asthma and their parents PURPOSE This study was done to evaluate the effectiveness of an education program for patients with asthma who use inhalers . METHODS The research design for this study was a non-equivalent control group quasi-experimental study . Participants in this study were 36 patients for the control group , and 43 patients for the experimental group . The experimental group participated in the education program . The control group received the usual care . Data were collected before and 1 month and 2 months after the program finished and were analyzed using the SPSS 12.0 program . RESULTS The experimental group had significantly higher scores of knowledge of inhalers , and inhalation technique compared to the control group . However , no significant differences were found between two groups for PEFR , asthma instability , and satisfaction with inhalers . CONCLUSION According to the results , the education program was effective in improving knowledge of inhalers , and inhalation technique . Therefore , it is recommended that this education program be used in clinical practice as an effective nursing intervention for patients with asthma on inhalers This study was design ed to answer three main questions : 1 ) Does asthma self-management education reduce asthma morbidity ? 2 ) Are the two programmes " Living With Asthma " and " Open Airways " equally effective in doing so ? 3 ) Is a shortened version of these programmes ( 4 weeks ) as effective as the longer original programme ( 8 weeks ) ? Twelve Italian centres of paediatric bronchopneumology selected 312 children with asthma , who were stratified by disease severity , gender and age , and then r and omly assigned to an Experimental group which received an educational programme or to a Comparison group , which did not . Of the 312 children selected , 209 ( 114 Experimental and 95 Comparison ) completed the educational protocol and a 1 year follow-up . Data recorded during the last 2 months of follow-up , 10 months after the educational intervention , showed that the Experimental group required significantly fewer emergency treatments : this reduction was more evident in the more severe asthma cases . In the Experimental , but not in the Comparison group , patients with more severe asthma consumed more medications than patients with milder asthma " Open Airways " yielded , in some cases , better results than " Living with Asthma " : but a type 2 error is possible . The st and ard and the shortened programmes proved equally effective . In conclusion , following education , regardless of receiving a short or long educational programme , asthma patients use emergency care services less and use medications more appropriately in comparison with st and ard care without education . This suggests that short educational programmes can be highly cost-effective in children with asthma Twenty-seven asthmatic children were allocated to three experimental conditions . The first group received an asthma self-management program ; the second group received the same program together with progressive relaxation training ; the third group was maintained initially as a control . The self-management program was effective in increasing the frequency of asthma care behavior , but no significant changes were observed in clinical or pulmonary function variables . The relaxation technique did not improve the efficacy of treatment . When the comparison was restricted to children who displayed a low level of self-care practice s , the self-management program proved to be effective in reducing attack duration , negative consequences of asthma for the child , and the level of therapeutic response to attacks BACKGROUND Despite significant medical advances , many ethnic and racial minority children who live in inner cities continue to experience disproportionately high levels of asthma morbidity and mortality compared with white children . As a result , a growing number of psychosocial asthma management interventions are being developed to address their needs ; however , only a few of these interventions have incorporated cultural variables into their treatments and have had their efficacy evaluated . OBJECTIVE To examine the efficacy of the Multifamily Asthma Group Treatment ( MFAGT ) , design ed to enhance asthma management and reduce emergency department ( ED ) visits among African American and Hispanic families . METHODS Twenty-four African American and Hispanic families who have children with asthma were r and omly assigned to either the MFAGT or the St and ard Psychoeducational Asthma Intervention . Differences in the number of ED visits and the level of asthma management in both groups were compared 1 year before and 1 year after the intervention . In addition , these groups were contrasted to a control group that did not receive any psychoeducational intervention . RESULTS The MFAGT was significantly ( P = .04 ) more effective than the St and ard Psychoeducational Asthma Intervention and the control in decreasing ED visits and increasing parental asthma knowledge . CONCLUSIONS These preliminary results suggest that the MFAGT is efficacious in enhancing asthma management and in reducing ED visits in inner-city African American and Hispanic children from a lower socioeconomic background OBJECTIVE To measure the effect of an asthma intervention on the functional status and morbidity of children with undiagnosed asthma . STUDY DESIGN Data from a r and omized trial were used to compare outcomes at baseline and follow-up for children with undiagnosed and diagnosed asthma . We studied 510 symptomatic children with diagnosed asthma ( diagnosed ) and 299 children with symptoms but no diagnosis ( undiagnosed ) . Baseline functioning and morbidity were similar for undiagnosed and diagnosed patients classified as moderate-severe . RESULTS There were fewer undiagnosed reported allergies , seasonal symptoms , and other respiratory diagnoses ( all P < 0.01 ) . Among the moderate-severe , functional status , for example , symptom-days ( P = .02 ) , symptom-nights ( P < .01 ) , and days of restricted activity ( P < .01 ) , was significantly reduced at follow-up for the undiagnosed in the intervention group but not for undiagnosed control subjects . Findings were similar for children with diagnosed asthma . CONCLUSIONS Children with undiagnosed asthma were generally nonatopic , although some had symptoms at a level comparable to children with a diagnosis . The intervention successfully improved functional status for children with undiagnosed asthma as well as for children with diagnosed asthma . These results can be applied to ongoing discussion s related to case detection OBJECTIVE To evaluate the outcome of a secondary intervention conducted with infants at risk for asthma . DESIGN Families of wheezing infants were r and omized to a 1-year intervention or control group ; outcome evaluation occurred from April 1 , 2000 , through September 30 , 2003 , when children reached 4 years of age . SETTING Home intervention and clinic evaluation . PARTICIPANTS A total of 149 children from low-income urban families with multiple wheezing episodes before the age of 2 years . INTERVENTION Nurse home visitors provided a multifaceted intervention ( environmental allergen and tobacco smoke reduction as well as illness management ) that lasted 12 months , with the goal of decreasing asthma onset and /or severity when children reached 4 years of age . MAIN OUTCOME MEASURES Asthma status ( parent-reported symptoms , impulse oscillometry , and documented asthma diagnosis ) , caregiver quality of life , medication use , and emergency department visits . RESULTS A total of 46.0 % of children from the intervention group and 54.9 % from the control group met criteria for asthma at the age of 4 years ( P = .33 ) . Caregiver quality of life was better for the intervention group ( P = .01 ) . Children in the intervention group were less likely to have reactive airways ( prebronchodilator-postbronchodilator decrease in impulse oscillometry resistance at 10 Hz of > or = 15 % ; P = .07 ) . Outcome was modified by baseline illness severity ; among children with low severity , odds of developing asthma by the age of 4 years were 3 times lower for intervention children than controls ( P = .04 ) , and symptom severity was lower for intervention children ( P = .03 ) . CONCLUSIONS Multifaceted intervention did not decrease asthma among children with early wheezing illness as a whole , but only for children with low illness severity in infancy . Despite having an impact on only less severely ill children , results demonstrate the possibility of ameliorating illness burden for some inner-city families with children at high risk for poor asthma outcomes The aim of this study was to evaluate the effectiveness of an asthma education programme in moderate and severe asthma patients in a longitudinal , prospect i ve and r and omized study with a control group . Fifty-three asthmatic patients were studied , 26 of whom were assigned to the educational group and 27 to the control group . The educational group attended the programme regularly for a period of 6 months . The programme included information about asthma , instruction on the appropriate use of medication and training in the metered dose inhaler ( MDI ) technique , and information about the identification and control of asthma attacks and the recognition of early signs of exacerbation . The control group was su bmi tted to the routine care provided at the Asthma Clinic , with no formal instruction regarding asthma control . The groups were identical with regard to severity parameters , skills , lung function and quality of life at the beginning of the trial . At the end of the study , the education group showed significant differences when compared with the control group ( education/control ( mean values ) ) with respect to : visits to the asthma emergency room over the previous 6 months , 0.7/2 ( p=0.03 ) ; nocturnal symptoms , 0.3/0.7 ( p=0.04 ) ; score of symptoms , 1.3/2 ( p=0.04 ) . Improvements were also observed in skills and quality of life , knowledge of how to deal with attacks and how to control the environmental triggering factors , 73/35 ( < 0.05 ) ; correct use of the MDI , 8/4 ( 0.001 ) ; underst and ing of the difference between relief and anti-inflammatory medication , 86/20 ( < 0.05 ) ; and in the global limitation quality of life score , 28/50 ( 0.02 ) . It is concluded that the educational programme led to a significant improvement in asthma morbidity and that the implantation of educational programmes is possible for special population s when these programmes are adapted to the socioeconomic profile of the patients , with a significant gain in terms of the reduction of symptoms and improved pulmonary function and quality of life of asthmatics Background : Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life ( QoL ) in asthma . The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms , QoL , other measures of disease control , and inhaled corticosteroid ( ICS ) dose . This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques . Methods : After a 2 week run in period , 57 subjects were r and omised to one of two breathing techniques learned from instructional videos . During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms . After week 16 , two successive ICS downtitration steps were attempted . The primary outcome variables were QoL score and daily symptom score at week 12 . Results : Overall there were no clinical ly important differences between the groups in primary or secondary outcomes at weeks 12 or 28 . The QoL score remained unchanged ( 0.7 at baseline v 0.5 at week 28 , p = 0.11 both groups combined ) , as did lung function and airway responsiveness . However , across both groups , reliever use decreased by 86 % ( p<0.0001 ) and ICS dose was reduced by 50 % ( p<0.0001 ; p>0.10 between groups ) . Peak flow monitoring did not have a detrimental effect on asthma outcomes . Conclusion : Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently , but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises BACKGROUND Airborne pollutants and indoor allergens increase asthma morbidity in inner-city children ; therefore , reducing exposure , if feasible , should improve asthma morbidity . OBJECTIVE To conduct a r and omized controlled trial of methods to reduce environmental pollutant and allergen exposure in the homes of asthmatic children living in the inner city . METHODS After the completion of question naires , spirometry and allergen skin tests , home inspection , and measurement of home air pollutant and allergen levels , 100 asthmatic children aged 6 to 12 years were r and omized to the treatment group ( home-based education , cockroach and rodent extermination , mattress and pillow encasings , and high-efficiency particulate air cleaner ) or to the control group ( treated at the end of the 1-year trial ) . Outcomes were evaluated by home evaluations at 6 and 12 months , clinic evaluation at 12 months , and multiple telephone interviews . RESULTS In the treatment group , 84 % received cockroach extermination and 75 % used the air cleaner . Levels of particulate matter 10 microm or smaller declined by up to 39 % in the treatment group but increased in the control group ( P < .001 ) . Cockroach allergen levels decreased by 51 % in the treatment group . Daytime symptoms increased in the control group and decreased in the treatment group ( P = .04 ) . Other measures of morbidity , such as spirometry findings , nighttime symptoms , and emergency department use , were not significantly changed . CONCLUSIONS A tailored , multifaceted environmental treatment reduced airborne particulate matter and indoor allergen levels in inner-city homes , which , in turn , had a modest effect on morbidity BACKGROUND Asthma is an important cause of morbidity , absence from school , and use of health services among children . Computer-based educational programs can be design ed to enhance children 's self-management skills and to reduce adverse outcomes . OBJECTIVE To assess the effectiveness of an interactive device programmed for the management of pediatric asthma . DESIGN A r and omized controlled trial ( 66 participants were in the intervention group and 68 were in the control group ) . SETTING Interventions conducted at home and in an outpatient hospital clinic . PARTICIPANTS Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician . INTERVENTION An asthma self-management and education program , the Health Buddy , design ed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers ( physicians , nurses , or other case managers ) through a secure Web site . Control group participants used an asthma diary . MAIN OUTCOME MEASURES Any limitation in activity was the primary outcome . Secondary outcomes included perceived asthma symptoms , absence from school , any peak flow reading in the yellow or red zone , and use of health services . RESULTS After adjusting for covariates , the odds of having any limitation in activity during the 90-day trial were significantly ( P = .03 ) lower for children r and omized to the Health Buddy . The intervention group also was significantly ( P = .01 ) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital ( P = .05 ) . Self-care behaviors , which were important correlates of asthma outcomes , also improved far more for the intervention group . CONCLUSION Compared with the asthma diary , monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes PURPOSE To determine the relationships of adherence to daily peak expiratory flow rate ( PEFR ) monitoring , recommended for asthma self-management , with self-concept and health locus of control in a sample of 42 children , ages 7 through 11 . DESIGN / METHODS Secondary analysis was conducted on data collected as part of our 5-week r and omized , controlled asthma self-management clinical trial . During the study , the Piers-Harris Children 's Self-Concept Scale ( PHCSC ) and Children 's Health Locus of Control Scale ( CHLOC ) were administered at baseline ( Week 1 ) and Week 5 for comparison , while adherence to electronically-measured peak flow monitor ( PFM ) was evaluated during Week 5 . RESULTS Adherence was positively correlated with higher self-concept ( r(s ) = .33 , p = .03 ) and internal health locus of control ( r(s ) = .30 , p = .05 ) . Adherence to PFM and the intellectual and anxiety subscales of the PHCSC also were positively associated ( r(s ) = .38 , p = .01 , in both cases ) . CONCLUSIONS Children who have a positive self-concept , particularly in the areas of intellect and anxiety , are more adherent to their recommended asthma regimen . Similarly , those who perceive their ability to control their health more positively adhere better to daily PEFR monitoring . These results suggest that children 's adherence interventions may need to include components aim ed at enhancing self-concept and health locus of control BACKGROUND Children of parents who perceive their children have increased asthma severity use more medical services and reliever medication . METHODS A r and omized control trial of the Roaring Adventures of Puff ( RAP ) education program was completed among 287 grade 2 - 5 children with asthma . Parents and children completed a quality of life ( QOL ) question naire pre-intervention , 6 and 12 months post-intervention . We hypothesized that RAP altered how parent 's assessed their child 's QOL with a result ant change in asthma management . RESULTS Pre-intervention , parents rated their child 's overall QOL higher than their child ( parent 5.41 [ 95 % CI 5.24 , 5.58 ] vs. child 4.54 [ 95 % CI 4.32 , 4.75 ] ; P < 0.001 : paired t-test ) . For every point increase in the parent 's overall QOL score , the child was 36 % less likely to receive inhaled corticosteroids in the prior 2 weeks ( OR 0.64 , 95 % CI 0.46 , 0.88 ; P = 0.024 ) and 46 % less likely to have missed school due to asthma in the prior 6 months ( OR 0.54 , 95 % CI 0.36 , 0.82 ; P = 0.016 : logistic regression ) . The child 's QOL assessment , beyond that provided by their parent , was not associated with the asthma management outcomes examined . The RAP program decreased parent 's symptoms QOL assessment by an improvement of 0.45 on a 7-point scale greater than control at 6 months ( 95 % CI -0.81 , -0.09 ; P = 0.06 ) . Moreover , the RAP interaction on parent symptoms rating was important in determining whether the child received a short-acting beta-agonist in the prior 2 weeks ( P = 0.05 ) . CONCLUSIONS Parent 's QOL perception , and not the child 's , is associated with asthma management . RAP decreased the parent 's QOL symptoms assessment and was important in determining the child 's asthma management The aim of this research was to measure the impact of home-based teaching on reducing asthma admissions and emergency department ( ED ) visits for Medicaid-managed care patients utilizing two different study design methods . This was an historical- prospect i ve study utilizing health plan administrative data , including membership files and medical cl aims . We identified 381 patients aged 2 - 56 with hospitalizations or ED visits for asthma . These high risk asthma members were recruited for a home-based teaching program to prevent future hospitalizations or ED visits . We evaluated program effectiveness using two quasi-experimental research design s : a " one-group pre/post-test design , " where enrolled members served as their own control , and a more rigorous " untreated control group design with pre/post test , " where results for enrolled members and a similar control group were compared pre/post test . Poisson regression models were used to investigate the dependence of member rates for asthma-related events on program enrollment , age , sex , race , and geographic region . Using the pre/post test design , members enrolled in the home-based teaching program demonstrated statistically significant reductions in hospital admissions and ED visits ( p < 0.001 ) . The untreated control group design , however , found no association between utilization and enrollment in the home-based teaching program ( p = 0.510 ) . Small differences were detected for subgroups . A marginally statistically significant impact of the program was found for Whites , but not for Blacks . The quasi-experimental design that utilized an external control group provided an approach that more accurately explained true disease management program impact . In addition , this approach allowed for subgroup analyses to detect opportunities for program improvement Objective . To compare three pediatric asthma interventions for their impact on improving the health status of inner-city asthmatic children and in achieving cost savings . Study Design . A total of 212 children 1 to 16 years of age were r and omized into three groups : group 1 ( n = 74 ) received one individualized asthma education session ; group 2 ( n = 68 ) received reinforced asthma education ; group 3 ( n = 70 ) received reinforced asthma education plus case management . Asthma-related health re source utilization and cost were primary outcomes . The cost-benefit analysis sought to estimate the expected cost savings to the Illinois Department of Healthcare and Family Services ( Medicaid administrator ) associated with the intervention . Results . Participants in all three groups used significantly fewer emergency health care services in the follow-up year . Averaged across all three groups , the magnitudes of declines were substantial : 81 % for hospitalizations , 69 % for hospital days , 64 % for emergency department visits , and 58 % for clinic visits . Although there were no statistically significant differences between study groups for three of the four main outcome measures , group 3 participants consistently improved to the greatest degree . All three interventions were associated with considerable cost savings ranging from $ 4,021/child/year for group 1 to $ 4,503/child/year for group 3 . Conclusion . Asthma education with or without case management services enhances the health of children with asthma thereby reducing associated costs Aim : To evaluate the effectiveness of a programme of asthma clubs in improving quality of life in primary school children with asthma . Methods : A cluster r and omised intervention trial was undertaken in 22 primary schools within the urban area of south and east Belfast , Northern Irel and . Schools were r and omised in pairs to immediate or delayed groups . The study subjects comprised 173 children aged 7–11 years whose parents had notified the school of their asthma diagnosis . Children attended school based weekly clubs over an 8 week period . The main outcome measures were the interview administered Paediatric Quality of Life Question naire scores , ranging from 1 ( worst ) to 7 ( best ) , spirometry , and inhaler technique . Results : Over 15 weeks , small but non-significant improvements in the overall quality of life score ( mean 0.20 ; 95 % confidence interval ( CI ) −0.20 to 0.61 ) and in each of its three components , activity limitation ( 0.20 ; −0.43 to 0.84 ) , symptoms ( 0.23 ; −0.23 to 0.70 ) , and emotional function ( 0.17 ; −0.18 to 0.52 ) , were observed in the immediate compared with the delayed group . Inhaler technique at week 16 was markedly better in the immediate group , with 56 % having correct technique compared with 15 % in the delayed group . No significant effect of the intervention on spirometry results could be demonstrated . Conclusion : This primary school based asthma education programme result ed in sustained improvements in inhaler technique , but changes in quality of life scores were not significant Background : The objective was to develop an educational instrument , to assess its impact as an intervention instrument and to examine quality of life ( QoL ) OBJECTIVE . We sought to study the impact of emergency department (ED)–based intensive primary care linkage and initiation of asthma case management on long-term , patient-oriented outcomes for children with an asthma exacerbation . METHODS . Our study was a r and omized , 3-arm , parallel-group , single-blind clinical trial . Children aged 2 through 17 years treated in a pediatric ED for acute asthma were r and omly assigned to st and ard care ( group 1 ) , including patient education , a written care plan , and instructions to follow up with the primary care provider within 7 days , or 1 of 2 interventions . Group 2 received st and ard care plus assistance with scheduling follow-up , while group 3 received the above interventions , plus enrollment in a case management program . OUTCOMES . The primary outcome was the proportion of children having an ED visit for asthma within 6 months . Other outcomes included change in quality -of-life score and controller-medication use . RESULTS . Three hundred fifty-two children were enrolled ; 78 % completed follow-up , 69 % were black , and 70 % had persistent asthma . Of the children , 37.8 % had a subsequent ED visit for asthma , with no difference among the treatment groups ( group 1 : 38.4 % ; group 2 , 39.2 % ; group 3 , 35.8 % ) . Children in all groups had a substantial , but similar , increase in their quality -of-life score . Controller-medication use increased from 69.4 % to 81.4 % , with no difference among the groups . CONCLUSION . ED-based attempts to improve primary care linkage or initiate case management are no more effective than our st and ard ED care in improving subsequent asthma outcomes over a 6-month period BACKGROUND Patients with asthma who visit the emergency department ( ED ) may benefit from education that optimizes self-management and treatment . OBJECTIVE To conduct a r and omized trial of asthma education ( AE ) after an ED visit . METHODS Patients who present with acute asthma and history consistent with moderate to severe persistent asthma or recent ED visits were stratified by age ( adult , child ) and r and omly assigned to intervention or usual care during the ED visit . The intervention was conducted by trained asthma educators and included a facilitated office visit with the primary care physician followed by a home visit . Intention-to-treat analysis was conducted , with time to first asthma relapse ( either ED or unscheduled urgent office visit ) during the 6-month follow-up period used as the primary outcome . RESULTS Of the 239 patients analyzed , 46 % were adults , 46 % were male , 30 % were African American , and 56 % had moderate to severe persistent asthma . Follow-up information was obtained on 191 patients ( 80 % ) at 6 months ; 23.1 % of the intervention group vs 31.1 % of the usual care group had an urgent asthma visit ( hazard ratio [ HR ] , 0.79 ; 95 % confidence interval [ CI ] , 0.48 - 1.29 ) . Overall , 39 % of the 117 patients assigned to the intervention group did not comply with any of the post-ED activities . Subgroup analysis suggested greater benefit among children ( HR , 0.62 ; 95 % CI , 0.33 - 1.19 ) than adults ( HR , 1.08 ; 95 % CI , 0.50 - 2.33 ) . CONCLUSIONS Delivery of a comprehensive AE program after an ED visit was ineffective in adult patients ; however , it may be effective in children . Further research on alternative AE delivery strategies appears warranted to reduce the burden of asthma visits to the ED Aim : To study the impact of both audiovisual information and nurse‐training on the use of budesonide Turbuhaler in preschool children who had never used a dry powder inhaler . Design : A single‐blind , r and omized , parallel‐group trial studied 72 children aged 3–5 y. All children and their parents were shown an instructional video and given written instruction . After this , peak inspiratory flow ( PIF1 ) through Turbuhaler was measured . Children in group A ( n= 36 ) then received individual training by a nurse while those in Group B ( n= 36 ) did not and PIF2 was measured . Afterwards , Group B received similar individual training while Group A received no additional training , and PIF3 was measured . Group A was given a placebo Turbuhaler and encouraged to practice at home . Two weeks later , both groups returned to the clinic where PIF4 was measured . Results : The number of children who were able to correctly perform PIF1 , PIF2 and PIF4 in Group A was 27 , 34 and 36 , respectively . The corresponding numbers for Group B were 30,29 , and 29 . No effect of training was seen in 3‐y‐old children . Individual training by a nurse was associated with a statistically significant increase inPIF2 ( 10l/min;p= 0:014 ) . Moreover , 2 weeks of home training was associated with an additional increase in PIF of 8l/min compared with Group B ( p < 0:015 ) . After individual instruction and home training , mean PIF in children aged 4 and 5 was 56 ( 42‐72 ) and 55 ( 41‐66 ) l/min , respectively . Conclusion : After individual instruction and training at home , the vast majority of children aged 4 and 5 y can use Turbuhaler correctly . Audiovisual information and individual instruction is not sufficient in the majority of these children . Few 3‐y‐old children can learn the correct use of Turbuhaler The most effective means of educating children with asthma and their families has not been clearly demonstrated in previous studies . Peer education is uniquely suited to the complex problems encountered in underserved population s. The purpose of this study was to show the feasibility of delivering a peer education program for children with asthma and the effect of the program on indoor allergen levels in an inner-city population in Chicago . Overall , the program was well received . Baseline allergen levels were consistent with some previous studies in showing low levels of mite allergens and high levels of cockroach allergens , with 79.6 % of sample s having levels > 8 U/g . A total of 28.2 % of sample s had cat allergen levels > 2 microg/g , although only 9.7 % of homes had cats , confirming previous reports that cat allergen is ubiquitous . Mold levels were seasonal , with the highest levels in the summer . Results from this study suggest that intervention programs should focus more on elimination of cockroaches than was previously appreciated , while minimizing the use of pesticides , and on identification of the sources of cat allergen . Structural and psychosocial issues in homes need to be addressed in future studies . This study has demonstrated the feasibility of delivering peer education in a inner-city population and highlighted the need for comprehensive intervention strategies addressing complex issues facing underserved neighborhoods OBJECTIVES This study tested the efficacy of coaching to reduce environmental tobacco smoke ( ETS ) exposure among asthmatic Latino children . DESIGN After asthma management education , families were r and omly assigned to no additional service ( control condition ) or to coaching for ETS exposure reduction ( experimental condition ) . SETTING The study was conducted in San Diego , California . PARTICIPANTS Two hundred four Latino children ( ages 3 - 17 years ) with asthma participated . INTERVENTION Approximately 1.5 hours of asthma management education was provided ; experimental families also obtained 7 coaching sessions ( approximately 45 minutes each ) to reduce ETS exposure . OUTCOME MEASURES Reported ETS exposure and children 's urine cotinine were measured . RESULTS Parents in the coached condition reported their children exposed to significantly fewer cigarettes than parents of control children by 4 months ( postcoaching ) . Reported prevalence of exposed children decreased to 52 % for the coached families , but only to 69 % for controls . By month 4 , mean cotinine levels decreased among coached and increased among control children . Cotinine prevalence decreased from 54 % to 40 % among coached families , while it increased from 43 % to 49 % among controls . However , cotinine levels decreased among controls to the same level achieved by coached families by the 13-month follow-up . CONCLUSIONS Asthma management education plus coaching can reduce ETS exposure more than expected from education alone , and decreases in the coached condition may be sustained for about a year . The delayed decrease in cotinine among controls is discussed BACKGROUND The purpose of the present analysis is to examine changes in rural children 's asthma self-management after they received lay health educator (LHE)-delivered classes . METHODS Elementary schools were r and omly assigned to the treatment or attention-control condition and their participating students received either asthma education or general health promotion education , respectively . The triethnic sample was composed of 183 children ( 46 % Hispanic , 29.5 % non-Hispanic white , 22 % African American , and 2.6 % other categories ) who had a mean age of 8.78 years ( SD = 1.24 ) . The time frame from baseline to postintervention was 12 weeks . RESULTS Repeated measures analysis of variance found main effects in changes in scores for children 's asthma knowledge , asthma self-management , self-efficacy for managing asthma symptoms , and metered dose inhaler ( MDI ) technique and significant group interaction effects for the treatment intervention on the measures of children 's asthma knowledge , asthma self-management , and MDI technique . CONCLUSIONS The delivery of an asthma health education intervention by trained LHEs to school-aged children was an effective means for improving children 's knowledge and skills in asthma self-management This article describes the evaluation of a community-based participatory research ( CBPR ) community health worker ( CHW ) intervention to improve children 's asthma-related health by reducing household environmental triggers for asthma . After r and omization to an intervention or control group , 298 households in Detroit , Michigan , with a child , aged 7 to 11 , with persistent asthma symptoms participated . The intervention was effective in increasing some of the measures of lung function ( daily nadir Forced Expiratory Volume at one second [ p = .03 ] and daily nadir Peak Flow [ p = .02 ] ) , reducing the frequency of two symptoms ( “ cough that wo n't go away , ” “ coughing with exercise ” ) , reducing the proportion of children requiring unscheduled medical visits and reporting inadequate use of asthma controller medication , reducing caregiver report of depressive symptoms , reducing concentrations of dog allergen in the dust , and increasing some behaviors related to reducing indoor environmental triggers . The results suggest a CHW environmental intervention can improve children 's asthma-related health , although the pathway for improvement is complex CONTEXT Increasing urban asthma prevalence and severity is found among minority , underserved population s. Improving asthma self-management includes home management of complex medical protocol s as well as environmental trigger removal . OBJECTIVE To study the effectiveness of a low-cost approach to improve control of asthma symptoms in an urban population through lay educators who promote a generalized approach to asthma trigger avoidance in the bedrooms of children with asthma . DESIGN AND PATIENTS Prospect i ve , r and omized controlled trial with two arms : historical controls and matched controls for each subject . SUBJECTS Two-hundred-eighty-one patients living in an urban environment , r and omized to receive home visits only ( n = 128 ) or home visits with environmental remediation ( n = 153 ) . One-hundred-fifteen controls matched according to age , gender and ethnicity did not receive any intervention . INTERVENTIONS In-home education visits covered asthma physiology , asthma trigger avoidance and asthma management . Environmental remediation was conducted together with the caregiver . OUTCOMES Primary outcomes include length of hospital stay , number of emergency visits and number of sick visits . Secondary outcomes are symptom frequency , medication management and trigger reduction . RESULTS Both intervention groups experienced reduction of hospitalizations , emergency room visits , sick visits and asthma symptoms . Both groups showed outcomes significantly superior to the matched control group . Intervention effectively reduced the presence of rodents and carpet in home and increased the use of mattress and pillow covers . CONCLUSIONS This study shows that low-cost in-home education and environmental remediation improve outcomes for children with asthma . Lay educators can deliver effective asthma-specific education that results in improved asthma control OBJECTIVE . The purpose of this study was to evaluate the impact and acceptability of an educational multimedia program design ed to promote self-management skills in children with asthma . METHODS . We conducted a r and omized , controlled trial with measures at baseline and 1- and 6-month follow-up . The trial was conducted in pediatric outpatient respiratory clinics in 3 United Kingdom hospitals . Participants included 101 children aged 7 to 14 years under the care of hospital-based asthma services . The children were r and omly assigned to receive an asthma information booklet alone or the booklet plus The Asthma Files , an interactive CD-ROM for children with asthma . Asthma knowledge was the primary outcome measure . Other measures included asthma locus of control , lung function , use of oral steroids , and school absence . RESULTS . At the 1-month follow-up ( n = 99 ) , children in the computer group had improved knowledge compared with the control group and a more internal locus of control . There were no differences in objective lung-function measures , hospitalizations , or oral steroid use . The study participants were positive in their evaluation of the intervention . At the 6-month follow-up ( n = 90 ) , significantly fewer children in the intervention group had required oral steroids and had had time off school for asthma in the previous 6 months . The difference did not reach statistical significance in the intention-to-treat analysis for both steroid use and school absence . CONCLUSION . The Asthma Files was found to be an effective and popular health education tool for promoting asthma self-management skills within pediatric care Objectives Childhood asthma is a growing public health concern in low-income urban communities . Indoor exposure to asthma triggers has emerged as an important cause of asthma exacerbations . We describe indoor environmental conditions related to asthma triggers among a low-income urban population in Seattle/King County , Washington , as well as caregiver knowledge and re sources related to control of these triggers . Methods Data are obtained from in-person , structured , closed-end interviews with the caretakers of children aged 4–12 years with persistent asthma living in households with incomes less than 200 % of poverty . Additional information is collected during a home inspection . The children and their caregivers are participants in the ongoing Seattle-King County Healthy Homes Project , a r and omized controlled trial of an intervention to empower low-income families to reduce exposure to indoor asthma triggers . We report findings on the conditions of the homes prior to this intervention among the first 112 enrolled households . Results A smoker was present in 37.5 % of homes . Mold was visible in 26.8 % of homes , water damage was present in 18.6 % of homes , and damp conditions occurred in 64.8 % of households , while 39.6 % of caregivers were aware that excessive moisture can increase exposures to allergens . Dust-trapping reservoirs were common ; 76.8 % of children 's bedrooms had carpeting . Cockroach infestation in the past 3 months was reported by 23.4 % of caregivers , while 57.1 % were unaware of the association of roaches and asthma . Only 19.8 % of the children had allergy-control mattress covers . Conclusions Many low-income urban children with asthma in King County live in indoor environments that place them at substantial risk of ongoing exposure to asthma triggers . Subst and ard housing and lack of re sources often underlie these exposures . Initiatives involving health educators , outreach workers , medical providers , health care insurers , housing agencies , and elected officials are needed to reduce these exposures BACKGROUND : Studies in urban emergency departments ( EDs ) have found poor quality of chronic asthma care and identified beliefs and barriers associated with low rates of follow-up with a primary care provider ( PCP ) . OBJECTIVES : To develop an ED-based intervention including asthma symptom screening , a video addressing beliefs and a mailed reminder ; and measure the effect on PCP follow-up and asthma-related outcomes . METHODS : This r and omized , controlled trial enrolled children aged 1 to 18 years who were discharged after asthma treatment in an urban pediatric ED . Control subjects received instructions to follow-up with a PCP within 3 to 5 days . In addition , intervention subjects ( 1 ) received a letter to take to their PCP if they screened positive for persistent asthma symptoms , ( 2 ) viewed a video featuring families and providers discussing the importance of asthma control , and ( 3 ) received a mailed reminder to follow-up with a PCP . All subjects were contacted by telephone 1 , 3 , and 6 months after the ED visit , and follow-up was confirmed by PCP record review . Asthma-related quality of life ( AQoL ) , symptoms , and beliefs about asthma care were assessed by using vali date d surveys . RESULTS : A total of 433 subjects were r and omly assigned , and baseline measures were similar between study groups . After the intervention and before ED discharge , intervention subjects were more likely to endorse beliefs about the benefits of follow-up than controls . However , rates of PCP follow-up during the month after the ED visit ( 44.5 % ) were similar to control subjects ( 43.8 % ) as were AQoL , medication use , and ED visits . CONCLUSIONS : An ED-based intervention influenced beliefs but did not increase PCP follow-up or asthma-related outcomes We compared the effectiveness of personalized asthma self-management recommendations with that of a group self-management program . We assigned each of 34 asthma patients r and omly to one of three conditions : individualized asthma self-management , group asthma self-management , and control . We derived individualized self-management recommendations from patient recordings of asthma occurrence , asthma precipitants , and peak expiratory flow rate made during a 3-month period . The group program we used was the Wheezers Anonymous program . As compared to a control group of patients who received no self-management training , the patients in both the individualized and group condition evidence d improvement of pulmonary function , as measured daily with a home peak flow meter . The improvement was equivalent for patients in the two conditions . Patients in the individualized condition also exhibited a drop in frequency of asthma attacks , but patients in the group condition did not . We concluded that individualized asthma self-management is effective in reducing symptoms of asthma The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age . Patients were r and omly assigned to an education or noneducation group . A st and ard education program regarding asthma and asthma medications was provided to the education group during four monthly visits . At each visit , all patients were assessed in terms of knowledge of asthma and medications , asthma-related symptoms , and pulmonary function . Patients were also asked to self-rate their compliance . The education program increased the patients ' knowledge of cromolyn , and appeared to result in increased cromolyn compliance . Post-hoc analyses , however , suggested that increased compliance did not correspond to improved medical status unless the quality of management ( by physician and parents ) of the child 's asthma was taken into account . These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance Parent education has proven to be effective in improving parents coping with their child 's asthma . Little is known about its effectiveness neither during inpatient rehabilitation nor about the different effectiveness of different approaches . A controlled clinical trial was conducted with 242 parents of asthmatic children aged less than 8 years . The aims were to develop a cognitive-behavioral training program for parents and compare its differential effectiveness with an information-centered st and ard-program as part of rehabilitation . Both groups reported a highly significant increase in their knowledge , self-efficacy and quality of life over time in a follow-up just after the end of their inpatient stay . There was a further increase from discharge to the 6-month follow-up for self-efficacy and quality of life . In respect to the functional severity of asthma , children of both groups showed a significant improvement . Whether these effects have long-term stability and which parents benefit from which type of intervention will be the objective of an ongoing 12-month follow-up STUDY OBJECTIVES To examine the effectiveness of an interdisciplinary intervention for pediatric asthma . DESIGN R and omized , controlled study . SETTING Urban tertiary-referral pediatric hospital . PARTICIPANTS One hundred seventy-five patients with asthma lacking written treatment plans and presenting with asthma-related emergency department visits ( two or more ) and /or hospitalizations ( one or more ) in the past year were r and omized to a comparison group receiving medical care alone ( n = 86 ) or to an interdisciplinary intervention group receiving medical care , asthma education , and problem-solving therapy ( n = 89 ) INTERVENTION All participants received written asthma management plans , peak flow meters , and spacer devices . The intervention group also received asthma education , an asthma risk profile assessment , brief problem-solving therapy , and access to a 24-h nurse advice line . The primary outcome measure was change in asthma symptoms , and secondary outcomes included health-care utilization and asthma-related quality of life . RESULTS Both groups demonstrated significant reductions in asthma symptoms and improvements in quality of life without any between-group differences identified over the course of follow-up . In contrast , the intervention group demonstrated less frequent health-care utilization than the comparison group , with 28 % of the intervention group requiring emergency department or inpatient services for asthma compared to 41 % of the comparison group ( adjusted odds ratio , 1.92 ; 95 % confidence interval , 1.00 to 3.69 ) over the 12-month follow-up period . CONCLUSIONS This study examined the effectiveness of an interdisciplinary intervention for undertreated asthma . The intervention did not result in improvements in asthma symptoms , but accomplished modest reductions in the utilization of acute medical care BACKGROUND Clinical ly relevant reductions in exposure to cockroach allergen , an important risk factor for asthma in inner-city households , have proven difficult to achieve in intervention trials . OBJECTIVE This study investigated a method for the abatement of cockroach allergen in low-income , urban homes . The goal was to reduce mean Bla g 1 concentrations below the previously proposed thresholds for allergic sensitization and asthma morbidity . METHODS A prer and omized , nonmasked trial with 16 intervention and 15 control homes was conducted . Study inclusion was based on 50 to 500 cockroaches trapped in a 3-day period . The interventions consisted of occupant education , placement of insecticide bait , and professional cleaning . Vacuumed dust and multiple swab sample s were collected at 0 , 1 , 2 , 4 , and 6 months in intervention homes and at 0 and 6 months in control homes . Room maps containing cockroach and allergen data were used to guide and monitor the interventions . RESULTS From 0 to 6 months among intervention homes , geometric mean Bla g 1 concentrations ( U/g dust ) decreased from 633 to 24 on kitchen floors ( 96 % reduction ) , from 25 to 4.3 on living room floors/sofas ( 83 % reduction ) , from 46 to 7.3 on bedroom floors ( 84 % reduction ) , and from 6.1 to 1.0 in bedroom beds ( 84 % reduction ) . These reductions , with the exception of that on the bedroom floor ( P = .06 ) , were statistically significant relative to changes in control homes . CONCLUSIONS Substantial reductions in cockroach allergen levels can be achieved in inner-city homes . In this study , allergen levels were reduced below the sensitization threshold ( 2 U/g ) in beds , arguably the most relevant site for exposure , and below the asthma morbidity threshold ( 8 U/g ) on bedroom floors and living room floors/sofas . The level on kitchen floors , although reduced 96 % , remained above the asthma morbidity threshold . Future studies will test the intervention 's effectiveness in asthma prevention trials OBJECTIVES We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers . METHODS We conducted a r and omized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4 - 12 years who had asthma . Community health workers provided in-home environmental assessment s , education , support for behavior change , and re sources . Participants were assigned to either a high-intensity group receiving 7 visits and a full set of re sources or a low-intensity group receiving a single visit and limited re sources . RESULTS The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality -of-life score ( P=.005 ) and asthma-related urgent health services use ( P=.026 ) . Asthma symptom days declined more in the high-intensity group , although the across-group difference did not reach statistical significance ( P=.138 ) . Participant actions to reduce triggers generally increased in the high-intensity group . The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were 189 - 721 dollars . CONCLUSIONS Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality -of-life score . Improvement was greater with a higher-intensity intervention OBJECTIVE To test whether community health workers are able to reach low-income parents of African American children hospitalized for asthma and to reduce rehospitalization among them . DESIGN A r and omized controlled evaluation of usual care vs 2-year asthma coach intervention . SETTING An urban children 's hospital and the surrounding community . PARTICIPANTS A population -based sample of 306 children hospitalized for asthma met the inclusion criteria of being 2 to 8 years of age , of African American ethnicity , and having Medicaid coverage . Of these , 200 were contacted and 191 recruited with commitment to evaluation activities but , in order to assess reach , no commitment to participating in intervention . INTERVENTIONS Coaches reinforced basic asthma education and encouraged key management behaviors through home visits and phone calls tailored to parent 's readiness to adopt management practice s and emphasizing a nondirective supportive style ( cooperative and accepting of feelings and choices ) . OUTCOME MEASURES The reach of intervention to parents , contacts with coaches , and rehospitalization over 2 years based on hospital records . RESULTS Within 3 months of r and omization to the asthma coach group , 89.6 % of parents had at least 1 substantive contact with the coach , with an average of 21.1 contacts per parent over the 24-month intervention . The proportion of children rehospitalized was 35 of 96 ( 36.5 % ) in the asthma coach group and 55 of 93 ( 59.1 % ) in the usual care group ( P < .01 ) , controlling for parental education and child age , sex , and hospitalization in the year prior to the index hospitalization . In surveys , parents indicated the importance of the nondirective approach to support . CONCLUSIONS An asthma coach can reach low-income parents of African American children hospitalized for asthma and reduce rehospitalization among the children Pediatric asthma is a growing public health issue , disproportionately affecting low-income people and people of color . Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma . We describe the implementation of the Seattle-King County Healthy Homes Project , a r and omized , controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home . We r and omly assigned 274 low-income children with asthma ages 4 - 12 to either a high- or a low-intensity group . In the high-intensity group , community health workers called Community Home Environmental Specialists ( CHES ) conducted initial home environmental assessment s , provided individualized action plans , and made additional visits over a 12-month period to provide education and social support , encouragement of participant actions , provision of material s to reduce exposures ( including bedding encasements ) , assistance with roach and rodent eradication , and advocacy for improved housing conditions . Members of the low-intensity group received the initial assessment , home action plan , limited education during the assessment visit , and bedding encasements . We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocol s addressing dust mites , mold , tobacco smoke , pets , cockroaches , rodents , dust , moisture , and toxic or hazardous chemicals . We also discuss the gap between the practice s recommended in the literature and what is feasible in the home . We accomplished home interventions and participants found the project very useful . The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers The goal of this study was to determine the effectiveness of an asthma educational intervention in improving asthma knowledge , self-efficacy , and quality of life in rural families . Children 6 to 12 years of age ( 62 % male , 56 % white , and 22 % Medicaid ) with persistent asthma ( 61 % ) were recruited from rural elementary schools and r and omized into the control st and ard asthma education ( CON ) group or an interactive educational intervention ( INT ) group geared toward rural families . Parent/caregiver and child asthma knowledge , self-efficacy , and quality of life were assessed at baseline and at 10 months post enrollment . Despite high frequency of symptom reports , only 18 % children reported an emergency department visit in the prior 6 months . Significant improvement in asthma knowledge was noted for INT parents and young INT children at follow-up ( Parent : CON = 16.3 ; INT = 17.5 , p < 0.001 ; Young children : CON = 10.8 , INT = 12.45 , p < 0.001 ) . Child self-efficacy significantly increased in the INT group at follow-up ; however , there was no significant difference in parent self-efficacy or parent and child quality of life at follow-up . Asthma symptom reports were significantly lower for the INT group at follow-up . For young rural children , an interactive asthma education intervention was associated with increased asthma knowledge and self-efficacy , decreased symptom reports , but not increased quality of life This study was conducted to evaluate the comparative effectiveness of two different asthma educational programs . One was self‐management asthma education based on the PRECEDE‐PROCEED model to change the influential factors based on a previous need assessment study in Taiwan . The other consisted of regular outpatient asthma education . The purpose s were : 1 ) to compare differences in the asthma knowledge , self‐efficacy , perceived effectiveness , children 's cooperation , doctor – patient communication , and self‐management behaviors in the experimental and control groups before education , and 2 weeks , 3 months , and 6 months after education ; and 2 ) to compare differences in drug use , medication utilization , asthma severity , signs/symptoms of asthma , school absenteeism , and exercise ability before education , and 2 weeks , 3 months , and 6 months after education . Parents of asthmatic children were recruited from among out patients of Chang Gung Children 's Hospital , Taoyuan , Taiwan . They were grouped by registration number : those with even numbers were assigned to the experimental group , and those with odd numbers were assigned to the control group . Measurements were collected four times from all parents by means of a question naire and chart review . The General Linear Model : Repeat Measurement was used to compare variance differences . The following results were found . 1 ) Asthma knowledge , self‐efficacy , perceived effectiveness , children 's cooperation , and self‐management behaviors significantly improved after the self‐management asthma educational program based on PRECEDE‐PROCEED . Except for perceived effectiveness , all variables still had good effectiveness after 6 months of follow‐up . The experimental group was better than the control group in knowledge , children 's cooperation , and self‐management behaviors at the 3‐month follow up , as well as in knowledge and children 's cooperation at the 6‐month follow‐up . 2 ) In both the experimental and control groups , the educational program had a good impact on the health outcome . The average degree of drug use was reduced from 2.7 to 2.1 . The number of visits was reduced from 4.75 to 3.55 per half year in the experimental group , and from 5.8 to 3.48 in the control group . The severity of asthma was reduced from 2.7 to 2.1 . The signs/symptoms of asthma decreased , school absenteeism was reduced , and exercise ability improved after education at the 6‐month follow‐up in both groups . From the results of this study , the theory‐based educational program had a good effect on self‐management behaviors . From the repeat measurement analysis , we can underst and the changing trend of the determinants , behaviors , and outcome indicators . The trend indicated that educational effects were sustained for at least 3 months , with some for 6 months . In order to maintain the educational effects , further specific series of educational programs can be design ed based on the patterns of self‐management behavior stages every 6 months . The effects of health outcomes may show significant differences using longer follow‐up times in future clinical trials We aim ed to evaluate a family-oriented psycho-educational asthma training program for the age group of 2–5 years , involving both parents and children . Children were included after having at least 3 obstructive episodes in their life plus chronic or recurrent wheeze in the 6 months before the start of the study . In the multicenter r and omized trial we had ( 1 ) a waiting group ( WG ) , ( 2 ) an instruction group ( IG ) trained in a structured way according to the national asthma guideline , and ( 3 ) an education group ( EG ) , having a st and ardized multiprofessional psycho-educational program , according to the national licensed asthma education for the age group of 6–18 years . All were assessed after 6 months . A subgroup analysis was performed on those being on regular inhaled corticosteroids at study entry ( 74.3 % ) . A total of 338 children were r and omized , and 288 ( 85 % ) completed the study . In the asthma emergency management , test scores increased most in EG , less in IG , and not in WG . For emergency visits the risk ratio for EG was 0.68 compared to IG : Patients regularly inhaling corticosteroids ( 74.3 % ) had an increased risk for emergency visits when having only an instruction ( OR 3.99 [ 1.89–8.40 ] ) or had been waiting ( OR 2.5 [ 1.16–5.37 ] ) when compared to those having an asthma education . We conclude that in the German health system , the family oriented psycho-educational program provided in a st and ardized manner by a multiprofessional team is effective also in the age group of 2–5 years . It should be made accessible to each asthmatic child OBJECTIVE To identify and educate members of ConnectiCare , Inc & Affiliates , a regional managed care organization , who were not using asthma medications as recommended by the National Heart , Lung , and Blood Institute , by means of a nurse-administered 6-month telephonic case management intervention called the Asthma Treatment Awareness Project . STUDY DESIGN A r and omized controlled design was used to evaluate intervention and control groups . Self-selected members who opted in , opted out , or did not respond to an invitation to participate were included in the analysis . METHODS Changes in asthma medication use , physician office visits , emergency department visits , hospitalizations , and quality of life were measured . A change in asthma medication use was measured using an asthma medication index ranging from 0 to 1.00 , with a higher score indicating a better prescribing pattern . RESULTS There was significant improvement in asthma medication use for all groups , but the asthma medication index increase of 0.176 for the intervention group was nearly 2 times the 0.091 increase for the control group . This difference remained significant ( P = .04 ) after using analysis of variance to control for age and the preintervention asthma medication index . There was also a significant increase in overall quality of life for the intervention group ( P = .04 ) but not for the control group . CONCLUSION Individualized telephonic case management from a specially trained registered nurse may be effective in improving asthma medication use and quality of life in subjects that do not use asthma medications according to National Heart , Lung , and Blood Institute guidelines BACKGROUND Improving asthma knowledge and self-management is a common focus of asthma educational programs , but most programs have had little influence on morbidity outcomes . We developed a novel multiple-component intervention that included the use of an asthma education video game intended to promote adoption of asthma self-management behaviors and appropriate asthma care . OBJECTIVE To determine the effectiveness of an asthma education video game in reducing morbidity among high-risk , school-aged children with asthma . METHODS We enrolled 119 children aged 5 to 12 years from low-income , urban areas in and around San Francisco , CA , and San Jose , CA . Children with moderate-to-severe asthma and parental reports of significant asthma health care utilization were r and omized to participate in the disease management intervention or to receive their usual care ( control group ) . Patients were evaluated for clinical and quality -of-life outcomes at weeks 8 , 32 , and 52 of the study . RESULTS Compared with controls , the intervention group had significant improvements in the physical domain ( P = .04 and P = .01 at 32 and 52 weeks , respectively ) and social activity domain ( P = .02 and P = .05 at 32 and 52 weeks , respectively ) of asthma quality of life on the Child Health Survey for Asthma and child ( P = .02 at 8 weeks ) and parent ( P = .04 and .004 at 32 and 52 weeks , respectively ) asthma self-management knowledge . There were no significant differences between groups on clinical outcome variables . CONCLUSIONS A multicomponent educational , behavioral , and medical intervention targeted at high-risk , inner-city children with asthma can improve asthma knowledge and quality of life OBJECTIVE To improve follow-up with primary care providers after acute Emergency Department ( ED ) asthma visits for children from low-income urban families . STUDY DESIGN A prospect i ve , r and omized , controlled trial evaluated combined telephone asthma coaching and monetary incentive . The primary outcome was asthma-planning visits with primary care providers within 15 days of index ED visits . The subjects were urban parents whose children were treated for asthma in the ED and had Medicaid or no insurance . RESULTS We enrolled 527 parents ( 264 control and 263 intervention ) . There was a significant difference ( P < .0001 ) between the intervention ( 35.7 % ) and control ( 18.9 % ) groups in the proportion of children who had asthma-planning visits and decreased mean nights/days with asthma symptoms by 4.36 intervention and 3.31 control at 2 weeks . The proportions of children with asthma-planning visits and acute asthma care visits during the 16-day to 6-month period were similar for both groups . CONCLUSIONS Telephone coaching and a monetary incentive significantly increased the proportion of low-income urban parents who brought their children for asthma-planning visits , and decreased asthma symptoms shortly after asthma ED visits . The intervention did not increase subsequent asthma-planning visits or decrease ED visits or hospitalizations Objective To determine whether asthma specialist nurses , using a liaison model of care , reduce unscheduled care in a deprived multiethnic area . Design Cluster r and omised controlled trial . Setting 44 general practice s in two boroughs in east London . Participants 324 people aged 4 - 60 years admitted to or attending hospital or the general practitioner out of hours service with acute asthma ; 164 ( 50 % ) were South Asian patients , 108 ( 34 % ) were white patients , and 52 ( 16 % ) were from other , largely African and Afro-Caribbean , ethnicities . Intervention Patient review in a nurse led clinic and liaison with general practitioners and practice nurses comprising educational outreach , promotion of guidelines for high risk asthma , and ongoing clinical support . Control practice s received a visit promoting st and ard asthma guidelines ; control patients were checked for inhaler technique . Main outcome measures Percentage of participants receiving unscheduled care for acute asthma over one year and time to first unscheduled attendance . Results Primary outcome data were available for 319 of 324 ( 98 % ) participants . Intervention delayed time to first attendance with acute asthma ( hazard ratio 0.73 , 95 % confidence interval 0.54 to 1.00 ; median 194 days for intervention and 126 days for control ) and reduced the percentage of participants attending with acute asthma ( 58 % ( 101/174 ) v 68 % ( 99/145 ) ; odds ratio 0.62 , 0.38 to 1.01 ) . In analyses of prespecified subgroups the difference in effect on ethnic groups was not significant , but results were consistent with greater benefit for white patients than for South Asian patients or those from other ethnic groups . Conclusion Asthma specialist nurses using a liaison model of care reduced unscheduled care for asthma in a deprived multiethnic health district . Ethnic groups may not benefit equally from specialist nurse intervention BACKGROUND Comprehensive management efforts to reduce asthma morbidity among children in urban areas with high levels of poverty and large minority population s have been inconclusive . The National Cooperative Inner-City Asthma Study ( NCICAS ) demonstrated improved symptom outcomes but did not evaluate cost-effectiveness in this population . OBJECTIVE We sought to examine the incremental cost-effectiveness of a comprehensive social worker-based education program and environmental control in children with asthma stratified by baseline level of asthma control . METHODS We performed a prospect i ve cost-effectiveness analysis alongside a r and omized trial . A total of 1033 children and their families residing in 8 inner-city urban areas in the United States were enrolled in the NCICAS . Outcomes included symptom-free days , cost per symptom-free day gained , and annual costs of asthma morbidity compared by baseline symptom control , previous hospitalization , and previous unscheduled physician visits . RESULTS The NCICAS intervention significantly reduced asthma symptoms . First-year intervention costs were 245 US dollars higher for the intervention children compared with those receiving usual care . There were no additional intervention-related costs during the second year . When compared with usual care , the intervention improved outcomes at an average additional cost of 9.20 US dollars per symptom-free day gained ( 95 % CI , -12.56 to 55.29 US dollars ) . The intervention was cost saving in 3 strata of children with increasing asthma severity . CONCLUSIONS A multifaceted asthma intervention program reduced symptom days and was cost-effective for inner-city children with asthma . In children with more severe disease , the intervention was substantially more effective and reduced costs compared with that seen in control children . Organizations serving this population should consider this strategy as part of a comprehensive disease-management program for asthma OBJECTIVE To study the effect of an asthma outreach program on emergency ward and hospital utilization . DESIGN Before and after trial . SETTING Ambulatory patients in a staff-model health maintenance organization with a 70 % black inner-city population . PATIENTS Fifty-three patients aged 1 to 17 years with the diagnosis of asthma based on usual clinical practice criteria . INTERVENTION Asthma emergency ward visits and hospitalizations were monitored over a 6-month to 2-year period after enrollment in the program . Patients were scheduled for one-on-one orientation visits with the asthma outreach nurse and instructed in asthma management , medications , triggers , and use of inhalers and peak flowmeters . An individualized step-care treatment program was outlined for each patient by the nurse , primary care pediatrician , and , when appropriate , an allergist . The outreach nurse maintained personal or telephone contact with the families on a regular basis to assure underst and ing of and compliance with the treatment plan . OUTCOME MEASURES Outcome was assessed by measuring annualized emergency ward and hospital admissions for each patient for an equal period before and after entry into the program . RESULTS Emergency ward admissions were reduced 79 % ( from a rate of 72 visits per year to 15 visits per year , P < .0001 ) and hospital admissions were reduced 86 % ( from 35 per year to five per year , P < .001 ) . These reductions were achieved by a single outreach nurse working an average of 8 hours per week at an annualized cost of $ 11,115 ; this saved approximately $ 87,000 in costs . CONCLUSIONS Patients enrolled in a pediatric asthma outreach program experienced a significant reduction in utilization of emergency ward and hospital admissions , result ing in reduced cost of care In r and omized clinical trials , children and adolescents improved their self care and reduced their emergency clinical utilization after playing health education and disease management video games . A diabetes game reduced diabetes-related urgent and emergency visits by 77 percent after diabetic youngsters had the game at home for six months , compared to no reduction in clinical utilization in a control group of diabetic youngsters who took home an entertainment video game that had no health content . Positive impacts were also found in clinical trials of games for asthma self-management and smoking prevention OBJECTIVE To evaluate the impact of a multifaceted environmental and educational intervention on the indoor environment and health in 5 - 12-year-old children with asthma living in urban environments . DESIGN Changes in indoor allergen levels and asthma severity measurements were compared between children who were r and omized to intervention and delayed intervention groups in a 14-month prospect i ve field trial . Intervention group households received dust mite covers , a professional house cleaning , and had roach bait and trays placed in their houses . RESULTS Of 981 eligible children , 410 ( 42 % ) were enrolled ; 161 ( 40 % ) completed baseline activities and were r and omized : 84 to intervention and 77 to delayed intervention groups . At the study 's end , dust mite levels were 163 % higher than at baseline for the delayed intervention group . Overall asthma severity scores did not change . However , the median functional severity score ( FSS ) component of the severity score improved more in the intervention group ( 33 % vs. 20 % ) than in the delayed intervention group . At the study 's end , the median FSSs for the intervention group improved 25 % compared with the delayed intervention group , ( p<0.01 ) . Differences between groups for medication use , emergency department ( ED ) visits or hospitalization were not significant . CONCLUSIONS Despite low retention , the intervention result ed in decreased dust mite allergen levels and increased FSSs among the intervention group . The interventions probably contributed to the improvements , especially among the more severely affected children . This study highlights the complexities of design ing and assessing the outcomes from a multifaceted asthma intervention We asked whether the addition of PEF recordings to a symptom-based self-management plan improved outcome in school children with asthma . In an open-r and omized , parallel-group , controlled trial , we studied children aged 7 - 14 years with moderate asthma . After a 4-week run-in , 90 children were r and omized to receive either PEF plus symptom-based management or symptom-based management alone for 12 weeks . Thresholds for action based on PEF were 70 % of best ( for increasing inhaled steroids ) and 50 % of best ( for commencing prednisolone ) . Children were asked to perform twice-daily spirometry at home ( using an electronic recording spirometer that revealed only PEF to the study group alone ) and to record a symptom diary . The mean daily symptom score was the main outcome . There were no differences between groups in mean symptom score or in spirometric lung function , PEF , quality of life score , or reported use of health services over 12 weeks . During acute episodes , children responded to changes in symptoms by increasing their inhaled steroids at a mean value of PEF of greater than 70 % of best so that overall PEF did not contribute to this important self-management decision . Knowledge of PEF did not enhance self-management even during acute exacerbations OBJECTIVE To evaluate the effects of educational and psychological intervention on the quality of life and psychological status of patients with asthma . METHODS Asthmatic patients were r and omized to study ( n = 228 ) and control ( n = 146 ) groups . Both groups received conventional pharmacotherapy for asthma . The study group also received education and psychological counseling . We assessed quality of life , mood states , and asthma knowledge before and after the educational and psychological interventions . RESULTS The study group 's mean quality -of-life score was higher than that of the control group immediately after the intervention ( 130.2 + /- 25.1 vs 111.6 + /- 27.4 , P < .001 ) and 3 months after the intervention ( 144.4 + /- 16.9 vs 121.5 + /- 25.6 , P < .001 ) . The study group 's mean asthma-knowledge score was higher immediately after the intervention ( 9.0 + /- 1.2 vs 7.5 + /- 1.8 , P < .001 ) and 3 months after the intervention ( 9.4 + /- 0.8 vs 7.5 + /- 1.5 , P < .001 ) . Two weeks after the intervention the mean increment of the asthma-knowledge score in the study group was greater than that in the control group ( 1.8 + /- 1.6 vs 0.6 + /- 1.7 , P = or < .01 ) . The study group 's mean Profile of Mood States score was lower than that of the control group immediately after the intervention ( 12.0 + /- 18.5 vs 23.0 + /- 22.7 , P < .001 ) and 3 months following the intervention ( 10.2 + /- 7.5 vs 22.8 + /- 11.4 , P < .001 ) . CONCLUSIONS Education and psychological counseling improves the quality of life and alleviates the psychological distress in patients with asthma . These interventions also enhance patient 's underst and ing of this chronic disease There is evidence that educational programmes may improve patient 's compliance with asthma treatment and control symptoms . Whilst medical parameters have been thoroughly studied , few data are available concerning psychological intervention . The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group ( ARG ) and in a Control Group ( CG ) . Forty consecutive asthmatics were r and omly enrolled , all of whom were diagnosed , treated and followed-up according to the International Guidelines . Both groups underwent a psychological assessment at baseline and after one year . A battery of question naires was used to obtain data relating to baseline characteristics ( anxiety , depression , psychophysiological disorders ) , emotional reactions to asthma attacks ( panic-fear , etc , ) and cognitive variables ( external control , psychological stigma , internal beliefs , external chance , etc . ) involved in the perceived illness . In addition , the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention . In both groups , a reduction of anxiety and depression scores was observed , as well as a significant improvement of the medical parameters evaluated . Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Question naire and on the External Control Subscale after 1 year . The Control Group reported higher score on the External Chance Scale . The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma . Larger scale studies on this topic are suggested To affect asthma-related knowledge , behavior , and morbidity , research ers tested a new educational intervention for children with asthma : an asthma-specific computer game called Asthma Comm and , which was specifically design ed for this study . Sixty-five children with moderately severe asthma were r and omly assigned to one of two groups , and 54 completed the study . Both groups were seen approximately six times during the 1 year of the study . Control subjects ( n = 29 ) played routine computer games . Experimental subjects ( n = 25 ) played Asthma Comm and . Compared with children in the control group , experimental subjects showed improvement in knowledge about asthma ( P less than .001 ) , behavior related to the management of asthma ( P less than .008 ) , and a trend toward the reduction of acute visits due to asthma ( P less than .13 ) . Children in the experimental group also scored higher on the assessment of behaviors related to the management of asthma that were specifically addressed by the intervention provided by Asthma Comm and ( P less than .01 ) . Differences between the control and experimental groups showed a greater improvement in the experimental group in 21 ( 84 % ) of the 25 outcome variables in the study ( P = .004 , Sign test ) . The study indicates that an asthma-specific computer game can significantly affect knowledge and behavior and may potentially affect morbidity in childhood asthma OBJECTIVE To compare the marginal benefit of in-home asthma self-management support provided by community health workers ( CHWs ) with st and ard asthma education from clinic-based nurses . DESIGN R and omized controlled trial . SETTING Community and public health clinics and homes . PARTICIPANTS Three hundred nine children aged 3 to 13 years with asthma living in low-income households . INTERVENTIONS All participants received nurse-provided asthma education and referrals to community re sources . Some participants also received CHW-provided home environmental assessment s , asthma education , social support , and asthma-control re sources . OUTCOME MEASURES Asthma symptom-free days , Pediatric Asthma Caretaker Quality of Life Scale score , and use of urgent health services . RESULTS Both groups showed significant increases in caretaker quality of life ( nurse-only group : 0.4 points ; 95 % confidence interval [ CI ] , 0.3 - 0.6 ; nurse + CHW group : 0.6 points ; 95 % CI , 0.4 - 0.8 ) and number of symptom-free days ( nurse only : 1.3 days ; 95 % CI , 0.5 - 2.1 ; nurse + CHW : 1.9 days ; 95 % CI , 1.1 - 2.8 ) , and absolute decreases in the proportion of children who used urgent health services in the prior 3 months ( nurse only : 17.6 % ; 95 % CI , 8.1%-27.2 % ; nurse + CHW : 23.1 % ; 95 % CI , 13.6%-32.6 % ) . Quality of life improved by 0.22 more points in the nurse + CHW group ( 95 % CI , 0.00 - 0.44 ; P = .049 ) . The number of symptom-free days increased by 0.94 days per 2 weeks ( 95 % CI , 0.02 - 1.86 ; P = .046 ) , or 24.4 days per year , in the nurse + CHW group . While use of urgent health services decreased more in the nurse + CHW group , the difference between groups was not significant . CONCLUSION The addition of CHW home visits to clinic-based asthma education yielded a clinical ly important increase in symptom-free days and a modest improvement in caretaker quality of life Twenty-seven children with light to moderate asthma were allocated to three groups matched with respect to a number of subjects with ( a ) high trait anxiety and ( b ) emotionally triggered attacks ( ET ) . The first group received an asthma self-management programme ( SM ) and the second the same programme including relaxation training ( SM + R ) ; the control group ( CG ) received only pharmacological treatment . Before and immediately after intervention , and at 6 and 12 month follow-ups , we evaluated a series of clinical and pulmonary function indicators of disease severity . Overall , patients receiving SM showed a significantly greater reduction in their subjective assessment of attack intensity and in the severity of the intervention measures employed . Inclusion of individual difference variables in the analysis also indicated that ET patients receiving SM + R showed significant decreases in attack duration , and improvements in peak expiratory flow rate ( PEFR ) with respect to ET patients in all other groups . Trait anxiety level did not affect response to either intervention OBJECTIVE Asthma morbidity and mortality continue to increase despite the availability of improved therapies . Little is known about the degree to which children with asthma use medications and health care services during symptomatic periods . This study documents prospect ively the use of medications and health care contacts among children with active asthma symptoms . METHODS Children age 6 - -19 years from 11 primary care setting s in upstate New York were eligible for this study if they had 3 or more asthma-related medical visits during the prior year . We collected extensive information on asthma symptoms , medication use , and contacts with health care providers from biweekly phone interviews and daily diaries during a 3-month period . Symptoms were evaluated as the average number of symptomatic days per week . We tabulated the proportion of children using anti-inflammatory medications and having health care contacts according to the frequency of their symptoms during this 3-month period . Chi-square and regression analyses were used . RESULTS One hundred sixty-five children participated ( 67 % White , 24 % Black , 9 % Other ) . Sixty-five percent of the children in this sample had an average of more than 2 symptomatic days per week or more than 2 symptomatic nights per month during the 3-month study period and thus had mild persistent to severe asthma . Among these children , 25 % received prednisone , and 46 % reported the use of an inhaled maintenance medication during the monitoring period . Ten percent of children in this sample experienced an average of 6 or more symptomatic days per week during the study period . Among these highly symptomatic children , only 19 % received prednisone , and 56 % used a maintenance medication . Further , the proportion of children having contact with a health care provider during this 3-month period was 50 % or less , even among the children experiencing the most frequent asthma symptoms . There were no differences in the proportion of children with health care contacts , prednisone use , or maintenance anti-inflammatory use among different gender or race categories or with different insurance types or places of residence . CONCLUSIONS Even among children experiencing almost daily asthma symptoms , inadequate anti-inflammatory therapy is common , and few contacts with health care providers occur . These children are silently suffering at home and likely are experiencing preventable morbidity Asthma prevalence is increasing among poor and minority children . We examined the effectiveness of a novel interactive device programmed for self-management of pediatric asthma in reducing asthma control problems and hospitalizations . A r and omized controlled trial ( 66 children in the intervention group and 68 in the control group ) was conducted at home and in an outpatient hospital clinic with 8 - 16-year-old inner-city children with physician-diagnosed asthma . During a 12-week period , children in the experimental group received an asthma self-management and education program , the Health Buddy ( Health Hero Network ) , design ed to enable them to monitor their symptoms and transmit this information to a case manager through a secure website . Control group participants used an asthma diary . After adjusting for baseline asthma control problems , asthma severity , and seasonality , children r and omized to automated self-management had a significantly lower mean number of asthma control problems at 6 weeks ( 2.0 , SD = 1.6 ) as compared to children assigned to the asthma diary ( 2.7 , SD = 1.6 ) ( p = 0.03 ) . By 12 weeks , after adjusting for time and the other covariates , asthma control problems dropped markedly in both groups , and did not differ by intervention modality ( p = .07 ) . The intervention modality was not a significant predictor of hospitalization . Educational interventions that encourage children 's active involvement in their own care and symptom monitoring would help children increase their control of asthma problems . Compared to the asthma diary , the automated self-management had a significant short-term impact on asthma control problems . Its initial effectiveness and more consistent use suggest that remote monitoring may be successfully used in short-term interventions and in setting s where staffing for case management is weak We have developed a tele-medicine system to monitor the airway status at home for patients with poorly controlled asthma , whereby a nurse provides instructions to individuals via the telephone to help them manage exacerbation under the supervision of their physicians . We examined the effectiveness of this system with a r and omized control study . Patients with high hospitalization risk were enrolled in the study by screening patients for those with multiple previous emergency room visits and r and omly assigned to either the tele-medicine or control group . After six months of participation in the program , the number of emergency room visits decreased significantly and the activities of daily living were improved in the tele-medicine group . Most of the patients in the tele-medicine group were able to continue measuring and transmitting peak expiratory flow ( PEF ) value successfully , and at six months had noticed an improvement in PEF . We therefore conclude that the system effectively contributes to the management of poorly controlled asthma . In addition , further consideration suggests that the reduction of emergency room visits may lead to reduction in hospitalization since we found a good correlation between number of emergency room visits and hospitalization from the studies published previously Background Cockroach allergy is common among inner city children with asthma , and exposure to cockroach allergen is associated with more severe disease . However , there has been little evaluation of educational approaches for controlling cockroach infestations and reducing allergen exposure STUDY OBJECTIVE This r and omized clinical trial tested a behavioral medicine program design ed to reduce asthmatic children 's exposure to environmental tobacco smoke ( ETS ) in the home . DESIGN Families were r and omly assigned to an experimental preventive medicine counseling group , a monitoring control group , or a usual treatment control group . Families were measured six times over 1 year . PARTICIPANTS Ninety-one families were recruited from four allergy clinics . INTERVENTION The experimental group received a 6-month series of counseling sessions design ed to decrease ETS exposure . This group also monitored smoking , exposure , and children 's asthma symptoms . The monitoring group did not receive counseling and the usual treatment control group received outcome measures only . MEASUREMENTS AND RESULTS Parents reported the daily number of cigarettes children were exposed to during the week preceding interviews . A nicotine air monitor and construct validity analysis confirmed the validity of exposure reports . Exposure to the parent 's cigarettes in the home decreased for all groups . The experimental group attained a 79 percent decrease in children 's ETS exposure , compared with 42 percent for the monitoring control and 34 percent for the usual treatment control group . Repeated- measures analysis of variance result ed in a significant ( F([10,350 ] = 1.92 , p < 0.05 ) group by time effect . At the final 12-month visit , the experimental/counseling group sustained a 51 % decrease in children 's exposure to cigarettes in the home from all smokers , while the monitoring control group showed an 18 % decrease and the usual treatment control group a 15 % decrease from pre-intervention [ corrected ] . CONCLUSION A behavioral medicine program was successful in reducing exposure to ETS in the home for these asthmatic children BACKGROUND Despite increased attention focused on the need to prevent patient attrition in long-term clinical trials , high dropout rates have threatened the success of numerous studies . OBJECTIVE To evaluate the disease , demographic , and psychological factors associated with missed visits and study dropout to help improve patient management in long-term clinical trials . METHODS Predictors of attrition were examined within the Childhood Asthma Management Program ( CAMP ) , a large , multicenter clinical trial that followed up 1,041 children with asthma for 4 to 6 years . RESULTS Eighty-two percent of patients attended all study visits . The tendency to miss visits was increased among older children with milder asthma , lower intellectual and social competence , and more symptoms of behavioral problems and emotional distress . Forty-two patients who missed 3 or more visits in a row and did not attend the final visit were considered study dropouts ; these patients at baseline had milder asthma ; lower cognitive , academic , and social competence skills ; and more family conflict and distress than found among participants who remained in the study . The 49 children who had erratic attendance but did not drop out also had lower intellectual and academic skills and less family social support . CONCLUSIONS The 4 % dropout rate in CAMP was lower than reported in any previous long-term asthma trial . The findings of milder disease , decreased psychological re sources , and increased distress in problem-attendance patients can assist in identifying patients who are at risk for missed visits or dropout during the trial either to block their entry into the trial or to focus efforts at maintaining their attendance once enrolled in the trial OBJECTIVE Caring for a child with asthma can affect the parent 's coping and well-being and coping strategies . This study examined the influence of a home-based asthma health education program on parental coping and quality of life . DESIGN R and omized controlled non-blinded clinical trial . SETTING Northern community pediatrician 's office . PATIENTS Families whose children , under the age of 11 , had chronic stable asthma , and who presented to the pediatrician 's office for continuing care ; those with an acute exacerbation of asthma were excluded . INTERVENTIONS Families were r and omly assigned to receive either a single two-hour , st and ardized home-based asthma health education session or a booklet representing conventional care . MAIN OUTCOME MEASURES One and three-months following the intervention , assessment s were obtained for coping measured by Hymovich 's Parent Perception Inventory ( PPI ) , quality of life measured by the Pediatric Asthma Caregiver Quality of Life Question naire ( PACQLQ ) and change in asthma measured by the Caregiver Perception of Change ( CPC ) survey . RESULTS Forty families were recruited and r and omized ; baseline characteristics were similar between groups . At the final follow-up , reduction in parental need for asthma information ( p = 0.04 ) , reduction in parental concerns ( p = 0.02 ) and increased use of coping strategies ( p = 0.04 ) were observed in the home-based care group . Improvement was noted in the parent 's perception of their child 's asthma in the home-based asthma education group ( p = 0.01 ) . Quality of life as measured by the PACQLQ remained unchanged over the intervention period ( p > 0.05 ) . CONCLUSIONS These results suggest the use of a one-time , flexible , home-based intervention to assist families caring for children with asthma should be considered and appears effective OBJECTIVE To determine whether health outcomes of children who have asthma can be improved through the use of an Internet-enabled interactive multimedia asthma education program . METHODS Two hundred twenty-eight children with asthma visiting a pediatric pulmonary clinic were r and omly assigned to control and intervention groups . Children and caregivers in both groups received traditional patient education based on the National Asthma Education and Prevention Program . Intervention group participants received additional self-management education through the Interactive Multimedia Program for Asthma Control and Tracking . Pediatric Asthma Care Knowledge Survey , Pediatric Asthma Caregiver 's Quality of Life Question naire , asthma symptom history , spirometry , and health services utilization data were collected at the initial visit and at 3 and 12 months . RESULTS Interactive Multimedia Program for Asthma Control and Tracking significantly increased asthma knowledge of children and caregivers , decreased asthma symptom days ( 81 vs 51 per year ) , and decreased number of emergency department visits ( 1.93 vs 0.62 per year ) among the intervention group participants . The intervention group children were also using a significantly lower average daily dose of inhaled corticosteroids ( 434 vs 754 micro g [ beclomethasone equivalents ] ) at visit 3 . Asthma knowledge of all 7- to 17-year-old children correlated with fewer urgent physician visits ( r = 0.37 ) and less frequent use of quick-relief medicines ( r = 0.30 ) . CONCLUSIONS Supplementing conventional asthma care with interactive multimedia education can significantly improve asthma knowledge and reduce the burden of childhood asthma BACKGROUND Prevention of study patient attrition and assessment of its impact on outcome data are problems that receive little attention despite their obvious importance in asthma research . OBJECTIVE The medical , demographic , and psychologic characteristics of asthmatic children and adults who dropped out of a yearlong medication trial were assessed to determine whether this group differed from those who completed the study , potentially introducing bias into the data set and interfering with completion of the study 's objectives . METHODS Profiles of 362 adult and pediatric asthmatic patient dropouts from the multicenter trial were contrasted with profiles of those who completed the study . Despite a 1-month prer and omization screening , 24 % of patients failed to complete the trial for varied reasons , which largely included noncompliance and treatment dissatisfaction . RESULTS Although attrition rates were equal among adults and children , dropout-completer differentiation was not . Adult completers did not differ from dropouts in any variables . However , pediatric dropouts were more likely than completers to be female ( 67 % and 36 % , p = 0.008 ) and to have more reactive airways ( PD20 , 2.29 + /- 1.32 and 5.2 + /- 1.23 , p = 0.05 ) , to have reduced scores on tests of intelligence ( Full Scale IQ , 102.2 + /- 2.6 and 112.5 + /- 1.6 , p = 0.002 ) and problem solving ( Wisconsin Card Sorting Test Error Scores , 39.8 + /- 4.1 and 29.1 + /- 2.0 , p = 0.01 ) , and to have increased behavioral problems ( Child Behavior Checklist Total Problem Score , 60.7 + /- 2.5 and 53.6 + /- 1.1 , p = 0.003 ) . CONCLUSION These findings demonstrate the potential of patient attrition to bias outcome in clinical trials and underscore the necessity of : ( 1 ) preventing its occurrence , ( 2 ) correctly assessing its causes , and ( 3 ) determining its ultimate impact on study results . Strategies for each of these three tasks should be implemented at the study 's initial planning stages The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity , knowledge , and compliance with inhaled corticosteroid treatment using a prospect i ve , r and omized , controlled , one-year-before/one-year-after protocol . After rigorous optimization of asthma therapy under the care of respirologists , patients were assigned to one of three groups : Group C ( control group : no formal education ) , Group P ( education and action plan based on peak-flow monitoring ) , and Group S ( education with action plan based on monitoring of asthma symptoms ) . A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study . Asthma morbidity decreased significantly in all groups ( p = 0.001 ) . Mean values one-year-before/one-year-after in Groups C , P , and S were : unscheduled medical visits , 2.4/0.8 , 2.3/0.7 , and 1.9/ 0.7 ; hospitalizations , 0.21/0.04 , 0.24/0.04 , and 0.40/0.09 ; oral steroid treatments ; 1.3/0.5 , 1.2/0.7 , and 1.3/0.9 ; absenteeism from work/school , 9.6/5.2 , 8.8/2.2 , and 6.3/2.9 . Between-group differences did not reach statistical significance ( p > 0.05 ) . Asthma knowledge increased in both educated groups compared with the control group ( p < 0.001 ) as did short-term compliance with inhaled corticosteroids . These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity . In such clinical setting s , structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma , although it could not add extra benefit with regard to morbidity . Nevertheless , this study does not refute the potential benefit of educational interventions aim ed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors The increased prevalence , morbidity , mortality , and health costs associated with asthma among children suggest the need for accessible asthma education . This study examined the effect of telepharmacy counseling , using interactive compressed video , on metered-dose inhaler ( MDI ) technique and patient satisfaction among adolescents with asthma in rural Arkansas . The telepharmacy counseling provided accessible education regarding MDI technique for adolescents in this study . Twenty percent of the adolescents who participated had never been shown the appropriate use of an MDI . The study used an experimental design with r and om assignment of participants to a telepharmacy counseling group ( n = 15 ) or a control group ( n = 21 ) . Both groups participated in pre-test , post-test , and 2- to 4-week follow-up assessment s for MDI technique and patients satisfaction ( follow-up assessment only ) via interactive compressed video . Results indicated that from pre-test to follow-up the telepharmacy counseling group showed more improvement in MDI technique than participants in the control group ( p < 0.001 ) . There was no significant difference between the telepharmacy counseling group and control group in satisfaction with the instructional sessions ( p = 0.132 ) . Both groups had high levels of satisfaction with the telepharmacy sessions . The study findings demonstrated that patient education provided by pharmacists via interactive compressed video was superior to education provided via written instructions on an inhaler package insert . Interactive compressed video is an effective medium for teaching and improving MDI technique in this rural , adolescent , predominantly African-American population OBJECTIVE . The goal was to determine whether home asthma telemonitoring with store- and -forward technology improved outcomes , compared with in-person , office-based visits . METHODS . A total of 120 patients , 6 to 17 years of age , with persistent asthma were assigned r and omly to the office-based or virtual group . The 2 groups followed the same ambulatory clinical pathway for 12 months . Office-based group patients received traditional in-person education and case management . Virtual group patients received computers , Internet connections , and in-home , Internet-based case management and received education through the study Web site . Disease control outcome measures included quality of life , utilization of services , and symptom control . RESULTS . A total of 120 volunteers ( 45 female ) were enrolled . The groups were clinical ly comparable ( office-based : 22 female/38 male ; mean age : 9.0 ± 3.0 years ; virtual : 23 female/37 male ; mean age : 10.2 ± 3.1 years ) . Virtual patients had higher metered-dose inhaler with valved holding chamber technique scores than did the office-based group at 52 weeks ( 94 % vs 89 % ) , had greater adherence to daily asthma symptom diary su bmi ssion ( 35.4 % vs 20.8 % ) , had less participant time ( 636 vs 713 patient-months ) , and were older . Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline . There were no other differences in therapeutic or disease control outcome measures . CONCLUSIONS . Virtual group patients achieved excellent asthma therapeutic and disease control outcomes . Compared with those who received st and ardized office-based care , they were more adherent to diary su bmi ssion and had better inhaler scores at 52 weeks . Store- and -forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma Despite the availability of effective treatments , morbidity and mortality in asthma are increasing . Patient education is essential if adverse factors in the control of asthma are to be overcome . St and ard information and education given to patients in a respiratory clinic is insufficient . A formal asthma education programme delivered by an asthma nurse specialist improves patients ' underst and ing of asthma and their inhaler technique BACKGROUND Previous studies have shown that asthma education and case management may reduce asthma emergency care , hospitalizations , and expenditures . OBJECTIVE We sought to study the effect of an asthma outreach program ( AOP ) , a team-based , case-management intervention , on emergency ward ( EW ) and hospital use . METHODS Fifty-seven patients aged 1 to 15 years with the diagnosis of asthma based on the usual clinical practice criteria who were continuously enrolled in a staff-model health maintenance organization for a period of at least 2 consecutive years were r and omized into 2 intervention groups . The control group received a single intensive asthma education intervention , and the AOP group received the same initial education but then was followed-up by an asthma case management nurse throughout the intervention period . RESULTS EW visits , hospitalizations , and total outside-of-health-plan expenditures ( consisting of EW and hospital expenses , as well as miscellaneous costs , such as ambulance , durable medical equipment , tertiary referrals , and home care ) were assessed from cl aims filed for a year before and after enrollment . Control group patients experienced significant reductions in EW visits ( 39 % ) , hospitalizations ( 43 % ) , and outside-of-health-plan costs ( 28 % ) , possibly as a result of the baseline educational intervention received by all enrolled patients , in conjunction with regression to the mean . AOP group patients experienced significant reductions in EW visits , ( 73 % , P = .0002 ) , hospitalizations ( 84 % , P = .0012 ) , and outside-of-health-plan use ( 82 % , P < .0001 ) . When compared with the control group , AOP group patients demonstrated additional significant reductions in EW visits ( 57 % , P < .05 ) , hospitalizations ( 75 % , P < .05 ) , and outside-of-health-plan use ( 71 % , P < .001 ) . Estimates of direct savings to the health plan ranged from $ 7.69 to $ 11.67 for every dollar spent on the AOP nurse 's salary , depending on assumptions . CONCLUSIONS Asthma patients in a staff-model health maintenance organization decreased their re source use between 57 % to 75 % by participation in an AOP as compared with a r and omized control group receiving only an educational intervention . Substantial savings were achieved compared with the cost of the AOP nurse A research project , which looks at the value of health education in the prevention of childhood asthma , is described . The project was a controlled trial by a health visitor focused within the community . This exploratory research looked at three groups of children over a 2-year period , and compared the effect of : ( a ) individual health education , and ( b ) group health education . During the first year , two groups were active , one receiving individual health education , the other collecting data of the same type . During the second year , a third group was involved in health education sessions . The findings have been similar in both cases , in that both groups have demonstrated a good improvement in knowledge of asthma and its treatment . Through the active involvement of using a peakflow meter and diary records in the health education programme , both groups receiving health education have shown a significant improvement in the morbidity indicators related to night symptoms and restricted activities . The qualitative analysis of the research also highlighted the value parents of asthmatic children place on counselling Our purpose was to examine school‐age children 's self‐reports of characteristics of their asthma episodes including the precipitating events , symptoms experienced during the episodes , and interventions used to resolve the episodes . Children 's self‐reports of their asthma episodes were assessed over a 6‐week period for 42 children with persistent asthma who participated in a r and omized , controlled clinical trial to evaluate the efficacy of an asthma self‐management program on adherence to recommended daily peak expiratory flow rate monitoring . Children were instructed to answer the following questions on the Asthma Report Form each time they experienced an asthma episode : 1 ) What were you doing ; 2 ) How did you feel ; and 3 ) What did you do to help your breathing ? Of the children , 71 % experienced at least one asthma episode during the 6 weeks . There were a total of 206 episodes . Physical activity ( 51 % ) was the most cited trigger , cough alone or combined with other symptoms ( 84 % ) was the predominant symptom , and rescue asthma medication ( 59 % ) was identified most often as the intervention used by the children to resolve the asthma episode . Children 's self‐reports provided valuable information about their asthma episodes . The finding that most of the children experienced at least one asthma episode during the 6‐week period underscores the importance of family education on how to h and le asthma episodes effectively at home . Because physical activity was cited most often as a trigger for asthma episodes , families should receive education on preventive steps for averting an asthma episode prior to the child engaging in physical activity A sample of 310 low income urban children with asthma from 290 families was r and omized into a control group and an experimental group that received health education to improve asthma management at home . No significant decreases in subsequent health care use were observed when the experimental group was compared to the control group without regard to previous hospitalization . When the comparison was restricted to children who had been hospitalized during the preceding year , however , the experimental group was found to have decreased its use of the emergency room significantly more than the control group ( p less than 0.05 ) and to have experienced a significantly greater reduction in the mean number of hospitalizations ( p less than 0.05 ) during the year of follow-up . The program reduced health care costs for children with one or more hospitalizations , saving $ 11.22 for every $ 1.00 spent to deliver health education PURPOSE To examine the relationship between self-reported and electronically monitored adherence to a recommended asthma treatment and to assess the accuracy of the diary data reported by school-age children . DESIGN A r and omized , controlled clinical trial of the effectiveness of an asthma self-management program . The relationship between self-reported and electronically recorded daily peak expiratory flow rate ( PEFR ) adherence was assessed in a sample of 42 children , ages 7 through 11 years with moderate to severe asthma in one community in West Virginia , USA . Cognitive social learning theory served as the framework for the intervention . METHODS At-home adherence to PEFR monitoring during the 5-week study was evaluated using the self-report Asthma Diary and an electronic PEFR meter . Recommended twice daily ( morning and evening ) PEFR monitoring was measured . RESULTS Self-reported and electronically recorded PEFR adherence were modestly correlated . Self-reported adherence was significantly higher than electronically monitored adherence during Week 5 . Accuracy of the self-reported PEFR declined over time , and over half of the children fabricated at least one PEFR value during the final week of the study . CONCLUSIONS Clinicians often evaluate the efficacy of prescribed treatment for children with chronic conditions based on the children 's self-reported diary data . The findings indicate that these children 's self-reported adherence behaviors contained errors . Parent education regarding supervision of children 's adherence , including validating the accuracy of diary data , is critical for successful self-management in children with chronic conditions OBJECTIVE To evaluate a family-focused asthma intervention design ed for inner-city children 5 to 11 years old with moderate to severe asthma . STUDY DESIGN R and omized , multisite , controlled trial to minimize symptom days ( wheeze , loss of sleep , reduction in play activity ) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period . The intervention was tailored to each family 's individual asthma risk profile assessed at baseline . RESULTS Averaged over the first 12 months , participants in the intervention group ( n = 515 ) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group ( n = 518 ) , a difference of 0.55 ( 95 % CI , 0.18 to 0.92 , P = .004 ) . The reduction among children with severe asthma was approximately 3 times greater ( 1.54 d/2 wk ) . More children in the control group ( 18.9 % ) were hospitalized during the intervention compared with children in the intervention group ( 14 . 8 % ) , a decrease of 4.19 % ( CI , -8.75 to 0.36 , P = .071 ) . These improvements were maintained in the intervention group during the second year of follow-up , during which they did not have access to the asthma counselor . CONCLUSIONS We demonstrated that an individually tailored , multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city An educational program for children with asthma design ed to reduce emergency room ( ER ) use enrolled all eligible children ( n = 253 primarily low-income Black ) within a health maintenance organization ( HMO ) who had used the hospital or ER for asthma during the pre-enrollment period and r and omized them into two groups . Twenty-four of the experimental group patients had 55 ER visits and 18 of the control patients had 39 ER visits during the first 12 months post-intervention . This program did not achieve its goal BACKGROUND Mounting evidence suggests that indoor allergens and irritants contribute to childhood asthma . National asthma guidelines highlight the importance of their reduction as part of comprehensive asthma treatment . OBJECTIVES To assess the prevalence of potential environmental triggers , to identify risk factors for such exposures , and to determine whether prior parental education about trigger avoidance is associated with fewer such exposures . SETTING AND PATIENTS Children with asthma in practice s affiliated with 3 managed care organizations . INTERVENTIONS Parents of 638 children , aged 3 to 15 years , were interviewed on enrollment in a r and omized trial of asthma care improvement strategies . Parents reported recent asthma symptoms and exposures to potential environmental triggers . Multivariate models were used to identify specific demographic risk factors for environmental exposures and to determine if prior education was associated with fewer such exposures . RESULTS Exposures to environmental triggers were frequent : 30 % of households had a smoker , 18 % had household pests , and 59 % had furry pets . Other exposures included bedroom carpeting ( 78 % ) and forced-air heat ( 58 % ) . Most children did not have mattress ( 65 % ) or pillow ( 84 % ) covers . Of the parents , 45 % reported ever receiving written instructions regarding trigger avoidance and 11 % reported them given in the past year . However , 42 % reported discussing triggers in the home environment with a clinician in the past 6 months . In multivariate models , predictors of smoking at home included low annual family income and lower parental educational attainment . Dog ownership was associated with low educational attainment , and dog and cat ownership were less likely with black race . Reports of pests were increased for black children compared with white children . Black race was associated with lower rates of other exposures , including bedroom carpeting . After controlling for potential confounders , there was no association of reduced exposures with prior receipt of environmental control instructions . CONCLUSIONS Exposure to potential environmental triggers is common , and recommended trigger avoidance measures are infrequently adopted . While specific exposures may vary with demographic and socioeconomic variables , all children are at risk . New methods for educating parents to reduce such exposures should be tested Background : Low-income African-American adolescents suffer a disproportionate burden of asthma morbidity . Purpose : To evaluate the ability of our intervention , the Adolescents ’ Disease Empowerment and Persistency Technology ( ADEPT ) for asthma , to increase asthma knowledge in our target population . Methods : This was a 14-week ( 2-week run-in and 12-week treatment ) r and omized , double-blind , placebo-controlled pilot study in which 28 inner-city African-American adolescents with asthma , between 10 and 18 years of age , were r and omized to receive ( 1 ) celebrity asthma messages ( experimental group ) , or ( 2 ) general health messages ( control group ) between music tracks on an MP3 player . The asthma messages were recorded by famous athletes , musicians , and other celebrities popular among this group of teenagers . Asthma knowledge , assessed by the ZAP Asthma Knowledge instrament , was collected pre- and post-intervention . Results : Mean improvement in ZAP score was significantly higher in the experimental group ( 8.1 % , SD 7.2 % ) than the control group ( 0.4 % , SD 7.2 % ) ( p = 0.05 ) . Conclusion : These findings suggest that this may be an innovative and promising new approach to improving asthma outcomes in this difficult-to-reach population PURPOSE Adherence to peak expiratory flow rate monitoring by children with asthma was evaluated , and a behavioral strategy to enhance adherence to daily monitoring was tested . DESIGN AND METHODS Forty-two 7- through 11-year-old children with persistent asthma were recruited into a 5-week r and omized , controlled clinical trial . Adherence data were collected electronically by PeakLog and the self-report Asthma Diary . RESULTS Adherence declined over time . At week 5 , intervention group adherence ( Median = 79 % ) was higher than the usual care group adherence ( Median = 64 % ) , but the difference was not statistically significant . The effect size did suggest that differences between groups were present . CONCLUSIONS Even small improvements in adherence to asthma treatment may be clinical ly significant in light of the alarming increases in asthma morbidity and mortality . Contingency management shows promise for improving adherence outcomes . Future research should engage larger sample sizes and increase the number and intensity of sessions to teach behavioral strategies Asthma care management programs may improve outcomes , but it is not clear which aspects of such management are responsible for the improvement . We performed a r and omized controlled trial of a limited intervention ( one visit with asthma self-management education and provision of inhaled budesonide ) compared to this visit plus regular asthma care manager follow-up . Quality of life , symptom-free days , emergency hospital care , and beta-agonist dispensings did not differ between groups at 12 months . Patients who entered the study did receive significantly less beta-agonists in the follow-up year than patients who did not enter the study . These data suggest that the limited intervention in our setting improved outcomes but that regular care manager follow-up thereafter did not add significantly to this intervention A r and omised controlled trial , involving 112 adolescents with asthma , and a 2-year follow-up was conducted to assess the impact of an intervention programme aim ed at enhancing adherence to asthma medication . This programme had a duration of 1 year and consisted of an experimental group which received usual care from a paediatrician , but additionally attended individual and group sessions with an asthma nurse , and a control group which received usual care only . The programme aim ed at enhancing adherence by stimulating a positive attitude , increasing feelings of social support , and enhancing self-efficacy . At baseline , and after 12-month ( T1 ) and 24-month ( T2 ) follow-up , the participants filled in question naires which were based on the concepts of the ASE-model . Adherence was assessed by self-report ( range : 1 - 10 ) at the same points in time . After 12 months , 97 adolescents ( 87 % ) were available for follow-up , decreasing to 86 adolescents ( 77 % ) after 24 months . No statistically significant differences were found between the control and the experimental group , except for one . At T2 , self-reported adherence appeared to be statistically significantly higher in the experimental group . In conclusion , there seems to have been no substantial effect of the intervention programme This study describes the implementation of a nurse home visiting asthma education program for low-income African American families of young children with asthma . Of 55 families , 71 % completed the program consisting of eight lessons . The achievement of learning objectives was predicted by caregiver factors , such as education , presence of father or surrogate father in the household , and safety of the neighborhood , but not by child factors , such as age or severity of asthma as implied by the prescribed asthmamedication regimen . Incompatibility between the scheduling needs of the families and the nurse home visitors was a major obstacle in delivering the program on time , despite the flexibility of the nurse home visitors . The authors suggest that future home-based asthma education programs contain a more limited number of home visits but add telephone follow-ups and address the broader needs of low-income families that most likely function as barriers to program success We hypothesized that an educational intervention based on a readiness model would lead to improved health outcomes among patients with asthma . Within a r and omized control design in an urban Latino and African-American community , we conducted an intensive three-month pediatric intervention . A Family Coordinator provided patient education based on a readiness-to-learn model , and facilitated improved interactions between the patient and the doctor . Family education addressed the most basic learning needs of patients with asthma by improving their perception of asthma symptom persistence using asthma diaries and peak flow measures . The physician intervention focused clinicians ’ attention on patients ’ diary records and peak flow measures , and encouraged physicians to use stepped action plans . Patients were also tested for allergic sensitization and provided strategies to reduce contact with allergens and other asthma triggers . The results showed significant improvements by intervention group families on measures of knowledge , health beliefs , self-efficacy , self- regulatory skill , and adherence ; decreases in symptom persistence and activity restriction ; and increased prescription of anti-inflammatory medication by the physicians of the intervention group families PURPOSE To test the hypothesis that compared with the control group , 7 through 11-year-old children with persistent asthma who received asthma education plus a contingency management behavioral protocol would show higher adherence to peak expiratory flow ( PEF ) monitoring for asthma self-management and would report fewer asthma episodes . DESIGN AND METHODS A r and omized , controlled trial was conducted with 77 children with persistent asthma in a southeastern U.S. state . Both the intervention and control groups received instruction on PEF monitoring . Only the intervention group received asthma education plus contingency management , based on cognitive social learning theory , including self-monitoring , a contingency contract , tailoring , cueing , and reinforcement . At-home adherence to daily PEF monitoring during the 16-week study was assessed with the AccuTrax Personal Diary Spirometer , a computerized h and -held meter . Adherence was measured as a percentage of prescribed daily PEF uses at Weeks 4 ( baseline ) , 8 ( postintervention ) , and 16 ( maintenance ) . RESULTS At the end of the baseline period , the groups did not differ in adherence to daily PEF monitoring nor at Week 8 . At Week 16 , the intervention group 's adherence for daily electronically monitored PEF was higher than that of the control group . Children in either group who were > or= 80 % adherent to at least once-daily PEF monitoring during the last week of the maintenance period ( weeks 8 to 16 ) were less likely to have an asthma episode during this period compared with those who were less adherent . CONCLUSIONS The intervention to teach children to adhere to the recommended regimen for managing their asthma at home was effective BACKGROUND In the first 6 months of this previously published , r and omized trial , the combined intervention of occupant education , insecticide bait application , and professional cleaning significantly reduced cockroach numbers and Bla g 1 allergen levels in inner-city homes . OBJECTIVE This continuation study investigated whether the cockroach allergen reductions achieved by month 6 could be maintained through month 12 with insecticide application alone . METHODS Because we had agreed to place insecticide bait in control homes at the conclusion of the first study , intervention and control homes were treated with insecticide bait at months 6 and 9 . No other intervention was conducted in either arm . Vacuumed dust and swab sample s were collected at month 12 . Twenty-one of the 31 original homes completed the 12-month study . RESULTS Among the original intervention homes , Bla g 1 concentrations remained essentially unchanged from months 6 to 12 . However , among the crossed-over control homes , the geometric mean Bla g 1 concentrations ( Units per gram of dust ) decreased from 287 to 14.4 for kitchen floors ( 95 % reduction ) , from 28.8 to 5.6 for living room floors/sofas ( 81 % reduction ) , from 26.7 to 4.7 for bedroom floors ( 82 % reduction ) , and from 7.2 to 2.4 for beds ( 67 % reduction ) . At month 12 , Bla g 1 concentrations did not significantly differ between intervention and crossed-over control homes ( P > .64 at each location ) . Similar results were seen for the allergen Bla g 2 . CONCLUSIONS Reductions in cockroach allergen concentrations achieved through the combined intervention of occupant education , insecticide application , and professional cleaning can be maintained with continued cockroach control . Surprisingly , and in contrast to other studies , insecticide application alone significantly lowered allergen concentrations in the crossed-over control homes . This unexpected result is being tested further in another r and omized trial Abstract Twenty-one asthmatic children , aged 15 months to 13 years and from low-income families , who used the emergency room as their primary source of asthma care , were evaluated by the physicians of the Pediatric Allergy Division at baseline . These children were then r and omly assigned to either a control group or a clinical nurse specialist group . All children were scheduled for follow-up in the hospital clinic with pediatric residents and staff ( control group ) or with the clinical nurse specialist ( CNS ) . After assessing individual family needs , the CNS counseled each family regarding preventive health measures , focusing on early recognition of asthma exacerbations and self-care . During the 12-month study period , the frequency of allergy physician contacts and the total number of outpatient department visits were similar in both groups . However , compared with the 12-month period prior to enrollment , the CNS group subjects demonstrated a significant reduction in the frequency of emergency room ( ER ) visits ( 2.6 ± 1.1 versus 0.6 ± 0.9 ER visits per patient ; Asthma is a common , costly , and chronic disease that has a significant impact on children , their families , and the health care system . This study investigated whether formal asthma education can reduce asthma severity and morbidity and further question ed whether the method of education is an important factor in this process . Study subjects were recruited from the emergency department of the Royal Children 's Hospital , Melbourne ( RCHM ) , and controls were recruited from the neighboring Western Hospital , Sunshine ( WHS ) . Subject parents were r and omized to receive face-to-face education , group education , or home-based video education . Controls had similar medical treatment but received no formal asthma education . Subject and control parents were asked to complete question naires before the intervention and at 1 , 6 , and 12 months . These question naires measured demographics , the levels of parent asthma knowledge , anxiety , child asthma severity , and morbidity . Results showed that any method of education increased parent asthma knowledge and immediately decreased their anxiety and child asthma morbidity scores . Despite this , asthma severity was reduced only when knowledge was imparted in an interactive , face-to-face setting . When this happened , asthma severity scores were significantly reduced in both the short- and long-term . These findings call into question mass asthma education campaigns and have important implication s for the design of future asthma education programs Asthma education programs result in clinical improvement . However , most studies involved programs of up to 1 year of follow-up , and their efficacy in improving quality of life ( QoL ) is still controversial . The aim of this study was to evaluate the effectiveness of a program of patient education in asthmatics over 2 years . Thirty-seven asthmatic patients were r and omly allocated to group A ( usual treatment ) and 32 to group B ( usual treatment plus patient education program ) . The effectiveness of the education program was evaluated by comparing morbidity outcomes at baseline and 12 and 24 months afterwards . At baseline , no intergroup difference emerged in age , sex , smoking , asthma severity , atopy , FEV1 , symptom-free days , use of rescue salbutamol , and QoL. One year later , group B subjects had an improvement in the overall QoL ( from 5.8 ± 0.8 to 6.1 ± 0.7 , p < 0.005 ) , and in “ Activities ” ( from 5.3 ± 0.9 to 5.7 ± 0.8 , p < 0.05 ) and “ Environment ” ( from 6.4 ± 1.0 to 6.8 ± 0.4 , p < 0.05 ) domains . Two years later the “ Activities ” domain score increased in group B ( from 5.3 ± 0.9 to 5.7 ± 1.1 , p < 0.05 ) . QoL did not vary in group A. The education program was ineffective in all other parameters at both follow-up time-points . In group A , a significant increase in medication expenses and a significant decrease in rescue salbutamol use was found 1 and 2 years after baseline , respectively . In conclusion , this education program improved QoL for 1 year , but the improvement was not sustained in the 2nd year A r and omized control trial of the Wee Wheezers asthma education program was conducted with 76 children < 7 years of age , 31 % of whom were on a medication regimen consistent with mild , 51 % with moderate , and 18 % with moderately severe/severe asthma . Treatment children showed improved morbidity at 3-month follow-up relative to the changes in the controls : increased symptom-free days in the preceding 2 weeks ( mean change of + 2.2 vs. -2.6 in the controls ; p = .004 ) and month ( + 2.0 vs. -3.8 ; p < .02 ) , fewer nights of parental sleep interruption in a typical week ( + 0.7 vs. + 1.8 ; p < or = .05 ) , and a trend toward fewer asthma sick days ( -0.2 vs + 0.7 ; p = ns ) . These improvements were accompanied by significantly better parental asthma management compared with controls ( more consistent use of preventive medications , p < or = .01 ; early symptom intervention , [ corrected ] p < or = .05 ) and trends toward more restrictions on smoking in the home ( p < .07 ) and decreased parental confusion about asthma treatment ( p < .11 ) . This study provides evidence that a multisession program of asthma education for parents can improve parental asthma management and clinical outcomes in very young children and provides information on the validity and sensitivity of various asthma outcome measures in this age group We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site r and omized control study . In this program , a nurse under physician supervision monitors the patient 's airway status at home and provides instructions to individuals via the telephone , helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan . Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and r and omly assigned to either the telemedicine or control group . After a six-month study period , an 83 % reduction in hospitalization was demonstrated in the telemedicine group versus the control group , with a P value of 0.01 . Improvement of peak expiratory flow and symptoms were also shown in the study group . We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring , compliance with prescribed daily prophylactic anti-inflammatory steroid medications , and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration This study evaluated the benefits produced by " Superstuff " , a self-help program for asthmatic children aged 7 - 12 . Forty-three children with a confirmed diagnosis of moderate to severe asthma were r and omly assigned to either the totally self-administered Superstuff condition or to a nocontact Control condition . Self-report , parental , physician , and school data were collected at pre-intervention , and two , six , and twelve months post-intervention . Children receiving Superstuff reported increased asthma self-control skills , but no gains in general self-control abilities or self-esteem . Superstuff subjects also evidence d fewer interruptions of parents , greater improvement in the progression of asthma as reported by physicians ( but not in the severity of the disease or intensity of average attack ) , and tended toward decreased school absenteeism . Superstuff did not reduce scheduled or emergency medical contacts . The demonstration of important , but modest , benefits from a low-cost , easily disseminated , self-administered intervention is discussed in the context of self-help treatment in general This article reports on the development of a personalized , Web-based asthma-education program for parents whose 4- to 12-year-old children have moderate to severe asthma . Personalization includes computer-based tailored messages and a human coach to build asthma self-management skills . Computerized features include the Asthma Manager , My Calendar/Reminder , My Goals , and a tailored home page . These are integrated with monthly asthma-education phone calls from an asthma-nurse case manager . The authors discuss the development process and issues and describe the current r and omized evaluation study to test whether the year-long integrated intervention can improve adherence to a daily asthma controller medication , asthma control , and parent quality of life to reduce asthma-related healthcare utilization . Implication s for health education for chronic disease management are raised The adherence and disease-control outcomes associated with the use of an Internet-based store- and -forward video home telehealth system to manage asthma in children were studied . Pediatric patients with persistent asthma were provided with home computers and Internet access and monitored biweekly over the Internet . All patients were seen in the pediatric clinic at 0 , 2 , 6 , 12 , and 24 weeks . Half of the patients received asthma education in person and half via an interactive Web site . Adherence measures were assessed by therapeutic and diagnostic monitoring . Therapeutic monitoring included digital videos of patients using their controller medication inhaler . Diagnostic monitoring included an asthma symptom diary and a video of peak flow meter use . Videos were su bmi tted electronically twice a week by using in-home telemonitoring with store- and -forward technology . Feedback was provided electronically to each patient . Disease control was assessed by examining quality of life , utilization of services , rescue-therapy use , symptom control , satisfaction with home telemonitoring , and retention of asthma knowledge . Patients were r and omly assigned to an asthma education group ( Internet versus office ) , and the data were analyzed by comparing results for study days 0 - 90 and 91 - 180 . Ten children participated . A total of 321 videos of inhaler use and 309 videos of peak flow meter use were su bmi tted . Inhaler technique scores improved significantly in the second study period . Su bmi ssion of diagnostic monitoring videos and asthma diary entries decreased significantly . Peak flow values as a percentage of personal best values increased significantly . Overall , there was no change in quality of life reported by patients . However , the caregivers in the virtual-education group reported an increase in the patients ' quality -of-life survey scores . Emergency department visits and hospital admissions for asthma were avoided . Rescue therapy was infrequent . A high rate of satisfaction with home telemonitoring was reported . Internet-based , store- and -forward video assessment of children 's use of asthma medications and monitoring tools in their homes appeared effective and well accepted PURPOSE Data from the general population suggest that habitual exercise decreases bronchial responsiveness , but the possible role of exercise in asthmatics is undefined . The leukotriene receptor antagonist montelukast decreases bronchial responsiveness and exercise-induced symptoms in asthmatic children . This r and omized study in children with mild asthma evaluated the combined effects of aerobic training for 12 wk and montelukast or placebo on bronchial responsiveness ( BHR ) to methacholine , exercise-induced bronchoconstriction ( EIB ) , inflammatory markers in exhaled breath condensate ( EBC ) , and asthma exacerbations . METHODS Fifty children ( mean age + /- SD : 10.2 + /- 2.4 yr ) with mild stable asthma were r and omly assigned to placebo ( N = 25 ) or montelukast ( N = 25 ) . Before and after training , we assessed BHR and EIB and markers of airway inflammation-that is , exhaled nitric oxide ( eNO ) , pH , and cysteinyl-leukotriene concentration-in EBC . RESULTS Training increased maximal workload and peak minute ventilation . After training , the methacholine dose causing a 20 % fall in FEV1 ( PD20 ) increased in both groups . A decreased slope of FEV1 decline at increasing methacholine dose was found only in montelukast-treated children . EIB prevalence halved after training in both groups ( EIB + children , placebo group : 10 pretraining , 4 posttraining ; EIB + children , montelukast group : 8 pretraining , 5 posttraining ; P < 0.05 by chi on all children ) . Resting eNO was unaffected , whereas the pH of EBC decreased after training in both groups . Cysteinyl-leukotriene concentrations were low in most children at both times . During training , montelukast-treated children showed fewer asthma exacerbations compared with the same period of the previous year . CONCLUSIONS In children with mild stable asthma , exercise training decreased bronchial responsiveness to methacholine . Montelukast also decreased bronchial reactivity ( FEV1 slope ) and protected against exacerbations , suggesting a beneficial synergistic action of these two interventions in mild asthma INTRODUCTION The purpose of this r and omized control trial was to evaluate the effects of a computer-assisted instructional ( CAI ) game on asthma symptoms ( eg , coughing , wheezing , shortness of breath , and nighttime awakenings ) in 7- to 12-year-old inner-city children over 12 weeks . METHOD A CAI that focused on reducing environmental irritants/allergens and the correct use of prescribed medications to prevent asthma symptoms was used with 101 children ( 56 in the intervention group and 45 in the control group ) . The primary outcome evaluated a change in children 's asthma symptoms as measured by responses to nine symptom questions in Juniper 's Pediatric Asthma Quality of Life Question naire ( PAQOL ) and measurements of lung function . RESULTS No significant changes in asthma symptoms occurred between the two groups before and after the intervention . No significant changes were noted in PAQOL scores for activities , emotions , and total PAQOL score , lung function measurements , and asthma severity between the two groups . Asthma knowledge of both groups was high before intervention , but there were no significant changes between groups after the intervention . DISCUSSION Findings indicate that this CAI game was not effective in improving asthma symptoms in this group of children A r and omized clinical trial is in progress to evaluate an asthma educational program for Latino children and their parents . The intervention , " ACT — Asma Control y Trata miento Para Ninos , " was adapted from ACT for Kids , an asthma self-management pro gram for English-speaking families . Results of a pilot study indicated that socioeco nomic status was a critical variable to be considered in the design of such programs . Latino children and parents encounter significant barriers to access and continuity of medical care . Therefore , the intervention was re design ed to include " linkages " using a nurse to reduce barriers and to coordinate care . The lesson plans emphasize concrete , experimental learning experiences , with repetition of key points in each session BACKGROUND It is postulated that children with asthma who receive an interactive , comprehensive education program would improve their quality of life , asthma management and asthma control compared with children receiving usual care . OBJECTIVE To assess the feasibility and impact of ' Roaring Adventures of Puff ' ( RAP ) , a six-week childhood asthma education program administered by health professionals in schools . METHODS Thirty-four schools from three health regions in Alberta were r and omly assigned to receive either the RAP asthma program ( intervention group ) or usual care ( control group ) . Baseline measurements from parent and child were taken before the intervention , and at six and 12 months . RESULTS The intervention group had more smoke exposure at baseline . Participants lost to follow-up had more asthma symptoms . Improvements were significantly greater in the RAP intervention group from baseline to six months than in the control group in terms of parent 's perceived underst and ing and ability to cope with and control asthma , and overall quality of life ( P<0.05 ) . On follow-up , doctor visits were reduced in the control group . CONCLUSION A multilevel , comprehensive , school-based asthma program is feasible , and modestly improved asthma management and quality of life outcomes . An interactive group education program offered to children with asthma at their school has merit as a practical , cost-effective , peer-supportive approach to improve health outcomes This study investigated the effectiveness of different educational programs in obtaining better asthma control and asthma-related quality of life ( QoL ) . In 60 adult patients with moderate persistent asthma we tested the benefit of individual verbal instructions ( IVI ) , written information ( " asthma booklet " , B ) , and integrated asthma classes ( " asthma school " , AS ) . At the enrollment and at the end of the study , all participants completed the question naires regarding their asthma-related knowledge ( ArK ) and QoL. During the 12-week period all patients recorded their asthma symptoms , morning and evening peek expiratory flow rates ( PEFR ) , and the use of rescue medication . AS and IVI groups showed a significantly greater improvement in QoL than the B group . AS group obtained the highest ArK but no difference in the level of improvement among the groups has been documented . The improved average asthma symptom score and decreased utilization of the rescue medication were documented in all groups without significant differences among them . We also found significant improvements in both morning and evening PEFR in IVI group as well as in the morning PEFR in AS group . We conclude that among tested educational interventions the AS caused the best improvement in QoL while IVI produced the best overall response in both parameters of the asthma control and An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment , despite adequate medical treatment . Mild-to-moderate asthma patients ( n=23 ) were r and omly assigned to a programme or waiting list condition . Outcome measures were : McMaster Asthma Quality of Life Question naire , Asthma Symptom Checklist , Negative Emotionality Scale , Knowledge , Attitude and Self-Efficacy Asthma Question naire , Adherence Scale , and peak flow measurements . Both groups were evaluated at three consecutive moments , each separated by 3 months ; the programme was delivered between the first two evaluations . At onset the patient received a workbook containing information , exercises and homework assignments . Psycho-education , behavioural and cognitive techniques were introduced during six 1‐h individual sessions . Compared with controls the programme group reported less symptoms ( obstruction , fatigue ) , better quality of life ( activity , symptoms , emotions ) , decreased negative affectivity , and increased adherence , immediately after finishing the programme and at 3 months follow-up . All three cognitive variables ( knowledge , attitude towards asthma , self-efficacy ) and day and night peak flow ratings improved in the programme group but not in the waiting list group . Participation in an individualised programme result ed in improvement of asthma morbidity , and asthma-related behaviour and cognitions , in subjects reporting symptoms and impairment despite adequate medical therapy OBJECTIVE To conduct a r and omized clinical trial of the Spanish version of an educational program design ed to be an adjuvant to adequate medical care of children with asthma . DESIGN R and omized , clinical trial . SETTING Los Angeles County , Calif. PARTICIPANTS One hundred thirty-eight Hispanic children , ages 7 to 12 years , from disadvantaged families . All had used emergency facilities of major local hospitals in the previous year . MEASUREMENT/MAIN RESULTS : As the study proceeded , it became apparent that subjects were receiving inadequate medical and nursing care and had numerous barriers to applying knowledge and self-care skills gained from the program . Realizing this , we considered it unethical to allow the control children to suffer for the duration of the trial ( 1 year ) . Therefore , all children received " adequate " care from the research staff , and the r and omized clinical trial , as originally design ed , was ended . The emergency department/hospital use by both groups was significantly reduced compared with previous experience . CONCLUSION Those research ers conducting r and omized trials involving poor children should be aware of the potential ethical problems inherent in such ventures Patients need to underst and their asthma to be able to react appropriately . At least 30 minutes is needed by a trained asthma professional to teach asthma self-management effectively . Many patients accept symptoms and attacks unnecessarily through insufficient knowledge of their condition and treatment . In this small study , those who were educated by a trained asthma nurse had a significantly higher knowledge of their condition and management . Most of those who were educated by a trained asthma nurse had symptoms less frequently . Those who were educated by a trained asthma nurse had no time off work whereas 49 % of the control group had time off work Educational self-management programs for children with asthma have now become a routine feature in the management of the disease , as international guidelines underline . We design ed this trial to find out whether Aironet , an educational program developed for children with asthma , influenced asthma severity and improved parents ' knowledge of the disease . In a multicenter , prospect i ve , r and omized controlled trial we enrolled 123 children , 72 boys , mean age 8.78 yr ( + /-2.33 s.d . ) , with intermittent or mild persistent asthma . Participants were r and omly assigned to an education group , who received Aironet at baseline and 2 months later ( 60 children ) , or to a control group who did not ( 63 children ) . Follow-up lasted 12 months and included out-patient clinic visits and spirometry at 2 , 4 and 12 months . At baseline and at 12 months follow-up , parents were question ed about their knowledge of asthma , and their children 's asthmatic attacks , use of systemic corticosteroids , family physician or hospital emergency room visits , hospitalizations and asthma-related school absences . Question naire replies at 12-month follow-up reported significantly fewer asthma attacks in patients who received the program than in those who did not ( 1.65 + /- 1.21 vs. 2.34 + /- 1.73 ; p < 0.05 ) . For the subgroup of children who had > or =3 asthma attacks at baseline , parents ' knowledge improved significantly more in the educational group than in the control group . The out-patient educational program Aironet reduces the number of asthma attacks in children with intermittent or mild persistent asthma and improves knowledge of the disease Background and purpose . Asthma management programs ( AMP ) may reduce costs and improve outcomes in patients with moderate to severe asthma . However , it is not known which personnel are best able to deliver such interventions and what setting s are most effective . The purpose of this study was to compare the effects of an in-home AMP provided by respiratory therapists ( RTs ) to an AMP provided by nurses ( RNs ) and to usual care ( UC ) provided in physician offices or clinics . Methods . Subjects ( age 18–64 ) who had been admitted to the emergency department ( ED ) or hospital for acute asthma exacerbation were r and omized to three groups : AMP-RT , AMP-RN or UC . The AMP groups received five ( 5 ) weekly home visits to provide assessment and instruction ; the UC group was instructed to return to their physician for routine follow-up . Outcomes assessed at 6 months included hospitalizations , in patient days , hospitalization cost , ED visits and cost , clinic visits , pulmonary function , symptoms , health related quality of life ( HRQOL ) , asthma episode self-management score ( AESM ) , environmental assessment , and patient satisfaction ( PS ) . Variables were compared using ANOVA with a Neuman-Keuls follow-up for multiple comparisons using an intent-to-treat approach . Results . Upon enrollment , ( n = 159 ) there were no differences ( p > . 05 ) between groups for age , gender , pulmonary function or HRQOL ( SF-36 and St. Georges Respiratory Question naire – SGRQ ) . At 6 months , both AMP groups ( AMP-RN n = 54 ; AMP-RT n = 46 ) had significantly fewer ( p < 0.05 ) hospitalizations and in-patient days , lower hospitalization costs , and greater HRQOL physical component summary change scores ( PCS ) and PS than UC ( n = 59 ) . AMP-RT also had greater PEFR , SGRQ Total and SGRQ Symptoms change scores when compared to UC and significantly better AESM and PS scores as compared to AMP-RN and UC . Conclusions . An in-home asthma management program can be effectively delivered by respiratory therapists and may reduce hospitalizations , in-patient days , cost and improve measures of HRQOL and PS in a population prone to asthma exacerbation Asthma case management and education programs improve pediatric asthma outcomes , but design ing rigorous r and omized controlled studies that accurately measure effects while encouraging parent participation is challenging . This is especially so for low-income African American families , who face significantly more severe asthma and social stress than their middle-class counterparts . Action research can help health education research ers negotiate between the elegant and complex design s favored by scientists with the real-life challenges of recruitment , implementation , and retention . This article discusses how a multidisciplinary team uses action research concepts to continuously adjust originally proposed protocol s through the planning and implementation phases to encourage participation in a year-long r and omized controlled trial of a program that combines telephone asthma case management and comprehensive online asthma education . As a result of these efforts , a higher proportion of low-income African American families are recruited into the study than originally proposed |
10,939 | 21,169,286 | Findings suggest high levels of evidence for using daily dosing schedules , especially during the initial phase in the presence of cavitation , isoniazid resistance and advanced HIV co-infection , to reduce the risk of treatment failure , recurrence and acquired drug resistance including acquired rifamycin resistance . | Intermittent tuberculosis treatment regimens have been developed to facilitate treatment supervision .
Their efficacy has been substantiated by clinical trials and tuberculosis control programmes , notwithst and ing the lack of head-to-head comparison between daily and intermittent regimens .
Recently , there has been opposing evidence from observational studies , pharmacokinetic-pharmacodynamic studies and animal models that intermittent treatment increases the risk of relapse , treatment failure or acquired rifamycin resistance , especially among HIV-infected patients . | BACKGROUND The occurrence of acquired rifamycin resistance despite use of directly observed therapy for tuberculosis is associated with advanced human immunodeficiency virus ( HIV ) disease and highly intermittent administration of antituberculosis drugs . Beyond these associations , the pathogenesis of acquired rifamycin resistance is unknown . METHODS We performed a pharmacokinetic sub study of patients in a trial of treatment with twice-weekly rifabutin and isoniazid . RESULTS A total of 102 ( 60 % ) of 169 patients in the treatment trial participated in the pharmacokinetic sub study , including 7 of 8 patients in whom tuberculosis treatment failure or relapse occurred in association with acquired rifamycin-resistant mycobacteria ( hereafter , " ARR failure or relapse " ) . The median rifabutin area under the concentration-time curve ( AUC(0 - 24 ) ) was lower for patients with than for patients without ARR failure or relapse ( 3.3 vs. 5.2 microg*h/mL ; P = .06 , by the Mann-Whitney exact test ) . In a multivariate analysis adjusted for CD4 + T cell count , the mean rifabutin AUC(0 - 24 ) was significantly lower for patients with ARR failure or relapse than for other patients ( 3.0 microg*h/mL [ 95 % confidence interval { CI } , 1.9 - 4.5 ] vs. 5.2 microg*h/mL [ 95 % CI , 4.6 - 5.8 ] ; P = .02 , by analysis of covariance ) . The median isoniazid AUC(0 - 12 ) was not significantly associated with ARR failure or relapse ( 20.6 vs. 28.0 microg*h/mL ; P = .24 , by the Mann-Whitney exact test ) . However , in a multivariate logistic regression model that adjusted for the rifabutin AUC(0 - 24 ) , a lower isoniazid AUC(0 - 12 ) was associated with ARR failure or relapse ( OR , 10.5 ; 95 % CI , 1.1 - 100 ; P = .04 ) . CONCLUSIONS Lower plasma concentrations of rifabutin and , perhaps , isoniazid were associated with ARR failure or relapse in patients with tuberculosis and HIV infection treated with twice-weekly therapy This report from the Tuberculosis Chemotherapy Centre , Madras , summarizes the progress over a 5-year period of 193 patients with newly diagnosed , sputum-positive pulmonary tuberculosis who were admitted to a concurrent comparison of home and sanatorium treatment for one year with isoniazid plus PAS . Previous reports have shown that , despite the traditional advantages of sanatorium treatment-rest , adequate diet , nursing and supervised drug-administration-the home patients responded nearly as well as the sanatorium patients in the first year ; further , the relapse rates over a 2-year period of follow-up were similar . The findings in the present report are based on a 4-year period of follow-up and extend these conclusions , the relapse rates over the period being 7 % for the home patients and 10 % for the sanatorium patients . Patients who failed to respond to treatment in the first year and those who had a bacteriological relapse in the second or subsequent years were usually re-treated with reserve regimens , first with streptomycin plus pyrazinamide and , if this was ineffective , with cycloserine plus ethionamide . Considering the findings over the entire 5-year period , five home patients and three sanatorium patients died from non-tuberculous causes . Of the remainder , 5 % of the home patients and 6 % of the sanatorium patients died of tuberculosis , 4 % in each series had bacteriologically active disease at five years and 90 % and 89 % , respectively , had bacteriologically quiescent disease at that time . These findings are very encouraging , particularly for developing countries such as India , where tuberculosis is a major problem and sanatorium beds are very few This report is the last of a series of nine publications from the Tuberculosis Chemotherapy Centre , Madras , concerning various aspects of an investigation of the role of ambulatory chemotherapy for pulmonary tuberculosis . It presents the attack rates of tuberculosis over a 5-year period of follow-up of close family contacts of patients , all of whom were treated for one year with isoniazid plus PAS , half ( selected at r and om ) in sanatorium and half at home . The incidence of active tuberculosis and of tuberculous infections was no greater in the contacts of patients treated at home than in the contacts of patients treated in sanatorium , either in the first year or over the subsequent four years . The major risk to the contacts result ed from exposure to the patient before diagnosis . These findings reaffirm that close family contacts of patients treated at home were at no additional risk of developing tuberculosis , provided the patients received effective chemotherapy . Finally , this study has shown that it is possible in South India to obtain extremely good co-operation from a group of families over a period of several years While directly observed treatment ( DOT ) has been recommended as the st and ard approach to tuberculosis control , empirical data on its feasibility and efficiency are still scarce . We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thail and . A total of 836 patients diagnosed between August 1996 and October 1997 were r and omly assigned to be treated either under DOT or self-supervised using monthly drug supplies ( SS ) . Options for treatment supervisors were health staff , community members or members of the patients ' families . Treatment outcomes were compared on the basis of cure , treatment-completion , default and death rates . In both study arms , treatment outcomes were improved compared to pre- study conditions . Cure and treatment-completion rates were significantly higher in the DOT cohort ( 76 % and 84 % ) than in the SS group ( 67 % and 76 % ) . The benefits of DOT were more pronounced at district and provincial hospitals ( DOT cure rate 81 % vs. 69 % in the SS group ) , while differences for patients treated at referral centres were non-significant ( DOT cure rate 72 % vs. 66 % in the SS group ) . No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors . DOT appears especially suited for treatment at de central ized facilities . While a general focus on programme performance can improve outcomes , DOT provides significant additional benefits . If basic conditions are met , a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options , without decreasing its effectiveness The bacteriological relapse rates up to 30 months after the start of chemotherapy have been compared for 4 daily short-course regimens for pulmonary tuberculosis . All 4 had the same initial 2-month intensive phase of streptomycin , isoniazid , rifampicin and pyrazinamide ( SHRZ ) followed by isoniazid plus rifampicin for 4 months ( 4HR ) , or isoniazid plus pyrazinamide for 4 months ( 4HZ ) , or isoniazid alone for 4 months ( 4H ) , or isoniazid alone for 6 months ( 6H ) . In patients with fully sensitive strains pretreatment , the 6-month regimen with rifampicin throughout ( 4HR ) was highly effective , only 2 % of 166 patients relapsing bacteriologically in 24 months of follow-up after stopping chemotherapy . This regimen was significantly better than the 4H regimen which had a relapse rate of 10 % in 156 patients ( P less than 0.02 ) and the 4HZ regimen which had a relapse rate of 8 % in 164 patients ( P = 0.05 ) . The 6H regimen was also highly effective , only 3 % of the 123 patients relapsing , compared with 10 % of the 156 on the 4H regimen ( P = 0.06 ) . The relapse rate of the regimen with pyrazinamide throughout ( 4HZ ) , was not significantly different from that of either of the regimens with isoniazid alone in the continuation phase . All except 3 ( 1 4HR , 1 4HZ , 1 4H ) of the 36 relapses were with fully drug-sensitive strains . In patients with strains resistant to isoniazid alone pretreatment none of the 23 on the 4HR or 4HZ regimens had an unfavourable bacteriological status at the end of chemotherapy compared with 8 of the 17 patients ( P less than 0.005 ) on 4H or 6H regimens . Of the patients assessed , 3 of 20 receiving rifampicin or pyrazinamide throughout relapsed compared with 2 of 8 who did not To underst and why once-weekly isoniazid/rifapentine therapy for tuberculosis was less effective than twice-weekly isoniazid/rifampin , we studied human immunodeficiency virus-seronegative patients with either failure ( n = 4 ) , relapse ( n = 35 ) , or cure ( n = 94 ) , recruited from a comparative treatment trial . In multivariate analyses that were adjusted for severity of disease , low plasma concentrations of isoniazid were associated with failure/relapse with once-weekly isoniazid/rifapentine ( median isoniazid area under the concentration-time curve for 12 hours after the dose [ AUC(0 - 12 ) ] was 36 microg x hour/ml in failure/relapse versus 56 microg x hour/ml in control cases p = 0.005 ) , but not with twice-weekly isoniazid/rifampin . Furthermore , two patients who relapsed with Mycobacterium tuberculosis monoresistant to rifamycin had very low concentrations of isoniazid . Finally , isoniazid acetylator status determined by N-acetyltransferase type 2 genotype was associated with outcome with once-weekly isoniazid/rifapentine ( p = 0.03 ) but not twice-weekly isoniazid/rifampin . No rifamycin pharmacokinetic parameter was consistently and significantly associated with outcome ( p > 0.10 ) . Because low isoniazid concentrations were associated with failure/relapse , a drug with consistently greater area under the concentration-time curve than isoniazid may be needed to achieve highly active once-weekly therapy with rifapentine One daily and 3 thrice weekly retreatment regimens given for 12 months under programme conditions were compared . The daily regimen was rifampicin and ethambutol ( RE7 ) . The three intermittent regimens also contained rifampicin and ethambutol : one of them , rifampicin and ethambutol throughout ( RE3 ) ; the next one supplemented with pyrazinamide for the first 3 months ( REZ3 ) ; the last one supplemented with prothionamide for the first 3 months ( REPt3 ) . The pyrazinamide containing regimen was subdivided into ordinary and high dose groups . The subjects for retreatment were those who have had , at least , more than 6 months of initial triple chemotherapy of isoniazid , PAS and streptomycin at the health centres , and failed to convert to bacteriologically negative status . Among 419 patients who were available for sensitivity tests before commencing retreatment , 393 ( 94.3 % ) were resistant to isoniazid . Six hundred and seventy-four patients ( 674 ) were allocated r and omly to the regimens : 64 patients were excluded due to various pretreatment reasons and 109 did not complete 12 months of chemotherapy . There remain 501 patients who completed their retreatment . As assessed at 12 months , a bacteriologically favourable response was achieved in 68 % of 135 RE7 patients , 62 % of 129 RE3 patients , 74 % of 132 REZ3 patients , and in 79 % of 108 REPt3 patients . Adverse reactions were uncommon : 4 % in RE7 , 5 % in RE3 and 9 % in REZ3 , but 32 % in REPt3 . Relapse rates during 2 years after termination of chemotherapy were 15 % in RE7 , 14 % in RE3 and REZ3 , and 26 % in REPt3 , as calculated by life table analysis BACKGROUND Tuberculosis is a major public-health problem in South Africa , made worse by poor adherence to and frequent interruption of treatment . Direct observation ( DO ) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome . We compared DO with self-supervision , in which patients on the same drug regimen are not observed taking their pills , to assess the effect of each on the success of tuberculosis treatment . METHODS We undertook an unblinded r and omised controlled trial in two communities with large tuberculosis caseloads . The trial included 216 adults who started pulmonary tuberculosis treatment for the first time , or who had a second course of treatment ( retreatment patients ) . No changes to existing treatment delivery were made other than r and omisation . Analysis was by intention to treat . Individual patient data from the two communities were combined . FINDINGS Treatment for tuberculosis was more successful among self-supervised patients ( 60 % of patients ) than among those on DO ( 54 % of patients , difference between groups 6 % [ 90 % CI -5.1 to 17.0 ] ) . Retreatment patients had significantly more successful treatment outcomes if self-supervised ( 74 % of patients ) than on DO ( 42 % of patients , difference between groups 32 % [ 11%-52 % ] ) . INTERPRETATION At high rates of treatment interruption , self-supervision achieved equivalent outcomes to clinic DO at lower cost . Self-supervision achieved better outcomes for retreatment patients . Supportive patient-carer relations , rather than the authoritarian surveillance implicit in DO , may improve treatment outcomes and help to control tuberculosis BACKGROUND Rifapentine has a long half-life in serum , which suggests a possible treatment once a week for tuberculosis . We aim ed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week . METHODS We did a r and omised , multicentre , open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen . We r and omly allocated patients directly observed treatment with either 600 mg rifapentine plus 900 mg isoniazid once a week or 600 mg rifampicin plus 900 mg isoniazid twice a week . Primary outcome was failure/relapse . Analysis was by intention to treat . FINDINGS 1004 patients were enrolled ( 502 per treatment group ) . 928 successfully completed treatment , and 803 completed the 2-year 4-month study . Crude rates of failure/relapse were 46/502 ( 9.2 % ) in those on rifapentine once a week , and 28/502 ( 5.6 % ) in those given rifampicin twice a week ( relative risk 1.64 , 95 % CI 1.04 - 2.58 , p=0.04 ) . By proportional hazards regression , five characteristics were independently associated with increased risk of failure/relapse : sputum culture positive at 2 months ( hazard ratio 2.8 , 95 % CI 1.7 - 4.6 ) ; cavitation on chest radiography ( 3.0 , 1.6 - 5.9 ) ; being underweight ( 3.0 , 1.8 - 4.9 ) ; bilateral pulmonary involvement ( 1.8 , 1.0 - 3.1 ) ; and being a non-Hispanic white person ( 1.8 , 1.1 - 3.0 ) . Adjustment for imbalances in 2-month culture and cavitation diminished the association of treatment group with outcome ( 1.34 ; 0.83 - 2.18 ; p=0.23 ) . Of participants without cavitation , rates of failure/relapse were 6/210 ( 2.9 % ) in the once a week group and 6/241 ( 2.5 % ) in the twice a week group ( relative risk 1.15 ; 95 % CI 0.38 - 3.50 ; p=0.81 ) . Rates of adverse events and death were similar in the two treatment groups . INTERPRETATION Rifapentine once a week is safe and effective for treatment of pulmonary tuberculosis in HIV-negative people without cavitation on chest radiography . Clinical , radiographic , and microbiological data help to identify patients with tuberculosis who are at increased risk of failure or relapse when treated with either regimen SETTING The tuberculosis component of the Infectious and Endemic Disease Control Project in the People 's Republic of China is the largest single tuberculosis control project in the world using directly-observed therapy and st and ardized intermittent regimens . OBJECTIVE To determine the two-year relapse and mortality rates following completion of treatment . DESIGN A prospect i ve cohort study of 649 cases cured in this project . The 306 new and 343 retreatment cases were treated under field conditions with 2H3R3Z3S3/4H3R3 and 2H3R3Z3E3S3/6H3R3E3 , respectively . Following treatment completion , two sputum sample s were collected every six months for two years and examined for acid-fast bacilli . Causes of death were identified . RESULTS The two-year relapse rates for new and retreatment cases were 3.3 % and 5.6 % , respectively . Retreatment cases with delayed sputum conversion had a greater risk for subsequent relapse . The two-year mortality rate for new and retreatment cases was 3.3 % and 8.5 % , respectively . The higher mortality rate in retreatment cases was not attributable to relapse of disease , but rather to non-infectious sequelae of tuberculosis . CONCLUSION The use of directly-observed intermittent regimens is effective in permanently removing infectious tuberculosis cases from the community BACKGROUND Isoniazid-resistant tuberculosis ( INHr-TB ) can be treated successfully with several treatment regimens . However , the optimal regimen and duration are unclear . STUDY OBJECTIVE To analyze the efficacy of treatment regimens used for INHr-TB in the southeastern Texas region . DESIGN Retrospective cohort study . SETTING Health-care facilities reporting tuberculosis ( TB ) patients in the Houston and Tyler areas . SUBJECTS All patients reported to have INHr-TB from 1991 to 1998 . Exclusion criteria included poor compliance , additional first-line drug-resistance ( except aminoglycosides ) , and death before completion of 1 month of treatment . MEASUREMENTS AND RESULTS Main treatment outcomes were treatment failure , relapse , and TB-related death . Fifty-three of 83 patients were included in the study ; aminoglycoside resistance coexisted in 37.5 % of isolates . Seven types of treatment regimens were identified . Eighteen patients ( 34 % ) received rifampin , pyrazinamide , and ethambutol thrice weekly for 9 months . Four patients ( 7.5 % ) had a total effective treatment duration of < 9 months . Thirty patients ( 56.6 % ) and 16 patients ( 30.2 % ) received thrice-daily and daily treatment regimens , respectively . Forty-nine patients achieved sputum conversion . Treatment failure and death occurred in one patient ( 1.9 % ) . Three patients ( 5.7 % ) experienced relapses . There was a significant difference in total effective treatment time between patients with and without relapses ( 8.3 + /- 1.1 months vs 11.1 + /- 2.1 months ; p < 0.02 ) . Twice-weekly treatment regimens were associated with relapse ( p = 0.05 ) . CONCLUSIONS Several treatment regimens were prescribed for INHr-TB in southeastern Texas . INHr-TB treatment duration s were > 7 months , and treatment regimen efficacy was adequate . Twice-weekly treatment was associated with relapse , whereas thrice-weekly and daily treatments performed similarly . A prospect i ve study with different treatment duration s is needed to determine the optimal treatment regimen for patients with INHr-TB BACKGROUND DOTS is the control strategy for tuberculosis promoted by WHO . Pakistan is currently developing its National Tuberculosis Programme , and requires guidance on types of direct observation of treatment appropriate for the local conditions . We did a r and omised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan . METHODS We enrolled 497 adults with new sputum-positive tuberculosis . 170 were assigned DOTS with direct observation of treatment by health workers ; 165 were assigned DOTS with direct observation of treatment by family members ; and 162 were assigned self-administered treatment . The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purpose s of the research , with a st and ard daily short-course drugs regimen ( 2 months of isoniazid , rifampicin , pyrazinamide , and ethambutol , followed by 6 months of isoniazid and ethambutol ) . The main outcome measures were cure , and cure or treatment completion . Analysis was by intention to treat . FINDINGS Within the strengthened tuberculosis services , the health-worker DOTS , family-member DOTS , and self-administered treatment strategies gave very similar outcomes , with cure rates of 64 % , 55 % , and 62 % , respectively , and cure or treatment-completed rates of 67 % , 62 % , and 65 % , respectively . INTERPRETATION None of the three strategies tested was shown to be superior to the others , and direct observation of treatment did not give any additional improvement in cure rates . The effectiveness of direct observation of treatment remains unclear , and further operational research is needed SETTING Tertiary level tuberculosis ( TB ) institute in Delhi , India . OBJECTIVE To study the risk factors for new pulmonary TB ( PTB ) patients failing treatment . DESIGN Prospect i ve case-control study . The profile of new PTB patients failing treatment ( i.e. , sputum smear-positive at 5 months of treatment ) and responders under the Revised National Tuberculosis Control Programme ( RNTCP ) were compared and risk factors associated with treatment failure were analysed . RESULTS A total of 42 treatment failure cases and 76 controls were enrolled in the study . The presence of cavity on chest X-ray ( CXR ) , sputum acid-fast bacilli ( AFB ) smear positivity at 2 months of treatment and the number of interruptions in treatment were independently associated with failures . Among failure patients at 5 months , 17 ( 40.5 % ) had negative sputum culture for Mycobacterium tuberculosis , and only six ( 14.3 % ) had multidrug-resistant TB ( MDR-TB ) . When put on retreatment , patients with smear-positive , culture-negative sputum had cure rates of 88.2 % compared to 28.6 % among culture-positive patients . CONCLUSIONS The presence of cavity on CXR , sputum smear positivity at 2 months of treatment and the number of interruptions of treatment are risk factors for failure . Among failures based on smear examination , the prevalence of MDR-TB is low and many patients have negative cultures for M. tuberculosis . Smear positivity at the end of treatment may not be a reliable indicator of treatment failure BACKGROUND A WHO-recommended 8-month regimen based on ethambutol and isoniazid was evaluated in a r and omised clinical trial against a 6-month st and ard regimen . METHODS 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were r and omly assigned one of three regimens : daily ethambutol , isoniazid , rifampicin , and pyrazinamide for 2 months , followed by ethambutol and isoniazid for 6 months ( 2EHRZ/6HE ) ; the same drugs but given three times weekly in the initial intensive phase ( 2[EHRZ]3/6HE ) ; or the same initial intensive phase as the first regimen , followed by 4 months of daily rifampicin and isoniazid ( 2EHRZ/4HR ) . Follow-up was to 30 months after the start of chemotherapy . Sputum was regularly examined by microscopy and culture . Unfavourable outcome was defined as failure during treatment or relapse afterwards . Analyses were by intention to treat . FINDINGS At 2 months , a significantly higher proportion of patients assigned the daily intensive phase than of those assigned the three-times-weekly regimen were culture negative ( 700/828 [ 85 % ] vs 333/433 [ 77 % ] , p=0.001 ) . 12 months after the end of chemotherapy , the proportions of unfavourable outcomes were 36 of 346 ( 10 % ) with 2EHRZ/6HE , 48 of 351 ( 14 % ) with 2(EHRZ)3/6HE , and 17 of 347 ( 5 % ) with 2EHRZ/4HR . Both 8-month regimens were significantly inferior to the control 6-month st and ard regimen ( difference between control and 2EHRZ/6HE 5.5 % [ 95 % CI 1.6 to 9.4 ] ; between control and 2(EHRZ)3/6HE 8.8 % [ 4.5 to 13.0 ] ) . Adverse effects leading to interruption of treatment for 7 days or longer occurred in 28 patients ( 12 2EHRZ/6HE , five 2[EHRZ]3/6HE , 11 2EHRZ/4HR ) . INTERPRETATION The results of this study must be taken into account in recommendations on management of new cases of smear-positive tuberculosis |
10,940 | 28,878,718 | This is despite the findings from an associated systematic review which concluded that EMDR leads to loss of PTSD diagnosis and symptom reduction .
Depression symptoms were also found to improve more with EMDR than control conditions .
In that review , EMDR was marked down on strength of evidence ( SOE ) for symptom reduction for PTSD .
Secondly , even if the original measure was chosen , we highlight inconsistencies with the way SOE was assessed for EMDR , CT , and CPT .
Including both studies results in st and ard mean difference and confidence intervals that were better for EMDR than for CPT or CT . | null | null |
10,941 | 27,445,838 | The impact of sexual activity before a sport competition is still unclear , but most studies generally seem to exclude a direct impact of sexual activity on athletic aerobic and strength performance .
The most important aspect seems to be the interval from the time of the sports competition that affects negatively the performance if it is shorter than 2 h. There are possible negative effects from some possible concurrent wrong behaviors such as smoking or alcohol abuse .
There are no investigations about the effect of masturbation in this context . | Sexual activity before competition has been considered as a possible cause for reduced performance since ancient Greece and Rome .
Recently , the hypothesis that optimal sport performance could be influenced by a variety of factors including sexual activity before competition has been investigated .
However , few scientific data are available , with the exception of anecdotal reports of individual experiences .
The present systematic review focused on the current scientific evidence on the effects of sexual activity on sport performance regardless of sport type . | OBJECTIVE To use youth and parent demographic factors , youth assets ( strengths ) , and community constructs to develop age-group-specific profiles for youth who abstain from sexual activity . METHODS Data were collected using in-person interviews of youth ( N = 1253 ) residing in r and omly selected , inner-city neighborhood households . Data were analyzed to create classification trees . RESULTS Results indicated that assets typically were the most important factors related to abstinence and that the profiles differed for each age group . CONCLUSIONS When sexual abstinence is considered , the influence of youth and parent demographics , youth assets , and community factors appears to vary across adolescent developmental age periods BACKGROUND The purpose of this study was to investigate the effect of sexual activity on cycle ergometer stress test parameters , on plasmatic testosterone levels and on concentration capacity in high-level male athletes . METHODS Experimental design . Analysis of two days of testing accomplished in a laboratory setting , comparing a day with to a day without sexual activity ( control day ) . Participants . Fifteen high-level male athletes , consisting of 8 team players , 5 endurance athletes and 2 weight-lifters , participated in the study . Measures . Each subject completed the following on each test day : two maximal grade d stress tests on a cycle ergometer and a one-hour exercise stress test coupled to an arithmetic mental concentration test . Blood sample s of testosterone were obtained and cardiac activity of each athlete was monitored with a 24-hour ECG tape recording over the two test days . RESULTS Significantly higher differences were achieved for post-effort heart rate ( HR ) values at 5 minutes ( p<0.01 ) and at 10 minutes ( p<0.01 ) during the recovery phase of the morning stress test 2 hours after sexual activity . These differences disappeared during the recovery phase of the afternoon stress test performed approximately 10 hours after sexual intercourse took place . CONCLUSIONS Our findings show that sexual activity had no detrimental influence on the maximal workload achieved and on the athletes ' mental concentration . However , the higher posteffort HR values after the maximal stress test on the morning of sexual intercourse suggest that the recovery capacity of an athlete could be affected if he had sexual intercourse approximately 2 hours before a competition event It is well known that athletes in the United States are told to abstain from sexual intercourse prior to athletic competition . The rationale for such a policy appears to be related to the hypothesis that sexual intercourse decreases the athletes ' ability to perform efficiently and /or maximally . But the effect that sexual intercourse may have on exercise performance has not been examined widely . Very likely , the restrictions placed on athletes have little to do with the athletes ' physiological ability to substain a particular exercise intensity and /or perform maximally . The purpose of this study was to determine the effects of sexual intercourse 12 hours prior to maximal treadmill exercise on aerobic power , oxygen pulse , and double product ( i.e. , an index of relative cardiac work ) . Eleven male subjects were tested on the treadmill with and without prior sexual intercourse . The results from the maximal exercise tests showed that aerobic power , oxygen pulse , and double product were not different . Therefore , the data suggest that it is justified to dismiss the point of view that sexual intercourse decreases maximal exercise performance |
10,942 | 27,716,496 | Study -specific results suggested that bone-modifying agents reduce the incidence of SREs and bone pain in lung cancer patients .
Data from included trials suggests benefit of bone-targeted agents in lung cancer for the prevention of SREs and bone pain . | BACKGROUND Patients with advanced lung cancer commonly have bone metastases .
Compared with other malignancies , the use of bone-targeted agents ( e.g. bisphosphonates and denosumab ) is less common in lung cancer patients .
This may be due to the perception that bone-targeted agents are less effective in this population .
OBJECTIVE To perform a systematic review to evaluate data from r and omized trials of bone-targeted agents in lung cancer patients with bone metastases . | 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 e18015 Background : Significant advances in the systemic management of metastatic non-small cell lung cancer ( NSCLC ) have occurred over the past decade , with options now including multiple lines of chemotherapy , EGFR inhibitors , and anti-angiogenic agents . Improvements in overall survival have been demonstrated in r and omized controlled trials comparing these newer agents to best supportive care ( BSC ) or st and ard therapy . This study examined uptake of these therapies in general practice and their impact on survival . METHODS This retrospective cohort study compared demographic , treatment and survival data among 987 patients diagnosed with stage IV NSCLC at two institutions in 1998 , 2003 , and 2008 . Cohorts were selected based on intervals when doublet chemotherapy , second line chemotherapy , and targeted agents were incorporated into the st and ard treatment regimen . RESULTS The proportion of patients receiving systemic therapy increased over time ( 20 % in 1998 , 42 % in 2008 ) . Treated patients diagnosed in 2008 were more likely to receive ≥2 lines of systemic therapy ( 60 % vs. 7 % in 1998 ) . Overall survival improved significantly across cohorts ( P < 0.001 ) , with 2 year survival rates of 0.3 % in 1998 , 4 % in 2003 , and 15 % in 2008 . After controlling for other variables , risk of death was diminished by 55 % in patients receiving 1 line of systemic therapy and 72 % in those receiving ≥2 lines , compared with BSC alone . Elderly patients ( age ≥70 years ) were also more likely to receive systemic therapy over time , with improved overall survival ( P < 0.001 ) . CONCLUSIONS Over the past decade , there has been increased use of systemic therapy in stage IV NSCLC patients , including the elderly . This has been associated with significantly improved overall survival Bisphophonates are the treatment of choice to prevent skeletal events in patients with multiple myeloma . Some pre clinical studies suggested that bisphophonates can be useful as antitumor drugs in some malignancies . We conducted a controlled clinical trial to assess if zoledronic acid can have this clinical activity . Ninetyfour patients with previously untreated multiple myeloma were treated with a conventional chemotherapy program : cyclophosphamide , vincristine , melphalan , and prednisone ( CVMP ) and were r and omized to received either zoledronic acid ( 4 mg , iv , every 28 d ) or not ( control group ) . The end-point of the present study was to assess improvement in outcome , measured by event-free survival ( EFS ) and overall survival ( OS ) , and the second-end point was to confirm the efficacy in preventing skeletal events . In an intent-to-treat analysis , all patients were available for efficacy and toxicity . Median follow up was 49.6 mo ( range : 34–72 mo ) . Five year actuarial curves showed that EFS was 80 % in the zoledronic acid group , which was statistically different from 52 % in the control group ( p < 0.01 ) . Actuarial 5 yr OS was 80 % in the zoledronic acid arm , and 46 % in the control group ( p < 0.01 ) . Sketeletal events were more frequent in the control group when compared to zoledronic acid . Toxicity was mild . We confirm the efficacy of zoledronic acid to prevent skeletal events , but we felt that we can demonstrate that zoledronic acid has a clinical antitumor effect measured from a increase in complete response rate and EFS and OS that were better when compared with the control group . We began a controlled clinical trial with modern treatment ( including transplant procedures ) in combination with zoledronic acid to define the role of zoledonic acid in this setting of patients Summary Background Bisphosphonates reduce the risk of skeletal events in patients with malignant bone disease , and zoledronic acid has shown potential anticancer effects in pre clinical and clinical studies . We aim ed to establish whether bisphosphonates can affect clinical outcomes in patients with multiple myeloma . Methods Patients of age 18 years or older with newly diagnosed multiple myeloma were enrolled from 120 centres in the UK . Computer-generated r and omisation sequence was used to allocate patients equally , via an automated telephone service , to receive 4 mg zoledronic acid as an infusion every 3–4 weeks or 1600 mg oral clodronic acid daily . Patients also received intensive or non-intensive induction chemotherapy . No investigators , staff , or patients were masked to treatment allocation , and bisphosphonate and maintenance therapy continued at least until disease progression . The primary endpoints were overall survival , progression-free survival , and overall response rate . We assessed between-group differences with Cox proportional hazards models for progression-free survival and overall survival , and with logistic regression models for overall response rate . Analysis was by intention to treat . This trial is registered , number IS RCT N68454111 . Findings 1970 patients were enrolled between May , 2003 , and November , 2007 , of whom 1960 were eligible for intention-to-treat analysis : 981 in the zoledronic acid group ( 555 on intensive chemotherapy , 426 on non-intensive chemotherapy ) ; and 979 on clodronic acid ( 556 on intensive chemotherapy , 423 on non-intensive chemotherapy ) . The treatment cutoff was Oct 5 , 2009 , with patients receiving bisphosphonates for a median of 350 days ( IQR 137–632 ) before disease progression , with a median of 3·7 years ' follow-up ( IQR 2·9–4·7 ) . Zoledronic acid reduced mortality by 16 % ( 95 % CI 4–26 ) versus clodronic acid ( hazard ratio [ HR ] 0·84 , 95 % CI 0·74–0·96 ; p=0·0118 ) , and extended median overall survival by 5·5 months ( 50·0 months , IQR 21·0 to not reached vs 44·5 months , IQR 16·5 to not reached ; p=0·04 ) . Zoledronic acid also significantly improved progression-free survival by 12 % ( 95 % CI 2–20 ) versus clodronic acid ( HR 0·88 , 95 % CI 0·80–0·98 ; p=0·0179 ) , and increased median progression-free survival by 2·0 months ( 19·5 months , IQR 9·0–38·0 vs 17·5 months , IQR 8·5–34·0 ; p=0·07 ) . Rates of complete , very good partial , or partial response did not differ significantly between the zoledronic acid and clodronic acid groups for patients receiving intensive induction chemotherapy ( 432 patients [ 78 % ] vs 422 [ 76 % ] ; p=0·43 ) or non-intensive induction chemotherapy ( 215 [ 50 % ] vs 195 [ 46 % ] ; p=0·18 ) . Both bisphosphonates were generally well tolerated , with similar occurrence of acute renal failure and treatment-emergent serious adverse events , but zoledronic acid was associated with higher rates of confirmed osteonecrosis of the jaw ( 35 [ 4 % ] ) than was clodronic acid ( 3 [ < 1 % ] ) . Interpretation Consistent with the potential anticancer activity of zoledronic acid , overall survival improved independently of prevention of skeletal-related events , showing that zoledronic acid has treatment benefits beyond bone health . These findings support immediate treatment with zoledronic acid in patients with newly diagnosed multiple myeloma , not only for prevention of skeletal-related events , but also for potential antimyeloma benefits . Funding Medical Research Council ( London , UK ) , with unrestricted educational grants from Novartis , Schering Health Care , Chugai , Pharmion , Celgene , and Ortho Biotech Objective Questions remain regarding the optimal use of bone-targeted agents in patients with metastatic bone disease . The purpose of this study was to assess current clinical practice regarding the use and administration of bone-targeted agents by Canadian oncologists in patients with metastatic breast and prostate cancer . Methods A survey was design ed to explore ; bone-targeted agent use in metastatic bone disease , variability in the choice and the frequency of administration of these agents . Opinions were sought on potential outcomes for future trials . Results A total of 193 clinicians were contacted and 90 completed our survey ( response rate 49 % after adjustment for inactivity ) . Survey respondents were medical oncologists ( 71.1 % ) , radiation oncologists ( 21.1 % ) and urologists ( 7.8 % ) . The findings suggest that once bone-targeted agents are started they are rarely discontinued . More agents are used in breast cancer than in prostate cancer . There was considerable interest in performing studies of de-escalated therapy in both breast and prostate cancer . Physicians requested ( 86 % ) that the primary study endpoint be the occurrence of skeletal related events and not biomarker driven . Conclusions Despite clinical practice guidelines and widespread use , significant areas of clinical equipoise with respect to use of bone-targeted agents exist . Findings from this survey suggest that physicians are interested in de-escalated therapy for both breast and prostate patients . However , the use of multiple agents in breast cancer and the desire for skeletal related events to be the primary endpoint means that very large r and omized studies will be required The aim of this open‐label , multicenter , r and omized phase II trial was to evaluate the efficacy and safety of zoledronic acid in combination with docetaxel in previously treated patients with non‐small‐cell lung cancer ( NSCLC ) and bone metastases . In this study , patients r and omly received docetaxel ( 60 mg/m2 ) with ( group DZ ) or without ( group D ) zoledronic acid every 21 days . There were 50 patients in each group , and the primary endpoint was progression‐free survival . In an efficacy analysis of 94 patients ( DZ , 48 ; D , 46 ) , the median progression‐free survival was 2.7 months ( 95 % confidence interval [ CI ] , 1.5–3.5 months ) for the DZ group and 2.6 months ( 95 % CI , 1.5–3.4 months ) for the D group ( stratified log‐rank test , P = 0.89 ) . The median overall survival was 10.4 months ( 95 % CI , 7.0–15.8 months ) for the DZ group and 9.7 months ( 95 % CI , 6.1–12.5 months ) for the D group ( stratified log‐rank test , P = 0.62 ) . There were no clinical ly relevant differences in the frequencies of grade 3 or 4 adverse events between the two groups . No treatment‐related deaths occurred in the DZ group . Zoledronic acid combined with docetaxel was well tolerated but did not meet the primary endpoint of demonstrating a longer progression‐free survival in advanced NSCLC patients with bone metastases compared with docetaxel alone . This trial was registered with the University Hospital Medical Information Network ( UMIN000001098 ) Men with prostate cancer are at high risk of developing bone metastases that can lead to clinical ly significant skeletal morbidity . Recently , a r and omized , placebo-controlled , phase III trial in 422 men with hormone-refractory prostate cancer and bone metastases demonstrated that zoledronic acid ( 4 mg every 3 weeks ) significantly reduced the incidence and onset of skeletal complications and provided significant long-term reductions in bone pain compared with placebo . Patients received zoledronic acid for a 15-month core phase , with the option to continue therapy for 9 more months on the extension phase . To evaluate the continuing benefit of long-term zoledronic acid therapy , retrospective exploratory analyses were conducted based on the incidence of skeletal-related events ( SREs ; defined as pathologic bone fracture , spinal cord compression , surgery or radiation therapy to bone , or change in antineoplastic therapy for bone pain ) occurring only during the extension phase of this trial . Quality of life parameters included assessment with the Brief Pain Inventory . Similar to results reported for the 15-month core phase and the entire 24-month study , the 9-month extension phase demonstrated that zoledronic acid significantly reduced the percentage of patients with an SRE ( P = 0.017 ) , prolonged the median time to first SRE ( P = 0.036 ) , reduced the annual incidence of SREs by 52 % ( P = 0.016 ) , and reduced the risk of SREs by 53 % ( P = 0.022 ) compared with placebo . Furthermore , zoledronic acid was safe and well tolerated . Therefore , zoledronic acid provides long-term continuing clinical benefit for men with prostate cancer and bone metastases and represents a new therapeutic option for this population PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type |
10,943 | 12,535,396 | The meta-analyses of emotional state show no treatment effects .
REVIEW ER 'S CONCLUSIONS Despite its initial promise , ie the potential neuroprotective properties , and its role in the treatment of Parkinson 's disease sufferers , selegiline for Alzheimer 's disease has proved disappointing .
Although there is no evidence of a significant adverse event profile , there is also no evidence of a clinical ly meaningful benefit for Alzheimer 's disease sufferers .
This is true irrespective of the outcome measure evaluated , ie cognition , emotional state , activities of daily living , and global assessment , whether in the short , or longer term ( up to 69 weeks ) , where this has been assessed .
There would seem to be no justification , therefore , to use it in the treatment of people with Alzheimer 's disease , nor for any further studies of its efficacy in Alzheimer 's disease | BACKGROUND Alzheimer 's disease is the most common cause of dementia in older people accounting for some 60 % of cases with late-onset cognitive deterioration .
It is now thought that several neurotransmitter dysfunctions are involved from an early stage in the pathogenesis of Alzheimer 's disease-associated cognitive decline .
The efficacy of selegiline for symptoms of Alzheimer 's disease remains controversial and is reflected by its low rate of prescription and the lack of approval by several regulatory authorities in Europe and elsewhere .
Reasons for this uncertainty involve the modest overall effects observed in some trials , the lack of benefit observed in several trials , the use of cross-over design s which harbour method ological problems in a disease like dementia and the difficulty in interpreting results from trials when a variety of measurement scales are used to assess outcomes .
OBJECTIVES The objective of this review is to assess whether or not selegiline improves the well-being of patients with Alzheimer 's disease . | Objective . The purpose of this study was to examine the behavioural and cognitive effects of selegiline in a group of moderately behaviourally disturbed AD patients Background : Short-term studies of L-deprenyl in Alzheimer 's disease ( AD ) suggest a beneficial effect , whereas longer-term studies are less convincing . Accordingly , we undertook a 6-month , r and omized , double-blind , placebo-controlled clinical trial to assess the potential benefit of L-deprenyl in AD . Methods : Sixty subjects were assigned to L-deprenyl ( 10 mg daily ) or placebo . After 4 weeks of single-blind placebo , 51 subjects entered the double-blind phase . The Brief Psychiatric Rating Scale ( BPRS ) was the primary outcome measure . Secondary outcome measures were the Mini-Mental State Examination , Global Deterioration Scale , Alzheimer 's Disease Assessment Scale ( noncognitive ) , Cornell Scale for Depression in Dementia , Buschke Selective Reminding Test(BSRT ) , Relative 's Assessment of Global Symptomatology-Elderly ( RAGS-E ) , Controlled Oral Word Association Test , and Modified Continuous Performance Test . In addition , several exploratory tasks were included for future hypothesis testing . Results : We found no significant differences between the L-deprenyl and placebo groups on the primary or secondary measures . However , several measures appeared to be sensitive to change over time , including the total score on the BPRS and some of its components as well as parts of the BSRT and the RAGS-E. Conclusion : Oral L-deprenyl provides no detectable benefit on general behavior , neuropsychiatric symptoms , or cognitive function in AD after 6 months of treatment . Protocol s for future drug studies should utilize measures that are sensitive to change over time such as the BPRS Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer 's disease , there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis . This report focuses on the concept of " combination chemotherapy " in Alzheimer 's disease as the next generation of therapeutic strategies . Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor , 1-deprenyl , the authors speculate that a combination of physostigmine , the short-acting cholinesterase inhibitor , and 1-deprenyl might be more beneficial than either agent alone . The authors outline a sample paradigm for such combination studies , report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl , and point to other possible " combination chemotherapy " strategies for future study In a double blind r and omized crossover trial lasting 6 months selegiline , a selective MAO-B inhibitor , was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia ( DAT ) . Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment , at the time scheduled for crossover ( 90 days ) and at the end of the trial ( 180 days ) . The results suggest that selegiline possesses significant activity on some memory parameters , which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisitionSommarioIn uno studio doppio cieco cross-over , r and omizzato verso placebo della durata di sei mesi , è stata analizzata l'influenza della selegilina , inibitore selettivo delle MAO-B , sulle prestazioni di memoria verbale di 22 pazienti con diagnosi clinica di demenza tipo Alzheimer ( DAT ) . L'esame della memoria verbale è stato effettuato con il Rey-Auditory Verbal Learning test all'inizio del trattamento , dopo 90 giorni , momento previsto per il cross-over , e dopo 180 giorni , al termine della sperimentazione . I risultati suggeriscono una significativa efficacia della selegilina su alcuni parametri di memoria , che sembrano riconducibili ad un miglioramento sia delle capacità di elaborazione delle informazioni , sia delle strategie di apprendimento al momento dell'acquisizione The present study evaluated the safety of and obtained preliminary data on the cognitive effects of L-deprenyl and physostigmine in patients with Alzheimer 's Disease . Seventeen out patients with Alzheimer 's Disease participated in a double-blind crossover study in which they received 4 weeks of L-deprenyl at a dose of 10 mg p.o . , q.d . , and 4 weeks of placebo in r and om order . During both the L-deprenyl and placebo periods , patients received cognitive assessment s during physostigmine ( 0.5 mg ) and placebo infusions separated by 2 days . The cognitive effects of these agents alone and in combination were measured with digit span , verbal fluency , list learning , praxis , delayed recall , and delayed recognition tasks . Fifteen patients completed the study . The two drugs , used alone or in combination , were safe and well tolerated . Analyses of variance demonstrated that neither physostigmine nor L-deprenyl , whether given alone or in combination , significantly improved cognition , when compared with the double placebo condition The efficacy and tolerability of the monoamine oxidase B inhibitor selegiline and of the nootropic agent oxiracetam were compared in a single-blind , controlled , parallel study . The trial involved 22 men and 18 women with mild-to-moderate senile and presenile dementia of the Alzheimer type . The treatments were administered for 90 consecutive days as follows : one 10-mg selegiline tablet once daily and one 800-mg oxiracetam tablet twice daily . Efficacy was evaluated by means of a complex battery of neuropsychological tests , administered monthly for three months , starting from baseline . Safety was evaluated by monitoring adverse drug reactions as well as any pathological changes in hematology , blood chemistry , or liver and kidney function , measured at baseline and again at the conclusion of the study . Analysis of the results demonstrates that , at the dosage used , selegiline is more effective than oxiracetam in improving higher cognitive functions and reducing impairment in daily living . In particular , short- and long-term memory , sustained concentration , attention , verbal fluency , and visuospatial abilities were , for the most part , positively affected by selegiline . Gastroenteric and systemic tolerability of both drugs was also very good Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type , with a mild to moderate cognitive and behavioral impairment , were studied in a double blind design when taking for 60 days 5 mg twice a day of L-deprenyl or placebo . Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory , attention , and language efficiency measures and by SPECT-99TcHMPAO procedure . Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency . At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF , while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF BACKGROUND There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer 's disease . METHODS We conducted a double-blind , placebo-controlled , r and omized , multicenter trial in patients with Alzheimer 's disease of moderate severity . A total of 341 patients received the selective monoamine oxidase inhibitor selegiline ( 10 mg a day ) , alpha-tocopherol ( vitamin E , 2000 IU a day ) , both selegiline and alpha-tocopherol , or placebo for two years . The primary outcome was the time to the occurrence of any of the following : death , institutionalization , loss of the ability to perform basic activities of daily living , or severe dementia ( defined as a Clinical Dementia Rating of 3 ) . RESULTS Despite r and om assignment , the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups , and this variable was highly predictive of the primary outcome ( P<0.001 ) . In the unadjusted analyses , there was no statistically significant difference in the outcomes among the four groups . In analyses that included the base-line score on the Mini-Mental State Examination as a covariate , there were significant delays in the time to the primary outcome for the patients treated with selegiline ( median time , 655 days ; P=0.012 ) , alpha-tocopherol ( 670 days , P=0.001 ) or combination therapy ( 585 days , P=0.049 ) , as compared with the placebo group ( 440 days ) . CONCLUSIONS In patients with moderately severe impairment from Alzheimer 's disease , treatment with selegiline or alpha-tocopherol slows the progression of disease The potential efficacy of oral l-deprenyl ( 5 mg b.i.d . ) added to the regimen of 10 patients with Alzheimer 's disease receiving either tacrine or physostigmine was assessed in a double-blind , placebo-controlled , 4-week , two-period crossover pilot study . l-Deprenyl was associated with significant improvement in scores on the cognitive subscale of the Alzheimer 's Disease Assessment Scale , suggesting possible additive effects of l-deprenyl to the effects of cholinesterase inhibitors Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration BACKGROUND Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer 's disease that does not cause significant patient sedation . Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens . The purpose of this study was to document the efficacy of selegiline in Alzheimer 's patients with behavior problems . METHOD Eight Alzheimer 's patients ( 6 women and 2 men ) ranging in age from 50 to 82 years ( mean + /- SD = 74.0 + /- 10.5 ) were enrolled in this single-blind study . Patients received selegiline 10 mg each day for 8 weeks . Prior to drug administration and at the end of Weeks 1 , 2 , 4 , 6 , and 8 , patients were evaluated for behavior ( BEHAVEAD ) , cognitive function ( Mini-Mental State Examination ) , and caregiver stress ( Caregiver Burden Scale ) . RESULTS Of eight enrolled patients , five were available for analysis . No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests . However , clinical significance was noted by improvement in cognition ( orientation and recall ) , caregiver stress , and behavior . Behavior was noted to improve in the areas of paranoid and delusional ideation , hallucinations , activity disturbances , anxiety , and phobias . CONCLUSION These data suggest that some Alzheimer 's patients with behavior problems may benefit from selegiline therapy This report describes the rationale and design of a clinical trial using selegiline ( 10 mg/day ) and alpha-tocopherol ( 2,000 IU/day ) to slow the progression of dementia in Alzheimer disease ( AD ) . This study was developed by the Alzheimer 's Disease Cooperative Study ( ADCS ) , a consortium of clinical research centers actively involved in AD research . The major goal of the consortium is to design and conduct clinical investigations leading to the development of treatments for AD . This study uses a r and omized double-blind , placebo-controlled , 2 x 2 factorial , parallel group design to test two drugs for the treatment of AD . The primary outcome of the study is the time to reach any one of the following four endpoints : death , institutionalization , loss of two of three basic activities of daily living , and progression of Clinical Dementia Rating ( CDR ) stage from 2 to 3 . Patients with moderately severe disease ( CDR = 2 ) were enrolled and evaluated 10 times over a period of 2 years to determine if these agents reduce the time to reach any endpoint . A data base from the Consortium to Establish a Registry for Alzheimer 's Disease indicated adequate power analyses to observe a treatment effect on this clinical ly meaningful outcome measure . Recruitment and baseline characteristics of the population are provided . The rationale for the choice of a factorial design , the use of a novel , clinical ly meaningful endpoint , and the selection of a cohort of patients with AD of moderate severity are discussed The authors have previously reported mild improvement of behavior and cognition in a group of 17 nondepressed patients with dementia of the Alzheimer type ( DAT ) treated with two doses of L-deprenyl ( 10 and 40 mg/day ) . Seven of these patients subsequently received double-blind , placebo-controlled treatment with tranylcypromine . The patients experienced significant side effects , particularly orthostatic hypotension without compensatory pulse increase , during tranylcypromine treatment . These effects were more severe than those occurring during L-deprenyl treatment , and they occurred at substantially lower doses ( mean dose , 16 mg/day ) . These data support the role of the inhibition of monoamine oxidase type A in the development of orthostatic hypotension in patients treated with monoamine oxidase inhibitors . They also raise the question of whether the observed sensitivity to monoamine oxidase inhibition is a function of age or disease . In either case , the greater toxicity of tranylcypromine makes inferences difficult regarding the relative efficacies of these drugs in treating patients with dementia of the Alzheimer type and may limit the potential usefulness of tranylcypromine in ameliorating some symptoms of this disease BACKGROUND While cognitive and functional deficits are the hallmark of Alzheimer 's disease ( AD ) , loss of social function ( and the dependence this implies ) is also critical , especially in early stages of disease . Little attention has been directed to this facet of dementing disease . We describe a scale for assessing dependency in AD and present a baseline profile of dependency in a cohort of AD patients . METHODS In a study of the predictors of the course of AD , 233 patients in early stages of disease ( modified MMS > or = 30 ) were assessed . Psychometric properties of the dependence scale were established . To vali date the scale , dependence scores at baseline were correlated with a series of measures assessing cognition and function . The course of dependency over 18 months of follow-up was also analyzed . RESULTS The scale shows adequate reliability ( test-retest , intraclass correlation ) . Dependence stage was related to other measures of disease severity . Scalogram analysis shows that the dependence scale is consistent with the course of functional loss established for dementing disease . Prospect i ve data indicate sensitivity of the scale to disease progression . CONCLUSION Dependency is a distinct , measurable component of dementing disease and should be considered an important outcome in studies of AD Abstract Background : A beneficial effect of selegiline ( l-deprenyl ) in Alzheimer 's disease ( AD ) has been reported in several clinical studies . Methods : The brain tissue from 17 deceased patients , members of a double-blind clinical trial to assess the potential benefit of selegiline in AD , were analysed . Findings : In our study , the decrease in the Mini-Mental State Examination ( MMSE ) scores during the progress of the disease had been significantly influenced by selegiline treatment . Prior to death , the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo . However , according to our results , none of the lesions critical for AD diagnosis , such as counts of senile/neuritic plaques , neurofibrillary tangles or β-A4 load , were influenced by the selegiline treatment . Interpretation : In conclusion , according to our study , mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment , leading to the functional benefit found in AD The purpose of this pilot study was to evaluate the usefulness of the Assessment of Motor and Process Skills ( AMPS ) as an outcome measure of instrumental activities of daily living ( IADL ) in pharmacologic studies of people with Alzheimer 's disease . The AMPS simultaneously measures motor and process skills and their effect on the ability of the person to perform familiar IADL tasks . We administered the AMPS to 11 Alzheimer in patients in a 3 1/2-month , double-blind , placebo-controlled , crossover study of fluoxetine and selegiline administered as single agents and in combination with physostigmine . Results indicated that there was a significant difference in IADL ability among study conditions for process skills , but not for motor skills , thereby suggesting that the AMPS is useful as a sensitive outcome measure of IADL ability in drug trials with this population Forty elderly patients ( 13 men and 27 women , aged 56 to 80 years ) were enrolled in a single-blind , r and omized , parallel study to assess the efficacy and safety of selegiline ( 10 mg , once daily ) and that of L-acetylcarnitine ( 500 mg , twice daily ) in the treatment of patients with mild-to-moderate Alzheimer-type disorders . The treatments lasted 90 days , after a run-in period of 15 days . An extensive psychometric examination , carried out at baseline and subsequently at every 30 days of treatment , was used for evaluation of efficacy . Drug safety was assessed by noting any adverse effects that occurred during treatment and by performing laboratory tests at the beginning and end of treatment . According to the result ing data , selegiline therapy led to a global improvement in the capacity for the processing , storage , and retrieval of given information . Improvements in verbal fluency and visuospatial abilities were also noted . The marked between-group differences demonstrate that , at the dosage used , selegiline was far more effective than L-acetylcarnitine with respect to the degree of improvement . Finally , tolerability of both drugs was excellent , inasmuch as neither the monitoring for adverse drug reactions nor laboratory tests revealed any abnormalities result ing from therapy Monoamine neurotransmitter systems , along with cholinergic systems , are known to play important roles in cognition , and are disrupted in at least some patients with dementia of the Alzheimer type ( DAT ) . This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT . l-Deprenyl is a monoamine oxidase ( MAO ) inhibitor which may selectively inhibit MAO-B at low doses , while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT . Two doses of l-deprenyl ( 10 mg/day and 40 mg/day ) and placebo were compared in a double-blind , serial treatment design . Episodic learning and memory , knowledge memory , attention , recognition , and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions . Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with l-deprenyl 10 mg/day . Knowledge memory , intrusions , and other cognitive functions relevant to DAT were not altered by l-deprenyl at either dose As a follow-up to an earlier study showing short-term benefit in in patients with more severe dementia , the authors studied the short-term cognitive , functional , and behavioral effects of selegiline in out patients with mild-to-moderate dementia of the Alzheimer type ( DAT ) by means of a double-blind , r and omized , crossover study of placebo vs. selegiline . Fifty out patients with mild-to-moderate DAT and no behavioral disturbances were given selegiline in two 8-week treatment periods separated by a 4-week washout . Outcome was assessed with st and ardized measures of dementia severity , daily functioning , behavior , and cognition . There was no drug-placebo difference in any outcome measure . Selegiline did not show short-term benefit in this study , contrary to the earlier study , perhaps because the patients were studied less intensively and /or lacked behavioral problems that could show response , although the medication was well tolerated OBJECTIVE To examine the short-term cognitive and behavioral effects of L-deprenyl in persons with mild dementia of the Alzheimer type ( DAT ) over a 2-month period . DESIGN A 15-month r and omized , double-blind , placebo-controlled trial using a parallel-group design . This report deals with the first 2 months of the trial . PARTICIPANTS 39 subjects with mild DAT ( CDR 1 ) selected using NINCDS-ADRDA criteria . MEASURES A battery of neuropsychological tests and clinical rating scales . RESULTS The placebo and L-deprenyl subjects were similar at baseline on the clinical and neuropsychological tests . There was no evidence of a L-deprenyl effect on any clinical or neuropsychological measures after 2 months . CONCLUSION L-deprenyl did not have a measurable impact on behavior or cognitive function over a 2-month period in this group of subjects with mild DAT The monoaminergic neurotransmission defect seen in dementia of the Alzheimer type ( DAT ) is linked to a known increased activity of type B cerebral monoamine oxidases ( MAO-Bs ) . The use of drugs that are able to block this abnormal activity could therefore be useful in the treatment of some cognitive deficits that characterize DAT . Twenty patients with a clinical diagnosis of DAT and with a slight-moderate mental deterioration were treated with 10 mg/day of L-deprenyl , a selective MAO-B inhibitor , according to a double-blind crossover design vs. placebo . Initial treatment ( drug or placebo ) was r and omly assigned . The patients ' cognitive functions were evaluated at baseline and then after 3 and 6 months of treatment with drug or placebo . The patients crossed over treatment after 3 months , without a washout interval . The results of the study show the higher and statistically significant effects of L-deprenyl on memory and attention that seem to be due to an improved function of the monoaminergic systems involved in the process of neuronal degeneration OBJECTIVE To evaluate the efficacy and adverse effects of the type B monoamine oxidase inhibitor selegiline ( also known as I-deprenyl ) in the treatment of Alzheimer 's disease . DESIGN Long-term , double-blind , placebo-controlled trial . SETTING Seven cities ( 1 or 2 nursing homes in each city ) in the Czech and Slovak Republics . PATIENTS A total of 173 nursing-home residents fulfilling the DSM-III criteria for mild to moderate Alzheimer 's disease . INTERVENTIONS Selegiline ( 10 mg per day ) or placebo ( both including 50 mg ascorbic acid ) administered for 24 weeks . OUTCOME MEASURES Clinical Global Impressions scale and Nurses Observation Scale for Inpatient Evaluation at baseline and at weeks 6 , 12 and 24 ; Clock Drawing Test at baseline and 24 weeks , results of which were evaluated as normal or pathologic , and quantitatively on a modified 6-point scale ; Sternberg 's Memory Scanning test at baseline and at weeks 6 , 12 and 24 ; Mini Mental State Examination , and electroencephalogram at baseline and 24 weeks ; Structured Adverse Effects Rating Scale ; physical , laboratory , hematological and electrocardiographic examinations at baseline and weeks 12 and 24 . RESULTS A total of 143 subjects completed enough of the trial to be entered in the analysis . Subjects were analyzed by 2 subgroups depending on whether they had a normal or pathologic result of the Clock Drawing Test . Analysis of variance showed significant improvement with selegiline versus placebo among those with a normal result of the Clock Drawing Test on the Mini Mental Status Examination ( total score and orientation-place subscale ) and among those with a pathologic result of the Clock Drawing Test of Sternberg 's Memory Scanning test ( for both speed and accuracy ) , on the Clinical Global Impressions scale as well as in terms of the dominant frequency on electroencephalograms . CONCLUSION Selegiline has a long-term beneficial effect in Alzheimer 's disease on memory modalities that reflect the function of the prefrontal areas of the brain , which are rich in dopamine receptors . The delayed appearance of differences between selegiline and placebo supports the notion that the mechanism of action is through neuronal rescue or neuroprotection . The differential response of patients with normal and pathologic results of the Clock Drawing Test may reflect the fact that the evaluation methods ' sensitivity to change depends on the severity of dementia Selegiline , an inhibitor of monoamine oxidase B , was tested on patients with mild to moderate dementia of the Alzheimer type . Its efficacy and tolerability were compared with that of phosphatidylserine in a r and omized , single-blind , parallel fashion . Forty patients ( 24 men and 16 women ) entered the trial . Selegiline was administered in 10-mg tablets once daily and phosphatidylserine in 100-mg capsules twice daily , both treatments lasting three months . Drug efficacy was assessed at baseline and then each month by means of an extensive battery of neuropsychological tests . The assessment of drug safety was based on monitoring for adverse drug reactions and on routine laboratory tests performed before and after treatment . At the end of the study the selegiline group showed improvements statistically significantly superior to those obtained in the phosphatidylserine group on most of the cognitive areas examined . Furthermore , of particular interest was the discovery , found only in the selegiline group , of an increased degree of autonomy in day-to-day activities . Tolerability was good , the only side effect reported in both groups being slight or moderate nausea , which was severe enough to warrant withdrawal from treatment only in one case , a patient in the selegiline group with a history of gastroduodenitis The early follow-up of patients treated by simple mastectomy alone or simple mastectomy combined with radical radiotherapy is presented . Both groups were well matched for age , menopausal status , duration of symptoms , size of tumour , and lymph-node involvement . There was no significant difference in survival of patients in the two groups at three years , but local recurrence was significantly more frequent ( 28 % ) in the mastectomy-alone patients . Early survival was not adversely affected by radiotherapy Altered monoaminergic neurotransmission could play an important role in the cognitive dysfunctions typical of dementia of the Alzheimer type ( DAT ) . DAT is not , however , a homogenous phenomenon inasmuch as two forms are distinguishable : early onset ( EO ) and late onset ( LO ) . Moreover , focal patterns of neuropsychological deterioration fall into various subgroups . According to our hypothesis , DAT patients , who at the onset of the disease mainly manifest memory disorders , also represent a specific subgroup characterized by impaired cortically projecting catecholaminergic pathways . In a 6-month r and omized , double-blind , cross-over study versus placebo we analysed the influence of L-deprenyl on the verbal memory of 19 amnesic EO-DAT patients . Verbal memory was assessed by means of the Rey Auditory Verbal Learning Test . The results obtained show significantly better performances for L-deprenyl treated patients in learning and long-term memory skills . We suggest that L-deprenyl , through selective inhibition of MAO-B and by increasing the activity of the catecholaminergic systems , positively influences cognitive functions and behaviour founded on memory efficiency 119 patients were enrolled in a double-blind r and omized parallel study versus placebo carried out to assess both the efficacy and tolerability of L-deprenyl ( 10 mg/day ) for treatment of patients with organic mental disorders of the Alzheimer type ( DAT ) . The treatments were given for 3 months , starting after a run-in period of 15 days to evaluate efficacy . A complete neuropsychological battery was administered monthly after the start of treatment whereas tolerability was assessed by checking , recording and classifying all the unfavorable experiences occurring . According to the results , L-deprenyl would seem to be a useful and reliable tool for the treatment of DAT patients in an attempt to improve their cognitive functions and reduce behavioral alterations , without frequent or severe side effects |
10,944 | 17,880,013 | The majority of studies noted greater in-hospital mortality in women than in men , with mortality differences resolving with longer follow-up .
Early mortality differences were reduced but not consistently eliminated after adjustment for comorbidities , procedural characteristics , and body habitus .
Gender was an independent risk factor for complications after both CABG and PCI .
Women experience greater complications and early mortality after revascularization . | Gender differences exist in outcomes , particularly early mortality , for percutaneous interventions ( PCI ) and coronary artery bypass graft surgery ( CABG ) .
Better underst and ing of this issue may target areas for improvement for all patients undergoing revascularization .
Therefore , we summarized the evidence on gender differences in PCI and CABG outcomes , particularly early mortality , and mediators of this difference . | BACKGROUND Numerous studies have shown that women undergoing coronary revascularization procedures do so at a higher risk for an adverse outcome compared with men . However , the impact of advances in technology and improvements in techniques on in-hospital and long-term outcome after revascularization in women is unclear . METHODS AND RESULTS We evaluated 1829 patients with symptomatic multivessel coronary disease r and omized to CABG or PTCA in the Bypass Angioplasty Revascularization Investigation ( BARI ) , of whom 27 % were women . As expected , women were older ( 64.0 versus 60.5 years ) , with more congestive heart failure ( 14 % versus 7 % ) , hypertension ( 68 % versus 42 % ) , treated diabetes mellitus ( 31 % versus 15 % ) , and unstable angina ( 67 % versus 61 % ) than men but had similar preservation of left ventricular function and extent of multivessel disease . Women assigned to surgery received the same number of total grafts but fewer internal mammary artery grafts ( 72 % versus 85 % , P<0 . 01 ) , and those assigned to angioplasty had more intended lesions ( 76 % versus 71 % , P<0.01 ) successfully dilated than men . At an average of 5.4 years ' follow-up , crude mortality rates were similar in women ( 12.8 % ) and men ( 12.0 % ) . The Cox regression model adjusting for baseline differences revealed that women had a significantly lower risk of death ( relative risk , 0.60 ; 95 % CI , 0.43 to 0.84 ; P=0 . 003 ) but not a significantly lower risk of death plus myocardial infa rct ion ( relative risk , 0.84 ; 95 % CI , 0.66 to 1.07 ; P=0.16 ) than men . CONCLUSIONS Although the unadjusted mortality rate suggests that women and men undergoing CABG and PTCA have a similar 5-year mortality , women have higher risk profiles ; consequently , contrary to previous reports , female sex is an independent predictor of improved 5-year survival after we control for multiple risk factors BACKGROUND Blockade of the platelet glycoprotein IIb/IIIa receptor with abciximab ( a monoclonal-antibody Fab fragment directed against the receptor ) has been shown to diminish ischemic complications among patients undergoing high-risk coronary angioplasty or directional atherectomy but increases bleeding complications . The widespread applicability of this treatment is unknown , particularly in view of the observed risk of hemorrhage . METHODS In a prospect i ve , double-blind trial , we r and omly assigned patients undergoing urgent or elective percutaneous coronary revascularization at 69 centers to receive abciximab with st and ard-dose , weight-adjusted heparin ( initial bolus of 100 U per kilogram of body weight ) ; abciximab with low-dose , weight-adjusted heparin ( initial bolus of 70 U per kilogram ) ; or placebo with st and ard-dose , weight-adjusted heparin . The primary efficacy end point was death from any cause , myocardial infa rct ion , or urgent revascularization within 30 days of r and omization . RESULTS The trial was terminated at the first interim analysis , with 2792 of the planned 4800 patients enrolled . At 30 days , the composite event rate was 11.7 percent in the group assigned to placebo with st and ard-dose heparin ; 5.2 percent in the group assigned to abciximab with low-dose heparin ( hazard ratio , 0.43 ; 95 percent confidence interval , 0.30 to 0.60 ; P<0.001 ) ; and 5.4 percent in the group assigned to abciximab with st and ard-dose heparin ( hazard ratio , 0.45 ; 95 percent confidence interval , 0.32 to 0.63 ; P<0.001 ) . There were no significant differences among the groups in the risk of major bleeding , although minor bleeding was more frequent among patients receiving abciximab with st and ard-dose heparin . CONCLUSIONS Inhibition of the platelet glycoprotein IIb/IIIa receptor with abciximab , together with low-dose , weight-adjusted heparin , markedly reduces the risk of acute ischemic complications in patients undergoing percutaneous coronary revascularization , without increasing the risk of hemorrhage OBJECTIVE The quality of target vessels may affect gender differences in outcome after coronary artery bypass grafting . This prospect i ve study compares preoperative angiographic assessment of vessel quality with intraoperative visual assessment of size and presence or absence of diffuse disease . The effect of vessel quality on operative mortality and late survival is examined . METHODS Data were prospect ively collected on 1939 consecutive patients undergoing isolated coronary artery bypass grafting by a single surgeon . Quality of target vessels was assessed preoperatively ( angiogram ) and intraoperatively by inspection and probe calibration . RESULTS Vessels were poorly visualized in 29 % of female patients and 37 % of male patients ( P = .004 ) , although all but 1.6 % of target vessels were grafted . Women were no more likely than men to have small vessels ( < 1.5 mm ) ( 57 % vs 59 % , P = .449 ) and were less likely to have distal disease ( 45 % vs 53 % , P = .005 ) . Operative mortality was low , not statistically different in women versus men ( 1.3 % vs 0.7 % , P = .237 ) , and increased in patients with distal disease ( 1.3 % vs.03 % , P = .021 ) . Late survival was decreased in patients with poor left ventricle function , congestive heart failure , and peripheral vascular disease . Late survival was decreased in men with increased age , class IV symptoms , small size , and no left internal thoracic artery graft , and in women with recent myocardial infa rct ion and preoperative cerebrovascular accident . CONCLUSION We conclude that in most patients with poorly visualized vessels in the preoperative angiogram , complete revascularization can be achieved if one is willing to graft small or diffusely diseased vessels . Women are no more likely than men to have vessels less than 1.5 mm in size and are less likely to have diffuse disease . Such an approach is associated with a low operative mortality and good long-term survival . Predictors of late survival were different for men and women . Neither small vessel size nor diffuse disease was an independent predictors of poor late outcome Background —Women with acute myocardial infa rct ion ( AMI ) undergoing primary angioplasty have higher rates of morbidity and mortality than do men . Whether contemporary interventional treatment strategies have improved outcomes for women compared with men is unknown . Methods and Results —In the CADILLAC trial , 2082 patients ( 27 % women ) with AMI within 12 hours of symptom onset were r and omized to balloon angioplasty ( PTCA ; n=518 ) , PTCA+abciximab ( n=528 ) , stenting ( n=512 ) , and stenting+abciximab ( n=524 ) . As compared with men , women had a lower body surface area ; had a greater prevalence of diabetes , hypertension , and hyperlipidemia ; experienced significant delays to treatment ; and had better baseline and final TIMI grade 3 flows . Unadjusted 1-year event rates were higher for women , including death ( 7.6 % versus 3.0 % , P<0.001 ) , ischemic target-vessel revascularization ( TVR ; 16.7 % versus 12.1 % , P=0.006 ) , and major adverse cardiac events ( MACE ; 23.9 % versus 15.3 % , P<0.001 ) . Female gender was an independent predictor of MACE and bleeding complications , although comorbid risk factors and body surface area but not gender predicted 1-year death . For women , primary stenting result ed in a reduction in 1-year MACE from 28.1 % to 19.1 % ( P=0.01 ) and in ischemic TVR from 20.4 % to 10.8 % ( P=0.002 ) compared with PTCA . The addition of abciximab to primary stenting significantly reduced the 30-day ischemic TVR without increasing bleeding or stroke rates . Conclusions —The higher mortality rate in women compared with men after interventional treatment for AMI may be explained by differences in body size and clinical risk factors , although female gender remains an important independent determinant of overall adverse outcomes . For women in the CADILLAC trial , the addition of abciximab reduced 30-day TVR without increasing bleeding risk , and primary stenting reduced 1-year TVR and MACE rates compared with PTCA Background —Although most r and omized clinical trials have suggested that long-term survival rates after percutaneous coronary intervention ( PCI ) or surgical multivessel coronary revascularization ( CABG ) are equivalent , some post hoc analyses in high-risk groups and adjustment for severity of coronary disease have suggested higher mortality after PCI . Methods and Results —We studied 6033 consecutive patients who underwent revascularization in the late 1990s . PCI was performed in 872 patients ; 5161 underwent CABG . Half the patients had significant left ventricular dysfunction or diabetes . Propensity analysis to predict the probability of undergoing PCI according to 22 variables and their interactions was used . The C-statistic for this model was 0.90 , indicating excellent discrimination between treatments . There were 931 deaths during 5 years of follow-up . The 1- and 5-year unadjusted mortality rates were 5 % and 16 % for PCI and 4 % and 14 % for CABG ( unadjusted hazard ratio , 1.13 ; 95 % CI , 1.0 to 1.4 ; P = 0.07 ) . PCI was associated with an increased risk of death ( propensity-adjusted hazard ratio , 2.3 ; 95 % CI , 1.9 to 2.9 ; P < 0.0001 ) . This difference was observed across all categories of propensity for PCI and in patients with diabetes or left ventricular dysfunction . Other independent predictors of mortality ( P ≤0.01 for all ) were renal dysfunction , age , diabetes mellitus , chronic lung disease , peripheral vascular disease , left main trunk stenosis , and extent of coronary disease ( Duke angiographic score ) . Conclusions —In patients with multivessel coronary artery disease and many high-risk characteristics , CABG was associated with better survival than PCI after adjustment for risk profile Background —The effectiveness of sirolimus-eluting stents in unselected patients treated in the daily practice is currently unknown . Methods and Results —Sirolimus-eluting stent implantation has been used as the default strategy for all percutaneous procedures in our hospital as part of the R apamycin-E luting S tent E valuated A t R otterdam C ardiology H ospital ( RESEARCH ) registry . Consecutive patients with de novo lesions ( n=508 ) treated exclusively with sirolimus-eluting stents ( SES group ) were compared with 450 patients who received bare stents in the period just before ( pre-SES group ) . Patients in the SES group more frequently had multivessel disease , more type C lesions , received more stents , and had more bifurcation stenting . At 1 year , the cumulative rate of major adverse cardiac events ( death , myocardial infa rct ion , or target vessel revascularization ) was 9.7 % in the SES group and 14.8 % in the pre-SES group ( hazard ratio [ HR ] , 0.62 [ 95 % CI , 0.44 to 0.89 ] ; P = 0.008 ) . The 1-year risk of clinical ly driven target vessel revascularization in the SES group and in the pre-SES group was 3.7 % versus 10.9 % , respectively ( HR , 0.35 [ 95 % CI , 0.21 to 0.57 ] ; P < 0.001 ) . Conclusions —Unrestricted utilization of sirolimus-eluting stents in the “ real world ” is safe and effective in reducing both repeat revascularization and major adverse cardiac events at 1 year compared with bare stent implantation BACKGROUND Coronary artery diameter is known to be inversely associated with perioperative mortality related to coronary artery bypass grafting ( CABG ) . This association is believed to be responsible for increased risk among women and smaller people . However , the associations between sex , body size , and coronary size have not been carefully examined because direct information about coronary size is rarely available . Also , whether sex has an independent effect on vessel size is largely unknown . METHODS AND RESULTS Height , weight , sex , age , status at hospital discharge , and luminal diameter of the midleft anterior descending coronary artery ( mid-LAD ) were recorded prospect ively in 1325 patients undergoing CABG . Small vessel size was associated with substantially increased risk of in-hospital mortality ( 15.8 % for 1.0-mm vessels , 4.6 % for 1.5- to 2.0-mm vessels , and 1.5 % for 2.5- to 3.5-mm vessels , P[trend ] < .001 ) . Vessel size was strongly related to both sex and measures of body size . In multiple linear regression analysis , vessel size was positively correlated with body surface area ( P[trend ] < .01 ) , body mass index ( P[trend ] = .004 ) , height ( P[trend ] = .001 ) , and weight ( P[trend ] = .001 ) . After controlling for differences in age and body size , sex remained an important predictor of coronary size . Within each quartile of each body-size measure , mid-LAD diameter in men was greater than that in women ( mean difference [ range ] , 0.14 to 0.23 mm ) . CONCLUSIONS Small mid-LAD diameter is associated with substantially increased risk of in-hospital mortality with CABG . Although body size is correlated with mid-LAD diameter , women have smaller coronary arteries than men after controlling for differences in body size . These findings further support the hypothesis that smaller coronary arteries explain higher perioperative mortality with CABG in women and smaller people BACKGROUND We prospect ively assess if there are any outcome differences between men and women undergoing coronary artery bypass graft surgery . STUDY DESIGN This is an eight-year , prospect i ve , hospitalization cohort study . Data were collected on 225 variables concurrently with admission . The main outcome was mortality . In addition , we evaluated 12 morbidity outcomes . To minimize confounding , we controlled for 18 other variables . RESULTS We analyzed 5,324 patients ( 1,742 women ; 3,582 men ) . Women were significantly older , with more African Americans and more Medicaid-insured ( p < 0.05 ) . Men had significantly higher body surface area , creatinine , tobacco history , prior myocardial infa rct ions , left ventricular hypertrophy , and cardiac pump time ( p < 0.05 ) . Women had significantly more diabetes , hypercholesterolemia , hypertension , previous cerebrovascular disease , urgency of the surgical procedure , fewer arterial grafts , and reduced functional capacity by the New York Heart Association classification ( p < 0.05 ) . Using multiple regression analysis there was no difference for mortality , positive bacterial cultures , ICU length of stay , arrhythmias , reoperation for bleeding , pulmonary complications , gastrointestinal complications , and return to the ICU . Women had significantly more intraoperative complications ( RR = 2.09 , 95 % CI 1.35 - 3.23 ) , length of stay ( RR = 1.01 , 95 % CI 1.002 - 1.027 ) , and low cardiac output conditions ( RR = 1.10 , 95 % CI 1.01 - 1.20 ) . Males developed more neurologic complications ( RR = 0.85 , 95 % CI 0.75 - 0.95 ) . CONCLUSIONS Women undergoing coronary artery bypass graft surgery have more comorbidities at surgical presentation compared with men . Women have more unadjusted mortality , which is confounded by the difference in age and body surface area . But , even after multiple adjustments , female gender is a predictor of higher morbidity in patients undergoing coronary artery bypass graft OBJECTIVES A simple risk score on admission to estimate the likelihood of in-hospital coronary artery bypass graft surgery ( CABG ) might be useful in selecting patients for early clopidogrel therapy . BACKGROUND Routine early use of clopidogrel in patients with unstable angina ( UA ) and non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) is associated with increased risk of bleeding in patients who undergo early CABG . METHODS The test cohort utilized to derive the score was the 2,220 patients with UA/NSTEMI enrolled in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy -Thrombolysis in Myocardial Infa rct ion-18 ( TACTICS-TIMI-18 ) trial . Patients who underwent CABG after r and omization during index hospitalization were identified and were compared with patients who did not undergo in-hospital CABG . RESULTS Overall , 362 patients ( 16.3 % ) underwent CABG during the index hospitalization . Patients with a history of prior CABG ( n = 484 ) were significantly less likely to undergo in-hospital CABG ( odds ratio [ OR ] , 0.34 ) . Five additional variables independently associated with CABG were identified : elevated troponin ( OR , 3.9 ) , prior stable angina ( OR , 1.8 ) , ST-segment deviation > or=0.5 mm ( OR , 1.7 ) , male gender ( OR , 1.6 ) , and history of peripheral arterial disease ( OR , 1.6 ) . A CABG risk score was generated by assigning numerical values to each of the variables based upon these odds ratios . Coronary artery bypass surgery rates increased significantly with increasing risk scores ( 6.2 % for a risk score < 3.0 , 21.9 % for 3 to 5 , and 54.6 % for > 5.0 ) . The association of the risk score with CABG was highly significant ( p < 0.0001 , c-statistic 0.72 ) . The association remained significant in the validation cohorts from TIMI-11B trial and TIMI-III registry . CONCLUSIONS Among patients with UA/NSTEMI , a novel risk score based on admission clinical variables can be used to estimate the likelihood of CABG . These data may assist in the identification of patients who might derive optimal benefit from early initiation of clopidogrel therapy BACKGROUND In the setting of percutaneous coronary revascularization , agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infa rct ion at 30 days . We assessed whether there are differences in safety or efficacy between two such inhibitors , tirofiban and abciximab . METHODS Using a double-blind , double-dummy design at 149 hospitals in 18 countries , we r and omly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting . The primary end point was a composite of death , nonfatal myocardial infa rct ion , or urgent target-vessel revascularization at 30 days . The trial was design ed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab . RESULTS The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group ( 7.6 percent vs. 6.0 percent ; hazard ratio , 1.26 ; one-sided 95 percent confidence interval of 1.51 , demonstrating lack of equivalence , and two-sided 95 percent confidence interval of 1.01 to 1.57 , demonstrating the superiority of abciximab over tirofiban ; P=0.038 ) . The magnitude and the direction of the effect were similar for each component of the composite end point ( hazard ratio for death , 1.21 ; hazard ratio for myocardial infa rct ion , 1.27 ; and hazard ratio for urgent target-vessel revascularization , 1.26 ) , and the difference in the incidence of myocardial infa rct ion between the tirofiban group and the abciximab group was significant ( 6.9 percent and 5.4 percent , respectively ; P=0.04 ) . The relative benefit of abciximab was consistent regardless of age , sex , the presence or absence of diabetes , or the presence or absence of pretreatment with clopidogrel . There were no significant differences in the rates of major bleeding complications or transfusions , but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia . CONCLUSIONS Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab , the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab Background There is uncertainty as to the relative efficacy of coronary artery bypass graft surgery ( CABG ) in men and women . Differences between sexes may be of greater importance than heretofore because of increased frequency of risk factors for adverse outcome . It is the purpose of this study to examine the changing clinical characteristics of patients undergoing CABG and to determine the influence of these changes on the results of CABG in men and in women . Methods and Results The source of data was the clinical data base at Emory University Hospitals . The population comprised 13 368 patients ( 2648 women , 10 720 men ) who had cardiac catheterization followed by CABG between 1974 and 1991 . The patients were divided into the time periods 1974 through 1979 ( 532 women , 2792 men ) , 1980 through 1983 ( 727 women , 3151 men ) , 1984 through 1987 ( 695 women , 2619 men ) , and 1988 through 1991 ( 694 women , 2158 men ) . Data were collected prospect ively and entered into a computerized data base . The women were older ( 63±10 versus 58±10 years , P<.0001 ) and more frequently had diabetes ( 26.0%1 versus 15.4 % P<.0001 ) . The in-hospital mortality was 3.8 % in women and 1.6 % in men . The multivariate correlates of death were older age , emergent surgery , reduced ejection fraction , female sex , diabetes , and more severe distribution of coronary arterial narrowings . Each of these risk factors for death became more prevalent , such that the mortality in men increased from 1.0 % in 1974 through 1979 to 2.7 % in 1988 through 1991 , whereas the mortality in women increased from 1.3 % in 1974 through 1979 to 5.4 % in 1988 through 1991 . Conclusions The population undergoing CABG has aged , with correlates of in-hospital death becoming more common . The higher mortality in women could only partially be explained by other clinical variables . In addition , the risk of death after CABG has increased in women more than in men because women have consistently been older , have more emergent surgery and diabetes , and in recent years more women undergoing CABG have three-vessel or left main disease At 12 centers , 395 patients , including 288 men ( 73 % ) and 107 women ( 27 % ) with acute myocardial infa rct ion ( AMI ) , were prospect ively r and omized to treatment with tissue plasminogen activator ( t-PA ) or primary percutaneous transluminal coronary angioplasty ( PTCA ) . Compared with men , women were older ( 65.7 vs 57.7 years , p < 0.0001 ) , more often had diabetes mellitus ( 19 % vs 10 % , p = 0.03 ) , systemic hypertension ( 54 % vs 39 % , p = 0.005 ) , prior congestive heart failure ( 5 % vs 0 % , p = 0.002 ) , and presented later after symptom onset ( 229 vs 174 minutes , p = 0.0004 ) . The in-hospital mortality in women was 3.3-fold higher than men ( 9.3 % vs 2.8 % , p = 0.005 ) . After adjustment for comorbid baseline characteristics , however , only advanced age independently correlated with mortality . Among t-PA-treated patients , mortality was significantly higher in women than in men ( 14.0 % vs 3.5 % , p = 0.006 ) . Intracranial hemorrhage after t-PA was also more common in women than in men ( 5.3 % vs 0.7 % , p = 0.037 ) . In contrast , women and men had similar in-hospital mortality after primary PTCA ( 4.0 % vs 2.1 % , respectively , p = 0.46 ) . No intracranial bleeding occurred in PTCA-treated patients . A univariate trend was present for reduced in-hospital mortality in women treated with PTCA rather than t-PA ( 4.0 % vs 14.0 % , p = 0.07 ) . By multiple logistic regression analysis of 15 clinical variables , treatment with PTCA rather than t-PA , as well as younger age , were independently predictive of in-hospital survival in women . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Compared to men , women undergoing coronary artery bypass grafting appear to have a higher morbidity and mortality , particularly in the perioperative period . This study was design ed to answer the questions of whether such differences in clinical outcomes between men and women still exist with improvements in surgical techniques and determine whether it is gender or associated comorbid conditions in women that lead to higher morbidity . METHODS An analysis of a single center 's contemporary experience ( 1994 to 1997 ) of 1,743 consecutive patients undergoing primary coronary artery bypass grafting was performed . Only reoperations were excluded . Data were collected prospect ively and presented as mean + /- st and ard deviation ( p<0.05 ) . RESULTS Women represented 30.0 % of patients . Compared with men , women were older ( 68.4 versus 63.8 years ; p<0.05 ) , and had more urgent surgical interventions ( 70.0 % versus 56.7 % ; p<0.05 ) , a higher incidence of diabetes ( 42.1 % versus 26.7 % ; p<0.05 ) , hypertension ( 82.0 % versus 73.9 % ; p<0.05 ) , lower body surface area ( 1.73+/-0.18 m2 versus 2.03+/-0.19 m2 ; p<0.05 ) , and hematocrit ( 31.7%+/-3.9 % versus 36.2%+/-3.9 % ; p<0.05 ) . Ejection fraction , incidence of previous myocardial infa rct ion , chronic obstructive pulmonary disease , left main ( LM ) disease , renal insufficiency , extent of coronary disease , and preoperative intraaortic balloon pump were similar . Women received fewer arterial grafts ( 91.0 % versus 95.5 % ; p<0.05 ) and distal anastomoses ( 3.31+/-0.88 versus 3.49+/-0.94 p<0.05 ) . Despite these differences , there were no statistical differences in the incidence of postoperative death ( 1.5 % versus 1.0 % ) , myocardial infa rct ion ( 0.6 % versus 0.6 % ) , or cerebrovascular accident/transient ischemic attack ( 1.1 % versus 0.4 % ) between men and women . Women had a higher inotropic support ( 10.2 % versus 4.4 % ; p<0.05 ) and longer hospital stays ( 7.3+/-5.7 days versus 6.3+/-4.2 days ; p<0.05 ) . Using multivariate analysis , female gender was not an independent predictor of death or postoperative complications but was a predictor of length of hospital stay , use of arterial grafts , and extent of coronary revascularization . CONCLUSIONS After accounting for differences in their risk variables , the incidences of death , perioperative myocardial infa rct ion and cerebrovascular accident/ transient ischemic attack after coronary artery bypass grafting in women and men were not statistically significant . Perioperative complications are related to comorbid risk factors but not to female gender itself . Further studies are warranted G lycoprotein ( GP ) IIb/IIIa inhibitors are potent antiplatelet agents that play a crucial role in preventing thrombus formation and have been shown to decrease ischemic complications after percutaneous coronary interventions ( PCIs ) . We hypothesized that with the use of GP IIb/IIIa inhibitors there would be no gender differences in terms of early clinical outcome after PCI . • • • The Cardiac Catheterization Laboratory data base of our institution was queried and we identified 1,215 consecutive patients who received GP IIb/IIIa inhibitors during 1,852 PCIs between September 1996 and June 2000 . Of these , 322 patients ( 26.5 % ) were women ( 488 procedures ) . All patients underwent cardiac catheterization and PCI by st and ard techniques after informed consent was obtained . Operators selected interventional devices and antithrombotic regimens at their discretion . All patients received aspirin 325 mg 24 hours before the procedure and continued indefinitely afterward . After stent implantation , patients received either ticlopidine ( 250 mg orally twice a day for 2 to 4 weeks ) or clopidogrel ( 75 mg/day for 4 weeks ) . Weight-adjusted heparin dosage was administered during the procedure and was routinely discontinued at the end of the procedure . GP IIb/IIIa inhibitors and other medications were administered at the discretion of the operator . The dose for abciximab was an intravenous bolus of 0.25 mg/kg , followed by 0.125 g/kg/min ( to a maximum of 10 g/min ) for 12 hours . Eptifibatide was administered as a bolus ( 180 g/kg ) , followed by a 12-hour infusion of 2 g/kg/min . Tirofiban was given as a bolus of 10 g/kg followed by a 12-hour 0.15 g/kg/min maintenance infusion . Cine angiograms were analyzed using a vali date d system ( ARTEK , Quantitative Cardiac Systems , Ann Arbor , Michigan ) by a dedicated core laboratory blinded to the intravascular ultrasound and clinical data . These are st and ard qualitative and quantitative analyses and definitions that have been previously published . Prespecified clinical and laboratory demographic information was obtained from hospital charts that were review ed by independent research personnel who were unaware of the objectives of the study ; the demographics were entered prospect ively into the data base . St and ard definitions regarding Q-wave and non – Q-wave myocardial infa rct ion were used . Bleeding events were classified as major and minor according to the criteria used by the Thrombolysis in Myocardial Infa rct ion study group . Short-term clinical follow-up was performed by either telephone contact or office visit at 1 month . The occurrence of major clinical events was recorded , including death ( all-cause ) , Q-wave myocardial infa rct ion , and target lesion revascularization ( whether percutaneous or surgical ) . These data collection methods have been previously published . Statistical analysis was performed using Statview ( SAS Institute Inc. , Cary , North Carolina ) . Continuous variables are expressed as mean SD and categorical variables as numbers ( percentages ) . All 4 groups were compared after being stratified by gender status . Continuous variables were estimated using analysis of variance or unpaired t test . Categorical variables were compared with a chi-square or Fisher ’s exact test . A p value 0.05 was considered significant . Compared with men , women were more likely to have hypertension , diabetes , and older age but were less likely to be current smokers or have a history of coronary artery bypass graft surgery . There were no gender differences in relation to the specific GP IIb/ IIIa inhibitor agent used . Nevertheless , elective use of a GP IIb/IIIa inhibitor was less frequent in women compared with men ( Table 1 ) . In men , the treated lesions more often involved the left anterior descending coronary artery or a saphenous vein graft . The procedural data were essentially similar with regard to mean inflation pressure , total lesion length , and final diameter stenosis . However , a higher mean balloon size and a higher balloon-tovessel ratio was used in men . Procedural and angiographic success rates were similarly high in women and men . Reference vessel diameter and final lumen dimension were larger in men than women . Frequency of ostial lesions was similar in both groups as was the morphologic lesion classification ( Table 2 ) . Compared with men , women had similar rates of From the Cardiovascular Research Foundation , Lenox Hill Heart and Vascular Institute , New York , New York . Dr. Iakovou was supported in part by a grant from the Onassis Foundation , Athens , Greece . Dr. Dangas ’ address is : Lenox Hill Heart and Vascular Institute , Cardiovascular Research Foundation , 55 East 59th Street , 6th Floor , New York , New York 10022 . E-mail : [email protected] . Manuscript received August 13 , 2001 ; revised manuscript received and accepted January 9 , 2002 OBJECTIVES Patients undergoing coronary artery bypass grafting are older and have greater comorbidity than those operated on previously . We evaluated the changes in the predictors of in-hospital mortality among patients undergoing coronary artery bypass grafting during the last 12 years . METHODS Data on demographic characteristics , preoperative risk factors , operative variables , and hospital outcomes were collected prospect ively for all patients undergoing isolated coronary artery bypass grafting at a single institution from January 1 , 1990 , to December 31 , 2001 . To examine the effect of time on patient risk profiles and outcomes , we divided patients into three groups according to year of operation ( 1990 - 1993 n = 5171 , 1994 - 1997 n = 5977 , 1998 - 2001 n = 6893 ) . RESULTS In-hospital mortality declined from 2.4 % ( 1990 - 1993 ) to 1.2 % ( 1998 - 2001 , P < .0001 ) . Left ventricular dysfunction , increasing age , female gender , hypertension , diabetes , cardiogenic shock , congestive heart failure , peripheral vascular disease , reoperative coronary artery bypass grafting , left main disease , and urgent surgery independently predicted in-hospital mortality in the entire cohort of 18,041 patients . Severe left ventricular dysfunction was the most significant predictor of in-hospital mortality in the 12-year cohort , but it had a declining influence with time ( 1990 - 1993 odds ratio 7.1 , 1994 - 1997 odds ratio 5.1 , 1998 - 2001 not statistically significant ) because of improving outcomes . Reoperative coronary artery bypass grafting similarly decreased in significance as a predictor of mortality . Emergency coronary artery bypass grafting was performed less frequently in recent years , but the requirement for emergency surgery carried an increasing odds ratio for mortality . CONCLUSIONS Despite increasing patient age and comorbidity , improvements in perioperative management have reduced the significance of severe left ventricular dysfunction and reoperative coronary artery bypass grafting but not emergency surgery as predictors of in-hospital mortality OBJECTIVE This study explores the relative early and late mortality risks in women and men after coronary artery bypass graft surgery . METHODS This was a retrospective cohort study ( n = 54,425 patients , 12,079 women ) using clinical data for all patients who underwent isolated coronary artery bypass graft surgery in Ontario between fiscal years 1991 and 1999 obtained from the Cardiac Care Network data base , with outcomes of early ( < or = 1 year ) and late ( > 1 year up to 10 years ) interval mortality identified through linkage to administrative data bases . RESULTS Female surgical c and i date s were older ( 65 vs 62 years , P < .0001 ) and higher-risk patients . The risk-adjusted survival of female patients was worse than that of male patients in the first year after coronary artery bypass graft surgery , but their long-term mortality was similar to that of male patients . The Cox proportional hazards model for early mortality had an adjusted female hazard ratio of 1.44 ( 95 % confidence interval , 1.29 - 1.61 ; P = .02 ) . This significantly differed from the late mortality model , which had a hazard ratio of 0.89 ( 95 % confidence interval , 0.78 - 1.0 ; P = .06 ) . CONCLUSIONS Early mortality was significantly higher for women after coronary artery bypass graft surgery , despite adjustment for confounding factors . However , the long-term relative mortality risk for women appeared equivalent to or even better than that experienced by men as early as 1 year after coronary artery bypass graft surgery . This population -based study of long-term mortality supports the benefits of coronary artery bypass graft surgery for women in the current era . However , further research is needed to identify ways to reduce early postoperative mortality in women AIMS The RITA 3 trial r and omized patients with non-ST-elevation myocardial infa rct ion or unstable angina to strategies of early intervention ( angiography followed by revascularization ) or conservative care ( ischaemia or symptom driven angiography ) . The aim of this analysis was to investigate the impact of gender on the effect of these two strategies . METHODS AND RESULTS In total , 1810 patients ( 682 women and 1128 men ) were r and omized . The risk factor profile of women at presentation was markedly different to men . There was evidence that men benefited more from an early intervention strategy for death or non-fatal myocardial infa rct ion at 1 year ( adjusted odds ratios 0.63 , 95 % confidence interval 0.41 - 0.98 for men and 1.79 , 95 % confidence interval 0.95 - 3.35 for women ; interaction p-value=0.007 ) . Men who underwent the assigned angiogram were more likely to be put forward for coronary artery bypass surgery , even after allowing for differences in disease severity . CONCLUSION An early intervention strategy result ed in a beneficial effect in men which was not seen in women although caution is needed in interpretation . Further research is needed to evaluate why women do not appear to benefit from early intervention and to identify treatments that improve the prognosis of women |
10,945 | 28,437,434 | Stimulation days ( mean difference ( MD ) [ 95 % confidence interval ( CI ) ] = -0.8 [ -1.36 , -0.23 ] , P = 0.006 ) , gonadotrophin ( Gn ) dosage ( MD [ 95 % CI ] = -3.52 [ -5.56 , -1.48 ] , P = 0.0007 ) , estradiol ( E2 ) level on the day of human chorionic gonadotrophin ( HCG ) administration ( MD [ 95 % CI ] = -365.49 [ -532.93 , -198.05 ] , P<0.0001 ) , the number of oocytes retrieved ( MD [ 95 % CI ] = -1.41 [ -1.84 , -0.99 ] , P<0.00001 ) , the embryos obtained ( MD [ 95 % CI ] = -0.99 [ -1.38 , -0.59 ] , P<0.00001 ) , incidence of ovarian hyperstimulation syndrome ( OHSS ) ( OR [ 95 % CI ] = 0.69 [ 0.57 , 0.83 ] , P<0.0001 ) were statistically significantly lower in GnRH-ant protocol than GnRH-a long protocol .
GnRH-ant protocol substantially decreased the incidence of OHSS without influencing the pregnancy rate and live birth rate compared to GnRH-a long protocol among patients with normal ovarian reserve | OBJECTIVE To evaluate the effectiveness and safety of gonadotropin-releasing hormone antagonist ( GnRH-ant ) protocol and gonadotropin-releasing hormone agonist ( GnRH-a ) long protocol in patients with normal ovarian reserve . | PURPOSE To compare outcome following in vitro fertilization-embryo transfer ( IVF-ET ) using controlled ovarian hyperstimulation ( COH ) regimens using either the gonadotropin-releasing hormone ( GnRH ) agonist leuprolide acetate vs the GnRH antagonist ganirelix . METHODS Women needing IVF for conception were r and omly assigned to 300 IU of gonadotropins with ganirelix used in the follicular phase when a follicle with a 14 mm average diameter was attained vs a regimen using leuprolide acetate from the mid-luteal phase of the previous cycle . RESULTS There were no differences found in clinical , ongoing , delivered pregnancy rates or implantation rates between groups . CONCLUSIONS The use of GnRH antagonists do not seem to reduce IVF outcome compared to using GnRH agonists in COH regimens OBJECTIVE Both gonadotropin-releasing hormone ( GnRH ) analogs and antagonists have been used for pituitary desensitization during controlled ovarian hyperstimulation ( COH ) . We aim ed to determine the minimum effective daily dose of GnRH antagonist in women undergoing COH . We also compared the efficiency of a GnRH antagonist and a GnRH agonist . MATERIAL S AND METHODS Women undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer were divided into five groups : ( 1 ) cetrorelix 0.25 mg ( n = 86 ) ; ( 2 ) cetrorelix 0.2 mg ( n = 28 ) ; ( 3 ) cetrorelix 0.15 mg ( n = 30 ) ; ( 4 ) leuprolide acetate ( LA ) 0.5 mg/day ( n = 58 ) ; ( 5 ) single half-dose LA depot 1.88 mg ( n = 49 ) . Cetrorelix was administered daily from menstrual day 8 until the day of human chorionic gonadotropin administration . LA or LA depot was started on day 21 of the previous menstrual cycle . RESULTS We observed lower gonadotropin ( Gn ) dosages , estradiol ( E2 ) levels and reduced risk of ovarian hyperstimulation syndrome ( OHSS ) in the GnRH antagonist groups . A higher risk of luteinizing hormone ( LH ) surge was noted in cetrorelix 0.2 and 0.15 mg groups . Gn dosages (IU)/E2 levels ( pg/mL ) in each group were : ( 1 ) 1,949.4/1,191.1 ; ( 2 ) 1,869.6/1,010.8 ; ( 3 ) 1,856.7/1,023.6 ; ( 4 ) 2,184.5/1,323.6 ; and ( 5 ) 2,103.5/1,313.5 , respectively . LH/OHSS risks were : ( 1 ) 3.5%/5.8 % ; ( 2 ) 7.1%/3.6 % ; ( 3 ) 13.3%/3.3 % ; ( 4 ) 3.4%/8.6 % ; and ( 5 ) 2%/8.2 % , respectively . Number of oocytes/embryos/ grade I , II embryos were : ( 1 ) 9.4/7.9/5.8 ; ( 2 ) 7.5/4.2/3.6 ; ( 3 ) 6.3/4.1/3.1 ; ( 4 ) 12.3/8.9/6.6 ; and ( 5 ) 11.8/8.4/6.1 , respectively . There was no significant difference in terms of clinical outcomes between groups 1 , 4 and 5 , except for higher abortion rates ( AR ) in group 1 . Pregnancy rate (PR)/implantation rate ( IR ) ratios in groups 1 , 4 , and 5 were statistically higher than those in groups 2 and 3 . Chemical PR/IR/AR were : ( 1 ) 30.2%/5.9%/7 % ; ( 2 ) 21.4%/5.1%/7.1 % ; ( 3 ) 16.7%/4.1%/10 % ; ( 4 ) 32.8%/5.5%/8.6 % ; and ( 5 ) 30.6%/5.7%/8.2 % , respectively . CONCLUSION The lowest effective dosage of cetrorelix for pituitary desensitization during COH luteolysis is 0.25 mg , result ing in a comparable PR but a higher AR when compared with GnRH agonist Purpose To evaluate the results of gonadotropin-releasing hormone agonist ( GnRHa ) and gonadotropin-releasing hormone antagonist ( GnRHant ) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection ( IVF/ICSI ) patients in a prospect i ve study . Methods We r and omised 93 patients undergoing IVF/ICSI between May 2005 and August 2006 . Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia , women older than 38 years and those with follicle-stimulating hormone ( FSH ) ≥10 IU/ml . Patients were stimulated with st and ard 225 IU recombinant FSH . In Group I ( n=45 ) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of ≥14 mm . Group II ( n=48 ) patients were desensitised with the GnRHa , leuprolide acetate , in a long protocol . Human chorionic gonadotropin ( hCG ) was administered when at least three follicles of 18 mm in diameter were observed . Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval . Results The two groups were homogenous for age , infertility duration , basal FSH and serum oestradiol ( E2 ) ( P=0.537 , P=0.911 , P=0.103 and P=0.733 , respectively ) . In Group II ( the GnRHa group ) more antral follicles ( P<0.001 ) , a longer induction duration ( P=0.017 ) and higher peak E2 levels ( P<0.001 ) were observed . No differences were observed in the number of oocytes retrieved ( P=0.749 ) , embryos achieved and transferred ( P=0.677 ) , or fertilisation rates ( P=0.839 ) between the two groups . There was no statistically significant difference between groups in clinical pregnancy rates , cycle cancellation and ovarian hyperstimulation ( P=0.437 , P=0.109 and P=0.415 , respectively ) . Conclusion GnRHant and GnRHa provide comparable results in normoresponder patients , while GnRHant allows a greater flexibility in their treatment OBJECTIVE To compare the effects of oral contraceptive ( OC ) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization ( IVF ) patients , and to evaluate optimization of retrieval day . DESIGN Prospect i ve , r and omized , multicenter study . SETTING Private practice and university centers . PATIENT(S ) Eighty patients undergoing IVF who met the appropriate inclusion criteria . INTERVENTION(S ) Four study centers recruited 80 patients . The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days . The recombinant FSH regimen was begun on the following Friday . The GnRH-agonist group was treated with a long protocol ; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm . When two follicles had reached 16 to 18 mm , hCG was administered . MAIN OUTCOME MEASURE(S ) The primary outcome measures were the number of cumulus-oocyte complexes , day of the week for oocyte retrieval , and total dose and days of stimulation of recombinant FSH . Secondary efficacy variables included pregnancy and implantation rate ; serum E(2 ) levels on stimulation day 1 ; serum E(2 ) , P , and LH levels on the day of hCG administration ; follicle size on day 6 and day of hCG administration ; the total days of GnRH-analogue treatment ; total days on OC ; total days from end of OC to oocyte retrieval ; and the cycle cancellation rate . RESULT ( S ) Patient outcomes were similar for the days of stimulation , total dose of gonadotropin used , two-pronuclei embryos , pregnancy ( 44.4 % GnRH-antagonist vs. 45.0 % GnRH-agonist , P=.86 ) and implantation rates ( 22.2 % GnRH-antagonist vs. 26.4 % GnRH-agonist , P=.71 ) . Oral contraceptive cycle scheduling result ed in 78 % and 90 % of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist . A one day delay in OC discontinuation and recombinant FSH start would result in over 90 % of oocyte retrievals occurring Monday through Friday in both groups . CONCLUSION ( S ) The OC pretreatment in recombinant FSH/GnRH-antagonist protocol s provides a patient-friendly regimen and can be optimized for weekday retrievals . No difference was seen in number of 2PN embryos , cryopreserved embryos , embryos transferred , implantation and pregnancy rates between the two stimulation protocol STUDY QUESTION Is the risk of severe ovarian hyperstimulation syndrome ( OHSS ) similar in a short GnRH antagonist and long GnRH agonist protocol in first cycle IVF/ICSI patients less than 40 years of age ? . SUMMARY ANSWER There is an increased risk of severe OHSS in the long GnRH agonist group compared with the short GnRH antagonist protocol . WHAT IS KNOWN ALREADY ? : In the most recent Cochrane review , the GnRH antagonist protocol was associated with a similar live birth rate ( LBR ) , a similar on-going pregnancy rate ( OPR ) , and a lower incidence of OHSS ( odds ratio ( OR ) = 0.43 95 % confidence interval ( CI ) : 0.33 - 0.57 ) compared with the traditional GnRH agonist protocol . Previous trials comparing the two protocol s mainly included selected patient population s , a limited number of patients and the applied OHSS criteria differed , making direct comparisons difficult . In two recent large meta-analyses , no significant differences in LBR ( OR = 0.86 ; 95 % CI : 0.72 - 1.02 ) or in the incidence of severe OHSS were reported , while others found a lower LBR ( OR = 0.82 ; 95 % CI : 0.68 - 0.97 ) and a reduced risk of severe OHSS using the GnRH antagonist protocol ( OR = 0.60 ; 95 % CI : 0.40 - 0.88 ) . STUDY DESIGN , SIZE , DURATION Phase IV , dual-centre , open-label , RCT including 1050 women allocated to either short GnRH antagonist or long GnRH agonist protocol in a 1:1 ratio and enrolled over a 5-year period using a web-based concealed r and omization code . This is a superiority study design ed to detect a difference in severe OHSS , the primary outcome , between the two groups with a power of 80 % and stratified for age , assisted reproductive technology ( ART ) clinic and planned fertilization procedure ( IVF/ICSI ) . The secondary aims were to compare rates of mild and moderate OHSS , positive plasma (p)-hCG , on-going pregnancy and live birth between the two arms . None of the women had undergone previous ART treatment . PARTICIPANTS / MATERIAL S , SETTING , METHODS All infertile women referred for their first IVF/ICSI at two public fertility clinics , less than 40 years of age and with no uterine malformations were asked to participate . A total of 1099 subjects were r and omized , including women with poor ovarian reserve , polycystic ovary syndrome and irregular cycles . A total of 49 women withdrew their consent , thus 1050 subjects were allocated to the GnRH antagonist ( n = 534 ) and agonist protocol ( n = 516 ) , respectively . In total 1023 women started recombinant human follitropin-β ( rFSH ) stimulation , 528 in the GnRH antagonist group and 495 in the GnRH agonist group . All subjects were given a fixed rFSH dose of 150 IU or 225 IU according to age ≤36 years or > 36 years , with the option to adjust dose at stimulation day 6 . Clinical OHSS parameters were collected at oocyte retrieval , and Days 3 and 14 post-transfer . On-going pregnancy was determined by transvaginal ultrasonography at gestational weeks 7 - 9 . In the intention-to-treat ( ITT ) analysis for reproductive outcomes , 1050 subjects were included . For the ITT analyses on OHSS 1023 subjects who started gonadotrophin stimulation were included . MAIN RESULTS AND THE ROLE OF CHANCE The incidence of severe OHSS [ 5.1 % ( 27/528 ) versus 8.9 % ( 44/495 ) ( difference in proportion percentage point ( Δpp ) = -3.8pp ; 95 % CI : -7.1 to -0.4 ; P = 0.02 ) ] and moderate OHSS [ 10.2 % ( 54/528 ) versus 15.6 % ( 77/495 ) ( Δpp = -5.3pp ; 95 % CI : -9.6 to -1.0 ; P = 0.01 ) ] was significantly lower in the GnRH antagonist group compared with the agonist group , respectively . In the GnRH antagonist and agonist group , respectively , 4.7 % ( 25/528 ) versus 8.5 % ( 42/495 ) women were seen by a physician due to OHSS ( P = 0.01 ) , and 1.7 % ( 9/528 ) versus 3.6 % ( 18/495 ) were admitted to hospital due to OHSS ( P = 0.06 ) . No women had ascites-puncture in the GnRH antagonist group versus 2.0 % ( 10/495 ) in the GnRH agonist group ( P < 0.01 ) . LBRs were 22.8 % ( 122/534 ) versus 23.8 % ( 123/516 ) ( Δpp = -1.0pp ; 95 % CI : -6.3 to 4.3 ; P = 0.70 ) and OPRs were 24.9 % ( 133/528 ) versus 26.2 % ( 135/516 ) ( Δpp = -1.3pp ; 95 % CI : -6.7 to 4.2 ; P = 0.64 ) per r and omized subject in the GnRH antagonist versus agonist group , with a mean number of 1.1 versus 1.2 embryos transferred in the two groups . Pregnancy rates ( PR ) per r and omized subject , per started gonadotrophin stimulation and per embryo transfer were all similar in the two groups . LIMITATIONS , REASONS FOR CAUTION A possible limitation is the duration of the trial , with new methods , such as ' freeze all ' and ' GnRH agonist triggering ' , being developed during the trial , the new methods were sought avoided , however a total number of 32 women had ' freeze all ' and ' GnRH agonist triggering ' was performed in three cases . Ultrasonic measurements were performed by different physicians and inter-observer bias may be present . Measures of anti-Mullerian hormone and antral follicle count , to estimate ovarian reserve and thus predict risk of OHSS , were not performed . Finally , the physicians were not blinded to GnRH treatment group after r and omization . WIDER IMPLICATION S OF THE FINDINGS The short GnRH antagonist protocol should be the protocol of choice for patients undergoing their first ART cycle in females < 40 years of age including both low and high responders when an age-dependent initially fixed gonadotrophin dose is used , as an increased risk of severe OHSS and the associated complications is seen in the long GnRH agonist group and as PRs and LBRs are similar in the two groups . Patients at risk of OHSS particularly benefit from the short GnRH antagonist treatment as GnRH agonist triggering can be used . STUDY FUNDING /COMPETING INTERESTS An unrestricted research grant is funded by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co. , Inc. , Kenilworth , NJ , USA ( MSD ) . The funders had no influence on the data collection , analyses or conclusions of the study . No conflict of interests to declare . TRIAL REGISTRATION NUMBER EudraCT # : 2008 - 005452 - 24 . Clinical Trial.gov : NCT00756028 . Trial registration date : 18 September 2008 . Date of first patient 's enrolment : 14 January 2009 Background . The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and r and omised to receive GnRH-antagonist or the GnRH-agonist . The endpoints were the pattern of follicular growth , the maturity of the oocytes collected , the embryo quality and the pregnancy outcome . Methods . A total of 136 patients undergoing IVF were included . Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist . GnRH antagonist was administered when the leading follicle reached a diameter of 12–14 mm . GnRH agonist was administered in a long luteal protocol . Results . The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group ( p < 0.02 and p < 0.01 , respectively ) . Embryo quality , implantation rate , clinical pregnancy rates , ongoing pregnancy rate and miscarriage rate were similar in both groups . Conclusions . Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment . However , both regimens seem to have similar efficacy in terms of implantation and pregnancy rates . Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed , as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration BACKGROUND To test whether ovarian stimulation for in-vitro fertilization ( IVF ) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development , preimplantation genetic screening of embryos was employed in a prospect i ve , r and omized controlled trial , comparing two ovarian stimulation regimens . METHODS Infertile patients under 38 years of age were r and omly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone ( GnRH ) antagonist co-treatment ( 67 patients ) , which does not disrupt secondary follicle recruitment , or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment ( 44 patients ) . Following IVF , embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres . RESULTS The study was terminated prematurely , after an unplanned interim analysis ( which included 61 % of the planned number of patients ) found a lower embryo aneuploidy rate following mild stimulation . Compared with conventional stimulation , significantly fewer oocytes and embryos were obtained following mild stimulation ( P < 0.01 and < 0.05 , respectively ) . Consequently , both regimens generated on average a similar number ( 1.8 ) of chromosomally normal embryos . Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors . CONCLUSIONS Future ovarian stimulation strategies should avoid maximizing oocyte yield , but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology BACKGROUND In view of the current debate concerning possible differences in efficacy between the two GnRH analogues used in IVF stimulated cycles , the current study aim ed to explore whether progesterone control in the late follicular phase differs when GnRH antagonist is used as compared with GnRH agonist , and if so , to what extent the progesterone rise affects the probability of pregnancy . METHODS Overall 190 patients were r and omized : 94 in the GnRH-agonist group and 96 in the GnRH-antagonist group . The GnRH-agonist long protocol started on Day 21 of the preceding cycle with intranasal buserelin ( 600 mg per day ) . The GnRH-antagonist protocol started on Day 6 of the stimulation with ganirelix or cetrorelix ( each 0.25 mg ) . All blood sample s were analysed with the Elecsys analyzer . An intention-to-treat analysis was applied . RESULTS A progesterone rise > 1.5 ng/ml was noticed in 23.0 % of the antagonist group , comparable with 24.1 % incidence within the agonist group . Per patient r and omized , delivery rates were also comparable : 28.1 % in the antagonist group and 24.5 % in the agonist group ( odds ratio = 1.21 , 95 % confidence interval : 0.63 - 2.31 , P= 0.56 ) . However , there was a reduction in delivery rates when progesterone exceeded the threshold of 1.5 ng/ml , both in the agonist group ( 9.5 versus 31.8 % , P= 0.03 ) and in the antagonist group ( 14.3 versus 34.3 % , P= 0.07 ) . CONCLUSIONS Although the incidence of a progesterone rise was similar between the two analogues , our findings reconfirm previous observations that insufficient progesterone control ( > 1.5 ng/ml ) on the day of ovulation triggering is related to poor delivery rates in both protocol s. The current study has shown that the reproductive outcomes with the two GnRH analogues are comparable . Possible modes of action to circumvent late follicular progesterone rise should be explored . TRIAL REGISTRATION NUMBER NCT01191710 BACKGROUND This r and omized controlled trial was design ed to assess the impact of oral contraceptive ( OC ) scheduling with a GnRH antagonist ( ganirelix ) regimen on the ovarian response of women undergoing recombinant FSH ( rFSH ) stimulation for IVF , compared with a non-scheduled ganirelix regimen and a long GnRH agonist ( nafarelin ) protocol . METHODS A total of 110 women was treated with an OC and ganirelix , 111 with ganirelix alone and 111 with nafarelin . The OC ( containing 30 microg ethinylestradiol/150 microg desogestrel ) was taken for 14 - 28 days and stopped 2 days prior to the start of rFSH treatment . Primary efficiency parameters were the number of cumulus-oocyte complexes ( per attempt ) and the number of grade 1 or 2 embryos ( per attempt ) . RESULTS In terms of follicular growth and hormone profiles , the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the ( non-scheduled ) GnRH antagonist regimen . In the OC-scheduled GnRH antagonist group and the nafarelin group ( versus the non-scheduled antagonist group ) , pituitary suppression was more profound at the start of stimulation ( P < or = 0.001 ) , there was a slower start of follicular growth ( P < or = 0.001 ) , longer stimulation was required ( 11.7 and 10.3 days respectively versus 9.4 ; P < or = 0.001 ) , and more rFSH was used ( 2667 and 2222 IU versus 1966 IU ; P < or = 0.001 ) . In the three groups , the number of oocytes was similar ( 13.1 , 12.9 and 11.5 respectively ; not significant ) as well as the number of good quality embryos ( 5.1 , 5.7 and 5.0 respectively ; not significant ) . CONCLUSION OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients , although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen A multicentre , open-label , r and omized study of the gonadotrophin-releasing hormone ( GnRH ) antagonist ganirelix ( Orgalutran((R))/Antagon((TM ) ) ) was performed in women undergoing ovarian stimulation with recombinant FSH ( rFSH : Puregon((R ) ) ) . The study was design ed as a non-inferiority study using a long protocol of buserelin ( intranasal ) and rFSH as a reference treatment . A total of 730 subjects was r and omized in a treatment ratio of 2:1 ( ganirelix : buserelin ) using an interactive voice response system which stratified for age , type of infertility and planned fertilization procedure [ IVF or intracytoplasmic sperm injection ( ICSI ) ] . The median duration of GnRH analogue treatment was 5 days in the ganirelix group and 26 days in the buserelin group , whereas the median total rFSH dose was 1500 IU and 1800 IU respectively . In addition , in the ganirelix group the mean duration of stimulation was 1 day shorter . During ganirelix treatment the incidence of LH rises ( LH > /=10 IU/l ) was 2.8 % versus 1.3 % during rFSH stimulation in the buserelin group . On the day of triggering ovulation by human chorionic gonadotrophin ( HCG ) , the mean number of follicles > /=11 mm diameter was 10.7 and 11.8 , and the median serum oestradiol concentrations were 1190 pg/ml and 1700 pg/ml in the ganirelix and buserelin groups respectively . The mean number of oocytes per retrieval was 9.1 and 10.4 respectively , whereas the mean number of good quality embryos was 3.3 and 3.5 respectively . The fertilization rate was equal in both groups ( 62.1 % ) , and the same mean number of embryos ( 2.2 ) was replaced . The mean implantation rates were 15.7 % and 21.8 % , and the ongoing pregnancy rates per attempt were 20.3 % and 25.7 % in the ganirelix and buserelin groups respectively . Evaluation of all safety data indicated that the ganirelix regimen was safe and well tolerated . The overall incidence of ovarian hyperstimulation syndrome was 2.4 % in the ganirelix group and 5.9 % in the reference group . The results of this study support a safe , short and convenient treatment regimen of ganirelix , result ing in a good clinical outcome for patients undergoing ovarian stimulation for IVF or ICSI Background : Given the controversies regarding the effectiveness of gonadotropin-releasing hormone ( GnRH ) antagonists in prevention of ovarian hyper stimulation syndrome stimulation , this study was design ed to compare GnRH agonist protocol with GnRH antagonist protocol in patients who were c and i date for assisted reproductive techniques ( ARTs ) . Material s and Methods : This investigation was performed on 136 patients who were r and omly allocated to two groups of GnRH agonist and GnRH antagonist . In the first group stimulation was performed by administration of Buserelin , and in the second group , it was performed by giving Cetrorelix . Then patients were compared regarding results of ovarian stimulation , pregnancy outcomes and rate of ovarian hyper stimulation syndrome ( OHSS ) . Results : There were not significant differences between 2 groups regarding the ovarian stimulation , pregnancy outcomes and rate of OHSS ( P value > 0.05 ) . Conclusion : Administration of GnRH antagonists in ovarian stimulation will be a reasonable option to GnRH agonists in assessment reproduction treatment ; however , further studies are suggested OBJECTIVE To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges . DESIGN Multicenter r and omized , prospect i ve study . SETTING Reproductive medicine units . PATIENT(S ) Infertile patients undergoing ovarian stimulation for IVF-ET . INTERVENTION(S ) A single dose of 3 mg of cetrorelix ( Cetrotide ; ASTA Medica , Frankfurt , Germany ) ( 115 patients ) was administered in the late follicular phase . A depot preparation of triptorelin ( Decapeptyl ; Ipsen-Biotech , Paris , France ) was chosen as a control agent ( 39 patients ) . Ovarian stimulation was conducted with hMG ( Menogon ; Ferring , Kiel , Germany ) . MAIN OUTCOME MEASURE(S ) Premature LH surges ( LH level > 10 IU/L ) , progesterone level greater than 1 ng/L , and IVF results . RESULT ( S ) No LH surge occurred after cetrorelix administration . The patients in the cetrorelix group had a lower number of oocytes and embryos . The percentage of mature oocytes and fertilization rates were similar in both groups , and the pregnancy rates were not statistically different . The length of stimulation , number of hMG ampules administered , and occurrence of the ovarian hyperstimulation syndrome were lower in the cetrorelix group . Tolerance of cetrorelix was excellent . CONCLUSION ( S ) A cetrorelix single-dose protocol prevented LH surges in all patients studied . It compares favorably to the " long protocol " and could be a protocol of choice in IVF-ET OBJECTIVE To determine the efficiency of a single-dose and a multiple-dose protocol for GnRH antagonist administration . DESIGN R and omized clinical trial . SETTING University hospital , tertiary medical center . PATIENT(S ) Sixty-one patients undergoing controlled ovarian stimulation ( COS ) and IVF/ICSI . INTERVENTION(S ) COS with either a multiple-dose ( MD ) or a single-dose ( SD ) protocol for GnRH antagonist ( cetrorelix ) administration , or with a long protocol ( LP ) for GnRH agonist ( buserelin ) administration , followed by oocyte retrieval , IVF/ICSI , and embryo transfer . MAIN OUTCOME MEASURE(S ) Follicular development and serum levels of E2 and LH . RESULT ( S ) The SD protocol for cetrorelix was associated with a more reduced level of follicular development , lower levels of serum estradiol on the day of HCG administration , and a more reduced number of zygotes than the LP for buserelin . The pregnancy and implantation rates did not differ significantly for the three study groups . CONCLUSION ( S ) The MD and SD GnRH antagonist protocol s were effective for preventing LH surge and appear to elicit an equivalent pregnancy rate to that corresponding to a LP GnRH agonist . In terms of follicular development , the SD protocol requires further modification , including flexible scheduling or possibly a small reduction of the dosage of the administered cetrorelix In this prospect i ve and r and omized study , 188 patients received the luteinizing hormone-releasing hormone ( LHRH ) antagonist cetrorelix , and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone ( LH ) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection ( ICSI ) cycles . Ultimately , 181 patients ( 96.3 % ) in the cetrorelix group , and 77 ( 90.6 % ) in the buserelin group , reached the day of the human chorionic gonadotrophin ( HCG ) injection . The mean number of human menopausal gonadotrophin ( HMG ) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group ( P < 0.01 ) . A rise in LH and progesterone concentrations was observed in three of the 188 patients ( 1.6 % ) who received cetrorelix . On the day of the HCG administration , more follicles of a small diameter ( 11 - 14 mm ) were observed in the buserelin group than in the cetrorelix group ( P = 0 . 02 ) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix ( P < 0.01 ) . Similar results were observed in fertilization , cleavage and pregnancy rates in the two groups . In conclusion , the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion , so allowing a reduction in the treatment time in a clinical ly significant manner OBJECTIVE Evaluate the effectiveness of a new ovarian stimulation ( OS ) protocol before IVF . DESIGN Prospect i ve clinical r and omized trial . SETTING Private centers . PATIENT(S ) Three hundred and twenty-three intended-to-treat women c and i date s for IVF . INTERVENTION(S ) Patients were divided into three groups and administered the following treatments : group A , recombinant hFSH from day 3 until follicles reached 13 - 14 mm , when recombinant hFSH was lowered to 75 IU daily and daily injections of 200 IU of hCG and a GnRH antagonist were administered until final maturation ; group B , recombinant hFSH and a GnRH antagonist ; group C , recombinant hFSH and a GnRH agonist . MAIN OUTCOME MEASURE(S ) Primary outcome was the number of mature oocytes . Secondary outcomes included average initial and total recombinant hFSH dosage , serum E2 level on day of ovulation , number of oocytes retrieved , fertilization , number of top- quality embryos , endometrial thickness , implantation rate , pregnancy rate ( PR ) , and incidence of ovarian hyperstimulation syndrome ( OHSS ) . RESULT ( S ) The numbers of oocytes retrieved , mature oocytes , fertilization , top- quality embryos , and embryos transferred were comparable in all groups . Implantation rate , PR , and incidence of OHSS were also comparable . The total dose of recombinant hFSH was significantly lower in group A ( 1,674.7 + /- 59.4 IU , vs. 2,197.9 + /- 77.8 IU in group B and 2,156.7 + /- 80.9 IU in group C ) . CONCLUSION ( S ) This new OS protocol permits follicles and oocytes to fully develop , helps generate top- quality embryos , avoids premature ovulation , establishes clinical pregnancies , reduces administration of recombinant hFSH , minimizes costs , and does not increase the chances of OHSS An open label , r and omized , multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH . Normo-ovulatory women ( n = 74 ) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate ( n = 25 ) before ovarian stimulation with recombinant human FSH ( r-hFSH ) or with cetrorelix 3 mg on stimulation day 7 ( with ( n = 25 ) or without ( n = 24 ) r-hLH 150 IU on days 7 - 10 ) . The main outcome measures were the number of metaphase II ( MII ) oocytes retrieved ; secondary efficacy end-points ; adverse events ( AE ) and other safety measures . There were no significant differences between groups for MII oocytes retrieved , duration of stimulation , total r-hFSH dose and pregnancy rates . The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups . The majority of AE were mild to moderate in severity . Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety , although cetrorelix has the advantage of typically requiring only one injection Abstract Purpose This prospect i ve study evaluated the efficacy of gonadotropin-releasing hormone ( GnRH ) antagonist protocol in comparison with the GnRH agonist protocol in the first cycle of assisted reproductive technique ( ART ) . Methods We r and omized 235 patients undergoing ART for the first time . The first group was stimulated with a st and ard long protocol and the second group stimulated with GnRH antagonis . Results There was no statistically significant difference in the age , infertility cause , basal FSH , BMI , the number of oocytes retrieved , number of M2 oocytes , embryo obtained and endometrial thickness between the two groups . But Serum estradiol , consumption of gonadotropins and ovarian hyperstimulation syndrome were significantly lower in the antagonist protocol . Cancellation rate of embryo transfer due to poor- quality embryo in the antagonist protocol was higher , but it was not significant . There was no significant difference in the clinical pregnancy and ongoing pregnancy between the two groups . Conclusion GnRH-antagonist is an effective , safe , and well-tolerated alternative to agonist in the first cycle of ART BACKGROUND Mild in-vitro fertilisation ( IVF ) treatment might lessen both patients ' discomfort and multiple births , with their associated risks . We aim ed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy result ing in term livebirth within 1 year compared with st and ard treatment , and can also reduce patients ' discomfort , multiple pregnancies , and costs . METHODS We did a r and omised , non-inferiority effectiveness trial . 404 patients were r and omly assigned to undergo either mild treatment ( mild ovarian stimulation with gonadotropin-releasing hormone [ GnRH ] antagonist co-treatment combined with single embryo transfer ) or a st and ard treatment ( stimulation with a GnRH agonist long- protocol and transfer of two embryos ) . Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after r and omisation ( with a non-inferiority threshold of -12.5 % ) , total costs per couple up to 6 weeks after expected date of delivery , and overall discomfort for patients . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Clinical Trial , number IS RCT N35766970 . FINDINGS The proportions of cumulative pregnancies that result ed in term livebirth after 1 year were 43.4 % with mild treatment and 44.7 % with st and ard treatment ( absolute number of patients = 86 for both groups ) . The lower limit of the one-sided 95 % CI was -9.8 % . The proportion of couples with multiple pregnancy outcomes was 0.5 % with mild IVF treatment versus 13.1 % ( p<0.0001 ) with st and ard treatment , and mean total costs were 8333 euros and 10745 euros , respectively ( difference 2412 euros , 95 % CI 703 - 4131 ) . There were no significant differences between the groups in the anxiety , depression , physical discomfort , or sleep quality of the mother . INTERPRETATION Over 1 year of treatment , cumulative rates of term livebirths and patients ' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for st and ard stimulation with two embryos transferred . However , a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs OBJECTIVE To assess the efficacy , safety , and local tolerance of ganirelix acetate for the inhibition of premature luteinizing hormone ( LH ) surges in women undergoing controlled ovarian hyperstimulation ( COH ) . DESIGN Phase III , multicenter , open-label r and omized trial . SETTING In vitro fertilization ( IVF ) centers in North America . PATIENT(S ) Healthy female partners ( n = 313 ) in subfertile couples for whom COH and IVF or intracytoplasmic sperm injection were indicated . INTERVENTION(S ) Patients were r and omized to receive one COH cycle with ganirelix or the reference treatment , a long protocol of leuprolide acetate in conjunction with follitropin-beta for injection . OUTCOME MEASURE(S ) Number of oocytes retrieved , pregnancy rates , endocrine variables , and safety variables . RESULT ( S ) The mean number of oocytes retrieved per attempt was 11.6 in the ganirelix group and 14.1 in the leuprolide group . Fertilization rates were 62.4 % and 61.9 % in the ganirelix and leuprolide groups , respectively , and implantation rates were 21.1 % and 26.1 % . Clinical and ongoing pregnancy rates per attempt were 35.4 % and 30.8 % in the ganirelix group and 38.4 % and 36.4 % in the leuprolide acetate group . Fewer moderate and severe injection site reactions were reported with ganirelix ( 11.9 % and 0.6 % ) than with leuprolide ( 24.4 % and 1.1 % ) . CONCLUSION ( S ) Ganirelix is effective , safe , and well tolerated . Compared with leuprolide acetate , ganirelix therapy has a shorter duration and fewer injections but produces a similar pregnancy rate OBJECTIVE Testing the ability to program IVF GnRH-antagonist cycles to avoid weekend oocyte retrieval . STUDY DESIGN Preliminary r and omized clinical trial . Patients presenting an indication for IVF or IVF-ICSI were assigned into either the Treatment Group - GnRH antagonist protocol , programmed to start stimulatory agents on a Friday , with oral 2 mg estradiol valerate twice a day from the 2nd day of cycle until the first Friday to follow , or to the Control Group - long luteal GnRH agonist protocol . RESULTS The performance of 27 Treatment Group patients and 24 Control Group patients was analyzed . Cycle dynamics were not clinical ly or statistically different except for a significant difference in the number of follicles measuring ≥18 mm on hCG administration day . There were no differences in the number of aspirated ova , fertilization rates , embryo quality or number of embryos to be transferred . Pregnancy rate was 41.7 % in the Treatment Group and 50 % in the Control Group ( P>0.5 ) . Only one patient assigned to the Treatment Group had a weekend retrieval . CONCLUSIONS Preliminary results demonstrate no compromise related to follicular estrogen programming in a GnRH antagonist protocol and provide reassurance regarding the ability to achieve programming goals Gonadotropin-releasing hormone ( GnRH ) antagonists for controlled ovarian stimulation ( COS ) were only recently introduced into China . The efficacy and safety of the GnRH antagonist ganirelix was assessed in a multicenter , controlled , open-label study , in which Chinese women were r and omized to either ganirelix ( n = 113 ) or a long GnRH agonist protocol of triptorelin ( n = 120 ) . The primary end point was the amount of recombinant follicle-stimulating hormone ( rFSH ) required to meet the human chorionic gonadotropin criterion ( three follicles ≥17 mm ) . The amount of rFSH needed was significantly lower for ganirelix ( 1272 IU ) vs. triptorelin ( 1416 IU ; P < 0.001 ) . Ongoing pregnancy rates per started cycle were 39.8 % ( ganirelix ) and 39.2 % ( triptorelin ) . Although both treatments were well tolerated , cancellation due to risk of ovarian hyperstimulation syndrome ( OHSS ) was less frequent with ganirelix ( 1.8 % ) than triptorelin ( 7.5 % ) ( P = 0.06 ) . Less rFSH was needed in the ganirelix protocol than the long GnRH agonist protocol , with fewer reported cases of OHSS and similar pregnancy rates The purpose of this prospect i ve r and omized study was to compare stimulation characteristics and IVF outcomes of the st and ard long GnRH agonist protocol for ovarian stimulation with a modified GnRH antagonist protocol . Starting GnRH antagonist in a flexible protocol according to the size of the leading follicle , with simultaneous augmentation of 75 IU recombinant FSH , failed to increase clinical pregnancy rates This multicentre , r and omized study was performed to assess the efficacy and safety of 0.25 mg ganirelix ( Orgalutran , Antagon ) treatment , using triptorelin ( Decapeptyl ) in a long protocol as a reference treatment . In total , 236 subjects were r and omized to treatment with ganirelix ( 0.25 mg , s.c . ) and 119 to triptorelin ( 0.1 mg , s.c . ) treatment ( treatment ratio 2:1 ) . Treatment with ganirelix started on day 6 of stimulation , whereas treatment with triptorelin started on menstrual cycle day 21 to 24 of the previous cycle ( i.e. the midluteal phase ) . The ganirelix regimen was on average 17 days shorter ( 9 versus 26 days ) compared to the triptorelin regimen . The median total dose of recombinant FSH ( Puregon ) used was 450 IU less ( 1350 versus 1800 IU ) in the ganirelix protocol . The initial follicular growth was faster and , consequently , oestradiol concentrations were higher in the ganirelix group . On the day of human chorionic gonadotrophin ( HCG ) , the mean number of follicles > or = 11 mm was 10.1 and 10.7 and the median serum oestradiol concentration was 1090 and 1370 pg/ml in the ganirelix and triptorelin groups respectively . Per attempt , 7.9 and 9.6 oocytes ( mean ) were retrieved in the ganirelix and triptorelin groups respectively . The fertilization rates ( 64.0 % ganirelix and 64.9 % triptorelin ) and the mean number of good quality embryos ( 2.7 and 2.9 ) were comparable in both treatment groups . The implantation rate was identical ( 22.9 % ) . The ongoing pregnancy rate per attempt was 31.0 and 33.9 % in the ganirelix and triptorelin groups respectively . The ganirelix regimen showed an improved local tolerance in that the percentage of subjects with at least one local skin reaction was 2-fold lower than in the triptorelin group ( 11.9 versus 24.1 % ) . Taking all data together , it may be concluded that ganirelix offers a new treatment regimen in ovarian stimulation that is short , safe and well-tolerated , optimizing convenience for the patient BACKGROUND The aim of this study was to investigate the effect of GnRH antagonists ( GnRH-ant ) on follicular fluid vascular endothelial growth factor ( FF VEGF ) . METHODS Sixty women undergoing assisted reproduction were r and omised ( computer-generated r and omisation list ) and assigned to two different GnRH analogue regimens : GnRH agonist ( GnRH-a ) ( Group A ; n = 30 ) and GnRH-ant ( Group B ; n = 30 ) . RESULTS Mean ( + /-S.D. ) FF VEGF concentrations were 1598+/-612 pg/mL and 2906+/-1558 pg/mL for Groups A and B , respectively ( p < 0.001 ) . In the women treated with GnRH-ant , we found a statistically significant reduction in serum LH levels ( 1.72+/-0.74 IU/L in Group A versus 0.93+/-0.43 IU/L in Group B , p < 0.001 ) , in serum oestradiol ( E2 ) levels ( 1562.1+/-410.7 pg/mL in Group A versus 1214.67+/-779.9 pg/mL in Group B , p < 0.05 ) , in FF E2 levels ( 1146+/-593 ng/mL in Group A versus 621+/-435 ng/mL in Group B , p < 0.05 ) , and in FF and rostenedione levels ( 136+/-55 ng/mL in Group A versus 78+/-31 ng/mL in Group B , p < 0.001 ) , as well as a reduction in the number of pregnancies , though not statistically significant ( 23.3 % in Group A versus 16.6 % in Group B ) . CONCLUSION The increase in FF VEGF levels in women treated with GnRH-ant might be explained by a suppression of LH and E2 levels Due to inherent differences between gonadotrophin-releasing hormone ( GnRH ) antagonists and agonists , their late effect on ovarian steroidal production during the luteal phase of IVF cycles may differ . The aim of this study was to characterize and compare the luteal phase hormonal profile after the use of GnRH antagonists or agonists in ovarian stimulation protocol s for IVF , in non-conception cycles , to avoid the effect of human chorionic gonadotrophin ( HCG ) during the luteal phase in conception cycles . Seventy-eight normo-ovulatory patients < 35 years old , undergoing IVF due to male or tubal infertility were r and omly allocated either to a GnRH antagonist ( study group ) or GnRH agonist treatment ( control group ) . Similar st and ard luteal support was given to all patients , using vaginal micronized progesterone . In non-conception cycles , no statistically significant differences were found comparing luteal phase . oestradiol or progesterone levels in the study and control groups . No statistically significant differences were found comparing the hormonal profile dynamics , the mid-luteal ( HCG day + 8) oestradiol/progesterone ratio and the percentage of mid-luteal oestradiol decline between the study and control groups . In conclusion , similar characteristics and dynamics of luteal phase oestradiol and progesterone were demonstrated comparing ovarian stimulation for IVF using GnRH agonist or antagonists , under similar luteal support OBJECTIVE To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation ( COS ) . STUDY DESIGN Phase III , r and omized , single center study of 131 patients undergoing COS and IVF with or without ICSI , in a University affiliated Hospital . Sixty-six patients were allocated to the protocol with antagonist and 65 to the agonist protocol arm . The Student 's t-test , the Mann-Whitney test and the chi-square test were applied as required , using SPSS for Windows with a two-sided 5 % significance level . RESULTS The mean ( + /-S.D. ) duration of stimulation was 9.5+/-1.7 days in the antagonist group and 10.6+/-2.1 days in the agonist group ( P=0.02 ) . The mean ( + /-S.D. ) duration of suppression was 4.6+/-1.3 days in the antagonist group and 27.3+/-5.2 days in the agonist group ( P<0.0001 ) . No significant differences were noted in other outcome measures : amount of rFSH required , estradiol level on hCG day , number of follicles > or=15 mm and endometrial thickness on oocyte retrieval day , number of oocytes retrieved , fertilization rate and number of OHS cases . Clinical pregnancy rates per-attempt and per-transfer were 15.1 % and 17.0 % in the antagonist group and 16.9 % and 20.0 % in the agonist group ( P=0.79 and 0.71 , respectively ) . CONCLUSIONS GnRH antagonists are an effective , safe and well tolerated alternative to agonists for COS |
10,946 | 24,167,538 | Compared with usual care , there was moderate quality evidence that individualized discharge planning is more effective at reducing readmissions or hospital LOS but not mortality , and very low quality evidence that it is more effective at improving HRQOL or patient satisfaction .
Compared with usual care , there was low quality evidence that the discharge planning plus postdischarge support is more effective at reducing readmissions but not more effective at reducing hospital LOS or mortality .
There was very low quality evidence that it is more effective at improving HRQOL or patient satisfaction | BACKGROUND Chronically ill people experience frequent changes in health status accompanied by multiple transitions between care setting s and care providers .
Discharge planning provides support services , follow-up activities , and other interventions that span pre-hospital discharge to post-hospital setting s. OBJECTIVE To determine if discharge planning is effective at reducing health re source utilization and improving patient outcomes compared with st and ard care alone . | BACKGROUND Case management is believed to promote continuity of care and decrease hospitalization rates , although few controlled trials have tested this approach . OBJECTIVE To assess the effectiveness of a st and ardized telephonic case-management intervention in decreasing re source use in patients with chronic heart failure . METHODS A r and omized controlled clinical trial was used to assess the effect of telephonic case management on re source use . Patients were identified at hospitalization and assigned to receive 6 months of intervention ( n = 130 ) or usual care ( n = 228 ) based on the group to which their physician was r and omized . Hospitalization rates , readmission rates , hospital days , days to first rehospitalization , multiple readmissions , emergency department visits , inpatient costs , outpatient re source use , and patient satisfaction were measured at 3 and 6 months . RESULTS The heart failure hospitalization rate was 45.7 % lower in the intervention group at 3 months ( P = .03 ) and 47.8 % lower at 6 months ( P = .01 ) . Heart failure hospital days ( P = .03 ) and multiple readmissions ( P = .03 ) were significantly lower in the intervention group at 6 months . Inpatient heart failure costs were 45.5 % lower at 6 months ( P = .04 ) . A cost saving was realized even after intervention costs were deducted . There was no evidence of cost shifting to the outpatient setting . Patient satisfaction with care was higher in the intervention group . CONCLUSIONS The reduction in hospitalizations , costs , and other re source use achieved using st and ardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes Abstract Objectives : To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure . Design : R and omised controlled trial . Setting : Acute medical admissions unit in a teaching hospital . Participants : 165 patients admitted with heart failure due to left ventricular systolic dysfunction . The intervention started before discharge and continued thereafter with home visits for up to 1 year . Main outcome measures : Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure . Results : 31 patients ( 37 % ) in the intervention group died or were readmitted with heart failure compared with 45 ( 53 % ) in the usual care group ( hazard ratio=0.61 , 95 % confidence interval 0.33 to 0.96).Compared with usual care , patients in the intervention group had fewer readmissions for any reason ( 86 v 114 , P=0.018 ) , fewer admissions for heart failure ( 19 v 45 , P<0.001 ) and spent fewer days in hospital for heart failure ( mean 3.43 v 7.46 days , P=0.0051 ) . Conclusions : Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure . What is already known on this topic Studies have suggested that nurse intervention may reduce readmission in patients with heart failure What this study adds Home based intervention from nurses reduces readmissions for worsening heart failure Regular contact to review treatment and patient education are likely to contribute to this To select patients for early discharge planning , a r and omized clinical trial evaluated a protocol that used risk factors identified upon hospital admission . The goal of the study was to determine if intervention with high-risk patients could reduce the need for hospital admission or skilled care . Of 13,255 patients screened , 835 study participants were identified as " at risk " for frequent health care re source use . Half of the high-risk patients were r and omly assigned to the experimental group ( n=417 ) and received discharge planning from day 3 of their hospital stay , while the control group ( n=418 ) received discharge planning only if there was a written physician request . Those patients receiving early , systematic discharge planning experienced an increased likelihood of successful return to home after hospital admission and a decreased chance of unscheduled readmission for the 9-month study period . Length of the index hospital stay was not affected by early planning , however . The major clinical implication is the potential for discharge planners to decrease the need for , and use of , health care re sources after hospital admission OBJECTIVE To determine whether enhanced access to primary care affects the diagnostic evaluation , pharmacologic management , or health outcomes of patients hospitalized with congestive heart failure ( CHF ) . DESIGN Multisite r and omized , controlled trial . SETTING Nine Veterans Affairs medical centers . PATIENTS 443 patients who were hospitalized with a diagnosis of CHF . INTERVENTION Enhanced access to primary care , including assignment of a primary care nurse and physician , increased telephone contact , additional outpatient visits , and patient education . MAIN OUTCOME MEASURES Diagnostic evaluation , pharmacologic management , health-related quality of life , and hospital readmission rates . RESULTS About 80 % of patients who had enhanced access to care and patients receiving usual care underwent recommended evaluation of left ventricular ejection fraction . Among the subset of patients for whom an angiotensin-converting enzyme ( ACE ) inhibitor was recommended ( i.e. , ejection fraction < 40 % ) , three quarters of the patients in both the enhanced access and usual care groups received the drug ( 75 % vs. 73 % ; P > 0.2 ) . Enhanced access to primary care did not improve quality of life and increased hospital readmissions , with an average of 1.5 + /- SD 2.0 readmissions per 6 months of follow-up for patients who had enhanced access compared with 1.1 + /- SD 1.8 for those who received usual care ( P = 0.02 ) . CONCLUSIONS Compliance with recommended CHF testing and treatment guidelines was equally high in both study groups . Enhanced access to primary care did not improve patients ' self-reported health status and was associated with more frequent hospitalizations PURPOSE This work addresses the unanswered question of whether multidisciplinary care ( MDC ) of heart failure ( HF ) can reduce readmissions when optimal medical care is applied in both intervention and control groups . METHODS In a r and omized , controlled study , 98 patients ( mean age , 70.8 + /- 10.5 years ) admitted to hospital with left ventricular failure ( New York Heart Association Class IV ) were assigned to routine care ( RC , n = 47 ) or MDC ( n = 51 ) . All patients received the same components of inpatient , optimal medical care of HF : specialist-led inpatient care ; titration to maximum tolerated dose of angiotensin-converting enzyme inhibitor before discharge ; attainment of predetermined discharge criteria ( weight stable , off all intravenous therapy , and no change in oral regimen for 2 days ) . Only those in the MDC group received inpatient and outpatient education and close telephone and clinic follow-up . The primary study endpoint was rehospitalization or death for a HF-related issue at 3 months . MAIN FINDINGS At 3 months , four people had events in the MDC group ( 7.8 % rate over 3 months ) compared with 12 people ( 25.5 % rate over 3 months ) in the RC group ( P = 0.04 ) . CONCLUSION These data demonstrate for the first time the intrinsic benefit of MDC in the setting of protocol -driven , optimal medical management of HF . Moreover , the event rate of 7.8 % at 3 months , as the lowest reported rate for such a high-risk group , underlines the value of this approach to the management of heart failure PURPOSE Several r and omized trials have found that discharge planning improves outcomes for hospitalized patients . We do not know if adding a clinical nurse specialist ( CNS ) to physician teams in hospitals that already have discharge planning services makes a difference . METHODS In 2 teaching hospitals , patients were r and omly assigned to regular hospital care or care with a clinical nurse specialist . The clinical nurse specialist facilitated hospital care by retrieving preadmission information , arranging in-hospital consultations and investigations , organizing postdischarge follow-up visits , and checking up on patients postdischarge with a telephone call . In-hospital outcomes included mortality and length of stay . Postdischarge outcomes included time to readmission or death , patient satisfaction , and the risk of adverse event . Adverse events were poor outcomes due to medical care rather than the natural history of disease . RESULTS A total of 620 sequential patients were r and omized ( CNS n = 307 , control n = 313 ) , of which 361 were followed after discharge from hospital ( CNS n = 175 , control n = 186 ) . The groups were similar for the probability of in-hospital death ( CNS 9.3 % vs control 9.7 % ) or being discharged to the community ( 58.0 % vs 60.0 % ) . The groups did not differ for postdischarge outcomes including readmission or death ( 21.6 % vs 15.6 % ; P = 0.16 ) or risk of adverse event ( 23.6 % vs 22.8 % ) . Mean [ SD ] patient ratings of overall quality of care on a scale of 10 was higher in the clinical nurse specialist group ( 8.2 [ 2.2 ] vs 7.6 [ 2.4 ] ; P = 0.052 ) . CONCLUSION The addition of a clinical nurse specialist to a medical team improved patient satisfaction but did not impact hospital efficiency or patient safety OBJECTIVE To determine the impact of a hospital-coordinated discharge care plan , involving a multidisciplinary team of primary health care providers , on hospital length of stay , quality of life , and both patient and general practitioner inclusion in , and satisfaction with , discharge procedures . DESIGN This investigation comprised a prospect i ve , r and omized , controlled , clinical trial . SETTING This multicentre and cross-jurisdictional study focused on areas of tertiary and primary health care as well as community allied health in Western Australia . PARTICIPANTS Patients ( n = 189 ) with chronic cardiorespiratory diagnoses were recruited from respiratory , cardiovascular , and general medical wards at two tertiary hospitals . INTERVENTION Subjects were r and omly assigned to one of two groups . Intervention group patients received a discharge care plan in accordance with that outlined in the Australian Enhanced Primary Care Package , completed before discharge and sent to the patient 's general practitioner and other community service providers for review . Control patients were discharged under existing hospital processes . Outcome measures . Patients and general practitioners were surveyed pre-discharge and 7 days post-discharge for quality of life and opinion of discharge procedures . Hospital length of stay was also determined . RESULTS Significant improvements in discharge planning involvement , health service access , confidence with discharge procedures , and opinion of discharge based on previous experience were seen for patients who received the discharge care plan . Further , improved perceptions of mental quality of life were observed within the first week post-discharge for intervention patients . Length of stay showed no difference between groups . Extent and speed of hospital-general practitioner communication were significantly improved via the intervention . CONCLUSIONS Our results indicate that a multidisciplinary discharge care plan , initiated before separation , improves quality of life , involvement , and satisfaction with discharge care , and hospital-general practitioner integration . As such , it possesses benefits over current Western Australian hospital discharge procedures for the care of chronically ill population Background . The growing number of patients with congestive heart failure has increased both the pressure on hospital re sources and the need for community management of the condition . Improving hospital-to-home transition for this population is a logical step in responding to current practice guidelines ’ recommendations for coordination and education . Positive outcomes have been reported from trials evaluating multiple interventions , enhanced hospital discharge , and follow-up through the addition of a case management role . The question remains if similar gains could be achieved working with usual hospital and community nurses . Methods . A 12-week , prospect i ve , r and omized controlled trial was conducted of the effect of transitional care on health-related quality of life ( disease-specific and generic measures ) , rates of readmission , and emergency room use . The nurse-led intervention focused on the transition from hospital-to-home and supportive care for self-management 2 weeks after hospital discharge . Results . At 6 weeks after hospital discharge , the overall Minnesota Living with Heart Failure Question naire ( MLHFQ ) score was better among the Transitional Care patients ( 27.2 ± 19.1 SD ) than among the Usual Care patients ( 37.5 ± 20.3 SD;P = 0.002 ) . Similar results were found at 12 weeks postdischarge for the overall MLHFQ and at 6- and 12-weeks postdischarge for the MLHFQ ’s Physical Dimension and Emotional Dimension subscales . Differences in generic quality life , as assessed by the SF-36 Physical component , Mental Component , and General Health subscales , were not significantly different between the Transition and Usual Care groups . At 12 weeks postdischarge , 31 % of the Usual Care patients had been readmitted compared with 23 % of the Transitional Care patients ( P = 0.26 ) , and 46 % of the Usual Care group visited the emergency department compared with 29 % in the Transitional Care group ( & khgr;2 = 4.86 , df 1 , P = 0.03 ) . Conclusions . There were significant improvements in health-related quality of life ( HRQL ) associated with Transitional Care and less use of emergency rooms BACKGROUND We examined the effect of a home-based intervention ( HBI ) on readmission and death among " high-risk " patients with congestive heart failure discharged home from acute hospital care . METHODS Hospitalized patients with congestive heart failure and impaired systolic function , intolerance to exercise , and a history of 1 or more hospital admissions for acute heart failure were r and omized to either usual care ( n=48 ) or HBI at 1 week after discharge ( n=49 ) . Home-based intervention comprised a single home visit ( by a nurse and pharmacist ) to optimize medication management , identify early clinical deterioration , and intensify medical follow-up and caregiver vigilance as appropriate . The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge . Secondary end points included duration of hospital stay and overall mortality . RESULTS During follow-up , patients in the HBI group had fewer unplanned readmissions ( 36 vs 63 ; P=.03 ) and fewer out-of-hospital deaths ( 1 vs 5 ; P=.11 ) : 0.8+/-0.9 vs 1.4+/-1.8 ( mean + /- SD ) events per patient assigned to HBI and usual care , respectively ( P=.03 ) . Patients in the HBI group also had fewer days of hospitalization ( 261 vs 452 ; P=.05 ) and fewer total deaths ( 6 vs 12 ; P=.11 ) . Patients assigned to usual care were more likely to experience 3 or more readmissions for acute heart failure ( P=.02 ) . Predictors of unplanned readmission were ( 1 ) 14 days or more of unplanned readmission during the 6 months before study entry ( odds ratio [ OR ] , 5.2 ; 95 % confidence interval [ CI ] , 1.8 - 16.2 ) , ( 2 ) previous admission for acute myocardial ischemia ( OR , 3.3 ; 95 % CI , 1.2 - 9.1 ) , and ( 3 ) an albumin plasma concentration of 38 g/L or less ( OR , 2.4 ; 95 % CI , 1.2 - 6.0 ) . Home-based intervention was also associated with a trend toward reduced risk of unplanned readmission ( OR , 0.4 ; 95 % CI , 0.2 - 1.1 ) . CONCLUSION Among a cohort of high-risk patients with congestive heart failure , HBI was associated with reduced frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge from the hospital BACKGROUND AND PURPOSE Integrated Care Pathway ( ICP ) is an organized , goal -defined , and time-managed plan that has the potential of facilitating timely interdisciplinary coordination , improving discharge planning , and reducing length of hospital stay . METHODS An ICP for stroke rehabilitation based on evidence of best practice , professional st and ards , and existing infrastructure was developed . Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were r and omized to receive ICP care coordinated by an experienced nurse ( n=76 ) or conventional multidisciplinary care ( n=76 ) . RESULTS The age , sex , premorbid functional ability , and stroke characteristics of the 2 groups were comparable . There were no differences in mortality rates ( 10 [ 13 % ] versus 6 [ 8 % ] ) , institutionalization ( 10 [ 13 % ] versus 16 [ 21 % ] ) , or length of hospital stay ( 50+/-19 versus 45+/-23 days ) between patients receiving ICP or multidisciplinary care . Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks ( median change in Barthel Activities of Daily Living Index 6 versus 2 ; P<0.01 ) and had higher Quality of Life scores at 12 weeks ( 65 versus 59 ; P=0.07 ) and 6 months ( 72 versus 63 ; P<0.005 ) . There were no significant differences in the mean duration of physiotherapy ( 42.8+/-41.2 versus 39.4+/-36.4 hours ) or occupational therapy ( 8.5+/-7.5 versus 8.0+/-7.5 hours ) received between the 2 groups . CONCLUSIONS ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit . Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care To determine the feasibility and efficacy of early discharge planning , initiated by admitting department personnel , a r and omized , controlled trial was undertaken in 2 acute care , university-affiliated hospitals . The intervention tested was referral of patients by admitting personnel to nursing , social work , physiotherapy , occupational therapy , or dietary services for potential discharge planning . A 1-page , 65-item question naire was design ed to identify patients for referral to the various allied health services . A copy of this was sent to the appropriate service , according to predefined criteria . The question naire took an average of 4 min to complete . The criteria used were highly predictive of length of stay , the most important being age , followed by living outside St. John 's , admission within the previous 3 months , emergency admission , and being in need of community services . In Hospital A , the cases ( n = 421 ) referred for early discharge planning had significantly shorter length of stay ( Mantel-Cox , p = 0.03 ) than controls ( n = 420 ) , who were identical for all factors predictive of prolonged length of stay . The reduction in length of stay amounted to a mean of 0.8 d. In Hospital B ( n = 758 ) , the intervention was less effective because of a lower proportion of patients with factors associated with prolonged hospital stay and , perhaps , because of inadequate implementation of the program . We conclude that identification , by admitting department personnel , of patients who may benefit from early discharge planning is feasible . This process will reduce length of hospital stay , but its effectiveness is dependent on case mix variables and enthusiastic implementation of the program Objective : To evaluate the impact of a hospital based community liaison pharmacy service on a range of outcomes in patients aged more than 55 years and taking more than 3 prescribed drugs , who had been admitted to the medical unit of a district general hospital in Northern Irel and . Methods : Having recruited 243 patients , a total of 162 patients completed the full protocol ( 81 r and omly assigned to intervention and 81 to control ; mean age of control patients 75 years ; mean age of intervention patients 73 years ) . The interventions by the community liaison pharmacist included : preparation of an accurate medication record following a full review of current medication use ; medication counselling ; provision of a medicines record sheet informing the patient how to take their drugs ; provision of a pharmaceutical discharge letter detailing changes made to drug therapy ( this was faxed to the patient 's GP and community pharmacist on the day of discharge ) ; provision of a Medicines Helpline . Results : The key findings were as follows : problems were identified in 80 % of the intervention patients ' prescription charts , 49 % of which related to drug omissions from the patients ' domiciliary prescriptions . The GP practice record was the most accurate ( mean error rate 12.6 % ) while the GP referral letter was the least accurate ( mean error rate 47.3 % ) source of medication information . Drugs patients brought to hospital were also an inaccurate source ( mean error rate 44.0 % ) . The intervention group patients , when compared with control patients , had a significant reduction ( P=0.005 ) in drug mismatch between drugs prescribed at discharge and taken at home , and had a greater knowledge of their drug regimen 10–14 days after discharge ( P |Ld 0.001 ) . The vast majority of patients ( 96 % ) felt that the provision of a medicine helpline was a useful service . Conclusions : The study indicated clear benefits from the involvement of a hospital based community liaison pharmacist in achieving seamless pharmaceutical care between the primary and secondary healthcare setting BACKGROUND Hospital admissions among patients with congestive heart failure ( CHF ) are a major contributor to health-care costs . Previous investigations suggest that the therapeutic efficacy of pharmacotherapy in CHF may be improved by strategies incorporating home visits to identify and address factors precipitating deterioration and result ant readmission . METHODS Chronic CHF patients discharged home after acute hospital admission were r and omly assigned usual care ( n=100 ) or a multidisciplinary , home-based intervention ( n=100 ) , consisting of a home visit by a cardiac nurse 7 - 14 days after discharge . The primary endpoint of the study was frequency of unplanned readmission plus out-of-hospital death within 6 months . FINDINGS During 6 months ' follow-up there were 129 primary endpoint events in the usual-care group and 77 in the intervention group ( p=0.02 ) . More intervention-group than usual-care patients remained event-free ( 38 vs 51 ; p=0.04 ) . Overall , there were fewer unplanned readmissions ( 68 vs 118 ; p=0.03 ) and associated days in hospital ( 460 vs 1173 ; p=0.02 ) among intervention-group patients . Hospital-based costs were Australian $ 490,300 for the intervention group and A$ 922,600 for the usual-care group ( p=0.16 ) ; the mean cost of the intervention was A$ 350 per patient , and other community-based costs were similar for both groups . INTERPRETATION A home-based intervention has the potential to decrease the rate of unplanned readmissions and associated health-care costs , prolong event-free and total survival , and improve quality of life among patients with chronic CHF BACKGROUND Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure , persistently high rates of readmission , especially within the first month of discharge , continue to be documented . AIMS As part of an ongoing r and omized study on the value of multidisciplinary care in a high risk ( NYHA Class IV ) , elderly ( mean age 69 years ) heart failure population , we examined the effects of this intervention on previously high ( 20 % ) 1-month readmission rates . METHODS Unlike previous studies of this approach , both multidisciplinary ( MC ) and routine care ( RC ) population s were cared for by the cardiology service , complied with adherence to clinical stability criteria prior to discharge ( 100 % of patients ) and received at least target dose angiotensin-converting enzyme ( ACE ) inhibition with perindopril prior to discharge ( 94 % of indicated patients ) . We analysed death and unplanned readmission for heart failure at 1 month . RESULTS This early report from the first 70 patients ( 67 % male , 71 % systolic dysfunction with a mean ejection fraction of 31.0+/-6.7 % ) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups . This unexpected result represents a dramatic improvement both for this patient cohort ( 20 % 30-day readmission rate prior to enrollment reduced to 0 % following the index admission in both care groups ) and in comparison with available data . CONCLUSIONS Critical contributors to this improvement appear to be specialist cardiology care , adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge . Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition OBJECTIVE To test the impact of a geriatric evaluation and management model on the costs of acute hospital management of emergently admitted older adults . DESIGN R and omized controlled trial . Patients were followed in the acute hospital from admission through discharge . Results based on both univariate and multiple regression analyses . SETTING Private , nonprofit , academic medical center in a densely populated urban area . PATIENTS Adults 70 years of age and older admitted from the Emergency Department to the medicine service ( non-ICU admission ) who did not have an internist on staff at the admitting hospital . Of 141 r and omized patients , 111 ( 78.7 % ) met eligibility criteria . INTERVENTION Assignment of a geriatrician and a social worker as the primary managing team during the hospital stay . MAIN OUTCOME MEASURES Length of stay , total cost of acute hospital care , cost of laboratory , pharmacy , and rehabilitation services . RESULTS Patients in the intervention group had 2.1 fewer days of hospitalization , but this shorter length of stay was not statistically significant ( P = 0.108 ) . There were no differences in mortality or discharge disposition . In risk-adjusted , multiple regression analysis the intervention group had a statistically significant lower predicted total cost per patient than the usual care group ( -$2,544 , P = 0.029 ) ; assignment to the intervention group was associated with a lower predicted cost per patient for laboratory ( including cardiology graphics ) services ( P = 0.007 ) and pharmacy costs ( P = 0.047 ) . CONCLUSIONS When controlled for important predictors of expected re source use , care provided by a geriatric management team result ed in a significant reduction in the cost of hospitalization . A reduction in the cost of laboratory , cardiographic , and pharmacy services is consistent with the team 's philosophy of defining the services needed based on goals related to functional outcomes OBJECTIVES We determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure ( HF ) . BACKGROUND Disease management programs for patients with HF including medical components may reduce readmissions by 40 % or more , but the value of an intervention focused on education and support is not known . METHODS We conducted a prospect i ve , r and omized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF . RESULTS Among the 88 patients ( 44 intervention and 44 control ) in the study , 25 patients ( 56.8 % ) in the intervention group and 36 patients ( 81.8 % ) in the control group had at least one readmission or died during one-year follow-up ( relative risk = 0.69 , 95 % confidence interval [ CI ] : 0.52 , 0.92 ; p = 0.01 ) . The intervention was associated with a 39 % decrease in the total number of readmissions ( intervention group : 49 readmissions ; control group : 80 readmissions , p = 0.06 ) . After adjusting for clinical and demographic characteristics , the intervention group had a significantly lower risk of readmission compared with the control group ( hazard ratio = 0.56 , 95 % CI : 0.32 , 0.96 ; p = 0.03 ) and hospital readmission costs of $ 7,515 less per patient . CONCLUSIONS A formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF BACKGROUND Many patients encounter problems in the first weeks after discharge from hospital . Telephone follow-up ( TFU ) is reputed to be a good tool for providing medical advice , managing symptoms , identifying complications and giving reassurance after discharge . Therefore , we aim ed to study whether tight TFU would increase patient satisfaction , improve compliance and reduce re-hospitalization rate . METHODS The study population included 400 patients , hospitalized in an Internal Medicine Department , r and omly divided into two groups ; TFU and control . TFU took place one week and one month after discharge . Three months later , members of both groups were contacted by telephone . RESULTS Satisfaction was increased in the TFU group compared with control group by 6 - 12 % in most fields . Notably , 87 % of patients in the TFU group indicated that earlier telephone contact increased their satisfaction . In addition , 78.2 % of the patients in the control group reported that they performed the tests that were recommended at discharge and 86.5 % reported that they received explanations regarding their medications . In the TFU group , this percentage was increased significantly to 86.9 % ( P=0.02 ) and 96.7 % ( P<0.0001 ) , respectively . As to treatment results , 93 % of the patients in the TFU group as compared to 84 % in the control group reported improvement in their symptoms . A non-significant trend towards fewer readmission was observed in the TFU group ( 26 % vs. 35 % P=0.062 ) . CONCLUSIONS TFU can improve medical treatment by increasing satisfaction and compliance . A trend towards decreased readmission rates was observed , which may lead to a reduction in the burden on the medical system OBJECTIVE To study the effects of a comprehensive discharge planning protocol , design ed specifically for the elderly and implemented by nurse specialists , on patient and caregiver outcomes and cost of care . DESIGN R and omized clinical trial . SETTING Hospital of the University of Pennsylvania . PATIENTS 276 patients and 125 caregivers . Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups . MEASUREMENTS Group differences in patient outcomes ( length of initial hospital stay , length of time between initial hospital discharge and readmission , and rehospitalization rates ) and charges for care ( charges for initial hospitalization , rehospitalizations , health services after discharge , and nurse specialist services ) were measured 2 , 6 , and 12 weeks after discharge . RESULTS From the initial hospital discharge to 6 weeks after discharge , patients in the medical intervention group had fewer readmissions , fewer total days rehospitalized , lower readmission charges , and lower charges for health care services after discharge . No differences in these outcomes were found between the surgical intervention and control groups during this period . CONCLUSIONS Study findings support the need for comprehensive discharge planning design ed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings . The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge Objective To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure . Design Prospect i ve , r and omised trial . Setting University hospital with a primary catchment area of 250 000 inhabitants . Patients 190 patients ( aged 65–84 years , 52.3 % men ) hospitalised because of heart failure . Intervention Two types of patient management were compared . The intervention group received education on heart failure and self management , with follow up at an easy access , nurse directed outpatient clinic for one year after discharge . The control group was managed according to routine clinical practice . Main outcome measures Time to readmission , days in hospital , and health care costs during one year . Results The one year survival rate was 71.8 % ( n = 79 ) in the control group and 70.0 % ( n = 56 ) in the intervention group ( NS ) . The mean time to readmission was longer in the intervention group than in the control group ( 141 ( 87 ) v106 ( 101 ) ; p < 0.05 ) and number of days in hospital tended to be fewer ( 4.2 ( 7.8 ) v 8.2 ( 14.3 ) ; p = 0.07 ) . There was a trend towards a mean annual reduction in health care costs per patient of US$ 1300 ( US$ 1 = SEK 7.76 ) in the intervention group compared with costs in the controls ( US$ 3594 v 2294 ; p = 0.07 ) . Conclusions A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission RATIONALE Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department ( ED ) visit rates . OBJECTIVE To assess the impact of a supplemental care bundle targeting high-risk elderly in patients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and /or ED visitation at 30 and 60 days following discharge . PATIENTS / METHODS R and omized controlled pilot study in 41 medical in patients predisposed to unplanned readmission or postdischarge ED visitation , conducted at Baylor University Medical Center . The intervention group care bundle consisted of medication counseling/reconciliation by a clinical pharmacist ( CP ) , condition specific education/enhanced discharge planning by a care coordinator ( CC ) , and phone follow-up . RESULTS Groups had similar baseline characteristics . Intervention group readmission/ED visit rates were reduced at 30 days compared to the control group ( 10.0 % versus 38.1 % , P = 0.04 ) , but not at 60 days ( 30.0 % versus 42.9 % , P = 0.52 ) . For those patients who had a readmission/postdischarge ED visit , the time interval to this event was longer in the intervention group compared to usual care ( 36.2 versus 15.7 days , P = 0.05 ) . Study power was insufficient to reliably compare the effects of the intervention on lengths of index hospital stay between groups . CONCLUSIONS A targeted care bundle delivered to high-risk elderly in patients decreased unplanned acute health care utilization up to 30 days following discharge . Dissipation of this effect by 60 days postdischarge defines reasonable expectations for analogous hospital-based educational interventions . Further research is needed regarding the impacts of similar care bundles in larger population s across a variety of inpatient setting OBJECTIVE To determine the effect of a medical team coordinator ( MTC ) on the length of stay in a teaching hospital . DESIGN R and omized controlled trial . SETTING Two of four general medical clinical teaching units ( CTUs ) . PATIENTS Patients admitted to the CTUs between July and October 1990 except those who were admitted directly to an intensive care unit or whose death was expected within 48 hours . The 267 patients were r and omly assigned to receive either st and ard medical care or st and ard medical care plus MTC services . INTERVENTION The MTC was a baccalaureate nurse whose role was to facilitate administrative tasks such as discharge planning , to coordinate tests and procedures , and to collect and collate patient information . MAIN OUTCOME MEASURES Length of hospital stay . A subgroup of 40 patients was asked to complete a brief survey on medical care information and satisfaction . RESULTS The MTC intervention reduced the mean length of stay by 1.97 days ( p less than or equal to 0.04 , 95 % confidence interval [ CI ] 1.02 to 2.92 days ) . Sub analysis by diagnostic group revealed that most of this effect was in an ill-defined group of disorders . In the survey more patients in the MTC group than in the other group reported being satisfied with their medical care ( 89 % v. 62 % ; p less than or equal to 0.05 , 95 % CI 2 % to 52 % ) . CONCLUSIONS The services of an MTC help to reduce the length of hospital stay for some groups of patients . Further research is necessary to examine which components of the MTC intervention are most effective and in what conditions In cooperation between the home care system in the Municipality of Rødovre and four hospital departments in the County of Copenhagen , a controlled and r and omized investigation was undertaken among the hospitalized patients of 65 years and over from the Municipality of Rødovre . A nurse employed by the Municipality particularly for this project visited the hospital daily and followed the 135 participants in the intervention group with the objects of obtaining information from the primary sector if necessary , discussing discharge with the patient and the hospital staff , coordinating possible supportive measures in the patient 's home and visiting the patient in his home immediately after discharge from hospital in order to ensure continuity in care and treatment . The 138 participants in the control group underwent the usual procedures in connection with admission to hospital . In this article , the consequences of the contributions by the health visitor in the hospital are described in relation to the course of hospitalization . The intervention group had an average stay in hospital of 11.0 days as compared with 14.3 days in the control group ( p greater than 0.05 ) , and the total number of bed-days were 1,490 and 1,970 , respectively . In addition , the two groups were compared as regards the number of diagnostic procedures during hospitalization , the number of deaths , the diagnoses on discharge and the functional capacity . No differences were observed in these respects between the two groups . Three patients from the control group were discharged to residential institutions as compared with none in the intervention group . ( ABSTRACT TRUNCATED AT 250 WORDS Pardessus V , Puisieux F , Di Pompeo C , Gaudefroy C , Thevenon A , Dewailly P : Benefits of home visits for falls and autonomy in the elderly : A r and omized trial study . Am J Phys Med Rehabil 2002;81:247–252 . Objective To investigate whether home visits by a occupational therapist reduces the risk of falling and improves the autonomy of older patients hospitalized for falling . Design In this r and omized , controlled trial set in a geriatric hospital , 60 patients ( mean age , 83.5 yr ) who were hospitalized for falling were recruited from the acute medicine department . A home visit from an occupational therapist and an ergotherapist assessed patients ’ homes for environmental hazards and recommended modifications . The outcomes measured were falls , autonomy , hospitalization for falling , institutionalization , and death . Results During the follow-up period , the rate of falls , hospitalization for falls , institutionalization , and death were not significantly different between the two groups . Both groups had a loss of dependence at 12 mo . This loss of dependence was significant in the control group but not in the intervention group . Conclusions Home visits from occupational therapists during hospitalization of older patients at risk for falling can help to preserve the patient ’s autonomy A r and omised controlled trial was conducted to assess whether a single intervention by a health visitor reduced the unplanned re-admission of elderly people discharged from geriatric wards . Two hundred and four consecutive discharges from geriatric wards were r and omly allocated to receive either a single visit from the health visitor at 72 h in addition to normal follow-up services or to a control group receiving the normal follow-up services . The primary outcome measure was the unplanned re-admissions over the following 6 months . There were 40 cases and 43 control patients with unplanned re-admissions in the first 6 months . The total lengths of the unplanned re-admissions were 1237 days for cases and 1427 for controls , an average of 12.1 days for cases and 14.0 for controls ( 95 % confidence interval -4.9 to 8.7 days , not significant ) . A visit by a health visitor to elderly patients after discharge from geriatric wards is unlikely to be of sufficient benefit to the patients for the service to be funded from a saving in unplanned re-admissions BACKGROUND Both r and omized and nonr and omized controlled studies have linked congestive heart failure ( CHF ) case management ( CM ) to decreased readmissions and improved outcomes in mostly homogeneous setting s. The objective of this r and omized controlled trial was to test the effect of CHF CM on the 90-day readmission rate in a more heterogeneous setting . METHODS A total of 287 patients admitted to the hospital with the primary or secondary diagnosis of CHF , left ventricular dysfunction of less than 40 % , or radiologic evidence of pulmonary edema for which they underwent diuresis were r and omized . The intervention consisted of 4 major components : early discharge planning , patient and family CHF education , 12 weeks of telephone follow-up , and promotion of optimal CHF medications . RESULTS The 90-day readmission rates were equal for the CM and usual care groups ( 37 % ) . Total inpatient and outpatient median costs and readmission median cost were reduced 14 % and 26 % , respectively , for the intervention group . Patients in the CM group were more likely to be taking CHF medication at target doses , but dosages did not increase significantly throughout 12 weeks . Although both groups took their medications as prescribed equally well , the rest of the adherence to treatment plan was significantly better in the CM group . Subgroup analysis of patients who lived locally and saw a cardiologist showed a significant decrease in CHF readmissions for the intervention group ( P = .03 ) . CONCLUSIONS These results suggest several limitations to the generalizability of the CHF CM-improved outcome link in a heterogeneous setting . One explanation is that the lack of coordinated system supports and varied accessibility to care in an extended , nonnetworked physician setting limits the effectiveness of the CM OBJECTIVES To examine the effectiveness of a transitional care intervention delivered by advanced practice nurses ( APNs ) to elders hospitalized with heart failure . DESIGN R and omized , controlled trial with follow-up through 52 weeks postindex hospital discharge . SETTING Six Philadelphia academic and community hospitals . PARTICIPANTS Two hundred thirty-nine eligible patients were aged 65 and older and hospitalized with heart failure . INTERVENTION A 3-month APN-directed discharge planning and home follow-up protocol . MEASUREMENTS Time to first rehospitalization or death , number of rehospitalizations , quality of life , functional status , costs , and satisfaction with care . RESULTS Mean age of patients ( control n=121 ; intervention n=118 ) enrolled was 76 ; 43 % were male , and 36 % were African American . Time to first readmission or death was longer in intervention patients ( log rank chi(2)=5.0 , P=.026 ; Cox regression incidence density ratio=1.65 , 95 % confidence interval=1.13 - 2.40 ) . At 52 weeks , intervention group patients had fewer readmissions ( 104 vs 162 , P=.047 ) and lower mean total costs ( $ 7,636 vs $ 12,481 , P=.002 ) . For intervention patients , only short-term improvements were demonstrated in overall quality of life ( 12 weeks , P<.05 ) , physical dimension of quality of life ( 2 weeks , P<.01 ; 12 weeks , P<.05 ) and patient satisfaction ( assessed at 2 and 6 weeks , P<.001 ) . CONCLUSION A comprehensive transitional care intervention for elders hospitalized with heart failure increased the length of time between hospital discharge and readmission or death , reduced total number of rehospitalizations , and decreased healthcare costs , thus demonstrating great promise for improving clinical and economic outcomes BACKGROUND Congestive heart failure is the most common indication for admission to the hospital among older adults . Behavioral factors , such as poor compliance with treatment , frequently contribute to exacerbations of heart failure , a fact suggesting that many admissions could be prevented . METHODS We conducted a prospect i ve , r and omized trial of the effect of a nurse-directed , multidisciplinary intervention on rates of readmission within 90 days of hospital discharge , quality of life , and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure . The intervention consisted of comprehensive education of the patient and family , a prescribed diet , social-service consultation and planning for an early discharge , a review of medications , and intensive follow-up . RESULTS Survival for 90 days without readmission , the primary outcome measure , was achieved in 91 of the 142 patients in the treatment group , as compared with 75 of the 140 patients in the control group , who received conventional care ( P = 0.09 ) . There were 94 readmissions in the control group and 53 in the treatment group ( risk ratio , 0.56 ; P = 0.02 ) . The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group ( 54 vs. 24 , P = 0.04 ) , whereas the number of readmissions for other causes was reduced by 28.5 percent ( 40 vs. 29 , P not significant ) . In the control group , 23 patients ( 16.4 percent ) had more than one readmission , as compared with 9 patients ( 6.3 percent ) in the treatment group ( risk ratio , 0.39 ; P = 0.01 ) . In a subgroup of 126 patients , quality -of-life scores at 90 days improved more from base line for patients in the treatment group ( P = 0.001 ) . Because of the reduction in hospital admissions , the overall cost of care was $ 460 less per patient in the treatment group . CONCLUSIONS A nurse-directed , multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure Context Emergency department visits and rehospitalizations are common after hospital discharge . Contribution This trial demonstrated that a nurse discharge advocate and clinical pharmacist working together to coordinate hospital discharge , educate patients , and reconcile medications led to fewer follow-up emergency visits and rehospitalizations than usual care alone . Caution The trial was conducted at a single center , and not all eligible patients were enrolled . Implication A systematic approach to hospital discharges can reduce unnecessary health service use . The Editors One in 5 hospitalizations is complicated by postdischarge adverse events ( 1 , 2 ) , some of which may lead to preventable emergency department visits or readmissions . Despite this finding , hospital discharge procedures have not been st and ardized ( 3 ) . In addition , the declining presence of primary care providers ( PCPs ) in hospitals has not been adequately accompanied by systems to ensure that patient data are transferred to subsequent caregivers ( 4 , 5 ) . For example , discharge summaries frequently lack critical data and are not sent to the PCP in a timely fashion ( 6 , 7 ) , result ing in outpatient clinicians being unaware of test results that were pending at discharge ( 8) and evaluations that were scheduled to be done after discharge not being completed ( 9 ) . Similarly , patients are often left unprepared at discharge ; many do not underst and their discharge medications and can not recall their chief diagnoses ( 10 ) . With more than 32 million adult discharges in the United States each year ( 11 ) , these deficiencies in the transition of care increase illness , unnecessary hospital utilization , and cost . Some peridischarge interventions have shown a reduction in hospital readmission rates and cost ( 1214 ) , emergency department visits ( 15 ) , and postdischarge adverse events ( 16 ) , whereas some have shown little or no effect ( 1720 ) . Peridischarge interventions have also shown improved PCP follow-up and outpatient work-ups ( 21 ) and higher patient satisfaction ( 15 ) . Most of these studies have focused on specific diagnoses ( 14 , 22 , 23 ) or highly selected population s , such as geriatric adults ( 12 , 13 , 19 , 24 ) . Some have focused on specific aspects of the discharge , such as increasing access to primary care follow-up ( 25 ) , connecting with transitional nursing services ( 26 ) , or improving patients ' ability to advocate for themselves after discharge ( 12 ) . To date , no study has evaluated a st and ardized discharge intervention that includes patient education , comprehensive discharge planning , and postdischarge telephone reinforcement in a general medical population . In 2004 , we began an in-depth examination of hospital discharge , for which we design ed a package of services to minimize discharge failuresa process called reengineered discharge ( RED ) ( Table 1 ) ( 3 , 27 ) . We did a r and omized , controlled trial to evaluate the clinical effect of implementing RED among patients admitted to a general medical service . Table 1 . Components of Reengineered Hospital Discharge Methods Setting and Participants We conducted a 2-group , r and omized , controlled trial of English-speaking patients 18 years of age or older who were admitted to the medical teaching service of Boston Medical Center , Boston , Massachusettsa large , urban , safety-net hospital with an ethnically diverse patient population . Patients had to have a telephone , be able to comprehend study details and the consent process in English , and have plans to be discharged to a U.S. community . We did not enroll patients if they were admitted from a skilled nursing facility or other hospital , transferred to a different hospital service before enrollment , admitted for a planned hospitalization , were on hospital pre caution s or suicide watch , or were deaf or blind . Boston University 's institutional review board approved all study activities . R and omization Each morning , a list of admitted patients was review ed for initial eligibility ( hospital location , age , date and time of admission , and previous enrollment ) . Last names of potential participants were ranked by using a r and om-number sequence to determine the order in which to approach patients for enrollment . A trained research assistant then approached each patient and further determined eligibility according to inclusion and exclusion criteria ( Figure 1 ) . Figure 1 . Study flow diagram . * Patients did not meet inclusion criteria if they were admitted from or planned discharge to an institutional setting ( n= 74 ) , planned hospitalization ( n= 3 ) or discharge to a non-U.S. community ( n= 5 ) , were transferred to different hospital service ( n= 8) , did not speak English ( n= 371 ) or have a telephone ( n= 71 ) , were on hospital pre caution s ( n= 274 ) or suicide watch with a sitter ( n= 10 ) , were unable to consent ( n= 181 ) , had sickle cell disease as the admitting diagnosis ( n= 38 ) , had privacy status ( n= 8) , were deaf or blind ( n= 2 ) , or other ( n= 4 ) . Usual care participants did not meet eligibility criteria if they were discharged to a nursing facility ( n= 28 ) , were transferred to another hospital service ( n= 1 ) , were previously enrolled ( n= 1 ) , died during index admission ( n= 2 ) , requested to be removed ( n= 5 ) , or other ( n= 3 ) . Intervention participants did not meet eligibility criteria if they were discharged to a nursing facility ( n= 21 ) , were transferred to another hospital service ( n= 6 ) , died during index admission ( n= 1 ) , requested to be removed ( n= 2 ) , or other ( n= 8) . 107 intervention participants did not receive a reinforcement call because they could not be reached by telephone ( n= 93 ) , they were readmitted the same or next day ( n= 2 ) , there was no staffing coverage ( n= 8) , or other ( n= 4 ) . By using block r and omization ( 28 ) with varying block sizes of 6 and 8 , we r and omly arranged index cards indicating either the usual care or intervention group . We placed the cards in opaque envelopes labeled consecutively with study numbers . We assigned eligible participants who consented to enrollment to a study group by revealing the concealed index card . This process continued until 2 participants were enrolled each day of the week ( or 3 participants if the first 2 participants were r and omly assigned to the usual care group ) . This protocol ensured that research assistants could not selectively choose potential participants for enrollment or predict assignment . Participants r and omly assigned to usual care received no further intervention . There were 40 participants in the usual care group and 38 in the intervention group who were enrolled but no longer met inclusion criteria at discharge ( most commonly because they were discharged to a nursing facility ) . Because the primary analysis was by intention to treat , we included these participants in the analysis , with the exception of those who died before index discharge , requested to be removed , or were previously enrolled ( Figure 1 ) . Interventions Nurse discharge advocates ( DAs ) carried out all aspects of the in-hospital intervention . We hired 6 part-time DAs to work with intervention participants to ensure coverage by 1 DA 7 days a week , 5 hours a day . We trained all DAs to deliver the RED intervention by using a manual containing detailed scripts , observation of relevant clinical interactions , and simulated practice sessions . The primary goals of the DA were to coordinate the discharge plan with the hospital team and educate and prepare the participant for discharge . At admission , the DA completed the RED intervention components outlined in Table 1 . Additional information about the DA training manual is published elsewhere ( 3 ) and can be found on our Web site ( www.bu.edu/fammed/projectred/index.html ) . With information collected from the hospital team and the participant , the DA created the after-hospital care plan ( AHCP ) , which contained medical provider contact information , date s for appointments and tests , an appointment calendar , a color-coded medication schedule , a list of tests with pending results at discharge , an illustrated description of the discharge diagnosis , and information about what to do if a problem arises . Information for the AHCP was manually entered into a Microsoft Word ( Microsoft , Redmond , Washington ) template , printed , and spiral-bound to produce an individualized , color booklet design ed to be accessible to individuals with limited health literacy . By using scripts from the training manual , the DA used a teach-back methodology ( 29 ) to review the contents of the AHCP with the participant . On the day of discharge , the AHCP and discharge summary were faxed to the PCP . A clinical pharmacist telephoned the participants 2 to 4 days after the index discharge to reinforce the discharge plan by using a scripted interview . The pharmacist had access to the AHCP and hospital discharge summary and , over several days , made at least 3 attempts to reach each participant . The pharmacist asked participants to bring their medications to the telephone to review them and address medication-related problems ; the pharmacist communicated these issues to the PCP or DA . Outcomes Measures and Follow-up At the time of recruitment , research assistants collected baseline data , including sociodemographic characteristics ; the Short Form-12 Health Survey , Version 2 ( 30 ) ; the depression subscale from the Patient Health Question naire-9 ( 31 ) ; and the Rapid Estimate of Adult Literacy in Medicine ( 32 ) . We calculated the Charlson Comorbidity Index score by using primary and secondary diagnoses recorded on the index admission discharge summary ( 33 ) . We determined the number of hospital admissions and emergency department visits in the 6 months before index admission through medical record review ( Boston Medical Center hospital utilization ) and participant report ( all other hospital utilization ) . The primary end point was the rate of hospital utilizationthe total number of emergency department visits and readmissions per participant within 30 days of the index discharge . AIM This paper is a report of a study to determine whether home visits can reduce hospital readmissions . Background . The phenomenon of hospital readmission raises concerns about the quality of care and appropriate use of re sources . Home visits after hospital discharge have been introduced to help reduce hospital readmission rates , but the results have not been conclusive . METHOD A r and omized controlled trial was carried out from 2003 to 2005 . The control group ( n = 166 ) received routine care and the study group ( n = 166 ) received home visits from community nurses within 30 days of hospital discharge . Data were collected at baseline before discharge and 30 days after discharge . FINDINGS Patients in the study group were statistically significantly more satisfied with their care . There were no statistically significant differences in other outcomes , including readmission rate , ADL score , self-perceived life satisfaction and self-perceived health . Regression analysis revealed that self-perceived life satisfaction , self-perceived health and disease category other than general symptoms were three statistically significant variables predicting hospital readmissions . CONCLUSION Preventive home visits were not effective in reducing hospital readmissions , but satisfaction with care was enhanced . Subjective well-being is a key variable that warrants attention in the planning and evaluation of postdischarge home care AIMS AND OBJECTIVES To evaluate the effectiveness and cost-effectiveness of a community nurse-supported hospital discharge programme in preventing hospital re-admissions , improving functional status and h and icap of older patients with chronic heart failure . DESIGN R and omized controlled trial ; 105 hospitalized patients aged 60 years or over with chronic heart failure and history of hospital admission(s ) in previous year were r and omly assigned into intervention group ( n = 49 ) and control group ( n = 56 ) for six months . Intervention group subjects received community nurse visits before discharge , within seven days of discharge , weekly for four weeks , then monthly . Community nurse liaised closely with a design ated specialist in hospital and were accessible to subjects during normal working hours . Control and intervention group subjects were followed up in the same specialist medical clinics . Primary outcome was the rate of unplanned re-admission at six months . Secondary outcomes were number of unplanned re-admissions , six-minute walking distance , London H and icap Scale and public health care and personal care costs . RESULTS At sixth months , the re-admission rates were not significantly different ( 46 vs. 57 % in control subjects , p = 0.233 , Chi-square test ) . But the median number of re-admissions tended to lower in the intervention group ( 0 vs. 1 in control group , p = 0.057 , Mann Whitney test ) . Intervention group subjects had less h and icap in independence ( median change 0 vs. 0.5 in control subjects , p = 0.002 , Mann Whitney test ) , but there was no difference in six-minute walking distance . There was no significant group difference in median total public health care and personal care costs . CONCLUSION Community nurse-supported post-discharge programme was effective in preserving independence and was probably effective in reducing the number of unplanned re-admissions . The cost benefits to public health care were not significant . RELEVANCE TO CLINICAL PRACTICE Older chronic heart failure patients are likely to benefit from post-discharge community nurse intervention programmes . More comprehensive health economic evaluation needs to be undertaken AIMS Disease management programs can reduce hospitalizations in high-risk heart failure ( HF ) patients , but generalizability to the population hospitalized for HF remains to be proven . We aim ed to assess the effectiveness of a discharge and outpatient management program in a non-selected cohort of patients hospitalized for HF . METHODS AND RESULTS Patients admitted with decompensated HF were r and omized to receive usual care ( n=174 ) or an intervention ( n=164 ) consisting of a comprehensive hospital discharge planning and close follow-up at a HF clinic . After a median of 509 days , there were fewer events ( readmission or death ) in the intervention as compared with the control group ( 156 vs. 250 ) , which represents 47 % ( 95%CI : 29 - 65 ; P<0.001 ) event reduction per observation year . At 1-year , time to first event , time to first all-cause and HF readmission , and time to death were increased in the intervention group ( P<0.001 ) . All-cause and HF readmission rates per observation year were significantly lower , quality of life improved and overall cost of care was reduced in the intervention group . CONCLUSIONS This comprehensive hospital discharge and outpatient management program prolonged time to first event , reduced hospital readmissions , improved survival and quality of life of patients hospitalized for HF , while reducing cost of management OBJECTIVES To evaluate the effectiveness of an intensive community nurse (CN)-supported discharge program in preventing hospital readmissions of older patients with chronic lung disease ( CLD ) . DESIGN R and omized , controlled trial . SETTING Two acute hospitals in the same health region in Hong Kong . PARTICIPANTS One hundred fifty-seven hospitalized patients aged 60 and older with a primary diagnosis of CLD and at least one hospital admission in the previous 6 months . INTERVENTION CNs made home visits within 7 days of discharge , then weekly for 4 weeks and monthly until 6 months . CNs coordinated closely with a geriatric or respiratory specialist in hospital . Subjects had telephone access to CNs during normal working hours from Monday to Saturday . MEASUREMENTS The primary outcome was the rate of unplanned readmission within 6 months . The secondary outcomes were the rate of unplanned readmission within 28 days , number of unplanned readmissions , hospital bed days , accident and emergency room attendance , functional and psychosocial status , and caregiver burden . RESULTS One hundred forty hospitalized patients completed the trial . Intervention group subjects had a higher rate of unplanned readmission within 6 months than control group subjects ( 76 % vs 62 % , P=.080 , chi2 test ) . There was no significant group difference in any of the secondary outcomes except that intervention group subjects did better on social h and icap scores . CONCLUSION There was no evidence that an intensive CN-supported discharge program can prevent hospital readmissions in older patients with CLD AIM To test the effects of a postdischarge transitional care programme among patients with coronary heart disease . BACKGROUND . Coronary heart disease is a leading cause of death worldwide . Effective postdischarge care can help patients maintain a healthy lifestyle and thereby control the risk factors . Transitional care is under-developed in mainl and China . DESIGN A r and omised controlled trial . METHOD The control group ( n = 100 ) received routine care and the study group ( n = 100 ) received the postdischarge transitional care programme , which consisted of predischarge assessment , structured home visits and telephone follow-ups within four weeks after discharge . Subjects were recruited in 2002 - 2003 , with data collected at baseline before discharge , two days and four and 12 weeks after discharge . RESULTS Participants in the study group had significantly better underst and ing in diet , medications and health-related lifestyle behaviour at day 2 and in weeks 4 and 12 and better underst and ing in exercise at weeks 4 and 12 . There were significant differences between the control and study groups in diet and health-related lifestyle at day 2 and weeks 4 and 12 , in medication at weeks 4 and 12 and exercise at week 12 . There was no difference in hospital readmission between the two groups . The study group was very satisfied with the care . There was no difference in willingness to pay for nurse follow-up services between groups . CONCLUSION This study is an original effort to establish and test a nurse-led transitional care model in China . Results demonstrate that transitional care is effective in mainl and China , concurring with studies done elsewhere . RELEVANCE TO CLINICAL PRACTICE This study has constructed a transitional care model for patients with coronary heart disease in the context of the Chinese population which is effective in enhancing healthy lifestyle among these patients |
10,947 | 25,270,409 | No difference in all-cause mortality was found .
Complications included pain associated with compression , as well as skin abrasion and contact rash as a result of the cuff rubbing against the skin .
In conclusion , the limited available results suggest that IPC may be associated with improved limb salvage , wound healing and pain management . | Intermittent pneumatic compression ( IPC ) is design ed to aid wound healing and limb salvage for patients with critical limb ischaemia who are not c and i date s for revascularisation .
We conducted a systematic review of the literature to identify and critically appraise the evidence supporting its use in this population . | BACKGROUND Although the acute effect of intermittent pneumatic compression ( IPC ) therapy had been documented for patients with symptomatic peripheral arterial obstructive disease ( PAOD ) , its efficacy in improving quality of life ( QOL ) , especially for those with infrapopliteal diffuse lesions , remains unclear . METHODS AND RESULTS Thirty-one patients with infrapopliteal diffuse or multiple segmental lesions were enrolled in the study . Based on receipt of IPC therapy ( 3 h daily for 3 months ) , patients were allocated to a study ( n=23 ) or control ( n=8 ) group . The 6-min walking test , transcutaneous oxygen tension ( TcPO₂ ) , and QOL evaluated with the Short-Form 36 question naire were measured at the beginning and end of the study . In the QOL analysis , scores for physical functioning , physical and emotional role functioning , bodily pain , and general and mental health showed significant changes after IPC therapy . In the 6-min walking test , duration , and the initial and absolute claudication distances were significantly increased in the study group . The TcPO₂ also significantly increased in the distal end of the target limb after IPC therapy . CONCLUSIONS Patients at high risk for amputation with infrapopliteal diffuse or multiple segmental lesions can improve their walking ability , TcPO₂ of the target limb and QOL after IPC therapy BACKGROUND Traditional teaching assumes that the distal arterial tree is maximally dilated in patients with critical limb ischemia ( CLI ) . Endovascular or arterial bypass procedures are the commonly used interventions to increase distal perfusion . However , other forms of treatment such as spinal cord stimulation or intermittent pneumatic compression ( IPC ) have been shown to improve limb salvage rates . This prospect i ve study was design ed to determine if the use of IPC increases popliteal , gastrocnemial , collateral arterial , and skin blood flow in patients with CLI . METHODS Twenty limbs with CLI in 20 patients ( mean age , 74 years ) were evaluated with duplex ultrasound scans and laser Doppler fluxmetry in the semi-erect position before , during , and after IPC . One pneumatic cuff was applied on the foot and the other on the calf . The maximum inflation pressure was 120 mm Hg and was applied for 3 seconds at three cycles per minute . All patients had at least two-level disease by arteriography . Fourteen limbs were characterized as inoperable , and six were considered marginal for reconstruction . Flow volumes were measured in the popliteal , medial gastrocnemial , and a genicular collateral artery . Skin blood flux was measured on the dorsum of the foot at the same time . RESULTS Significant flow increase during the application of IPC was found in all three arteries ( 18/20 limbs ) compared with baseline values ( P < .02 ) . The highest change was seen in the popliteal , followed by the gastrocnemial and the collateral artery . After the cessation of IPC , the flow returned to baseline . This was attributed to the elevation of time average velocity , as the diameter of the arteries remained unchanged . The skin blood flux increased significantly as well ( P < .03 ) . In the two limbs without an increase in the arterial or skin blood flow , significant popliteal vein reflux was found . Both limbs were amputated shortly after . CONCLUSIONS IPC increases axial , muscular , collateral , and skin blood flow in patients with CLI and may be beneficial to those who are not c and i date s for revascularization . Patients with significant venous reflux may not benefit from IPC . This supports the theory that one of the mechanisms by which IPC enhances flow is by increasing the arteriovenous pressure gradient The SF-36 Health Survey is the most widely used self-report measure of functional health . It is commonly used in both r and omized controlled trials ( RCT ) and non-controlled evaluation of medical or other health services . However , determining a clinical ly significant change in SF-36 outcomes from pre-to-post-intervention , in contrast to statistically significant differences , is often not a focus of medical outcomes research . We propose use of the Reliable Change Index ( RCI ) in combination with SF-36 norms as one method for research ers , provider groups , and health care policy makers to determine clinical ly significant healthcare outcomes when the SF-36 is used as a primary measure . The RCI is a statistic that determines the magnitude of change score necessary of a given self-report measure to be considered statistically reliable . The RCI has been used to determine clinical ly significant change in mental health and behavioral medicine outcomes research , but is not widely applied to medical outcomes research . A usable table of RCIs for the SF-36 has been calculated and is presented . Instruction and a case illustration of how to use the RCI table is also provided . Finally , limitations and caution ary guidelines on using SF-36 norms and the RCI to determine clinical ly significant outcome are discussed BACKGROUND Patients with chronic critical limb ischemia following a failed bypass graft or with non-reconstructable distal disease diagnosed angiographically , have a very poor prognosis . This is a prospect i ve pilot study to assess the influence of the ArtAssist Device on pedal blood flow and amputation rate . METHODS Thirty-three legs in 25 patients were evaluated . Ten legs presented with rest pain , and 23 legs with tissue loss . Nine legs had previously undergone bypass surgery . RESULTS At a mean follow-up of 3 months , 14 ( 42 % ) legs were amputated , and 19 ( 58 % ) were saved . Eleven of the amputated legs were in patients with chronic renal failure , a known risk factor . The amputation rate , excluding this group , was 13.6 % ( 3/22 ) . Toe pressures measured initially and after 3 months on the pump showed a significant improvement ( p=0.03 ) . Forty percent of patients presenting with rest pain improved , while 26 % of foot ulcers healed on the pump . Mortality rate was 12 % . CONCLUSIONS The results from this prospect i ve study are encouraging but need to be vali date d in a larger prospect i ve r and omized study |
10,948 | 24,027,097 | Because of considerable clinical heterogeneity ( different clinical scenarios , as well as considerable method ological variability amongst the studies ) , we did not perform a meta- analysis on the combined data .Subgroup analysis of major interventions and surgical procedures showed no significant influence of interventions on reported mortality and acute renal injury .
No reliable evidence from the available literature suggests that interventions during surgery can protect the kidneys from damage . | BACKGROUND Various methods have been used to try to protect kidney function in patients undergoing surgery .
These most often include pharmacological interventions such as dopamine and its analogues , diuretics , calcium channel blockers , angiotensin-converting enzyme ( ACE ) inhibitors , N-acetyl cysteine ( NAC ) , atrial natriuretic peptide ( ANP ) , sodium bicarbonate , antioxidants and erythropoietin ( EPO ) .
OBJECTIVES This review is aim ed at determining the effectiveness of various measures advocated to protect patients ' kidneys during the perioperative period .
We considered the following questions : ( 1 ) Are any specific measures known to protect kidney function during the perioperative period ? (
2 ) Of measures used to protect the kidneys during the perioperative period , does any one method appear to be more effective than the others ? (
3 ) Of measures used to protect the kidneys during the perioperative period , does any one method appear to be safer than the others ? | OBJECTIVES To investigate the renoprotective effect of nicardipine in patients undergoing robot-assisted laparoscopic radical prostatectomy ( RALRP ) in a prospect i ve trial . Superior visualization of the increasingly performed RALRP requires pneumoperitoneum and extreme head-down tilt , both of which are associated with a decrease in postoperative renal function . Nicardipine causes preferential dilation of the renal arterioles and attenuates renal dysfunction after cardiac surgery . METHODS After we obtained institutional review board approval , we r and omly treated 100 patients undergoing RALRP with a continuous infusion of nicardipine at a rate of 0.5 microg/kg/min ( nicardipine group , n = 50 ) or with normal saline ( control group , n = 50 ) during surgery . We measured the serum creatinine ( Cr ) level and estimated glomerular filtration rate ( eGFR ) 1 day before surgery and the first and third postoperative days ( POD 1 and 3 , respectively ) . RESULTS Patients ' characteristics and operative data were similar between groups . The serum Cr was significantly higher and the eGFR was significantly lower in the control group at POD 1 . The number of patients having renal insufficiency ( eGFR < 60 mL/min/1.73 m(2 ) ) and abnormal serum creatinine level ( > 1.4 mg/dL ) was significantly greater in the control group ( 9 vs 1 , and 4 vs none , respectively ) at POD 1 . CONCLUSIONS Continuous infusion of low-dose nicardipine during RALRP seems to offset the deleterious effects of inevitable pneumoperitoneum and extreme head-down tilt on renal function in preserving the eGFR and attenuating the development of renal insufficiency in the immediate postoperative period OBJECTIVES Cardiopulmonary bypass ( CPB ) is widely regarded as an important contributor to renal failure , a well recognized complication following coronary artery surgery ( coronary artery bypass grafting ( CABG ) ) . Anecdotally off-pump coronary surgery ( OPCAB ) is considered renoprotective . We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass ( ONCAB ) . METHODS Forty low-risk patients with normal preoperative cardiac and renal functions awaiting elective CABG were prospect ively r and omized into those undergoing OPCAB ( n=20 ) and ONCAB ( n=20 ) . Glomerular and tubular injury were measured respectively by urinary excretion of microalbumin and retinol binding protein ( RBP ) indexed to creatinine ( Cr ) . Daily measurements were taken from admission to postoperative day 5 . Fluid balance , serum Cr and blood urea were also monitored . RESULTS No mortality or renal complication were observed . Both groups had similar demographic makeup , Parsonnet score , functional status and extent of coronary revascularization ( 2.1+/-1.0 vs. 2.5+/-0.7 grafts ; P=0.08 ) . Serum Cr and blood urea remained normal in both groups throughout the study . A significant and similar rise in urinary RBP : Cr occurred in both groups peaking on day 1 ( 3183+/-2534 vs. 4035+/-4079 ; P=0.43 ) before reapproximating baseline levels . These trends were also observed with urinary microalbumin : Cr ( 5.05+/-2.66 vs. 6.77+/-5.76 ; P=0.22 ) . Group B patients had a significantly more negative fluid balance on postoperative day 2 ( -183+/-1118 vs. 637+/-847 ml ; P=0.03 ) . CONCLUSIONS Although renal complication or serum markers of kidney dysfunction were absent , sensitive indicators revealed significant and similar injury to renal tubules and glomeruli following either OPCAB or ONCAB . These results suggest that avoidance of CPB does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG Deterioration of renal function , which can lead to postoperative renal failure , is a complication of surgery involving the suprarenal aorta and surgery involving the renal arteries . Fifty-four patients who were at risk for developing this complication were enrolled in a double-blind , r and omized , placebo-controlled trial of insulin-like growth factor ( IGF-I ) as a therapeutic agent to prevent the decline in renal function . The primary end point was the incidence of renal dysfunction , defined as a reduction of the glomerular filtration rate ( creatinine clearance ) at each of three measurements over 72 h. IGF-I ( 100 microg/kg subcutaneously every 12 h for 6 doses ) or placebo was administered on admission to the intensive care unit immediately postoperatively . IGF-I- and placebo-treated groups were well matched for sex , age , type of surgery , renal ischemic time during surgery ( ischemic index ) , baseline creatinine clearance , and baseline serum creatinine . No patient in the study developed acute renal failure postoperatively . IGF-I was well tolerated . A smaller proportion of patients in the IGF-I group had a postoperative decline in renal function ( 22 % ) than in the placebo-treated group ( 33 % ) . There were no significant differences in levels of serum creatinine at time of discharge , length of hospital stay , length of intensive care unit stay , length of intubation , or incidence of dialysis or death . Our findings establish the feasibility and potential utility for the use of IGF-I to reduce the incidence of postoperative renal dysfunction in high-risk patients OBJECTIVES We aim ed to evaluate the renoprotective role of renal-dose dopamine on cardiac surgical patients at high risk of postoperative renal dysfunction . The latter included older patients or those with pre-existing renal disease , elevated preoperative serum creatinine ( Cr ) , poor ventricular function , hypertension , diabetes mellitus and unstable angina requiring intravenous therapy . METHODS Fifty patients undergoing cardiopulmonary bypass ( CPB ) who fulfilled the entry criteria were prospect ively r and omized into two groups : Group 1 received a ' renal-dose ' ( 3 microg kg(-1 ) min(-1 ) ) dopamine infusion starting at anaesthetic induction for 48 h whilst saline infusion acted as placebo in Group 2 . The anaesthetic and CPB regimes were st and ardized . Urinary excretion of retinol binding protein ( RBP ) indexed to Cr , an accurate and sensitive marker of early renal tubular damage , was assessed daily for 6 days . Additional outcome measures included daily fluid balance , blood urea and serum Cr . Statistical comparisons were made using ANOVA and Mann-Whitney U-test . RESULTS No significant difference was found between the groups in their age , gender , preoperative NYHA class , ejection fraction , baseline serum Cr and duration of CPB and aortic cross-clamping . Renal replacement therapy was not required in any instance . Both groups demonstrated a similar and significant rise in urinary RBP throughout the study period . Dopamine-treated patients achieved more negative average fluid balance than those on placebo ( 5 vs. 229 ml , P<0.05 ) . CONCLUSIONS Renal-dose dopamine therapy failed to offer additional renoprotection to patients considered at increased risk of renal dysfunction after CPB BACKGROUND Low-dose dopamine is commonly administered to critically ill patients in the belief that it reduces the risk of renal failure by increasing renal blood flow . However , these effects have not been established in a large r and omised controlled trial , and use of dopamine remains controversial . We have done a multicentre , r and omised , double-blind , placebo-controlled study of low-dose dopamine in patients with at least two criteria for the systemic inflammatory response syndrome and clinical evidence of early renal dysfunction ( oliguria or increase in serum creatinine concentration ) . METHODS 328 patients admitted to 23 participating intensive-care units ( ICUs ) were r and omly assigned a continuous intravenous infusion of low-dose dopamine ( 2 microg kg(-1 ) min(-1 ) ) or placebo administered through a central venous catheter while in the ICU . The primary endpoint was the peak serum creatinine concentration during the infusion . Analyses excluded four patients with major protocol violations . FINDINGS The groups assigned dopamine ( n=161 ) and placebo ( n=163 ) were similar in terms of baseline characteristics , renal function , and duration of trial infusion . There was no difference between the dopamine and placebo groups in peak serum creatinine concentration during treatment ( 245 [ SD 144 ] vs 249 [ 147 ] micromol/L ; p=0.93 ) , in the increase from baseline to highest value during treatment ( 62 [ 107 ] vs 66 [ 108 ] micromol/L ; p=0.82 ) , or in the numbers of patients whose serum creatinine concentration exceeded 300 micromol/L ( 56 vs 56 ; p=0.92 ) or who required renal replacement therapy ( 35 vs 40 ; p=0.55 ) . Duration s of ICU stay ( 13 [ 14 ] vs 14 [ 15 ] days ; p=0.67 ) and of hospital stay ( 29 [ 27 ] vs 33 [ 39 ] days ; p=0.29 ) were also similar . There were 69 deaths in the dopamine group and 66 in the placebo group . INTERPRETATION Administration of low-dose dopamine by continuous intravenous infusion to critically ill patients at risk of renal failure does not confer clinical ly significant protection from renal dysfunction Activation of the renin-angiotensin system during open heart surgery may have consequences both beneficial in sustaining blood pressure and deleterious in compromising renal hemodynamics . The influence of short-term pretreatment with captopril on blood pressure and renal function was assessed double-blind versus placebo in 18 patients without pre-existing cardiac or renal failure , and undergoing coronary artery bypass . No difference in blood pressure and fluid requirement during the surgical period was observed between groups receiving captopril or placebo . Effective renal plasma flow and glomerular filtration rate decreased in the placebo group whereas they remained unaltered in the captopril group ; during cardiopulmonary bypass , urinary excretion of sodium was greater in patients receiving captopril than those receiving placebo . These results suggest that captopril pretreatment does not compromise the control of blood pressure and renal function during open heart surgery ; additional studies on the protective value of angiotensin-converting enzyme inhibitors are warranted in patients at higher risk for developing renal failure BACKGROUND AND OBJECTIVE Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping . Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate , a selective dopamine ( DA1 ) agonist , would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping . METHODS A prospect i ve , r and omized , double blind controlled clinical trial was performed . Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied . According to r and om allocation , patients received either fenoldopam ( 0.1 microg kg(-1 ) min(-1 ) ) or placebo intravenously prior to surgical skin incision until release of the aortic clamp . Plasma creatinine , creatinine clearance , urinary output , fractional excretion of sodium , and free water clearance were measured : ( a ) prior to admission to hospital ; ( b ) during the period from insertion of the urinary catheter until application of the aortic cross-clamp ; ( c ) during the period of aortic cross-clamping ; ( d ) 0 - 4 h , and ( e ) 4 - 8 h after release of the clamp and on days 1 , 2 , 3 , and 5 postoperatively . RESULTS Fenoldopam ( 0.1 microg kg(-1)min(-1 ) ) administration was not associated with haemodynamic instability . On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo ( 83 + /- 20 to 42 + /- 29 mL min(-1 ) ( mean + /- SD ) ) ( P < 0.01 ) but not in the fenoldopam group , and this decrease persisted for at least 8 h after release of the cross-clamp ( 83 + /- 20 to 54 + /- 33 mL min(-1 ) ( mean + /- SD ) ) ( P < 0.05 ) . Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group ( 87 + /- 12 to 103 + /- 28 micromolL(-1 ) ( mean + /- SD ) ) ( P < 0.01 ) but not in the fenoldopam group . CONCLUSIONS These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping In a prospect i ve r and omized trial of 16 patients undergoing abdominal vascular reconstructive procedures , changes in plasma volume , serum oncotic pressure ( pis ) , serum albumin and total protein concentration , alveolar to arterial oxygen tension differences ( AaDO2 , FIO2 = 1.0 ) , creatinine clearance , body weight , and fluid and sodium intake were examined . By r and om assignment patients received either an albumin- or a sodium-rich intraoperative fluid regimen . Pulmonary arteriovenous admixture was significantly less in the albumin group ( n = 7 ) than in the electrolyte group ( n = 9 ) on the first postoperative day . The change in AaDO2 correlated positively with the total sodium intake in the electrolyte group . Despite the larger fluid load and significantly greater gain of body weight , patients in the electrolyte group had a postoperative plasma volume significantly lower than the preoperative value . Postoperative values of albumin concentration , circulating albumin mass and pis were significantly greater in the albumin group in comparison to the electrolyte group . Creatinine clearance values were not different between the two groups . The change in pis correlated significantly with sodium intake and circulating albumin mass . Pulmonary shunting and expansion of the extracellular fluid volume may be minimized without adverse effects on renal function by administration of fluids rich in albumin in preference to sodium Background : Preoperative renal insufficiency is an important predictor of the need for postoperative renal replacement therapy ( RRT ) . Serum creatinine ( sCr ) has a limited ability to identify patients with preoperative renal insufficiency because it varies with age , sex , and muscle mass . Calculated creatinine clearance ( CrCl ) is an alternative measure of renal function that may allow better estimation of renal reserve . Methods : Data were prospect ively collected for consecutive patients who underwent cardiac surgery requiring cardiopulmonary bypass at a tertiary care center . The relation between CrCl ( Cockcroft-Gault equation ) and RRT was initially described using descriptive statistics , logistic regression , and receiver operating curve analysis . Based on these analyses , preoperative renal insufficiency was defined as CrCl of 60 ml/min or less . Preoperative renal function was classified as moderate insufficiency ( sCr > 133 & mgr;m ) , mild insufficiency ( 100 & mgr;m < sCr ≤ 133 & mgr;m ) , occult insufficiency ( sCr ≤ 100 & mgr;m and CrCl ≤ 60 ml/min ) , or normal function ( sCr ≤ 100 & mgr;m and CrCl > 60 ml/min ) . The independent association of preoperative renal function with RRT was subsequently determined using multiple logistic regression . Results : Of the 10,751 patients in the sample , 137 ( 1.2 % ) required postoperative RRT . Approximately 13 % of patients with normal sCr had occult renal insufficiency . Occult renal insufficiency was independently associated with RRT ( odds ratio , 2.80 ; 95 % confidence interval , 1.39–5.33 ) . The magnitude of this risk was similar to patients with mild renal insufficiency ( P = 0.73 ) . Conclusions : The inclusion of a simple CrCl-based criterion in preoperative assessment s may improve identification of patients at risk of needing postoperative RRT CONTEXT The antioxidant acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who undergo computed tomography scanning . However , its role in coronary angiography is unclear . OBJECTIVE To determine whether oral acetylcysteine prevents acute deterioration in renal function in patients with moderate renal insufficiency who undergo elective coronary angiography . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , placebo-controlled trial conducted from May 2000 to December 2001 at the Grantham Hospital at the University of Hong Kong . PARTICIPANTS Two hundred Chinese patients aged mean ( SD ) 68 ( 6.5 ) years with stable moderate renal insufficiency ( creatinine clearance < 60 mL/min [ 1.00 mL/s ] ) who were undergoing elective coronary angiography with or without intervention . INTERVENTION Participants were r and omly assigned to receive oral acetylcysteine(600 mg twice per day ; n = 102 ) or matching placebo tablets ( n = 98 ) on the day before and the day of angiography . All patients received low-osmolality contrast agent . MAIN OUTCOME MEASURES Occurrence of more than a 25 % increase in serum creatinine level within 48 hours after contrast administration ; change in creatinine clearance and serum creatinine level . RESULTS Twelve control patients ( 12 % ) and 4 acetylcysteine patients ( 4 % ) developed a more than 25 % increase in serum creatinine level within 48 hours after contrast administration ( relative risk , 0.32 ; 95 % confidence interval [ CI ] , 0.10 - 0.96 ; P = .03 ) . Serum creatinine was lower in the acetylcysteine group ( 1.22 mg/dL [ 107.8 micromol/L ] ; 95 % CI , 1.11 - 1.33 mg/dL vs 1.38 mg/dL [ 122.9 micromol/L ] ; 95 % CI , 1.27 - 1.49 mg/dL ; P = .006 ) during the first 48 hours after angiography . Acetylcysteine treatment significantly increased creatinine clearance from 44.8 mL/min ( 0.75 mL/s ) ( 95 % CI , 42.7 - 47.6 mL/min ) to 58.9 mL/min ( 0.98 mL/s ) ( 95 % CI , 55.6 - 62.3 mL/min ) 2 days after the contrast administration ( P<.001 ) . The increase was not significant in the control group ( from 42.1 to 44.1 mL/min [ 0.70 to 0.74 mL/s ] ; P = .15 ) . The benefit of acetylcysteine was consistent among various patient subgroups and persistent for at least 7 days . There were no major treatment-related adverse events . CONCLUSION Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures , with minimal adverse effects and at a low cost Patients undergoing surgery for idiopathic scoliosis were studied to determine the incidence and aetiology of oliguria during the perioperative period and to evaluate the efficacy of low dose dopamine in preventing its occurrence . Thirty patients , aged 6 - 18 years undergoing elective surgery were studied . Anaesthesia was st and ardized . Patients were r and omized to receive either dopamine infusion ( 3 micrograms.kg-1.min-1 ) ( Group A ) ( n = 15 ) or dextrose infusion ( control ) ( Group B ) ( n = 15 ) . Serum and urinary electrolytes and osmolalities and serum antidiuretic hormone ( ADH ) concentrations were measured . Urine output and haemodynamic parameters were recorded . Intraoperative oliguria occurred in 7 % of patients in Group A and 47 % in Group B ( P < 0.05 ) . Postoperative oliguria occurred in 20 % of patients in Group A and 47 % in Group B ( P > 0.05 ) . Urine and serum biochemical analysis revealed a statistically significant decrease in serum sodium and osmolality ( P < 0.005 ) and an increase in urinary sodium and osmolality in both groups . Serum ADH concentrations were increased in both groups ( P < 0.05 ) , returning to baseline 18 h postoperatively . We conclude that oliguria during corrective spinal surgery occurs in association with excess ADH secretion as opposed to perioperative hypovolaemia . Dopamine increases urine output in the perioperative period but does not prevent the release of ADH and its subsequent biochemical effects Background : Acute renal failure is a common complication of cardiac surgery , with oxidants found to play an important role in renal injury . We therefore assessed whether the supplemental antioxidant vitamin E and the inhibitor of xanthine oxidase allopurinol could prevent renal dysfunction after coronary artery bypass graft ( CABG ) surgery . Methods : Of 60 patients with glomerular filtration rate ( GFR ) < 60 mL/min scheduled to undergo CABG surgery , 30 were r and omized to treatment with vitamin E and allopurinol for 3–5 days before surgery and 30 to no treatment . Serum creatinine levels and potassium and creatinine clearances were measured preoperatively and daily until day 5 after surgery . Results : The patients consisted of 31 males and 29 females , with a mean age of 63 ± 9 years . After surgery , there were no significant differences in mean serum creatinine ( 1.2 ± 0.33 vs 1.2 ± 0.4 mg/dL ; p = 0.43 ) concentrations , or creatinine clearance ( 52 ± 12.8 vs 52 ± 12.8 mL/min ; p = 0.9 ) . The frequency of acute renal failure did not differ in treatment group compared with control ( 16 % vs 13 % ; p = 0.5 ) . Length of stay in the intensive care unit ( ICU ) was significantly longer in the control than in the treated group ( 3.9 ± 1.5 vs 2.6 ± 0.7 days ; p < 0.001 ) . Conclusion : Prophylactic treatment with vitamin E and allopurinol had no renoprotective effects in patients with pre-existing renal failure undergoing CABG surgery . Treatment with these agents , however , reduces the duration of ICU stay OBJECTIVES Despite avoiding cardiopulmonary bypass , off-pump coronary artery bypass surgery is associated with reduction in PaO2 and postoperative respiratory compliance . Also , transient interruption of coronary flow is necessary during distal anastomoses and may impose ischemia-reperfusion myocardial injury . Mannitol is an osmotic diuretic with free radical scavenging properties , and we have evaluated the effects of mannitol on oxygenation and cardiac enzyme release in patients undergoing multivessel off-pump bypass surgery in a prospect i ve , r and omized , controlled , double-blind trial . METHODS Fifty patients were r and omly allocated to receive either 20 % mannitol 0.5 g/kg ( n = 25 ) or normal saline 2.5 mL/kg ( n = 25 ) during Y-graft construction . Pulmonary variables and serum sodium concentrations were measured 15 minutes after induction of anesthesia and sternum closure . Creatine kinase MB was measured before and after the operation . Intraoperative and postoperative fluid input and output , time to extubation , and intraoperative hemodynamic variables were also recorded . RESULTS PaO2 after sternum closure was significantly higher in the mannitol group , with faster time to extubation and shorter length of stay in the intensive care unit . Intraoperative urine output was significantly greater in the mannitol group , without significant differences in fluid input , serum sodium concentration , and hemodynamic variables . Number of patients with a creatine kinase MB level more than 3 times the upper limit of normal was significantly higher in the control group . CONCLUSION Mannitol could be safely used without adverse side effects in patients undergoing multivessel off-pump bypass surgery with beneficial effects in terms of preserving oxygenation , earlier extubation , and fewer patients with significant creatine kinase MB elevation Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine ( D ) and dopamine-nitroprusside ( DN ) on renal function during cardiopulmonary bypass ( CPB ) . No differences from the control group ( C ) were found in creatinine clearance , fractional sodium excretion , osmolarity and free-water clearance . Sodium output/intake ratio during CPB was higher in group D than in groups C and DN ( P less than 0.05 ) ; water output/intake ratio was higher in group D than in group C ( P less than 0.05 ) . Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups , suggesting ischemic tubular cell damage . No patients showed acute postoperative renal failure or a worsening of their renal dysfunction . The data suggest an increased water and sodium excretion during CPB with a dopamine infusion , possibly result ing from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration Acute renal failure continues to be a frequent complication after vascular operations with interruption of renal circulation . Aim of the study was to evaluate two methods to prevent postischemic renal failure after suprarenal aortic surgery : the pretreatment with Prostagl and in E1 and the organ perfusion with cold saline solution . 24 patients , who did not receive Prostagl and in E1 or cold organ perfusion were used as control ( Group A ) . 37.5 % of these patients ( n = 9/24 ) developed acute renal failure . 3 needed hemodialysis postoperatively . Only 3 out of 26 patients ( 11.5 % ) , who received PGE1 ( Group B ) , showed deterioration of renal function with plasma creatinine values greater than 2 mg % and no patient needed dialysis . 6 out of 26 patients ( 23 % ) , who received organ perfusion with cold saline ( Group C ) , developed acute renal failure and in one case temporary hemodialysis was necessary . Plasma creatinine increased in the group A from 1.1 ( 0.1 ) mg % to 1.95 ( 0.4 ) mg % on third postoperative day and to 2.1 ( 0.4 ) mg % on discharge , while after pretreatment with PGE1 ( Group B ) plasma creatinine increased from 1.25 ( 0.1 ) mg % to 1.44 ( 0.1 ) mg % . In the group C creatinine increased from 1.3 ( 0.1 ) mg % to 1.77 ( 0.1 ) mg % . On discharge from the hospital plasma creatinine decreased to mean values of 1.25 ( 0.1 ) mg % in the group B and 1.5 ( 0.1 ) mg % in the group C. Intraoperative organ perfusion with cold saline and Prostagl and in E1 allows today complicated arterial reconstructions of both aorta and renal arteries with minimal risk of postischemic renal damage Background —Acute renal failure is a serious complication of cardiac surgery causing high morbidity and mortality . The aim of this study was to evaluate the usefulness of fenoldopam , a specific agonist of the dopamine-1 receptor , in patients at high risk of perioperative renal dysfunction . Methods and Results —A prospect i ve single-center , r and omized , double-blind trial was performed after local ethical committee approval and after written consent was obtained from 80 patients undergoing cardiac surgery . Patients received either fenoldopam at 0.05 & mgr;g/kg per minute or dopamine at 2.5 & mgr;g/kg per minute after the induction of anesthesia for a 24-hour period . All these patients were at high risk of perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac Surgery Program score > 10 . Primary end point was defined as 25 % creatinine increase from baseline levels after cardiac surgery . The 2 groups ( fenoldopam versus dopamine ) were homogeneous cohorts , and no difference in outcome was observed . Acute renal failure was similar : 17 of 40 ( 42.5 % ) in the fenoldopam group and 16 of 40 ( 40 % ) in the dopamine group ( P=0.9 ) . Peak postoperative serum creatinine level , intensive care unit and hospital stay , and mortality were also similar in the 2 groups . Conclusions —Despite an increasing number of reports of renal protective properties from fenoldopam , we observed no difference in the clinical outcome compared with dopamine in a high-risk population undergoing cardiac surgery BACKGROUND Endotoxaemia due to intraluminal bile salt depletion may be a cause of renal failure in patients with obstructive jaundice . Administration of bile salts to these patients has been reported to decrease portal and systemic endotoxaemia during surgery and improve renal function . However , such changes have not been shown with bile refeeding . We compared the effect of preoperative bile salt administration with preoperative bile refeeding on renal function in patients with obstructive jaundice . METHODS Sixteen patients with obstructive jaundice underwent percutaneous transhepatic biliary drainage -- eight received oral bile salts ( 500 mg of sodium deoxycholate 8-hourly for 48 hours preoperatively ) and the other 8 were refed the total bile output for the entire period of biliary drainage ( median 13 days ) . Blood endotoxin levels and renal function were assessed before , during and after the operation . RESULTS The number of patients with intraoperative portal and postoperative systemic endotoxaemia decreased after both forms of therapy . Renal function also improved in both the groups -- all 4 patients with renal failure recovered . There was a significant increase in creatinine clearance postoperatively after bile salt therapy ( from 65 ml/minute preoperatively to 87 ml/minute postoperatively ) . CONCLUSION Refeeding of bile obtained by percutaneous catheter drainage is an effective , cost-free substitute for oral bile salts in patients with obstructive jaundice Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation , respectively . We hypothesised that fenoldopam , a selective dopamine receptor agonist , would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects , and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation . We examined the effects of fenoldopam on haemodynamic parameters , creatinine clearance , fractional excretion of sodium , urine output , free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation . Patients were r and omly assigned to receive continuous infusions of fenoldopam 0.1 µg.kg−1.min−1 ( n = 16 ) or placebo ( n = 15 ) . Renal parameters were measured : during a 24‐h period before hospital admission , during cardiopulmonary bypass , from completion of cardiopulmonary bypass until 4 h later , from 4 to 8 h after cardiopulmonary bypass , and from 8 to 14 h after cardiopulmonary bypass . Gastric intramucosal pH was measured using a gastric tonometer before , during and after cardiopulmonary bypass . In the placebo group , but not the fenoldopam group , mean ( SD ) creatinine clearance decreased after separation from cardiopulmonary bypass , from 107 ( 36 ) to 71 ( 22 ) ml.min−1 ( p < 0.01 ) and from 107 ( 36 ) to 79 ( 26 ) ml.min−1 ( p < 0.01 ) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass , respectively . Changes in intramucosal pH were similar in both groups . The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass BACKGROUND The recent introduction of normothermic cardiopulmonary bypass ( CPB ) perfusion has raised concerns regarding the associated risk of renal dysfunction through its potential to exacerbate the systemic inflammatory response and end-organ injury . This study was design ed to investigate the influence of CPB perfusion temperature on renal function . METHODS A prospect i ve , r and omized , controlled trial of CPB perfusion temperature ( 28 degrees C , 32 degrees C , and 37 degrees C ) was performed in 30 patients undergoing routine coronary artery bypass grafting with normal preoperative renal function . Creatinine clearance was measured before induction of anesthesia , during CPB , and during every 12-hour period thereafter for 48 hours postoperatively . Glomerular and tubular function were assessed further by measurement of urinary creatinine , albumin , total protein , and retinol binding protein levels preoperatively , during CPB , and on days 1 and 3 postoperatively . RESULTS Creatinine clearance increased on CPB by 51 % ( 28 degrees C ) , 185 % ( 32 degrees C ) , and 112 % ( 37 degrees C ) ( all p < 0.01 versus preoperative values ) and returned to preoperative values by 24 hours postoperatively in all three groups . Urinary albumin/creatinine ratios rose significantly from a mean of 0.4 + /- 0.1 ( st and ard deviation ) to 10 + /- 12.5 ( 28 degrees C ) , from 0.55 + /- 0.3 to 5.2 + /- 4.9 ( 32 degrees C ) , and from 0.96 + /- 0.8 to 7.8 + /- 7.0 ( 37 degrees C ) during CPB ( all p < 0.001 ) but decreased gradually thereafter . Also , urinary total protein/creatinine ratios rose significantly from a mean of 0.009 + /- 0.007 to 0.034 + /- 0.02 ( 28 degrees C ) , from 0.01 + /- 0.006 to 0.026 + /- 0.01 ( 32 degrees C ) , and from 0.011 + /- 0.008 to 0.033 + /- 0.02 ( 37 degrees C ) during CPB ( all p < 0.005 ) ; however , there was a further increase by 24 hours , and ratios decreased gradually thereafter . Similarly , urinary retinol binding protein/creatinine ratios rose significantly in all three groups during CPB ( all p < 0.0001 ) and increased further by 24 hours . There was no statistically significant difference between the renal markers in the three temperature groups in any of the observations . CONCLUSION These data suggest that cardiopulmonary bypass perfusion temperature does not influence renal function in patients undergoing coronary artery bypass grafting BACKGROUND Injections of radiocontrast agents are a frequent cause of acute decreases in renal function , occurring most often in patients with chronic renal insufficiency and diabetes mellitus . METHODS We prospect ively studied 78 patients with chronic renal insufficiency ( mean [ + /- SD ] serum creatinine concentration , 2.1 + /- 0.6 mg per deciliter [ 186 + /- 53 mumol per liter ] ) who underwent cardiac angiography . The patients were r and omly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography , saline plus mannitol , or saline plus furosemide . The mannitol and furosemide were given just before angiography . Serum creatinine was measured before and for 48 hours after angiography , and urine was collected for 24 hours after angiography . An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter ( 44 mumol per liter ) within 48 hours after the injection of radiocontrast agents . RESULTS Twenty of the 78 patients ( 26 percent ) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography . Among the 28 patients in the saline group , 3 ( 11 percent ) had such an increase in serum creatinine , as compared with 7 of 25 in the mannitol group ( 28 percent ) and 10 of 25 in the furosemide group ( 40 percent ) ( P = 0.05 ) . The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group ( P = 0.01 ) than in the saline group . CONCLUSIONS In patients with chronic renal insufficiency who are undergoing cardiac angiography , hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide OBJECTIVE To evaluate the influence of the alpha2-adrenergic receptor agonist clonidine on creatinine clearance as a measure of renal function . DESIGN Prospect i ve , double-blind , r and omized , placebo-controlled clinical trial . SETTING University hospital . PATIENTS Patients undergoing coronary artery bypass graft surgery ( n = 48 ) with normal risk . INTERVENTIONS Administration of clonidine ( 4 micrograms/kg iv ) ) or placebo 1 hr before induction of anesthesia . MEASUREMENTS AND MAIN RESULTS Induction and maintenance of anesthesia ( etomi date , midazolam , and fentanyl ) and cardiopulmonary bypass technique ( nonpulsatile , normothermic , intermittent cold blood cardioplegia ) were st and ardized in all patients . The night before surgery and the first and third night after surgery , creatinine clearance was calculated from a 12-hr urine collection period . Venous blood sample s for determination of plasma antidiuretic hormone ( ADH ) concentrations were taken the evening before surgery , immediately before induction of anesthesia and the evening after surgery ( n = 16 ) . Arterial catecholamine plasma concentrations were determined ( high-performance liquid chromatography ) before induction , 15 mins after induction of anesthesia , immediately after sternotomy , before initiation of cardiopulmonary bypass , as well as 5 , 15 , and 30 mins after initiation of cardiopulmonary bypass ( n = 16 ) . The total amount of anesthetics , infusions , transfusions , diuresis , and blood loss was not different between the groups . Creatinine clearance decreased over the first postoperative night from 98 + /- 18 ( preoperatively ) to 68 + /- 19 mL/min ( p < .05 ) in placebo-treated patients . Creatinine clearance remained unchanged in clonidine-treated patients ( 90 + /- 19 [ preoperatively ] to 92 + /- 17 mL/min ) . There was a significant difference in creatinine clearance between the groups during the first postoperative night ( p < .05 ; Mann-Whitney U test ) . In the third postoperative night , mean creatinine clearance of both groups was not different ( 75 + /- 31 vs. 86 + /- 28 mL/min ) . ADH concentrations were not different between the groups at any time , while plasma catecholamine concentrations were always significantly lower in clonidine-treated patients . CONCLUSIONS Preoperative treatment with clonidine ( 4 microgram/kilogram ) prevents the deterioration of renal function after cardiac surgery . This effect might be due to clonidine-induced reduction in the sympathetic nervous system response to coronary artery bypass graft surgery BACKGROUND Renal failure after lower torso ischemia is a serious problem , partly caused by hypotension and indirect reperfusion injury . This injury is partly due to the formation of oxygen free radicals by activated neutrophils . This injury results in albuminuria and renal function impairment . There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion . METHODS In this prospect i ve r and omised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair . The patients received either st and ard treatment ( n=22 ) or st and ard treatment with additional antioxidants perioperatively ( Allopurinol , vitamin E and C , N-acetylcysteine and mannitol ) . For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance . RESULTS Despite significantly increased serum total antioxidant capacity , the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine . There was however a significantly higher creatinine clearance in this group at day 2 . CONCLUSIONS The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy BACKGROUND Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species . Whether the reduction can be prevented by the administration of antioxidants is unknown . METHODS We prospect ively studied 83 patients with chronic renal insufficiency ( mean [ + /-SD ] serum creatinine concentration , 2.4+/-1.3 mg per deciliter [ 216+/-116 micromol per liter ] ) who were undergoing computed tomography with a nonionic , low-osmolality contrast agent . Patients were r and omly assigned either to receive the antioxidant acetylcysteine ( 600 mg orally twice daily ) and 0.45 percent saline intravenously , before and after administration of the contrast agent , or to receive placebo and saline . RESULTS Ten of the 83 patients ( 12 percent ) had an increase of at least 0.5 mg per deciliter ( 44 micromol per liter ) in the serum creatinine concentration 48 hours after administration of the contrast agent : 1 of the 41 patients in the acetylcysteine group ( 2 percent ) and 9 of the 42 patients in the control group ( 21 percent ; P=0.01 ; relative risk , 0.1 ; 95 percent confidence interval , 0.02 to 0.9 ) . In the acetylcysteine group , the mean serum creatinine concentration decreased significantly ( P<0.001 ) , from 2.5+/-1.3 to 2.1+/-1.3 mg per deciliter ( 220+/-118 to 186+/-112 micromol per liter ) 48 hours after the administration of the contrast medium , whereas in the control group , the mean serum creatinine concentration increased nonsignificantly ( P=0.18 ) , from 2.4+/-1.3 to 2.6+/-1.5 mg per deciliter ( 212+/-114 to 226+/-133 micromol per liter ) ( P<0.001 for the comparison between groups ) . CONCLUSIONS Prophylactic oral administration of the antioxidant acetylcysteine , along with hydration , prevents the reduction in renal function induced by contrast agents in patients with chronic renal insufficiency BACKGROUND We evaluated the effects of human atrial natriuretic peptide ( hANP ) during cardiopulmonary bypass ( CPB ) . METHODS Forty patients undergoing coronary artery bypass grafting were investigated . A group of patients given hANP for 24 hours from the start of CPB ( hANP group ) was compared with a non-hANP group . Parameters examined were hemodynamics , urine volume , dosage of furosemide , respiratory index , pleural effusion , ANP , cyclic guanosine monophosphate , renin activity ( renin ) , angiotensin-II , aldosterone , and glomerular filtration rate . RESULTS Central venous pressure , systemic vascular resistance index , and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group . The hANP group showed significantly higher levels of ANP , cyclic guanosine monophosphate , glomerular filtration rate , and respiratory index , and significantly lower levels of renin , angiotensin-II , aldosterone , and pleural effusion , as compared with the non-hANP group . The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group . CONCLUSIONS hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance , suppressing the renin-angiotensin-aldosterone system , and exerting a strong diuretic effect BACKGROUND In cardiac surgery with cardiopulmonary bypass ( CPB ) , corticosteroids are administered to attenuate the physiological changes caused by the systemic inflammatory response . The effects of corticosteroids on CPB-associated renal damage have not been documented . The purpose of this study was to evaluate the effects of dexamethasone on perioperative renal dysfunction in patients undergoing cardiac surgery with CPB . METHODS Renal damage was prospect ively studied in 20 patients without concomitant morbidity undergoing coronary artery surgery with CPB . Patients were r and omized in a double-blind fashion to receive dexamethasone or placebo . Markers of glomerular function ( creatinine clearance ) and damage ( microalbuminuria ) , and markers of tubular function ( fractional excretion of sodium and free water clearance ) and damage ( N-acetyl-beta-D glucosaminidase ( NAG ) ) were evaluated in addition to plasma and urinary glucose levels . Plasma and urinary specimens were obtained at the following time periods : ( 1 ) baseline , during the 12 h before surgery ; ( 2 ) skin incision before heparinization ; ( 3 ) from heparinization until the end of CPB ; ( 4 ) during the 2 h following weaning from CPB ; ( 5 ) in the intensive care unit from 2 to 6 h after weaning of CBP ; ( 6 ) and from 36 to 60 h after weaning of CPB . RESULTS CPB was associated with an increase in markers in the placebo group , which returned to baseline during the second postoperative day , demonstrating a transient impairment of glomerular and tubular renal function . Similar patterns were observed in patients treated with dexamethasone . While postoperative glycosuria was significantly higher in the dexamethasone-treated group , no other differences between groups were observed . CONCLUSION Dexamethasone administration before CPB has no protective effect on perioperative renal dysfunction in low-risk cardiac surgical patients OBJECTIVE The purpose of this study was to evaluate the renoprotective effects of fenoldopam in patients at high risk of postoperative acute kidney injury undergoing elective cardiac surgery requiring cardiopulmonary bypass . DESIGN A double-blind r and omized clinical trial . SETTING Hospital . PARTICIPANTS One hundred ninety-three patients . INTERVENTIONS Patients undergoing cardiac surgery were r and omly assigned to receive a continuous infusion of fenoldopam , 0.1 microg/kg/min ( 95 patients ) , or placebo ( 98 patients ) for 24 hours . Patients were included if at least 1 of the following risk factors was present : preoperative serum creatinine > or = 1.5 mg/dL , age > 70 years , diabetes mellitus , or prior cardiac surgery . Serum creatinine and urinary output were measured at baseline ( T1 ) , 24 hours ( T2 ) , and 48 hours after surgery ( T3 ) . Acute kidney injury was defined as a postoperative serum creatinine level of > or = 2 mg/dL with an increase in serum creatinine level of 0.7 mg/dL or greater from preoperative to maximum postoperative values . MEASUREMENTS AND MAIN RESULTS Acute kidney injury developed in 12 of 95 ( 12.6 % ) patients receiving fenoldopam and in 27 of 98 ( 27.6 % ) patients receiving placebo ( p = 0.02 ) , whereas renal replacement therapy was started in 0 of 95 and 8 of 98 ( 8.2 % ) patients , respectively ( p = 0.004 ) . Serum creatinine was similar at baseline ( 1.8 + /- 0.4 mg/dL v 1.9 + /- 0.3 mg/dL ) in the fenoldopam and placebo groups but differed significantly ( p < 0.001 and p < 0.001 ) 24 hours ( 1.6 + /- 0.2 mg/dL v 2.5 + /- 0.6 mg/dL ) and 48 hours ( 1.5 + /- 0.3 mg/dL v 2.8 + /- 0.4 mg/dL ) after the operation . CONCLUSIONS A 24-hour infusion of 0.1 mug/kg/min of fenoldopam prevented acute kidney injury in a high-risk population undergoing cardiac surgery We prospect ively studied the effects of renal protection intervention in 17 patients with preoperative abnormal renal function ( plasma creatinine > 1.5 mg/dL ) scheduled for elective coronary surgery . Patients were r and omized to either dopamine 2.0 micro g [ center dot ] kg-1 [ center dot ] min-1 ( Group 1 , n = 10 ) or perfusion pressure > 70 mm Hg during cardiopulmonary bypass ( CPB ) ( Group 2 , n = 7 ) . Glomerular filtration rate and effective renal plasma flow were measured with inulin and 125 I-hippuran clearances before the induction of anesthesia , after sternotomy and before CPB , during hypo- and normothermic CPB , after sternal closure , and 1 h postoperatively . Plasma and urine electrolytes were measured , and free water , osmolar , and creatinine clearances , as well as fractional excretion of sodium and potassium , were calculated before and after surgery . Significant differences between groups were found before CPB for glomerular filtration rate ( higher in Group 1 ) , urine output ( 2.0 vs 0.29 mL/min in Group 1 versus Group 2 ) , urinary creatinine ( 66 vs 175 mg/dL ) , urinary osmolarity ( 370 vs 627 mOsm/L ) , osmolar clearance ( 2.1 vs 0.7 mL/min ) , and urinary potassium ( 33 vs 71 mEq/L ) . There were no differences between groups during hypo- and normothermic CPB . After CPB , the only difference was a slightly higher urinary creatinine in Group 2 . Renal plasma flow was lower than normal in all patients before the induction of anesthesia . A nonsignificant trend toward increased flow was seen during hypothermic CPB . Filtration fraction was high before CPB , which suggests efferent arteriolar vasoconstriction , descending toward normal during and after CPB . The same pattern of changes was present in both groups . In conclusion , there were no clinical ly relevant differences between the two treatment modalities during and after CPB . However , significant differences were observed before CPB , when dopamine seemed to partially revert renal vasoconstriction . Implication s : Two protective interventions were compared in patients undergoing heart surgery to prevent deterioration of renal function ; these were dopamine infusion throughout the operation and phenylephrine infusion during cardiopulmonary bypass . We found clinical ly relevant differences only during surgery before cardiopulmonary bypass PURPOSE Patients with renal impairment undergoing conventional coronary artery bypass grafting ( CABG ) have a significant risk of postoperative deterioration of kidney function . We investigated the outcome of patients with and without renal impairment treated by off-pump coronary artery surgery . METHODS From January 1997 until January 2000 , 158 consecutive patients ( mean age 63 + /- 9.8 years , 126 male , 32 female ) underwent minimally LIMA-to-LAD bypass operations . The patients were divided into three groups : group I patients ( n = 133 ) had a preoperative creatinine of < 1.3 mg/dL , group II patients ( n = 21 ) had a creatinine of > 1.3 mg/dL , and patients of group III ( n = 4 ) required chronic dialysis due to terminal kidney dysfunction . Monitoring of the blood creatinine was performed during the entire hospital stay . A postoperative angiogram was performed in 113 of the 158 patients . RESULTS All operations were performed without intraoperative complications . Postoperative angiograms revealed a patent LIMA-to-LAD bypass in all but one patient , who demonstrated a dissection of the left internal mammary artery ( LIMA ) graft . Mean creatinine value on admission was 1.0 + /- 0.1 mg/dL in group I and 2.7 + /- 1.9 mg/dL in group II . The maximal postoperative creatinine value was 1.1 + /- 0.4 mg/dL in group I and 2.9 + /- 2.7 mg/dL in group II . Neither hemofiltration nor hemodialysis was necessary in any patient of group I or group II during the postoperative course . CONCLUSION Minimally invasive LIMA-to-LAD bypass is a safe and effective procedure with low morbidity and no mortality in the first 158 patients . Preoperative renal impairment had no adverse effect on outcome or residual kidney function . Thus , higher doses of diuretics and hemofiltration/dialysis were not used , result ing in a cost reduction . Therefore , this approach may be worthwhile to consider in patients with significant renal impairment who have to undergo CABG BACKGROUND In order to evaluate the effect of the combined use of dopamine and diltiazem on renal function in patients undergoing coronary artery bypass grafting ( CABG ) , we conducted a prospect i ve r and omized study . MATERIAL / METHODS Sixty patients ( 8F , 52 M ) with normal preoperative renal function undergoing CABG were divided r and omly into four groups , including control ( n=15 ) , use of dopamine-only ( n=15 ) , use of diltiazem-only ( n=15 ) , and combined use of dopamine and diltiazem ( n=15 ) . The patients ranged in age from 38 to 74 years ( mean 59.3 ) . Drug administration ( diltiazem : intravenous infusion of 2 microg x kg(-1 ) x min(-1 ) , dopamine : 2 microg x kg(-1 ) x min(-1 ) ) was initiated 24 hours before surgery and was continued for 72 hours . RESULTS Creatinine and osmotic clearances were found to be significantly higher in the combined group compared with the other groups 24 hours after surgery ( p<0.05 ) . There was no significant difference in respect to creatinine clearance , osmotic clearance , and free water clearance in the dopamine-only and diltiazem-only groups compared to the control group . The free water clearance at 24 and 72 hours after surgery were significantly higher in the combined group compared with the other groups ( p<0.05 ) . In the control group , dopamine-only , and diltiazem-only groups beta(2)-microglobulin was statistically higher 72 hours postoperative than preoperatively ( p<0.05 ) . There were no significant changes in beta(2)-microglobulin levels in the combined group . CONCLUSIONS The combined use of dopamine and diltiazem may provide a positive contribution and sufficient protection for early postoperative renal function in patients undergoing CABG STUDY OBJECTIVES Cardiopulmonary bypass ( CPB ) represents a specific risk factor for renal damage during coronary revascularization . The purpose of this study was to compare the perioperative renal damage in patients undergoing on-pump and off-pump coronary surgery . DESIGN AND PATIENTS The progress and extent of renal damage was prospect ively studied in two groups of patients undergoing cardiac surgery without concomitant morbidity , undergoing elective coronary revascularization with ( n = 12 ) and without ( n = 10 ) CPB . Markers of glomerular function ( creatinine clearance ) and damage ( microalbuminuria ) , and markers of tubular function ( fractional excretion of sodium [ FENa ] and free water clearance ) and damage ( N-acetyl-beta-D glucosaminidase [ NAG ] ) were evaluated . Measuring plasma concentrations of free hemoglobin assessed hemolysis . Plasma and urinary specimens were obtained at the following points : ( 1 ) baseline ; ( 2 ) heparinization ; ( 3 ) the end of CPB or completing graft for off-pump surgery ; ( 4 ) skin closure ; ( 5 ) the sixth hour in the ICU ; and ( 6 ) the second postoperative day . Free water and creatinine clearances , FENa , and the urinary excretion of microalbumin and NAG were calculated for the corresponding time intervals . SETTING University hospital . RESULTS We found that off-pump coronary revascularization induced significantly less changes in microalbuminuria , FENa , free water clearance , NAG , and free hemoglobin as compared with operations with CPB . Markers returned to baseline within 2 days after the operation , and there was no clinical or laboratory evidence of overt renal dysfunction in both groups . CONCLUSION Off-pump coronary surgery attenuates transient renal injury compared with traditional on-pump coronary artery bypass grafting Background — Renal insufficiency is associated with increased morbidity and mortality after cardiopulmonary bypass cardiac surgery . B-type natriuretic peptide is a cardiac hormone that enhances glomerular filtration rate and inhibits aldosterone . Cystatin has been shown to be a better endogenous marker of renal function than creatinine . Methods and Results — We performed a double-blinded placebo-controlled proof of concept pilot study in patients ( n=40 ) with renal insufficiency preoperatively ( defined as an estimated creatinine clearance of < 60 mL/min determined by the Cockroft-Gault formula ) , undergoing cardiopulmonary bypass cardiac surgery . Patients were r and omized to placebo ( n=20 ) or IV low dose nesiritide ( n=20 ; 0.005 & mgr;g/Kg/min ) for 24 hours started after the induction of anesthesia and before cardiopulmonary bypass . Patients in the nesiritide group had an increase of plasma B-type natriuretic peptide and its second messenger cGMP with a decrease in plasma cystatin levels at the end of the 24-hour infusion . These changes were not observed in the placebo group . There was a significant activation of aldosterone in the placebo group at the end of the 24-hour infusion , but not in the nesiritide group . At 48 and 72 hours , there was a decrease in estimated creatinine clearance and an increase in plasma cystatin as compared with end of the 24-hour infusion in the placebo group . In contrast , renal function was preserved in the nesiritide group with no significant change in estimated creatinine clearance and a trend for plasma cystatin to increase as compared with end of the 24-hour infusion . Conclusion — This proof of concept pilot study supports the conclusion that perioperative administration of low dose nesiritide is biologically active and decreases plasma cystatin in patients with renal insufficiency undergoing cardiopulmonary bypass cardiac surgery . Further studies are warranted to determine whether these physiological observations can be translated into improved clinical outcomes BACKGROUND Pre-existing chronic renal failure is a significant risk factor for acute renal failure ( ARF ) after cardiac surgery . N-acetylcysteine ( NAC ) has been shown to prevent contrast media-induced ARF . Our objective was to evaluate whether i.v . NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery . METHODS In this prospect i ve , r and omized , double-blind study , 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited . All received either i.v . NAC ( n=38 ) or placebo ( n=39 ) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase ( NAG ) and urine creatinine ratio , plasma creatinine , and serum cystatin C levels indicated renal function . RESULTS Levels of urinary NAG/creatinine ratio , plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days . Urine NAG/creatinine ratio increased over 30 % in 100 % of patients in the NAC group vs 92.3 % in the placebo group ( P=0.081 ) . Plasma creatinine increased by 25 % from baseline or over 44 mumol litre(-1 ) in 42.1 % in NAC group vs 48.7 % in placebo group ( P=0.560 ) . Serum cystatin C exceeded 1.4 mg litre(-1 ) in 78.9 % in NAC group vs 61.5 % in placebo group ( P=0.096 ) . CONCLUSIONS Prophylactic treatment with i.v . N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery ABSTRACT Objective : Renal function impairment is a common complication in cardiac surgery patients . Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals , which have been shown to impair various organs including the kidneys , radical scavenging may protect renal function . Therefore , the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine ( NAC ) versus placebo on peri-operative renal function in cardiac surgery patients . Research design and methods : We reanalyzed the data of our previous study in which 40 coronary artery surgery patients ( 66 ± 9 [ SD ] years , 9 women and 31 men ) with normal pre-operative renal function had been r and omized in a double-blind fashion to receive either NAC ( 100 mg/kg into the cardiopulmonary bypass prime followed by infusion at 20 mg/kg/h ; n = 20 ) or placebo ( n = 20 ) . We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication . Creatinine clearance was calculated according to Cockcroft and Gault . Results : Biometric and intra-operative patient data were similar between both groups . In the placebo group , serum creatinine increased from 93.1 ± 35.4 µmol/L pre-operatively to 115.9 ± 47.2 µmol/L on post-op day 1 ( p < 0.001 ) . In contrast , serum creatinine in the NAC group remained unchanged ( 92.3 ± 31.3 µmol/L pre-op ; 99.3 ± 25.4 µmol/L on post-op day 1 ; p = 0.084 ) . Accordingly , creatinine clearance decreased by 16.9 ± 14.3 mL/min in the placebo group as compared to 7.5 ± 17.7 mL/min in the NAC group ( p = 0.039 ) . Urinary output and diuretic medication were similar between NAC and placebo . Conclusions : Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass Background Sympathetic vascular insult and hemodynamic changes represent the most reliable explanation of renal impairment result ing from acute intraabdominal pressure . We evaluated the effects of low-dose dopamine administration during a long-lasting surgical laparoscopic procedure . Methods For this study 40 , patients su bmi tted to a colorectal laparoscopic procedure with 15 mmHg of intraabdominal pressure were r and omly allocated to two groups : 20 receiving 2μg/kg/min of dopamine and 20 receiving the same perfusion of saline . Hemodynamic parameters , renal function , urinary output , and creatinine clearance , were studied . Results The hemodynamic parameters were similar in both groups . The urinary output decreased during the intraoperative period only the saline group ( p=0.4 ) . Then 2 h postoperatively , it increased in both groups , and no statistically significant differences were found between the groups . The creatinine clearance decreased in both groups during the intraoperative time , but it was worse in the saline group ( −28±120 vs −194±106 ; p=0.022 ) . During the postoperative period , both groups showed improvement , but in control group the values remained lower than at baseline ( p=0.04 ) , and significantly lower than in the dopamine group ( 230±337 vs 100±192 ; p=0.012 ) . Conclusions An intrabdominal pressure of 15 mmHg induces a time-limited renal dysfunction , and low doses of dopamine could prevent this undesirable effect BACKGROUND The incidence of acute renal failure ( ARF ) after cardiac surgery remains high , despite improvements in surgical techniques and perioperative care , and is associated with an unacceptably high mortality . The adenosine receptor antagonist theophylline has been shown to confer some benefit in experimental and clinical ARF due to ischaemia , contrast media and various nephrotoxic agents . METHODS In a double-blind , r and omized , placebo-controlled trial , the effectiveness of theophylline for prevention of renal impairment after elective coronary artery bypass grafting ( CABG ) was evaluated . Fifty-six patients with normal renal function received a bolus of 4 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h theophylline ( n=28 ) or isotonic saline ( n=28 ) for up to 96 h. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery , and the glomerular filtration rate ( GFR ) ( [(51)Cr]EDTA-clearance ) was determined preoperatively , and at days 1 , 3 and 5 after surgery . RESULTS Serum creatinine and GFR were the same in both groups . The number of patients with increases of serum creatinine > or = 0.4 mg/dl were five in the theophylline group and four in the placebo group . Volumes of infused fluid and urine volumes were not different between groups , both ranging from approximately 7.5 to 8 l during the first 24 h after surgery . The number of patients with termination of study medication due to presumed side effects was not different between placebo and theophylline groups . CONCLUSIONS Theophylline administration for renal protection after CABG appears to be ineffective in a pilot study in well-hydrated patients . However , the statistical power of our study was not sufficient to exclude a possible protective effect of theophylline . The present study demonstrated the feasability of a larger trial with theophylline or one of the new specific adenosine A1 receptor antagonists in the setting of ARF after cardiac surgery BACKGROUND Renal dysfunction and acute renal failure are serious complications of open heart operations . Previous reports have suggested beneficial effects of exogenous glutathione for preservation of renal function after ischemic renal injury . We prospect ively studied the effect of perioperative administration of glutathione on renal function in patients who underwent coronary artery bypass operation . STUDY DESIGN Two hundred mg per kg of glutathione was administered to the treated group ( n = 10 ) before cardiopulmonary bypass , and on the first and second postoperative days . The control group was administered placebo in the same volume . Hemodynamics , renal function , and plasma hormone levels were measured consecutively . RESULTS In the glutathione group , the mean arterial pressure and systemic vascular resistance index were lower than in the control group . Urine volume , creatinine clearance , and renal excretory index were well preserved in the group treated with glutathione . Moreover , the fractional excretion of sodium was lower and urine and plasma osmolarity was higher in the group treated with glutathione . No differences in plasma renin activity , angiotensin II , or aldosterone concentrations between the two groups were observed . CONCLUSIONS Perioperative glutathione treatment has a salutary effect on perioperative renal function through effects on both renal hemodynamics and tubular mechanism Background and objective : Patients with impaired renal function are at risk of developing renal dysfunction after abdominal aortic surgery . This study investigated the safety profile of a recent medium‐molecular‐weight hydroxyethyl starch ( HES ) preparation with a low molar substitution ( HES 130/0.4 ) in this sensitive patient group . Methods : Sixty‐five patients were r and omly allocated to receive either 6 % hydroxyethyl starch ( Voluven ® ; n = 32 ) or 3 % gelatin ( Plasmion ® ; n = 33 ) for perioperative volume substitution . At baseline , renal function was impaired in all study patients as indicated by a measured creatinine clearance < 80 mL min−1 . The main renal safety parameter was the peak increase in serum creatinine up to day 6 after surgery . Results : Both treatment groups were compared for non‐inferiority ( pre‐defined non‐inferiority range hydroxyethyl starch < gelatin + 17.68 & mgr;mol L−1 or 0.2 mg dL−1 ) . Other renal safety parameters included minimum postoperative creatinine clearance , incidence of oliguria and adverse events of the renal system . Baseline characteristics , surgical procedures and the mean total infusion volume were comparable . Non‐inferiority of hydroxyethyl starch vs. gelatin could be shown by means of the appropriate non‐parametric one‐sided 95 % CI for the difference hydroxyethyl starch − gelatin [ −∞ , 11 & mgr;mol L−1 ] . Oliguria was encountered in three patients of the hydroxyethyl starch and four of the gelatin treatment group . One patient receiving gelatin required dialysis secondary to surgical complications . Two patients of each treatment group died . Conclusion : As we found no drug‐related adverse effects of hydroxyethyl starch on renal function , we conclude that the choice of the colloid had no impact on renal safety parameters and outcome in patients with decreased renal function undergoing elective abdominal aortic surgery BACKGROUND This prospect i ve , r and omized study assessed the effect of dopamine on renal tubular function in patients who had coronary artery bypass grafting . METHODS Two groups of patients with normal preoperative renal function were r and omly divided into a dopamine group ( n=11 ) , who received dopamine in a dose of 2 mg/kg x min , and a control group ( n=11 ) , who received no treatment . Dopamine infusion was initiated 24 hours before the operation and was continued for 48 hours postoperatively . Measurements of renal function obtained 2 days before the operation were considered preoperative and were repeated on the 1st , 3rd , and 7th postoperative days . Urinary excretion of b2-Microglobulin ( b2-M ) , considered a sensitive means for diagnosing proximal tubular damage , was measured during the early ( day 3 ) and late ( day 7 ) postoperative period . RESULTS There were no significant differences respect to the clearances of creatinine , osmotic , and free-water in the dopamine group compared with the control group ( p>0.05 ) . Urine microalbumin levels significantly increased on postoperative day 3 in both groups . During the early postoperative period , excretion of urine b2-M was significantly greater in the dopamine group than in the control group ( p<0.05 ) . CONCLUSIONS Consequently , in patients with normal preoperative renal and cardiac function scheduled for elective coronary artery bypass grafting , renal dose dopamine infusion alone may not provide sufficient protection on tubular function and increases renal tubular injury during the early postoperative period UNLABELLED Elderly patients are at risk of developing renal dysfunction . Synthetic colloids are often used perioperatively , but they may have detrimental effects on renal function . In a prospect i ve , r and omized study , we assessed the influence of different intravascular volume replacement regimens on renal function in elderly ( > 65 yr ) and younger ( < 65 yr ) patients without preoperative renal dysfunction who were undergoing major abdominal surgery . Either 6 % low molecular weight hydroxyethyl starch ( HES ) solution ( mean molecular weight 70,000 D , degree of substitution 0.5 ; HES 70/0.5 ) [ each group n = 10 ] ) , 6 % medium-molecular weight HES ( molecular weight 200,000 D , degree of substitution 0.5 ( HES 200/0.5 ) [ each group n = 10 ] ) , or modified gelatin ( molecular weight 35,000 D [ each group n = 10 ] ) was administered to maintain mean arterial blood pressure > 65 mm Hg and central venous pressure between 10 and 14 mm Hg . After the induction of anesthesia ( T0 ) ; at the end of surgery ( T1 ) ; 4 h after surgery ( T2 ) ; and on the first ( T3 ) , second ( T4 ) , and third postoperative days ( T5 ) , alpha1-microglobulin ( alpha1-M ) , N-acetyl-beta-glucosaminidase , fractional sodium clearance , and creatinine clearance ( CC ) were measured . Colloids ( 1300 - 3000 mL ) were infused until the first postoperative day . At T0 , urine concentrations of alpha1-M were higher in the elderly than in the younger patients in all groups ( P < 0.05 ) . alpha1-M remained increased only in the gelatin group . N-acetyl-beta-glucosaminidase and fractional sodium clearance were not affected during the study period in any groups . At baseline , CC was significantly higher in the younger than in the elderly patients , but CC did not decrease in any of the intravascular volume replacement groups . We conclude that intravascular volume therapy with gelatin and two different HES preparations did not adversely affect renal function in elderly patients without preoperative renal malfunction . IMPLICATION S We studied the influence of three different intravascular volume replacement regimens on renal function in elderly patients without renal dysfunction who were undergoing major abdominal surgery . Two hydroxyethyl starch and one gelatin preparation were administered perioperatively to maintain stable hemodynamics . As assessed by sensitive markers of renal function , all three regimens can be used safely for volume replacement without risking significant renal dysfunction Background and objectives : Postoperative acute renal failure predicts morbidity and mortality . We investigated the effect of nifedipine infusion on glomerular filtration rate in patients with impaired renal function undergoing cardiopulmonary bypass surgery . Methods : Twenty patients accepted for coronary bypass and /or heart valve surgery were enrolled prospect ively and r and omized to nifedipine infusion or no treatment . Males and females with creatinine ⩾150 & mgr;mol L−1 and ⩾130 & mgr;mol L−1 , respectively , were included . Patients with unstable angina pectoris , ejection fraction ⩽35 % and those on dialysis were excluded . Glomerular filtration rate was measured preoperatively and 48 h postoperatively . Creatinine clearance was measured preoperatively and 0‐4 , 20‐24 and 44‐48 h postoperatively . There were no statistically significant differences in patient characteristics . Biochemical markers in plasma and urine were measured before and 48 h after surgery . Results : The mean ± SD preoperative glomerular filtration rates were 32.2 ± 11.5 and 31.4 ± 17.0 mL min−1 per 1.73 m2 in the nifedipine and control groups ( P = 0.90 ) , respectively . There was no statistically significant change in the glomerular filtration rate or in creatinine clearance over time within or between groups . A linear mixed model showed no effect of nifedipine ( P = 0.44 ) , time ( P = 0.97 ) or interaction of nifedipine and time ( P = 0.99 ) on creatinine clearance . Perioperative arterial pressure was kept within predefined targets . Three patients received dialysis postoperatively , all in the control group ( P = 0.21 ) . There were no statistically significant differences between groups in changes of urinary or plasma biochemistry . Conclusions : Renal function was well preserved after cardiopulmonary bypass surgery in patients with impaired renal function when maintaining thorough intensive care surveillance . Nifedipine did not influence early postoperative renal function PURPOSE Dopamine continues to be used for preventing and treating acute renal failure . We determined the effects of dopamine on postoperative renal function in patients with a solitary kidney undergoing partial nephrectomy . MATERIAL S AND METHODS We performed a prospect i ve r and omized controlled study at a tertiary care referral center involving 24 patients with a solitary kidney undergoing partial nephrectomy secondary to malignancy . Patients were r and omized to receive dopamine ( 11 ) [ corrected ] or no dopamine ( 13 ) [ corrected ] . Intraoperatively those assigned to the dopamine group received a 3 microg./kg . per minute dopamine infusion . Patients in each group received an adequate amount of fluid to maintain good urine production , systemic blood pressure and central venous pressure . Serum electrolytes , blood urea nitrogen , creatinine , serum and urine osmolality , and urine output were measured at baseline , intraoperatively and through postoperative day 4 . Preoperatively and postoperatively renal blood flow and the glomerular filtration rate were measured . RESULTS In the 2 groups blood urea nitrogen and serum creatinine increased postoperatively . Although the degree of this increase showed a trend to be lower in the dopamine group , the difference did not reach statistical significance . There was no difference in renal blood flow or the glomerular filtration rate in the treatment groups . CONCLUSIONS Administering dopamine to patients with a solitary kidney undergoing partial nephrectomy provided no renoprotective effect 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 OBJECTIVE Acute renal failure remains a common and serious complication of cardiac surgery . In this r and omized trial , we aim ed to assess whether sodium nitroprusside ( SNP ) infusion during cardiopulmonary bypass ( CPB ) could prevent renal dysfunction after coronary artery bypass grafting ( CABG ) surgery . METHODS Between October 2004 and May 2006 , 240 consecutive patients with stable angina undergoing elective CABG for multi-vessel coronary artery disease were prospect ively r and omized into control ( n=116 , 72 men , mean age 61.3+/-9.7 years ) or SNP groups ( n=124 , 81 men , 60.8+/-10.8 years ) . SNP group received SNP after initiation of rewarming period during CPB at a dose of 0.1mg/kg/h and the infusion was concluded by weaning from CPB . The anesthetic and CPB regimes were st and ardized . Blood urea nitrogen ( BUN ) , serum creatinine ( SCr ) , estimated glomerular filtration rate ( eGFR ) , creatinine clearance ( C(Cr ) ) , urine output , serum cardiac specific troponin I ( cTnI ) , creatine kinase cardiac isoenzyme ( CKMB ) , and CPK were measured preoperatively and daily until day 5 after surgery . RESULTS There were no differences in baseline levels of BUN , SCr , eGFR , C(Cr ) , cTnI , CKMB , CPK levels and EuroSCORES between the groups . Although the duration s of cross clamp , CPB times , and postoperative cardiac enzymes were similar in both groups ; in the control group , there was a significantly lower urine excretion during CPB ( p=0.002 ) and the operation ( p=0.041 ) . Peak postoperative SCr levels were significantly ( p=0.001 ) lower in the SNP group than in the control group ( 1.29+/-0.28 vs 1.42+/-0.34mg/dl ) . The incidence of > or=50%DeltaSCr was significantly higher in the control group when compared with the SNP group ( 35.3 vs 13.7 % , p<0.001 ) . Development of new C(Cr ) less than 50ml/min postoperatively was significantly higher in the control group compared with the SNP group ( 14 vs 38 % , p<0.001 ) . CONCLUSION SNP administration during rewarming period of non-pulsatile CPB in patients undergoing CABG surgery is associated with improved renal function compared with conventional medical treatment providing adequate preload and mean arterial pressures Effects of dopamine and dobutamine on renal function and urinary excretion of prostagl and in E2 ( UPGE ) were studied in 21 elderly patients who underwent abdominal surgery . Fractional sodium excretion ( FeNa ) , creatinine clearance ( Ccr ) , urinary volume ( UV , ml.kg-1.min-1 ) and UPGE were measured on the first and second postoperative day . These patients were divided into three groups : i.e. C ( control ) , DA ( dopamine ) and DB ( dobutamine ) groups . Group DA received dopamine 2 mcg.kg-1.min-1 beginning at six o'clock on the first postoperative day . Group DB received dobutamine 2 mcg.kg-1.min-1 . There were no significant differences in UV and UPGE among these three groups . Ccr was significantly higher on the second postoperative day than that on the first postoperative day in DA group . FeNa in DA group was higher than in C group on the second postoperative day . The relationship between UPGE and UV was not determined . These results suggest that DA improve renal functions in the elderly Even during adequate general anesthesia , hypertension is a common phenomenon in patients undergoing aortocoronary bypass grafting ( CABG ) . In such cases application of vasodilators is recommended in order to decrease myocardial oxygen consumption . This study was performed to compare two commonly used substances , i.e. , nitrates and nifedipine , with regard to their influence on hemodynamics , renal blood flow , kidney function , and the requirement for homologous blood transfusions . METHODS . Forty-four patients gave their informed consent to the study . They were r and omly divided into 2 groups : group 1 received nitroglycerin ( 3.0 micrograms/kg.min ) , group 2 nifedipine ( Adalat , 0.5 microgram/kg.min ) in order to prevent hypertension in the phase before onset of cardiopulmonary bypass ( CPB ) . Anesthesia was induced by etomi date and succinylcholine and maintained as a modified neuroleptanalgesia with fentanyl ( up to 50 micrograms/kg ) , midazolam ( 0.3 mg/kg.h ) , and pancuronium ( 0.1 mg/kg ) . Systolic blood pressure was kept within the range of 120 - 160 mm Hg ; in case of higher values boluses of either 0.25 mg nitroglycerin or 0.5 mg nifedipine were administered . Cardiac index , stroke volume index , rate-pressure product , intrapulmonary shunt , and pulmonary and total peripheral resistances were evaluated at five predefined points : ( 1 ) after induction of anesthesia ; ( 2 ) before incision ; ( 3 ) before cannulating the aorta ; ( 4 ) after decannulating the aorta ; and ( 5 ) at the end of operation . Creatinine and free-water clearances as well as sodium and potassium excretion were calculated for three phases of the operation : ( A ) induction of anesthesia -- onset of CPB ; ( B ) during CPB ; and ( C ) end of CPB -- end of operation . CPB was performed using a membrane oxygenator ( Sorin 51 ) and a nonpulsatile blood flow of 2.5 1/min.m2 , which was reduced during mild hypothermia of 30 - 32 degrees C to 1.7 l/min.m2 . Mean arterial pressure in both groups was kept at approximately 70 mm Hg . In case of lower pressures norepinephrine ( 50 - 100 micrograms/bolus ) was administered ; higher pressures were treated as described above . Volume substitution was performed initially by 500 ml hydroxyethyl starch and continued , if necessary , by homologous blood or 5 % human albumin in order to keep the hematocrit greater than 30 in the phases before and after CPB . RESULTS . Group 2 showed significantly higher values of cardiac index and stroke volume index at point 3 while the rate-pressure product was clearly lower , indicating better myocardial performance and lower oxygen consumption than in group 1 . Creatinine and free-water clearances in all three phases did not differ . However , sodium excretion during CPB was significantly higher in the nifedipine group while potassium excretion showed no differences . The average requirement for blood and blood substitutes was lower in group 2 , but the difference could not be confirmed statistically because of the large dispersion of values . Nevertheless , 4 patients in the nifedipine group but no patient in group 1 did not need homologous blood transfusion . CONCLUSION . In comparison to nitrates , nifedipine showed some advantages in the treatment of hypertension during CABG : ( 1 ) it provided better myocardial performance ; ( 2 ) it had a more reliable but not too long-lasting effect on elevated total peripherial resistance , leading to better hemodynamic stability ; and ( 3 ) by not affecting the capacitance vessels it may necessitate fewer homologous blood transfusions BACKGROUND Intestinal mucosal barrier dysfunction observed in patients undergoing transperitoneal abdominal aortic aneurysm ( AAA ) repair may contribute to the development of the systemic inflammatory response syndrome and dysfunction of various organs . The aim of this study is to investigate whether an extraperitoneal approach reduces intestinal mucosal barrier and renal dysfunction in elective infrarenal AAA repair . METHODS Twenty patients admitted for elective infrarenal AAA repair were r and omized into either the transperitoneal approach ( n=10 ) or the extraperitoneal approach ( n=10 ) . Intestinal permeability was measured preoperatively , and at day 1 and day 3 after surgery using the lactulose/mannitol test by calculating the differential urinary excretion ratio of the two sugars after oral administration . Renal dysfunction was assessed by measuring the urinary albumin/creatinine ratio ( ACR ) at the same time points . RESULTS Intestinal permeability was significantly increased in the transperitoneal group at day 1 [ 0.124+/-0.035 ( mean+/-s.e.m . ) ] compared to the preoperative level ( 0.020+/-0.003 ) , ( p=0.001 ) and to the extraperitoneal group at day 1 ( 0.025+/-0.008 ) , ( p<0.05 ) which showed no change in comparison with the preoperative level ( 0.020+/-0.003 ) . The ACR was also significantly increased in the transperitoneal group at day 1 ( 16.69+/-5.12 ) compared to the preoperative level ( 5.71+/-2.89 ) , ( p<0.05 ) and to the extraperitoneal group at day 1 ( 4.33+/-1.49 ) , ( p<0.05 ) which showed no significant change at any of the times examined . No correlation was observed between the lactulose/mannitol ratio and the albumin/creatinine ratio , or between age , operating time , aortic clamping time , amount of blood lost or blood transfused . CONCLUSIONS These results support the suggestion that minimising intestinal manipulation using an extraperitoneal approach in AAA repair preserves intestinal mucosal barrier and renal glomerular functions We have examined the possible renoprotective effect of felodipine 5 mg orally , given daily for 5 days before operation , in 29 patients undergoing elective infrarenal aortic surgery in a r and omized , blinded and placebo-controlled study . Effective renal plasma flow ( ERPF ) , glomerular filtration rate ( GFR ) , urine output , fractional sodium clearance and plasma concentrations of angiotensin II , aldosterone , arginine vasopressin and atrial natriuretic peptide did not differ between the felodipine and placebo groups . ERPF and GFR were not reduced after operation in the placebo group . In the felodipine group , GFR was higher 24 h after operation compared with before operation . We conclude that increased GFR in the felodipine group , measured 24 h after operation , may indicate a beneficial effect of felodipine but in the present context this was not clinical ly important . Felodipine had no significant effect on vasoactive hormones Objective To compare a solution of 3 % dextran-60 ( D60 ) in Ringer 's lactate ( RL ) with RL alone as maintenance fluids for abdominal aortic surgery . Design R and omized control trial of 20 consecutive patients undergoing elective aortic reconstructive surgery . Setting A surgical ICU in a university hospital . Patients Consecutive patients , mean age 64 yr . Five patients had abdominal aneurysm , 12 had aortic obstruction disease , and three had aortic renal bypass surgery . These patients were followed for 1 month . Interventions Pulmonary artery occlusion pressure of at least 10 mm Hg and a urine output > 30 mL/h were used to guide the intraoperative fluid infusion rates , which were 36 and 104 mL/kg of D60 and RL , respectively ( ratio 1:2.9 ) . Measurements and Main Results Body weight at 24 hr had increased more with RL ( 7.8 kg ) than with D60 ( 3.2 kg ) infusion ( p < .01 ) , despite intraoperative urine volumes of 151 and 92 mg/kg with RL and D60 , respectively . Total intravascular albumin decreased from 0.7 g/kg ( 1.4 to 0.7 g/kg ) in both groups , corresponding to a plasma volume ( PV ) loss of 13 mg/kg without fluid infusions . A total intravascular dextran of 0.5 g/kg result ed in a PV expansion at 1 hr of 4.4 mL/kg above preoperative level , in sharp contrast to 7.0 mL/kg decrease in PV with RL . Of the intraoperative 3 % D60 and RL infused , an estimated 51 % D60 and 6 % RL remained as PV expansion at 1 hr . Conclusion A diluted colloid solution in Ringer 's lactate is of significant value in maintaining intravascular volumes and hemodynamics during and after major operative procedures . ( Crit Care Med 1991 ; 19:36 Surgical treatment for the relief of obstructive jaundice is still complicated by postoperative acute renal failure in almost 10 per cent of patients . Renal failure in the patient with jaundice is associated with the presence of bacterial endotoxin in the peripheral blood , and enteric endotoxin absorption is facilitated by the absence of bile salts from the intestine . Oral replacement of bile salts should prevent endotoxemia and renal failure . Forty-six patients with jaundice were studied . Twelve patients received sodium deoxycholate preoperatively , 12 received chenodeoxycholic acid and 22 acted as controls . Endotoxemia was measured by the limulus test and renal function assessed by 24 hour creatinine clearance . No patient given deoxycholate preoperatively had systemic endotoxemia or postoperative impairment of renal function . Endotoxemia was reduced in the chenodeoxycholic acid group , but not significantly , and renal function was not protected . Sodium deoxycholate is undergoing further evaluation in a multicenter r and omized prospect i ve study Hemodynamic , pulmonary , and renal variables were measured in 24 patients scheduled for major abdominal aortic operations . Control values were obtained before preoperative medications were given . All patients received 5 % dextrose in Lactated Ringer 's solution intraoperatively . Postoperatively , group 1 patients received 5 % dextrose in water plus albumin , group 2 received 5 % dextrose in 0.45 sodium chloride solution , and group 3 received 5 % dextrose in lactated Ringer 's solution . There were significant increases in Qs/Qt and AaDO2 , 48 hours after operation in group 3 . Oxygen consumption and cardiac output increased in all groups 24 hours after operation . Twenty-four hours later , these two variables returned to control values in group 1 but continued to rise in the other two groups . Significant diuresis occurred in group 1 , 48 hours postoperatively , whereas the other two groups continued to retain water . Use of albumin and 5 % dextrose in water in the postoperative period seemed to produce less deviations from control values of most measured variables , than the other two groups Bowel preparation using purgatives has previously been shown significantly to increase haemoglobin concentration and decrease weight . This prospect i ve r and omized study assessed the effects of administering intravenous fluid during bowel preparation The role of preoperative lactulose and bile salts in the prevention of postoperative renal failure in patients with obstructive jaundice has been evaluated in a prospect i ve r and omized trial . One hundred and two patients undergoing surgery for obstructive jaundice ( bilirubin > 100 μmol/l ) were r and omized into three groups : those receiving preoperative oral lactulose ( n = 35 ) , those receiving oral sodium deoxycholate ( n = 32 ) and a control group of patients receiving no specific treatment ( n = 35 ) . All patients received intravenous fluids commencing the night before surgery . One patient in the control group and none in the treatment groups developed postoperative renal failure . Postoperative deterioration of renal function in patients with normal preoperative function was significantly more common in the control group than in the treatment groups ( χ2 = 8·1 , d.f . = 2 , P<0·02 ) . The incidence of renal failure and impairment was lower in this control group than that reported in previous studies . This may be due to the introduction of adequate preoperative hydration . Additional protection occurs by the preoperative administration of either lactulose or sodium deoxycholate The effect of optimal hydration on haemodynamics and renal function during infrarenal aortic cross clamping was studied in 26 consecutive patients operated on because of an infrarenal aortic aneurysm . The patients were r and omly divided over two groups . The patients of group B ( n = 13 ) were optimally hydrated before the operation . The Starling curve was used as st and ard . Patients of group A ( n = 13 ) served as control . The pre-operative and postoperative renal functions of both groups were compared , as were the haemodynamic parameters . The haemodynamic parameters were measured at five minutes intervals during the entire procedure . During aortic clamping the heart rate was significantly lower in patients of group B , indicating a lower myocardial oxygen consumption . Neither the haemodynamic parameters nor the renal function showed other beneficial effects on optimal hydration OBJECTIVES To evaluate in a cohort of ESCAD patients ( pts ) the effects of on-pump/beating-heart versus conventional CABG in terms of early and mid-term survival and morbidity and LV function improvement . METHODS Between January 1993 and December 2000 , 78 ( Group I ) ESCAD pts underwent on-pump/beating-heart surgery . Mean age in Group I was 66.2+/-6 ( 58 - 79 ) , NYHA and CCS class were 3.2+/-0.6 and 3.3+/-0.4 respectively , Myocardial viability index 0.69+/-0.1 ( % ) , LVEF ( % ) 24.8+/-4 , LVEDP ( mmHg ) 28.1+/-5.8 and LVEDD(mm ) 69.5+/-6 . Group II consisted in 78 ESCAD patients undergoing conventional CABG selected in a r and omized fashion from an age , sex , and LVEF corrected group of patients . Mean age in Group II was 65.7+/-5 ( 57 - 78 ) , NYHA 3.1+/-0.7 , CCS 3.4+/-0.8 , LVEF(% ) 25+/-5 , LVEDP(mmHg ) 27.9+/-4.4 and LVEDD(mm ) 69.2+/-7.2 . RESULTS Postoperatively , 5(7.7 % ) patients died in Group I versus 7(11.5 % ) patients in Group II ( P>0.1 ) . CPB time result ed to be in Group II patients ( P=0.001 ) and the mean distal anastomoses per patient was similar between groups ( P = Ns ) . Perioperative AMI ( P=0.039 ) , LCOS ( P=0.002 ) , necessity for ultrafiltration ( P=0.018 ) and bleeding>1000 ml ( P=0.029 ) were significantly higher in Group II . None of the Group I patients underwent surgical revision for bleeding versus 8(10.3 % ) patients in Group II ( P=0.011 ) . At 6 months after surgery , the LV function improved significantly in Group I patients , demonstrated by an increased LVEF=27.2+/-4(%)(P=0.001 ) , lower LVEDP=26.4+/-3(mmHg)(P=0.029 ) and LVEDD=67+/-4(mm ) ( P=0.004 ) instead of a lower LVEDD=66.8+/-6(mm)(P=0.032 ) versus the preoperative data in Group II . The actuarial survival at 1 , 3 and 5 yr were 90 , 82 and 71 % in Group I and 89 , 83 and 74 % in Group II ( P = Ns ) . CONCLUSION In ESCAD patients who may poorly tolerate cardioplegic arrest , on-pump/beating-heart CABG may be an acceptable alternative associated with lower postoperative mortality and morbidity . Such a technique offers a better myocardial and renal protection associated with lower postoperative complications due to intraoperative hypoperfusion PURPOSE To evaluate the influence of dopamine and diltiazem on renal function and markers for acute renal failure , including urinary alpha-glutathion s-transferase ( alpha-GST ) , alpha-1-microglobulin ( alpha(1)-MG ) and N-acetyl-ss-glucosaminidase ( ss-NAG ) after extracorporeal circulation . METHODS In a r and omized , placebo-controlled , double-blind trial we evaluated the efficacy of dopamine ( 2.5 micro g x kg(-1 ) x min(-1 ) ) , diltiazem ( 2 micro g x kg(-1 ) x min(-1 ) ) or placebo administered over 48 hr postoperatively to maintain renal tubular integrity in 60 elective cardiac surgery patients . alpha-GST , alpha(1)-MG , ss-NAG , and creatinine clearance were measured from urine collected during surgery ( T0 ) , the first four hours ( T1 ) , 24 hr ( T2 ) and 48 hr ( T3 ) postoperatively . RESULTS Cumulative urine output in the diltiazem group ( 9.0 + /- 2.8 L ) increased significantly compared with placebo ( 7.0 + /- 1.6 L ) , but not compared with dopamine ( 7.8 + /- 1.8 L ) . Creatinine clearance showed no significant intergroup differences . In all groups alpha(1)-MG increased from T0 to T3 , but we found no significant intergroup differences . alpha-GST increased significantly from T0 to T3 in the placebo ( 2.1 + /- 1.8 to 11.4 + /- 8.6 micro g x L(-1 ) ) and in the dopamine groups ( 2.7 + /- 1.8 to 13.6 + /- 14.9 micro g x L(-1 ) ) , but not in the diltiazem group ( 1.8 + /- 1.4 to 3.2 + /- 3.2 micro g x L(-1 ) ) . Forty-eight hours postoperatively alpha-GST was significantly lower in the diltiazem group than in both other groups . CONCLUSIONS Diltiazem stimulates urine output , reduces excretion of alpha-GST and ss-NAG and may be useful to maintain tubular integrity after cardiac surgery OBJECTIVES The purpose of this study was to investigate the efficacy of carperitide ( human atrial natriuretic peptide [ h-ANP ] ) in perioperative management in patients with renal dysfunction , especially its kidney-protecting effects . PATIENTS AND METHODS The subjects were 18 patients who underwent elective cardiac surgery using cardiopulmonary bypass ( CPB ) with a preoperative serum creatinine ( Cr ) level of 1.2 mg/dl or more . The subjects were prospect ively assigned to 2 groups : an h-ANP-treated group ( Group H , n = 10 ) and a non-h-ANP-treated group ( Group N , n = 8) . At the beginning of surgery , h-ANP administration was initiated and continued for 5 days or more . The central dose was 0.02 microg/kg/min . The primary end point included the serum Cr level and creatinine clearance ( Ccr ) . RESULTS In Group H , Cr level significantly decreased after surgery compared to the preoperative level . The Ccr values were significantly higher 2 and 3 days after surgery than the preoperative values . And the intraoperative urine volume significantly increased . In Group H , an increase in urinary N-acetyl-beta-D-glucosaminidase ( NAG ) level the day after surgery was significantly inhibited in comparison with Group N. CONCLUSION The results of this study suggest that in patients with renal dysfunction before cardiac surgery , continuous low-dose h-ANP therapy maintains renal function , preventing its deterioration OBJECTIVES a ) To determine if antidiuretic hormone ( ADH ) is elevated in patients undergoing spinal fusion , especially in those who have clinical evidence of syndrome of inappropriate antidiuretic hormone ( SIADH ) ; b ) to evaluate the relationship between ADH secretion and the secretion of atrial natriuretic peptide ( ANP ) . SETTING Tertiary care pediatric intensive care unit ( ICU ) in a university hospital . DESIGN A prospect i ve cross-sectional , observational study with factorial design . PATIENTS Thirty patients > or = 10 yrs of age undergoing spinal fusion admitted to the ICU for postoperative care . INTERVENTIONS Patients underwent anterior , posterior , or both anterior/posterior spinal fusion . Blood was collected for serial measurements of ADH , ANP and serum electrolyte levels . Heart rate , blood pressure and central venous pressure were measured . MEASUREMENTS AND MAIN RESULTS Thirty children were studied . Nineteen had idiopathic scoliosis , nine had neuromuscular scoliosis , one had Marfan 's disease , and one had congenital scoliosis . Ten ( 33 % ) children met clinical criteria of SIADH . There was no difference in duration of surgery , blood loss , volume of iv fluid administration pre- and intraoperatively , or type of scoliosis between those who developed SIADH and those who did not . Hemodynamic variables were similar in both groups . ADH levels increased in both groups immediately postoperatively and at 6 hrs after surgery , but were much more elevated in those patients with SIADH . Patients with SIADH also had significantly higher ADH levels preoperatively . In relation to serum osmolality , ADH was considerably higher in those with SIADH compared with those who did not . Although ANP values tended to be higher in the group with SIADH , this did not reach statistical significance . CONCLUSION SIADH occurs in a subset of children who undergo spinal fusion . The diagnosis of SIADH can be made easily using clinical parameters which are well-defined . In the face of SIADH , continued volume expansion may be harmful , and should therefore be avoided The purpose of this study was to assess the effects of the calcium entry blocker nicardipine and alpha human atrial natriuretic peptide ( hANP ) on antihypertensive and diuretic activity in hypertensive surgical patients . The site of the diuretic actions of these drugs along the nephron were also investigated by measuring the excretion rate of inorganic phosphate ( PO4 ) . Hypertension during gastrectomy was treated by increasing the concentration of enflurane , by nicardipine infusion ( 0.5 - 2.0 μg · kg−1 · min−1 ) , or by hANP infusion ( 0.05–0.2 μg · kg−1 · min−1 ) under general anaesthesia . Enflurane , nicardipine and hANP all decreased arterial pressure to the same extent . Urine flow , Na and PO4 excretion increased following the administration of nicardipine or hANP . Fractional distal reabsorption of sodium was suppressed from 89.7 ± 2.8 % to 82.1 ± 5.0 % by the hANP , but not by the nicardipine infusion . Creatinine clearance was increased by hANP infusion , but did not change in the nicardipine group . It is concluded that nicardipine and hANP can be used safely for the treatment of hypertension during surgery . Both drugs induced phosphaturic diuresis , but the site of action of the two drugs on the nephron may be different . Phosphate reabsorption is considered to occur largely in the renal proximal tubule , so that its appearance in the urine in increased quantities without the change of renal circulation in the nicardipine group suggests a proximal tubular action of this drug . However , the site of action of hANP in the kidney was not determined because GFR increased and distal sodium reabsorption was suppressed due to the drug infusion . RésuméCette étude évalue les effets de l’inhibiteur calcique nicardipine et du peptide atrial alpha natriurique humain ( hANP ) sur l’activité antihypertensive et diurétique chez le patient hypertendu . Sur le néphron , on a aussi recherché le site de l’activité diurétique de ces produits par la mesure de la vitesse d’excrétion du phosphate inorganique ( PO4 ) . L’hypertension survenant pendant la gastrectomie a été traitée par l’augmentation de la concentration d’enflurane , par une perfusion de nicardipine , ( 0,5–0,2 ( μg · kg−1 ) ou par une perfusion de hANP sous anesthésie générate . L’enflurane , la nicardipine et l’hANP ont tous abaissé au même degré la pression artérielle . Le débit urinaire , le sodium et l’excrétion de PO4 ont augmenté à la suite de l’administration de nicardipine ou de hANP . La réabsorption fractionnée distale du sodium est diminuée de 89,7 ± 2,8 % à 82,1 ± 5,0 % par l’hANP contrairement à la perfusion de nicardipine . La clearance de la créatinine est augmentée par la perfusion d’hANP , mais ne change pas pour le groupe nicardipine . On conclut que l’hANP et la nicardipine peuvent être utilisés en toute sécurité pour le traitement de l’hypertension pendant la chirurgie . Les deux médicaments provoquent une diurése phosphaturique , mais le site d’action des deux médicaments pourrait être différent . On croit que la réabsorption du phosphate survient principalement au niveau du tube proximal , alors que son apparition dans l’urine en plus gr and e quantité sans changement de circulation rénale , dans le groupe nicardipine , suggère une action tubulaire proximale . Cependant , le site rénal de l’action de l’hANP n’a pu être déterminé parce que la filtration glomérulaire augmente et la réabsorption distale du sodium ést supprimée par sa perfusion STUDY OBJECTIVES Preoperative renal dysfunction is a risk factor for adverse events in cardiac surgery . This study compared creatinine clearance ( ClCr ) , estimated from the Cockroft and Gault formula , and plasma creatinine level as predictors of outcome after cardiac surgery . DESIGN Prospect i ve , observational . SETTING University hospital . PATIENTS A total of 6,364 cardiac surgical patients . METHODS The measured outcomes were postoperative renal failure requiring dialysis , and mortality and major morbidity . For each outcome , two multivariable risk models were developed , using either estimated ClCr as a measure of renal function , or plasma creatinine level . Risk-adjusted odds ratios ( ORs ) and their 95 % confidence intervals ( CIs ) were calculated for each outcome . Discrimination was compared using receiver operating characteristic ( ROC ) curves . RESULTS For each 10 mL/min/1.73 m(2 ) decrement of estimated ClCr , the ORs for renal failure requiring dialysis , mortality , and major morbidity in the whole population were 1.52 ( 95 % CI , 1.35 to 1.67 ) , 1.27 ( 95 % CI , 1.19 to 1.35 ) , and 1.18 ( 95 % CI , 1.14 to 1.21 ) , respectively ; for each 0.2 mg/dL increment of plasma creatinine , ORs were 1.20 ( 95 % CI , 1.15 to 1.26 ) , 1.08 ( 95 % CI , 1.04 to 1.13 ) , and 1.12 ( 95 % CI , 1.09 to 1.15 ) , respectively . The areas under the ROC curves for prediction of renal failure requiring dialysis were 0.83 with both risk models . For prediction of mortality and major morbidity , areas under the ROC curves were 0.83 and 0.72 , respectively , with the models using estimated ClCr , and 0.74 and 0.65 , respectively , with the models using plasma creatinine level ( p < 0.001 vs estimated ClCr for both outcomes ) . In patients with normal plasma creatinine levels ( n = 4,603 ) , estimated ClCr remained a significant predictor of each outcome with similar ORs , but plasma creatinine level was not a predictor of any outcome . CONCLUSION The risk-adjusted association between preoperative renal dysfunction and adverse events after cardiac surgery is stronger with estimated ClCr than with plasma creatinine level , particularly in patients with normal plasma creatinine levels . The routine preoperative estimation of ClCr may improve the identification of higher-risk cardiac surgical patients Fenoldopam , a selective dopamine-1-receptor agonist , decreases arterial blood pressure rapidly , with a brief duration of action similar to sodium nitroprusside ( SNP ) , but in contrast to SNP , it increases renal blood flow . We compared the hemodynamic and renal effects of fenoldopam in patients undergoing abdominal aortic surgery requiring cross-clamping of the aorta with another therapeutic option , dopamine and SNP . Fenoldopam or 2 mcg · kg−1 · min−1 of dopamine and SNP was infused before incision in 60 r and omly selected patients in a double-blind fashion . Hemodynamic variables were recorded before incision , immediately before clamping the aorta , 5 min after cross-clamp release and upon completion of surgery . Urine output , serum creatinine , and creatinine clearance were measured intraoperatively and postoperatively . Characteristics were compared between groups using two- sample rank sum test for continuous variables and Fisher ’s exact test for discrete variables . The occurrence of severe hypotension , maximum systolic blood pressure , and need for additional antihypertensive drugs were not different between the groups . Most intraoperative hemodynamic variables and all indices of renal function did not differ according to treatment . Therefore , fenoldopam has no therapeutic advantage compared with similar therapies in patients undergoing major vascular surgery involving cross-clamping of the aorta Purpose : To compare endovascular ( EVR ) to open repair ( OR ) of abdominal aortic aneurysm ( AAA ) for cytokine activation , changes in the intestinal mucosal barrier , and renal dysfunction . Methods : In a prospect i ve nonr and omized study , 15 patients admitted to a university hospital for elective infrarenal AAA repair ( 8 OR and 7 EVR ) were recruited . Intestinal permeability was assessed preoperatively ( PO ) , at day 1 ( D1 ) , and at day 3 ( D3 ) after surgery using the lactulose/mannitol differential excretion ( LMR ) test . Renal damage was assessed from measurements of the urinary albumin : creatinine ratio ( ACR ) ; cytokine activation was based on the urinary concentration of tumor necrosis factor receptor p55 ( TNF-Rp55 ) at the same time points . Serum creatinine and urea concentrations were measured preoperatively and daily for 5 days postoperatively . Results : A significant increase in LMR was found in the OR group at D1 and D3 compared to PO ( p<0.05 ) . The LMR increase at D3 was significantly greater in the OR group ( p<0.01 ) . A significant difference was observed in the percentage rise in ACR on D1 in the OR group compared to the EVR group ( p<0.005 ) . The urinary TNF-Rp55 concentration was significantly elevated in the OR group at D1 ( p<0.05 ) and D3 ( p<0.05 ) compared to baseline ; in the EVR group , it was elevated at D1 ( p<0.05 ) compared to PO . The difference was also significant for this marker between the 2 groups at D1 ( p<0.01 ) . No significant change was observed in the serum creatinine or urea concentrations in either group perioperatively Conclusions : Endovascular AAA repair is associated with less cytokine production and less intestinal and renal dysfunction compared to the open approach OBJECTIVE To compare the hemodynamic efficacy of a new hydroxyethyl starch ( HES ) preparation ( 130/0.4 ) with an HES 200/0.5 solution . DESIGN Prospect i ve , r and omized , double-blind , phase II study . SETTING An urban , university-affiliated hospital . PARTICIPANTS Twenty patients undergoing elective first-time cardiac surgery . INTERVENTIONS After induction of anesthesia and before the start of surgery , a new HES 130/0.4 ( molecular weight , 130,000 d ; degree of substitution , 0.4 ) ( n = 10 ) or HES 200/0.5 ( molecular weight , 200,000 d ; degree of substitution , 0.5 ) ( n = 10 ) was infused ( 10 mL/kg ) within 30 minutes when pulmonary capillary wedge pressure was less than 10 mmHg . MEASUREMENTS AND MAIN RESULTS Extensive hemodynamic monitoring was performed 30 and 60 minutes after the end of infusion . Then surgery was started . St and ard laboratory parameters were measured before surgery and on the 1st postoperative day . A similar amount of HES was given in both groups ( HES 130 , 795+/-75 mL ; HES 200 , 820+/-90 mL ) . Filling pressures ( central venous pressure , pulmonary capillary wedge pressure ) and cardiac index increased similarly in both groups and remained significantly elevated 60 minutes after the end of infusion . All other hemodynamic parameters were similar between the two volume groups . Renal ( creatinine ) and hepatic function ( aspartate aminotransferase , alanine aminotransferase ) and hemostasis ( platelet count , activated partial thromboplastin time , blood loss ) were without group differences until the morning of the 1st postoperative day . CONCLUSIONS The new 6 % HES 130/0.4 was as effective as a 6 % HES 200/0.5 preparation in regard to hemodynamic efficacy . No negative side effects on organ function were seen . The 6 % HES 130/0.4 solution may become an alternative strategy for volume therapy in cardiac surgery Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary bypass ( CPB ) may be responsible for endotoxin-mediated systemic inflammation and acute phase responses . We examined the effects of dopexamine on hemodynamic parameters , creatinine clearance , systemic and splanchnic oxygenation , gastric mucosal pH ( pHi ) , and mixed and hepatic venous plasma levels of endotoxin , interleukin-6 ( IL-6 ) , serum amyloid A ( SAA ) , and C-reactive protein ( CRP ) in 44 patients scheduled for coronary artery bypass grafting . Patients were r and omized to receive continuous infusions of 0.5 , 1.0 , or 2 micro g [ centered dot ] kg-1 [ centered dot ] min-1 dopexamine ( n = 10 per group ) or placebo ( n = 14 ) prior to surgery , intraoperatively , and postoperatively . Dopexamine infusion increased systemic oxygen delivery ( P < or = to 0.01 ) . Hepatic venous oxygen saturation did not change , and pHi decreased during and after CPB in all patients ( P < or = to 0.01 ) . Postoperative increases in IL-6 were smallest in patients who received 2.0 micro g [ centered dot ] kg-1 [ centered dot ] min-1 dopexamine ( P < or = to 0.02 ) . SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study . Creatinine clearance was elevated in all dopexamine groups ( P < or = to 0.025 ) . This elevation was higher with lower dopexamine doses ( P < or = to 0.025 ) . We conclude that dopexamine improves creatinine clearance and reduces systemic inflammation without affecting splanchnic oxygenation . ( Anesth Analg 1997;84:950 - 7 Objective : To assess the effect of high-dose N-acetylcysteine on renal function in cardiac surgery patients at higher risk of postoperative renal failure . Design : Multiblind , placebo-controlled , r and omized , phase II clinical trial . Setting : Operating rooms and intensive care units of two tertiary referral hospitals . Patients : A total of 60 cardiac surgery patients at higher risk of postoperative renal failure . Interventions : Patients were allocated to either 24 hrs of high-dose N-acetylcysteine infusion ( 300 mg/kg body weight in 5 % glucose , 1.7 L ) or placebo ( 5 % glucose , 1.7 L ) . Measurements and Main Results : The primary outcome measure was the absolute change in serum creatinine from baseline to peak value within the first five postoperative days . Secondary outcomes included the relative change in serum creatinine , peak serum creatinine level , serum cystatin C , and in urinary output . Further outcomes were needed for renal replacement therapy , length of ventilation , and length of stay in the intensive care unit and hospital . R and omization was successful and patients were well balanced for preoperative and intraoperative characteristics . There was no significant attenuation in the increase in serum creatinine from baseline to peak when comparing N-acetylcysteine with placebo ( 64.5 ± 91.2 and 38.0 ± 42.4 & mgr;mol/L , respectively ; p = .15 ) . Also , there was no attenuation in the increase in serum cystatin C from baseline to peak for N-acetylcysteine compared with placebo ( 0.45 ± 0.43 and 0.30 ± 0.33 mg/L , respectively ; p = .40 ) . Likewise , there was no evidence for differences in any other clinical outcome . Conclusions : In this phase II , r and omized , controlled trial , high-dose N-acetylcysteine was no more effective than placebo in attenuating cardiopulmonary bypass – related acute renal failure in high-risk cardiac surgery patients BACKGROUND Off-pump coronary artery bypass surgery is becoming increasingly popular despite the lack of sufficient evidence from r and omized trials . The aim of our prospect i ve , r and omized , single-center study was to examine the role of off-pump revascularization among nonselected patients . METHODS A total of 400 consecutive nonselected patients ( mean age 63 years ) scheduled for isolated coronary revascularization were r and omized by a cardiologist into two groups : A ( on-pump ) and B ( off-pump ) . The cardiac surgeon was allowed to change the operative technique at any time after r and omization . The only exclusion criterion was an emergency procedure . The primary end point was any of the following within 30 days : death , myocardial infa rct ion , stroke , or new renal failure requiring hemodialysis . The study was analyzed on the intention-to-treat principle . RESULTS The primary end point occurred in 4.9 % of patients in group A versus 2.9 % in group B ( not significant ) . Mortality was 1.1 % in group A versus 2.0 % in group B ( not significant ) . Preoperative crossover occurred in 5.4 % of patients in each group ( not significant ) . Intraoperative conversion was necessary in 9.8 % of patients in group B versus 1.1 % of patients in group A ( p < 0.001 ) . Group B patients had fewer distal anastomoses ( 2.3 versus 2.7 in group A ; p < 0.001 ) , less blood loss ( 560 versus 680 mL ; p < 0.001 ) , lower postoperative creatine kinase MB levels ( 0.15 versus 0.56 microkat/L ; p < 0.001 ) and lower total hospital costs ( 3,451 versus 4,387 ; p < 0.001 ) . CONCLUSIONS In our study off-pump technique was applicable in 85 % of nonselected patients and is at least as clinical ly safe and effective as on-pump surgery The efficacy of renal-dose dopamine to improve renal function or reduce renal impairment was studied in 52 patients undergoing elective coronary artery bypass surgery . The patients were prospect ively r and omised in a double-blind fashion to receive dopamine at 200 μg/min ( group D ) or placebo ( group P ) from induction for 24 hours . Although dopamine improved haemodynamics , there was no effect on urine output at 4 hours ( D = 917 , P=1231 ml : P = 0.066 ) ; urine output at 24 hours ( D=3659 , P=3304 ml : P = 0.36 ) ; creatinine clearance at 0–4 hours ( D = 104 , P=127 ml/min : P = 0.27 ) ; creatinine clearance on admission to ICU-4 hours ( D=94.8 , P=83.4 ml/min : P = 0.48 ) ; creatinine clearance at 20–24 hours ( D = 91.2 , P=107 ml/min : P = 0.48 ) ; free-water clearance at 0–4 hours ( D=29.6 , P= -59.8 ml/hr : P = 0.069 ) ; free-water clearance at 20–24 hours ( D=43.2 , P= -48.9 ml/hr : P = 0.55 ) . The incidence of transient renal impairment was similar in both groups ( D=36 % , P=50 % : P = 0.65 ) . Our study failed to demonstrate that routine prophylactic renal-dose dopamine is associated with improvement in renal function , or with prevention of transient renal impairment in patients undergoing coronary artery bypass surgery In this prospect i ve , r and omized , placebo-controlled , double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery . Seventy patients without previously documented renal dysfunction were r and omly allocated to receive either N-acetylcysteine ( 150 mg/kg mixed in 250 mL of 5 % dextrose infused in 20 min , followed by an infusion of 150 mg/kg in 250 mL of 5 % dextrose over 24 h ) or placebo . The infusion was started after the induction of anesthesia . The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-β-d-glucosaminidase (NAG)/creatinine ratio ( indicator of renal tubular injury ) and urinary albumin/creatinine ratio ( indicator of glomerular injury ) . Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations . The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups . The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group . However , the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups . Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups . In conclusion , N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function , and some degree of tubular injury seems to occur before aortic crossclamp A r and omized trial was undertaken to reassess the effectiveness of mannitol in preventing postoperative renal impairment in patients with obstructive jaundice . The study included 31 patients with obstructive jaundice ( bilirubin , 3 mg/dl or higher ) r and omly allocated in two groups to receive ( n = 17 ) or not receive ( n = 14 ) preoperative mannitol . Sixty-five percent of patients had a creatinine clearance below 70 ml/min before surgery . Serum bilirubin and bacteribilia had no relation with preoperative renal function . No relation was found between serum bilirubin value and the percentage fall in postoperative creatinine clearance . Compared with the preoperative values , the postoperative creatinine clearance was significantly impaired in the mannitol group ( p = 0.03 ) and remained almost unaltered in the no-mannitol group . Three patients ( 9.7 % ) died of acute renal failure ; two were in the mannitol group and one was in the no-mannitol group . Serum fibrin degradation products were not sensitive markers for impending renal failure . There was no significant difference in postoperative serum sodium concentration or in the urinary sodium excretion . Administration of mannitol did not improve the postoperative renal function of jaundiced patients , nor did it prove beneficial in preventing renal failure . Our results suggest that severe disturbances of body-fluid compartments may be the basic mechanism underlying kidney dysfunction in obstructive jaundice and that further water depletion induced by mannitol may indeed prove detrimental Forty-five patients who underwent open heart surgery were divided into a short-perfusion group ( SPG , 21 patients ) with a perfusion time shorter than 60 minutes and a long-perfusion group ( LPG , 24 patients ) with a perfusion time longer than 60 minutes . Nine patients in the SPG and 13 in the LPG received furosemide prophylactically prior to the perfusion . The furosemide dose was 20 - 60 mg . During the perfusion and postoperatively all patients were given furosemide when necessary , i.e. when the volume for diuresis per hour declined below 40 ml/h . The patients who received prophylactic furosemide in the LPG subsequently had clearly less need for furosemide ( 3.9 mg/h ) than the control subjects ( 7.9 mg/h/3 day ) . The patients with furosemide prophylaxis in the LPG had significantly ( less than 0.05 ) higher creatinine clearance and lower serum creatinine values during the postoperative night period and on the 3rd day . In perfusions lasting less than 60 minutes the patients with furosemide prophylaxis had significantly higher urine flow ( p less than 0.001 ) , sodium excretion ( p less than 0.001 ) and potassium excretio-n ( p less than 0.01 ) during bypass surgery and postoperatively compared with that of controls . According to our findings , the prophylactic use of furosemide had a beneficial effect on glomerular filtration rate ( endogenous creatinine clearance ) and postoperative serum creatinine level in LPG . In perfusion shorter than 60 minutes furosemide prophylaxis may be harmful owing to the increased excretion of water , sodium and potassium The effects of mannitol on renal impairment following infrarenal aortic aneurysm repair were studied . Patients received either mannitol 0.3 g/kg ( n = 15 ) or saline ( n = 13 ) as a rapid intravenous infusion before aortic cross‐clamping . One patient in the control group developed fatal postoperative renal failure but there was no renal failure in the mannitol group . Two patients treated with mannitol died from perioperative myocardial infa rct ion . There were no significant differences in postoperative blood urea level , serum creatinine concentration or creatinine clearance between mannitol and control groups . In patients who had mannitol there was a significant diuresis on the first day after operation ( mean urine output 2250 ml ) compared with before operation ( 1557ml ) ( P = 0.007 ) . Compared with controls , patients treated with mannitol had lower mean(s.e.m . ) postoperative levels of urinary albumin ( 160(32 ) versus 500(140 ) mg per mmol creatinine ; P = 0.036 ) and N‐acetyl glucosaminidase ( 143(34 ) versus 271(70 ) μmol per mmol creatinine ; P = 0.04 ) indicating a reduced level of sub clinical glomerular and renal tubular damage . These data demonstrate that mannitol reduces sub clinical renal injury following infrarenal aortic aneurysm repair OBJECTIVE To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction . DESIGN Prospect i ve , r and omized , placebo-controlled , double-blind , clinical study . SETTING Cardiothoracic anesthesia department at a university hospital . PARTICIPANTS Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass , with a preoperatively elevated serum creatinine level ( n = 24 ) . INTERVENTIONS R and omized infusions of diltiazem ( bolus 0.25 mg/kg followed by a continuous infusion of 1.7 microg/kg/min ) ( DTZ , n = 12 ) or placebo ( C , n = 12 ) were started 30 minutes before induction of anesthesia and continued for 24 hours . MEASUREMENTS AND MAIN RESULTS Median plasma concentrations of diltiazem ( DTZ group ) were 79 microg/L before cardiopulmonary bypass , 67 microg/L at the end of cardiopulmonary bypass , and 164 microg/L at 24 hours postoperatively . Serum creatinine levels ; on postoperative days 1 , 3 , and 5 ; and 3 weeks postoperatively were similar between groups . Iohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery ( median , 51 v 40 mL/min/1.73 m(2 ) ; p < 0.05 ) . Urinary N-acetyl-beta-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively . CONCLUSION Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass . Within the limits of this study , the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage result ing from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery BACKGROUND Hypothermia is a potential strategy for visceral organ protection during cardiopulmonary bypass ( CPB ) . We report data from two r and omized studies evaluating mild hypothermia and rewarming on postoperative renal function in cardiac surgical patients . METHODS Patients undergoing nonemergency , isolated coronary artery bypass grafting were enrolled into two studies . In the first , 223 patients were cooled to 32 degrees C during CPB and r and omly assigned to rewarming to 37 degrees C ( RW-37 degrees ) or 34 degrees C ( RW-34 degrees ) . The second study r and omized 267 patients to sustained mild hypothermia at 34 degrees C ( S-34 degrees ) or normothermia ( S-37 degrees ) without rewarming . Serum creatinine levels were measured . Creatinine clearance was calculated . Significant renal dysfunction was defined as a 25 % increase in serum creatinine or a 25 % decrease in creatinine clearance postoperatively . RESULTS Postoperative serum creatinine levels were persistently higher in the RW-37 degrees patients than in the RW-34 degrees group ( p < 0.01 ) . RW-37 degrees patients had a higher incidence of renal dysfunction ( 17 % ) than RW-34 degrees patients ( 9 % , p = 0.07 ) . Sustained mild hypothermia had no beneficial effect on postoperative serum creatinine levels ( p = 0.44 ) or significant renal dysfunction : S-34 degrees , 20 % vs S-37 degrees , 15 % ( p = 0.28 ) . Diabetes ( odds ratio [ OR ] , 1.6 ; 95 % confidence interval [ CI ] 1.3 to 2.1 ) , prolonged CPB time ( OR , 1.1 ; 95 % CI , 1.0 to 1.2 ) , and rewarming ( OR , 1.4 ; 95 % CI , 1.0 to 1.9 ) were independent risk factors for significant renal dysfunction . Renal dysfunction was associated with longer hospital stay ( 8.4 + /- 0.8 vs 6.8 + /- 04 days , p < 0.001 ) . CONCLUSIONS Sustained mild hypothermia does not improve renal outcome . However , rewarming on CPB is associated with increased renal injury and should be avoided 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 : Ischemia-reperfusion injury is an important cause of renal dysfunction after abdominal aortic aneurysm repair . Human atrial natriuretic peptide ( hANP ) is a potent endogenous natriuretic , diuretic , and vasorelaxant peptide . The objective of the present study was to evaluate the effects of hANP on renal function in patients undergoing abdominal aortic aneurysm repair . Design : A prospect i ve , r and omized , placebo-controlled study Setting : Intensive care unit of a university hospital . Patients : Forty patients undergoing elective abdominal aortic aneurysm repair . Interventions : The patients were r and omized to receive a continuous infusion of either hANP ( 0.01–0.05 & mgr;g/kg/min ) ( n = 20 ) or placebo ( n = 20 ) immediately before aortic cross-clamping . The infusion of hANP or placebo continued for 48 hrs . Measurements and Main Results : Blood and urine sample s were taken before surgery , at admission to the intensive care unit , and on days 1 , 2 , and 3 postoperatively , for measurement of serum concentrations of sodium , creatinine , and blood urea nitrogen and plasma concentrations of ANP and brain natriuretic peptide ( BNP ) . Urine volume and urinary concentrations of N-acetyl-&bgr;-D-glucosaminidase ( NAG ) , sodium , and creatinine were also measured . The mean plasma concentration of ANP was significantly higher in the hANP group than in the placebo group . The mean plasma BNP concentration was significantly lower in the hANP group than in the placebo group . The mean serum concentrations of creatinine and blood urea nitrogen were significantly ( p < .05 ) lower in the hANP group than in the placebo group . The mean urine volume and mean creatinine clearance were significantly ( p < .05 ) higher in the hANP group than in the placebo group . The mean urinary NAG/creatinine ratio was significantly ( p < .05 ) lower in the hANP group than in the placebo group . Conclusions : The intraoperative and postoperative infusion of low-dose hANP preserved renal function in patients undergoing abdominal aortic aneurysm repair . Further studies are needed to assess the efficacy of prophylactic hANP infusion on perioperative renal outcome A r and omized double-blind study was carried out on 20 patients after coronary artery bypass surgery to investigate the effects of grade d doses of dopexamine hydrochloride or placebo on systemic haemodynamic responses and renal vascular resistance index ( RVRI ) measured using Doppler ultrasound . Pre-operatively , all patients had good left ventricular function and normal renal function . Eleven were allocated r and omly to receive incremental infusions of dopexamine 0.5 , 1 , 2 , and 4 micrograms kg-1 min-1 for 40 min each , and nine received corresponding infusions of placebo . One patient was withdrawn from the dopexamine group because of tachycardia . In the remaining 19 , heart rate ( HR ) and cardiac index ( CI ) were significantly ( P < 0.05 ) increased from base-line with dopexamine : the HR values with dopexamine differed significantly from those with placebo at the 2 and 4 micrograms kg-1 min-1 dose and at 4 micrograms kg-1 min-1 for CI . Systemic vascular resistance index ( SVRI ) fell significantly in both groups : the reduction was significantly greater with dopexamine 4 micrograms kg-1 min-1 than with the corresponding infusion of placebo . RVRI increased and urine output decreased significantly during the infusions in both groups , but with no significant difference between groups . There were no changes in systemic arterial pressures , pulmonary artery occlusion pressures , stroke volume index or left ventricular stroke work index . Where changes from base-line occurred in either group , they had not returned to base-line within 40 min of stopping the infusions ( except perhaps for CI in the dopexamine group ) . Dopexamine appears to offer no particular protection to the renal vascular bed Purpose Treatment with angiotensin-converting enzyme ( ACE ) inhibitors affects the autoregulation of renal blood flow and glomerular filtration and provides renal protective effects . The purpose of this case-control study was to investigate the effects of chronic ACE inhibition on perioperative renal hemodynamics and function . Method We prospect ively studied renal function in two groups of patients , chronically treated or not , with ACE inhibitors ( ACEI and control ; n = 16 , in each group ) who underwent elective cardiac surgery under hypothermic cardiopulmonary bypass . Glomerular filtration rate , effective renal plasma flow , osmolar clearance and fractional excretion of sodium and potassium were determined before , during and after CPB . Additional measurements included plasma atrial natriuretic factor ( ANF ) as well as plasma and urinary cyclic GMP ( cGMP ) , thromboxane B2 ( T × B2 ) and 6-keto-PGF1 . Results Renal functional and hemodynamic variables did not differ between the two groups , at any period . Cardiopulmonary bypass induced increases in urinary flow , osmolar clearance and fractional excretion of sodium and potassium in both groups . Plasma and urinary ratio of 6-keto-PGF1O T × B2 increased markedly and reflected a prédominent systemic and renal release of vasodilatory prostagl and ins . Intraoperatively , ANF was higher in ACEIs than in control patients . Conclusions Long term treatment with ACE inhibitors does not influence the perioperative changes in renal hemodynamics and function . During cardiopulmonary bypass , a transient impairment in solute reabsorption is associated with renal release of vasodilatory mediators ( nitric oxide and prostacyclin).RésuméObjectifLe traitement avec les inhibiteurs de l’enzyme de conversion de l’angiotensine ( ECA ) agit sur l’autorégulation du débit sanguin rénal et la filtration glomérulaire et a un effet de protection rénale . Lobjectif de cette étude cas-témoins est d’examiner les effets d’une inhibition de longue durée de l’ECA sur l’hémodynamie et la fonction rénales périopératoires . MéthodeNous avons réalisé une étude prospect i ve de la fonction rénale chez les patients de deux groupes , traités ou non à long terme avec des inhibiteurs de l’ECA ( IECA et témoin ; n = 16 dans chacun ) , et qui subissent une intervention cardiaque élective avec circulation extracorporelle hypothermique . On a déterminé avant , pendant et après la CEC , la vitesse de filtration glomérulaire , le débit sanguin rénal efficace , la clairance osmolaire et la fraction excrétée du sodium et du potassium . D’autres mesures concernent : le facteur natriurétique auriculaire ( FNA ) et la guanosine monophosphate cyclique urinaire ( GMPc ) , la thromboxane B2 ( T × B2 ) et la 6-céto-PGFRésultatsÀ aucun moment , les variables rénales fonctionnelles et hémodynamiques n’ont présenté de différences intergroupes . La CEC a induit une hausse du débit urinaire , de la clairance osmolaire et de la fraction excrétée du sodium et du potassium dans les deux groupes . Les taux plasmatiques et urinaires de 6-céto-PGF1 par rapport à la Tx B2 ont beaucoup augmenté , reflet d’une libération systémique et rénale de prostagl and ines vasodilatatrices . Le FNA peropératoire était plus élevé dans le groupe IECA que dans le groupe témoin . Conclusion Un traitement à long terme avec les inhibiteurs de l’ECA n’influence pas les changements périopératoires de l’hémodynamie et de la fonction rénales . Une altération transitoire de la réabsorption osmotique pendant la circulation extracorporelle est associée à la libération rénale de médiateurs vasodilatateurs ( l’oxyde nitrique et la prostacycline ) BACKGROUND Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients . To examine the safety and dose-related efficacy of aprotinin , a prospect i ve , multicenter , placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft ( CABG ) surgery . METHODS AND RESULTS Two hundred eighty-seven patients were r and omly assigned to receive either high-dose aprotinin , low-dose aprotinin , pump-prime-only aprotinin , or placebo . Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume . The percentage of patients requiring donor-red-blood-cell ( RBC ) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups ( high-dose aprotinin , 54 % ; low-dose aprotinin , 46 % ; pump-prime only , 72 % ; and placebo , 75 % ; overall P = .001 ) . The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo ( high-dose aprotinin , 1.6 + /- 0.2 U ; low-dose aprotinin , 1.6 + /- 0.3 U ; pump-prime-only , 2.5 + /- 0.3 U ; and placebo , 3.4 + /- 0.5 U ; P = .0001 ) . There was also a significant difference in total blood-product exposures among treatment groups ( high-dose aprotinin , 2.2 + /- 0.4 U ; low-dose aprotinin , 3.4 + /- 0.9 U ; pump-prime-only , 5.1 + /- 0.9 U ; placebo , 10.3 + /- 1.4 U ) . There were no differences among treatment groups for the incidence of perioperative myocardial infa rct ion ( MI ) . CONCLUSIONS This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI Introduction : The objective of this study was to evaluate the effects of dopexamine on renal function in 4 groups of patients either with or without renal dysfunction . Transient renal dysfunction is often not clinical ly relevant in patients with normal renal function , but it is an important clinical factor in patients with pre-existing renal failure . Dopexamine ( DX ) is a commonly used catecholamine which probably exerts a selective effect at the splanchnic bed . Material and Methods : 24 patients with normal renal function and 24 patients with impaired renal function ( creatinine in serum ≥ 1.5 mg/dL ) were each r and omly allocated to 2 groups . Group 1 ( control ) without renal dysfunction and group 3 ( control/dysfunction ) with renal dysfunction were considered as control groups , while the patients in DX and DX/dysfunction groups received 1 μg/kg/min dopexamine until the end of surgery . Kidney function was investigated using st and ard parameters and by investigating specific proteins and enzymes . Results : All patients showed pathologic excretions of the investigated parameters during cardiopulmonary bypass ( CPB ) with no differences between the study groups . The distal tubule , the lysosomal regions , Henle 's loop and the glomerular tuft were all damaged . Heart rate and cardiac index increased significantly in the DX-groups , first until the end of surgery , second until the start of ECC . Conclusion : Dopexamine at a dose of 1 μg/kg/min had no influence on renal function and protein excretion and can not be regarded as a kidney function protecting substance OBJECTIVE To determine whether dopamine prevents deterioration of central haemodynamics and renal function in aortoiliac surgery . DESIGN Prospect i ve , r and omised and placebo-controlled . SETTING University hospital . MATERIAL S Thirty patients for elective vascular surgery with implantation of an aortobifemoral or an aortobiiliac graft due to aortoiliac arteriosclerosis had infusion of dopamine 3 micrograms/kg/min or placebo during the operation and 24 h postoperatively . Thoracic epidural analgesia and general anaesthesia were used . CHIEF OUTCOME MEASURES Central haemodynamic measurements were registered . The effective renal plasma flow ( ERPF ) , the glomerular filtration rate ( GFR ) , angiotensin II , aldosterone , arginine vasopressin ( AVP ) , atrial natriuretic peptide ( ANP ) , endothelin and excretion of water and electrolytes were measured preoperatively , 1 h postoperatively and 24 h postoperatively . MAIN RESULTS During the operation the dopamine group had higher cardiac index and heart rate together with lower pulmonary artery wedge blood pressure . ERPF and GFR did not differ between the groups . In the dopamine group ERPF was increased in all patients at the first postoperative clearance . The fractional excretion of sodium , the per- and postoperative diuresis and AVP were increased in the dopamine group as compared to the placebo group . Postoperatively , ANP in the placebo group was raised as compared to the preoperative level . CONCLUSIONS Peroperatively , dopamine counteracted depression of left ventricular function . The increased ERPF at the first postoperative clearance in the dopamine group indicates either improved peroperative haemodynamics or a synergistic effect between dopamine and epidural sympathetic blockade . Dopamine also improved diuresis and natriuresis This study was undertaken to compare the effects of combined aprotinin and prostagl and in E1 therapy on aortic arch replacement . Twenty patients were divided into 2 groups with ( group A ; n = 10 ) or without ( group B ; n = 10 ) the treatment ( 200 KIU of aprotinin and 0.01 - 0.02 microgram/kg/min of prostagl and in E1 during cardiopulmonary bypass ( CPB ) and the first postoperative day . Preoperative evaluation of respiratory function and all parameters related to CPB procedure were revealed to be equal between the groups . Postoperative A-a DO2 and respiratory index ( RI ) as functional parameters of oxygenation capacity , dosage of dopamine were monitored at 0 , 3 , 6 , 12 , 18 and 24 hr after termination of CPB and at extubation period . Serum creatinine , platelet numbers and blood coagulation function ( PT , APTT ) were also assayed postoperatively . The recovery of respiratory and cardiac function were superior in group A with treatment , but renal and blood coagulation function showed no difference in the groups . We suggest the combined therapy with aprotinin and prostagl and in E1 for aortic arch replacement may emerge as a valuable treatment to save postoperative respiratory and cardiac function BACKGROUND Biological activity of endogenous atrial natriuretic peptide ( ANP ) may decrease during cardiopulmonary bypass . To evaluate the effects of intraoperative administration of exogenous ANP in patients undergoing cardiopulmonary bypass , we conducted a prospect i ve r and omized study . METHODS Eighteen patients undergoing mitral valve surgery were r and omized to receive either ANP treatment ( ANP group ; n = 9 ) or no ANP treatment ( control group ; n = 9 ) . Atrial natriuretic peptide was given immediately after initiation of cardiopulmonary bypass for 6 hours ( 0.05 microg x kg(-1 ) x min(-1 ) ) . Plasma ANP , brain natriuretic peptide and cyclic guanosine monophosphate ( cGMP ) levels , hemodynamic variables and renal function were assessed perioperatively . RESULTS Administration of ANP increased plasma cyclic guanosine monophosphate levels , urine output and fractional sodium excretion , and decreased preload , afterload and plasma brain natriuretic peptide levels significantly ( p < 0.05 ) . Plasma cyclic guanosine monophosphate levels correlated with plasma ANP levels ( r = 0.95 , p = 0.0001 ) , correlated with fractional sodium excretion ( r = 0.53 , p = 0.02 ) , and correlated inversely with systemic vascular resistance ( r = -0.54 , p = 0.02 ) . CONCLUSIONS Intraoperative administration of ANP had potent effects on natriuresis and systemic vasodilation by elevating cyclic guanosine monophosphate levels . The results suggest that the technique is useful for the management of hemodynamics and water-sodium retention after cardiopulmonary bypass OBJECTIVE To evaluate the usefulness of low-dose fenoldopam mesylate in patients at risk of developing renal dysfunction after cardiac surgery requiring cardiopulmonary bypass . DESIGN A prospect i ve , single-center , observational study . SETTING University teaching hospital . PARTICIPANTS Seventy patients scheduled for elective cardiac surgery with one or more predefined risk factors for renal dysfunction . INTERVENTIONS After induction of anesthesia , fenoldopam ( 0.03 microg/kg/min ) was administered throughout surgery and into the postoperative period , until the patient was stable and weaned from all other vasoactive agents . Perioperatively , fenoldopam was also used as a second-line antihypertensive agent as required . MEASUREMENTS AND MAIN RESULTS No patient developed renal failure that required dialysis , whereas 7.1 % ( 5/70 ) developed non-dialysis-dependent renal dysfunction . Four out of these 5 patients had 2 or more risk factors ( 9.5 % ) . Higher preoperative creatinine levels , a history of hypertension , myocardial infa rct ion within 5 days of surgery , and a preoperative diagnosis of chronic renal insufficiency were all good predictors of postoperative non-dialysis-dependent renal dysfunction . Discharge serum creatinine levels were lower than preoperative levels ( 1.16 + /- 0.36 mg/dL v 1.26 + /- 0.34 mg/dL , p < 0.05 ) . CONCLUSION These findings suggest that renal function was preserved in patients at increased risk for renal dysfunction after cardiac surgery when low-dose fenoldopam was used in the perioperative period . However , a r and omized , controlled trial is required to establish efficacy BACKGROUND Intraoperative oliguria is common during laparoscopic operations . The objective of this study was to evaluate the effects of prolonged pneumoperitoneum during laparoscopic gastric bypass ( GBP ) on intraoperative urine output and renal function . METHODS 104 patients with a body mass index between 40 and 60 kg/m2 were r and omly assigned to laparoscopic ( n = 54 ) or open ( n = 50 ) GBP . Intraoperative urine output was recorded at 30-min intervals . Blood urea nitrogen and creatinine levels were measured at baseline and on postoperative days 1 , 2 , and 3 . Levels of antidiuretic hormone , aldosterone , and plasma renin activity were also measured in a subset of laparoscopic ( n = 22 ) and open ( n = 24 ) GBP patients at baseline , 2 hours after surgical incision , and in the recovery room . RESULTS The laparoscopic and open groups were similar in age , gender , and body mass index . There was no significant difference in amount of intraoperative fluid administered between groups ( 5.4 + /- 1.6 L , laparoscopic versus 5.8 + /- 1.7 L , open ) , but operative time was longer in the laparoscopic group ( 232 min versus 200 min , p < 0.01 ) . Urinary output during laparoscopic GBP was 64 % lower than during open GBP at 1 hour after surgical incision ( 19 mL versus 55 mL , p < 0.01 ) and continued to remain lower than that of the open group by 31 - 50 % throughout the operation . Postoperative blood urea nitrogen and creatinine levels remained within the normal range in both groups . Serum levels of antidiuretic hormone , aldosterone , and plasma renin activity peaked at 2 hours after surgical incision with no significant difference between the two groups . CONCLUSION Prolonged pneumoperitoneum during laparoscopic gastric bypass significantly reduced intraoperative urine output but did not adversely alter postoperative renal function Sixteen patients diagnosed with an aneurysm of abdominal aorta or Leriche disease underwent elective aortic surgery involving crossclamping of infrarenal aorta ( ICC ) . These patients were r and omized into two equal groups and 8 patients were infused with nifedipine starting from the isolation of aorta until the end of surgery ( group A ) while another 8 patients were infused with low-dose dopamine ( group B ) over the same surgical course . Plasma endothelin ( ET ) was measured before the induction of anesthesia , at the beginning and at the end of the clamp period and at the end of the operation . Intraoperatively , creatinine clearance and urinary excretion of PGE2 , 6-keto PGF1 alpha and TxB2 were also determined before , during and after aortic crossclamping . Preoperative GFR as well as preinduction cardiac index ( CI ) and pulmonary capillary wedge pressure ( PCWP ) of the two groups did not differ . During cross-clamping plasma ET rose significantly in both groups . However , after clamp removal , plasma ET decreased in group A while it remained elevated in group B. Urinary excretion of TxB2 , PGE2 and 6-keto PGF1 alpha increased during clamp in both groups , but the ratio of PGE2 + 6-keto PGF1 alpha/TxB2 during and after clamp was significantly higher in group A than in B. Postclamp creatinine clearance decreased in group B , and increased in group A ; postoperative value of GFR was unchanged in group A and decreased significantly in group B. In conclusion , infusion of nifedipine , in contrast to dopamine , prevented the decrease of GFR in patients undergoing aortic surgery . This effect could be mediated by a nifedipine modulation of ET vascular synthesis and /or a preferential renal synthesis of vasodilating prostanoids BACKGROUND To reduce blood consumption in cardiac surgery , aprotinin has been widely used for years . Because aprotinin is metabolized in the kidney , damage of the renal system has been discussed . METHODS To study these possibly unfavorable effects of aprotinin , a prospect i ve , r and omized , placebo-controlled study of 20 patients undergoing aortocoronary bypass operations was performed . A placebo group P was compared with group A , in which patients received high-dose aprotinin according to the " Hammersmith " regimen . Renal function was assessed for 5 postoperative days using sodium dodecyl sulfate gel electrophoresis and quantitative protein analysis of the urine . RESULTS During and after the operation , temporary renal dysfunction was found in all patients , with a substantial increase of all investigated indices . The alpha 1-microglobulin level in the urine was significantly increased in the aprotinin group for 5 days in comparison with the placebo group , with a maximum on the third postoperative day ( 64.8 + /- 13.7 versus 21.0 + /- 6.5 mg/L ; p < 0.05 ) . Similarly , after sodium dodecyl sulfate-polyacrylamide gel electrophoresis , the b and s of proteins filtrated in the renal tubular system were almost tripled in the aprotinin group 5 days postoperatively ( 5.0 + /- 0.8 versus 2.1 + /- 0.2 ; p < 0.05 ) . Although urine production was significantly increased in group A ( 4789 + /- 580 versus 3653 + /- 492 mL/24 h postoperatively ; p < 0.05 ) , no relevant changes in serum or urine creatinine levels could be observed in either group . CONCLUSIONS Patients undergoing aortocoronary bypass operations demonstrate a temporary renal dysfunction . Aprotinin impairs renal function in addition by overloading the tubular reabsorption mechanisms . Patients with normal renal function preoperatively -- as were included in this study --are able to compensate for both the perioperative renal dysfunction caused by the extracorporeal circulation and the additional tubular damage due to aprotinin Purpose The aim of this study was to evaluate the efficacy of carperitide in maintaining renal function during intraoperative and postoperative management of patients with renal dysfunction undergoing elective cardiovascular surgery . Methods The subjects were 88 patients with a preoperative serum creatinine level ≥1.2 mg/dl who underwent elective cardiovascular surgery using cardiopulmonary bypass . They were prospect ively divided into a group that received carperitide from the start of surgery ( carperitide group , n = 44 ) and a group that was not given carperitide ( control group , n = 44 ) . Carperitide infusion was initiated at the beginning of surgery and was continued for ≥5 days , with the central dose being 0.02 g/kg/min . The primary endpoint was the serum creatinine level on postoperative day ( POD ) 3 . Results The serum creatinine levels on PODs 3 , 4 , and 7 were significantly lower , and creatinine clearance on PODs 2 and 3 was significantly higher in the carperitide group than in the controls . One patient in the control group and no patient in the carperitide group required continuous hemodiafiltration , but the difference was not statistically significant . Conclusion Continuous low-dose infusion of carperitide from the start of cardiovascular surgery maintained renal function in patients with preoperative renal dysfunction Background : Increased intra-abdominal pressure ( IAP ) postoperatively can adversely affect cardiovascular , pulmonary , and renal function . In this prospect i ve , r and omized trial , we compared the IAP in morbidly obese patients after laparoscopic and open gastric bypass ( GBP ) surgery . Methods : 64 patients with a body mass index of 40 to 60 kg/m2 were r and omized to undergo laparoscopic or open GBP.IAPs were obtained at baseline ( after induction of anesthesia ) , immediately after the operation , and on post-operative day ( POD ) 1 , 2 , and 3 . Intraoperative and postoperative fluid requirements , urine output , and creatinine clearance were recorded . Results : Demographics of the two groups were similar . IAP increased from baseline immediately after laparoscopic and open GBP ( p < 0.05 ) . IAP returned to baseline by POD 2 after laparoscopic GBP but remained elevated through POD 3 after open GBP . In fact , IAP was lower after laparoscopic GBP than after open GBP on POD 1 , 2 and 3 ( p < 0.05).The amount of intraoperative IV fluid was similar between groups , but laparoscopic GBP required less IV fluid and facilitated higher urine output post-operatively than open GBP.There was no significant difference in creatinine clearance between groups . Conclusions : Laparoscopic GBP result ed in significantly lower IAP , less postoperative fluid required , and greater postoperative urine output than open GBP The authors analyzed different modes of prevention of acute renal failure ( ARF ) in the planned surgical treatment of abdominal aortic aneurysms . A hundred patients r and omly divided into 4 groups were examined . In patients from a control group , prevention of renal failure included no use of aminoglycosides , prevention of hyperglycemia , and provision of steady-state hemodynamics . In Group 2 patients , the reperfusion syndrome was prevented through a preventive load and early administration of antioxidants , for which they were enterally fed with Berlamine-modular for 5 days before surgery and in the postoperative period . The authors made efforts for Group 3 patients to have high oxygen supply values at all stages of surgical treatment . For this , they optimized infusion therapy and compensated for intraoperative blood loss by preoperatively prepared autoblood and through reinfusion of the blood collected from an operation wound with " Cell saver " apparatus . In Group 4 patients , the prevention of ischemia and reperfusion were simultaneously made and blood oxygen-transporting function was optimized . Renal function was evaluated from the activity of urinary enzymes and from nitrogen metabolic parameters . The studies have indicated that activation of free radical lipid peroxidation in the presence of ischemia/reperfusion and blood oxygen-transporting dysfunction plays an important role in the genesis of renal failure during surgical treatment for infrarenal aortic aneurysms . According to the data on changes occurring in urinary enzymatic activities , the preventive load with antioxidants and their early postoperative use ameliorate renal lesion . The similar effect is achieved by the provision of high tissue oxygen supply and uptake at all the stages of surgical treatment . The best effect shown , in addition to enzymuria diminution , by a clinical reduction in the frequency of renal dysfunction is achieved by applying a comprehensive approach to preventing ARF The technique of warm heart surgery is defined as continuous warm blood cardioplegia and normothermic cardiopulmonary bypass . Although the systemic effects of traditional myocardial protection are well known , the effects of warm heart surgery are not . In a prospect i ve trial , 204 patients undergoing coronary artery bypass grafting were r and omized to the warm heart surgery technique ( normothermic group ) or traditional intermittent cold blood cardioplegia and cardiopulmonary bypass ( hypothermic group ) . The groups had similar heparin sodium requirement , activated clotting times , urine output , hematocrit , and blood product utilization . There were no differences in hemodynamics immediately after cardiopulmonary bypass . The normothermic patients had a higher incidence of spontaneous defibrillation at cross-clamp removal ( 84 % ) than the hypothermic patients ( 33 % ) ( p less than 0.01 ) . An increase in the flow rate of low K+ cardioplegia was necessary to eradicate electrical activity during aortic occlusion more often in the normothermic patients ( 20 % ) than in the hypothermic patients ( 3 % ) ( p less than 0.01 ) . When low K+ cardioplegia was ineffective , high K+ cardioplegia was necessary to eradicate electrical activity in 31 % of the normothermic patients compared with 10 % of the hypothermic patients ( p less than 0.05 ) . The total cardioplegia volume delivered to the normothermic group ( 4.7 + /- 1.9 L ) was higher than that delivered to the hypothermic group ( 2.6 + /- 0.8 L ) ( p less than 0.01 ) . Although urine output was similar in both groups , the serum K+ levels were higher in the normothermic group ( 5.7 + /- 0.8 mmol/L ) than in the hypothermic group ( 5.3 + /- 0.8 mmol/L ) ( p less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE In an investigation of the effects of isovolemic hemodilution , 39 consecutive patients undergoing elective infrarenal aortic operation had detailed measurements of renal function , renal artery blood flow , and cardiac hemodynamics . METHODS The patients were r and omly allocated to receive acute preoperative isovolemic hemodilution to a hematocrit of 28 % , with 20 patients receiving hemodilution and 19 being control subjects . RESULTS Twelve ( 63 % ) of the control group had renal impairment , compared with only four ( 20 % in the group receiving hemodilution ( p < 0.01 ) . Hemodilution also prevented the fall in cardiac output induced by cross-clamping ( p < 0.01 ) and significantly reduced the need for transfusion of donor blood ( p < 0.01 ) . CONCLUSIONS Acute isovolemic hemodilution is clearly a useful adjunct in the management of patients undergoing elective aortic operation Ten patients who had undergone temporary occlusion of the abdominal aorta below the origin of the renal arteries were studied to evaluate the effect of ulinastatin on the postoperative renal function after abdominal aortic cross-clamping . They were divided into two groups : ulinastatin group ( ulinastatin 300,000 units.day-1 during intraoperative and postoperative three days , N = 5 ) , control group ( N = 5 ) . In ulinastatin group , the increase of N-acetyl-beta-D-glucosaminidase on the third postoperative day was inhibited and renal function was well maintained . These results suggest that the administration of ulinastatin in perioperative day prevents postoperative renal dysfunction after abdominal aortic cross-clamping OBJECTIVES A large number of experimental studies have indicated that blood cardioplegia might be superior to crystalloid cardioplegia for myocardial protection during ischemic arrest . However , no prospect ively r and omized studies of large patient series have been undertaken to prove potential differences in clinical course . METHODS Over a 52-month period , all patients undergoing on-pump coronary artery bypass operated on by 2 surgeons were prospect ively r and omized to receive either cold crystalloid cardioplegia ( group C ) or cold blood cardioplegia ( group B ) during aortic crossclamping . RESULTS Altogether , 1440 patients aged 37 to 89 years ( median , 66 years ) entered the study ( group C , n = 719 ; group B , n = 721 ) . The groups were comparable in all major demographic , preoperative , and operative variables . The clinical course turned out to be nearly identical for both groups . No statistically significant differences were seen concerning spontaneous sinus rhythm after aortic declamping , use of inotropic drugs or intra-aortic balloon pumping , postoperative ventilatory support , bleeding and rate of allogeneic blood transfusions , perioperative myocardial infa rct ion , episodes of atrial fibrillation , stroke or minor neurologic dysfunction , renal function , infections , physical rehabilitation , or mortality . Also , in subgroups of patients at higher operative risk ( female sex , age > 70 years , unstable angina , diabetes , emergency operation , ejection fraction < 0.50 , crossclamping time > 50 minutes , and EuroSCORE > 4 ) , no statistically significant differences could be demonstrated between the groups . CONCLUSIONS There were no significant differences whether myocardial protection was performed with cold blood cardioplegia or cold crystalloid cardioplegia during aortic crossclamping in patients undergoing coronary artery bypass grafting . The extra costs related to blood cardioplegia might be saved The value of human albumin ( HA ) for treating hypovolemia is controversial . Less expensive alternatives such as hydroxyethyl starch ( HES ) are sometimes refused because of unwanted side effects . We prospect ively r and omized 50 patients older than 70 years old undergoing major abdominal surgery to receive either 5 % HA ( n = 25 ) or a third generation HES preparation ( 6 % HES 130/0.4 ; n = 25 ) when mean arterial blood pressure was < 60 mm Hg and central venous pressure was < 10 mm Hg . Hemodynamics , inflammation ( interleukin-6 ) , endothelial activation-integrity ( adhesion molecules ) , coagulation ( thrombelastography ) , and renal function ( including kidney-specific proteins ) were monitored after the induction of anesthesia , after surgery , 5 h in the intensive care unit , and on the first postoperative day . HA patients received 3960 + /- 590 mL of HA and 5070 + /- 1030 mL of Ringer 's lactate solution , and HES patients received 3500 + /- 530 mL of HES and 4550 + /- 880 mL of Ringer 's lactate solution . Total protein remained normal only in the HA-treated patients . No significant differences ( P > 0.1 ) between the groups were seen with regard to hemodynamics , coagulation , and kidney function . Plasma levels of interleukin-6 and soluble adhesion molecules were significantly ( P < 0.05 ) higher in the HA- than in the HES-treated patients . We conclude that HA in elderly patients undergoing major abdominal surgery can easily be replaced by a modern HES preparation . Because of the decreased inflammatory response and endothelial activation-injury , HES 130/0.4 seems to be the more appropriate fluid strategy for these patients Thirty-two patients undergoing elective infrarenal aortic surgery were r and omly assigned to receive a perioperative infusion of either dopexamine hydrochloride at a rate of 2 μg/kg/min ( n = 15 ) or 0.9 % saline solution as placebo ( n = 17 ) . Renal function was monitored by regular measurements of serum creatinine levels . There were significant mean percentage increases in serum creatinine ( p < 0.001 ) at all time points up to 3 days postoperatively in the placebo group but only at 2 and 12 hours in the dopexamine group . It was concluded that dopexamine hydrochloride confers renal protection in patients undergoing aortic reconstruction Objective Renal failure after bypass is still a threatening problem prolonging hospital care and reducing overall survival . The following pilot study was aim ed to analyze whether perioperative low-dose prostacyclin infusion is able to preserve renal function in a selected group of patients who according to a poor cardiac function were stratified as high risk for the development of renal failure after bypass . Design Prospect i ve r and omized study . Setting Tertiary care university medical center . Patients Thirty-four patients scheduled for primary cardiac bypass surgery were included in the study ( prostacyclin n = 17 , control n = 17 ) . Inclusion criteria were normal renal function before surgery and a cardiac ejection fraction < 40 % . Interventions Low-dose prostacyclin ( 2 ng/kg/min ) was added to the st and ard anesthetic protocol . Infusion was started immediately before surgery and was continued for a maximum of 48 hrs . Measurements and Main Results Significant differences in the endogenous creatinine clearance were found between the prostacyclin and the control group . Whereas there was a significant drop in the creatinine clearance at 6 hrs after surgery in the control group with a prolonged recovery period , values in the prostacyclin group remained stable . Creatinine clearance before intervention was 100 ± 22 mL/min in the control group and 91 ± 22 mL/min in the prostacyclin group , values at 24 hr were 68 ± 34 mL/min vs. 103 ± 37 mL/min , respectively ( p < .01 ) . Significant findings in favor for the prostacyclin group were also found for urine output and the fractional excretion rate of sodium . Conclusion This first pilot study indicates that low-dose prostacyclin may be of substantial value for preserving renal function in high-risk patients after coronary bypass surgery Summary We have evaluated the effect of prostagl and in E1(PGE1 ) on renal function after cardiac surgery with cardiopulmonary bypass in 20 patients , ten of whom received 0.02 μg·kg−1·min−1 of PGE1 by infusion into the oxygenator during bypass ; ten patients served as controls . Serum β2-microglobulin fell significantly and urine β2-microglobulin increased significantly after surgery in both groups . Urine N-acetyl-β-D-glucosaminidase was high after surgery in both groups , but it was significantly lower in the PGE1 group . Free water clearance fell significantly on the 1st , 3rd , and 5th postoperative days compared with preoperative values in the control but not in the PGE1 group . These results suggest that PGE1 may prevent renal dysfunction after cardiopulmonary bypass Background : Cross-clamping of the descending aorta during operative repairs causes sudden , significant reductions in renal function that may persist well beyond arterial clamp release . Commonly used agents , such as dopamine and mannitol , have not consistently affected renal outcome in these high-risk patients . Fenoldopam mesylate is a novel , highly selective dopamine type-I agonist that preferentially dilates the renal and splanchnic vasculature , but has not been investigated in patients undergoing prolonged aortic clamping for whom adverse renal outcomes should be more likely . Methods and Results : Twenty-two adult patients without significant pre-existing renal dysfunction and presenting for elective repairs of abdominal aortic aneurysms were studied . Fenoldopain mesylate was infused after obtaining baseline values ranging from 0.1 to 1.0 pg/kg/min for the first 24 hours postoperatively to maintain mean arterial pressure ±25 % baseline . Serial renal function indices , including creatinine clearance and electrolyte fractional excretions , were measured at baseline , at aortic clamping and unclamping , and post-clamp release , and were estimated through hospital discharge . Creatinine clearance fell during abdominal exploration and clamping , reaching a nadir with clamp removal . Partial recovery occurred by 2 hours after clamp removal , and returned to baseline values by postoperative day 1 and thereafter . Fractional excretions rose rapidly throughout the operative phase . Total fenoldopam dose was directly related to the baseline creatinine clearance ; after clamp removal , creatinine clearance was directly related to the mean arterial pressure at the lowest dose of fenoldopam , and inversely related to the mean arterial pressure at clamp release . Conclusions : In elderly patients with severe vascular disease undergoing aneurysmal repairs , the use of a fenoldopam infusion in this open-label , uncontrolled trial was associated with a relatively rapid return of renal function to baseline values , despite profound decreases during aortic cross-clamping . Further studies will be necessary to investigate how fenoldopam infusions compare with traditional therapies BACKGROUND Acute kidney injury ( AKI ) after heart surgery is associated with increased mortality . We sought to determine whether prophylactic perioperative administration of N-acetylcysteine ( NAC ) prevents postoperative AKI in patients with chronic kidney disease undergoing cardiac surgery ( clinical trials.gov identifier NCT00211653 ) . METHODS In this prospect i ve , r and omized , placebo-controlled , double-blinded clinical trial , 102 patients with chronic kidney disease who underwent heart surgery at the Minneapolis Veterans Affairs Medical Center were r and omized to either NAC ( n = 50 ) 600 mg PO twice daily or placebo ( n = 52 ) for a total of 14 doses ( 3 preoperative ) . The primary outcome was maximum change in creatinine from baseline within 7 days after surgery . Secondary outcome was AKI ( ie , > 0.5 mg/dL or > or=25 % increase in creatinine from baseline ) . RESULTS Creatinine increased in both groups ( 0.45 + /- 0.7 mg/dL in NAC vs 0.55 + /- 0.9 mg/dL in placebo , P = .53 ) and peaked on postoperative day 5 . Acute kidney injury occurred in 41 patients ( 22 NAC vs 19 placebo , P = .44 ) by postoperative day 5 , but persisted in only 14 ( 7 NAC vs 7 placebo , P = .94 ) by day 30 . In multivariable analysis , perioperative NAC was unassociated with AKI ( relative risk 1.2 , 95 % CI , 0.8 - 1.9 , P = .34 ) . Five patients ( 3 NAC vs 2 placebo , P = .68 ) underwent hemodialysis , and 5 ( 2 NAC vs 3 placebo , P = 1.0 ) died perioperatively . There was no difference in lengths of stay in the intensive care unit ( 4.9 + /- 7 days in NAC vs 6.5 + /- 9 days in placebo , P = .06 ) and the hospital ( 13.2 + /- 13 days in NAC vs 16.7 + /- 17 days in placebo , P = .12 ) . CONCLUSION Prophylactic perioperative NAC administration does not prevent AKI after cardiac surgery OBJECTIVE To test whether the administration of calcium channel antagonists , such as verapamil ( V ) , on the day before , during , and for 24 - 36 h after an important abdominal intervention , can lower the onset of acute renal failure ( ARF ) , mostly in renal-risk patients , such as the aged . DESIGN R and omized , nonblinded study . SETTING Three surgical care university departments and two intensive care units of the same hospital ( S. Anna , Ferrara , Italy ) . PATIENTS Thirty-five elderly patients ( 61 - 83 years old ) entered the study : 18 of them were given V ; 17 were not treated and were considered as controls . The two study groups were overlapping as regards age , renal risk , and surgical challenge . The patients who underwent ARF ( 5 in the treated group , 7 among the controls ) were rejected from the study . INTERVENTIONS V was given on the eve of surgery at a dose of 80 mg/8 h per os and then through slow infusion ( 5 mg/4 - 6 h ) during the next intra- and postoperative 24 - 36 h. Abdominal surgery was performed owing to gastric cancer ( 8 cases ) , colorectal neoplasia ( 10 cases ) , gallstone disease ( 4 cases ) , subrenal aortic aneurysm ( 6 cases ) , and iliofemoral obstructive arteriopathy ( 7 cases ) . MEASUREMENTS Serum creatinine ( SCr ) was assessed to test renal function ; 24-h urinary levels of brush-border enzymes ( gamma glutamyl transferase , or gGT ) , lysosomal enzymes ( N-acetyl-beta-D-glucosaminidase , or NAG ) , and beta 2-microglobulin ( or beta 2 M ) were determined at T0 ( on the eve of surgery ) , T1 ( first and second day after ) , and T2 ( 7th and 8th day after ) to demonstrate possible tubule cell damage . RESULTS In the evaluated patients ( 13 treated with V and 10 untreated ) : ( a ) the 24-h urinary levels of gGt and NAG persisted unchanged throughout the study in the treated patients , whereas in the controls the same indices exhibited significant ( p < 0.01 ) increases at T1 and T2 ; ( b ) the 24-h urinary levels of beta 2 M showed significant ( p < 0.01 ) increases in both groups from T0 to T1 ; however , at T2 these values tended to return to normal ranges in the treated patients , whereas they continued to be elevated in the untreated group . As regards the patients who underwent postoperative ARF , in the treated group urine output was significantly larger ( p < 0.01 at T1 and p < 0.001 at T2 ) , SCr was significantly ( p < 0.05 ) lower , and the renal function recovered earlier ( within 10 + /- 3 vs. 22 + /- 9 days ) than in the controls . CONCLUSIONS The administration of calcium channel antagonists to renal-risk patients during surgery and immediately before and after it has failed to prevent the onset of postoperative ARF . Nevertheless this procedure has been shown to somehow reduce surgery-mediated lesions of the tubule cells , as demonstrated by the finding of elevated urinary enzymes only in the untreated group Background Morbid obesity and bariatric surgery are both risk factors for the development of postoperative rhabdomyolysis ( RML ) . RML results from injury to skeletal muscle , and a serum creatine phosphokinase ( CK ) level > 1,000 IU/L is considered diagnostic of RML . The aim of this study was to determine if intraoperative intravenous fluid ( IVF ) volume affects postoperative CK levels following laparoscopic bariatric operations . Study Design Prospect i ve , single blinded , and r and omized trial was conducted . Methods Patients scheduled to undergo laparoscopic sleeve gastrectomy , adjustable gastric b and , or Roux-en-Y gastric bypass operations were r and omized into two groups . Subjects in Group A received 15 ml/kg total body weight ( TBW ) of IV crystalloid solution during surgery , while subjects in Group B received 40 ml/kg TBW . Preoperative and postoperative CK and creatinine levels and intra- and postoperative urine output were monitored and recorded . Results Forty-seven patients were assigned to Group A and 53 patients to Group B. Group B patients had significantly higher urine output in the operating room , in the post-anesthesia care unit ( PACU ) , and on postoperative days 0 and 1 . Group B patients also had significantly lower serum creatinine level in the PACU and a trend towards lower creatinine levels on postoperative days 0 , 1 , and 2 . There were no statistical differences in CK levels at any time between the two groups . Four patients in Group A and three patients in Group B developed postoperative RML . Conclusions Conservative ( 15 ml/kg ) versus liberal ( 40 ml/kg ) intraoperative IVF administration did not change the incidence of RML in patients undergoing laparoscopic bariatric operations . Since the occurrence of RML in this patient population is relatively high , postoperative CK levels should be routinely obtained in patients at special risk Renal dysfunction occurring after open heart surgery is multifactorial in origin but activation of the renin-angiotensin system may have a prominent role . Fourteen patients with ischaemic heart dysfunction scheduled for elective coronary artery bypass graft ( CABG ) surgery were allocated to a treatment group [ enalaprilat for 2 days ; ACEI ( angiotensin-converting enzyme inhibitor ) group , n=7 ] or a control group ( n=7 ) . The cardiac index was significantly higher in ACEI-treated patients than in the controls before and after cardiopulmonary bypass ( CPB ) ( P<0.05 ) and on postoperative day 2 ( P<0.05 ) . The systemic vascular resistance was significantly lower in the ACEI-treated patients than in the controls before and after CPB ( P<0.05 ) . Renal plasma flow , measured as [131I]orthoiodohippuran clearance ( ClH ) , was higher in the ACEI group than in the control group before CPB , as was endogenous creatinine clearance after CPB ( P<0.05 ) . On post-operative day 7 , ClH was significantly higher in the ACEI group than in the control group ( P<0.05 ) . Plasma renin activity and vasopressin concentration increased in both groups during CPB ( P<0.05 ) . The study demonstrates that administration of an i.v . ACEI , enalaprilat , improves cardiac output during CABG surgery in patients with ischaemic heart dysfunction . Moreover , renal perfusion was better maintained during surgery , and this effect was sustained up to post-operative day 7 OBJECTIVES The purpose of this comparative study is to prove the efficacy of the human atrial natriuretic peptide ( hANP ) in patients with chronic kidney disease ( CKD ) undergoing coronary artery bypass graft surgery ( CABG ) . BACKGROUND CKD is an important risk factor for cardiac surgery . METHODS This was a r and omized controlled study of 303 patients with CKD who underwent CABG , and were divided into a group who received carperitide infusion and another group without carperitide . The primary endpoints were : 1 ) the post-operative dialysis-free rate ; and 2 ) serum creatinine ( sCr ) and estimated glomerular filtration rate . The secondary endpoints were : 1 ) the early post-operative outcome ; 2 ) outcome at 1 year post-operatively ; 3 ) the maximum sCr , the rate of increase of sCr , and an increase of sCr by ≥ 0.3 mg/dl compared with the pre-operative value ; and 4 ) ANP and cyclic-guanosine monophosphate levels . RESULTS The post-operative sCr was significantly lower in the hANP group not only in the post-operative acute stage but also in the first year . The maximum Cr and Cr increase rate were significantly lower in the hANP group ( p = 0.00665 , p < 0.0001 ) . There was no difference in mortality rate in the first year post-operatively , and fewer cardiac events and patients going on dialysis were found in the hANP group ( p < 0.0001 and p = 0.0014 , respectively ) . CONCLUSIONS In the post-operative acute stage , carperitide showed cardiorenal protective effects that prevented post-operative cardiac events and initiation of dialysis . Thus , perioperative infusion of low-dose carperitide may have a significant role in management of patients with renal dysfunction undergoing on-pump CABG . ( Effectiveness of hANP for Cardiac Surgery in Patients With Moderate to Severe Preoperative Renal Dysfunction Without Dialysis [ NU-HIT for CRF ] ; UMIN000001462 ) OBJECTIVES /HYPOTHESIS The syndrome of inappropriate antidiuretic hormone or arginine vasopressin secretion ( SIADH ) is a disorder in which release of antidiuretic hormone is independent of plasma osmolarity , result ing in fluid retention and development of dilutional hyponatremia . The incidence of SIADH following neck dissection was found to be 18 % to 30 % in two separate reports . The incidence of SIADH in a cohort of patients who underwent neck dissection was prospect ively studied . METHODS Eighty-six patients were included in the study , along with a control group of 19 patients who underwent other neck procedures . Patient gender , age , physical condition ( American Society of Anesthesiologists score ) , type of neck dissection , prior treatment , and smoking history were noted . Blood and urine osmolarity and sodium levels were sample d before surgery and during the first 24 hours after the surgery . These were recorded daily in cases with SIADH until the syndrome resolved . RESULTS The incidence of SIADH was only 1.15 % in patients before surgery . The syndrome developed in seven patients following neck dissection ( 8.14 % ) and in none of the patients in the control group . SIADH resolved within 72 hours at the latest . No association was found with patient gender , age , physical condition , or type or laterality of neck dissection . A statistically significant connection between the syndrome and history of smoking was noted ( P < .05 ) , and it was more commonly seen in patients with node-positive necks ( P = .1231 ) . CONCLUSIONS SIADH following neck dissection may be less common than formerly reported . Previous studies have presented contradicting data concerning the influence of tumor recurrence or prior radiation therapy on its incidence . Our results indicate no such association . A statistically significant connection between smoking and the syndrome was found . No clinical symptoms developed in the patients with SIADH , but it seems prudent to suggest limiting fluid intake in the first postoperative 24 hours for patients following neck dissection 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 Patients with chronic kidney disease ( CKD ) are at risk to develop acute renal failure ( ARF ) after open heart surgery . This complication is associated with high morbidity , mortality , and cost . Because the ability to concentrate urine is lost early in the progression of CKD , renal patients kept on fluid restriction prior to surgery may develop severe dehydration , a situation consistently found to be one of the most critical risk factors for postoperative ARF . Our goal was to investigate whether intravenous hydration for 12 h prior to cardiac surgery could prevent acute renal injury in patients with CKD . This is a prospect i ve study in a tertiary cardiac surgery center . Forty-five patients admitted for elective open heart surgery with moderate-to-severe CKD , as evidence d by a quantified glomerular filtration rate less than 45 mL/min , were assigned using a 2/1 r and omization process , to either receive an intravenous infusion of half-isotonic saline ( 1 mL/kg/h ) for 12 h before the operation ( hydration group , n = 30 , 29 men , 64 + 1.7 years old ) , or to be simply kept on fluid restriction ( control group , n = 15 , 14 men , 64.2 + 2.8 years old ) . Groups were not different in clinical and intraoperative variables associated with postoperative renal injury . ARF developed in 8 of 15 ( 53 % ) patients in the control group , but in only 9 of the 30 ( 30 % ) patients in the hydration group . Four patients in the control group ( 27 % ) , but no one in the hydration group , required dialysis after the operation ( P < 0.01 ) . Peak creatinine and blood urea nitrogen values were two to three times higher in the control group than in the hydration group . Preoperative intravenous hydration may ameliorate renal damage in patients with moderate-to-severe renal insufficiency undergoing cardiac surgery To evaluate plasma dopamine concentration and the effects of low doses infusion on urinary output after abdominal vascular surgery in patients with renal function impairment we performed a prospect i ve clinical study . Twenty hemodynamically stable patients ( mean age 66.6 years ) , with serum creatinine concentration < 2 mg % , who undergoing general anesthesia for major vascular surgery participated . A low dose of dopamine ( 3 micrograms/kg/min ) was administrated to patients with postoperative protracted urinary output < 0.5 ml/kg/hr for at least eight hours . Plasmatic determinations were taken at T0 ( no dopamine administration ) , when urinary output began to increase , or if not , after two hours ( T1 ) , at eight ( T2 ) , and 24 ( T3 ) hours after the beginning of infusion . After 24 hours the dopamine infusion was stopped and the patient 's plasmatic level was measured four hours later ( T4 ) . Dopamine plasma concentrations were measured using high-performance liquid chromatography . Plasma dopamine concentration increased in all patients and reached a steady state at T2 ( T2 = 76.41 + /- 16.84 ng/ml ) . Dopamine induced a concentration-dependent increase in urinary output ( T0 = 0.45 + /- 0.14 ; T1 = 1.49 + /- 1.11 ; T2 = 2.34 + /- 1.44 ; T3 = 1.57 + /- 0.57 ; T4 = 0.85 + /- 0.7 ml/kg/hr ) . Three patients did not have an enhanced urinary output after dopamine infusion ; they did have a prolonged clamping time and operation time ( 162 + /- 24 and 570 + / 30 min , respectively ) . We conclude that low dose dopamine induces a dose-dependent increase of urinary output . This phenomenon also has been found in patients when their plasma concentration had not yet reached the steady-state . Lack of responsiveness to dopamine suggests a renal function impairment probably due to the prolonged aortic clamping time AIM To test whether short-term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury ( AKI ) in cardiac surgical patients . METHODS We conducted a double-blind , r and omized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI . Patients were r and omized to atorvastatin ( 40 mg once daily for 4 days starting preoperatively ) or identical placebo capsule . Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy . Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification ( RIFLE R , I or F ) , change in urinary neutrophil gelatinase-associated lipocalin ( NGAL ) concentration , requirement for renal replacement therapy , length of stay in intensive care , length of stay in hospital and hospital mortality . RESULTS Study groups were well matched . For each patient maximal increase in creatinine during the 5 days after surgery was assessed ; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group ( P = 0.62 ) . RIFLE R or greater occurred in 26 % of patients with atorvastatin and 32 % with placebo ( P = 0.65 ) . Postoperatively urine NGAL changes were similar ( median NGAL : creatinine ratio at intensive care unit admission : atorvastatin group 1503 ng/mg , placebo group 1101 ng/mg ; P = 0.22 ) . Treatment was well tolerated and adverse events were similar between groups . CONCLUSION Short-term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL . ( Clinical Trials.gov NCT00910221 ) BACKGROUND High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting , but the safety and effectiveness of smaller doses is unclear . Furthermore , patient selection criteria for optimal use of the drug are not well defined . METHODS Seven hundred and four first-time coronary artery bypass grafting patients were r and omized to receive one of three doses of aprotinin ( high , low , and pump-prime-only ) or placebo . The patients were stratified as to risk of excessive bleeding . RESULTS All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements . Consistent efficacy was not , however , demonstrated in the subgroup of patients at low risk for bleeding . There were no differences in mortality or the incidences of renal failure , strokes , or definite myocardial infa rct ions between the groups , although the pump-prime-only dose was associated with a small increase in definite , probable , or possible myocardial infa rct ions ( p = 0.045 ) . CONCLUSIONS Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens . Although safe , aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding . The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infa rct ions Controversy continues as to whether hypotension during cardiopulmonary bypass ( CPB ) impairs intraoperative and postoperative renal function . Therefore , 21 patients with normal renal function ( plasma creatinine less than 1.2 mg/dL , creatinine clearance greater than 70 mL/min ) , aged 50 to 70 years , without associated pathology , scheduled for elective coronary surgery were studied prospect ively . Patients were r and omized into two groups : group 1 included 14 patients whose arterial blood pressure during CPB was left untreated , and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg . Plasma and urine creatinine , sodium , potassium , and osmolality were measured preoperatively , intraoperatively and postoperatively . Creatinine , osmolal and free water clearances , and excreted sodium fraction were calculated . Plasma creatinine remained normal throughout the study in all patients . Creatinine clearances were similar preoperatively ( 101.9 + /- 36.7 in group 1 and 120.6 + /- 50.7 mL/min in group 2 ) . In group 1 , creatinine clearance decreased during CPB to 88.7 + /- 39.7 mL/min , whereas in group 2 it increased to 157.6 + /- 79.5 mL/min ; the difference between groups was significant . Early postoperatively , there was no difference : 136.2 + /- 86.6 mL/min in group 1 and 100 + /- 21.4 mL/min in group 2 . One week postoperatively , values were 100.5 + /- 37.9 and 101.9 + /- 18.4 , respectively . There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively , but not postoperatively . Osmolal clearance also correlated with perfusion pressure intraoperatively , but it was significantly lower in the phenylephrine group postoperatively . Postoperative renal function was normal in all patients ; no deleterious effect of a low arterial pressure during bypass could be identified BACKGROUND Preoperative creatinine values higher than 2.5 mg/dL are associated with markedly increased risk for both mortality and morbidity in patients undergoing coronary artery bypass surgery . We aim ed to determine the effects of prophylactic perioperative hemodialysis on operative outcome in patients with nondialysis-dependent moderate renal dysfunction . METHODS Forty-four adult patients with creatinine levels greater than 2.5 mg/dL but not requiring dialysis underwent coronary artery bypass surgery with cardiopulmonary bypass . The patients were r and omly divided into two groups . In group 1 ( dialysis group , 21 patients ) , perioperative prophylactic hemodialysis was performed in all patients . Group 2 ( 23 patients ) was taken as a control group and hemodialysis was performed only if postoperative acute renal failure was diagnosed . RESULTS The hospital mortality was 4.8 % ( 1 patient ) in the dialysis group , and 30.4 % ( 7 patients ) in the control group ( p = 0.048 ) . Postoperative acute renal failure requiring hemodialysis was seen in 1 patient ( 4.8 % ) in the dialysis group and in 8 patients ( 34.8 % ) in the control group ( p = 0.023 ) . Thirty-three postoperative complications were observed in the control group for an early morbidity of 52.2 % ( 12 patients ) and 13 complications occurred in 8 patients in the dialysis group ( 38.1 % ) . The average length of the intensive care unit and postoperative hospital stay were shorter in the dialysis group than in the control group ( p = 0.005 and p = 0.023 , respectively ) . CONCLUSIONS Preoperative creatinine levels higher than 2.5 mg/dL , increase the risk of mortality and the development of acute renal failure and prolong the length of hospital stay after on-pump coronary artery bypass surgery . Perioperative prophylactic hemodialysis decreases both operative mortality and morbidity in these high-risk patients Objective : To determine whether fenoldopam and N-acetylcysteine prevent renal deterioration and improve hospital outcome for patients with chronic renal insufficiency undergoing cardiac surgery . Design : Prospect i ve , r and omized , double-blinded , placebo-controlled trial . Setting : A community hospital that is a cardiac referral center . Patients : Seventy-nine adult patients with chronic renal insufficiency ( creatinine clearance ≤40 mL/min ) who underwent cardiac surgery . Interventions : Group 1 received intravenous fenoldopam 0.1 & mgr;g/kg/min started at surgical induction and continued for 48 hrs . Group 2 received N-acetylcysteine 600 mg orally twice a day , from preoperative day 1 to postoperative day 1 . Group 3 received both fenoldopam and N-acetylcysteine , and group 4 patients served as controls . Measurements and Main Results : Using multiple comparisons ( analysis of variance ) with change scores , and statistically adjusting for group differences in aortic cross-clamp time , use of intraoperative aprotinin , and preoperative use of statin , we found that the change in creatinine clearance from preoperative to postoperative day 3 was statistically less for group 1 ( −1.47 mL/min ± 2.06 se , p = .0286 ) and for group 2 ( −0.67 mL/min ± 2.11 se , p = .0198 ) and less but not quite significant for group 3 ( −3.08 mL/min ± 1.95 se , p = .0891 ) compared with controls ( −8.15 mL/min ± 2.18 se ) . Furthermore , the adjusted weight gain on postoperative day 3 was 5.55 kg ± 1.00 se ( p = .0988 ) for group 1 , 5.06 kg ± 1.06 se ( p = .0631 ) for group 2 , and 5.14 kg ± .91 se ( p = .0445 ) for group 3 compared with 8.03 kg ± 1.07 se for group 4 . However , there was no decrease in length of critical care or hospital stay or hospital costs . Finally , fenoldopam contributed to perioperative hypotension . Conclusions : Perioperative fenoldopam and N-acetylcysteine abrogate the early postoperative decline in renal function of patients who have chronic renal insufficiency , although these agents do not affect other parameters of cardiac surgical outcome OBJECTIVE To evaluate the possible protective effects of fenoldopam on renal function in patients undergoing cardiopulmonary bypass . DESIGN Prospect i ve , r and omized trial . SETTING University teaching hospital . PARTICIPANTS One hundred sixty consecutive patients with serum creatinine > 1.5 mg/dL who underwent uncomplicated moderate hypothermic cardiopulmonary bypass for cardiac surgery . INTERVENTIONS A r and om group of 80 patients was managed conventionally ( group A ) , whereas another r and om group of 80 patients received continuous intravenous administration of low-dose fenoldopam ( 0.1 - 0.3 microg/kg/min ) during cardiopulmonary bypass and in the early postoperative period ( group B ) . MEASUREMENTS AND MAIN RESULTS An improvement of postoperative renal parameters were observed only in group B : preoperative serum creatinine 1.82 + /- 0.2 versus 1.43 + /- 0.73 postoperatively ( p < 0.001 ) , preoperative creatinine clearance 51.34 + /- 22.26 versus 67.14 + /- 18.55 postoperatively ( p < 0.001 ) . CONCLUSIONS In this study , fenoldopam was an effective agent in the prevention of renal dysfunction after cardiopulmonary bypass Within a daily dose of 20 mL/kg , medium-molecular hydroxyethyl starch ( HES ) is a safe and effective colloid for intravascular blood volume replacement . The effect of large doses on coagulation and renal function is unknown . We prospect ively studied 41 patients undergoing total hip arthroplasty during the perioperative period . Inevitable blood loss was replaced with HES ( HES group ) or albumin ( ALB group ) in combination with packed red blood cells ( PRBC ) , fresh frozen plasma ( FFP ) , and platelets . Hemodynamic , oncotic , coagulation , and renal functions were compared initially , at the end of surgery , during the postoperative period ( 1 , 3 , and 6 h ) , and also with respect to the volume of colloid solution administered ( 1500 , 2000 , and 3000 mL ) . Total intake and output balances , as well as the costs of blood replacement therapy , were registered at the end of the study . We found differences in oncotic variables even at 6 h after surgery ( total serum proteins [ TSP ] : HES 36.4 + /- 7.9 g/L versus ALB 55.6 + /- 6.1 g/L , P < 0.01 ; serum albumin : HES 25.5 + /- 5.3 g/L versus ALB 42.0 + /- 5.6 g/L , P < 0.01 ) . Colloid osmotic pressure ( COP ) and hemodynamic , coagulation , and renal functions were comparable , as was total blood loss ( HES 4247 + /- 2090 mL versus ALB 4051 + /- 2830 mL ) . Total requirements for colloid solutions ( HES 35.9 + /- 7.4 mL/kg versus ALB 33.9 + /- 10.5 mL/kg ) , PRBC , FFP , or platelets were comparable , whereas total cost of blood replacement therapy was 33 % less in the HES group . With respect to efficacy and side effects on coagulation and renal function , medium molecular HES is an appropriate and economic alternative to albumin at daily doses of up to at least 36 mL/kg . ( Anesth Analg 1996;83:262 - 8 BACKGROUND Coronary revascularization with cardiopulmonary bypass has the potential risk of renal dysfunction related to the nonphysiologic nature of cardiopulmonary bypass . Recently , there has been a revival of interest in performing myocardial revascularization on the beating heart and we investigated whether this prevents renal compromise . METHODS A prospect i ve , r and omized , controlled trial was performed in 50 patients ( 45 males , mean age 61+/-3.7 years ) undergoing elective coronary artery bypass grafting . Patients were r and omly assigned to conventional revascularization with cardiopulmonary bypass ( on pump ) or beating heart revascularization ( off pump ) . Glomerular and tubular function were assessed up to 48 hours postoperatively . RESULTS There were no deaths , myocardial infa rct ions or acute renal failure in either group . Glomerular filtration as assessed by creatinine clearance and the urinary microalbumin/creatinine ratio was significantly worse in the on pump group ( p < 0.0004 and 0.0083 , respectively ) . Renal tubular function was also impaired in the on pump group as assessed by increased N-acetyl glucosaminidase activity ( p < 0.0272 ) . CONCLUSIONS These results suggest that off pump coronary revascularization offers a superior renal protection when compared with conventional coronary revascularization with cardiopulmonary bypass and cardioplegic arrest in first time coronary bypass patients We studied the long‐term efficacy and safety of medium‐molecular‐weight hydroxyethyl starch ( HES ) administered in doses above 20 mlkg−1 during major blood replacement therapy . Blood replacement for 50 patients used 6 % HES 200/0.5 ( HES group ) or 5 % albumin ( ALB group ) and additional blood components according to a defined protocol . We compared safety , efficacy and costs in 4 peri‐operative days . Colloid administration on the day of surgery was 38.4 mlkg−1 ( HES group ) and 35.1 mlkg−1 ( ALB group ) . Haemodynamic , coagulation and renal function parameters were similar . Although total serum protein was still different on the third postoperative day ( 53.45 gl−1 ( HES group ) and 60.6 gl−1 ( ALB group ) ( p < 0.01 ) ) the colloid osmotic pressure always remained above 19.5 ( 2.5 ) mmHg ( HES group ) . Blood loss ( 3810 ( 1632 ) ml ( HES group ) and 3455 ( 1733 ) ml ( ALB group ) ) and the requirement for blood components was comparable . Costs were reduced by 35 % ( p < 0.05 ) in the HES group . We conclude that using 6 % HES 200/0.5 as the only colloid for treatment even of large blood loss is a safe and economic alternative to albumin STUDY OBJECTIVES Cardiac surgery with cardiopulmonary bypass ( CPB ) results in perioperative organ damage caused by the systemic inflammatory response syndrome ( SIRS ) and ischemia/reperfusion injury . Administration of corticosteroids before CPB has been demonstrated to inhibit the activation of the systemic inflammatory response . However , the clinical benefits of corticosteroid therapy are controversial . This study was design ed to document the effects of dexamethasone on cytokine release and perioperative myocardial , pulmonary , renal , intestinal , and hepatic damage , as assessed by specific and sensitive biomarkers . DESIGN AND PATIENTS A prospect i ve , double-blind , placebo-controlled , r and omized trial for dexamethasone was conducted in 20 patients receiving either dexamethasone ( 1 mg/kg before anesthesia induction and 0.5 mg/kg after 8 h ; n = 10 ) or placebo ( n = 10 ) . Different markers were used to assess the SIRS : interleukin (IL)-6 , IL-8 , IL-10 , C-reactive protein ( CRP ) , and tryptase ; and organ damage : heart ( plasma heart-type fatty acid binding protein , cardiac troponin I [ cTnI ] , creatine kinase-MB ) , kidneys ( N-acetyl-glucosaminidase [ NAG ] , microalbuminuria ) , intestine ( intestinal-type fatty acid binding protein [I-FABP]/liver-type fatty acid binding protein [ L-FABP ] ) , and liver ( alpha-glutathione S-transferase ) . RESULTS Dexamethasone modulated the SIRS with lower proinflammatory ( IL-6 , IL-8 ) and higher antiinflammatory ( IL-10 ) IL levels . CRP and tryptase were lower in the dexamethasone group . cTnI values were lower in the dexamethasone group at 6 h in the ICU ( p = 0.009 ) . Patients in the dexamethasone group had a longer time to tracheal extubation ( 18.86 + /- 1.13 h vs 15.01 + /- 0.99 h , p = 0.02 [ mean + /- SEM ] ) , with a lower oxygenation index at that time : Pa(O2)/fraction of inspired oxygen ratio , 37.17 + /- 1.8 kPa vs 29.95 + /- 2.1 kPa ( p = 0.009 ) . The postoperative glucose level ( 10.7 + /- 0.6 mmol/L vs 7.4 + /- 0.5 mmol/L , p = 0.005 ) was higher in the dexamethasone group . Serum glucose was independently associated with intestinal injury ( urine I-FABP peak , R2 = 42.5 % , beta = 114.4 + /- 31.4 , significant at p = 0.002 ; urine L-FABP peak , R2 = 47.3 % , beta = 7,714.1 + /- 1,920.9 , significant at p = 0.001 ) and renal injury ( urine NAG , R2 = 32.1 % , beta = 0.21 + /- 0.07 , significant at p = 0.009 ) . Tryptase peaks correlated negatively with peaks of intestinal and renal injury biomarkers . CONCLUSION Even while inhibiting SIRS , dexamethasone treatment offered no protection against transient , sub clinical , perioperative abdominal organ damage . Tryptase release could have a preconditioning effect , offering protection against perioperative intestinal and renal damage . Dexamethasone treatment result ed in more pronounced postoperative pulmonary dysfunction , prolonged time to tracheal extubation , and initiated postoperative hyperglycemia in patients undergoing elective on-pump coronary artery bypass graft surgery BACKGROUND To evaluate hospital mortality and morbidity after myocardial revascularization in a prospect i ve and multicenter study , comparing on-pump versus off-pump in a special subset of patients with lesions in the left descending artery , alone or associated with the right coronary artery . METHODS A multicenter prospect i ve r and omized study was performed . One hundred and sixty selected low-risk patients were enrolled ; 80 patients were operated on-pump ( coronary artery bypass grafting [ CABG ] , group I ) and 80 patients were operated off-pump ( off-pump coronary artery bypass [ OPCAB ] , group II ) . One hundred and five were male and ages ranged from 39 to 70 years old ; mean 58.81 + /- 9.31 and median 59 . Preoperative clinical characteristics were similar in both groups ; only previous myocardial infa rct ion was higher in the OPCAB group . Patients with severe left ventricular dysfunction ( FE < /= 35 % ) , renal failure and lesions of the circumflex artery and its branches were excluded , as well as patients with significant comorbidities that were inappropriate for r and omization because we selected them for OPCAB procedures . RESULTS Hospital mortality was 2.5 % , three patients ( 3.7 % ) in group I ( on-pump ) and one patient ( 1.2 % ) in group II ( off-pump ) ( ns ) . The number of grafts per patients in group I was 1.81 + /- 0.6 , and 1.77 + /- 0.68 in group II ( p = 0.833 ) . There was no difference in the total operation time 205.10 + /- 54.30 minutes in group I and 189.50 + /- 55.44 in group II ( ns ) . Six patients ( 7.5 % ) had myocardial infa rct ion in group I and three ( 3.7 % ) in group II ( ns ) . Bleeding in the postoperative period was 680.50 + /- 434.1 mL in the on-pump group and 678.6 + /- 357.0 mL in the off-pump group ( ns ) . Three patients ( 3.7 % ) presented transient neurologic dysfunction in group I and six patients ( 7.5 % ) in group II ( ns ) . Intensive care stay was 2.4 + /- 1.0 days in the CABG and 2.3 + /- 0.98 days in the OPCAB group ( ns ) . CONCLUSIONS We did not find any statistical difference in hospital mortality and morbidity using on-pump or off-pump techniques for low-risk patients Purpose Cardiac surgery performed under cardiopulmonary bypass ( CPB ) causes abnormalities of the renin-angiotensin-aldosterone system , result ing in decreased urine output and an accumulation of water in the third space . We studied the efficacy of continuous low-dose human atrial natriuretic peptide ( hANP ) in patients undergoing thoracic aortic surgery . Methods We divided 40 patients undergoing thoracic aortic surgery into two groups : the hANP group , which received 0.02 μg/kg per minute of hANP and the non-hANP group , which did not . The hemodynamics , urine output , intensive care unit ( ICU ) and hospital stay , bleeding volume , homologous blood transfusion volume , furosemide dose , corrected KCl volume , and postoperative respiratory , hepatic , and renal function were compared in the two groups . Results The urine output during CPB and from CPB weaning to return to ICU was significantly better in the hANP group . The bleeding volume , homologous blood transfusion volume , furosemide dose , and corrected KCl volume were all significantly less in the hANP group . Conclusions These findings support the consensus that hANP exerts its diuretic effects to their full potential when administered continuously at low doses during thoracic aortic surgery . We found it to be effective for postoperative hemostasis and for preventing ischemic reperfusion injury 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 Study Design The present study examined the hypothesis that hypotonic saline therapy before surgery was a major factor in the development of the syndrome of inappropriate antidiuretic hormone secretion . Objectives The influence of fluid therapy and its relationship to the syndrome of inappropriate antidiuretic hormone secretion was studied by measuring patient electrolyte and osmolar responses at given times after surgery . Summary of Background Data Mild renal dysfunction and increased plasma antidiuretic hormone occurs after surgery . Occurrence of the syndrome of inappropriate secretion of antidiuretic hormone after spine surgery is rare . The development of the syndrome of inappropriate secretion hormone after surgery may be related to hypotonic fluid replacement during and after surgery . Methods Twelve patients undergoing surgery for correction of idiopathic scoliosis were assigned r and omly to two groups . The control group ( five patients ) was given isotonic saline , and the trial group ( seven patients ) was given hypotonic saline . Results The trial group developed syndrome of inappropriate antidiuretic hormone secretion with a significant decrease in serum sodium and osmolarity . The control group did not develop syndrome of inappropriate antidiuretic hormone secretion . Conclusions Hypotonic saline therapy predisposes to the development of syndrome of inappropriate antidiuretic hormone secretion , whereas isotonic saline protects patients from syndrome of inappropriate antidiuretic hormone secretion when undergoing surgery for To better underst and the diagnostic and predictive performance of urinary biomarkers of kidney injury , we evaluated γ-glutamyltranspeptidase ( GGT ) , alkaline phosphatase ( AP ) , neutrophil-gelatinase-associated lipocalin ( NGAL ) , cystatin C ( CysC ) , kidney injury molecule-1 ( KIM-1 ) , and interleukin-18 ( IL-18 ) in a prospect i ve observational study of 529 patients in 2 general intensive care units ( ICUs ) . Comparisons were made using the area under the receiver operator characteristic curve ( AUC ) for diagnosis or prediction of acute kidney injury ( AKI ) , dialysis , or death , and reassessed after patient stratification by baseline renal function ( estimated glomerular filtration rate , eGFR ) and time after renal insult . On ICU entry , no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI . Several biomarkers ( NGAL , CysC , and IL-18 ) predicted dialysis ( AUC over 0.7 ) , and all except KIM-1 predicted death at 7 days ( AUC between 0.61 and 0.69 ) . Performance was improved by stratification for eGFR or time or both . With eGFR < 60 ml/min , CysC and KIM-1 had AUCs of 0.69 and 0.73 , respectively , within 6 h of injury , and between 12 and 36 h , CysC ( 0.88 ) , NGAL ( 0.85 ) , and IL-18 ( 0.94 ) had utility . With eGFR > 60 ml/min , GGT ( 0.73 ) , CysC ( 0.68 ) , and NGAL ( 0.68 ) had the highest AUCs within 6 h of injury , and between 6 and 12 h , all AUCs except AP were between 0.68 and 0.78 . Beyond 12 h , NGAL ( 0.71 ) and KIM-1 ( 0.66 ) performed best . Thus , the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI OBJECTIVE A prospect i ve double-blind r and omized study undertaken to assess the effect of postoperative prophylactic " renal-dose " dopamine on post-coronary artery bypass grafting surgery 's clinical outcome . METHODS Eighty-five consecutive patients undergoing CABG operation were r and omized to receive either 3 - 5 microg/kg/min dopamine ( group D , n = 41 ) or saline as placebo ( group P , n = 45 ) for 48 postoperative hours . Clinical outcome parameters were collected for four postoperative days . RESULTS Preoperative and operative parameters were similar in both groups . Four patients from group P and none from group D reached an end-point of the study ( oliguria , renal dysfunction ) and received dopamine . Two patients from group P and none from group D needed an additional inotropic support . Mean arterial pressure values were similar during the first 24 hours after operation , but left atrial pressure values tended to be higher in group P ( 10 + /- 4 vs 7 + /- 3 mmH2O , p = 0.18 ) . The mean pH was higher in group D at 8 hours after operation ( 7.38 + /- 0.2 vs 7.36 + /- 0.3 , p = NS ) , due to higher bicarbonate levels ( 23 + /- 2 mmol/l vs 21 + /- 2 , p = 0.49 ) . The incidence of lung congestion in chest X-rays and CT scans was significantly higher in group P ( 50 % vs 29 % , p = 0.073 at 48 hours postoperatively ) . Room air blood O2 saturation and maximal expiratory volume tended to be higher in group D ( at 72 hours after operation- 92 + /- 4 vs 90%+/- 5 , p = 0.29 and 646 + /- 276 vs 485 ml + /- 206 , p = 0.16 , respectively ) . There was no statistical difference in urine output but the amount of furosemide given to patients in group P was significantly higher ( during the first 8 hours 2.5 + /- 0.5 vs. 0.3 mg + /- 1.6 , p = 0.07 ) . Plasma creatinine levels were significantly lower in group D ( at 24 hours 0.93 + /- 0.02 vs 1.05 mg/dL + /- 0.02 , p = 0.02 ) . Mobilization after surgery was faster in group D. CONCLUSIONS Prophylactic dopamine administration after coronary artery bypass grafting surgery improves patient hemodynamic and renal status , reduces the need for additional medical support ( inotropes and furosemide ) and thus , provides stable postoperative course Forty patients with obstructive jaundice ( bilirubin > 100 μmol/l ) were entered into a r and omized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy . Pre‐operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients ( P < 0.001 ) . Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients ( P < 0.05 ) . There was no significant difference in systemic venous endotoxaemia , renal function or postoperative morbidity or mortality . This study suggests pre‐operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice Fifty-eight patients who were to undergo aortic reconstruction were prospect ively r and omized into two groups to compare the effects of perioperative fluid replacement with isotonic and hypertonic crystalloid solutions . Blood loss was replaced with packed red blood cells , and additional fluid was given as either Ringer 's lactate solution ( RL , 130 mEq sodium/L , 274 mOsm/L ) or a hypertonic balanced salt solution ( HSL , 250 mEq sodium/L , 514 mOsm/L ) . Fluid was administered to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output ( CO ) at or above the preoperative level . The groups were similar with respect to age , preexisting disease , duration of operation , and operative blood loss . During the operation , the RL group required 9.5 + /- 0.8 L of fluid , whereas the HSL group required 4.5 + /- 0.3 L ( P less than 0.001 ) . Pulmonary , cardiac , and renal functions were adequately maintained in both groups . There were no significant differences between the groups with regard to CO , urine output , or creatinine clearance during the operation and early postoperative period . Postoperatively , the intrapulmonary shunt was 20 + /- 1 % in the RL group and it was 16 + /- 1 % in the HSL group ( P less than 0.05 ) . The amount of sodium infused and the cumulative sodium balance at the completion of the study period were similar in both groups . Serum sodium and osmolarity were significantly greater in the HSL group ( P less than 0.001 ) , reaching a maximum of 151 + /- 1 mEq/L and 305 + /- 2 mOsm/L , respectively . Two patients in the HSL group had a persistent elevation in serum osmolarity ( greater than 320 mOsm/L ) during operation , for which they received RL for the balance of the resuscitation . There were no complications that could be attributed to the hypertonicity of the solution . HSL is effective for resuscitation of patients with extracellular fluid deficit and is safe provided that the serum sodium and osmolarity are monitored during periods of large volume administration A prospect i ve study was undertaken to assess postoperative renal dysfunction in patients with obstructive jaundice and to determine the effectiveness of dopamine in reducing its incidence . A total of 23 patients undergoing surgical relief of obstructive jaundice ( serum bilirubin level above 100 μmol l−1 ) were r and omized into two groups . Those in the control group ( n = 10 ) received 3 litres 5 per cent dextrose intravenously during the 24 h before surgery plus a bolus of intravenous frusemide 1 mg kg−1 at induction of anaesthesia . The second group ( n = 13 ) received a similar fluid and frusemide regimen plus an infusion of dopamine 3 μg kg−1 min−1 starting at induction of anaesthesia and continuing for 48 h after surgery . Postoperative oliguria occurred in two of the ten patients in the control group and in three of the 13 given dopamine ( P = 0.74 ) . No patient developed acute renal failure . There was no significant difference in mean levels of serum bilirubin , urea and creatinine , creatinine clearance and 24‐h urinary output , on the day before and on days 1–5 after operation , between the two groups . It is concluded that , with careful preoperative resuscitation and control of fluid and electrolyte balance , the incidence of postoperative renal dysfunction in patients with obstructive jaundice is not as high as in some previous studies and is unaltered by administration of perioperative low‐dose dopamine In this prospect i ve , r and omized , placebo-controlled , double-blinded study , we determined the effects of two commonly used adjuncts , mannitol and dopamine , on & bgr;2-microglobulin ( & bgr;2 M ) excretion rates in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass ( CPB ) . & bgr;2 M excretion rate has been described as a sensitive marker of proximal renal tubular function . One-hundred patients with a preoperative serum creatinine level ≤1.5 mg/dL were prospect ively r and omized into 4 groups : 1 ) placebo , 2 ) mannitol 1 g/kg added to the CPB prime , 3 ) dopamine 2 & mgr;g · kg−1 · min−1 from the induction of anesthesia to 1 h post-CPB , or 4 ) mannitol plus dopamine . The primary outcome measure was & bgr;2 M excretion rate at 1 h post-CPB . Secondary outcome measures included & bgr;2 M excretion rate at 6 and 24 h post-CPB ; urinary flow rate and creatinine clearance at 1 , 6 , and 24 h post-CPB ; and the highest postoperative serum creatinine level . Length of intensive care stay and hospitalization , as well as adverse events , were also considered secondary outcomes . Dopamine significantly increased & bgr;2 M excretion rate at 1 h post-CPB ( 2.48 ± 3.61 & mgr;g/min ) compared with placebo ( 0.59 ± 1.04 & mgr;g/min ; P = 0.001 ) . This effect was not ameliorated by the addition of mannitol ( & bgr;2 M excretion rate , 2.05 ± 2.77 & mgr;g/min ; P = 0.007 compared with placebo ) . & bgr;2 M excretion rate was similar in patients given placebo or mannitol alone ( P = 0.831 ) . Rather than being a protective drug in the setting of CPB , dopamine alone or in combination with mannitol increases & bgr;2 M excretion rate , which may be a measure of renal tubular dysfunction . The clinical implication s of this increase and whether it is also seen in patients with established renal dysfunction undergoing CPB require additional investigation BACKGROUND There are conflicting reports on the effects of diltiazem treatment on renal function in surgical patients . We sought to determine whether diltiazem treatment alters renal function in patients undergoing major thoracic surgery . METHODS In a prospect i ve study , 330 patients scheduled for elective thoracic surgery received either IV diltiazem ( n = 167 ) or placebo ( n = 163 ) immediately after the operation and orally thereafter for 14 days in an effort to prevent postoperative atrial arrhythmias . Serum creatinine and BUN levels were compared before and during the first postoperative week . RESULTS Patients treated with diltiazem were similar to control subjects in terms of age ( mean + /-SD , 66 + /- 10 years vs 67 + /- 10 years , respectively ) , baseline serum creatinine or BUN levels , prevalence of comorbid conditions , and surgical characteristics . During the first 5 postoperative days , the two groups did not differ in terms of serum creatinine or BUN levels . The incidence of renal failure was 0.6 % in the diltiazem group and 1.2 % in the placebo group ( difference was not significant ) . There was no difference in the length of hospitalization or mortality rate . CONCLUSIONS In patients without renal disease who are undergoing elective thoracic surgery , prophylactic diltiazem treatment did not alter postoperative renal function BACKGROUND Emergency abdominal surgery carries a high risk of postoperative morbidity and mortality . Goal directed therapy has been advocated to improve outcome in high-risk surgery . The aim of the present pilot study was to examine the effect of goal directed therapy using fluid alone on postoperative renal function and organ failure score in patients undergoing emergency abdominal surgery . METHODS This prospect i ve r and omised pilot study included patients over the age of 50 undergoing emergency abdominal surgery . In the intervention group pulse pressure variation measurements were used to guide fluid boluses of 6 % Hydroxyethylstarch 130/0.4 . The control group received st and ard care . Serum urea , creatinine and cystatin C levels were measured prior to and at the end of surgery and postoperatively on day 1 , day 3 and day 5 . RESULTS Thirty patients were recruited . One patient died prior to surgery and was excluded from the analysis . The intervention group received a median of 750 ml of hydroxyethylstarch . The peak values of postoperative urea were 6.9 ( 2.7 - 31.8 ) vs. 6.4 (3.5 - 11.5)mmol/l ( p=0.425 ) , creatinine 100 ( 60 - 300 ) vs. 85 ( 65 - 150 ) micromol/l ( p=0.085 ) and cystatin C 1.09 ( 0.66 - 4.94 ) vs. 1.01 (0.33 - 2.29)mg/dl ( p=0.352 ) in the control and intervention group , respectively . CONCLUSIONS In the present pilot study replacing the identified fluid deficit was not associated with a change in renal function . These results do not preclude that goal directed therapy using fluid alone may have an effect on renal function but they would suggest that the effect size of fluid optimisation alone on renal function is small Background / Aims : Depending on the specific definition , acute kidney injury ( AKI ) occurs in 7–40 % of patients undergoing cardiac surgery . Even small changes in serum creatinine ( SCr ) levels are associated with increased mortality after cardiac surgery . However , there are no current methods for preventing AKI after cardiac surgery . Erythropoietin ( EPO ) has been shown to elicit tissue-protective effects in various experimental models . In this pilot trial , we evaluated the effectiveness of EPO in the prevention of AKI after coronary artery bypass grafting ( CABG ) . Methods : 71 patients scheduled for elective CABG r and omly received either 300 U/kg of EPO or saline intravenously before surgery . AKI was defined as a 50 % increase in SCr levels over baseline within the first 5 postoperative days . Estimated glomerular filtration rate ( eGFR ) was calculated from the Cockcroft-Gault equation . Results : Of 71 patients , 13 developed postoperative AKI : 3 of the 36 patients in the EPO group ( 8 % ) and 10 of the 35 patients in the placebo group ( 29 % ; p = 0.035 ) . The increase in postoperative SCr concentration and the decline in postoperative eGFR were significantly lower in the EPO group than in the placebo group . Conclusions : In our small , pilot trial , prophylactic administration of EPO prevents AKI and improves postoperative renal function . These data are preliminary and require confirmation in a larger clinical trial We studied 22 patients undergoing aortic surgery , allocated r and omly to receive , before induction of anaesthesia , a single i.v . dose of enalapril 50 micrograms kg-1 or saline . During infrarenal aortic cross-clamping , we observed similar reductions in oxygen uptake in the two groups , despite greater systemic oxygen delivery in enalapril-treated patients ; angiotensin-converting enzyme inhibition prevented the reduction in cardiac output and attenuated the decrease in glomerular filtration . Changes in glomerular filtration secondary to aortic clamping were related positively to changes in renal plasma flow ( r = 0.83 ( saline group ) and r = 0.65 ( enalapril group ) ) . Creatinine clearance on the first day after operation was significantly higher in the enalapril compared with the saline group . We conclude that enalapril pretreatment is effective in improving systemic oxygen delivery , renal plasma flow and glomerular filtration during aortic abdominal surgery We prospect ively studied perioperative changes of renal function in 12 previously normal patients ( plasma creatinine < 1.5 mg/dL ) scheduled for elective coronary surgery . Glomerular filtration rate ( GFR ) and effective renal plasma flow ( ERPF ) were measured with inulin and 125 I-hippuran clearances before induction of anesthesia , before cardiopulmonary bypass ( CPB ) , during hypo- and normothermic CPB , after sternal closure , and 1 h postoperatively . Renal and systemic vascular resistances were calculated . Urinary N-acetyl-beta-D-glucosaminidase ( NAG ) and plasma and urine electrolytes were measured , and free water , osmolal , and creatinine clearances , and fractional excretion of sodium and potassium were calculated before and after surgery.125 I-hippuran clearance was lower than normal in all patients before surgery . During hypothermic CPB , ERPF increased significantly ( from 261 + /- 107 to 413 + /- 261 mL/min ) and returned toward baseline values during normothermia . GFR was normal before and after surgery and decreased nonsignificantly during CPB . Filtration fraction was above normal before surgery and decreased significantly during CPB ( 0.38 + /- 0.09 to 0.18 + /- 0.06 ) . Renal vascular resistance ( RVR ) was high before surgery and further increased after sternotomy ( from 18,086 + /- 6849 to 30,070 + /- 24,427 dynes centered dot s centered dot cm-5 ) , decreasing during CPB to 13,9647 + /- 14,662 dynes centered dot s centered dot cm-5 . Urine NAG , creatinine , and free water clearances were normal in all patients both pre- and postoperatively . Osmolal clearance and fractional excretion of sodium increased postoperatively from 1.54 + /- 0.06 to 12.47 + /- 11.37 mL/min , and from 0.44 + /- 0.3 to 6.07 + /- 6.27 , respectively . We conclude that renal function does not seem to be adversely affected by CPB . Significant functional alterations , such as decreased ERPF and increased RVR , were found before and during surgery , preceding CPB . These periods could contribute to postoperative renal dysfunction . ( Anesth Analg 1995;81:446 - 51 Thirty-five male patients undergoing coronary artery surgery were studied to investigate renal function during a continuous infusion of the calcium channel blocker diltiazem . All patients had preoperative renal function within normal limits ( serum creatinine below 0.133 mmol/L ) and were r and omly divided into three groups : Control ( C ) , Diltiazem 1 ( D1 ) , and Diltiazem 2 ( D2 ) . Diltiazem was infused in D1 ( 1 microgram/kg/min ) and D2 ( 2 micrograms/kg/min ) patients throughout surgery and during the following 36 hours . Glomerular function was investigated using the endogenous creatinine clearance while tubular function was assessed by means of water and sodium reabsorption tests , as well as urinary enzyme activity measurements . Hemodynamic monitoring was performed using a pulmonary artery catheter . The glomerular filtration rate of C and D1 patients showed a significant fall during cardiopulmonary bypass ( CPB ) with respect to the prebypass period and returned to the baseline values only in the postoperative period . A similar change was not observed in D2 patients . The analysis of variance demonstrated that the glomerular filtration rate was significantly higher in Group D2 versus Group C during and after CPB ( P = 0.03 and P = 0.04 , respectively ) . Furthermore , after CPB , urinary output was significantly improved in D2 patients , both versus C and D1 patients ( P = 0.003 ) , notwithst and ing a lower mean arterial pressure in the D2 Group ( P = 0.04 v C Group ) . Tubular function was not influenced by diltiazem infusion . It is concluded that a continuous diltiazem infusion , at a dose of 2 micrograms/kg/min during cardiac surgery , may be useful to prevent a decrease in glomerular function secondary to cardiopulmonary bypass Objective : To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients . Design : Double-blind , r and omized controlled trial . Setting : Operating rooms and intensive care unit at a tertiary hospital . Patients : Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction . Intervention : Patients were r and omized to either 24 hrs of intravenous infusion of sodium bicarbonate ( 4 mmol/kg ) or sodium chloride ( 4 mmol/kg ) . Measurements and Main Results : The primary outcome measure was the proportion of patients developing acute renal dysfunction defined as a postoperative increase in plasma creatinine concentration > 25 % of baseline within the first five postoperative days . Secondary outcomes included changes in plasma creatinine , plasma urea , urinary neutrophil gelatinase-associated lipocalin , and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio . Patients were well balanced for baseline characteristics . Sodium bicarbonate infusion increased plasma bicarbonate concentration ( p < 0.001 ) , base excess ( p < 0.001 ) , plasma pH ( p < 0.001 ) , and urine pH ( p < 0.001 ) . Fewer patients in the sodium bicarbonate group ( 16 of 50 ) developed a postoperative increase in serum creatinine compared with control ( 26 of 50 ) ( odds ratio 0.43 [ 95 % confidence interval 0.19–0.98 ] ) , ( p = 0.043 ) . The increase in plasma creatinine , plasma urea , urinary neutrophil gelatinase-associated lipocalin , and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio was less in patients receiving sodium bicarbonate , ( p = 0.014 ; p = 0.047 ; p = 0.009 ; p = 0.004 ) . There were no significant side effects . Conclusions : Sodium bicarbonate loading and continuous infusion was associated with a lower incidence of acute renal dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass . The findings of this pilot study justify further investigation . ( Clinical Trials.gov , NCT00334191 ) Mannitol is often included in the priming solution of the heart-lung machine used during cardiopulmonary bypass ( CPB ) . This study was set up to evaluate the effect of different doses of mannitol on human patients . Patients receiving 10 g of mannitol ( n = 18 ) had an increased diuresis only during the bypass period ( mean time = 87 min ) when compared with a control group ( n = 19 ) who did not receive mannitol . Patients receiving 20 g of mannitol ( n = 19 ) had a significantly greater diuresis than both the control group and the 10 g group and the diuresis continued on throughout the immediate postbypass period ( total mean time approximately 3 h ) . Patients receiving 30 g of mannitol ( n = 20 ) also had a significantly greater diuresis that continued on during the first hour in the intensive care unit ( ICU ) ( total mean time approximately 4 h ) . After 6 h in the ICU , all three groups of mannitol-treated patients equally demonstrated a trend towards an increased diuresis over the control group , which became a significant increase by 12 h in the ICU ( p = 0.001 ) despite indications that the mannitol had been cleared from the body . These results suggest that there is an improvement of renal function post-CPB if mannitol is included in the CPB prime which may be due to an amelioration of the ischaemic effects of bypass on the kidneys STUDY OBJECTIVE Acute renal failure , which is a serious complication following open heart surgery , has a high mortality rate . Previous reports have shown that the calcium antagonist diltiazem is beneficial either as an adjunct to cardioplegic solution or perioperative treatment for preservation of postoperative cardiovascular function . We studied the effects of diltiazem on renal function , plasma atrial natriuretic peptide levels , and the renin-angiotensin-aldosterone system in patients who had undergone coronary artery bypass grafting . PATIENTS AND MEASUREMENTS Diltiazem was administered , 0.1 mg/kg , in a bolus injection followed by continuous infusion at a rate of 2 micrograms/kg/min during surgery , and 30 mg through a nasogastric tube at every 8 h. Hemodynamics , renal function , and plasma hormone levels were measured in the diltiazem-treated group ( n = 13 ) and the nontreated group ( n = 10 ) . RESULTS Heart rate , mean arterial pressure , and systemic vascular resistance index in the diltiazem-treated group were significantly lower than those in the nontreated group following cardiopulmonary bypass . Urine volume , creatinine clearance , and free water clearance were well preserved in the diltiazem-treated group . However , plasma renin activity and aldosterone levels were significantly higher in the diltiazem-treated group with the same changes in plasma atrial natriuretic peptide levels . CONCLUSION Perioperative treatment with diltiazem has a beneficial effect on postoperative renal function , and reflex sympathetic activation induced by peripheral vasodilation activated the renin-angiotensin-aldosterone system OBJECTIVE Dopexamine hydrochloride is a novel synthetic adrenergic agonist that combines the renal effects of dopamine with the hemodynamic effects of dobutatmine . Our study is design ed to compare the hemodynamic , diuretic , and natriuretic effects of dopexamine and dobutamine in patients with reduced cardiac index following heart surgery . DESIGN Prospect ively r and omized , blinded study . SETTING Operating room and intensive care unit of a large , urban , academic medical center . PATIENTS Twenty-eight patients undergoing elective coronary artery bypass grafting ( CABG ) with preoperative ejection fraction of at least 40 percent gave informed consent . The study group consisted of the ten patients who had a cardiac index < or = 2.5 L/min/m2 ( while receiving no inotropic medication ) immediately after separation from cardiopulmonary bypass . INTERVENTIONS AND MEASUREMENTS Study patients were r and omly given a starting dose of either 5 micrograms/kg/min of dobutamine ( n = 5 ) or 2 micrograms/kg/min of dopexamine ( n = 5 ) . During the initial 30 min following separation from bypass , dosages were titrated incrementally to maintain cardiac index > or = 3.0/L/min/m2 . Further titrations of the drug were done only if cardiac index fell below 3.0 L/min/m2 or if sustained tachycardia occurred during the 24-h study period . Data were collected at 5- and 10-min intervals for the first 30 min after separation from bypass , hourly for the next 8 h , then every 2 h for the remainder of the study period . RESULTS Both drugs increased cardiac index by more than 50 percent over baseline ( dobutamine 2.2 + /- 0.1 to 3.5 + /- 0.2 [ p < 0.05 ] ; dopexamine , 2.3 + /- 0.1 to 3.5 + /- 0.1 [ p < 0.05 ] L/min/m2 ) . The mean dose required to maintain cardiac index > or = 3.0L/min/m2 was 1.5 micrograms/kg/min for dopexamine and 3.5 micrograms/kg/min for dobutamine . There were no significant differences in either urinary output or net sodium excretion in the dopexamine group compared with the dobutamine group , and tachycardia ( heart rate > 120 beats/min ) was more common in the dopexamine group . CONCLUSIONS Our study demonstrates that dopexamine produces hemodynamic , diuretic , and natriuretic effects similar to dobutamine in patients with reduced cardiac index following CABG OBJECTIVE Acute renal failure complicating open heart surgery is not uncommon . Dopamine infusion ( 2.5 - 4.0 microg/kg per min ) has often been advocated for prophylactic ' renal protection ' in this setting despite little objective evidence of real benefit . We aim ed to investigate whether dopamine offers any ' renal protection ' in patients with normal heart and kidney functions undergoing routine coronary artery bypass grafting ( CABG ) . Urinary excretion of retinol-binding protein ( RBP ) , previously vali date d as a sensitive and accurate marker of early renal tubular injury , was used to assess the renal effects of dopamine during the first postoperative week . METHODS Forty consecutive patients from the elective waiting list were prospect ively r and omized into two equal groups : those in Group A received dopamine infusion at ' renal dose ' ( 2.5 - 4.0 microg/kg per min ) starting from induction of anaesthesia for 48 h , whereas those in Group B served as untreated controls . Daily measurements were made of weight-adjusted urine output ( ml/kg ) , fluid balance ( input/output ) , serum creatinine , blood urea and urinary RBP . Statistical comparisons were made using Mann-Whitney U-test . RESULTS The two groups matched in terms of age , time and temperature on cardiopulmonary bypass , number of grafts performed and perioperative haemodynamic status . No differences were detected in the weight-adjusted urine output , fluid balance , serum creatinine and blood urea between the groups . Control subjects ( Group B ) showed an increase in urinary RBP during the first and second postoperative days ( 323+/-4 microg/ mmolCr and 50+/-3 microg/mmolCr ; mean+/-SD ) . However , patients treated with dopamine ( Group A ) demonstrated much greater urinary excretion of RBP over the same period ( 1257+/-15 microg/mmolCr and 449+/-21 microg/mmolCr ; P = 0.0006 and 0.03 ) than those in Group B. CONCLUSIONS Dopamine given at ' renal-dose ' appears to offer no renal protection in patients with normal heart and kidney functions undergoing elective coronary surgery . On the contrary , it exacerbates the severity of renal tubular injury during the early postoperative period . Based on these findings we do not recommend the use of dopamine for routine renal prophylaxis in this group of patients BACKGROUND / AIMS The effectiveness of dopamine alone or in combination with mannitol or furosemide in preventing postoperative renal dysfunction in patients with obstructive jaundice was assessed in this study . METHODOLOGY Forty patients having obstructive jaundice were r and omly allocated into 4 equal groups . Preoperative hydration was performed by infusing all patients 1L of 5 % dextrose the night before surgery and another 1L in the morning before surgery . Intra- and postoperative maintenance of adequate intravascular volume was assured by fluid and blood replacement guided by the monitoring of central venous pressure urine output and blood pressure . The 1st group was kept as a control . The other 3 groups received dopamine 2.5 micrograms/kg/min for 2 postoperative days starting before surgery . The 2nd group was maintained on dopamine alone , while mannitol ( 0.25 g/kg ) , every 12 hours for 2 postoperative days , was added to the 3rd group . Similarly furosemide ( 1 mg/kg ) every 12 hours for 2 postoperative days , was infused to the patients of the 4th group . Postoperative renal functions were assessed by 24-hour urine output , serum creatinine , creatinine clearance and urine to plasma osmolality ratio . RESULTS All these tests did not show significant changes in the 1st , 2nd and 7th postoperative days . Only transient decreased creatinine clearance and elevated serum creatinine were observed in the patients of the 4th group in the 1st and 2nd postoperative days . This may be attributed to fluid imbalance induced by furosemide in these patients who were older than the other groups . CONCLUSIONS The study showed that careful attention to perioperative hydration is the cornerstone in preserving adequate renal function following surgery in patients with obstructive jaundice . Administration of dopamine alone or in combination with mannitol or furosemide did not confer more renal protection Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction , the mechanism of which remains under debate . To assess the renal effect of two potent renal vasodilators ( enalapril , a converting enzyme inhibitor , and nicardipine , a calcium antagonist ) , 24 patients scheduled for reconstructive aortic surgery were r and omly allocated to one of three treatment groups ( n = 8 each ) and received either a placebo , nicardipine , or enalapril . Anesthesia consisted of flunitrazepam , fentanyl , pancuronium , and , occasionally , droperidol . Although aortic cross-clamping was associated with no change in mean arterial blood pressure , decreased cardiac output and increased systemic vascular resistance occurred in control patients ( 33 % and 43 % , respectively , both P less than 0.05 versus baseline ) and nicardipine-treated patients ( 51.7 % and 67.7 % , respectively , both P less than 0.05 versus baseline ) ; however , changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients . Glomerular filtration rate ( technetium 99-diethylenetriaminepentacetic acid clearance ) and effective renal plasma flow ( iodo-Hippuran 131 clearance ) decreased for the duration of aortic cross-clamping in control patients ( 42.9 % and 18.5 % , respectively , both P less than 0.05 versus baseline ) and enalapril-treated patients ( 34.0 % and 38.1 % , respectively , both P less than 0.05 versus baseline ) , but no change was observed in nicardipine-treated patients . These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping . In contrast , renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine , which probably acts at the level of the preglomerular resistance vessels Background and objective Coronary artery bypass graft surgery in high-risk patients may be associated with postoperative renal dysfunction . N-Acetylcysteine is a powerful antioxidant and has been used to prevent contrast-induced renal dysfunction . The efficacy of N-acetylcysteine in preventing postoperative renal dysfunction following off-pump coronary artery bypass graft surgery was studied . Methods A prospect i ve , r and omized , controlled study was conducted in patients undergoing off-pump coronary artery bypass graft . The study group ( 37 patients ) received N-acetylcysteine in the perioperative period , whereas the control group ( 37 patients ) did not . The data obtained were analysed using the independent sample t-test ( Student 's t-test ) and χ2-test . Results There was no significant difference in the incidence of renal dysfunction between the two groups . Three patients ( 8.6 % ) in the N-acetylcysteine group and four ( 11.4 % ) in the control group developed renal dysfunction ( P value was 1.00 ) . Conclusion N-Acetylcysteine does not have any beneficial effect on renal function in high-risk patients undergoing off-pump coronary artery bypass graft |
10,949 | 29,845,595 | Based on very low quality evidence , primary whole gl and cryotherapy has uncertain effects on oncologic outcomes , QoL , and major adverse events compared to external beam radiotherapy . | BACKGROUND Traditionally , radical prostatectomy and radiotherapy with or without and rogen deprivation therapy have been the main treatment options to attempt to cure men with localised or locally advanced prostate cancer .
Cryotherapy is an alternative option for treatment of prostate cancer that involves freezing of the whole prostate ( whole gl and therapy ) or only the cancer ( focal therapy ) , but it is unclear how effective this is in comparison to other treatments .
OBJECTIVES To assess the effects of cryotherapy ( whole gl and or focal ) compared with other interventions for primary treatment of clinical ly localised ( cT1-T2 ) or locally-advanced ( cT3 ) non-metastatic prostate cancer . | BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) Purpose : We evaluated focal therapy with high intensity focused ultrasound hemiablation in a prospect i ve trial . Material s and Methods : We performed a prospect i ve , multicenter , single arm study in patients with unilateral low/intermediate risk prostate cancer who were treated from April 2013 through March 2016 in Germany in AUO ( Arbeitsgemeinschaft Urologische Onkologie ) Study Protocol AP 68/11 . Unilateral prostate cancer was assessed by transrectal ultrasound guided biopsy and multiparametric magnetic resonance imaging . Hemiablation was done using the Ablatherm ® or the Focal One ® device . The oncologic outcome was assessed by the salvage treatment rate , multiparametric magnetic resonance imaging and rebiopsy at 12 months . Functional outcome , quality of life , anxiety and depression were measured by vali date d question naires at baseline and every 3 months . Results : Of the 54 recruited patients 51 completed 12‐month or greater visits . Mean ± SD followup was 17.4 ± 4.5 months . Mean prostate specific antigen decreased from 6.2 ± 2.0 to 2.9 ± 1.9 ng/ml at 12 months ( p < 0.001 ) . Biopsy at 12 months was positive for any prostate cancer and for clinical ly significant prostate cancer in 13 ( 26.5 % ) and 4 ( 8.2 % ) of the 49 patients , respectively . Posttreatment multiparametric magnetic resonance imaging had limited 25 % sensitivity for clinical ly significant prostate cancer . Ten patients ( 19.6 % ) underwent salvage treatment . Potency was maintained in 21 of the 30 men who were potent preoperatively . There was no increase in incontinence . Quality of life , anxiety and depression did not change postoperatively . The study was limited by a short followup and the lack of a control arm . Conclusions : Focal therapy hemiablation is safe with little alteration of functional outcome . The oncologic outcome is acceptable on short‐term followup . Followup multiparametric magnetic resonance imaging performed poorly and should not replace repeat biopsy . Focal therapy has no impact on posttreatment anxiety and depression PURPOSE Cryosurgical ablation of the prostate is a novel therapeutic modality that induces cell lysis in the prostate by direct application of low temperatures . We have been conducting an ongoing prospect i ve pilot study of the use of cryosurgical prostate ablation in treating patients with nonmetastatic prostate adenocarcinoma since January 1993 . Results in 145 consecutive patients with mean 36 months and minimum 12 months of followup are presented . MATERIAL S AND METHODS Accrual was open to patients with clinical stages T1a to T3c prostate adenocarcinoma . Pelvic lymph node dissections were recommended but not required for patients with prostate specific antigen ( PSA ) greater than 15 ng./ml . before study entry . PSA changes , r and om prostate biopsy findings and morbidities after cryosurgical prostate ablation were recorded for each patient . RESULTS Overall actuarial rates at 42 months for maintaining PSA less than 0.3 and less than 1.0 were 59 % and 66 % , respectively . The overall actuarial progression-free rate at 60 months was 56 % . Among 160 biopsies performed 16 % showed some evidence of residual carcinoma . Overall crude rates of maintaining either a negative biopsy or PSA less than 0.3 at 6 and 24 months after cryosurgical prostate ablation were 87 % and 73 % , respectively . Significantly higher morbidities were seen in previously radiated patients undergoing cryosurgical prostate ablation compared to those with no prior radiation . Among nonradiated patients 85 % experienced no significant morbidity after cryosurgical prostate ablation . CONCLUSIONS Although preliminary , short-term outcomes after cryosurgical prostate ablation appear to be comparable to identical outcomes reported for external beam radiotherapy . Based on these results cryosurgical prostate ablation appears to be an effective therapeutic alternative for treating patients with localized prostate adenocarcinoma Introduction Focal therapy offers the possibility of cancer control , without the side effect profile of radical therapies . Early single centre prospect i ve development studies using high intensity focused ultrasound ( HIFU ) have demonstrated encouraging genitourinary functional preservation and short-term cancer control . Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery . We describe the study design of an investigator-led UK multi-centre , single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer . Methods One-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer ( PSA < 15 , Gleason ≤ 7 , ≤ T2cN0M0 ) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping ( TPM ) biopsies . Unilateral dominant tumours , the so-called index lesion , will be eligible for treatment provided the contra-lateral side is free of ‘ clinical ly significant ’ disease ( as defined by Gleason ≥ 7 or maximum cancer core length ≥ 4 mm ) . Patients will receive focal therapy using HIFU ( Sonablate 500 ® ) . Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months . Results Primary outcome is the absence of clinical ly significant disease based on 36-month post-treatment TPM biopsies . Secondary outcomes address a ) genitourinary function using vali date d patient question naires ( IPSS , IPSS-QoL , IIEF-15 , EPIC-Urinary , EPIC-Bowel , FACT-P , EQ-5D ) , b ) the predictive validity of imaging , and c ) risk factors for treatment failure . Conclusions INDEX will be the first multi-centre , medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer using the TPM-ablate-TPM strategy Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies OBJECTIVE To determine the minimal important difference ( MID ) in generic and prostate-specific health-related quality of life ( HRQoL ) using distribution- and anchor-based methods . STUDY DESIGN AND SETTING Prospect i ve cohort study of 602 newly diagnosed prostate cancer patients recruited from an urban academic hospital and a Veterans Administration hospital . Participants completed generic ( SF-36 ) and prostate-specific HRQoL surveys at baseline and at 3 , 6 , 12 , and 24 months posttreatment . Anchor-based and distribution-based methods were used to develop MID estimates . We compared the proportion of participants returning to baseline based on MID estimates from the two methods . RESULTS MID estimates derived from combining distribution- and anchor-based methods for the SF-36 subscales are physical function = 7 , role physical = 14 , role emotional = 12 , vitality = 9 , mental health = 6 , social function = 9 , bodily pain = 9 , and general health = 8 ; and for the prostate-specific scales are urinary function = 8 , bowel function = 7 , sexual function = 8 , urinary bother = 9 , bowel bother = 8 , and sexual bother = 11 . Proportions of participants returning to baseline values corresponding to MID estimates from the two methods were comparable . CONCLUSIONS This is the first study to assess the MID for generic and prostate-specific HRQoL using anchor-based and distribution-based methods . Although variation exists in the MID estimates derived from these two methods , the recovery patterns corresponding to these estimates were comparable A recent r and omized trial to compare external beam radiation therapy ( EBRT ) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival . We report on the quality of life ( QOL ) outcomes for this trial PURPOSE Patients currently diagnosed with low risk prostate cancer are often overtreated and experience complications , result ing in detriment to quality of life . Targeted focal therapy is a minimally invasive procedure design ed to ablate tumor foci while minimizing collateral damage to maintain quality of life . MATERIAL S AND METHODS This institutional review board approved , prospect i ve study was done to assess the safety and efficacy of targeted focal therapy using cryotherapy in men 40 to 85 years old diagnosed with low risk , organ confined prostate cancer at our institution between 2006 and 2009 . Low risk , organ confined prostate cancer was defined as Gleason score 7 or less ( 3 + 4 ) on transrectal ultrasound biopsy , tumor burden 50 % or less and prostate specific antigen less than 10 ng/dl . Patients were evaluated for eligibility after undergoing 3-dimensional mapping biopsy . Median followup was 28 months ( IQR 26 - 31 ) . RESULTS A total of 62 men with low risk disease met study inclusion criteria . At 1 year biopsy was negative in 50 of 62 patients ( 81 % ) . All 12 men who tested positive on repeat biopsy had a Gleason score of 3 + 3 = 6 with 1 or 2 positive cores . The median prostate specific antigen change was a 3.0 ng/dl decrease ( p < 0.01 ) . The median American Urological Association symptom score change was a 1.5-point decrease ( p < 0.01 ) . No significant change was observed in Sexual Health Inventory for Men score ( p = 0.6 ) . No urinary incontinence episodes and no severe side effects were noted . CONCLUSIONS Targeted focal therapy in carefully selected patients provides a feasible , practical option for treating low risk prostate cancer with minimal impact on quality of life PURPOSE We examined the role of percutaneous cryoablation of the prostate in the treatment of prostate cancer . MATERIAL S AND METHODS We performed 95 percutaneous cryoablations of the prostate on 87 patients with prostate cancer . Of the patients 6 had positive lymph nodes preoperatively , radiation failed in 9 and 9 began postoperative hormonal therapy because of treatment failure . Mean patient age , prostate specific antigen ( PSA ) level ( ng./ml . ) and Gleason score were 65.4 , 12.60 and 6.03 , respectively . Median followup was 12 months ( mean 9.3 , range 1 to 24 ) . In 49 of the 87 patients ( 56 % ) the lymph nodes were evaluated before cryoablation based on the treatment protocol . RESULTS Median PSA level at 12 months was 0.55 ng./ml . ( mean 1.73 ) with a 17 % positive biopsy rate at 3 months . When the positive lymph node , radiation failure and postoperative hormonal therapy groups were removed from analysis , the median PSA level was 0.80 ng./ml . ( mean 1.86 ) with a 5 % positive biopsy rate . Of the patients in the radiation failure group 37 % had a positive biopsy at 3 months . Cases were classified according to stage , grade and PSA level , and the biopsy results were presented . The complications of percutaneous cryoablation of the prostate were review ed . CONCLUSIONS The low percentage of positive biopsies is encouraging but the significance of the persistent PSA levels remains uncertain 78 Background : Our primary objective is to assess and compare the survival outcomes between cryoablation ( CRYO ) and external beam radiation therapy ( EBRT ) in locally advanced prostate cancer . METHODS This is a single institution , retrospective study . Our institution ethics board had approved this study . Patients were initially recruited for the trial between 1999 and 2002 . The inclusion criteria for the trial were patients with cT2c-cT3b prostate cancer , PSA < 25ng/ml , with negative metastatic evaluation on CT and bone scan . Patients with evidence of metastasis , prior pelvic radiotherapy or hormone therapy , prostate volume > 75 ml or American Society of Anesthesiology Risk class > 3 were excluded . The biochemical failure was based on the Phoenix criteria ( PSA nadir + 2ng/dl ) . Patients were subjected for regular trans-rectal ultrasound and biopsy until 24 months of follow-up ( at 3 , 6 , 12 , 18 , 24 months for CRYO and at 18 , 24 months for EBRT ) and then as clinical ly indicated . Biochemical disease-free survival ( bDFS ) , disease-specific survival ( DSS ) and overall survival ( OS ) were analyzed with Kaplan-Meier curve . RESULTS Sixty-two patients completed the trial with a median follow-up of 105.2 ( ± 35.8 ) months . Preoperative demographic and clinicopathological characteristics of both groups were comparable . All patients received neoadjuvant hormonal therapy for 3 months prior and continued for 3 months after the procedures . The prostate volume before the therapy was smaller in the CRYO group ( 31.3 ml vs 40.9 ml ; p≤0.01 ) . There was greater reduction in the prostate volume in the CRYO group after the intervention ( -54 % vs 34 % ; p≤0.01).Three patients in the cryotherapy arm and 2 patients in the radiotherapy arm were crossed over to the other modality at the time of biochemical or biopsy proven progression . The DSS and the OS were comparable between both groups . The 8-year bDFS rate was significant lower in the CRYO group ( 17.4 % vs 59.1 % ; p=0.01 ) . CONCLUSIONS This r and omized trial showed that CRYO was suboptimal in attaining bDFS at 8 years in patients with locally advanced prostate cancer ( cT3 ) . Other recent r and omized trial showed favorable outcome with CRYO for localized prostate cancer . No significant financial relationships to disclose OBJECTIVES Percutaneous cryosurgical ablation of the prostate ( CSAP ) was performed on patients with localized or locally advanced adenocarcinoma of the prostate . To assess local disease control , post-treatment biopsy and serum prostate-specific antigen ( PSA ) levels were obtained at 3 and 24 months post-treatment . METHODS From June 1990 through May 1994 , CSAP was performed 448 times on 383 patients under Institutional Review Board protocol s. A urethral warming catheter was used for all procedures . A total of 239 patients were followed for a minimum of 21 months after treatment . None of this group had received prior local treatment . The group consisted of patients who were newly diagnosed and treated solely with cryotherapy ( virgin ) ; the remainder had been on and rogen deprivation therapy ( ADT ) prior to CSAP . RESULTS Biopsies were obtained from 114 patients at 21 months or more after treatment . In the virgin group , 79 % had a negative biopsy after one or more treatments , and 88 % of the ADT group are negative after one or more treatments . Overall , 69 % had a negative biopsy after one treatment and 82 % had a negative biopsy following one or more CSAP treatments . Of a group of 163 patients , PSA data were evaluable at 21 months or more after treatment . In the virgin group , 60 % had a PSA 0.4 ng/mL or less , and 77 % had a PSA 1.0 ng/mL or less . In the ADT group , 40 % had a PSA 0.4 ng/mL or less , and 69 % had a PSA value of 1.0 ng/m Lor less . Complications were minimal , the most common one being urethral tissue sloughing , which occurred in 10 % of patients . CONCLUSIONS CSAP appears to be effective in obtaining local control as measured by biopsy and PSA 21 months or more post-treatment . When retrospectively comparing our results with recently published radiotherapy series , CSAP was more effective in obtaining nadir PSA values 1.0 ng/mL or less and negative biopsies at 21 months or more after treatment OBJECTIVE To study the complications and oncological outcome after cryosurgical ablation of the prostate ( CSAP ) . METHODS Fifty-four patients with prostate cancer were entered into this prospect i ve phase II trial of CSAP . Patients were followed with serum PSA determinations , follow-up biopsies at 3 - 6 months postoperatively and a question naire to assess complications . A PSA of > 1 ng/ml or a positive biopsy was interpreted as progression . RESULTS Mean follow-up was 58.5 months . Patients needed a suprapubic catheter postoperatively for in mean 18 days . Transient penile numbness occurred in 15 % . Bothersome sloughing of dead tissue was noticed by 15 % of patients and 15 % needed a transurethral resection . Nine patients ( 17 % ) developed strictures and five patients stone formation in the prostatic urethra . One patient developed a perennial fistula . Thirty-nine out of 43 patients reporting on potency become impotent , nine patients developed a slight stress incontinence and one severe incontinence . At median follow-up , the actuarial progression-free survival was 38.9 % . Fourteen out of 50 patients biopsied ( 28 % ) had remaining cancer in their prostates . CONCLUSION High complication rates in combination with poor oncological outcome has made us stop using this treatment modality Localized prostate cancer can be treated several different ways , but head‐to‐head comparisons of treatments are infrequent . The authors of this report conducted a r and omized , unblinded , noninferiority trial to compare cryoablation with external beam radiotherapy in these patients The objective was to evaluate the relative efficacy of cryoablation ( CRYO ) versus external beam radiation ( EBRT ) for clinical ly locally advanced prostate cancer in a r and omized clinical trial . Patients with histologically proven , clinical ly staged as T2C , T3A or T3B disease were r and omized with 6 months of perioperative hormone therapy to one of the two procedures . Owing largely to a shift in practice to longer term adjuvant hormonal therapy and higher doses of radiation for T3 disease , only 64 out of the planned 150 patients were accrued . Twenty-one of 33 ( 64 % ) in the CRYO group and 14 of 31 ( 45 % ) in the EBRT-treated group who had met the ASTRO definition of failure were also classified as treatment failure . The mean biochemical disease-free survival ( bDFS ) was 41 months for the EBRT group compared to 28 months for the CRYO group . The 4-year bDFS for EBRT and CRYO groups were 47 and 13 % , respectively . Disease-specific survival ( DSS ) and overall survival ( OS ) for both groups were very similar . Serious complications were uncommon in either group . EBRT patients exhibited gastrointestinal ( GI ) adverse effects more frequently . Taking into account the relative deficiency in numbers and the original trial design , this prospect i ve r and omized trial indicated that the results of CRYO were less favorable compared to those of EBRT , and was suboptimal primary therapy in locally advanced prostate cancer PURPOSE We assessed and compared the survival outcomes between cryoablation and external beam radiation therapy in patients with locally advanced prostate cancer ( cT2c-cT3b ) . MATERIAL S AND METHODS Patients with locally advanced prostate cancer , recruited from 1999 to 2002 , were r and omized to primary cryoablation or external beam radiotherapy . All patients received neoadjuvant hormonal therapy for 3 months before and 3 months after the procedures . Patients underwent followup transrectal ultrasound guided biopsy ( at 3 , 6 , 12 , 18 and 24 months for cryoablation , and at 18 and 24 months for external beam radiotherapy ) and as clinical ly indicated thereafter . Biochemical failure was based on the Phoenix criterion ( prostate specific antigen nadir + 2 ng/dl ) . RESULTS A total of 62 patients completed the trial . Median followup was 105.2 months ( SD ±35.8 ) . Accrual was limited due to newer data favoring longer neoadjuvant hormonal therapy and higher external beam radiotherapy dose for locally advanced prostate cancer . There was a greater reduction in prostate volume in the cryoablation group after intervention ( -54 % vs -34 % , p ≤0.01 ) . Disease specific survival and overall survival were comparable between the groups . However , the 8-year biochemical disease-free survival rate was significantly lower in the cryoablation group ( 17.4 % vs 59.1 % ) ( p = 0.01 ) . CONCLUSIONS This r and omized trial with median followup approaching 9 years showed that cryoablation was inferior in attaining biochemical disease-free survival in patients with locally advanced prostate cancer ( cT2c-T3 ) . Cryoablation may be more suited for less bulky prostate cancer . Longer duration neoadjuvant hormonal therapy or a multimodal approach may provide optimal biochemical disease-free survival in this patient population OBJECTIVES To determine in a prospect i ve pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma . METHODS A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998 . All patients had histologically proved adenocarcinoma of the prostate , with prostate-specific antigen ( PSA ) readings of less than 30 ng/mL. Clinical evaluations , PSA determinations , and patient self-reported quality -of-life question naires ( functional assessment of cancer treatment-prostate ; FACT-P ) were used to determine biochemical and clinical disease-free status and complications . Patients had a mean follow-up of 50 months ( minimum 36 ) . RESULTS Follow-up biopsies were performed in 73 patients , and 72 were negative for malignancy after one or more treatments . Ten patients required two treatments and 1 patient required three treatments . The 5-year overall and cancer-specific survival rate was 89 % ( 95 % confidence interval , 83 % to 97 % ) and 98.6 % ( 95 % confidence interval , 96 % to 100 % ) , respectively . The undetectable PSA rate ( less than 0.3 ng/mL ) for low-risk patients ( n = 13 ) was 60 % at 5 years ; for moderate-risk patients ( n = 23 ) , it was 77 % , and for high-risk patients ( n = 40 ) , 48 % . The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75 % , 89 % , and 76 % . Sloughing occurred in 3 patients ( 3.9 % ) , incontinence in 1 ( 1.3 % ) , and testicular abscess in 1 ( 1.3 % ) . At 3 years , 18 ( 47 % ) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse , 5 spontaneously and 13 with sildenafil or prostagl and in . CONCLUSIONS The results of this prospect i ve evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer The current study was design ed to describe the long-term life quality and sexuality of men enrolled in a phase 2 clinical trial of cryosurgery for the treatment of localized prostate cancer . A total of 75 men were administered the Functional Assessment of Cancer Treatment-Prostate ( FACT-P ) before treatment and after treatment at 6 weeks , and at 3 , 6 , 12 , 24 , and 36 months . Additionally , these men completed a Sexuality Follow-Up Question naire ( SFQ ) 3 years after cryosurgery . By 12 months after cryosurgery , most FACT-P subscales had returned to pretreatment levels . Quality of life remained stable over the subsequent 2 years . The only exception to this general trend was persistent impairment in measures of social/family well-being . At 36 months , 13 % ( 5 of 38 ) of patients had regained erectile functioning , and an additional 34 % ( 13 of 38 ) of patients were sexually active with the help of aids . The 3-year quality -of-life outcomes support the renewed interest in cryosurgery . No late complications were observed . Whereas improvements in erectile function were observed between years 1 and 3 for some patients , most continue to experience erectile dysfunction . For these patients , aids are an important adjunct to the treatment of their erectile dysfunction Purpose The aim of this study was to conduct a prospect i ve , single-institutional comparison for primary whole-gl and cryoablation and high-intensity focused ultrasound ( HIFU ) in localized prostate cancer with respect to oncological and functional outcomes . Methods From October 2008 to December 2013 , a total of 114 and 120 patients with primary whole-gl and cryoablation and HIFU for localized prostate cancer , respectively , were enrolled in the study . Prostate-specific antigen ( PSA ) biochemical recurrence defined by Phoenix definition , salvage treatment-free rate , metastasis-free rate , and PSA biochemical recurrence-free survival analyzed using the Kaplan – Meier method were for oncological outcomes . Functional outcomes included complications and serial International Index of Erectile Function (IIEF)-5 scores , International Prostate Symptom Score ( IPSS ) , and related quality of life ( QoL ) scores . Results During the mean follow-up duration of approximately 2 years , the PSA biochemical recurrence rates of the two groups were similar ( cryoablation 25.4 % , HIFU 18.3 % ) . In terms of functional outcomes , patients with HIFU had significantly lower IPSS ( 5.70 vs. 9.04 at 24 months ; p = 0.030 ) , lower erectile dysfunction rate ( 65.6 vs. 88.0 % ; p = 0.015 ) , and higher IIEF-5 score ( 9.36 vs. 4.18 at 24 months ; p = 0.028 ) than patients with cryoablation . Conclusions In this study , both primary whole-gl and cryoablation and HIFU demonstrated good oncological outcomes for localized prostate cancer . We vali date d the safety of the two treatment modalities and identified the importance of combined HIFU and transurethral resection of the prostate . The HIFU patients experienced better urinary function improvement and more possible sexual function preservation than the cryoablation patients ; therefore , HIFU may provide better quality of life for patients with localized prostate cancer CONTEXT Comorbidities may increase the negative effects of specific anticancer treatments such as and rogen suppression therapy ( AST ) . OBJECTIVES To compare 6 months of AST and radiation therapy ( RT ) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality . DESIGN , SETTING , AND PATIENTS At academic and community-based medical centers in Massachusetts , between December 1 , 1995 , and April 15 , 2001 , 206 men with localized but unfavorable-risk prostate cancer were r and omized to receive RT alone or RT and AST combined . All-cause mortality estimates stratified by r and omized treatment group and further stratified in a postr and omization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test . MAIN OUTCOME MEASURE Time to all-cause mortality . RESULTS As of January 15 , 2007 , with a median follow-up of 7.6 ( range , 0.5 - 11.0 ) years , 74 deaths have occurred . A significant increase in the risk of all-cause mortality ( 44 vs 30 deaths ; hazard ratio [ HR ] , 1.8 ; 95 % confidence interval [ CI ] , 1.1 - 2.9 ; P = .01 ) was observed in men r and omized to RT compared with RT and AST . However , the increased risk in all-cause mortality appeared to apply only to men r and omized to RT with no or minimal comorbidity ( 31 vs 11 deaths ; HR , 4.2 ; 95 % CI , 2.1 - 8.5 ; P < .001 ) . Among men with moderate or severe comorbidity , those r and omized to RT alone vs RT and AST did not have an increased risk of all-cause mortality ( 13 vs 19 deaths ; HR , 0.54 ; 95 % CI , 0.27 - 1.10 ; P = .08 ) . CONCLUSIONS The addition of 6 months of AST to RT result ed in increased overall survival in men with localized but unfavorable-risk prostate cancer . This result may pertain only to men without moderate or severe comorbidity , but this requires further assessment in a clinical trial specifically design ed to assess this interaction . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116220 |
10,950 | 31,372,186 | Conclusion CMI was not significantly different between fallers and non-fallers or people with and without CoF ; however , our taxonomy revealed a large variety of cognitive conditions and a higher number of studies using mental tracking tasks , which make it impossible to draw firm conclusions . | Background Walking in natural environments can be considered a dual-task ( DT ) scenario that requires increasing cognitive re sources with advancing age .
Previous review s concluded that gait speed under DT conditions is equivalent to gait speed as a single task ( ST ) in the prediction of future falls in older people .
However , without a clear taxonomy , these conclusions might be premature .
The aim of this review is to use a taxonomy for classifying cognitive tasks of cognitive-motor interference ( CMI ) paradigms while walking to identify which task domains lead to more pronounced cognitive-motor decrements due to fall risk and concern about falling ( CoF ) in older people . | Background Recent findings suggest that executive function ( EF ) plays a critical role in the regulation of gait in older adults , especially under complex and challenging conditions , and that EF deficits may , therefore , contribute to fall risk . The objective of this study was to evaluate if reduced EF is a risk factor for future falls over the course of 5 years of follow-up . Secondary objectives were to assess whether single and dual task walking abilities , an alternative window into EF , were associated with fall risk . Methodology /Main Results We longitudinally followed 256 community-living older adults ( age : 76.4±4.5 yrs ; 61 % women ) who were dementia free and had good mobility upon entrance into the study . At baseline , a computerized cognitive battery generated an index of EF , attention , a closely related construct , and other cognitive domains . Gait was assessed during single and dual task conditions . Falls data were collected prospect ively using monthly calendars . Negative binomial regression quantified risk ratios ( RR ) . After adjusting for age , gender and the number of falls in the year prior to the study , only the EF index ( RR : .85 ; CI : .74–.98 , p = .021 ) , the attention index ( RR : .84 ; CI : .75–.94 , p = .002 ) and dual tasking gait variability ( RR : 1.11 ; CI : 1.01–1.23 ; p = .027 ) were associated with future fall risk . Other cognitive function measures were not related to falls . Survival analyses indicated that subjects with the lowest EF scores were more likely to fall sooner and more likely to experience multiple falls during the 66 months of follow-up ( p<0.02 ) . Conclusions / Significance These findings demonstrate that among community-living older adults , the risk of future falls was predicted by performance on EF and attention tests conducted 5 years earlier . The present results link falls among older adults to cognition , indicating that screening EF will likely enhance fall risk assessment , and that treatment of EF may reduce fall risk BACKGROUND Executive function ( EF ) deficits may increase fall risk , even among older adults with no overt cognitive impairment . Indeed , the effects of dual tasking ( DT ) on gait , a challenge to executive control , are more exaggerated in persons with a history of falls . Prospect i ve evidence is , however , lacking . METHODS We prospect ively evaluated whether EF predicts falls over a 2-year period among 262 community-living , healthy , and well-functioning older adults , focusing on the 201 who reported no falls during the previous year . At baseline , participants completed a computerized cognitive battery that generated an index of EF and other cognitive domains . Gait was assessed using performance-based tests and by quantifying walking during single- and dual-task conditions . RESULTS The 262 participants ( mean age : 76.3 ± 4.3 years , 60.3 % women ) had intact cognitive function on testing , a low comorbidity index , and good mobility . The EF index predicted future falls . Among those who reported no previous falls , participants in the worst EF quartile were three times more likely to fall during the 2 years of follow-up , and they were more likely to transition from nonfaller to faller sooner . DT gait variability also predicted future falls and multiple falls , whereas other measures of cognitive function , gait , and mobility did not . CONCLUSIONS Among healthy older adults , individuals with poorer EF are more prone to falls . Higher-level cognitive functions such as those regulated by the frontal lobes are apparently needed for safe everyday navigation that dem and s multitasking . Optimal screening , early detection , and treatment of falls should , apparently , also target this cognitive domain Background Older adults with concerns of falling show decrements of gait stability under single ( ST ) and dual task ( DT ) conditions . To compare the effects of a DT training integrating task managing strategies for independent living older adults with and without concern about falling ( CoF ) to a non-training control group on walking performance under ST and DT conditions . Methods Single center parallel group single blind r and omized controlled trial with group-based interventions ( DT-managing balance training ) compared to a control group ( Ninety-five independent living older adults ; 71.5 ± 5.2 years).A progressive DT training ( 12 sessions ; 60 min each ; 12 weeks ) including task-managing strategies was compared to a non-training control group . Setting : group based intervention for independent living elderly in a gym . ST and DT walking ( visual verbal Stroop task ) were measured on a treadmill . Gait parameters ( step length , step width , and gait line ) and cognitive performance while walking were compared with a 2x2x2 Repeated Measures Analyses of Variance . Results Participants in the intervention group showed an increased step length under ST and DT conditions following the intervention , for both people with and without CoF compared to their respective control groups . Foot rolling movement and cognitive performance while walking however only improved in participants without CoF. Conclusions The results showed that DT managing training can improve walking performance under ST and DT conditions in people with and without CoF. Additional treatment to directly address CoF , such as cognitive behavioural therapy , should be considered to further improve the cautious gait pattern ( as evidence d by reduced foot rolling movements).Trial registration The study was retrospectively registered in the German Clinical Trials Register ( DRKS ; Identification number DRKS00012382 , 11.05.2017 ) Objective : To determine whether brain activity over the prefrontal cortex measured in real time during walking predicts falls in high-functioning older adults . Method : We examined166 older persons ( mean age 75 years , 51 % women ) enrolled in a prospect i ve aging study . High-functioning status defined as the absence of dementia or disability with normal gait diagnosed by study clinicians . The magnitude of task-related changes in oxygenated hemoglobin levels over the prefrontal cortex was measured with functional near-infrared spectroscopy during motor ( walking at normal pace ) and cognitive ( reciting alternate letters of the alphabet ) single tasks and a dual-task condition ( walking while reciting alternate letters of the alphabet ) . Incident falls were prospect ively assessed over a 50-month study period . Results : Over a mean follow-up of 33.9 ± 11.9 months , 116 falls occurred . Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls ( hazard ratio adjusted for age , sex , education , medical illnesses and general mental status 1.32 , 95 % confidence interval 1.03–1.70 ) . Neither behavioral outcomes ( velocity or letter rate ) on the dual task nor brain activation patterns on the single tasks ( normal walk or talk alone ) predicted falls in this high-functioning sample . The results remained robust after accounting for multiple confounders and for cognitive status , slow gait , previous falls , and frailty . Conclusions : Prefrontal brain activity levels while performing a cognitively dem and ing walking condition predicted falls in high-functioning seniors . These findings implicate neurobiological processes early in the pathogenesis of falls OBJECTIVE As 90 % of fractures are caused by falls , and as fractures are more common in elderly women than in elderly men , a better underst and ing of potential sex differences in fall rates and underlying mechanisms is needed . The purpose of this study was to determine whether women are more prone than men to falling , and to evaluate whether the risk of falling is associated with variations in gait patterns . DESIGN , SETTING , AND PARTICIPANTS The cohort for this prospect i ve observational study consisted of 1390 community-dwelling men and women aged 70 years , examined in a health survey between July 2012 and November 2014 . MEASUREMENTS Gait patterns were measured using a computerized walkway system during normal-speed , fast-speed , and dual-task trials . Triaxial accelerometers were used to collect objective data on physical activity , and self-reported fall data were collected by telephone 6 and 12 months after examination . Incident low-energy falls were defined as unexpected events in which participants came to rest on the ground . RESULTS During the follow-up period , 148 study participants ( 88 women , 60 men ; P = .01 ) reported falls . After adjusting for multiple confounders , including objective measures of physical activity , socioeconomic factors , cardiovascular disease , and cognitive function , the odds ratio for falling in women was 1.49 ( 95 % confidence interval [ CI ] 1.02 - 2.19 ) . Variations in gait pattern were significantly ( 20%-40 % ) increased in fallers compared with nonfallers during the dual-task trial for step width , step length , stride length , step time , stance time , stride velocity , and single support time ( all P < .05 ) . Furthermore , women showed 15 % to 35 % increased variability in all of these gait parameters during the dual-task trial compared with men ( all P < .01 ) . CONCLUSION In the present cohort , 70-year-old women were at greater risk of falls compared with their male counterparts . This increased risk was associated with increased variation in gait pattern during dual-task activities , and may contribute to women 's greater fracture risk compared with men Objective : To evaluate the long-term effects of a progressive and specific balance group-based program in healthy elderly individuals with increased risk of falling . Design : Follow-up of a r and omized controlled trial at nine and 15 months on a population that has previously been described at three months . Setting : The study was conducted in Stockholm , Sweden . Subjects : 59 community-dwelling elderly ( age 67–93 years ) , recruited by advertisement , were r and omly allocated to training or to serve as controls . Intervention : Group balance training three times per week during 12 weeks with a 15 month follow-up time . Main measures : Participants were assessed at baseline , three , nine , and 15 months thereafter for gait function ( preferred and fast walking ) , rapid step execution ( single and dual task ) , fear of falling , and likelihood of depression . Results : Fast gait speed ( p = 0.004 ) , dual task step execution ( p = 0.006 ) and fear of falling ( p = 0.001 ) were still improved in the training group at nine months follow-up . Only self-perceived fear of falling remained significantly improved ( p = 0.012 ) at 15 months follow-up . Although fast gait speed had decreased to baseline level in the training group ( 1.49 m/s ) it remained significantly higher than in the control group ( 1.37 m/s ) at the end of the study , a difference between the groups that was not seen at baseline . Conclusion : This training program provided important positive short and long-term benefits to gait , balance function , and fear of falling OBJECTIVES To determine whether dual task-related changes in walking speed were associated with recurrent falls in frail older adults . DESIGN Twelve-month prospect i ve cohort study . SETTING Thirteen senior housing facilities . PARTICIPANTS Two hundred thirteen subjects ( mean age 84.4+/-5.5 ) . MEASUREMENTS Usual and dual-tasking walking speeds ( m/s ) were calculated on a 10-m straight walkway at baseline . Information on incident falls during the follow-up year was collected monthly , and participants were divided into three groups based on the occurrence of falls ( 0 , 1 , and > or=2 ) . Recurrent falls were defined as two or more falls during the 12-month follow-up period . RESULTS Twenty subjects ( 9.4 % ) were classified as recurrent fallers . The occurrence of recurrent falls was associated with age ( crude odds ratio (OR)=1.11 , P=.02 ) , number of drugs ( crude OR=1.28 , P=.002 ) , and walking speed under both walking conditions ( crude OR=0.96 , P=.002 for usual walking and crude OR=0.60 , P=.005 for walking while counting backward ) . Multiple Poisson regression showed that only walking speed while dual tasking and number of drugs were associated with incident falls ( incident rate ratio (IRR)=0.84 , P=.045 and IRR=1.10 , P=.004 ) . CONCLUSION Slower walking speed while counting backward was associated with recurrent falls , suggesting that changes in gait performance while dual tasking might be an inexpensive way of identifying frail older adults prone to falling Objective : To evaluate the effects of a new , individually adjusted , progressive and specific balance group training programme on fear of falling , step execution , and gait in healthy elderly people with fear of falling and tend to fall . Design : R and omized controlled trial . Setting : The study was conducted in Stockholm County , Sweden . Subjects : Fifty-nine community dwelling elderly people were recruited by advertisement , and allocated at r and om to an intervention group ( n = 38 ) or a control group ( n = 21 ) . Intervention : Individually adjusted , progressive and specific balance group training was given three times a week for three months . The training incorporated elements included in , and required for , independent activities of daily living , and for reactions to loss of balance during dual or multiple tasks . Main measures : Fear of falling was assessed with Falls Efficacy Scale International ( FES-I ) . The reaction time of step execution was measured with the step-execution test , and gait was measured with GAITRite ® . Results : After three months the intervention group showed significant positive changes in the FES-I ( P = 0.008 ) , in the step-execution phase of dual-task performance ( P = 0.012 ) , and in gait at preferred speed during single-task performance ; in cadence ( P = 0.030 ) and , at fast speed , in velocity ( P = 0.004 ) and cadence ( P = 0.001 ) . Significant decreases were also found for the likelihood of depression after participating in the training programme . Conclusion : This new balance training programme is feasible and leads to decreased fear of falling , decreased time for step execution during dual-task performance and increased velocity during fast walking OBJECTIVE To determine , in a cohort of ambulatory older adults , whether spatial-temporal measures of foot placement during gait can predict the likelihood of future falls or whether these measures are more likely to be indicative of adaptations associated with pre-existing fear of falling . DESIGN Prospect i ve cohort study . SETTING Baseline gait measurements were performed in a gait and balance laboratory ; subsequent history of falling was monitored prospect ively for 1 year in two self-care facilities . PARTICIPANTS Fourteen male and 61 female consecutive volunteers ( mean age = 82 , SD = 6 ) who were independent in activities of daily living and able to walk 10 m unaided . MEASUREMENTS Spatial gait parameters were derived from digitized " footprints " ; temporal parameters were derived using footswitches . A clinical activity-based gait assessment was also performed . The dependent variables were pre-existing fear of falling ( reported at baseline ) and future falling ( experiencing one or more falls during the 1-year follow-up ) . MAIN RESULTS Reduced stride length , reduced speed , increased double-support time , and poorer clinical gait scores were associated with fear but showed little evidence of an independent association with falling . Conversely , increased stride-to-stride variability in stride length , speed , and double-support was associated independently with falling but showed little evidence of relationship to fear . Increased stride width showed some evidence of association with both falling and fear . Stride-to-stride variability in speed was the single best independent predictor of falling . CONCLUSIONS Changes in gait cited previously as risk factors for falling , i.e. , decreased stride length and speed and prolonged double support , may in fact be stabilizing adaptations related to fear of falling . Stride-to-stride variability in the control of gait is an independent predictor of falling and may be a useful measure for identifying high-risk individuals and evaluating preventive interventions . Stride width may also be a useful outcome measure . Contrary to common expectation , a wider stride does not necessarily increase stability but instead seems to predict an increased likelihood of experiencing falls OBJECTIVES To examine the association between poorer performance on concurrent walking and reaction time and recurrent falls . DESIGN Cross-sectional analysis . SETTING Community . PARTICIPANTS Three hundred seventy-seven older community-dwelling adults ( mean age+/-st and ard deviation 78+/-3 ) . MEASUREMENTS Reaction times on push-button and visual-spatial decision tasks were assessed while seated and while walking a 20-m course ( straight walk ) and a 20-m course with a turn at 10 m ( turn walk ) . Walking times were recorded while walking only and while performing a reaction-time response . Dual-task performance was calculated as the percentage change in task times when done in dual-task versus single-task conditions . A history of recurrent falls ( > or = 2 vs < or = 1 falls ) in the prior 12 months was self-reported . Multivariate logistic regression models were used to predict the st and ardized odds ratios ( ORs ) of recurrent falls history . The st and ardized unit for dual-task performance ORs was interquartile range/2 . RESULTS On the push-button task during the turn walk , poorer reaction time response ( slower ) was associated with 28 % lower ( P=.04 ) odds of recurrent fall history . On the visual-spatial task , poorer walking-time response ( slower ) was associated with 34 % ( P=.02 ) and 42 % ( P=.01 ) higher odds of recurrent falls history on the straight and turn walks , respectively . CONCLUSION These findings suggest that walking more slowly in response to a visual-spatial decision task may identify individuals at risk for multiple falls . Prospect i ve studies are needed to confirm the prognostic value of poor walking responses in a dual-task setting for multiple falls OBJECTIVES To compare the value of dual tasking in predicting falling in the general population of oldest old with that of easy-to-administer single tasks . DESIGN Prospect i ve population -based follow-up study . SETTING Municipality of Leiden , the Netherl and s. PARTICIPANTS Representative cohort of 380 individuals , all aged 85 at baseline . MEASUREMENTS During enrollment , walking time over a 12-meter distance was measured , as well as the verbal fluency to recite names of animals or professions during a 30-second period . In the dual task , performance was assessed when participants combined walking with reciting names . Incidence of falls and fractures was assessed by interviewing participants and checking their medical histories . RESULTS After 1 year of follow-up , 42 % of the participants reported one or more falls , and 4 % suffered a fracture . Total walking time , number of steps , and verbal fluency were all strongly related to incident falls ( P for trend for all < .01 ) , but dual-task performance was not a better predictor for incident falls than single-task performance . CONCLUSION The dual-task test in this study had no predictive value above that of a single-task test to predict falling . Dual tasks with more-sensitive measures of impaired dual-task execution might have better test characteristics . In this study , history of falls and performance on an easy-to-administer single walking task identified old persons at higher risk for falling who could benefit from fall preventive strategies Contrary to general findings in the attention and memory literature , some studies have shown that performing a secondary cognitive task produces an improvement in balance performance . The purpose of the present experiment was to investigate under what condition such an improvement would occur . Young and older adults were asked to hold as still as possible on a platform that measured sway while performing or not performing the encoding phase of the Brooks ' ( 1967 ) spatial or non-spatial memory task . The difficulty of maintaining balance was manipulated by varying the availability of visual input and sway-referenced motion of the platform . Sway scores were computed based on the distance between the individual pressure centres and the average centre of pressure during each 20-s trial . The results indicated that both the spatial and non-spatial memory tasks improved balance for older adults under the most difficult balance condition Background : Dual-task-based assessment tests failed to establish a dependable relationship between dual-task-related gait changes and the risk of falls in the elderly . Objective : The aim of this study was to examine whether changes in gait while counting backward could be associated with the occurrence of a first fall among older adults . Methods : Walking while counting backward was investigated prospect ively in a cohort of 187 older adults living independently in senior housing facilities . During enrollment , walking time , number of steps , and frequency of lateral line stepping-over and stops were measured while walking only and while walking with backward counting aloud . Information on the incident falls during the follow-up year was collected monthly . Results : Walking time and the number of steps increased significantly under the dual-task condition compared to the single-task condition among fallers and non-fallers ( p < 0.001 ) . Compared to non-fallers , fallers had significantly lower scores in the Mini-Mental State Examination ( p = 0.029 ) and higher scores in the 15-item Geriatric Depression Scale ( p = 0.003 ) and Timed Up & Go Test ( p = 0.006 ) and increased walking time under both walking conditions ( p = 0.030 for single-task condition and p = 0.007 for dual-task condition ) . After adjusting for these variables , depressive symptoms ( adjusted OR = 2.6 with p = 0.041 and adjusted OR = 2.5 with p = 0.045 when walking time while walking only and walking with backward counting is considered , respectively ) and walking time while walking only ( OR = 2.3 with p = 0.032 ) were significantly associated with falls . Conclusion : Dual-task-related gait changes were poorly associated with the occurrence of a first fall and provided no additional predictive value compared to gait performance under a single task , suggesting that changes in basic clinical gait parameters while counting backward are unsuccessful to predict the first fall among older adults |
10,951 | 25,123,257 | AUTHORS ' CONCLUSIONS We found very low quality evidence that was insufficient to support or refute whether periodontal therapy can prevent the recurrence of CVD in the long term in patients with chronic periodontitis .
No evidence on primary prevention was found | BACKGROUND There is an association between chronic periodontitis and cardiovascular disease ( CVD ) .
However , it is not known whether periodontal therapy could prevent or manage CVD in patients with chronic periodontitis .
OBJECTIVES The objective of this systematic review was to investigate the effects of periodontal therapy in preventing the occurrence of , and management or recurrence of , CVD in patients with chronic periodontitis . | AIM This study aim ed to compare the effect of single-visit full-mouth mechanical debridement ( FMD ) and quadrant-wise mechanical debridement ( QMD ) on the levels of serum interleukin (IL)-6 , C-reactive protein ( CRP ) and soluble thrombomodulin . MATERIAL AND METHODS Thirty-six subjects with chronic periodontitis were r and omly allocated to three groups : undergoing QMD , single-visit FMD with povidone iodine or with water . Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay , and serum CRP was measured by the latex-enhanced nephelometric method . RESULTS Serum IL-6 level increased significantly immediately after debridement in all the three groups , with this increase being greatest in the full-mouth groups . However , the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group . In the quadrant-wise group , serum IL-6 level decreased significantly 1 month after debridement compared with baseline . Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group . Changes in CRP level were not significant at baseline or after debridement in all the three groups . CONCLUSIONS FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD , suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter Background Periodontal disease ( PD ) is an infectious clinical entity characterized by the destruction of supporting tissues of the teeth as the result of a chronic inflammatory response in a susceptible host . It has been proposed that PD as sub clinical infection may contribute to the etiology and to the pathogenesis of several systemic diseases including Atherosclerosis . A number of epidemiological studies link periodontal disease/edentulism as independent risk factor for acute myocardial infa rct ion , peripheral vascular disease , and cerebrovascular disease . Moreover , new r and omized controlled clinical trials have shown an improvement on cardiovascular surrogate markers ( endothelial function , sICAM , hsPCR level , fibrinogen ) after periodontal treatment . Nonetheless , such trials are still limited in terms of external validity , periodontal treatment strategies , CONSORT-based design and results consistency/extrapolation . The current study is design ed to evaluate if periodontal treatment with scaling and root planning plus local delivered chlorhexidine improves endothelial function and other biomarkers of cardiovascular disease in subjects with moderate to severe periodontitis . Methods / Design This r and omized , single-blind clinical trial will be performed at two health centers and will include two periodontal treatment strategies . After medical/periodontal screening , a baseline endothelium-dependent brachial artery flow-mediated dilatation ( FMD ) and other systemic surrogate markers will be obtained from all recruited subjects . Patients then will be r and omized to receive either supragingival/subgingival plaque cleaning and calculus removal plus chlorhexidine ( treatment group ) or supragingival plaque removal only ( control group ) . A second and third FMD will be obtained after 24 hours and 12 weeks in both treatment arms . Each group will consist of 49 patients ( n = 98 ) and all patients will be followed-up for secondary outcomes and will be monitored through a coordinating center . The primary outcomes are FMD differences baseline , 24 hours and 3 months after treatment . The secondary outcomes are differences in C-reactive protein ( hs-CRP ) , glucose serum levels , blood lipid profile , and HOMA index . Discussion This RCT is expected to provide more evidence on the effects of different periodontal treatment modalities on FMD values , as well as to correlate such findings with different surrogate markers of systemic inflammation with cardiovascular effects . Trial registration number Clinical Trials.gov Identifier : NCT00681564 Much work has been published on the association between periodontal disease and systemic disease , including original reports , narrative review s , systematic review s , and meta-analyses . Based on the existent work , one can assign an evidence level and grade , using st and ard evidence -based criteria , to the data available in the four major categories of medical outcomes studied : cardiovascular/cerebrovascular , pregnancy , pulmonary , and diabetes . We discuss method ologic and conceptual problems in the study of oral-systemic associations , focusing as an example on the association between periodontal disease and cardiovascular/cerebrovascular disease . We argue that the hierarchical ranking of studies by levels of evidence may be misleading . In particular , while r and omized controlled trials ( RCTs ) are needed to determine the efficacy of periodontal treatment to reduce the risk of cardiovascular events , they may be of limited value in determining the etiologic role of periodontal disease on coronary heart disease and stroke . We discuss limitations of RCTs as well as the limitations of currently available data from epidemiologic studies , including study design and confounding and misclassification errors . We conclude that well- design ed observational studies into the associations between periodontal disease and systemic disease need to remain an integral component of future research efforts in order to fully underst and such associations BACKGROUND Rheumatoid arthritis ( RA ) and periodontitis are common chronic inflammatory conditions . Recent studies showed a beneficial effect of periodontal treatment on the severity of active RA . This study was undertaken to further examine the effect of non-surgical periodontal treatment on the signs and symptoms of RA in patients treated with or without anti-tumor necrosis factor-alpha ( anti-TNF-alpha ) medications . The effect of anti-TNF-alpha therapy on periodontitis also was assessed . METHODS Forty participants diagnosed with moderate/severe RA ( under treatment for RA ) and severe periodontitis were r and omly assigned to receive initial non-surgical periodontal therapy with scaling/root planing and oral hygiene instructions ( n = 20 ) or no periodontal therapy ( n = 20 ) . To control RA , all participants had been using disease-modifying anti-rheumatic drugs , and 20 had also been using anti-TNF-alpha before r and omization . Probing depth ( PD ) , clinical attachment level ( CAL ) , bleeding on probing ( BOP ) , gingival index ( GI ) , plaque index ( PI ) , RA disease activity score 28 ( DAS28 ) , and erythrocyte sedimentation rate ( ESR ) were measured at baseline and 6 weeks later . Linear mixed models were used to identify significant differences between subjects who received periodontal treatment and those who did not . RESULTS Patients receiving periodontal treatment showed a significant decrease in the mean DAS28 , ESR ( P < 0.001 ) , and serum TNF-alpha ( P < 0.05 ) . There was no statistically significant decrease in these parameters in patients not receiving periodontal treatment . Anti-TNF-alpha therapy result ed in a significant improvement in CAL , PD , BOP , and GI . CONCLUSIONS Non-surgical periodontal therapy had a beneficial effect on the signs and symptoms of RA , regardless of the medications used to treat this condition . Anti-TNF-alpha therapy without periodontal treatment had no significant effect on the periodontal condition BACKGROUND Chronic infections , such as periodontitis , are associated with increased risk of systemic diseases driven by a persistent low- grade systemic inflammation and metabolic changes . Severity of periodontitis has also been associated with increased systolic blood pressure ( BP ) . However , the issue remains poorly investigated . We aim ed to estimate the effect of periodontal therapy on traditional and novel cardiovascular risk factors in systemically healthy individuals who have periodontitis . METHODS We enrolled 40 otherwise healthy patients with severe chronic generalized periodontitis in a 6-month pilot intervention trial . Individuals were r and omized either to a st and ard course of periodontal therapy ( subgingival scaling and root planing ) or an intensive one ( including the adjunctive use of a locally delivered antimicrobial , IPT ) . RESULTS Compared to control , IPT produced significant reductions in a cluster of inflammatory markers at 1 ( P = .0406 ) and 2 ( P = .0060 ) months together with an improvement in lipid markers at 2 ( P = .0320 ) and 6 ( P = .0432 ) months after therapy . Intensive periodontal therapy produced greater reductions in IL-6 at 1 ( 0.4 + /- 0.2 ng/L difference , 95 % CI 0.03 - 0.9 , P = .0284 ) and 2 months ( 0.3 + /- 0.2 ng/L difference , 95 % CI 0.1 - 0.8 , P = .0284 ) , together with decreases in C-reactive protein ( 0.4 + /- 0.2 mg/L difference , 95 % CI 0.01 - 0.8 , P = .0438 ) and total cholesterol ( 0.3 + /- 0.1 mmol/L difference , 95 % CI 0.04 - 0.6 , P = .0254 ) . Moreover , a 7 + /- 3-mm Hg decrease in systolic BP was observed at 2 months in the IPT group ( 95 % CI 1 - 12 , P = .0211 ) , and this difference was greater in current smokers ( 14 + /- 5 mm Hg 95 % CI 3 - 25 , P = 0.0124 ) . Intensive periodontal therapy subjects exhibited a 1.53 % + /- 1.20 % ( 95 % CI 1.05 - 2.24 , P = .0290 ) and 2.00 % + /- 1.42 % ( 95 % CI 0.98 - 4.09 , P = .0568 ) decreases in cardiovascular risk scores ( Framingham ) at 2 and 6 months , respectively , when compared to those in the st and ard group . CONCLUSIONS Our findings suggest that intensive periodontal treatment reduces systemic inflammatory markers and systolic BP , and improves lipid profiles with subsequent changes in cardiovascular risk when compared to st and ard therapy AIM We studied the effect of atorvastatin ( ATV ) treatment on bone loss prevention in subjects with chronic periodontitis . MATERIAL AND METHODS In this controlled double-blind study , 38 subjects with chronic periodontitis were r and omized into two groups , paired by age to receive ATV ( 20 mg ) or placebo daily for 3 months . Periodontal mechanical treatment was carried out in both groups at baseline . Clinical and radiographic parameters and bone turnover markers were assessed at baseline and at 3 months . RESULTS Periodontal disease conditions improved in both groups . After comparing the figures of change , significant improvements were observed in cholesterol levels ( Δ=-58.5 ± 37.6 versusΔ=5.4 ± 41.2 mg/dl , p<0.0002 ) , low-density lipoprotein levels ( Δ=-48.1 ± 31.7 versusΔ=1.9 ± 42.8 mg/dl , p<0.002 ) , dental mobility ( Δ=-0.17 ± 0.11 versusΔ=-0.06 ± 0.11 % , p<0.04 ) , and the distance from the crestal alveolar bone to the cemento-enamel junction ( Δ=-0.75 ± 0.7 versusΔ=0.09 ± 0.4 mm , p<0.0006 ) in the ATV group . CONCLUSIONS The results suggest that ATV might have beneficial effects on bone alveolar loss and tooth mobility in subjects with periodontal disease BACKGROUND The present r and omized , double-masked , placebo-controlled , parallel-arm study examines the impact of adjunctive subantimicrobial-dose doxycycline ( SDD ) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid ( GCF ) sample s from patients with chronic periodontitis . METHODS Forty-six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD . GCF sample s were collected and clinical parameters including probing depth , clinical attachment level , gingival index , and plaque index were recorded every 3 months for 12 months . GCF tumor necrosis factor-α , interleukin (IL)-6 , IL-4 , IL-10 , IL-13 , IL-17 , macrophage inhibitory protein 1α , macrophage inhibitory protein 1β , monocyte chemoattractant protein 1 , and regulated on activated normal T-cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay . RESULTS Significant improvements were observed in all clinical parameters in both groups over 12 months ( P < 0.0125 ) , whereas the SDD group showed significantly better reduction in gingival index , probing depth , and gain in clinical attachment compared to the placebo group ( P < 0.05 ) . Decrease in IL-6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets ( P < 0.05 ) , whereas tumor necrosis factor-α was significantly reduced in moderately deep pockets ( P < 0.05 ) . SDD result ed in a stable IL-4 and IL-10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months ( P < 0.05 ) . CONCLUSIONS These results show that SDD , as an adjunct to non-surgical periodontal therapy , stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti-inflammatory cytokines . The chemokine activity would account for the regulation of the inflammatory response to SDD therapy ObjectiveS ubantimicrobial-dose doxycycline ( SDD ) treatment has been reported to reduce the severity of chronic inflammation and to increase serum high-density lipoprotein cholesterol . In a double-blind , placebo-controlled clinical trial , we determined whether SDD affects the ability of serum to facilitate cholesterol removal from macrophages . Methods Forty-five postmenopausal osteopenic women with periodontitis were r and omly assigned to take placebo ( n = 26 ) or doxycycline hyclate ( 20 mg , n = 19 ) tablets twice daily for 2 years . Serum sample s were collected at baseline , 1- , and 2-year appointments . The cholesterol efflux capacity of serum from cultured human macrophages ( THP-1 ) was measured . Results SDD subjects demonstrated a significant increase in serum-mediated cholesterol efflux from macrophages at both time points compared to baseline ( p < 0.04 for each ) . Mean cholesterol efflux levels over the first year of follow-up were 3.0 percentage points ( unit change ) higher among SDD subjects compared to placebo subjects ( p = 0.010 ) , while there was no significant difference in 2-year changes . There were no significant differences in the changes of apolipoprotein A-I , apolipoprotein A-II , or serum amyloid A levels between the groups . Conclusions Our results suggest that SDD treatment may reduce the risk of cardiovascular disease in this patient group by increasing the cholesterol efflux capacity of serum BACKGROUND Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes , periodontal status , and inflammatory biomarkers . METHODS A r and omized , delayed-treatment , controlled pilot trial was conducted to evaluate the effects of second-trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery ( < 37 weeks gestation ) . Secondary outcome measures included changes in periodontal status , levels of eight oral pathogens , levels of gingival crevicular fluid ( GCF ) interleukin-1beta ( IL-1beta ) , prostagl and in E(2 ) ( PGE(2 ) ) , 8-isoprostane ( 8-iso ) , and IL-6 , and serum levels of IL-6 , soluble intercellular adhesion molecule 1 ( sICAM1 ) , 8-isoprostane , soluble glycoprotein 130 ( sGP130 ) , IL-6 soluble receptor ( IL-6sr ) , and C-reactive protein ( CRP ) . Logistic regression models were used to test for effects of treatment on preterm delivery . Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values . RESULTS Periodontal intervention result ed in a significantly decreased incidence odds ratio ( OR ) for preterm delivery ( OR = 0.26 ; 95 % confidence interval = 0.08 to 0.85 ) , adjusting for baseline periodontal status which was unbalanced after r and omization . Pregnancy without periodontal treatment was associated with significant increases in probing depths , plaque scores , GCF IL-1beta , and GCF IL-6 levels . Intervention result ed in significant improvements in clinical status ( attachment level , probing depth , plaque , gingivitis , and bleeding on probing scores ) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia , serum IL-6sr , and GCF IL-1beta . CONCLUSIONS Results from this pilot study ( 67 subjects ) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes . Treatment was safe , improved periodontal health , and prevented periodontal disease progression . Preliminary data show a 3.8-fold reduction in the rate of preterm delivery , a decrease in periodontal pathogen load , and a decrease in both GCF IL-1beta and serum markers of IL-6 response . However , further studies will be needed to substantiate these early findings BACKGROUND Systemic inflammation may impair vascular function , and epidemiologic data suggest a possible link between periodontitis and cardiovascular disease . METHODS We r and omly assigned 120 patients with severe periodontitis to community-based periodontal care ( 59 patients ) or intensive periodontal treatment ( 61 ) . Endothelial function , as assessed by measurement of the diameter of the brachial artery during flow ( flow-mediated dilatation ) , and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1 , 7 , 30 , 60 , and 180 days after treatment . RESULTS Twenty-four hours after treatment , flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group ( absolute difference , 1.4 % ; 95 % confidence interval [ CI ] , 0.5 to 2.3 ; P=0.002 ) , and levels of C-reactive protein , interleukin-6 , and the endothelial-activation markers soluble E-selectin and von Willebr and factor were significantly higher ( P<0.05 for all comparisons ) . However , flow-mediated dilatation was greater and the plasma levels of soluble E-selectin were lower in the intensive-treatment group than in the control-treatment group 60 days after therapy ( absolute difference in flow-mediated dilatation , 0.9 % ; 95 % CI , 0.1 to 1.7 ; P=0.02 ) and 180 days after therapy ( difference , 2.0 % ; 95 % CI , 1.2 to 2.8 ; P<0.001 ) . The degree of improvement was associated with improvement in measures of periodontal disease ( r=0.29 by Spearman rank correlation , P=0.003 ) . There were no serious adverse effects in either of the two groups , and no cardiovascular events occurred . CONCLUSIONS Intensive periodontal treatment result ed in acute , short-term systemic inflammation and endothelial dysfunction . However , 6 months after therapy , the benefits in oral health were associated with improvement in endothelial function Background Indigenous Australians experience an overwhelming burden of chronic disease , including cardiovascular diseases . Periodontal disease ( inflammation of the tissues surrounding teeth ) is also widespread , and may contribute to the risk of cardiovascular diseases via pathogenic inflammatory pathways . This study will assess measures of vascular health and inflammation in Indigenous Australian adults with periodontal disease , and determine if intensive periodontal therapy improves these measures over a 12 month follow-up . The aims of the study are : ( i ) to determine whether there is a dose response relationship between extent and severity of periodontal disease and measures of vascular health and inflammation among Indigenous Australian adults with moderate to severe periodontal disease ; and ( ii ) to determine the effects of periodontal treatment on changes in measures of vascular health and inflammation in a cohort of Indigenous Australians . Methods / Design This study will be a r and omised , controlled trial , with predominantly blinded assessment of outcome measures and blinded statistical analysis . All participants will receive the periodontal intervention benefits ( with the intervention delayed 12 months in participants who are r and omised to the control arm ) . Participants will be Indigenous adults aged ≥25 years from urban centres within the Top End of the Northern Territory , Australia . Participants assessed to have moderate or severe periodontal disease will be r and omised to the study 's intervention or control arm . The intervention involves intensive removal of subgingival and supragingival calculus and plaque biofilm by scaling and root-planing . Study visits at baseline , 3 and 12 months , will incorporate question naires , non-fasting blood and urine sample s , body measurements , blood pressure , periodontal assessment and non-invasive measures of vascular health ( pulse wave velocity and carotid intima-media thickness ) . Primary outcome measures are pulse wave velocity and carotid intima-media thickness . Discussion The study will assess the periodontal-cardiovascular disease relationship among Indigenous Australian adults with periodontal disease , and the effectiveness of an intervention aim ed at improving periodontal and cardiovascular health . Efforts to underst and and improve Indigenous oral health and cardiovascular risk may serve as an important means of reducing the gap between Indigenous and non-Indigenous health in Australia . Trial Registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : BACKGROUND Periodontitis has been reported to be associated with coronary artery disease ( CAD ) . Research is needed to determine if therapies that improve periodontal health also reduce systemic measures of inflammation associated with both diseases . METHODS The study registrar r and omly assigned 128 eligible postmenopausal women with chronic periodontitis to a twice-daily regimen of subantimicrobial-dose-doxycycline ( SDD ) or placebo tablets for two years as an adjunct to periodontal maintenance therapy . Through a supplement to the main trial , in which they investigated alveolar bone and clinical attachment level changes , the authors assayed inflammatory mediators and lipid profiles in baseline , one-year and two-year serum sample s. The authors analyzed the data by using generalized estimating equations . RESULTS In the intent-to-treat analysis across two years , SDD treatment reduced median high-sensitivity C-reactive protein ( hs-CRP ) by 18 percent ( primary outcome ; P = .02 ) and reduced serum matrix metalloproteinase (MMP)-9 ( 92 kilodalton gelatinase ; difference in mean scanning units , -28.44 ; P < .001 ) , with no significant effect on serum lipids . However , in women more than five years postmenopausal , SDD elevated the level of high-density lipoprotein ( HDL ) cholesterol ( difference in means [ milligrams per deciliter ] , 5.99 ; P = .01 ) . CONCLUSION A two-year SDD regimen in postmenopausal women significantly reduced the serum inflammatory biomarkers hs-CRP and MMP-9 and , among women more than five years postmenopausal , increased the HDL cholesterol level . CLINICAL IMPLICATION S SDD significantly reduced the systemic inflammatory biomarkers hs-CRP and MMP-9 . More research is needed to determine whether SDD has a role in managing the care of patients at risk of developing CAD BACKGROUND Periodontitis is an infectious chronic insidious disease of the tooth supporting structures that causes a general inflammatory response . The aims of the study were to determine whether periodontitis is associated with markers of general inflammation high-sensitivity ( hs ) C-reactive protein ( CRP ) leading to cardiovascular disease , and whether proper management of the periodontal disease would improve inflammation and thus , may prevent cardiovascular disease in the future . METHODS This was a prospect i ve case-controlled pilot study . Nine patients ( 3 women , 6 men ; 40+/-5 yr ) took part . All had severe periodontitis , without systemic disorders , and were all treated conservatively without surgical intervention . All had a 2nd visit after 3 months of treatment at the Outpatient Dental Clinic of the Hospital . Periodontal status and hs-CRP were evaluated on entry to the study and 3 months after treatment . Nine age and sex-matched healthy volunteers without periodontal disease served as the control group . RESULTS Periodontal clinical parameters were improved after 3 months ' treatment : probing depth ( PD ) ( mean ) at baseline was 4.3 and after 3 months ' treatment improved to 3.2 ( P=0.001 ) , clinical attachment level ( CAL ) ( mean ) was 4.6 and changed to 3.7 ( P=0.01 ) , bleeding on probing ( BOP % ) changed from 64 % to 33 % ( P=0.001 ) , and Plaque index ( Pi ) changed from 49 % to 25 % ( P=0.001 ) . hs-CRP level was different between the patients ' group ( pre treatment ) and the healthy volunteers : 2.97+/-0.58 mg/L vs. 0.25+/-0.14 mg/L ( P=0.00002 ) . After completing 3 months ' treatment , hs-CRP levels were decreased from 2.97+/-0.58 mg/L to 2.3+/-0.7 mg/L ( P=0.009 ) . CONCLUSIONS Periodontitis is an infectious condition that may be an insidious cause of chronic inflammation and may be a risk factor for future cardiovascular disease . Treating periodontitis improved inflammation , and might be used as an important prevention tool for cardiovascular disease BACKGROUND Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications . This study aim ed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers ( interleukin [IL]-6 , C-reactive protein [ CRP ] , and fibrinogen ) in patients with severe periodontitis and refractory arterial hypertension . METHODS Twenty-two patients were examined and r and omly divided into two groups . The test group was composed of 11 patients ( mean age , 48.9 + /- 3.9 years ) who received periodontal treatment , whereas the control group had 11 patients ( mean age , 49.7 + /- 6.0 years ) whose treatment was delayed for 3 months . Demographic and clinical periodontal data were collected , and blood tests were performed to measure the levels of IL-6 , CRP , and fibrinogen at baseline and 3 months later . RESULTS The clinical results showed that the mean percentages of sites with bleeding on probing , probing depth ( PD ) 4 to 5 mm , PD > or = 6 mm , clinical attachment loss ( CAL ) 4 to 5 mm , and CAL > or = 6 mm were significantly reduced in the test group 3 months after periodontal treatment . There were no significant differences between the data at baseline and 3 months in the control group . Periodontal treatment significantly reduced the blood levels of fibrinogen , CRP , and IL-6 in the test group . CONCLUSION Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6 , CRP , and fibrinogen in hypertensive patients with severe periodontitis OBJECTIVES This study evaluated the effects of scaling and root planing ( SRP ) + /- sub-antimicrobial dose doxycycline ( SDD ) on gingival crevicular fluid ( GCF ) levels of matrix metalloproteinase ( MMP ) -1 , -8 , -13 and on serum levels of high-sensitivity C-reactive protein ( HsCRP ) and lipid fractions in patients with both chronic periodontitis ( CP ) and coronary artery disease ( CAD ) . MATERIAL AND METHODS Thirty-six patients were r and omly distributed into two groups ( Placebo or SDD ; 6 weeks ) and both received two regimens of SRP . At baseline and 6 weeks , GCF and blood were collected and clinical indices were recorded . MMPs , HsCRP and lipid fractions were assayed . RESULTS There were statistically significant improvements for all clinical parameters , GCF volumes , GCF MMPs and serum levels of HsCRP , apolipoprotein-A ( APO-A ) , high-density lipoprotein ( HDL ) and lipoprotein-a between pre- and post-treatment in both groups . Between groups , there were statistically significant greater improvements in pocket depth ( PD ) , gingival index ( GI ) , APO-A and HDL , favouring the group receiving SDD adjunctive to SRP ( p < 0.05 ) . CONCLUSION Greater improvement was detected for PD and GI , and for serum levels of APO-A and HDL cholesterol when using SRP+SDD compared with SRP+placebo in this study . An investigation with larger numbers of patients and a longer duration of drug treatment is needed to confirm these preliminary findings Observational studies indicate that chronic periodontal disease is associated with adverse cardiovascular outcomes . The aim of this study was to determine whether initial periodontal treatment has a beneficial effect on systemic markers of inflammation and cardiovascular risk . One hundred and thirty-six adults with chronic periodontitis were allocated to either intervention or control groups in a 3-month r and omized controlled intervention study . The intervention group received initial periodontal treatment , whereas the control group did not receive that treatment until after the study . Blood levels of cardiovascular risk factors , and of hematological , inflammatory , and metabolic markers , were measured at the beginning and the end of the study , and differences were calculated . Fibrinogen level was the primary outcome measure . Data for 61 persons in the intervention group and for 64 persons in the control group were available for statistical analysis . Compared with the control group , the intervention group showed a non-significant trend for a lower fibrinogen level . Significant increases in hemoglobin and hematocrit were seen after treatment , showing that initial periodontal treatment , a relatively simple and cost-effective intervention , has systemic effects BACKGROUND The purpose s of this study were to determine : 1 ) if periodontal treatment in pregnant women before 21 weeks of gestation alters levels of inflammatory mediators in serum ; and 2 ) if changes in these mediators are associated with birth outcomes . METHODS A total of 823 pregnant women with periodontitis were r and omly assigned to receive scaling and root planing before 21 weeks of gestation or after delivery . Serum obtained between 13 and 16 weeks , 6 days ( study baseline ) and 29 to 32 weeks of gestation was analyzed for C-reactive protein ; prostagl and in E(2 ) ; matrix metalloproteinase-9 ; fibrinogen ; endotoxin ; interleukin (IL)-1 beta , -6 , and -8 , and tumor necrosis factor-alpha . Cox regression , multiple linear regression , and the t , chi(2 ) , and Fisher exact tests were used to examine associations among the biomarkers , periodontal treatment , and gestational age at delivery and birth weight . RESULTS A total of 796 women had baseline serum data , and 620 women had baseline and follow-up serum and birth data . Periodontal treatment did not significantly alter the level of any biomarker ( P > 0.05 ) . Neither baseline levels nor the change from baseline in any biomarker were significantly associated with preterm birth or infant birth weight ( P > 0.05 ) . In treatment subjects , the change in endotoxin was negatively associated with the change in probing depth ( P < 0.05 ) . CONCLUSIONS Non-surgical mechanical periodontal treatment in pregnant women , delivered before 21 weeks of gestation , did not reduce systemic ( serum ) markers of inflammation . In pregnant women with periodontitis , levels of these markers at 13 to 17 weeks and 29 to 32 weeks of gestation were not associated with infant birth weight or a risk for preterm birth Severe periodontitis has been associated with increased systemic inflammation . In a three-arm preliminary r and omized trial , we investigated the impact of st and ard ( SPT ) and intensive periodontal therapy ( IPT ) on serum inflammatory markers and cholesterol levels . Medical and periodontal parameters , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , total cholesterol , and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis . Two months after treatment , both SPT and IPT result ed in significant reductions in serum CRP compared with the untreated control ( 0.5 ± 0.2 mg/L for SPT , P = 0.030 and 0.8 ± 0.2 mg/L for IPT , P = 0.001 ) . Similar results were observed for IL-6 . Changes in inflammation were independent of age , gender , body mass index , and ethnicity , but a significant interaction between cigarette smoking and treatment regimen was found . The IPT group also showed a decrease in total and LDL cholesterol after 2 months . Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects AIM Determine the efficacy of 2-year continuous subantimicrobial dose doxycycline ( SDD ; 20 mg bid ) on alveolar bone in post-menopausal osteopenic , oestrogen-deficient women undergoing periodontal maintenance in a 2-year double-blind , placebo-controlled , r and omized clinical trial . MATERIAL AND METHODS One-hundred and twenty-eight subjects r and omized to SDD or placebo ( n=64 each ) . Posterior vertical bite wings taken at baseline , 1 and 2 years for alveolar bone density ( ABD ) , using radiographic absorptiometry ( RA ) and computer-assisted densitometric image analysis ( CADIA ) , and alveolar bone height ( ABH ) . Statistical analyses utilized generalized estimating equations ; primary analyses were intent to treat ( ITT ) . Results are presented as SDD versus placebo . RESULTS Under ITT , there was no statistically significant effect of SDD on ABD loss ( RA : p=0.8 ; CADIA : p=0.2 ) or ABH loss ( p=0.2 ) . Most sites ( 81 - 95 % ) were inactive . For subgroup analyses , mean CADIA was higher with SDD for non-smokers ( p=0.05 ) and baseline probing depths > or = 5 mm ( p=0.003 ) . SDD was associated with 29 % lower odds of more progressive ABH loss in women > 5 years post-menopausal ( p=0.05 ) and 36 % lower among protocol -adherent subjects ( p=0.03 ) . CONCLUSIONS In post-menopausal osteopenic women with periodontitis , SDD did not differ overall from placebo . Based on exploratory subgroup analyses , additional research is needed to determine the usefulness of SDD in non-smokers , subjects > 5 years post-menopausal and in deeper pockets . Protocol registered at ( Clinical Trials.gov ) . Identifier : NCT00066027 AIMS Recent epidemiological work suggests an association between periodontal disease severity and cardiovascular disease risk . This study aim ed to ascertain if circulating levels of cardiovascular and systemic inflammatory markers could be modified following treatment of periodontal disease . METHOD Adult subjects were recruited from those awaiting periodontal treatment and r and omised to either immediate ( test , n=24 ) or delayed treatment ( control , n=15 ) . Demographic and clinical data were collected and venous blood was taken before and either 6 weeks after completion of treatment or after an equivalent 3-month control period . Periodontal examination included probing depth , loss of attachment , plaque scores and bleeding scores . Blood was analysed to determine serum and plasma fibrinogen , C-reactive protein , sialic acid , tumour necrosis factor-alpha and interleukin -6 and -1beta . Effects of treatment were assessed by paired tests and analysis of variance by treatment group with baseline covariates . RESULTS Treatment improved plaque and bleeding scores and reduced probing depths ( p<0.002 ) . However , there were no statistically significant changes in levels of any of the systemic markers . CONCLUSION Improvement in periodontal health did not influence the levels of vascular markers BACKGROUND The aim of this r and omized controlled clinical trial was to determine the effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise therapy . MATERIAL AND METHODS Thirty-six subjects with chronic periodontitis , were r and omly allocated to three groups -- quadrant-wise ultrasonic debridement , single-visit full-mouth ultrasonic debridement with povidone iodine and single-visit full-mouth ultrasonic debridement with water . Whole-mouth plaque , bleeding on probing ( BOP ) , pocket depth and attachment level were recorded before treatment and 1 , 3 and 6 months post-treatment . Plaque and saliva sample s were collected for microbiological analysis . RESULTS After treatment , all groups showed significant improvement in clinical parameters . Full-mouth treatments result ed in similar improvements in full-mouth mean plaque percentage , probing pocket depth and probing attachment level as conventional therapy . When data were analysed based on pocket depth and tooth type , there was no difference between groups in probing depth reduction or attachment gains . The full-mouth groups demonstrated greater reduction in BOP% and number of pockets > or = 5 mm and the total treatment time was significantly shorter . The detection frequencies of periodontal pathogens in plaque and saliva showed slight changes with no difference between groups . CONCLUSION Single-visit full-mouth mechanical debridement may have limited additional benefits over quadrant-wise therapy in the treatment of periodontitis , but can be completed in a shorter time OBJECTIVE To determine serum adiponectin , C-reactive protein ( CRP ) , TNF-α and IL-6 levels in impaired glucose tolerance ( IGT ) and type 2 diabetes mellitus ( T2DM ) patients with periodontitis before and after periodontal intervention , and to investigate the relationship between T2DM and periodontitis . METHODS A total of 50 IGT and 106 T2DM patients with periodontitis were enrolled . The T2DM patients were divided into two groups : T2DM without macrovascular disease ( DM1 ) group and T2DM with macrovascular disease ( DM2 ) group . Each group was r and omly divided into two subgroups according to whether they performed periodontal intervention . The normal control group ( NC group ) consisted of 30 healthy adults . The serum adiponectin , CRP , TNF-α and IL-6 levels were measured at baseline and 3 months after periodontal intervention . RESULTS The serum adiponectin levels at baseline had decreased tendency with significant difference between each two groups , while CRP , TNF-α , and IL-6 levels had increased tendency with significant difference between each two groups among NC , IGT , DM1 and DM2 groups ( all P<0.01 ) . At 3 months after periodontal intervention , the serum adiponectin levels were increased than those without periodontal intervention ( all P<0.01 ) , while CRP , IL-6 and TNF-α significantly decreased ( all P<0.05 ) in both IGT and DM1 groups . In DM2 group , only CRP levels at 3 months after periodontal intervention were significantly decreased ( P<0.05 ) . Moreover , the HbAlc levels in T2DM patients were improved at 3 months after periodontal invention ( P<0.01 ) . CONCLUSION Periodontal intervention is helpful for glucose control , which may be associated with increased serum adiponectin levels and decreased inflammatory cytokine levels AIM Periodontal disease elevates systemic inflammatory markers strongly associated with coronary heart disease ( CHD ) risk . The aim of this r and omized controlled trial was to investigate the effect of non-surgical periodontal therapy on systemic C-reactive protein ( CRP ) , fibrinogen and white blood cells in CHD patients . MATERIAL S AND METHODS Angiographically proven CHD patients with periodontitis ( n = 317 ) were r and omized to intervention ( n = 212 ) or control group ( n = 105 ) . Primary outcome was reduction in serum CRP levels ; secondary outcomes were reductions in fibrinogen and white blood cells . Periodontal treatment included scaling , root planing and oral hygiene instructions . Periodontal and systemic parameters were assessed at baseline and at 2-month follow-up . Intent-to-treat ( ITT ) analysis was performed . RESULTS Study was completed by 246 subjects ( intervention group = 161 ; control group = 85 ) . Significant improvements in periodontal and systemic parameters were observed in intervention group . The number of subjects with CRP > 3mg/L in intervention group decreased by 38 % and in control group increased by 4 % . ITT analysis gave a significant ( χ(2 ) = 4.381 , p = 0.036 ) absolute risk reduction of 12.5 % . CONCLUSION In CHD patients with periodontitis , non-surgical mechanical periodontal therapy significantly reduced systemic levels of C-reactive protein , fibrinogen and white blood cells BACKGROUND AND OBJECTIVE Data on whether periodontal therapy affects serum CRP levels are inconclusive . The aim of this study was to determine if nonsurgical periodontal therapy has any effect on CRP and serum lipid levels in patients with advanced periodontitis . MATERIAL AND METHODS Thirty-six systemically healthy patients , ≥ 40 years of age and with advanced periodontitis , were recruited for the study . Patients were r and omized consecutively to one of two groups : the treatment group ( n = 18 ) or the control group ( n = 18 ) . Treated subjects received nonsurgical periodontal therapy , which included oral hygiene instructions and subgingival scaling and root planing . Systemic levels of inflammatory markers [ C-reactive protein ( CRP ) and the lipid profile ] were measured at baseline and 3 mo after periodontal therapy . RESULTS Nonsurgical periodontal therapy in the treatment group result ed in a significant reduction in the serum CRP level . The average CRP level decreased from 2.3 mg/dL at baseline to 1.8 mg/dL ( p < 0.005 ) after 3 mo of periodontal therapy . The average reduction ( 95 % confidence interval ) in CRP was 0.498 ( 95 % confidence interval = 0.265 - 0.731 ) . In the treatment group , the reduction in CRP was significantly , linearly and directly correlated with the reduction in the plaque index , the gingival index and the percentage of sites with pocket depth ≥ 7 mm ( Pearson correlation coefficient = 0.746 , 0.425 and 0.621 , respectively ) . Nonsurgical periodontal therapy had no effect on the lipid parameters . CONCLUSION This study demonstrated that nonsurgical periodontal therapy results in a significant reduction in the serum CRP level . The effect of this outcome on systemic disease is still unknown Adverse effects of long-term usage of triclosan-containing toothpaste in humans are currently unknown . We assessed the effect of long-term use of 0.3 % triclosan-toothpaste on serious adverse events ( SAEs ) in patients with cardiovascular disease ( CVD ) . 438 patients with a history of stable CVD were entered into the 5-year longitudinal Cardiovascular and Periodontal Study at Prince Charles Hospital , Brisbane , Australia and r and omised into test ( triclosan ) or placebo groups . There were no significant differences in demographics or clinical features between the groups . Patients were examined at baseline , and annually for 5-years . SAEs were classified according to the System Organ Classes defined by MedDRA ( Medical Dictionary for Regulatory Activities ) . Results were analysed using chi square and Kaplan Meier analysis . Overall , 232 patients ( 123 in the triclosan group ; 109 in the placebo group ) experienced 569 SAEs ( 288 in the triclosan group and 281 in the placebo group ) . There was no significant difference between the groups in numbers of patients experiencing SAEs ( p=0.35 ) or specific cardiovascular SAEs ( p=0.82 ) , nor in time to the first SAE or first cardiovascular SAE , irrespective of gender , age or BMI after adjusting for multiple comparisons ( p>0.05 ) . The adjusted odds of experiencing an SAE were estimated to increase by 2.7 % for each year of age ( p=0.02 ) and the adjusted odds of experiencing a cardiovascular SAE were estimated to increase by 5.1 % for each unit increase in BMI ( p=0.02 ) . Most cardiovascular events were related to unstable angina or myocardial infa rcts , 21 were associated with arrhythmia and 41 were vascular events such as aortic aneurysm and cerebrovascular accident . Within the limitations of the present study the data suggest that the use of triclosan-toothpaste may not be associated with any increase in SAEs in this CVD population . The long-term impact of triclosan on hormone-related disease , such as cancer , in humans remains to be determined BACKGROUND AND OBJECTIVE Although some studies have attempted to eluci date the possible advantages of the use of Er : YAG laser radiation as a coadjuvant of scaling and root planing ( SRP ) , the results have often been contradictory . A new possibility to improve the results of the laser therapy is the control of the laser radiation by a feedback system that selectively detects subgingival calculus . This study compared the effects of fluorescence-controlled Er : YAG radiation after SRP with SRP alone on the treatment of chronic periodontitis . STUDY DESIGN / MATERIAL S AND METHODS Thirty patients with chronic periodontitis were r and omly distributed into two groups of 15 patients to receive : SRP or SRP followed by fluorescence controlled Er : YAG laser ( SRP+ERL ) . Clinical parameters including probing pocket depth ( PPD ) , bleeding on probing ( BOP ) , and plaque index ( PI ) were recorded and sample s of gingival crevicular fluid ( GCF ) and subgingival plaque were taken at baseline , 4 and 8 weeks postoperatively . The laser therapy was performed 1 day after the SRP procedure . The GCF sample s were analyzed for interleukin-1beta ( IL-1beta ) , tumor necrosis factor alpha ( TNF-alpha ) and total antioxidative status ( TAS ) . Subgingival plaque was examined by culture for 10 bacteria . RESULTS During the observation periods ( 4 and 8 weeks postoperatively ) , no statistically significant differences were detected for clinical , microbiological variables and TAS of GCF between SRP and SRP+ERL groups . However , the amount of IL-1beta and TNF-alpha in GCF was increased after SRP procedure in contrast to a slight decrease of their levels after SRP+ERL treatment , where in addition the process of recolonization seems to be more delayed . CONCLUSION SRP+ERL allowed a decrease of the levels of proinflammatory cytokines and prevented a fast process of recolonization BACKGROUND Serum anti-cardiolipin ( aCL ) antibodies are prevalent in patients with periodontal diseases . These increased aCL concentrations were identified to play a modulating role in cardiovascular diseases . The present study aims to explore the effect of phase I periodontal therapy on immunoglobulin (Ig)M and IgG aCL antibodies in patients with acute myocardial infa rct ion ( AMI ) associated with chronic periodontitis . METHODS A cross-sectional r and omized clinical study was conducted within two groups comprising a sample size of 72 patients ( n = 36 each ) . Group 1 had clinical features of AMI , and group 2 had clinical features of AMI associated with chronic periodontitis . After a thorough clinical and oral examination , the plaque index ( PI ) , gingival index ( GI ) , probing depth ( PD ) , and clinical attachment loss ( AL ) were recorded . Serum sample collection by venipuncture was done for estimation of serum IgM and IgG aCL concentration by using an enzyme-linked immunosorbent assay method . In group 2 , phase I periodontal therapy was performed , and clinical and biochemical parameters were reanalyzed after 1 month . RESULTS In group 2 , the mean PI , GI , PD , clinical AL , and serum IgM and IgG aCL antibody levels were significantly higher than in group 1 patients . In addition , study results showed significant alterations in concentrations of serum IgM ( P = 0.008 ) and IgG ( P < 0.001 ) aCL along with periodontal parameters after phase I periodontal therapy . CONCLUSION The phase I periodontal therapy altered levels of serum IgG and IgM aCL antibodies in patients with AMI associated with chronic periodontitis |
10,952 | 25,750,550 | Reporting of specific intervention design was suboptimal and impeded the identification of key intervention components for reducing patient delay .
The parallel delivery of public and professional interventions further limited the identification of successful intervention components .
The potential clinical benefits of public interventions are far-reaching , and the challenge remains in translating knowledge improvements and correct behavioral intentions to appropriate behavior when stroke occurs | BACKGROUND Patient delay in presenting to hospital with stroke symptoms remains one of the major barriers to thrombolysis treatment , leading to its suboptimal use internationally .
Educational interventions such as mass media campaigns and community initiatives aim to reduce patient delays by promoting the signs and symptoms of a stroke , but no consistent evidence exists to show that such interventions result in appropriate behavioral responses to stroke symptoms . | Background and Purpose — Thrombolysis with intravenous recombinant tissue plasminogen activator is an effective treatment for acute ischemic stroke , but the number of treatable patients is limited . The PRomoting ACute Thrombolysis in Ischemic StrokE ( PRACTISE ) trial evaluated the effectiveness of a multidimensional implementation strategy for thrombolysis with intravenous recombinant tissue plasminogen activator in acute ischemic stroke . Methods — The PRACTISE trial was a national multicenter cluster-r and omized controlled trial with r and omization after pairwise matching . Twelve hospitals , both urban and community , academic and nonacademic , in the Netherl and s participated . All patients admitted with stroke within 24 hours from onset of symptoms were registered . The intervention included 5 implementation meetings based on the Breakthrough Series model . The primary outcome was treatment with thrombolysis . Secondary outcomes were admission within 4 hours after onset of symptoms , death or disability at 3 months , and quality of life . Results — Overall 5515 patients were included in the study ' 308 patients ( 12.2 % ) in the control centers and 393 patients ( 13.1 % ) in the intervention centers were treated with thrombolysis ( adjusted OR , 1.25 ; 95 % CI , 0.93 to 1.68 ) . Among the 1657 patients with ischemic stroke admitted within 4 hours from onset , 391 ( 44.5 % ) of 880 in the intervention centers were treated with thrombolysis and 305 ( 39.3 % ) of 777 in the control centers ; the adjusted OR for treatment with thrombolysis was 1.58 ( 95 % CI , 1.11 to 2.27 ) . Conclusions — An intensive implementation strategy increases the proportion of patients with acute stroke treated with thrombolysis in real-life setting s. An apparently pivotal factor in the improvement of the treatment rate is better application of contraindications for thrombolysis Background and Purpose — An educational campaign by mass media has been associated with great increases in the knowledge about early symptoms of stroke . However , few studies were conducted with a controlled community intervention study . Methods — To clarify the effects of a 1-year television campaign for the whole population on improvement of knowledge about stroke symptoms in 2 cities , a campaign area and a control area in Japan were selected . Before and after the campaign , 1960 r and omly selected residents aged 40 to 74 years answered a telephone survey regarding knowledge of early stroke symptoms . We calculated the percentage and 95 % CIs of participants who correctly chose all 5 early symptoms of stroke in each area and in each year . Results — Before the campaign , 53 % of participants ( 95 % CI , 50%–55 % ) in the campaign area and 46 % ( 95 % CI , 44%–49 % ) in the control area correctly chose 5 early symptoms . After the 1-year television campaign , knowledge was significantly improved only in the campaign area ( campaign area , 63 % ; 95 % CI , 60%–66 % ; control area , 51 % ; 95 % CI , 48%–54 % ) . After sex stratification , only women showed improved knowledge of early symptoms . The audience rate for the campaign television programs was found to be higher in women than in men . Conclusions – A 1-year stroke educational television campaign effectively improved knowledge about early stroke symptoms among Japanese women aged 40 to 74 years . No impact was found among men in this age group . Future studies should examine the impact of this approach on stroke knowledge among younger individuals and whether there are any behavioral changes that contribute to earlier presentation for treatment BACKGROUND Many critical appraisal tools ( CATs ) exist for which there is little or no information on development of the CAT , evaluation of validity , or testing reliability . The proposed CAT was developed based on a number of other CATs , general research methods theory , and reporting guidelines but requires further study to determine its effectiveness . OBJECTIVES To establish a scoring system and to evaluate the construct validity of the proposed critical appraisal tool before undertaking reliability testing . METHODS Data obtained from this exploratory study along with information on the design of the proposed CAT were combined to evaluate construct validity using the St and ards for educational and psychological testing which consist of five types of evidence : test content , response process , internal structure , relations to other variables , and consequences of testing . To obtain data for internal structure and relations to other variables , the proposed CAT was analysed against five alternative CATs . A r and om sample of 10 papers from six different research design s across the range of health related research were selected , giving a total sample size of 60 papers . RESULTS In all research design s , the proposed CAT had significant ( p<0.05 , two-tailed ) weak to moderate positive correlations ( Kendall 's τ 0.33 - 0.55 ) with the alternative CATs , except in the Preamble category . There were significant moderate to strong positive correlations in the quasi-experimental ( τ 0.70 - 1.00 ) , descriptive/exploratory/observational ( τ 0.72 - 1.00 ) , qualitative ( τ 0.74 - 0.81 ) , and systematic review ( τ 0.62 - 0.82 ) design s and to a lesser extent in the true experimental ( τ 0.68 - 0.70 ) design . There were no significant correlations in the single system research design s. CONCLUSIONS Based on the results obtained , the theory on which the proposed CAT was design ed , and the objective of the proposed CAT there was enough evidence to show that inferences made from scores obtained from the proposed CAT should be sound OBJECTIVE Prolonged prehospital delay in persons experiencing acute coronary syndrome ( ACS ) remains a problem . Underst and ing which patients respond best to particular interventions design ed to decrease delay time would provide mechanistic insights into the process by which interventions work . METHODS In the PROMOTION trial , 3522 at-risk patients were enrolled from 5 sites in the United States ( 56.4 % ) , Australia and New Zeal and ; 490 ( N=272 intervention , N=218 control ) had an acute event within 2 years . Focusing on these 490 , we ( 1 ) identified predictors of a rapid response to symptoms , ( 2 ) identified intervention group subjects with a change in these predictors over 3 months of follow-up , and ( 3 ) compared intervention group participants with and without the favorable response pattern . Hypothesized predictors of rapid response were increased perceived control and decreased anxiety . Knowledge , attitudes , and beliefs were hypothesized to differ between responders and non-responders . RESULTS Contrary to hypothesis , responders had low anxiety and low perceived control . Only 73 ( 26.8 % ) subjects showed this pattern 3 months following the intervention . No differences in ACS knowledge , attitudes , or beliefs were found . CONCLUSION The results of this study challenge existing beliefs . PRACTICE IMPLICATION S New intervention approaches that focus on a realistic decrease in anxiety and perceived control are needed Background and Purpose — Only a small minority of acute stroke patients receive approved acute stroke therapy . We performed a community and professional behavioral intervention project to increase the proportion of stroke patients treated with approved acute stroke therapy . Methods — This study used a quasi-experimental design . Intervention and comparison communities were compared at baseline and during educational intervention . The communities were based in 5 nonurban East Texas counties . The multilevel intervention worked with hospitals and community physicians while changing the stroke identification skills , outcome expectations , and social norms of community residents . The primary goal was to increase the proportion of patients treated with intravenous recombinant tissue plasminogen activator ( rTPA ) from 1 % to 6 % of all cerebrovascular events in the intervention community . Results — We prospect ively evaluated 1733 patients and vali date d 1189 cerebrovascular events . Intravenous rTPA treatment increased from 1.38 % to 5.75 % among all cerebrovascular event patients in the intervention community ( P = 0.01 ) compared with a change from 0.49 % to 0.55 % in the comparison community ( P = 1.00 ) . Among the ischemic stroke patients , an increase from 2.21 % to 8.65 % was noted in the intervention community ( P = 0.02 ) . The comparison group did not appreciably change ( 0.71 % to 0.86 % , P = 1.00 ) . Of eligible intravenous rTPA c and i date s , treatment increased in the intervention community from 14 % to 52 % ( P = 0.003 ) and was unchanged in the comparison community ( 7 % to 6 % , P = 1.00 ) . Conclusions — An aggressive , multilevel stroke educational intervention program can increase delivery of acute stroke therapy . This may have important public health implication s for reducing disability on a national level Background and Purpose — Establishment of stroke centers , combined with accurate paramedic diagnosis and rapid transport , is essential to deliver acute stroke therapy . We wanted to measure and improve paramedic and hospital performance through implementation of the Brain Attack Coalition and American Stroke Association guidelines . Methods — Pre-intervention and active-intervention phases with parallel data measurement points were used . The study involved six hospitals comprising the majority of acute-stroke admissions in Houston , Tex . Hospital , paramedic , and patient data were collected prospect ively pre-intervention and during the active-intervention phase on all suspected acute-stroke patients admitted by Houston Fire Department-Emergency Medical Services . A multilevel educational intervention included paramedic , hospital , and community education . Paramedic diagnostic accuracy , hospital-performance efficiency , and thrombolytic treatment rates were the main outcome measures of the study . Results — Four hundred forty-six patients ( 74 per month ) were transported in the pre-intervention phase to participating hospitals ( 59.8 % of all suspected stroke patients transported city wide by Houston Fire Department — Emergency Medical Services ) , compared with 1072 patients ( 89 per month , or 68.7 % ) transported in the active-intervention phase ( P<0.001 ) . Accuracy of paramedic diagnosis of stroke increased from 61 % to 79 % . Admission within 2 hours of symptom onset increased from 58 % to 62 % ( P=0.002 ) . Thrombolysis rates increased in 4 of 6 centers , with 1 post- tissue plasminogen activator hemorrhage ( 3.7 % ) reported . Conclusions — A multilevel educational program improves rapid hospitalization and paramedic diagnostic accuracy and increases the number of patients presenting for evaluation within the 3-hour tissue plasminogen activator window . Stroke center development supports safe thrombolytic practice in community setting As part of the recruitment efforts for the National Institutes of Health Tissue Plasminogen Activator Pilot Study , public education and awareness campaigns were conducted to encourage early hospital arrival . We evaluated the change in arrival times during the course of the study for all stroke patients , including those who were not entered into study . Methods Data were gathered on all patients presenting within 24 hours of stroke onset to all of the study hospitals . Coincident with the start of the study , educational and promotional programs , which stressed signs and symptoms of stroke and the need to call 911 , were presented to physicians , paramedical personnel , and the public . The study was divided into four quartiles to analyze differences in time to hospital arrival and use of 911 . Results Of 2099 patients screened , time data were available on 1116 . During the course of the study , the mean time from symptom onset to hospital arrival declined significantly ( 3.2 hours versus 1.5 hours ) . Patients arrived for treatment sooner at community hospitals than at university/teaching hospitals . The use of 911 increased from 39 % in the first quartile of the study to 60 % in the fourth quartile . This was a consistent finding in all study sites . Increased use of 911 was seen almost exclusively in patients with nonhemorrhagic stroke . Conclusions Times from stroke onset to hospital arrival decreased significantly during the course of the National Institutes of Health Tissue Plasminogen Activator Pilot Study . Significantly increased use of 911 was the likely major explanation for the shortened arrival times . The decrease in arrival times may be a consequence of the public and professional education programs conducted at all study sites CONTEXT Poor public knowledge of stroke warning signs and risk factors limits effective stroke intervention and prevention . OBJECTIVE To examine temporal trends in public knowledge of stroke warning signs and risk factors . DESIGN AND SETTING Population -based r and om-digit telephone survey conducted in July-November 2000 among individuals in the greater Cincinnati , Ohio , region . PARTICIPANTS A total of 2173 survey respondents ( 69 % response rate ) were r and omly identified based on their demographic similarities to the ischemic stroke population with regard to age , race , and sex . MAIN OUTCOME MEASURES Spontaneous recall of at least 1 important stroke warning sign and 1 established stroke risk factor in comparison with findings from the same survey in 1995 . RESULTS In 2000 , 70 % of respondents correctly named at least 1 established stroke warning sign vs 57 % in 1995 ( P<.001 ) , and 72 % correctly named at least 1 established stroke risk factor vs 68 % in 1995 . Groups of individuals with the highest risk and incidence of stroke , such as persons at least 75 years old , blacks , and men , were the least knowledgeable about warning signs and risk factors . Television was the most frequently cited source of knowledge , 32 % in 2000 vs 24 % in 1995 ( P<.001 ) . CONCLUSIONS Public knowledge of stroke warning signs within the greater Cincinnati region has significantly improved from 1995 to 2000 , although knowledge of stroke risk factors did not improve significantly during the same time period . Public education efforts must continue and should focus on groups at the highest risk of stroke Excessive delay of presentation for stroke in China is reported . In this study , an intervention trial was conducted to promote urgent therapy for acute ischemic stroke . Two communities in Changsha were selected as either intervention or control community from November 2007 to December 2011 . Public and professional education was regularly implemented in the intervention community . Publics ’ knowledge about early identification and urgent therapy of ischemic stroke was surveyed before and after intervention in the two communities . During the intervention period , first-ever ischemic stroke cases occurring in the intervention community ( intervention group ) and that in the control community ( control group ) were collected and followed for 90 days . After intervention , the publics ’ knowledge levels in the intervention community improved significantly . Intervention group ’ average presentation time was shorter than control group ( 8.3 ± 5.8 vs. 10.5 ± 6.5 h , P = 0.018 ) . Percentage of presentation time within 3 h ( 48.0 % ) , the rate of ambulance use ( 59.0 % ) , and thrombolytic therapy ( 9.3 % ) in the intervention group was all obviously higher than that in the control group ( 21.5 , 41.3 , and 4.5 , respectively ) . When admitted , the intervention group had lower mean systolic blood pressure ( 160.8 ± 26.7 vs. 164.7 ± 26.8 mmHg , P = 0.000 ) than control group . Survivors in the intervention group were more likely to be in higher Barthel index scoring groups than that in the control group at day 90 [ ( 75 , 50–100 ) vs. ( 65 , 35–90 ) , P = 0.035 ] . Public and professional education may promote prompt presentation and urgent therapy for ischemic stroke , which may be helpful for patients ’ prognosis OBJECTIVE Current management of acute stroke is characterised by an aggressive approach including specific therapy i. e. reperfusion therapy . However currently stroke patients often arrive too late in hospitals offering adequate treatment . Therefore optimized logistics play a predominant role in modern stroke management . AIMS OF THE STUDY 1 . Does teaching of EMS staff and the public result in reduced prehospital latencies 2 . Will EMS personnel be able to effectively screen patients potentially suitable for thrombolysis ? METHODS During a six week-period all EMS patients presenting with possible signs of an acute stroke were prospect ively registered ( period 1 ) . Data of interest were age , mode of primary contact , prehospital latencies , mode of transportation , destination and final diagnosis . Next an algorithm was established allowing EMS personnel to transfer patients with an assumed stroke to the best suitable hospital . Teaching comprised clinical signs , indication of CT scanning , pathophysiology , specific therapeutic options ( thrombolysis ) , and criteria to identify patients suitable for thrombolysis . In a second step the public was continuously taught about stroke symptoms and the necessity to instantly seek EMS assistance . After 12 months data were compared to baseline ( period 2 ) . RESULTS ( period 2 vs. Period 1 ) : Rate of patients transferred to a stroke center : 60 % vs. 54 % ; rate of those transported to hospitals not offering CT scans : 17 % vs. 26 % ( p < 0.05 ) . Percentage of patients primarily contacting the EMS system : 33 % vs. 24 % . Median interval between onset of symptoms and emergency call : 54 vs. 263 minutes Median interval between the emergency call and arrival at the emergency department : 44 vs. 58 minutes ( p < 0.01 ) . Rate of patients admitted with a diagnosis other than stroke : 18 % vs. 25 % ( n. s. ) . Median interval between onset of symptoms and hospital admission : 140 vs. 368 minutes ( p < 0.001 ) . Median age : 69 vs. 75 years ( p < 0.01 ) . CONCLUSION This study demonstrates the efficacy of educational efforts in reducing latencies and in screening patients potentially suitable for thrombolysis . Future efforts will comprise more intense education of a high risk sub population In systematic review s , evidence -based practice and journal clubs critical appraisal tools are used to rate research papers . However , little evidence exists on whether the critical appraisal tool , subject matter knowledge or research design knowledge affect the appraisal of research papers . A match paired r and omised trial was conducted in August/September 2010 in the Faculty of Medicine , Health and Molecular Science , James Cook University , Australia . Ten participants in total were r and omly assigned to two groups using either an informal appraisal of research ( IA group ) or the Crowe Critical Appraisal Tool ( CCAT group ) , a general critical appraisal tool . Participant independently appraised five research papers , where each paper had a different research design . The scores allocated to the papers by each group were analysed . The intraclass correlation coefficient for absolute agreement was 0.76 for the informal appraisal group and 0.88 for the Crowe Critical Appraisal Tool group . The G study showed that in the informal appraisal group 24 % of variance in scores was attributable to either the rater or paper × rater interactions , whereas this was 12 % in the Crowe Critical Appraisal Tool group . Analysis of covariance showed that there were statistically significant results in the informal appraisal group for subject matter knowledge ( F(1,18 ) = 7.03 , P < 0.05 1 tailed , partial η² = 0.28 ) and rater ( F(4,18 ) = 4.57 , P < 0.05 1 tailed , partial η² = 0.50 ) . Kendall 's tau correlation coefficient also showed a significant weak positive relationship ( τ = 0.38 , P = 0.03 ) between total score and subject matter knowledge for the informal appraisal group . The Crowe Critical Appraisal Tool was more reliable than an informal appraisal of the research papers . In the informal appraisal group , there were significant effects for rater and subject matter knowledge , whereas the Crowe Critical Appraisal Tool almost eliminated the rater effect , and no subject matter knowledge effect was apparent . There was no research design knowledge effect in either group . The Crowe Critical Appraisal Tool provided much better score reliability and should help readers with different levels and types of knowledge to reach similar conclusions about a research paper Background : Increasing the public ’s awareness of stroke is a public health priority . Our objective was to assess changes in the public ’s knowledge of stroke risk factors and warning signs in Michigan during a 5-year period characterized by a sustained statewide public education effort . Methods : Questions regarding knowledge of stroke risk factors and warning signs were included in the 1999 and 2004 Michigan Behavioral Risk Factor Surveys – r and om-digit-dialed statewide surveys of adults . Respondents were asked to report up to 3 risk factors and warning signs for stroke . Results : Between 1999 and 2004 , the proportion of respondents who reported 3 correct stroke warning signs increased substantially from 14.3 to 27.6 % ( p < 0.001 ) , whereas the proportion reporting 3 correct risk factors remained almost unchanged ( 27.9 vs. 29.1 % ) . The reporting of 2 warning signs in particular increased substantially over the 5-year period ; ‘ any weakness or numbness ’ increased from 45.7 to 65.6 % , while ‘ confusion , trouble speaking or underst and ing ’ increased from 29.9 to 46.5 % . Knowledge of stroke warning signs increased across nearly all demographic subgroups , but remained poor for several high-risk groups including the elderly , minorities and those with less education . Conclusions : Knowledge of warning signs increased during this period while there was little change in knowledge of risk factors . The results suggest that these changes occurred in response to the public education campaign which focused primarily on warning signs . The findings further emphasize the need to target those subgroups who are at highest risk of stroke and where knowledge remains poorest Objectives : Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset . We analyzed the effect of interventions aim ed to reduce treatment delays in our single-center observational series . Methods : All consecutive ischemic stroke patients treated with IV alteplase ( tissue plasminogen activator [ tPA ] ) were prospect ively registered in the Helsinki Stroke Thrombolysis Registry . A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011 . In-hospital delays were analyzed as annual median door-to-needle time ( DNT ) in minutes , with interquartile range . Results : A total of 1,860 patients were treated between June 1995 and June 2011 , which included 174 patients with basilar artery occlusion ( BAO ) treated mostly beyond 4.5 hours from symptom onset . In the non-BAO patients , the DNT was reduced annually , from median 105 minutes ( 65–120 ) in 1998 , to 60 minutes ( 48–80 ) in 2003 , further on to 20 minutes ( 14–32 ) in 2011 . In 2011 , we treated with tPA 31 % of ischemic stroke patients admitted to our hospital . Of these , 94 % were treated within 60 minutes from arrival . Performing angiography or perfusion imaging doubled the in-hospital delays . Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival . Conclusions : With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes . The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that , while the patient is being transported Objective : To assess the knowledge of stroke risk factors and warning signs in a representative statewide sample of Michigan adults . Method : Respondents to the 1999 Michigan Behavioral Risk Factor Survey , a r and om-digit-dialed statewide survey of > 2,500 adults , were asked to report up to three risk factors and warning signs for stroke . Predictors of inadequate knowledge ( defined as not reporting any correct responses ) of stroke risk factors and warning signs were identified using multiple logistic regression . Results : Eighty percent reported at least one correct risk factor for stroke , and 28 % reported three . The most frequently mentioned risk factors were hypertension ( 32 % ) , smoking ( 29 % ) , and physical inactivity ( 26 % ) . Sixty-nine percent reported at least one correct warning sign of stroke , but only 14 % reported three . The most frequently mentioned warning signs were sudden weakness or numbness ( 46 % ) and sudden slurred speech , disorientation , or difficulty underst and ing ( 30 % ) . Predictors for inadequate knowledge of both stroke risk factors and warning signs were similar and included age , race , sex , education , hypertension , and smoking . Conclusions : Knowledge of stroke risk factors and warning signs was moderate at best . One in five respondents was not aware of any stroke risk factors , and almost one in three was not aware of any stroke warning signs . Stroke knowledge was poorest among groups that have the highest risk of stroke BACKGROUND In patients with acute stroke , systemic thrombolysis needs to be administered within 3 hours of symptom onset . The aim of the present study was to reduce prehospital delays in a population -based intervention . METHODS We performed a cluster-r and omized trial with 48 zip code areas as cluster units in the catchment area of 3 inner-city hospitals in Berlin , Germany . The primary end point was time between symptom onset and hospital admission . The intervention consisted of an educational letter indicating stroke symptoms and emphasizing the importance of calling the emergency medical services . We additionally included a bookmark and sticker with the emergency medical services ' telephone number . We fitted a series of log-normal survival regression models ( time to admission ) with frailty terms shared by inhabitants of the same zip code area . RESULTS A total of 75 720 inhabitants received the intervention . Between 2004 and 2005 , 741 patients with cerebrovascular events were admitted from the control areas ( n = 24 ) and 647 from the intervention areas ( n = 24 ) . A prehospital time of 2 hours or less and 3 hours or less was achieved by 22 % and 28 % of patients , respectively , in the control group compared with 26 % and 34 % , respectively , in the intervention group . In the log-normal model , time to hospital was reduced by 27 % in the intervention group in women ( acceleration factor , 0.73 ; 95 % confidence interval , 0.58 - 0.94 ) , while no significant effect was found in men . CONCLUSIONS The population -based intervention was effective in reducing prehospital delays in women but not in men . Future research should focus on the potential transferability of the intervention , its sustainability , and sex-specific impact OBJECTIVE To examine the reliability of scores obtained from a proposed critical appraisal tool ( CAT ) . STUDY DESIGN AND SETTING Based on a r and om sample of 24 health-related research papers , the scores from the proposed CAT were examined using intraclass correlation coefficients ( ICCs ) , generalizability theory , and participants ' feedback . RESULTS The ICC for all research papers was 0.83 ( consistency ) and 0.74 ( absolute agreement ) for four participants . For individual research design s , the highest ICC ( consistency ) was for qualitative research ( 0.91 ) and the lowest was for descriptive , exploratory and observational research ( 0.64 ) . The G study showed a moderate research design effect ( 32 % ) for scores averaged across all papers . The research design effect was mainly in the Sampling , Results , and Discussion categories ( 44 % , 36 % , and 34 % , respectively ) . The scores for research design s showed a majority paper effect for each ( 53 - 70 % ) , with small to moderate rater or paper × rater interaction effects ( 0 - 27 % ) . CONCLUSIONS Possible reasons for the research design effect were that the participants were unfamiliar with some of the research design s and that papers were not matched to participants ' expertise . Even so , the proposed CAT showed great promise as a tool that can be used across a wide range of research design Since stroke has become a medical emergency because intravenous tissue plasminogen activator improves outcome after ischemic stroke within 3 h of symptom onset , the focus of acute stroke management lies on the prehospital phase . Having the worst median time of emergency department arrival after stroke onset according to nationwide statistics , we examined the factors influencing a late admission of 174 consecutive patients to our stroke unit and the effects of a public campaign over 5 months . The median time from symptom onset to arrival was 5.2 h ; 36.4 % of patients presented within 3 h at hospital . A high level of education , knowledge of the time window , direct contact with an emergency facility after stroke onset , high number of known symptoms , not living alone , and a stroke in the past were connected with an earlier presentation . The public campaign had a positive effect on median time of symptom onset to arrival from 12 h in July , 7.2 in August , 4.7 in October , 5.2 in November , and 3.2 in December 2002 . This had a favorable effect on the number of thrombolysis |
10,953 | 27,629,261 | Regarding comfort , no clear differences were identified .
Conclusions There is not enough scientific evidence to support or not an association between FR design and gingival health , flossing frequency , or patient comfort . | Background The maintenance of gingival health around orthodontic fixed retainers ( FRs ) is difficult and different design s have been proposed .
Objective The goal of this systematic review was to analyse whether FR design s that allow unobstructed interproximal flossing , compared with the ones that do not , improve gingival parameters . | The purpose of this study was to evaluate the periodontal tissues of patients with m and ibular fixed retention for long or short periods of time . A total of 64 individuals were selected for this study using the following inclusion criteria : long-term lingual fixed retention ; identical type of lingual fixed retainer bonded with the same material s ; no cavities , restorations , or fractures of the m and ibular anterior teeth ; absence of habits and occlusal interferences ; and canine guidance bilaterally . The result ant sample comprised 32 patients ( mean age 25 years ) who had been in retention for a mean period of 9.65 years ( range 9 - 11 years ) and an equal number retained for a period between 3 and 6 months . Plaque , gingival , and calculus indices , probing pocket depth , marginal recession , and bone level at the m and ibular six anterior teeth were recorded for both groups . Demographic , clinical , and radiographic data were investigated with conventional descriptive statistics . Comparisons of the different variables between the two participant groups ( long- and short-term retention ) were carried out using a Mann-Whitney test for indices ( plaque , gingival , and calculus ) , and a Fisher 's exact test ( two sided ) for the remaining variables . No significant difference was found with respect to the plaque and gingival indices and bone level between the two groups . The long-term group presented higher calculus accumulation , greater marginal recession , and increased probing depth ( P < 0.05 ) . The results of this study raise the question of the appropriateness of lingual fixed retainers as a st and ard retention plan for all patients regardless of their attitude to dental hygiene . They also emphasize the importance of individual variability and cautious application of retention protocol s after a thorough consideration of issues related to the anatomy of tissues and oral hygiene Background Most orthodontists believe that fixed retainers are necessary to maintain ideal dental relationships . However , untoward side effects might result from their long-term placement . The aim of this study was to evaluate the clinical and radiographic effect of two commonly used fixed retainers on the health of the periodontium . Methods Thirty patients were r and omly divided into two groups to receive either a fiber-reinforced composite retainer or a spiral wire retainer extended on the lingual surfaces of both maxillary and m and ibular arches from canine to canine . Periapical radiographs were obtained from the patients at the time of placement of the retainers and after the 6-month period to assess the radiographic conditions of the periodontium . Clinical examination was carried out at the same two time intervals . Results Even though there were no significant differences between the two groups of study at the beginning of the trial , there were statistically significant differences after the 6-month follow-up regarding the main outcomes of the study . Nearly all indices showed to deteriorate after 6 months in the fiber-reinforced group , while in the spiral wire group , this was not the case . As for the secondary outcomes , radiographic examination did not reveal any statistically significant differences after 6 months or between the two groups . Conclusions It can be concluded that spiral wire retainers elicit less detrimental periodontal response in the short-term follow-up compared to fiber-reinforced composite retainers as revealed by the primary outcomes of the study .Trial registration Clinical Trials.gov : Abstract Background and Aim : In recent years , fixed lingual retainers have been gaining importance in relapse prevention . The aim of this prospect i ve , r and omized study was to compare different types of fixed retainers used for stabilization of the lower anterior segment with respect to detachment rate , relapse , periodontal and oral hygiene problems , as well as subjective patient discomfort . Patients and Method : Two types of fixed , customized canine-to-canine retainers ( attached to six teeth ) with wire diameters of 0.0215 ” and 0.0195 ” as well as one type of prefabricated canine- and -canine retainer ( bonded to two teeth ) were investigated in a total of 103 patients . Some retainers wer inserted under dry field conditions using a rubber dam , and the others under relatively dry conditions using cotton rolls . In addition , two types of composite , Heliosit ® and Concise ™ , were compared . Results : The canine- and -canine retainer displayed an 18 % detachment rate , a value significantly lower than the 29 % determined for the 0.0195 ” canine-to-canine retainers . The 0.0215 ” canine-to-canine retainer had the highest detachment rate ( 53 % ) . The 37 % detachment rate with dry field bonding was slightly higher than the 32 % with relatively dry field bonding . Comparison of the composites showed a significantly higher detachment rate for Heliosit ® ( 73 % ) than for Concise ™ ( 27 % ) . Plaque accumulation increased with all retainer types in the course of the study , but with no significant inter-group differences . Tooth position with canine-to-canine retainers showed a good degree of stability . The canine- and -canine retainer induced frequent relapse of incisors not bonded to the retainer . In view of their higher rate of subjective discomfort , canine- and -canine retainers were given a significantly poorer rating than their canine-to-canine counterparts . ZusammenfassungHintergrund und Ziel : In den letzten Jahren gewinnen die Lingualretainer zur Rezidivprophylaxe an Bedeutung . Ziel der Studie war es , prospektiv und r and omisiert verschiedene permanente Retainersysteme zur Stabilisierung der Unterkieferfront in Bezug auf Ablöseraten , Rezidive , parodontale und mundhygienische Probleme sowie subjektive Belastungen zu vergleichen . Patienten und Method e : Es wurden zwei an sechs Zähnen adhäsiv befestigte ( Sechspunktretainer ) der Drahtstärken 0,0215 ” und 0,0195 ” und ein konfektionierter , an zwei Zähnen befestigter Retainer ( Zweipunktretainer ) verwendet . Ein Teil der Retainer wurde unter Kofferdam eingesetzt , ein and erer unter relativer Trockenlegung mit Watterollen . Des Weiteren wurden die Komposite Heliosit ® Orthodontic und Concise ™ Orthodontic verglichen . Ergebnisse : Der Zweipunktretainer wies mit 18 % eine signifikant geringere Ablöserate auf als der Sechspunktretainer der Drahtstärke 0,0195 ” mit 29 % . Der Sechspunktretainer der Stärke 0,0215 ” hat mit 53 % die höchste Ablöserate . Die Ablösungsrate lag bei absoluter Trockenlegung mit 37 % geringfügig höher als bei relativer Trockenlegung mit 32 % . Der Vergleich der beiden Komposite ergab eine signifikant größere Ablösungsrate für Heliosit ® ( 73 % ) gegenüber Concise ™ ( 27 % ) . Die Plaqueakkumulation nahm bei allen drei Retainertypen i m Verlauf der Studie zu ohne signifikante Unterschiede zwischen den einzelnen Retainertypen . Die Zahnstellung blieb bei den beiden Sechspunktretainern weitgehend stabil . Bei dem Zweipunktretainer kam es gehäuft zu Rezidiven der nicht gefassten Schneidezähne . Zweipunktretainer schnitten durch die höhere Angabe subjektiver Beschwerden bei der Fragebogenauswertung zur Patientenbelastung signifikant schlechter ab als Sechspunktretainer BACKGROUND Different types and diameters of wire are used in bonded lingual retainers . Some clinicians bond a small diameter multistr and wire to each tooth , while other clinicians bond a large diameter wire to the lingual surfaces of the lower canines . AIM To compare the gingival health , plaque accumulation , tooth stability and integrity of multistr and wire and round wire bonded lingual retainers . METHODS Sixty-two subjects , who had completed treatment and who required fixed retention for the lower anterior segment , were assigned to either the Round wire retainer group or the Multistr and wire retainer group . In the Round wire retainer group , a 0.036 inch round , stainless steel wire was bonded to the lingual surfaces of both lower canines . The Multistr and retainer group had a 0.015 inch multistr and wire bonded to the lingual surfaces of all lower anterior teeth . At least 12 months after debonding , the subjects were recalled and the following variables were recorded : Oral Hygiene Index ( OHI ) , Plaque Index ( PI ) of the lower anterior teeth , Gingival Index ( GI ) of the lower anterior teeth , Irregularity Index ( IRI ) of the lower anterior teeth , and the number of broken retainers . RESULTS There were no significant differences between the PI ( p = 0.165 ) and GI ( p = 0.150 ) of the two groups . More plaque was found on the distal surfaces of the lower anterior teeth in the group with multistr and wire retainers ( p = 0.02 ) . The lower anterior teeth were significantly more irregular in the group with round wire retainers compared to the group with multistr and wire retainers ( p = 0.002 ) . Although the multistr and wire retainers fractured more frequently than the round wire retainers the difference was not statistically significant ( p = 0.325 ) . CONCLUSION More plaque accumulated on the distal surfaces of the lower anterior teeth in subjects with multistr and wire retainers than in subjects with round wire retainers . Multistr and wire retainers were better at maintaining incisor alignment than single span , round wire retainers The present study was performed to test whether bonded , orthodontic canine-to-canine retainers made of spiral wire tended to accumulate more plaque than retainers made of plain wire , and whether the presence of such retainers caused any damage to the teeth involved . 44 patients were classified in eight strata according to age , gender and gingival status . From each stratum , the patients were r and omly divided into 4 groups , each of which received either retainers made of thick plain wire bonded only to the canines , thick twisted wired bonded only to the canines , thin twisted wire bonded to each tooth or removable retainers . Accumulation of plaque and calculus along the gingival margin and gingival inflammation were scored in lingual areas from canine to canine at time of fixed appliance removal and again 4 months after retainer insertion . In addition , accumulation of plaque and calculus and development of caries along the retainer wires were scored after 4 months . The results revealed no differences between the groups for any of the variables . No differences in accumulation of plaque was found between baseline and follow-up examinations . Gingival bleeding was scored less frequently after 4 months in retention than at time of debonding White spot or areas of decalcification are carious lesions of varying extent . The incidence and severity of white spots after a full term of orthodontic treatment were studied among patients in the separate private practice s of two of the authors . To establish a base line of comparison , the presence of white spots in a r and om sample of untreated persons was observed . The incidence of white spots among patients treated by a multibonded technique was recorded at the time of debonding . In addition , white spots were sought in the before- and after-treatment Kodachrome slides of persons whose maxillary incisors had been h and ed . It was found that individual teeth , b and ed or bonded , exhibited significantly more white spot formation than was found in the control group . For the teeth studied , there was no difference in white spot formation in those that were b and ed or bonded . The labiogingival area of the maxillary lateral incisors had the highest incidence of white spots . When studied by segments , the highest incidence occurred among the maxillary incisors ; the lowest was in the maxillary posterior segment . No white spots were found on the lingual surfaces of m and ibular canines and incisors after prolonged use of a canine-to-canine bonded retainer . These findings suggest a relationship between resistance to white spot formation and the rate of salivary flow . Despite the lack of any preventive fluoride program among the study groups , 50 % of the patients demonstrated resistance to white spot formation . The obvious degree of latrogenic damage during orthodontic treatment suggests the need for preventive programs using fluoride . Further clinical research is needed |
10,954 | 26,453,387 | Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms . | The manifestations of nocturnal movements in Parkinson 's disease ( PD ) are protean , with major disabilities related to nocturnal hypokinesia .
While it can be assessed by clinical interviews and screening instruments , these are often inaccurate and prone to recall bias .
In light of advances in sensor technology , we explored the use of sensors in the study of nocturnal hypokinesia , by performing a systematic review of the professional literature on this topic .
Evidence suggests that nocturnal hypokinesia exists even in patients in the early stages , and PD patients turned significantly less and with much slower speed and acceleration than controls , partly related to low nocturnal dopamine level . | In a multinational , double-blind , placebo-controlled trial ( NCT00474058 ) , 287 subjects with Parkinson 's disease ( PD ) and unsatisfactory early-morning motor symptom control were r and omized 2:1 to receive rotigotine ( 2–16 mg/24 hr [ n = 190 ] ) or placebo ( n = 97 ) . Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks . Early-morning motor function and nocturnal sleep disturbance were assessed as co primary efficacy endpoints using the Unified Parkinson 's Disease Rating Scale ( UPDRS ) Part III ( Motor Examination ) measured in the early morning prior to any medication intake and the modified Parkinson 's Disease Sleep Scale ( PDSS-2 ) ( mean change from baseline to end of maintenance [ EOM ] , last observation carried forward ) . At EOM , mean UPDRS Part III score had decreased by −7.0 points with rotigotine ( from a baseline of 29.6 [ st and ard deviation ( SD ) 12.3 ] and by −3.9 points with placebo ( baseline 32.0 [ 13.3 ] ) . Mean PDSS-2 total score had decreased by −5.9 points with rotigotine ( from a baseline of 19.3 [ SD 9.3 ] ) and by −1.9 points with placebo ( baseline 20.5 [ 10.4 ] ) . This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III ( treatment difference : −3.55 [ 95 % confidence interval ( CI ) −5.37 , −1.73 ] ; P = 0.0002 ) and PDSS-2 ( treatment difference : −4.26 [ 95 % CI −6.08 , −2.45 ] ; P < 0.0001 ) . The most frequently reported adverse events were nausea ( placebo , 9 % ; rotigotine , 21 % ) , application site reactions ( placebo , 4 % ; rotigotine , 15 % ) , and dizziness ( placebo , 6 % ; rotigotine 10 % ) . Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction result ed in significant benefits in control of both motor function and nocturnal sleep disturbances . © 2010 Movement Disorder 1 . Insomnia is an even more frequent complaint in elderly patients with Parkinson 's disease than might be expected from the effect of age alone on sleep . 2 . A double-blind , placebo-controlled trial in eleven patients with Parkinson 's disease of mean ( s.d . ) age 80(5 ) years , showed that nocturnal dosing with levodopa produced a clinical ly significant improvement in sleep both as assessed subjectively and by measurement of number of spontaneous moves in bed . 3 . Despite the long interval between tablet administration and morning assessment , walking time was faster on mornings following active treatment This open-label study ( NCT00243945 ) investigated the efficacy of rotigotine transdermal system in 54 Parkinson ’s disease ( PD ) patients with unsatisfactory control of early morning motor impairment and sleep disturbances . Rotigotine dose was up titrated for 8 weeks and maintained for 4 weeks . Mean rotigotine dose at end of maintenance was 11.83 mg/24 h ( SD 3.86 ) . Patients had two overnight hospital stays at baseline and end of treatment during which early morning motor performance was assessed , prior to first morning dose of regular oral antiparkinsonian medication . Rotigotine improved mean Unified Parkinson ’s Disease Rating Scale ( UPDRS ) part III score by −9.3 points , mean Timed Up and Go test duration by −1.4 s and mean morning finger tapping by 26.5 taps/min ; 46 % of patients were considered responders ( ≥30 % improvement of UPDRS III ) . Mean Nocturnal Akinesia , Dystonia and Cramps Sum Score was reduced by 61 % ; mean number of nocturias decreased by 32 % . Rotigotine also improved sleep quality . These results suggest a role for rotigotine in treatment of nocturnal and early morning motor disabilities in PD patients We developed a mobility detection system to analyze pressure changes over time during side-turns in 29 healthy volunteers ( 17 males and 12 females ) with a mean age of 46.1 ± 19.64 years ( ranging from 23 to 86 years ) in order to determine the effect of gender , age , and BMI on performance during bed postural change . Center of gravity ( COG ) location , peak pressure of counteraction , and time to reach peak pressure were the main outcomes used to gauge the ability to make a spontaneous side-turn . Men exhibited significantly higher side-turning force ( P = 0.002 ) and back-turning force ( P = 0.002 ) compared with women . Subjects with BMI ≥27 kg/m2 had significantly higher side-turning force ( P = 0.007 ) and back-turning force ( P = 0.007 ) compared with those with BMI < 27 kg/m2 . After adjusting for other covariates , age positively correlated with back-turning time ( P = 0.033 ) and negatively correlated with side-turning speed ( P = 0.005 ) , back-turning speed ( P = 0.014 ) , side-turning force ( P = 0.010 ) , and back-turning force ( P = 0.016 ) , respectively . Turning times negatively correlated with time to reach peak pressure ( P = 0.008 ) . Our system was effective in detecting changes in turning swiftness in the bed-ridden subject We examined the effects of supplemental st and ard carbidopa/levodopa ( Std-L ) on early morning akinesia in patients with Parkinson 's disease ( PD ) who were being treated with sustained-release carbidopa/levodopa ( L-CR ) . We compared plasma dopa levels and clinical response in 15 PD patients after a dose of Std-L and L-CR ( 2 hours later ) and after a dose of L-CR and placebo in a double-blind , placebo-controlled , crossover study . Plasma dopa levels , total motor score , walking time , and finger tapping time were assessed every 15 minutes for the first 2 hours and then every 30 minutes for the next 3 hours . The time of onset in clinical benefit was significantly earlier with Std-L ( 47 minutes , range 15 to 75 minutes ) as the first dose as compared with L-CR ( 58 minutes , range 30 to 105 minutes ) . Similarly , there was a significant difference in the peak plasma dopa levels ( Cmax ) and the time to reach peak plasma dopa levels ( Tmax ) with administration of Std-L ( Tmax 36 minutes ; Cmax 1,501 mu g/ml ) as compared with L-CR ( Tmax 111 minutes , Cmax 1,260 mu g/ml ) . There was no significant difference in dyskinesias between the two treatment arms . An initial morning dose of Std-L alleviates the problem of delayed-onset clinical response that commonly occurs with L-CR . NEUROLOGY 1996;46 : 1059 - Objectives ‐ Nocturnal disabilities leading to fragmented sleep arising from parkinsonian off period related complications are common , under‐reported and are difficult to treat . In this study , we evaluate the use of nocturnal continuous subcutaneous overnight apomorphine infusion in Parkinson 's disease and restless legs syndrome . Methods ‐ Six parkinsonian patients and 2 patients with restless legs syndrome with nocturnal disabilities refractory to conventional oral therapy were assessed using a sleep diary while on st and ard treatment and during nocturnal apomorphine infusion . Three patients agreed to assessment s during placebo infusion with normal saline . Results ‐ Apomorphine led to a dramatic reduction of nocturnal awakenings , nocturnal off periods , pain , dystonia and nocturia in parkinsonian patients . In patients with restless legs syndrome , apomorphine reduced nocturnal discomfort , reduced leg movements and improved pain and spasm scores significantly . Placebo infusion reproduced pain , nocturnal spasms and sleep disruption . Conclusion ‐ This study suggests that overnight apomorphine infusion may be effective in overcoming refractory nocturnal disabilities in selected patients with Parkinson 's disease and restless legs syndrome Objective : The aim of this research is to characterize further the potential motor and non-motor benefits of rotigotine reported in the double-blind , placebo-controlled RECOVER trial primary publication , by performing a post hoc exploratory analysis of patient status ( symptom improvement/worsening ) . Methods : Full RECOVER trial method ological details have already been reported . The post hoc analyses presented here are done on individual items of the PDSS-2 and PDQ-8 for all patients and two subgroups ( baseline symptomatic and highly symptomatic patients ) . Results : Ten PDSS-2 and five PDQ-8 items show significant mean treatment difference versus placebo . In the overall population , items that most favor rotigotine in percentage of patients with improvement are ‘ limb pain causes waking ’ and ‘ uncomfortable in bed due to immobility ’ for PDSS-2 ; for PDQ-8 , rotigotine is most favored in ‘ difficulty dressing ’ , ‘ felt depressed ’ and ‘ difficulty getting around in public ’ . Among symptomatic and highly symptomatic patients , the PDSS-2 items that most favor rotigotine are both indicators of pain . On the PDQ-8 , the two items most favored in symptomatic patients are ‘ difficulty dressing ’ and ‘ embarrassed in public due to PD ’ , and in the highly symptomatic subgroup ‘ difficulty dressing ’ and ‘ difficulty getting around in public ’ . Conclusion : Though this trial was not powered for statistical subgroup analysis , these post hoc results indicate that treatment with rotigotine may benefit patients with sleep , pain , mood and quality -of-life issues BACKGROUND The LARGO study demonstrated that rasagiline 1 mg/day as adjunct to levodopa significantly reduces OFF time to the same magnitude as adjunct entacapone . This sub study of LARGO aim ed to assess the effect of rasagiline and entacapone on the motor symptoms of PD during the practically defined OFF state . METHODS LARGO was a r and omized , double-blind , multicenter trial that assessed the efficacy and safety of rasagiline ( 1 mg/day ) , entacapone ( 200 mg with each levodopa dose ) , and placebo in 687 levodopa-treated PD patients with motor fluctuations . A sub study of LARGO measured UPDRS motor scores in the practically defined OFF state in 32 rasagiline , 36 entacapone , and 37 placebo patients . RESULTS Treatment with rasagiline produced a significant improvement over placebo of 5.64 units in UPDRS motor OFF score ( P = 0.013 vs. placebo ) . By contrast , the effect of adjunct entacapone was not significant ( P = 0.14 vs. placebo ) . Whereas rasagiline also showed a trend in reducing the UPDRS-ADL OFF score ( P = 0.058 vs. placebo ) , no such trend was noted for entacapone ( P = 0.26 vs. placebo ) . Retrospective analysis , using the Bonferroni correction , of UPDRS motor subdomains further revealed that rasagiline , but not entacapone , significantly improved bradykinesia ( P < 0.001 ) and showed trends for improvements in facial expression , speech , and axial impairment during OFF time . CONCLUSIONS This study provides the first objective ly measured evidence that adjunct rasagiline 1 mg/day is effective in reducing the severity of motor symptoms in the OFF state . This suggests a continuous effect of rasagiline 1 mg/day throughout the day and night and is consistent with its extended duration of therapeutic action Clinical response to a new galenic formulation of levodopa plus benserazide , Madopar HBS , was studied in 25 fluctuating parkinsonians . This open study was planned in two phases . In the first phase , the administering of HBS alone result ed in a surprisingly high number of dropouts . In the second phase , Madopar st and ard in association with Madopar HBS , the follow-up period was 24 months . A stable long-lasting improvement in predictable fluctuations and their severity was maintained for the whole period without any change in drug dose . Nocturnal and early morning akinesia improved too . The study shows that Madopar HBS plus Madopar st and ard is effective in producing a prolonged and stable response in parkinsonian fluctuating patients BACKGROUND The 24-week , double-blind Efficacy and Safety Evaluation in PD-Adjunct ( EASE-PD Adjunct ) study r and omized patients with advanced Parkinson 's disease ( PD ) suboptimally controlled with levodopa to once-daily placebo or adjunctive ropinirole prolonged release ( 2 - 24 mg/day ) . We investigated the effect of ropinirole prolonged release on nocturnal symptoms in these patients . METHODS Total and grouped item PD Sleep Scale ( PDSS ) scores were analyzed post hoc in patients with baseline PDSS total scores ≤ 100 ( troublesome nocturnal symptoms ) and > 100 . RESULTS Baseline PDSS total score was ≤ 100 in 93 of 198 ( 47 % ) and 89 of 189 ( 47 % ) patients receiving ropinirole prolonged release and placebo , respectively ; this subgroup displayed evidence at baseline of greater daily awake ' off ' time , reduced night-time sleep and worse quality of life , than the PDSS > 100 subgroup . Significant improvements with ropinirole prolonged release versus placebo in PDSS score from baseline to Week 24 last observation carried forward were observed for those with baseline PDSS ≤ 100 [ adjusted mean treatment difference 9.0 ( 95 % CI : 2.76 , 15.33 ; P = 0.0051 ) ] , but not > 100 . The PDSS ≤ 100 subgroup demonstrated treatment benefits for PDSS groupings of motor symptoms on waking and global quality of sleep . Changes in daytime sleepiness were similar between treatment groups . The PDSS > 100 subgroup demonstrated significant treatment benefit for global quality of sleep . The unadjusted odds ratio for a positive response with ropinirole prolonged release relative to placebo , for the PDSS ≤ 100 subgroup , was 2.90 ( 95 % CI : 1.42 , 5.95 , P = 0.004 ) . CONCLUSIONS Once-daily ropinirole prolonged release improves nocturnal symptoms in patients with advanced PD not optimally controlled with levodopa who suffer troublesome nocturnal disturbance |
10,955 | 24,717,907 | Despite a demonstrated attenuation of cardiopulmonary bypass-induced inflammatory response by steroid administration , a systematic review of r and omized controlled trials performed so far reveals that steroid administration has potential clinical advantages ( lower mortality and significant reduction of renal function deterioration ) . | OBJECTIVE To evaluate the effects of prophylactic perioperative corticosteroid administration , compared with placebo , on postoperative mortality and clinical outcomes ( renal dysfunction , duration of mechanical ventilation , and ICU length of stay ) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass . | Background —Steroid administration during cardiopulmonary bypass is thought to improve cardiopulmonary function by modulating bypass-related inflammation . This study was design ed to compare preoperative and intraoperative methylprednisolone ( MP ) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome . Methods and Results —Twenty-nine pediatric patients undergoing bypass procedures were r and omly assigned to receive preoperative and intraoperative MP ( 30 mg/kg 4 hours before bypass and in bypass prime , n=14 ) or intraoperative MP only ( 30 mg/kg , n=15 ) . Myocardial inflammatory mediator mRNA expression was determined in paired atrial biopsies ( before and after bypass ) by ribonuclease protection . Before and after bypass , serum IL-6 and IL-10 were measured by ELISA . Postoperative outcome was assessed by intubation time , CICU length of stay , fluid balance , arterio-venous O2 difference ( & Dgr;A−Vo2 ) , and inotrope requirements . Compared with intraoperative MP alone , combined preoperative and intraoperative MP was associated with reduced myocardial mRNA expression for IL-6 , MCP-1 , and ICAM-1 both before and after bypass ( P < 0.05 ) . Patients who received combined steroids had lower serum IL-6 and increased IL-10 at end-bypass ( P < 0.05 ) , although differences were negligible by 24 hours . Combined MP treatment was associated with reduced fluid requirements , lower body temperature , and lower & Dgr;A−Vo2 for the first 24 hours after surgery ( P < 0.05 ) , along with trends toward improvement in other clinical outcomes . Conclusions —Compared with intraoperative steroid treatment , combined preoperative and intraoperative steroid administration attenuates inflammatory mediator expression more effectively and is associated with improved indexes of O2 delivery in the first 24 hours after congenital heart surgery . These findings need to be confirmed in a larger multicenter trial BACKGROUND Corticosteroids are widely used in pediatric open-heart surgery to reduce systemic inflammatory response and to mediate possible cardioprotective effects . However , the optimal dosing of corticosteroids is unknown and their administration varies considerably between different institutions . METHODS Forty neonates undergoing open-heart surgery were r and omized in a double-blind fashion equally into 2 groups . After the induction of anesthesia , 1 group received 30 mg/kg intravenous methylprednisolone and the other a placebo . Concentrations in plasma of interleukin 6 ( IL-6 ) , IL-8 , IL-10 , free methylprednisolone and total methylprednisolone were obtained for the following : ( 1 ) at anesthesia induction before the study drug was administered ; ( 2 ) 30 minutes on cardiopulmonary bypass ; ( 3 ) 5 minutes after protamine administration ; and ( 4 ) 6 hours after weaning from cardiopulmonary bypass . Troponin T was measured at time points T1 , T3 , T4 , and also at 6:00 on the first postoperative morning . Physiological and clinical outcome parameters were also recorded . RESULTS Intravenous methylprednisolone result ed in high plasma drug concentrations that peaked at T2 . Methylprednisolone significantly lowered concentrations of proinflammatory cytokines IL-6 and IL-8 and raised levels of anti-inflammatory IL-10 . No significant differences in troponin T levels were detected . Blood glucose levels were significantly higher in the methylprednisolone group , and patients in this group received more often insulin therapy than controls . No significant differences were observed in other clinical or physiological outcome measurements . CONCLUSIONS Intravenous 30 mg/kg methylprednisolone administered before cardiopulmonary bypass result ed in high effective plasma drug concentrations and a decreased inflammatory response . However , no cardioprotective effect or better clinical outcome was noticed OBJECTIVE To determine the influence of methylprednisolone on the cytokine balance during cardiac surgery . DESIGN Prospect i ve , r and omized , nonblinded study . SETTING University hospital . PATIENTS Twenty-one patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery . INTERVENTIONS According to a r and omized sequence , the patients either received methylprednisolone ( 30 mg/kg ) [ corrected ] before cardiopulmonary bypass and before declamping of the aorta ( MPS group , n = 11 ) or received nothing ( control group , n = 10 ) . MEASUREMENTS AND MAIN RESULTS Serum proinflammatory cytokines ( interleukin [IL]-8 , IL-6 ) and anti-inflammatory cytokines ( IL-10 , IL-1ra ) were measured by enzyme-linked immunosorbent assays . Serum IL-6 and IL-8 concentrations in the control group ( 15.2 + /- 4.1 and 14.1 + /- 1.9 pg/mL , preoperatively ) increased to 242 + /- 70.1 and 97.3 + /- 18.3 pg/mL at 60 mins after declamping of the aorta ( p < .01 , p < .01 , respectively ) . The increases were greater than those from 2.5 + /- 0.6 and 2.5 + /- 0.5 pg/mL to 109.5 + /- 29.0 and 33 + /- 4.1 pg/mL in the MPS group for IL-6 and IL-8 , respectively . Serum IL-10 concentrations increased significantly 60 mins after declamping of the aorta compared with its preoperative value in the two groups ( the control group , from 1.0 + /- 0 to 537.9 + /- 61.7 pg/mL ; the MPS group , from 0.3 + /- 0.2 to 654.9 + /- 24 pg/mL [ p < .01 , p < .01 , respectively ] ) . No difference was found between the two groups . Similarly , serum IL-1ra concentrations in the two groups increased the preoperative value in the control group from 304 + /- 120 to 44,374 + /- 14,631 pg/mL and in the MPS group from 616.5 + /- 109.6 to 35,598 + /- 9,074 pg/mL at 60 mins after declamping of the aorta ( p < .01 , p < .01 , respectively ) . There was no difference between the two groups . CONCLUSIONS Methylprednisolone reduces the production of IL-6 and IL-8 but not that of IL-10 and IL-1ra . These results suggest that one of the mechanisms of the cytoprotective effect of methylprednisolone may be to make changes in the proinflammatory and anti-inflammatory cytokine balance Introduction Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response ( IR ) and postoperative bleeding . Tranexamic acid ( TA ) reduces fibrinolysis and blood loss after cardiopulmonary bypass ( CPB ) . However , its effects on IR and vasoplegic shock ( VS ) are not well known and elucidating these effects was the main objective of this study . Methods A case control study was carried out to determine factors associated with IR after CPB . Patients undergoing elective CPB surgery were r and omly assigned to receive 2 g of TA or placebo ( 0.9 % saline ) before and after intervention . We performed an intention-to-treat analysis , comparing the incidence of IR and VS . We also analyzed several biological parameters related to inflammation , coagulation , and fibrinolysis systems . We used SPSS version 12.2 for statistical purpose s. Results In the case control study , 165 patients were studied , 20.6 % fulfilled IR criteria , and the use of TA proved to be an independent protective variable ( odds ratio 0.38 , 95 % confidence interval 0.18 to 0.81 ; P < 0.01 ) . The clinical trial was interrupted . Fifty patients were r and omly assigned to receive TA ( 24 ) or placebo ( 26 ) . Incidence of IR was 17 % in the TA group versus 42 % in the placebo group ( P = 0.047 ) . In the TA group , we observed a significant reduction in the incidence of VS ( P = 0.003 ) , the use of norepinephrine ( P = 0.029 ) , and time on mechanical ventilation ( P = 0.018 ) . These patients showed significantly lower D-dimer , plasminogen activator inhibitor 1 , and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB . Conclusion The use of TA attenuates the development of IR and VS after CPB.Trial registration numberIS RCT N05718824 BACKGROUND Anti-inflammatory treatment with glucocorticoids during cardiopulmonary bypass can reduce inflammatory mediator release , but the effects of glucocorticoid on outcome are controversial . METHODS We studied the effects of dexamethasone on clinical course , C-reactive protein , von Willebr and factor antigen ( vWf : Ag ) and S100B in a r and omized masked study of children after open cardiac surgery . Twenty children weighing > 10 kg received dexamethasone ( 1 mg kg(-1 ) ) and 20 controls received saline after induction of anaesthesia . We measured vWf : Ag as a marker of endothelial activation , S100B as a marker of cerebral protein release and C-reactive protein as a marker of inflammatory activity . Oxygenation , body temperature , fluid balance , leucocyte and platelet counts , days in the intensive care unit ( ICU ) and days on mechanical ventilation were noted . RESULTS Dexamethasone decreased C-reactive protein concentration on the first postoperative day ( P<0.05 ) , but did not affect the release of vWf : Ag or S100B . There was no significant difference in oxygenation , body temperature , fluid balance , leucocyte and platelet counts , days in the ICU or days on mechanical ventilation between the placebo and dexamethasone-treated groups . CONCLUSION Administration of dexamethasone before cardiopulmonary bypass for paediatric cardiac surgery decreased the inflammatory response , but did not affect the immediate features after surgery or changes in vWf : Ag or S100B OBJECTIVE A heightened inflammatory response occurs after cardiac surgery . The perioperative use of glucocorticoids has been advocated as a method to improve postoperative outcomes . R and omized prospect i ve studies to quantify the effect of methylprednisolone on perioperative outcomes in neonatal cardiac surgery have not been performed . We sought to determine whether preoperative methylprednisolone would improve postoperative recovery in neonates requiring cardiac surgery . METHODS Neonates scheduled for cardiac surgery were r and omly assigned to receive either 2-dose ( 8 hours preoperatively and operatively , n = 39 ) or single-dose ( operatively , n = 37 ) methylprednisolone ( 30 mg/kg per dose ) in a prospect i ve double-blind trial . The primary outcome was the incidence of low cardiac output syndrome ( st and ardized score ) or death 36 hours postoperatively . Secondary outcomes were death at 30 days , interleukin-6 levels , inotropic score , fluid balance , serum creatinine , and intensive care unit and hospital stay . RESULTS Preoperative plasma levels of the inflammatory cytokine interleukin-6 were reduced by 2-fold ( P < .001 ) in the 2-dose methylprednisolone group , consistent with the anti-inflammatory effects of methylprednisolone . However , the incidence of low cardiac output syndrome was 46 % ( 17/37 ) in the single-dose and 38 % ( 15/39 ) in the 2-dose methylprednisolone groups ( P = .51 ) . Two-dose methylprednisolone was associated with a higher serum creatinine ( 0.61 ± 0.18 mg/dL vs 0.53 ± 0.12 mg/dL , P = .03 ) and poorer postoperative diuresis ( -96 ± 49 mL , P = .05 ) . Inotropic requirement , duration of mechanical ventilation , intensive care unit , and hospital stay did not differ between the 2 groups . CONCLUSIONS Combined preoperative and intraoperative use of glucocorticoids in neonatal cardiac surgery does not favorably affect early clinical outcomes and may exacerbate perioperative renal dysfunction Cardiopulmonary bypass ( CPB ) is associated with a systemic inflammatory response . Pre-bypass steroid administration may modulate the inflammatory response , result ing in improved postoperative recovery . We performed a prospect i ve study in the departments of cardiovascular surgery and pediatric intensive care medicine of two university hospitals that included 50 infants who underwent heart surgery . Patients received either prednisolone ( 30 mg/kg ) added to the priming solution of the cardiopulmonary bypass circuit ( steroid group ) or no steroids ( nonsteroid group ) . Clinical outcome parameters include therapy with inotropic drugs , oxygenation , blood lactate , glucose , and creatinine , and laboratory parameters of inflammation include leukocytes , C-reactive protein , and interleukin-8 . Postoperative recovery ( e.g. , the number , dosage , and duration of inotropic drugs as well as oxygenation ) was similar in patients treated with or without steroids when corrected for the type of cardiac surgery performed . After CPB , there was an inflammatory reaction , especially in patients with a long CPB time . Postoperative plasma levels of interleukin-8 were correlated with the duration of CPB time ( r = 0.62 , p < 0.001 ) . Administration of steroids had no significant impact on the laboratory parameters of inflammation . Administration of prednisolone into the priming solution of the CPB circuit had no measurable influence on postoperative recovery and did not suppress the inflammatory response OBJECTIVE We previously demonstrated that dexamethasone treatment before cardiopulmonary bypass in children reduces the postoperative systemic inflammatory response . The purpose of this study was to test the hypothesis that dexamethasone administration before cardiopulmonary bypass in children correlates with a lesser degree of myocardial injury as measured by a decrease in cardiac troponin I release . DESIGN A prospect i ve , r and omized , double-blind study . SETTING The cardiac surgery operating room and intensive care unit of a pediatric referral hospital . SUBJECTS Twenty-eight patients who underwent open-heart surgery for congenital heart defects . INTERVENTIONS Patients received either placebo ( group I , n = 13 ) or dexamethasone , 1 mg/kg iv ( group II , n = 15 ) , 1 hr before initiation of cardiopulmonary bypass . Plasma cardiac troponin I sample s were obtained at three time points : immediately before study agent ( sample 1 ) , 10 mins after protamine sulfate administration after cardiopulmonary bypass ( sample 2 ) , and 24 hrs postoperatively ( sample 3 ) . MEASUREMENTS AND MAIN RESULTS Mean cardiac troponin I levels ( + /-sd ) were significantly lower at sample time 3 in group II ( dexamethasone ; 33.4 + /- 20.0 ng/mL ) vs. group I ( control ; 86.9 + /- 81.1 ) ( p = .04 ) . CONCLUSION Dexamethasone administration before cardiopulmonary bypass in children result ed in a significant decrease in cardiac troponin I levels at 24 hrs postoperatively . We postulate that this may represent a decrease in myocardial injury , and , thus , a possible cardioprotective effect produced by dexamethasone BACKGROUND This prospect i ve double-blinded r and omized study tested the hypothesis that preoperative treatment with dexamethasone would attenuate inflammatory priming of the myocardium , reduce the systemic inflammatory reaction upon cardiac operation , and provide organ protection in neonates . METHODS Twenty neonates ( age , 8 to 21 days ) with transposition of the great arteries scheduled for arterial switch operation were included . Nine received dexamethasone ( 1 mg/kg body weight ) 4 hours before cardiopulmonary bypass , and 11 received natrium chloride . We studied intramyocardial messenger RNA expression of interleukin (IL)-6 , IL-8 , IL-1β , and tumor necrosis factor-α ( TNF-α ) , as well as IL-10 and expression of TNF-α on protein level in right atrial tissue taken before institution of CPB . We measured plasma levels of IL-6 , IL-10 , lipopolysaccharide binding protein , and cardiac troponin T. Cytokine expression was related to postoperative outcome . RESULTS Pretreatment with dexamethasone led to a significant decrease in myocardial expression of IL-6 , IL-8 , IL-1β , and TNF-α messenger RNA and to a decrease in protein synthesis of TNF-α . Plasma concentrations of IL-6 were significantly lower and those of IL-10 significantly higher in pretreated patients . This was associated with lower cardiac troponin T values and lower dobutamine requirement . Levels of lipopolysaccharide binding protein were significantly higher postoperatively in pretreated neonates . CONCLUSIONS Dexamethasone administration before arterial switch operation leads to a shift in the myocardial and systemic cytokine expression profile in neonates with transposition of the great arteries , with downregulation of proinflammatory and upregulation of antiinflammatory cytokines . Lower myocardial cell damage and lower catecholamine requirement suggest myocardial protection in treated patients BACKGROUND : Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery , but have been limited by the lack of placebo control , limited power , and grouping of various steroid regimens together in analysis . We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates . METHODS : Clinical data from the Society of Thoracic Surgeons Data base were linked to medication data from the Pediatric Health Information Systems Data base for neonates ( ≤30 days ) undergoing heart surgery ( 2004–2008 ) at 25 participating centers . Multivariable analysis adjusting for patient and center characteristics , surgical risk category , and within-center clustering was used to evaluate the association of methylprednisolone regimen with outcome . RESULTS : A total of 3180 neonates were included : 22 % received methylprednisolone on both the day before and day of surgery , 12 % on the day before surgery only , and 28 % on the day of surgery only ; 38 % did not receive any perioperative steroids . In multivariable analysis , there was no significant mortality or length-of-stay benefit associated with any methylprednisolone regimen versus no steroids , and no difference in postoperative infection . In subgroup analysis by surgical-risk group , there was a significant association of methylprednisolone with infection consistent across all regimens ( overall odds ratio 2.6 , 95 % confidence interval 1.3–5.2 ) in the lower-surgical-risk group . CONCLUSIONS : This multicenter observational analysis did not find any benefit associated with methylprednisolone in neonates undergoing heart surgery and suggested increased infection in certain subgroups . These data reinforce the need for a large r and omized trial in this population Background —It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists . This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass ( the −174 G/C polymorphism of the promoter of the Interleukin-6 gene ) has a role in the pathogenesis of postoperative atrial fibrillation ( AF ) . Patients and Results —In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined . Interleukin-6 , fibrinogen and C-reactive protein plasma levels were determined preoperatively , 24 , 48 , and 72 hours after surgery and at discharge . Heart rate and rhythm were continuously monitored for the first 36 to 48 hours ; daily 12-lead electrocardiograms were performed thereafter until discharge . GG , CT , and CC genotypes were found in 62 , 38 , and 10 patients , respectively . Multivariate analysis ( which included genotype , age , sex , and classical risk factors for AF ) identified the GG genotype as the only independent predictor of postoperative AF . The latter occurred in 33.9 % of GG versus 10.4 % of non-GG patients ( hazard ratio 3.25 , 95%CI 1.23 to 8.62 ) . AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery ( P < 0.001 for difference between the area under the curve ) . Conclusion —The −174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF . These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication Abstract . Introduction : Cardiopulmonary bypass ( CPB ) induces an inflammatory response believed to contribute to postoperative morbidity . We hypothesized that the magnitude of the inflammatory response following CPB would be associated with adverse clinical outcomes .¶ Methods : Twenty-nine patients had plasma TNF , IL-6 , IL-8 , elastase , histamine , complement C5a , and complement C3a measured by ELISA before , during , and after cardiac operations employing CPB . Inflammatory mediator levels were analyzed with respect to outcomes .¶ Results : Mediator levels peaked at 4 h post-CPB and either returned to baseline or substantially decreased by 24 h. Patients with peak mediator levels above the median for the group as a whole were classified as ' hyper-responders ' ; those with levels below the median were classified as ' normal responders ' . While IL-8 , C3a , and IL-6 levels were independently associated with adverse outcomes , TNF , histamine , and C5a levels were not . Elastase levels trended towards adverse outcomes . IL-8 ' hyper-responders ' experienced significantly greater postoperative weight gain and had higher IL-8 levels at 24 h ( p<0.05 ) , with trends towards renal impairment and protracted supplemental oxygen requirements . C3a ' hyper-responders ' strongly trended towards increased bleeding , delayed extubation , greater postoperative weight gain , and decreased levels of independent functioning at discharge ( p≤0.10 ) . IL-6 ' hyper-responders ' experienced significantly more postoperative bleeding , delayed extubation , and higher IL-6 levels at 24 h compared to ' normal responders ' ( p<0.05 ) . They strongly trended towards greater postoperative weight gain and decreased levels of independent functioning at discharge (p≤0.10).¶ Conclusions : Patients who have an exaggerated inflammatory response to CPB tend to bleed more , require more respiratory support , demonstrate greater capillary leak via weight gain , and display a decline in independent functioning relative to normal responders . Thus , it appears that the magnitude of the inflammatory response to CPB adversely influences clinical outcomes OBJECTIVE To examine whether changes in interleukin (IL)-6 and IL-10 concentrations in patients with systemic inflammatory response syndrome ( SIRS ) can predict a poor outcome . DESIGN Prospect i ve study . SETTING Emergency and intensive care unit of a medical school hospital . PATIENTS Twenty-five patients who fulfilled the criteria for SIRS . INTERVENTIONS Blood sample s were collected for cytokine determinations . MEASUREMENTS AND MAIN RESULTS IL-6 and IL-10 concentrations were measured by enzyme-linked immunosorbent assay in plasma sample s. Blood sample s were obtained at 0 , 1 , 2 , and 4 days from patients who fulfilled the criteria for SIRS . Of 25 patients , 19 survived and the other six patients died of multiple organ failure . Although IL-6 and IL-10 concentrations in survivors decreased gradually from 186.1 + /- 34.4 to 93.6 + /- 18.9 ( SEM ) pg/mL ( p < .05 ) and from 77.4 + /- 21.2 to 32.0 + /- 11.8 pg/mL ( p < .05 ) , IL-6 concentrations in nonsurvivors did not . Although the ratio of IL-6 to IL-10 in survivors was almost stable , the ratio in nonsurvivors increased from 5.5 + /- 3.1 to 18.7 + /- 2.8 ( p < .05 ) . Multivariate analysis showed that when heart rate , mean arterial pressure , IL-6 , IL-10 , and the ratio of IL-6 to IL-10 were taken into account , there only remained a relationship between the ratio of IL-6 to IL-10 and outcome . CONCLUSIONS In nonsurvivors , IL-6 concentrations did not decrease , IL-10 concentration decreased , and the ratio of IL-6 to IL-10 increased . An increase in the ratio of IL-6 to IL-10 indicated a correlation with a poor outcome BACKGROUND A r and omized , prospect i ve , double-blind study of 29 children was performed to evaluate the hypothesis that dexamethasone administration prior to cardiopulmonary bypass would decrease the inflammatory mediator release and improve the postoperative clinical course . METHODS Fifteen children received dexamethasone ( 1 mg/kg intravenously ) and 14 ( controls ) received saline solution 1 hour prior to CPB . Serial blood analyses for interleukin-6 , tumor necrosis factor-alpha , complement component C3a , and absolute neutrophil count were performed . Postoperative variables evaluated included temperature , supplemental fluids , alveolar-arterial oxygen gradient , and days of mechanical ventilation . RESULTS Dexamethasone caused an eightfold decrease in interleukin-6 levels and a greater than threefold decrease in tumor necrosis factor-alpha levels after CPB ( p < 0.05 ) . Complement component C3a and absolute neutrophil count were not affected by dexamethasone . The mean rectal temperature for the first 24 hours postoperatively was significantly lower in the group given dexamethasone than in the controls ( 37.2 degrees + /- 0.4 degrees C versus 37.7 degrees + /- 4 degrees C ; p = 0.007 ) . Dexamethasone-treated patients required less supplemental fluid during the first 48 hours ( 22 + /- 28 mL/kg versus 47 + /- 34 mL/kg ; p = 0.04 ) . Compared with controls , dexamethasone-treated children had significantly lower alveolar-arterial oxygen gradients during the first 24 hours ( 144 + /- 108 mm Hg versus 214 + /- 118 mm Hg ; p = 0.02 ) and required less mechanical ventilation ( median duration , 3 days versus 5 days ; p = 0.02 ) . CONCLUSIONS Dexamethasone administration prior to CPB in children leads to a reduction in the postbypass inflammatory response as assessed by cytokine levels and clinical course The role of steroids in heart surgery was assessed in a group of 95 patients undergoing cardiopulmonary bypass . The treated group ( 47 patients ) received repeated doses ( every six hours ) of methylprednisolone ( 30 mg/kg IV ) in a double-blind , r and omized fashion . The control group ( 48 patients ) received a placebo in a fashion identical to the treated group . There were no significant ( P less than 0.1 ) hemodynamic or biochemical differences between the control group and the patients receiving methylprednisolone . An improvement in survival was observed in the group receiving methylprednisolone . This finding can not be explained with the data obtained from this study , in particular , when no other biochemical findings were improved . A more exhaustive hemodynamic and biochemical analysis is necessary to underst and the subtle changes that are incurred with the use of steroids for heart surgery |
10,956 | 23,542,923 | Results Both systemic and topical administrations reduced blood loss after TKA , but transfusion reducing effects varied in studies whether systemic or topical administrations .
The effects of TNA were influenced by doses and timings of administration .
No increased incidences of symptomatic DVT and PE were found for all reported doses , timings , and routes of TNA administration . | Purpose This systematic review was undertaken to answer three specific questions relating to the clinical values of tranexamic acid ( TNA ) in total knee arthroplasty ( TKA ) : ( 1 ) Whether there are differences in blood-saving effects between the systemic and topical administrations ; ( 2 ) Whether blood-saving effects of TNA differ by doses and timings of administration ; and ( 3 ) Whether the use of TNA is safe at all reported doses , timings , and routes of administration with respect to the incidences of symptomatic deep-vein thrombosis ( DVT ) and pulmonary embolism ( PE ) . | The aim of the present study was to investigate aspects of coagulation and fibrinolysis during knee arthroplasties in order to find out . 1 . whether an increased fibrinolysis is correlated to an increased blood loss 2 . whether there is a difference in markers for coagulation and fibrinolysis in peripheral venous blood compared to those in blood from the wounds 3 . whether the administration of tranexamic acid modifies the fibrinolytic response . Twenty-four patients were included . Twelve patients were given tranexamic acid intravenously at the end of the operation . The dose was repeated three hours later . The other 12 patients were given an equivalent amount of placebo . The administration was r and omised and double-blind . Levels of prothrombin fragments 1 + 2 , D-dimers , plasminogen , alpha 2-antiplasmin , tissue plasminogen activator ( tPA ) , and plasminogen activator inhibitor ( PAI-1 ) in venous blood were investigated just before the operation , at the end of the operation and three hours later . At the end of the operation blood for analysis was also drawn from the wound . Coagulation and fibrinolysis was activated during and after surgery . The activation was significantly higher in blood from the wounds than in peripheral venous blood . We found no direct correlation between the degree of fibrinolysis and blood loss . The administration of tranexamic acid reduced fibrinolysis in the wounds but not in peripheral venous blood . The postoperative blood loss was reduced by half The aim of this r and omized prospect i ve study was to clarify risks associated with a drain-clamping method using tranexamic acid and carbazochrome sodium sulfonate hydrate after total knee arthroplasty ( TKA ) . Subjects comprised 100 patients scheduled to undergo TKA , r and omized into 2 groups : 50 patients received the drain-clamping method using tranexamic acid and carbazochrome sodium sulfonate hydrate and 50 patients received drain-clamping with saline . Although bleeding volume was significantly lower in the group with tranexamic acid and carbazochrome sodium sulfonate hydrate , risk of asymptomatic deep venous thrombosis as detected by ultrasonography was comparable between groups . Tranexamic acid and carbazochrome sodium sulfonate hydrate in the drain-clamping method help reduce bleeding after TKA without increasing the risk of deep venous thrombosis BACKGROUND Total knee arthroplasty ( TKA ) is often carried out using a tourniquet and shed blood is collected in drains . Tranexamic acid decreases the external blood loss . Some blood loss may be concealed , and the overall effect of tranexamic acid on the haemoglobin ( Hb ) balance is not known . METHODS Patients with osteoarthrosis had unilateral cemented TKA using spinal anaesthesia . In a double-blind fashion , they received either placebo ( n=24 ) or tranexamic acid 10 mg kg(-1 ) ( n=27 ) i.v . just before tourniquet release and 3 h later . The decrease in circulating Hb on the fifth day after surgery , after correction for Hb transfused , was used to calculate the loss of Hb in grams . This value was then expressed as ml of blood loss . RESULTS The groups had similar characteristics . The median volume of drainage fluid after placebo was 845 ( interquartile range 523 - 990 ) ml and after tranexamic acid was 385 ( 331 - 586 ) ml ( P<0.001 ) . Placebo patients received 2 ( 0 - 2 ) units and tranexamic acid patients 0 ( 0 - 0 ) units of packed red cells ( P<0.001 ) . The estimated blood loss was 1426 ( 1135 - 1977 ) ml and 1045 ( 792 - 1292 ) ml , respectively ( P<0.001 ) . The hidden loss of blood ( calculated as loss minus drainage volume ) was 618 ( 330 - 1347 ) ml and 524 ( 330 - 9620 ) ml , respectively ( P=0.41 ) . Two patients in each group developed deep vein thrombosis . CONCLUSIONS Tranexamic acid decreased total blood loss by nearly 30 % , drainage volume by approximately 50 % and drastically reduced transfusion . However , concealed loss was only marginally influenced by tranexamic acid and was at least as large as the drainage volume Purpose The surgical stress of total knee arthroplasty ( TKA ) procedure and the application of intra-operative pneumatic thigh tourniquet increases local fibrinolytic activity , which contributes significantly to post-operative blood loss . Tranexamic acid , an antifibrinolytic drug , is commonly used to control post-operative blood loss . The recommended mode of administration of tranexamic acid is either oral or intravenous . However , the mechanism of action of the tranexamic acid points towards the possible effectiveness it may have following local/intra-articular application . This prospect i ve , double-blinded , r and omized preliminary study evaluated the efficacy of intra-articular tranexamic acid in reducing TKA-associated post-operative blood loss . Methods Fifty consenting patients with osteoarthritis of the knee scheduled for primary unilateral cemented-TKA were r and omly allocated to one of the two groups : Tranexamic Acid ( TA ) group ( n = 25 , 500 mg/5 ml tranexamic acid ) and the control group ( n = 25 , 5 ml 0.9 % saline ) . The drug and control solution were administered intra-articularly through the drain tube immediately after the wound closure . Parameters related to blood loss ( drop in haemoglobin , haematocrit differential ) and the drain output [ volume ( ml ) ] were compared between the two groups . Results On a comparative basis , TA-group obtained significant reduction in the drain output [ 95 % CI : 360.41–539.59 , p < 0.001 ] at 48 h post-operatively . Even though the control group received sixfold more blood transfusion than TA-group , it showed a greater drop in haemoglobin and haematocrit ( p < 0.05 ) . Conclusions Local application of tranexamic acid seems to be effective in reducing post-TKA blood loss as well as blood transfusion requirements . Level of evidence Therapeutic study , Level II After total knee arthroplasty ( TKA ) the technique of wound management is not st and ardised . In this prospect i ve study the efficacy of autologous blood reinfusion from the wound was investigated . One hundred patients ( 100 TKAs ) were enrolled in this sequential cohort study . In one-half of the operations , a reinfusion system with suction and in the other half one wound drain without suction were used . Blood loss , transfusion requirements , range of motion , Insall scores and the incidence of complications were studied . The use of a reinfusion system did not decrease the homologous transfusion requirements . The blood loss in the group with a suction drainage system was significantly higher . Our experiences since May 2002 with one drain without suction in 787 consecutive TKAs confirm all findings of the current study .RésuméAprès une arthroplastie totale du genou le problème des pertes sanguines , n’est pas aujourd’hui un problème st and ardisé . Lors d’une étude prospect i ve , l’efficacité de l’autotransfusion a été appréciée . Cent prothèses totales ont été enrôlées dans une cohorte . La moitié d’entre eux ont bénéficié d’une retransfusion des pertes sanguines du redon et pour l’autre moitié , le redon simple a été utilisé , sans récupération du sang post-opératoire . Les pertes de sang , la nécessité de transfusion , la mobilité , le score Insall et les complications ont été étudiés . L’utilisation d’une récupération avec retransfusion du sang post-opératoire ne diminue pas le nombre de transfusions homologues . Les pertes sanguines dans le groupe avec drainage simple sont plus importantes . Notre expérience depuis mai 2002 avec l’utilisation d’un drain sans aspiration dans 787 prothèses totales du genou consécutives confirment ses données Background The antifibrinolytic tranexamic acid reduces surgical blood loss , but studies have not identified an optimal regimen . Questions / purpose sWe studied different dosages , timings , and modes of administration to identify the most effective regimen of tranexamic acid in achieving maximum reduction of blood loss in TKA . Methods We prospect ively studied five regimens ( four intravenous , one local ; 40 patients each ) with a control group ( no tranexamic acid ) . The four intravenous ( 10-mg/kg dose ) regimens included ( 1 ) intraoperative dose ( IO ) given before tourniquet deflation , ( 2 ) additional preoperative dose ( POIO ) , ( 3 ) additional postoperative dose ( IOPO ) , and ( 4 ) all three doses ( POIOPO ) . The fifth regimen was a single local application ( LA ) . Two independent parameters of drain loss and total blood loss , calculated by the hemoglobin balance method , were evaluated statistically . Results Both parameters were reduced in all five regimens as against the control . A significant reduction in drain loss was seen in the POIO , IOPO , and POIOPO groups whereas total blood loss was significantly reduced in the POIO , POIOPO , and LA groups . The POIOPO group had the least drain loss ( 303 mL ) and least total blood loss ( 688 mL ) . The IO group had the greatest drain loss and the IOPO group the greatest total blood loss . Conclusions Single-dose tranexamic acid did not give effective results . The two-dose regimen of POIO was the least amount necessary for effective results . When compared against the control , this regimen produced reduction of drain loss and total blood loss , whereas the IOPO regimen did not . The three-dose regimen of POIOPO produced maximum effective reduction of drain loss and total blood loss . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Abstract There have been several attempts to reduce postoperative blood loss in patients undergoing total arthroplasty . Benoni et al. reported the usefulness of tranexamic acid in total knee arthroplasty ( TKA ) . We investigated its effect in TKA and total hip arthroplasty ( THA ) . Blood loss was significantly reduced in patients given tranexamic acid in both the TKA and THA groups , and no severe complications , such as venous or pulmonary thrombosis , were noted in any of the patients who received the agent . Administration of tranexamic acid seems to be useful for reducing postoperative blood loss in TKA and THA UNLABELLED Both acute normovolemic hemodilution ( NVHD ) and tranexamic acid ( TA ) are potentially useful allogeneic blood conservation strategies after total knee replacement . However , the relative efficacy of these blood-sparing techniques is unknown . Therefore , to compare the postoperative allogeneic blood sparing of NVHD and TA after total knee replacement , we investigated 40 patients in a prospect i ve , single-blinded study protocol . In Group TA , 30 min before deflating the limb tourniquet , an IV infusion of TA , 15 mg/kg , was administered over a 30-min period . Thereafter , a constant IV infusion of 10 mg x kg(-1 ) x hr(-1 ) was administered until 12 h after deflation of the limb tourniquet . Before induction of anesthesia , NVHD patients were bled to a target hematocrit of approximately 28 % . Intravascular blood volume was maintained with lactated Ringer 's solution . All autologous blood was transfused at the end of the surgery . Postoperatively , hematocrit was measured daily . In all cases , a hematocrit < 27 % was the postoperative transfusion trigger . Before discharge , deep vein thrombosis was excluded by Echo Doppler . Three months after surgery , the incidence of delayed thromboembolic events was assessed . The two groups were demographically comparable . In Group NVHD , 843 mL+/-289 of autologous blood was removed . Despite autologous blood transfusion , during the early postoperative period and until the third postoperative day , the NVHD group had significantly ( P < 0.01 ) lower mean hematocrits when compared with the TA group . Thereafter , because of a significantly ( P < 0.0008 ) greater allogeneic blood requirement in the NVHD group , no statistically significant difference in mean hematocrit recordings was noted among the groups . Blood accumulation in the surgical drain 12 h postoperatively , was significantly ( P < 0.0008 ) higher in the NVHD group ( 259 mL+/-156 ) when compared with the TA group ( 110 mL+/-62 ) . Significantly ( P < 0.0008 ) more allogeneic blood was transfused in the NVHD group ( 19 U/13 patients ) when compared with the TA group ( 2 U/2 patients ) . No abnormal Echo Doppler studies were reported . During the 3-mo follow-up period , a deep vein thrombosis and pulmonary embolus were documented in one patient in the NVHD group . We conclude that perioperative hemodynamic stability and allogeneic blood sparing is superior after tranexamic acid administration when compared with normovolemic hemodilution . IMPLICATION S For total knee replacement , when compared with normovolemic hemodilution , tranexamic acid administration is associated with superior perioperative hemodynamic stability and allogeneic blood sparing We investigated the effect of a fibrinolytic inhibitor , tranexamic acid , on blood loss and blood transfusion in knee arthroplasty by a r and omised , double-blind study of 86 patients . A dose of 10 mg/kg body-weight of either tranexamic acid or placebo was given intravenously shortly before the release of the tourniquet , and repeated three hours later . The mean total blood loss was 730 + /- 280 ml in the tranexamic acid group as against 1410 + /- 480 ml in the placebo group ( p < 0.001 ) . Both the number of patients receiving blood transfusion and the number of blood units transfused were reduced to one-third in the treated group , and mean postoperative Hb concentrations were significantly higher after prophylaxis . The number of thromboembolic complications was the same in both groups . Tranexamic acid should be given prophylactically in order to be effective We have investigated the effect of treatment with tranexamic acid , an inhibitor of fibrinolysis , on blood loss , blood transfusion requirements and blood coagulation in a r and omized , double-blind , placebo-controlled study of 42 patients after total knee arthroplasty . Tranexamic acid 15 mg kg-1 ( n = 21 ) or an equivalent volume of normal saline ( n = 21 ) was given 30 min before surgery and subsequently every 8 h for 3 days . Coagulation and fibrinolysis values , blood loss and blood units administered were measured before administration of tranexamic acid , 8 h after the end of surgery and at 24 and 72 h after operation . Coagulation profile was examined ( bleeding time , platelet count , prothrombin time ( PT ) , activated partial thromboplastin time ( aPTT ) , plasminogen , beta-thromboglobulin and fibrinogen ) . Fibrinolysis was evaluated by measurement of concentrations of D-dimer and fibrinogen degradation products ( FDP ) . Total blood loss in the tranexamic acid group was 678 ( SD 352 ) ml compared with 1419 ( 607 ) ml in the control group ( P < 0.001 ) , and occurred primarily during the first 24 h after surgery . Thirteen patients received 1 - 5 u. of packed red blood cells in the control group compared with two patients in the tranexamic acid group , who received 3 u. ( P < 0.001 ) . Postoperative packed cell volume values were higher in the tranexamic acid group despite fewer blood transfusions . Postoperative concentrations of plasminogen were decreased significantly in the tranexamic acid group ( P < 0.001 ) . Platelet count , PT , aPTT , bleeding time , beta-thromboglobulin , fibrinogen and FDP concentrations did not differ between groups , but D-dimer concentrations were increased in the control group . Thromboembolic complications occurred in two patients in the control group compared with none in the tranexamic acid group BACKGROUND Risks and costs of allogeneic blood transfusions m and ate strategies to reduce blood loss in surgery . The objective of this study was to assess the efficacy of antifibrinolytic treatment in reducing perioperative blood loss during total knee replacement . METHODS A double-blind , r and omized and placebo-controlled clinical trial was carried out on 127 patients undergoing total knee replacement . Patients in the study group received tranexamic acid 10 mg kg(-1 ) i.v . just before the tourniquet was deflated and 3 h later , or epsilon-aminocaproic acid 100 mg kg(-1 ) before tourniquet deflation followed by continuous perfusion ( 1 g h(-1 ) ) during 3 h. External perioperative blood loss was measured and total blood loss was calculated . The number of patients transfused and number of packed red cell ( PRC ) units transfused was recorded and possible postoperative thromboembolic complications were investigated . RESULTS Total blood loss [ mean ( sd ) ] was 1099 ml ( 535 ) in the group that received antifibrinolytic agents and 1784 ml ( 660 ) in the control group ( P<0.001 ) . Five patients ( 7.5 % ) in the study group and 23 ( 38.3 % ) in the control group ( P<0.001 ) received blood transfusions ; the first group received a mean of 0.10 PRC unit per patient and the second , 0.58 ( P<0.001 ) . Mean reduction in haemoglobin levels ( g dl(-1 ) ) between preoperative and fifth day postoperative readings was 2.5 ( 0.9 ) in the study group and 3.4 ( 1.2 ) in the control group ( P<0.001 ) . Clinical assessment did not reveal any thromboembolic complications . CONCLUSIONS Antifibrinolytic agents produce a significant decrease in blood loss in patients undergoing total knee replacement , reflected in a reduction in the number of blood transfusions required Background and Objectives For decades , hypotensive anesthesia has been used in an attempt to reduce intraoperative blood loss . Hypotensive epidural anesthesia ( HEA ) is a relatively new technique in hypotensive anesthesia . Use of a tourniquet has been shown to be associated with a higher risk of cardiovascular and thromboembolic complications . The effect of HEA on blood loss and need for transfusion in total knee replacement ( TKR ) is not known . Methods Thirty consecutive patients scheduled for TKR were r and omized to HEA without tourniquet or spinal anesthesia with the use of a tourniquet ( SPI ) . HEA was performed as an epidurally induced sympathetic block and there was an infusion of low-dose epinephrine to stabilize the circulation . Results Intraoperative mean arterial blood pressure was 48 mm Hg ( HEA ) versus 83 mm Hg ( SPI ) ( P < .001 ) . Intraoperative blood loss was 146 mL ( HEA ) versus 13 mL ( SPI ) ( P < .001 ) . Postoperative blood loss at any time was significantly reduced in the HEA group , and total loss of blood was 1,056 mL ( HEA ) versus 1,826 mL ( SPI ) ( P < .001 ) . Half of the bleeding took place during the first 3 postoperative hours and 80 % during the first 24 hours . In the HEA group , 57 % of the patients went through surgery and the hospital stay without receiving blood transfusion versus 19 % in the SPI group ( P < .05 ) . There was a significantly reduced amount of blood transfusion in the HEA group ( 193 mL ) versus 775 mL in the SPI group ( P < .005 ) . No cardiopulmonary , cerebral , or renal complications were registered . Conclusions We conclude that HEA is a safe technique that allows TKR without a tourniquet . Compared with spinal anesthesia , the use of HEA for TKR significantly reduces blood loss and the need for blood transfusion A prospect i ve , r and omised controlled trial compared the effects of two medications intended to reduce blood loss from total knee arthroplasty . Patients were r and omised to one of the following three treatment groups : 10mg/kg tranexamic acid at given at induction of anaesthesia , 10 ml of fibrin spray administered topically during surgery , or to a control group receiving neither treatment . Sixty six patients underwent elective cemented total knee arthroplasty ; computer navigation was used in all cases . There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups ( p=0.181 ) . There was no significant difference in blood loss between the tranexamic acid and fibrin spray groups(p=0.181 ) . The fibrin spray led to a significant reduction in blood loss compared to control ( p=0.007 ) . The effect of tranexamic acid did not reach significance ( p=0.173 ) . We conclude that fibrin spray was effective in reducing blood loss but that with a study of this power , we were unable to detect an effect of tranexamic acid in cemented navigated total knee replacement at the dose used STUDY OBJECTIVE To assess the influence of tourniquet inflation-deflation as well as desmopressin and tranexamic acid ( TA ) administration on prothrombin fragment 1.2 , fibrinogen , plasmin antiplasmin complex , and D-dimer concentrations during total knee replacement . DESIGN R and omized , placebo-controlled study . SETTING Large referral hospital . PATIENTS 30 ASA physical status I , II , and III patients undergoing total knee replacement . INTERVENTIONS Patients were r and omized to one of three treatment groups . Patients received either tranexamic acid , desmopressin , or an equal volume of saline , intravenously . MEASUREMENTS AND MAIN RESULTS Cubital blood was drawn immediately before induction of anesthesia , 1 hour after tourniquet application , and 2 and 15 minutes after tourniquet deflation . Fibrinogen and D-dimer levels were measured using the Clauss Method and latex agglutination , respectively . Plasmin antiplasmin complex and prothrombin fragment 1.2 levels were measured by enzyme-linked immunosorbent assay ( ELISA ) . All assays were performed in duplicate , and intra-assay variability was documented . No statistically significant difference in fibrinogen , D-dimer , plasmin antiplasmin complex , or prothrombin fragment 1.2 levels was demonstrated among the groups . Similarly , within each group there were no statistically significant differences in the variables studied . However , despite the lack of statistical significance , when compared with their levels during tourniquet application , an increase in D-dimer and plasmin antiplasmin complex levels was observed in all three groups at 2 and 15 minutes after tourniquet release . In contrast , no increase in prothrombin fragment 1.2 generation was noted . Significantly more allogeneic blood was transfused in the Control and Desmopressin Groups when compared with the tranexamic acid group ( p < 0.02 ) . CONCLUSIONS No evidence of tourniquet-induced fibrinolysis or thrombin generation was demonstrated in the systemic circulation . Desmopressin and tranexamic acid had no significant effect on the variables measured Purpose This is a r and omised controlled trial to examine whether intra-articular injection of tranexamic acid ( TXA ) decreases blood loss , as well as reducing leg swelling after total knee arthroplasty ( TKA ) . Methods We performed 100 TKA in osteoarthritis patients . At closure , a total of 2,000 mg/20 ml TXA was injected into the knee joint through a closed suction drain ( TXA group ) . For the control group , the same volume of physiological saline was injected . The pre-operative condition of the patients , post-operative haemoglobin ( Hb ) levels , discharge volumes from drain , D-dimer and needs for transfusion were compared between these two groups . Furthermore , leg diameters ( thigh , suprapatellar portion and calf girth ) were measured pre- and post-operatively to investigate whether TXA has an influence on leg swelling after surgery . Results The results revealed that post-operative decrease in Hb level was significantly reduced in the TXA group . Furthermore , knee joint swelling after operation was significantly suppressed in the TXA group compared to the control group . Conclusions The results revealed intra-articular administration of TXA decreased not only blood loss , but also knee joint swelling after TKA To assess the blood-sparing efficacy of tranexamic acid ( TA ) administered orally or via a variable IV infusion , 80 healthy patients undergoing elective total knee replacement were studied according to a prospect i ve , controlled , r and omized , single-blinded study design . Patients were allocated to one of four treatment groups . In group TA-long , 30 min before deflation of the limb tourniquet , an IV bolus dose of TA 15 mg/kg was administered over 30 min . Thereafter , a constant IV infusion of 10 mg · kg−1 · h−1 was administered until 12 h after final deflation of the limb tourniquet . In group TA-short , a similar regimen was followed ; however , the constant IV infusion was discontinued 2 h after final deflation of the limb tourniquet ( time of discharge from the postanesthesia care unit ) . Thereafter , oral TA 1 g was administered after 6 and 12 h. In group TA-oral , 60 min before surgery an oral dose of TA 1 g was administered . After surgery , a similar dose of TA was administered every 6 h for the next 18 h. In the control group , TA was not administered . At patient discharge , postoperative allogeneic blood administration was significantly more in group Control when compared with each of the three TA treatment groups . Because oral drug administration is simple and does not require specific infusion equipment , the authors suggest that oral TA is a superior blood-sparing strategy compared with IV drug administration We performed a r and omised , controlled trial involving 150 patients with a pre-operative level of haemoglobin of 13.0 g/dl or less , to compare the effect of either topical fibrin spray or intravenous tranexamic acid on blood loss after total knee replacement . A total of 50 patients in the topical fibrin spray group had 10 ml of the reconstituted product applied intra-operatively to the operation site . The 50 patients in the tranexamic acid group received 500 mg of tranexamic acid intravenously five minutes before deflation of the tourniquet and a repeat dose three hours later , and a control group of 50 patients received no pharmacological intervention . There was a significant reduction in the total calculated blood loss for those in the topical fibrin spray group ( p = 0.016 ) and tranexamic acid group ( p = 0.041 ) compared with the control group , with mean losses of 1190 ml ( 708 to 2067 ) , 1225 ml ( 580 to 2027 ) , and 1415 ml ( 801 to 2319 ) , respectively . The reduction in blood loss in the topical fibrin spray group was not significantly different from that achieved in the tranexamic acid group ( p = 0.72 ) A prospect i ve study was undertaken to assess the efficacy and financial cost of the use of an autologous blood transfusion device in the reduction of allogeneic blood requirements of patients undergoing primary unilateral total knee arthroplasty . Forty-nine consecutive patients received either the CellTrans blood salvage device ( group A of 32 patients ) or the Redivac high vacuum drainage system ( group B of 17 patients ) . The preoperative and postoperative haemoglobin levels were recorded at 72 or 96 hours . Nine percent of group A patients received an allogeneic blood transfusion compared to 59 % in group B. There was an average saving of 1.1 unit of allogeneic blood per patient in group A ( p<0.001 ) . The total cost per patient was about Euro 111 less for the group A patients . Autologous re-infusion was found in this study to be an effective method of reducing allogeneic blood requirements and to afford significant cost savings in primary unilateral knee arthroplasty Antifibrinolytics seem to reduce postoperative blood loss after total knee arthroplasty . Few studies have shown the impact of these drugs on the mechanisms of coagulation . The purpose of this study was to examine coagulation/fibrinolysis variables as well as blood loss after total knee arthroplasty with and without antifibrinolytics in the operated limb on a regional level . Thirty-six patients were r and omized into one of three groups to receive aprotinin , tranexamic acid , or no medication . We took blood sample s of the femoral vein before deflating the tourniquet and after 5 , 10 , 30 , 60 , 120 min and on the first postoperative day . The implantation of a knee prosthesis in artificial ischemia caused a significant activation of coagulation and fibrinolysis in the regional circulation . Tranexamic acid and aprotinin did not cause a significant modulation of fibrinolysis variables or a significant reduction of postoperative bleeding and transfusion requirements . One of the differences in comparison to other studies was the decreased total blood loss . The use of bone cement as well as surgical hemostasis before wound closure may be regarded as reasons for this . Therefore , primarily these methods should be used because there is no increased risk of adverse drug effects Background Tranexamic acid ( TEA ) reportedly reduces perioperative blood loss in TKA . However , whether it does so in minimally invasive TKA is not clear . Questions / purpose sWe asked whether TEA would reduce blood loss and blood transfusion requirements after minimally invasive TKA . Patients and Methods We prospect ively enrolled 100 patients who underwent minimally invasive TKAs : 50 received one intravenous injection of TEA before deflation of the tourniquet and a control group of 50 patients received an equivalent volume of placebo . We compared changes in hemoglobin , postoperative drainage , total blood loss , and transfusion rates between the two groups . Results The total blood loss was less for patients in the TEA group than for the control group : 833 mL ( 374–1014 mL ) versus 1453 mL ( 733–2537 mL ) , respectively . The rate of blood transfusion also was less for patients in the TEA group than in the control group ( 4 % versus 20 % ) . The hemoglobin levels on the second and fourth postoperative days were greater for patients in the TEA group than in the control group . Conclusions Our data suggest one intraoperative injection of TEA decreased the total blood loss and need for transfusion after minimally invasive TKA.Level of Evidence Level II , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence Tourniquets commonly are used during total knee arthroplasties to reduce intraoperative blood loss , despite their various side effects . The goal of this study was to determine whether tourniquet use could be avoided using epinephrine-augmented hypotensive epidural anesthesia during a total knee arthroplasty without negative effects on perioperative hemoglobin values . One hundred patients having total knee arthroplasties were included in a prospect i ve , observer-blinded , controlled , and r and omized study . Forty-nine patients received epinephrine-augmented hypotensive epidural anesthesia without use of a tourniquet ( Group A ) , and 51 patients received normotensive epidural anesthesia with use of a tourniquet ( Group B ) . Hemoglobin was evaluated and is reported preoperatively , immediately and 6 hours postoperatively , and on Days 1 , 2 , 3 , 5 , and 6 in absolute and relative values . Data were not collected for Day 4 . Greater absolute and relative postoperative hemoglobin values were observed in Group A immediately postoperative , on Day 5 , and on Day 6 . In patients who did not have transfusions , the mean relative hemoglobin values were greater in Group A at all times evaluated ( except on Day 1 ) . Epinephrine-augmented hypotensive epidural anesthesia is an effective method to avoid the use of a tourniquet during total knee arthroplasty without the negative effects on perioperative hemoglobin values . Level of Evidence : Therapeutic study , Level I-1a ( r and omized controlled trial , significant difference ) . See the Guidelines for Authors for a complete description of levels of evidence Four hundred fifteen patients undergoing coronary revascularization over a 12-month period were divided into two groups : 209 controls in the first 6 months received no tranexamic acid ( TA ) before cardiopulmonary bypass and 206 patients in the second 6 months received TA as a hemostatic agent . The demographics and the surgical techniques used were similar in the two groups . With TA there was a significant decrease in blood loss postoperatively , from 1,114.1 mL in the controls to 803.7 mL in those given TA ( p < 0.001 ) ; in red blood cell use , from 1.7 units/patient in the controls to 0.69 units/patient in those given TA ( p < 0.001 ) ; in fresh frozen plasma requirements , from 0.23 units/patient in the controls to 0.024 units/patient in those given TA ( p < 0.01 ) ; and in platelet transfusion , from 1.06 units/patient in the controls to 0.30 units/ patients in those given TA ( p < 0.01 ) . The percentages of patients not receiving any blood products were 65 % in those given TA versus 49 % in the controls ( p < 0.01 ) . There was no significant difference between the two groups in the incidence of perioperative myocardial infa rct ion , cerebrovascular accidents , pulmonary embolism , or venous thrombosis to clearly suggest hypercoagulability . In this study , TA profoundly affected the coagulopathy associated with bypass in patients undergoing coronary revascularization . It significantly reduced blood loss and blood product transfusions . Any potential increased thrombotic complications could not be clearly demonstrated in this study , but should not be ignored Aim . To assess the efficacy and safety of tranexamic acid in reducing blood loss at caesarian section ( CS ) . Method . A prospect i ve r and omised study conducted on 90 primiparas divided into two groups who underwent CS . The study group , 45 women , received tranexamic acid immediately before CS , whereas the control group , 45 women received placebo . Blood loss volume was measured from the end of CS to 2 h postpartum and compared between the two groups . Hemoglobin ( Hb ) and hematocrit ( Hct ) were tested 24 h after CS and compared between the two groups . Results . Tranexamic acid significantly reduced the blood loss from the end of CS to 2 h postpartum ; 28.02 ± 5.53 mL in the tranexamic group versus 37.12 ± 8.97 mL in the control group ( p = 0.000 ) . Hb 24 h after CS was significantly greater in tranexamic group than control group ( 12.57 ± 1.33 in the tranexamic group and 11.74 ± 1.14 in the control group , p = 0.002 ) . No complications or side effects were reported in either group . Conclusions . Tranexamic acid statistically reduces blood loss from end to 2 h after CS and its use was not associated with any side effects or complications . Consequently , tranexamic acid can be used safely and effectively to reduce bleeding result ing from CS The efficacy of an integrated autotransfusion regimen , including pre-donation and perioperative salvage of autologous blood , was prospect ively evaluated in 2884 patients undergoing total hip ( n = 2016 ) or knee arthroplasty ( n = 480 ) , and hip revision ( n = 388 ) with either balanced general , regional , or integrated epidural/general anaesthesia . Allogenic concentrated red blood cells were transfused in the presence of symptomatic anaemia or when haemoglobin concentration was < 6 g dL-1 ( 10 g dL-1 in patients affected by cerebrovascular or coronary artery disease ) after all salvaged and pre-donated autologous blood had been transfused . A total of 278 patients ( 9.6 % ) received allogenic blood . Risk factors for allogenic blood transfusion were : preoperative haemoglobin concentration < 10 g dL-1 ( after autologous blood pre-donations ) ( Odds ratio : 8.7 ; 95 % CI : 6.5 - 16.8 ; P = 0.004 ) , hip revision versus hip or knee arthroplasty ( Odds ratio : 5.8 ; 95 % CI : 3.9 - 8.5 ; P = 0 . 0001 ) and inability in obtaining the number of pre-donations required by the Maximum Surgery Blood Order on Schedule ( Odds ratio : 3.4 ; 95 % CI : 2.7 - 4.1 ; P = 0.0001 ) . The incidence of perioperative complications , including wound infection and haematoma , as well as myocardial ischaemia , respiratory failure and thromboembolic complications , was higher in those patients requiring allogenic blood transfusion ( 29.8 % ) than that observed in patients receiving only autologous blood ( 6.6 % ) ( P = 0.0005 ) ; while the mean time duration from surgical procedure to patient discharge from the orthopaedic ward was shorter in those patients not receiving allogenic blood transfusion ( 12 days ; 25 - 75th percentiles : 8 - 14 days ) than in those patients who required perioperative transfusion with allogenic blood ( 15 days ; 25 - 75th percentiles : 10 - 17 days ) ( P = 0.0005 ) . In conclusion , this prospect i ve study highlighted the clinical relevance of applying an extensive and integrated autotransfusion regimen in order to reduce allogenic blood transfusion and associated complications in patients undergoing major joint replacement INTRODUCTION Extensive blood loss related to knee arthroplasty is quite normal and many patients require blood transfusions . Surgery and the use of pneumatic tourniquets lead to an increase in the activity of the fibrinolytic system , which in turn may accentuate the blood loss . Drugs that inhibit the fibrinolytic system may thus be used to reduce blood loss . Tranexamic acid ( TA ) acts by binding to one of the enzymes at the start of the coagulation cascade , so inhibiting the fibrinolytic system . A concern is that this inhibition may have the side effect of increasing thromboembolic disease , a common complication of joint replacement surgery . We aim ed to confirm the reductions in blood loss and to assess the impact of TA usage on clinical and sub- clinical DVT . METHOD We performed a prospect i ve , r and omised , double blind , controlled trial , using patients due to undergo primary unilateral total knee arthroplasty . Patients were r and omised to receive either 15 mg/kg of tranexamic acid or a similar volume of normal saline at the time of cementing of the prosthesis . Perioperative blood loss was recorded and patients were screened for DVT with duplex ultrasound assessment of both legs on the fifth post-operative day . RESULTS A statistically significant ( p=0.006 ) decrease in blood loss in the early post-operative period was noted in the group receiving tranexamic acid . This was not associated with a significant difference in total blood loss ( p=0.55 ) or in transfusion requirements . There was no of evidence in DVT in either group on duplex ultrasound screening of the lower limbs . INTERPRETATION One injection of 15 mg/kg of tranexamic given at the time of cementing the prosthesis in total knee arthroplasty , before deflation of the tourniquet , significantly decreases the amount of blood loss in the early post-operative period . The treatment was not associated with an increase in thromboembolic complications Bleeding during the first 24 hours following cardiac surgery using cardio-pulmonary bypass ( CPB ) is a serious complication . Attempts to modify the degree of postoperative bleeding with pharmacologic therapy have met with limited success . Tranexamic acid , a potent inhibitor of plasminogen , may decrease the amount of mediastinal bleeding following surgery utilizing CPB . We assigned 30 patients who were about to undergo cardiac surgery to a double-blind r and omized trial . The treatment group received tranexamic acid , given intravenously as 10 mg/kg over 30 minutes , at the time of skin incision , followed by a 1 mg/kg/hr infusion for 12 hours . The control group received a placebo ( saline ) of equal volume . Measurements of shed mediastinal blood and transfused homologous blood were made at 6 , 12 , and 24 hours postoperatively . Mediastinal blood loss in the treatment and control groups was 382 mL versus 594 mL at 6 hours ( P = 0.08 ) , 502 mL versus 848 mL at 12 hours ( P = 0.04 ) , and 711 mL versus 1160 mL at 24 hours ( P = 0.02 ) . The mean transfusion volumes after 24 hours were 356 mL in the treatment group and 528 mL in the placebo group ( P = NS ) . Prophylactic tranexamic acid infusion decreases mediastinal blood loss following cardiopulmonary assisted cardiac surgery The application of a pneumatic tourniquet in orthopedic procedures enhances local fibrinolysis . Consequently , a short-term antifibrinolytic therapy may be indicated in this clinical situation to reduce postoperative blood loss . The purpose of this prospect i ve doubleblind study was to investigate the effect of tranexamic acid ( TA ) on blood loss associated with total knee arthroplasty ( TKA ) . Seventy-five patients scheduled for 77 TKAs were r and omized to receive either TA ( n = 39 ) or equal volume of normal saline ( NS , n = 38 ) . Before deflation of the tourniquet , 15 mg/kg of TA was given intravenously followed by two 10-mg/kg additional doses . Perioperative blood loss gathered in surgical gauzes , suction reservoirs , and postoperative drainage system was measured . The number of transfusions given during hospitalization was registered . Total blood loss ( mean + /- SD ) was 689 + /- 289 mL in the TA group and 1509 + /- 643 mL in the NS group ( P < 0.0001 ) . The mean number of transfused red cell units in the TA group was 1.0 + /- 1.2 compared to 3.1 + /- 1.6 in the NS group ( P < 0.0001 ) . Twenty-two patients in the TA group and four patients in the NS group were treated without transfusion ( P < 0.00003 ) . Two patients in the TA group and three in the NS group had a deep venous thrombosis , including a fatal case of pulmonary embolism in the NS group . We conclude that short-term TA therapy significantly reduces TKA-associated blood loss and transfusion requirements without increasing thromboembolic complications . ( Anesth Analg 1997;84:839 - 44 BACKGROUND Topical application of tranexamic acid to bleeding wound surfaces reduces blood loss in patients undergoing some major surgeries , without systemic complications . The objective of the present trial was to assess the efficacy and safety of the topical application of tranexamic acid on postoperative blood loss in patients undergoing primary unilateral total knee arthroplasty with cement . METHODS In a prospect i ve , double-blind , placebo-controlled trial , 124 patients were r and omized to receive 1.5 or 3.0 g of tranexamic acid in 100 mL of normal saline solution or an equivalent volume of placebo ( normal saline solution ) applied into the joint for five minutes at the end of surgery . The primary outcome was blood loss calculated from the difference between the preoperative hemoglobin level and the corresponding lowest postoperative value or hemoglobin level prior to transfusion . The safety outcomes included Doppler ultrasound in all patients and measurement of plasma levels of tranexamic acid one hour after release of the tourniquet . RESULTS Twenty-five patients were withdrawn for various reasons ; therefore , ninety-nine patients were included in the intention-to-treat analysis . The postoperative blood loss was reduced in the 1.5 and 3-g tranexamic acid groups ( 1295 mL [ 95 % confidence interval , 1167 to 1422 mL ] and 1208 mL [ 95 % confidence interval , 1078 to 1339 mL ] , respectively ) in comparison with the placebo group ( 1610 mL [ 95 % confidence interval , 1480 to 1738 mL ] ) ( p < 0.017 ) . The postoperative hemoglobin levels were higher in the 1.5 and 3.0-g tranexamic acid groups ( 10.0 g/dL [ 95 % confidence interval , 9.5 to 10.4 g/dL ] and 10.1 g/dL [ 95 % confidence interval , 9.8 to 10.5 g/dL ] , respectively ) in comparison with the placebo group ( 8.6 g/dL [ 95 % confidence interval , 8.2 to 9 g/dL ] ) ( p < 0.017 ) . With the numbers studied , there was no difference in the rates of deep-vein thrombosis or pulmonary embolism between the three groups . Minimal systemic absorption of tranexamic acid was observed . CONCLUSIONS At the conclusion of a total knee arthroplasty with cement , topical application of tranexamic acid directly into the surgical wound reduced postoperative bleeding by 20 % to 25 % , or 300 to 400 mL , result ing in 16 % to 17 % higher postoperative hemoglobin levels compared with placebo , with no clinical ly important increase in complications being identified in the treatment groups Purpose Reduction in blood loss during surgery stabilizes hemodynamic status and aids in recovery after total knee arthroplasty ( TKA ) . In this study , the authors examined whether different administration routes of tranexamic acid ( TNA ) might affect the amount of blood loss after TKA . Methods A total of 150 patients were prospect ively allocated to each of the three groups ( intravenous , intra-articular , and placebo group ) and underwent unilateral TKA . During closing the operative wound , TNA ( 1.5 g mixed in 100 cc of saline ) was administered intravenously or intra-articularly according to the enrolled group , and an equivalent volume of normal saline was administered into the knee joint cavity and intravenously in the placebo group , respectively . The amount of blood loss and transfusion , and changes in haemoglobin levels were documented accordingly . Results The mean blood loss in the intravenous , intra-articular , and placebo groups were 528 ± 227 , 426 ± 197 , and 833 ± 412 ml , respectively . About 66 % ( intravenous ) , 80 % ( intra-articular ) , and 6 % ( placebo ) of each group did not require transfusion for any reason , and the mean amount of transfusion was 273.6 , 129.6 , and 920.8 ml , respectively . Preoperative haemoglobin values decreased by 1.6 ± 0.8 , 1.8 ± 0.8 , and 2.0 ± 0.9 mg/dl , respectively . Conclusion Compared to intravenous administration , intra-articular administration of TNA seems to be more effective in terms of reducing blood loss and transfusion frequency . TNA may improve the general conditions of patients given TKA by maintaining a hemodynamically stable state , aiding in recovery , and reducing the chance of transfusion-associated side effects and complications . Level of evidence II Background : Extensive blood loss in total knee replacement ( TKR ) surgery is well known and is associated with a high transfusion rate of allogenic blood . Tranexamic acid ( TXA ) has been shown to reduce blood loss by 50 % in this patient group , but only in cases with a perioperative loss of 1400–1800 ml . This study was performed to see if TXA offers any advantages in knee replacement surgery with blood loss at 800 ml Background TKA may be associated with considerable blood loss , and transfusion carries substantial risk of immunologic reaction and disease transmission . Blood transfusion also involves additional cost , therefore a reduction in its use is important . Several methods reportedly reduce postoperative blood loss and avoid homologous blood transfusion with traditional TKA approaches , but it is unclear these reductions apply to a minimally invasive technique . Questions / purpose sWe asked whether tranexamic acid administration could reduce blood loss and blood transfusion requirements after TKA . Patients and Methods Between March 2008 and May 2008 , we enrolled 100 patients with primary osteoarthritis undergoing a unilateral cemented TKA in a prospect i ve , r and omized , double-blind study . Patients were r and omized into one of two groups : the control group received a placebo and the study group received tranexamic acid intravenously ( 10 mg/kg ) 10 minutes before inflation of the tourniquet and 3 hours postoperatively and orally ( 250 mg/capsule ; two capsules three times daily ) for 5 days . We measured volume of drained blood 48 hours postoperatively , decrease in hemoglobin levels 12 hours postoperatively , amount of blood transfused , and number of patients requiring allogenic blood transfusion . The minimum followup was 6 months ( mean , 10.4 months ; range , 6–12 months ) . Results Mean ( ± SD ) postoperative volume of drained blood was lower in the group receiving tranexamic acid ( 727.50 ± 234 mL ) than in control subjects ( 1208.77 ± 421 mL ) . The mean hemoglobin decrease 12 hours postoperatively was lower in patients receiving tranexamic acid ( 2.12 ± 0.64 g/dL ) than in control subjects ( 3.33 ± 0.88 g/dL ) . The amount of blood transfused and number of patients requiring blood transfusion were lower in patients receiving tranexamic acid than in control subjects . Conclusions Tranexamic acid reduced postoperative blood loss after TKA , as reflected in reduction in the number of blood transfusions . We did not observe any change in symptomatic thromboembolic phenomenon . Level of Evidence Level 1 , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence |
10,957 | 23,365,417 | Based on the studies with relevant sample size , high adherence to a strength-training protocol and close follow-up , we found that PFMT during pregnancy and after delivery can prevent and treat UI .
A supervised training protocol following strength-training principles , emphasising close to maximum contractions and lasting at least 8 weeks is recommended .
PFMT is effective when supervised training is conducted . | BACKGROUND Urinary incontinence ( UI ) is a common condition in women causing reduced quality of life and withdrawal from fitness and exercise activities .
Pregnancy and childbirth are established risk factors .
Current guidelines for exercise during pregnancy have no or limited focus on the evidence for the effect of pelvic floor muscle training ( PFMT ) in the prevention and treatment of UI .
AIMS Systematic review to address the effect of PFMT during pregnancy and after delivery in the prevention and treatment of UI . | Objective To assess the effect of pelvic floor education after vaginal delivery on pelvic floor characteristics in nulliparous women . Methods We examined 107 nulliparas during pregnancy and at 9 weeks and 10 months after vaginal delivery . Methods used included a question naire , clinical examination , perineosonography , urethral pressure profiles , and intravaginal and intra-anal pressure recordings during pelvic floor contraction . After the second examination , the women were assigned in alternating manner to either 12 sessions of pelvic floor exercises with biofeedback and electrostimulation ( n = 51 ) or no training ( n = 56 ) . The two groups were compared at the third examination . Results Stress urinary incontinence incidence decreased in 2 % of control subjects compared with 19 % of women who underwent pelvic floor education ( P = .002 ) , whereas the incidence of fecal incontinence ( 5 % versus 4 % , P = 1 ) and the percentage of women who recovered predelivery pelvic floor contraction strength ( 33 % versus 41 % , P = .4 ) were no different . We observed no significant differences in bladder neck position and mobility , urethral functional length , maximal urethral closure pressure , pressure transmission ratio , residual area of continence at stress st and ing , or intravaginal or intra-anal pressures during pelvic floor contraction between groups at the third examination . Conclusion Pelvic floor education , begun 2 months postpartum , significantly reduced the incidence of stress urinary incontinence , but not fecal incontinence or weak pelvic floor . Similarly , bladder neck behavior , urodynamic characteristics , intravaginal or intra-anal pressures during pelvic floor squeezing also were not modified A physiotherapist-delivered continence promotion program was recently implemented with postpartum women in Australia . A previous r and omised controlled trial demonstrated that the program was effective in promoting pelvic floor exercises and continence at 3 months postpartum . The present study compares pelvic floor exercise frequency and continence status for women in the intervention and ‘ usual care ’ control groups at 12 months postpartum . While there was no significant difference in continence status , women in the intervention group were more likely than those in the control group to be practising pelvic floor exercises at adequate frequencies . In turn , continued adherence to pelvic floor exercises at 12 months was predictive of continence at that time . Potential strategies for enhancing women ’s adherence to pelvic floor exercise regimes during and beyond the postpartum year are discussed Objective : To investigate the effect of supervised and unsupervised pelvic floor muscle exercises utilizing trunk stabilization for treating postpartum urinary incontinence and to compare the outcomes . Design : R and omized , single-blind controlled study . Setting : Outpatient rehabilitation hospital . Subjects : Eighteen subjects with postpartum urinary incontinence . Interventions : Subjects were r and omized to either a supervised training group with verbal instruction from a physiotherapist , or an unsupervised training group after undergoing a supervised demonstration session . Main measures : Bristol Female Lower Urinary Tract Symptom question naire ( urinary symptoms and quality of life ) and vaginal function test ( maximal vaginal squeeze pressure and holding time ) using a perineometer . Results : The change values for urinary symptoms ( −27.22 ± 6.20 versus −18.22 ± 5.49 ) , quality of life ( −5.33 ± 2.96 versus −1.78 ± 3.93 ) , total score ( −32.56 ± 8.17 versus −20.00 ± 6.67 ) , maximal vaginal squeeze pressure ( 18.96 ± 9.08 versus 2.67 ± 3.64 mmHg ) , and holding time ( 11.32 ± 3.17 versus 5.72 ± 2.29 seconds ) were more improved in the supervised group than in the unsupervised group ( P < 0.05 ) . In the supervised group , significant differences were found for all variables between pre- and post-test values ( P < 0.01 ) , whereas the unsupervised group showed significant differences for urinary symptom score , total score and holding time between the pre- and post-test results ( P < 0.05 ) . Conclusions : These findings suggest that exercising the pelvic floor muscles by utilizing trunk stabilization under physiotherapist supervision may be beneficial for the management of postpartum urinary incontinence A r and omized controlled trial was carried out to evaluate the extent to which a program of reinforced pelvic floor muscle exercises ( PFME ) reduces urinary incontinence 1 year after delivery . Two hundred and thirty women who were incontinent 3 months postpartum were r and omized to either a control group doing st and ard postnatal pelvic floor muscle exercises ( n=117 ) or to an intervention group ( n=113 ) who saw a physiotherapist for instruction at approximately 3 , 4 , 6 and 9 months postpartum . Results collected 12 months after delivery included prevalence and frequency of incontinence and PFME , sexual satisfaction , perineometry measurements and pad tests . Twenty-six ( 22 % ) of the control group and 59 ( 52 % ) of the intervention group withdrew before the final assessment . The prevalence of incontinence was significantly less in the intervention group than in the control group ( 50 % versus 76%,P=0.0003 ) , and this group also did significantly more PFME . There were no significant differences between the groups as regards sexual satisfaction , perineometry measurements or pad test results OBJECTIVE : To date , the evidence on pelvic floor injury in labor remains sketchy due to a lack of prospect i ve studies comparing pelvic floor imaging before and after childbirth . We intended to define the incidence of major trauma to the pubovisceral muscle . METHODS : A total of 61 nulliparous women were seen at 36–40 weeks of gestation in a prospect i ve observational study . The assessment included an interview and 3-dimensional translabial ultrasound and was repeated 2–6 months postpartum . RESULTS : Fifty women ( 82 % ) were seen postpartum . Of the 39 women delivered vaginally , levator avulsion was diagnosed in 14 ( 36 % , 95 % confidence interval 21–51 % ) . Among those delivered vaginally , there were associations with higher maternal age ( P = .10 ) , vaginal operative delivery ( P = .07 ) , and worsened stress incontinence postpartum ( P = .02 ) . CONCLUSIONS : Avulsion of the inferomedial aspects of the levator ani from the pelvic sidewall occurred in approximately one third of all women delivered vaginally and was associated with stress incontinence 3 months after childbirth . LEVEL OF EVIDENCE : OBJECTIVES This study was undertaken to estimate the association between pelvic floor muscle training and demographic and health related factors that may influence pelvic floor muscle training postpartum . STUDY DESIGN This analysis includes the first 17,978 women enrolled in the Norwegian Mother and Child Cohort Study who answered questions about pelvic floor muscle training ( n = 17,744 ) . We used logistic regression analyses , and the results are presented as crude and adjusted odds ratios with 95 % CI . RESULTS Women doing regular pelvic floor muscle training were more educated , likely to participate in general fitness activities , and had more children . Women experiencing urinary leakage and pelvic girdle pain postpartum were also more likely to do pelvic floor muscle training ( adjusted odds ratio = 1.26 , 95 % CI 1.18 - 1.35 ; adjusted odds ratio = 1.31 , 95 % CI 1.23 - 1.39 ) . Those who smoked daily or were delivered by cesarean were less likely to do pelvic floor muscle training ( adjusted odds ratio = 0.81 , 95 % CI 0.72 - 0.91 ; adjusted odds ratio = 0.56 , 95 % CI 0.51 - 0.61 ) . CONCLUSION There is a need for more research concerning effective strategies to enhance postpartum pelvic floor muscle training The process by which new therapies enter clinical practice is frequently suboptimal . Often , ideas for new therapies are generated by clinical observations or laboratory studies ; therapies based on those ideas may enter clinical practice without any further scrutiny . As a consequence , some ineffective practice s become widespread . This article proposes a six-stage protocol for the implementation of new therapies . Hypotheses about therapy based on pre clinical research should be subject to clinical exploration and pilot studies prior to rigorous assessment with r and omised clinical trials . If r and omised clinical trials suggest that the intervention produces clinical ly important effects , further r and omised studies can be conducted to refine the intervention . New interventions should not be recommended , or included in teaching curricula , or taught in continuing education courses until their effectiveness has been demonstrated in high- quality r and omised clinical trials OBJECTIVE Urinary incontinence is a chronic health complaint that severely reduces quality of life . Pregnancy and vaginal delivery are main risk factors in the development of urinary incontinence . The aim of this study was to assess whether intensive pelvic floor muscle training during pregnancy could prevent urinary incontinence . METHODS We conducted a single-blind r and omized controlled trial at Trondheim University Hospital and three outpatient physiotherapy clinics in a primary care setting . Three hundred one healthy nulliparous women were r and omly allocated to a training ( n = 148 ) or a control group ( n = 153 ) . The training group attended a 12-week intensive pelvic floor muscle training program during pregnancy , supervised by physiotherapists . The control group received the customary information . The primary outcome measure was self-reported symptoms of urinary incontinence . The secondary outcome measure was pelvic floor muscle strength . RESULTS At follow-up , significantly fewer women in the training group reported urinary incontinence : 48 of 148 ( 32 % ) versus 74 of 153 ( 48 % ) at 36 weeks ' pregnancy ( P = .007 ) and 29 of 148 ( 20 % ) versus 49 of 153 ( 32 % ) 3 months after delivery ( P = .018 ) . According to numbers needed to treat , intensive pelvic floor muscle training during pregnancy prevented urinary incontinence in about one in six women during pregnancy and one in eight women after delivery . Pelvic floor muscle strength was significantly higher in the training group at 36 weeks ' pregnancy ( P = .008 ) and 3 months after delivery ( P = .048 ) . CONCLUSION Intensive pelvic floor muscle training during pregnancy prevents urinary incontinence during pregnancy and after delivery . Pelvic floor muscle strength improved significantly after intensive pelvic floor muscle training Abstract Objectives : To assess the effect of nurse assessment with reinforcement of pelvic floor muscle training exercises and bladder training compared with st and ard management among women with persistent incontinence three months postnatally . Design : R and omised controlled trial with nine months ' follow up . Setting : Community intervention in three centres ( Dunedin , New Zeal and ; Birmingham ; Aberdeen ) . Participants : 747 women with urinary incontinence three months postnatally , allocated at r and om to intervention ( 371 ) or control ( 376 ) groups . Intervention : Assessment by nurses of urinary incontinence with conservative advice on pelvic floor exercises at five , seven , and nine months after delivery supplemented with bladder training if appropriate at seven and nine months . Main outcome measures : Primary : persistence and severity of urinary incontinence 12 months after delivery . Secondary : performance of pelvic floor exercises , change in coexisting faecal incontinence , wellbeing , anxiety , and depression . Results : Women in the intervention group had significantly less urinary incontinence : 167/279 ( 59.9 % ) v 169/245 ( 69.0 % ) , difference 9.1 % ( 95 % confidence interval 1.0 % to 17.3 % , P=0.037 ) for any incontinence and 55/279 ( 19.7 % ) v 78/245 ( 31.8 % ) , difference 12.1 % ( 4.7 % to 19.6 % , P=0.002 ) for severe incontinence . Faecal incontinence was also less common : 12/273 ( 4.4 % ) v 25/237 ( 10.5 % ) , difference 6.1 % ( 1.6 % to 10.8 % , P=0.012 ) . At 12 months women in the intervention group were more likely to be performing pelvic floor exercises ( 218/278 ( 79 % ) v 118/244 ( 48 % ) , P<0.001 ) . Conclusions : A third of women may have some urinary incontinence three months after childbirth . Conservative management provided by nurses seems to reduce the likelihood of urinary and coexisting faecal incontinence persisting 12 months postpartum . Further trials for faecal incontinence are needed . What is already known on this topic Vaginal delivery is a risk factor for urinary incontinence Three months after childbirth 20 - 30 % of women still experience urinary incontinence Most women do not seek treatment What this study adds Women will use conservative treatments such as pelvic floor exercises or bladder training Conservative management prevents persistent urinary incontinence in about one in 10 women who have postnatal incontinence Coexisting persistent faecal incontinence is also Abstract Objectives : To test the effectiveness of a physiotherapist delivered intervention design ed to prevent urinary incontinence among women three months after giving birth . Design : Prospect i ve r and omised controlled trial with women r and omised to receive the intervention ( which entailed training in pelvic floor exercises and incorporated strategies to improve adherence ) or usual postpartum care . Setting : Postpartum wards of three tertiary teaching hospitals in the Hunter region , New South Wales , Australia . Participants : Women who had forceps or ventouse deliveries or whose babies had a high birth weight ( 4000 g ) , or both—676 ( 348 in the intervention group and 328 in the usual care group ) provided endpoint data at three months . Main outcome measures : Urinary incontinence at three months measured as a dichotomous variable . The severity of incontinence was also measured . Self report of the frequency of performance of pelvic floor exercises was recorded . Results : At three months after delivery , the prevalence of incontinence in the intervention group was 31.0 % ( 108 women ) and in the usual care group 38.4 % ( 125 women ) ; difference 7.4 % ( 95 % confidence interval 0.2 % to 14.6 % , P=0.044 ) . At follow up significantly fewer women with incontinence were classified as severe in the intervention group ( 10.1 % ) v ( 17.0 % ) , difference 7.0 % , 1.6 % to 11.8 % ) . The proportions of women reporting doing pelvic floor exercises at adequate levels was 84 % ( 80 % to 88 % ) for the intervention group and 58 % ( 52 % to 63 % ) for the usual care group ( P=0.001 ) . Conclusions : The intervention promoting urinary continence reduced the prevalence of urinary incontinence after giving birth , particularly its severity , and promoted the performance of pelvic floor exercises at adequate levels ; both continence and adherence to the programme were measured at three months after delivery in women who had forceps or ventouse deliveries or babies weighing 4000 g or more . What is already known on this topic Intensive pelvic floor exercise programmes can reduce urinary incontinence in selected groups of female patients The effectiveness of interventions promoting continence in reducing urinary incontinence in the female population overall has not been investigated Pelvic floor exercises are widely held to be an important component of continence promotion programmes What this study adds Continence promotion programmes delivered to a selected population are able to prevent urinary incontinence in that population Few studies have examined the efficacy of compliance aiding strategies in helping women adhere to prescribed pelvic floor exercise The aim of this study was to evaluate the effect of postpartum pelvic floor muscle exercise in the prevention and treatment of urinary incontinence . A prospect i ve comparison design of 99 matched pairs ( n=198 ) of mothers , a training group and a control group , was used . Eight weeks postpartum the training group attended an 8-week intensive pelvic floor muscle exercise course , training in groups led by a physical therapist for 45 minutes once a week . In addition they were asked to exercise at home at least three times per week . The control group followed the ordinary written postpartum instructions from the hospital . Pelvic floor muscle strength was measured pretreatment at the eighth , and post-treatment at the 16th week after delivery , using a vaginal balloon catheter connected to a pressure transducer . Vaginal palpation and observation of inward movement of the balloon catheter during contraction were used to test the ability to perform correct the pelvic floor muscle contraction . Urinary leakage was registered by interview , specially design ed instruments to measure how women perceive SUI , and a st and ardized pad test . At baseline ( 8 weeks postpartum ) there was no significant difference in the number of women with urinary incontinence in the training group compared to the control group . At 16 weeks postpartum , after the 8-week treatment period , there was a significant ( P<0.01 ) difference in favor of the training group . In addition , a significantly greater improvement in pelvic floor muscle strength between test 1 and test 2 was found in the training group compared to the control group . The results show that a specially design ed postpartum pelvic floor muscle exercise course is effective in increasing pelvic floor muscle strength and reducing urinary incontinence in the immediate postpartum period OBJECTIVE : The aim of this study was to compare the effectiveness of multimodal supervised physiotherapy programs with the absence of treatment among women with persistent postnatal stress urinary incontinence . METHODS : This was a single-blind r and omized controlled trial . Sixty-four women with stress urinary incontinence were r and omly assigned to 8 weeks of either multimodal pelvic floor rehabilitation ( n = 21 ) , multimodal pelvic floor rehabilitation with abdominal muscle training ( n = 23 ) , or control non – pelvic floor rehabilitation ( n = 20 ) . The primary outcome measure consisted of a modified 20-minute pad test . The secondary outcome measures included a Visual Analog Scale describing the perceived burden of incontinence , the Urogenital Distress Inventory , the Incontinence Impact Question naire , and pelvic floor muscle function measurements . RESULTS : Two patients dropped out , leaving 62 for analysis . At follow-up , more than 70 % of the women in the treatment groups ( 14/20 in the pelvic floor and 17/23 in the pelvic floor plus abdominal group ) were continent on pad testing compared with 0 % of women in the control group . Scores on the pad test , Visual Analog Scale , Urogenital Distress Inventory , and Incontinence Impact Question naire improved significantly in both treatment groups ( all P < .002 ) , whereas no changes were observed in the control group . Pelvic floor muscle function , however , did not improve significantly in either active group . CONCLUSION : Multimodal supervised pelvic floor physiotherapy is an effective treatment for persistent postnatal stress urinary incontinence . LEVEL OF EVIDENCE : AIM This article is a report of a study of the effects of a pelvic floor muscle exercise programme on the severity of stress urinary incontinence in pregnant women . BACKGROUND Pregnancy is main risk factor for the development of stress urinary incontinence . Stress urinary incontinence can be cured by pelvic floor muscle exercise which is a safe inexpensive treatment with no complications and does not require the use of instruments . METHODOLOGY A quasi-experimental study , pre-post test with control group design was used at the antenatal care unit in a tertiary care hospital between June and October of 2006 . The participants were 66 pregnant women who had stress urinary incontinence with gestational ages of 20 - 30 weeks . The main outcome measure was severity of stress urinary incontinence which comprised frequency and amount of urine leakage and perceived severity of stress urinary incontinence . RESULTS After the experimental group 's participation in the pelvic floor muscle exercise programme , the frequency and amount of urine leakage and the score of perceived stress urinary incontinence severity were significantly lower than the same scores before participation in the programme . In addition , women in the experimental group had frequency and volume of urine leakage , and score of perceived stress urinary incontinence severity after participation significantly lower than those in the control group . CONCLUSION The 6-week pelvic floor muscle exercise programme was able to decrease the severity of symptoms in pregnant women with stress urinary incontinence Introduction and hypothesisThe aim of the study was to evaluate the effect of antenatal pelvic floor muscle exercise ( PFME ) in the prevention and treatment of urinary incontinence during pregnancy and postpartum period . Methods Three hundred women were r and omly assigned to the PFME group and control group . Urinary symptoms were measured by Urogenital Distress Inventory-6 ( UDI-6 ) , Incontinence Impact Question naire-7 ( IIQ-7 ) , and question of self-reported urinary incontinence . Question naire scores of the PFME and the control groups were compared and analyzed . Results During late pregnancy and the postpartum period , the PFME group had significantly lower total UDI-6 and IIQ-7 scores ; their self-report rate of urinary incontinence was also less than the control group . Additionally , we found whether in PFME or control , women who delivered vaginally were more likely to develop postpartum urinary leakage than women who delivered by cesarean section . Conclusions PFME applied in pregnancy is effective in the treatment and prevention of urinary incontinence during pregnancy , and this effect may persist to postpartum period Objective To evaluate the long term effect of a postpartum pelvic floor muscle training course in prevention and treatment of urinary incontinence Please cite this paper as : Stafne S , Salvesen K , Romundstad P , Torjusen I , Mørkved S. Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy ? A r and omised controlled trial . BJOG 2012;119:1270–1280 OBJECTIVE : To investigate morphological and functional changes after pelvic floor muscle training in women with pelvic organ prolapse . METHODS : This r and omized controlled trial was conducted at a university hospital and a physical therapy clinic . One hundred nine women with pelvic organ prolapse stages I , II , and III were r and omly allocated by a computer-generated r and om number system to pelvic floor muscle training ( n=59 ) or control ( n=50 ) . Both groups received lifestyle advice and learned to contract the pelvic floor muscles before and during increases in intraabdominal pressure . In addition the pelvic floor muscle training group did individual strength training with a physical therapist and daily home exercise for 6 months . Primary outcome measures were pelvic floor muscle ( pubovisceral muscle ) thickness , levator hiatus area , pubovisceral muscle length at rest and Valsalva , and resting position of bladder and rectum , measured by three-dimensional ultrasonography . RESULTS : Seventy-nine percent of women in the pelvic floor muscle training group adhered to at least 80 % of the training protocol . Compared with women in the control group , women in the pelvic floor muscle training group increased muscle thickness ( difference between groups : 1.9 mm , 95 % confidence interval [ CI ] 1.1–2.7 , P<.001 ) , decreased hiatal area ( 1.8 cm2 , 95 % CI 0.4–3.1 , P=.026 ) , shortened muscle length ( 6.1 mm , 95 % CI 1.5–10.7 , P=.007 ) , and elevated the position of the bladder ( 4.3 mm , 95 % CI 2.1–6.5 , P<.000 ) and rectum ( 6.7 mm , 95 % CI 2.2–11.8 , P=.007 ) . Additionally , they reduced the hiatal area and muscle length at maximum Valsalva indicating increased pelvic floor muscle stiffness . CONCLUSION : Supervised pelvic floor muscle training can increase muscle volume , close the levator hiatus , shorten muscle length , and elevate the resting position of the bladder and rectum . CLINICAL TRIAL REGISTRATION : www . clinical trials.gov , NCT00271297 . LEVEL OF EVIDENCE : OBJECTIVES Pelvic floor muscle training ( PFMT ) following vaginal assessment of correct contraction can prevent and treat urinary incontinence in the peripartum period . The aim of this study was to evaluate the effectiveness of PFMT instructed in a general fitness class for pregnant women . DESIGN Single-blind r and omised controlled trial . SETTING University-conducted primary care study . PARTICIPANTS One hundred and five sedentary primiparous women r and omised to a general fitness class including PFMT ( n=52 ) or a control group ( n=53 ) . Ten and 11 women were lost to follow-up in the exercise and control groups , respectively . INTERVENTION Twelve weeks of training comprising twice-weekly 1-hour fitness classes including three sets of eight to 12 maximal pelvic floor muscle contractions . The control group received usual care . OUTCOME MEASURE Number of women reporting urinary , flatus or anal incontinence . RESULTS No significant differences were found in the number of women reporting urinary , flatus or anal incontinence between the exercise group and the control group during pregnancy or at 6 weeks post partum . CONCLUSIONS No effect of PFMT was found when the exercises were taught in a general fitness class for pregnant women without individual instruction of correct PFM contraction . Low adherence and the small sample size may have contributed to the negative results . Further studies are warranted to assess the effect of population -based PFMT in the prevention of urinary and fecal incontinence Abstract Objective To determine the long term effects of a conservative nurse-led intervention for postnatal urinary incontinence . Design R and omised controlled trial . Setting Community based intervention in three centres in the United Kingdom and New Zeal and . Participants 747 women with urinary incontinence at three months after childbirth , of whom 516 were followed up again at 6 years ( 69 % ) . Intervention Active conservative treatment ( pelvic floor muscle training and bladder training ) at five , seven , and nine months after delivery or st and ard care . Main outcome measures Urinary and faecal incontinence , performance of pelvic floor muscle training . Results Of 2632 women with urinary incontinence , 747 participated in the original trial . The significant improvements relative to controls in urinary ( 60 % v 69 % ) and faecal ( 4 % v 11 % ) incontinence at one year were not found at six year follow up ( 76 % v 79 % ( 95 % confidence interval for difference in means −10.2 % to 4.1 % ) for urinary incontinence , 12 % v 13 % ( −6.4 % to 5.1 % ) for faecal incontinence ) irrespective of subsequent obstetric events . In the short term the intervention had motivated more women to perform pelvic floor muscle training ( 83 % v 55 % ) but this fell to 50 % in both groups in the long term . Both urinary and faecal incontinence increased in prevalence in both groups during the study period . Conclusions The moderate short term benefits of a brief nurse-led conservative treatment of postnatal urinary incontinence may not persist , even among women with no further deliveries . About three quarters of women with urinary incontinence three months after childbirth still have this six years later Objective To test the effect of pelvic muscle exercise on postpartum symptoms of stress urinary incontinence and pelvic muscle strength in primigravidas during pregnancy and postpartum . Methods A prospect i ve trial r and omized women into treatment ( st and ardized instruction in pelvic muscle exercise ) or control ( routine care with no systematic pelvic muscle exercise instruction ) . Urinary incontinence symptoms were measured by question naire . Pelvic muscle strength was quantified by an instrumented gynecologic speculum . Time points were 20 and 35 weeks ' gestation and 6 weeks , 6 months , and 12 months postpartum . Results Outcomes are reported for 46 women with vaginal or cesarean birth and for a sub sample of 37 women with vaginal birth . Longitudinal analyses are reported for cases with complete data across time points . Diminished urinary incontinence symptoms were seen in the treatment group , with significant treatment effects demonstrated at 35 weeks ' gestation ( F [ 1,43 ] = 4.36 , P = .043 ) , 6 weeks postpartum ( F [ 1,43 ] = 4.94 , P = .032 ) , and 6 months postpartum ( F [ 1,43 ] = 4.29 , P = .044 ) . A repeated measures analysis of variance showed a significant interaction between time and treatment for urinary incontinence ( F [ 4 , 41 ] = 2.83 , P = .037 ) . A significant effect of initial pelvic muscle strength was demonstrated ; ie , pelvic muscle strength at 20 weeks ' gestation predicted significantly 12-months postpartum strength ( F [ 1 , 13 ] = 8.12 , P = .014 ) . Group differences in pelvic muscle strength were observed ( the treatment group had greater strength at 6 weeks and at 6 months postpartum than did controls ) , but these differences were not statistically significant . Conclusion Practice of pelvic muscle exercise by primiparas results in fewer urinary incontinence symptoms during late pregnancy and postpartum AIM This article reports a r and omised controlled trial to determine the efficacy of antenatal pelvic floor muscle exercises in the primary prevention of postpartum stress incontinence in primiparous women . BACKGROUND Pelvic floor muscle exercises are effective in treating stress incontinence , yet prevention studies demonstrate equivocal findings . DESIGN R and omised controlled trial . METHOD Pregnant women recruited from two hospitals in North-west Engl and were r and omised to an intervention ( n = 141 ) or control group ( n = 145 ) . Data were collected from 2005 - 2006 . The intervention comprised four sessions of taught pelvic floor muscle exercise training during pregnancy and 8 - 12 maximal contractions repeated twice daily at home . A modified Bristol Female Lower Urinary Tract Symptom question naire , Leicester Impact Scale and Three Day Diary were administered at 20 and 36 weeks of pregnancy and three months postpartum . RESULTS The intervention group was more likely to exercise their pelvic floor muscles compared to controls at 36 weeks ( p = 0.019 ) and three months ( 0.022 ) , reporting fewer episodes of incontinence and a lower score on the Leicester Impact Scale . However , these differences were not statistically significant . CONCLUSION Significant differences were not demonstrated between the groups in relation to incontinence episodes and degree of bother of symptoms postpartum , although trends indicate a positive effect . Further research is necessary to address issues of adherence and the effect of pelvic floor muscle exercise undertaken during pregnancy on postpartum stress urinary incontinence . RELEVANCE TO CLINICAL PRACTICE A proportion of women did not meet the required attendance at antenatal class , furthermore , few exercised their pelvic floor muscles during pregnancy according to instructions . Health professionals need to find ways to instruct and motivate women to perform pelvic floor muscles exercises regularly during pregnancy and the postpartum 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 . The objective of this study was to test the short- and long-term effects of pelvic floor muscle training ( PFMT ) during pregnancy in women at risk , i.e. women who were already affected by urinary incontinence ( UI ) during pregnancy . The intervention consisted of three sessions of PFMT between week 23 and 30 during pregnancy and one session 6 weeks after delivery , combined with written information . The research design was a r and omised , controlled trial with four follow-ups up to 1 year after delivery . Participants in the study were 264 otherwise healthy women with UI during pregnancy , allocated at r and om to the intervention ( 112 ) or usual care ( 152 ) group . The main outcome measure was a UI severity scale and a 7-day bladder diary . No effect of pelvic floor muscle training was shown in this study at ( half ) a year after pregnancy . UI decreased strongly after pregnancy , irrespective of usual care or PMFT during pregnancy . For most women , usual care appears to be sufficient . The results support a ‘ wait and see ’ policy : wait for the urinary incontinence to take its natural course and see if , for women still incontinent half a year after pregnancy , pelvic floor muscle training is effective Summary We conducted a cohort study assessing risk factors for developing urinary incontinence following childbirth , and a pilot r and omized controlled trial of a physiotherapist-led intervention to reduce incidence of incontinence . A total of 723 women were recruited to the cohort study , of which 234 entered the nested trial and were r and omized to intensive training in pelvic floor exercises or st and ard information . At 6 months post-partum , 45 % of women reported some incontinence problems . A pre-existing incontinence problem was the best predictor of future incontinence ( odds ratio 4.49 , 95 % confidence interval ( CI ) 3.09–6.53 ) . Chronic constipation ( 1.86 , 1.03–3.34 ) and episiotomy in at least one delivery ( 1.96 , 1.25–3.07 ) were also independent risk factors , while an epidural or spinal ( 0.62 , 0.42–0.92 ) was protective . The intervention as design ed did not help in preventing future incontinence ( relative risk 1.28 , 95 % CI 0.98–1.67 ) , but this may be due to the failure to persuade the women to return for the classes . Any intervention aim ed at promoting postnatal pelvic floor exercises should be limited to women who have already been experiencing incontinence problems Abstract 1800 women recruited within 24 hours of vaginal delivery , were r and omly allocated to one of two pelvic floor exercise policies aim ed at preventing urinary incontinence . Nine hundred women received instruction currently available to all postnatal women in the West Berkshire Health District and 900 were encouraged to follow a more intensive regime endorsed by the use of a 4-week exercise diary . When assessed 10 days and 3 months after delivery , women allocated to the intensive policy were more likely to be persevering with their exercises . There were no differences between the two groups in terms of the prevalence or severity of urinary or faecal incontinence , but women in the intensive exercise group were less likely to report perineal pain and feelings of depression 3 months after delivery . These findings raise questions about the content of current postnatal exercise programmes . The components of these should now be formally evaluated in further r and omised trials |
10,958 | 28,723,513 | EVIDENCE SYNTHESIS Nomograms of prognostic factors ( eg , albumin , lactate dehydrogenase ) enable clinicians to estimate the prognosis of men with mCRPC .
Determination of AR-V7 in CTCs is a big step towards a more personalized treatment approach in mCRPC .
Genomic characterization of liquid biopsies such as CTCs , cfDNA , and circulating RNA are noninvasive tools to further personalize treatment in prostate cancer .
Only by conducting biomarker-driven studies , rather than large one-size-fits-all trials , will we be able to improve prostate cancer treatment . | CONTEXT Biomarkers for the treatment of metastatic castration-resistant prostate cancer ( mCRPC ) are urgently needed by clinicians to facilitate treatment decisions .
OBJECTIVE To review current prognostic and predictive biomarkers in mCRPC .
These prognostic tools may aid with when to trigger treatment , therapeutic monitoring , and follow-up .
However , vali date d predictive biomarkers in mCRPC are still lacking . | BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) BACKGROUND Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive and rogen-independent prostate cancer . We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic , hormone-independent prostate cancer . METHODS We r and omly assigned 770 men to one of two treatments , each given in 21-day cycles : 280 mg of estramustine three times daily on days 1 through 5 , 60 mg of docetaxel per square meter of body-surface area on day 2 , and 60 mg of dexamethasone in three divided doses before docetaxel , or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily . The primary end point was overall survival ; secondary end points were progression-free survival , objective response rates , and post-treatment declines of at least 50 percent in serum prostate-specific antigen ( PSA ) levels . RESULTS Of 674 eligible patients , 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone . In an intention-to-treat analysis , the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone ( 17.5 months vs. 15.6 months , P=0.02 by the log-rank test ) , and the corresponding hazard ratio for death was 0.80 ( 95 percent confidence interval , 0.67 to 0.97 ) . The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone ( P<0.001 by the log-rank test ) . PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients , respectively ( P<0.001 ) , and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease , respectively ( P=0.30 ) . Grade 3 or 4 neutropenic fevers ( P=0.01 ) , nausea and vomiting ( P<0.001 ) , and cardiovascular events ( P=0.001 ) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone . Pain relief was similar in both groups . CONCLUSIONS The improvement in median survival of nearly two months with docetaxel and estramustine , as compared with mitoxantrone and prednisone , provides support for this approach in men with metastatic , and rogen-independent prostate cancer BACKGROUND Abiraterone acetate ( AA ) is an and rogen bio synthesis inhibitor shown to prolong life in patients with castration-resistant prostate cancer ( CRPC ) already treated with chemotherapy . AA treatment results in dramatic declines in prostate-specific antigen ( PSA ) in some patients and no declines in others , suggesting the presence of molecular determinants of sensitivity in tumors . OBJECTIVE To study the role of transmembrane protease , serine 2 (TMPRSS2)-v-ets erythroblastosis virus E26 oncogene homolog ( ERG ) fusion , an and rogen-dependent growth factor , in circulating tumor cells ( CTCs ) as a biomarker of sensitivity to AA . DESIGN , SETTING , AND PARTICIPANTS The predictive value of TMPRSS2-ERG status was studied in 41 of 48 men with postchemotherapy-treated CRPC enrolled in sequential phase 2 AA trials . INTERVENTION Patients received AA 1000 mg daily and continuously . MEASUREMENTS TMPRSS2-ERG status was characterized by a sensitive , analytically valid reverse transcription polymerase chain reaction assay in CTCs enriched from ethylene-diaminetetraacetic acid anticoagulated blood obtained prior to AA treatment . Outcomes were measured by PSA Working Group 1 criteria . RESULTS AND LIMITATIONS St and ard procedures for specimen acquisition , processing , and testing using the vali date d TMPRSS2-ERG assay on a multiplex platform gave intra-assay and interassay coefficients of variation < 7 % . TMPRSS2-ERG fusion was present in 15 of 41 patients ( 37 % ) , who had a median baseline CTC count of 17 ( interquartile range : 7 - 103 cells per 7.5 ml ) . A PSA decline ≥50 % was observed in 7 of 15 patients ( 47 % ) with the fusion and in 10 of 26 patients ( 38 % ) without the fusion . Although limited by the low number of patients , a posttherapy CTC count of less than five per 7.5 ml was prognostic for longer survival relative to a CTC count five or more . TMPRSS2-ERG status did not predict a decline in PSA or other clinical outcomes . CONCLUSIONS Molecular profiles of CTCs with an analytically valid assay identified the presence of the prostate cancer-specific TMPRSS2-ERG fusion but did not predict for response to AA treatment . This finding demonstrates the role of CTCs as surrogate tissue that can be obtained in a routine practice setting . TRIAL REGISTRATION Clinical Trials.gov : NCT00474383 ( COU-AA-003 ) , NCT00485303 ( COU-AA-004 ) Background Treatment response biomarkers are urgently needed for castration-resistant prostate cancer ( CRPC ) . Baseline and post-treatment circulating tumor cell ( CTC ) counts of ≥5 cells/7.5 ml are associated with poor CRPC outcome . Objective To determine the value of a ≥30 % CTC decline as a treatment response indicator . Design , setting , and participants We identified patients with a baseline CTC count ≥5 cells/7.5 ml and evaluable post-treatment CTC counts in two prospect i ve trials . Intervention Patients were treated in the COU-AA-301 ( abiraterone after chemotherapy ) and IMMC-38 ( chemotherapy ) trials . Outcome measures and statistical analysis The association between a ≥30 % CTC decline after treatment and survival was evaluated using univariable and multivariable Cox regression models at three l and mark time points ( 4 , 8 , and 12 wk ) . Model performance was evaluated by calculating the area under the receiver operating characteristic curve ( AUC ) and c-indices . Results Overall 486 patients ( 122 in IMMC-38 and 364 in COU-AA-301 ) had a CTC count ≥5 cells/7.5 ml at baseline , with 440 , 380 , and 351 patients evaluable at 4 , 8 , and 12 wk , respectively . A 30 % CTC decline was associated with increased survival at 4 wk ( hazard ratio [ HR ] 0.45 , 95 % confidence interval [ CI ] 0.36–0.56 ; p < 0.001 ) , 8 wk ( HR 0.41 , 95 % CI 0.33–0.53 ; p < 0.001 ) , and 12 wk ( HR 0.39 , 95 % CI 0.3–0.5 ; p < 0.001 ) in univariable and multivariable analyses . Stable CTC count ( < 30 % fall or < 30 % increase ) was not associated with a survival benefit when compared with increased CTC count . The association between a 30 % CTC decline after treatment and survival was independent of baseline CTC count . CTC declines significantly improved the AUC at all time-points . Finally , in the COU-AA-301 trial , patients with CTC ≥5 cells/7.5 ml and a 30 % CTC decline had similar overall survival in both arms . Conclusions A 30 % CTC decline after treatment from an initial count ≥5 cells/7.5 ml is independently associated with CRPC overall survival following abiraterone and chemotherapy , improving the performance of a multivariable model as early as 4 wk after treatment . This potential surrogate must now be prospect ively evaluated . Patient summary Circulating tumor cells ( CTCs ) are cancer cells that can be detected in the blood of prostate cancer patients . We analyzed changes in CTCs after treatment with abiraterone and chemotherapy in two large clinical trials , and found that patients who have a decline in CTC count have a better survival outcome BACKGROUND And rogen receptor splice variant 7 ( AR-V7 ) in circulating tumor cells ( CTCs ) from patients with metastatic castration-resistant prostate cancer ( mCRPC ) was recently demonstrated to be associated with resistance to abiraterone and enzalutamide . Cabazitaxel might , however , remain effective in AR-V7-positive patients . OBJECTIVE To investigate the association between AR-V7 expression in CTCs and resistance to cabazitaxel . DESIGN , SETTING , AND PARTICIPANTS We selected patients with mCRPC from the multicenter , r and omized , phase 2 , r and omized , open-label , multicenter study in mCRPC on the pharmacodynamic effects of budesonide on cabazitaxel ( Jevtana ) ( CABARESC ) . Before the start of the first and third cabazitaxel cycle , CTCs were enumerated using the Cell Search System . In patients with ≥10 CTCs in 7.5 ml blood at baseline , the expression of AR-V7 was assessed by quantitative polymerase chain reaction . OUTCOME MEASURES AND STATISTICAL ANALYSIS The primary end point was the association between the AR-V7 status and the CTC response rate ( decrease to fewer than five CTCs in 7.5 ml blood during treatment ) . Secondary end points were the prostate-specific antigen ( PSA ) response rate ( RR ) and overall survival ( OS ) . Analyses were performed using chi-square and log-rank tests . RESULTS AND LIMITATIONS AR-V7 was detected in 16 of 29 patients ( 55 % ) with ≥10 CTCs and was more frequently found in abiraterone pretreated patients ( 5 of 5 [ 100 % ] treated vs 7 of 20 [ 35 % ] untreated ; p=0.009 ) . We found no differences in CTC and PSA RRs . The presence of AR-V7 in CTCs was not associated with progression-free survival ( hazard ratio [ HR ] : 0.8 ; 95 % confidence interval [ CI ] , 0.4 - 1.8 ) or overall survival ( HR 1.6 ; 95 % CI , 0.6 - 4.4 ) . CONCLUSIONS The response to cabazitaxel seems to be independent of the AR-V7 status of CTCs from mCRPC patients . Consequently , cabazitaxel might be a valid treatment option for patients with AR-V7-positive CTCs . PATIENT SUMMARY Tools are needed to select specific treatments for specific patients at specific times . The presence of the gene AR-V7 in CTCs has been associated with resistance to anti- and rogen receptor treatments . We investigated whether this holds true for cabazitaxel , but we found cabazitaxel to be effective independent of the presence of AR-V7 BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P<0.001 for both comparisons with mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone Purpose : The transition of prostate adenocarcinoma to a predominantly and rogen receptor ( AR ) signaling independent phenotype can occur in the later stages of the disease and is associated with low AR expression + /− the development of small-cell or neuroendocrine tumor characteristics . As metastatic tumor biopsies are not always feasible and are difficult to repeat , we sought to evaluate noninvasive methods to identify patients transitioning toward a neuroendocrine phenotype ( NEPC ) . Experimental Design : We prospect ively studied a metastatic tumor biopsy , serum biomarkers , and circulating tumor cells ( CTC , Epic Sciences ) from patients with castration-resistant prostate cancer ( CRPC ) including those with pure or mixed NEPC histology present on biopsy . CTCs labeled with the patient 's clinical status were used to learn features that discriminate NEPC patients , which was then applied to an independent cohort . Results : Twenty-seven patients with CRPC including 12 NEPC and 5 with atypical clinical features suggestive of NEPC transition were studied . CTCs from NEPC patients demonstrated frequent clusters , low or absent AR expression , lower cytokeratin expression , and smaller morphology relative to typical CRPC . A multivariate analysis of protein and morphologic variables enabled distinguishing CTCs of NEPC from CRPC . This CTC classifier was applied to an independent prospect i ve cohort of 159 metastatic CRPC patients and identified in 17/159 ( 10.7 % ) of cases , enriched in patients with high CTC burden ( P < 0.01 ) and visceral metastases ( P = 0.04 ) . Conclusions : CTCs from patients with NEPC have unique morphologic characteristics , which were also identified in a subset of CRPC patients with aggressive clinical features potentially undergoing NEPC transition . Clin Cancer Res ; 22(6 ) ; 1510–9 . © 2015 AACR Importance A critical decision in the management of metastatic castration-resistant prostate cancer ( mCRPC ) is when to administer an and rogen receptor signaling ( ARS ) inhibitor or a taxane . Objective To determine if pretherapy nuclear and rogen-receptor splice variant 7 ( AR-V7 ) protein expression and localization on circulating tumor cells ( CTCs ) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes . Design , Setting , and Participants For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center , 265 men with progressive mCRPC undergoing a change in treatment were considered ; 86 were excluded because they were not initiating ARS or taxane therapy ; and 18 were excluded for processing time constraints , leaving 161 patients for analysis . Between December 2012 and March 2015 , blood was collected and processed from patients with progressive mCRPC immediately prior to new line of systemic therapy . Patients were followed up to 3 years . Main Outcomes and Measures Prostate-specific antigen ( PSA ) response , time receiving therapy , radiographic progression-free survival ( rPFS ) , and overall survival ( OS ) . Results Overall , of 193 prospect ively collected blood sample s from 161 men with mCRPC , 191 were evaluable ( 128 pre-ARS inhibitor and 63 pretaxane ) . AR-V7-positive CTCs were found in 34 sample s ( 18 % ) , including 3 % of first-line , 18 % of second-line , and 31 % of third- or greater line sample s. Patients whose sample s had AR-V7-positive CTCs before ARS inhibition had resistant posttherapy PSA changes ( PTPC ) , shorter rPFS , shorter time on therapy , and shorter OS than those without AR-V7-positive CTCs . Overall , resistant PTPC were seen in 65 of 112 sample s ( 58 % ) without detectable AR-V7-positive CTCs prior to ARS inhibition . There were statistically significant differences in OS but not in PTPC , time on therapy , or rPFS for patients with or without pretherapy AR-V7-positive CTCs treated with a taxane . A multivariable model adjusting for baseline factors associated with survival showed superior OS with taxanes relative to ARS inhibitors when AR-V7-positive CTCs were detected pretherapy ( hazard ratio , 0.24 ; 95 % CI , 0.10 - 0.57 ; P = .035 ) . Conclusions and Relevance The results vali date CTC nuclear expression of AR-V7 protein in men with mCRPC as a treatment-specific biomarker that is associated with superior survival on taxane therapy over ARS-directed therapy in a clinical practice setting . Continued examination of this biomarker in prospect i ve studies will further aid clinical utility BACKGROUND Since 2004 , docetaxel has been the st and ard first-line systemic therapy for patients with metastatic castration-resistant prostate cancer ( mCRPC ) . With abiraterone recently becoming available in the predocetaxel setting , it is warranted to identify subgroups of patients who may obtain the greatest benefit from docetaxel and particularly qualify for receiving docetaxel as first-line treatment for mCRPC . OBJECTIVE We aim ed to identify factors that could characterize subgroups of patients who obtain the greatest benefit from the use of docetaxel . DESIGN , SETTING , AND PARTICIPANTS TAX327 was multinational , r and omized , phase 3 study that was conducted from 2000 to 2002 in 1006 men with mCRPC . INTERVENTION Patients were r and omized to receive docetaxel every 3 wk ( D3 ) , weekly docetaxel ( D1 ) , or mitoxantrone every 3 wk ( M3 ) , each with prednisone . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We investigated whether patients with poorly differentiated tumors ( Gleason score ≥7 ) at diagnosis had greater benefit from D3 compared with M3 than patients with better differentiated tumors ( Gleason score ≤6 ) . Using a Cox model , we compared overall survival ( OS ) between the treatment groups within each subgroup of Gleason score . RESULTS AND LIMITATIONS The TAX 327 data showed that the OS benefit of D3 versus M3 was greater in patients with high- grade tumors ( median OS : 18.9 vs 14.5 mo ; p=0.009 ) than in patients with low- grade tumors ( median OS : 21.6 vs 20.7 mo ; p=0.674 ) . Limitations of a retrospective analysis apply . CONCLUSIONS The survival benefit obtained with docetaxel is most pronounced in patients with high-Gleason-score tumors ( Gleason ≥7 ) . In a time of shifting paradigms in mCRPC , with abiraterone becoming available prior to docetaxel chemotherapy , Gleason score may help in selecting patients who obtain the greatest benefit from docetaxel as first-line treatment for mCRPC . Prospect i ve validation of these findings is warranted BACKGROUND The and rogen-receptor isoform encoded by splice variant 7 lacks the lig and -binding domain , which is the target of enzalutamide and abiraterone , but remains constitutively active as a transcription factor . We hypothesized that detection of and rogen-receptor splice variant 7 messenger RNA ( AR-V7 ) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone . METHODS We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospect ively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone . We examined associations between AR-V7 status ( positive vs. negative ) and prostate-specific antigen ( PSA ) response rates ( the primary end point ) , freedom from PSA progression ( PSA progression-free survival ) , clinical or radiographic progression-free survival , and overall survival . RESULTS A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled , of whom 39 % and 19 % , respectively , had detectable AR-V7 in circulating tumor cells . Among men receiving enzalutamide , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 53 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.4 months vs. 6.0 months ; P<0.001 ) , clinical or radiographic progression-free survival ( median , 2.1 months vs. 6.1 months ; P<0.001 ) , and overall survival ( median , 5.5 months vs. not reached ; P=0.002 ) . Similarly , among men receiving abiraterone , AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients ( 0 % vs. 68 % , P=0.004 ) and shorter PSA progression-free survival ( median , 1.3 months vs. not reached ; P<0.001 ) , clinical or radiographic progression-free survival ( median , 2.3 months vs. not reached ; P<0.001 ) , and overall survival ( median , 10.6 months vs. not reached , P=0.006 ) . The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length and rogen receptor messenger RNA . CONCLUSIONS Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone . These findings require large-scale prospect i ve validation . ( Funded by the Prostate Cancer Foundation and others . ) BACKGROUND The neutrophil-lymphocyte ratio ( NLR ) , proposed as an indicator of cancer-related inflammation , has known prognostic value in prostate cancer . We examine its association with survival ( OS ) and response in patients treated with second-line chemotherapy . METHODS We analysed patients with metastatic castration-resistant prostate cancer ( mCRPC ) treated in the TROPIC trial , evaluating cabazitaxel versus mitoxantrone . Cox regression models were used to investigate the association of baseline NLR ( BLNLR ) with OS and the significance of a change in NLR count with treatment . Logistic regression models were used to determine the association of BLNLR counts with prostate specific antigen ( PSA ) and RECIST responses . The optimal NLR cut-off was established based on the concordance index of different values . RESULTS Data from 755 , 654 and 405 patients was available for OS , PSA and RECIST response analysis respectively . Median OS was 14.0 months [ 95 % confidence interval ( CI ) 13.2 - 14.8 ] . Median NLR was 2.9 ( IQR : 1.9 - 5.1 ) . BLNLR was associated with survival ( HR 1.5 , 95 % CI 1.1 - 2.1 , P = 0.011 ) in multivariable analysis ( MVA ) independently of variables included in the Halabi nomogram , treatment arm and corticosteroid use . The optimal cut-off for a dichotomous NLR was selected at 3.0 based on its higher c-index related to survival . BLNLR ≥3.0 was associated with lower PSA response ( 40.1 % versus 59.9 % ; P < 0.001 ) and RECIST response ( 7.7 % versus 15.6 % , P = 0.022 ) in MVA . Conversion from high ( ≥3 ) to low ( <3 ) NLR was associated with improved survival ( HR 0.66 ; 95 % CI 0.51 - 0.85 ; P = 0.001 ) and higher PSA response rates ( 66.4 % versus 33.6 % ; P = 0.000 ) . Use of corticosteroids at baseline did not modify the association between NLR and survival . CONCLUSIONS NLR is a valid prognostic biomarker in CRPC and is associated with survival , PSA and RECIST responses in patients treated with second-line chemotherapy . Changes in NLR counts with treatment may indicate benefit . NLR prognostic value is independent of prior use of corticosteroids . CLINICAL TRIALSGOV NCT00417079 |
10,959 | 24,360,260 | The overall evidence was insufficient to assess which of indirect pulp capping , stepwise excavation , direct excavation and pulp capping/partial pulpotomy , pulpotomy or pulpectomy is the most effective treatment approach for teeth with deep caries .
CONCLUSIONS Because of the lack of good studies it is not possible to determine whether an injured pulp by deep caries can be maintained or whether it should be removed and replaced with a root canal filling . | BACKGROUND This systematic review assesses the effect of methods commonly used to manage the pulp in cases of deep caries lesions , and the extent the pulp chamber remains uninfected and does not cause pulpal or periapical inflammatory lesions and associated tooth-ache over time . | Three intermediary base material s , a zinc oxide-eugenol ( Cavitec ) and two calcium hydroxide liners ( Life and Dycal ) , were selected at r and om for use as a base beneath amalgam or composite restorations on humans following complete caries removal . Life and Dycal , selected at r and om , were also used as direct and indirect pulp capping agents as clinical ly indicated . Clinical evaluations of signs and symptoms were made before treatment and at one-week , six-month , and one-year intervals following treatment . Histological evaluations were performed on three complete caries removal teeth and 18 direct pulp capping teeth six months following treatment . No significant differences in clinical symptomatology result ed between the material s in the complete caries removal group or the indirect and direct pulp capping groups Objectives Root canal therapy ( RCT ) and tooth extraction have been conventional treatment options for management of human mature teeth with irreversible pulpitis . Excellent short-term treatment outcomes of vital pulp therapy with calcium-enriched mixture cement ( VPT/CEM ) , as a new treatment option , on postoperative pain relief was demonstrated ; if intermediate- and long-term treatment outcomes of the new treatment are also non-inferior compared to RCT , then VPT/CEM may become a viable treatment option for management of mature teeth with irreversible pulpitis . Material s and methods In 23 healthcare centers , 407 9- to 65-year-old patients were r and omly allocated into two study arms including one-visit RCT ( reference treatment ; n = 202 ) and VPT/CEM ( alternative treatment ; n = 205 ) . Six- and twelve-month clinical and radiographic successes were assessed . Results Mean follow-up times at 6- and 12-month follow-ups were “ 6.70 ± 0.68 and 6.72 ± 0.71 months ” and “ 12.96 ± 0.67 and 12.90 ± 0.66 months ” in the available cases of RCT and VPT/CEM arms , respectively . Favorable clinical success rates in the two study arms did not show statistical difference ; however , the radiographic success rate in the VPT/CEM was significantly greater than RCT arm at the two follow-ups ( P < 0.001 ) . The patients ’ age had no effect on the treatment outcomes ( P = 0.231 ) . Conclusions Treatment outcomes of VPT/CEM may be superior to RCT in mature molars with irreversible pulpitis . The performance of bio material s such CEM cement may assist in the shift towards more biologic treatments . Clinical relevance VPT/CEM may be a realistic alternative treatment for human mature molar teeth with symptoms of irreversible pulpitis ; the use of VPT/CEM is highly beneficial for patients as well as general dentists In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Aim : This r and omized , multicenter clinical trial by Maltz et al. [ 1 ] evaluated the effectiveness of two treatments for deep caries lesions — partial caries removal ( PCR ) and stepwise excavation (SW)—with respect to the primary outcome of pulp vitality for a 3-year follow-up period . Material and methods : Inclusion criteria were as follows : patients with permanent molars presenting deep caries lesions ( lesion affecting ≥1/2 of the dentin on radiographic examina tion ) , positive response to a cold test , absence of spontaneous pain , negative sensitivity to percussion , and absence of periapical lesions ( radiographic examination ) . Teeth r and omly assigned to PCR ( test ) received incomplete caries removal and filling in a single session . Outcome success was evaluated by assessment of pulp vitality , determined by pulp sensitivity to a cold test and the absence of periapical lesions . Data were analyzed by a Weibull regression model with shared frailty term ( survival analysis ) . Results : At baseline , 299 treatments were executed : PCR 152 and SW 147 . By the end of the 3-year follow-up period , 213 teeth had been evaluated . Adjusted survival rates were 91 % for PCR and 69 % for SW ( p=0.004 ) . Conclusion : These results suggest that there is no need to reopen a cavity and perform a second excavation for pulp vitality to be preserved ( Clinical trials registration NCT00887952 ) . Conflict of interest The corresponding author states that there are no conflicts of interest . Ziel : Diese r and omisierte , multizentrische klinische Studie untersuchte die Effektivitat von zwei Therapieansatzen zur Beh and lung tiefer karioser Lasionen : partielle Kariesentfernung ( PCR ) und mehrstufige Exkavation ( SW ) . Die primar zu untersuchende Auswirkung war die Vitalitat uber 3 Jahre . Material und Method e : Einschlusskriterien waren : Patienten deren permanente Molaren tiefe kariose Lasionen aufweisen ( rontgenologische Lasionen ≥½ des Dentins ) , positive Reak tion auf Kalte , Ausbleiben von Spontanschmerzen , negative Sensitivitat auf Perkussion , radiologisch keine apikalen Lasionen . Bei Zahnen , die in die PCR-Gruppe ( Test ) r and omisiert wurden , erfolgten eine unvollst and ige Kariesentfernung und die Fullung in einer Sitzung . I m Anschluss wurden die Vitalitat , das Ansprechen auf einen Kaltetest und das Ausbleiben von periapikalen Lasionen ermittelt . Die Auswertung erfolgte uber ein Weibull Regressionsmodell mit einem " shared frailty term " ( Lebensdaueranalyse ) Less invasive excavation methods have been suggested for deep caries lesions . We tested the effects of stepwise vs. direct complete excavation , 1 yr after the procedure had been carried out , in 314 adults ( from six centres ) who had received treatment of a tooth with deep caries . The teeth had caries lesions involving 75 % or more of the dentin and were central ly r and omized to stepwise or direct complete excavation . Stepwise excavation result ed in fewer pulp exposures compared with direct complete excavation [ difference : 11.4 % , 95 % confidence interval ( CI ) ( 1.2 ; 21.3 ) ] . At 1 yr of follow-up , there was a statistically significantly higher success rate with stepwise excavation , with success being defined as an unexposed pulp with sustained pulp vitality without apical radiolucency [ difference : 11.7 % , 95 % CI ( 0.5 ; 22.5 ) ] . In a subsequent nested trial , 58 patients with exposed pulps were r and omized to direct capping or partial pulpotomy . We found no significant difference in pulp vitality without apical radiolucency between the two capping procedures after more than 1 yr [ 31.8 % and 34.5 % ; difference : 2.7 % , 95 % CI ( -22.7 ; 26.6 ) ] . In conclusion , stepwise excavation decreases the risk of pulp exposure compared with direct complete excavation . In view of the poor prognosis of vital pulp treatment , a stepwise excavation approach for managing deep caries lesions is recommended OBJECTIVE The purpose of this project was to evaluate the performance of a dentin adhesive system on carious and noncarious primary dentin in vivo . METHOD AND MATERIAL S Forty-eight primary molars with carious lesions were r and omly assigned to 2 different treatments : group 1 ( control , n = 24)--All identifiable , irreversibly infected dentin was removed prior to the application of the bonding agent and restorative material ; group 2 ( experimental , n = 24)--Irreversibly infected dentin was partially removed prior to the application of the bonding agent and restorative material . The control and experimental teeth were clinical ly monitored every 3 months and evaluated 12 months after restoration . The teeth were extracted around the time of exfoliation and processed for scanning electron microscopy . RESULTS Retention rate , marginal integrity , and pulpal symptoms were identical in both groups . Radiographically , the radiolucent area associated with the experimental restorations did not increase with time in 75 % of the cases . For the control group , the adhesive system formed a hybrid layer . In the experimental group , there was morphologic evidence of the formation of an acid-resistant " altered hybrid layer . " An acid-resistant tissue , result ing from the interdiffusion of adhesive resin within the area of carious dentin , was observed adjacent to and under the altered hybrid layer . CONCLUSION Application of an adhesive restorative system to irreversibly infected dentin did not affect the clinical performance of the restoration PURPOSE The purpose of this prospect i ve and r and omized in vivo study was to compare the clinical and radiographic outcomes of an adhesive resin system vs a calcium hydroxide liner for protection of the dentin-pulp complex of primary molars treated with indirect pulp treatment . METHODS Forty-eight primary molars with deep occlusal caries , but without preoperative signs and symptoms of irreversible pulpitis , received indirect pulp treatment and were restored with a composite resin ( Z100 ) . The teeth were r and omly divided into 2 groups according to the material used for protection of the dentin-pulp complex : ( 1 ) adhesive resin system ( Scotchbond Multi Purpose ) ; and ( 2 ) calcium hydroxide liner ( Dycal ) . These teeth were evaluated clinical ly and radiographicaly for 2 years . RESULTS After 2 years , 83 % ( 19/23 ) of the teeth treated with calcium hydroxide and 96 % ( 24/25 ) of teeth treated with only the adhesive resin system presented a successful outcome , as determined by clinical and radiographic examination . Interradicular and /or periapical lesions were the most predominant signs of treatment failure , since 3 out of 23 teeth treated with calcium hydroxide and 1 out of 25 teeth treated with only adhesive resin presented this outcome . One tooth treated with the calcium hydroxide liner was diagnosed with internal root resorption at the 18-month examination . Of the 5 teeth diagnosed from radiographs as a failure of the indirect pulp treatment , none presented clinical signs/symptoms of pulpitis or necrosis such as the presence of fistula , enhanced tooth mobility , or pain . CONCLUSIONS This study demonstrates that protection of the dentin-pulp complex of primary molars with an adhesive resin system results in similar clinical and radiographic 2-year outcomes as compared to calcium hydroxide when indirect pulp treatment is performed in Class I composite restorations Aim : To prospect ively compare the clinical success rate of partial pulpotomy treatment in permanent molars using calcium hydroxide ( CH ) and mineral trioxide aggregates ( MTA ) as pulp dressing agents . Methods : Restorable permanent first molars ( 64 ) with carious pulp exposures were r and omly assigned to two groups ; CH and MTA . A st and ardized operative procedure was followed in both groups . Following isolation and caries removal , the exposed superficial pulp tissue layers were removed with a sterile flame shape diamond bur to a depth of 2–4 mm . Bleeding was controlled and pulp dressed with either a paste of non- setting Ca(OH)2 followed by a setting layer of Ca(OH)2 , or with grey MTA . The dressing material s in both groups were then covered with a layer of light cured glass ionomer cement . The teeth were either restored using amalgam , or where grossly carious with preformed metal crowns . Patients were scheduled for follow-up at 3 , 6 , 12 months and annually thereafter . Results : There were 34 patients ( 17 males and 17 females ) with 51 teeth available for evaluation . The age of patients at the time of restoration ranged between 6.8 to 13.3 years ( mean of 10.3 ±1.8 years ) . The follow-up period ranged from 25.4 to 45.6 months with an average of 34.8 ± 4.4 months . There was no statistically significant difference in the success rate of teeth treated with CH ( 91 % ) in comparison to teeth treated with MTA ( 93 % ) . Radiographically , a hard tissue barrier under CH was noticed in 12 ( 55 % ) teeth compared with 18 ( 64 % ) teeth under MTA ( p=0.4 ) . Conclusions : MTA has clinical success rate comparable to CH as a pulp dressing material for partial pulpotomy in permanent molars with carious The aim was to assess the prevalence of pulp exposure after stepwise versus direct complete excavation of permanent posterior teeth with deep carious lesions . The material , representing 116 patients aged 6 - 16 yrs ( mean = 10.2 yrs ) , consisted of 127 teeth with radiographs revealing carious lesions to such a depth that pulp exposure could be expected if direct complete excavation was performed . Teeth with clinical symptoms , other than transient pain shortly before treatment , were not accepted . The teeth were r and omly selected for either treatment procedure . Stepwise excavation implied removal of the bulk of carious tissue and application of calcium hydroxide , followed by sealing of the cavity with zinc-oxide eugenol cement . After a period of 8 - 24 weeks the rest of the carious dentin was removed and the cavity sealed with calcium hydroxide , zinc-oxide-eugenol ( ZOE ) and a restorative material . Direct complete excavation entailed removal of all carious dentin followed by sealing as mentioned above . In case of pulp exposure , pulp treatment was performed . The pulp was exposed in 40 of the teeth treated by direct complete excavation . The corresponding figure for those treated by stepwise excavation was 17.5 % . The difference was statistically significant . The teeth with no pulp exposure after direct or stepwise excavation showed normal clinical and radiographic conditions at the last check-up ( mean = 43 months ) PURPOSE The purpose of this study was to examine whether 1- or 2-visit indirect pulp therapy ( IPT ) is more successful and to determine if the operator can successfully decide when to stop removing caries without exposing the pulp . METHODS A total of 154 teeth ( 94 primary second molars and 60 young permanent first molars ) were included in the study from a total of 123 4- to 15-year-old patients . The teeth had deep carious lesions but lacked the preoperative signs and symptoms of irreversible pulpitis . The teeth were r and omly selected and treated either with 1-visit IPT , 2-visit IPT , or direct complete excavation ( DCE ) . Follow-up examinations were conducted on the teeth over 1 year at 3-month intervals . RESULTS The pulp was exposed in 12 teeth ( 22 % ) treated by DCE , whereas 3 teeth ( 6 % ) were treated by 1-visit IPT and 4 teeth ( 8 % ) with 2-visit IPT . A statistically significant difference was found between IPT and DCE groups in terms of pulp exposure ( P<.05 ) . The teeth without pulp exposure showed normal clinical and radiographic conditions during the 1-year follow-up , except for 3 primary teeth . CONCLUSIONS Indirect pulp therapy in both primary and young permanent teeth can be used successfully with a 1- or 2-visit approach Making a diagnosis is the bread and butter of clinical practice , but in light of the number of tests now available to clinician , diagnosing illness has become a complicated process . Guidelines for making an evidence -based diagnosis abound , but those making recommendations about diagnostic tests or test strategies must realize that clinicians require support to make diagnostic decisions that they can easily implement in daily practice . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group has developed a rigorous , transparent , and increasingly adopted approach for grading the quality of research evidence and strength of recommendations to guide clinical practice . This editorial summarizes GRADE 's process for developing recommendations for tests ( 1 ) . Clinicians are trained to use tests for screening and diagnosis ; identifying physiologic derangements ; establishing a prognosis ; and monitoring illness and treatment response by assessing signs and symptoms , imaging , biochemistry , pathology , and psychological testing techniques ( 2 ) . Sensitivity , specificity , positive predictive value , likelihood ratios , and diagnostic odds ratios are among the challenging terms that diagnostic studies typically deliver to clinicians , and all have to do with diagnostic accuracy . Not only do clinicians have difficulties remembering the definitions and calculations for these terms , application of the concepts to individual patients is often complicated . Many clinicians order a test despite uncertainty about how to interpret the result , and they also contribute to testing errors by incorrectly ordering tests ( 3 , 4 ) . GRADE 's framework for developing recommendations for diagnostic management studies is based on what is needed for practical clinical applicationthat is , how to weigh the benefits and harms of ordering and using a diagnostic test in caring for patients ( 1 ) . The approach begins with specifying the PICO : the relevant population ( P ) , diagnostic intervention or test ( I ) ( including its purpose , such as triage , replacement , or an add-on test ) , comparison test ( C ) , and patient-important outcomes ( O ) related to the use of a test for a focused clinical question . If a test fails to improve patient-important outcomes , there is no reason to use it , whatever its accuracy . For example , the results of genetic testing for Huntington chorea , an untreatable condition , may provide either welcome reassurance that a patient will not have the condition or the ability to plan for his future knowing that he will sadly fall victim ( 1 ) . Here , the ability to plan is analogous to an effective treatment , and the benefits of planning need to be balanced against the downsides of receiving an early diagnosis ( 5 - 7 ) . The best evidence of test performance comes from large r and omized trials of diagnostic strategies that directly measure patient-important outcomes ( 1 ) . However , these trials are few and far between : An informal review of the Cochrane data base of r and omized trials revealed < 100 such studies . Therefore , most recommendations about diagnostic testing are based on an implicit 2-step process of how the accuracy of a test indirectly changes patient-important outcomes . In the first step , a diagnostic-test accuracy study ( Figure ) , patients may receive both a new test and a reference test ( i.e. , the best available method for detecting the target condition ) . Investigators can then calculate the accuracy of the test compared with the reference test ( first step ) . In the second step , judgments about the patient importance of test accuracy are based on the consequences of being correctly or incorrectly classified as having or not having the disease . These include the benefits and harms of receiving treatment or follow-up tests for those correctly classified as having the disease , reassurance or receipt of other follow-up tests for those correctly classified as not having the disease , receipt of unnecessary treatment or additional tests for those incorrectly classified as having the disease , delayed or no treatment for those incorrectly classified as not having the disease , and any adverse effects of the diagnostic test ( e.g. , from invasive tests ) . Those making recommendations about diagnostic tests must then compare patient-important outcomes ( and costs ) in all patients receiving the new test with all patients receiving the old , or comparator , test . For the first step ( i.e. , assessing test accuracy ) , there are well-described method ological criteria for assessing risk for bias in an estimate of test accuracy , ideally based on a systematic review of relevant studies . For instance , studies of diagnostic test accuracy with a low risk for bias enroll consecutive patients for whom there is legitimate diagnostic uncertaintythat is , the type of patients to whom clinicians would apply the test in the course of regular clinical practice . If studies fail this criterion ( e.g. , only enroll patients with severe disease and healthy controls ) , the apparent accuracy of a test is likely to be misleadingly high ( 8 , 9 ) . The second step shown in the Figure is , in most situations , based on judgments of test accuracy as a surrogate for patient-important outcomes . The key issue about these judgments is that they should be made transparent to those using the recommendations . For example , in the diagnosis of suspected acute urolithiasis , well- design ed studies demonstrate fewer false-negative results with noncontrast helical computed tomography ( CT ) than with intravenous pyelography ( IVP ) ( 10 ) . However , those ureteric stones that CT detects but IVP misses are smaller and therefore are more likely to spontaneously pass . Before r and omized trials evaluating outcomes in patients treated for smaller stones , evidence from observational studies was of lower quality . Thus , it remained uncertain how patients were affected by missed cases and follow-up of incidental findings unrelated to renal calculi with CT . Recommendations about using one test ( IVP ) over the other ( helical CT ) were based on judgments of how the cases that were detected or missed would fare with or without treatment ( 11 ) . These judgments were likely to be based on indirect evidence and would be less certain than judgments based on direct evidence from a r and omized trial comparing the 2 tests . The GRADE approach requires making these judgments about the relation between accuracy and patient-important outcomes transparent . The example of IVP versus helical CT for patients with suspected acute shows exemplifies how the quality of evidence for an accurate test would be down grade d because of the lack of direct evidence on patient-important outcomes . Uncertainty about patient-important consequences and associated uncertainty about benefits and harms would probably have result ed in weak GRADE recommendations about the use of IVP compared with helical CT . Those making recommendations using the GRADE approach should also explicitly consider judgments and evidence about the values and preferences that patients attach to important consequences , as described more fully elsewhere ( 1 ) . Acknowledgments : This work was partially funded by a The human factor , mobility and Marie Curie Actions Scientist Reintegration European Commission Grant ( IGR 42192 ) GRADE to Dr. Schnemann |
10,960 | 31,262,293 | Conclusions There is a paucity of high- quality economic evaluations in the field of child oral health . | Background Economic evaluations provide policy makers with information to facilitate efficient re source allocation .
To date , the quality and scope of economic evaluations in the field of child oral health has not been evaluated .
Furthermore , whilst the involvement of children in research has been actively encouraged in recent years , the success of this movement in dental health economics has not yet been explored .
This review aim ed to determine the quality and scope of published economic evaluations applied to children ’s oral health and to consider the extent of children ’s involvement . | OBJECTIVE Economic evaluations provide an important basis for allocation of re sources and health services planning . The aim of this study was to evaluate and compare the costs of correcting anterior crossbite with functional shift , using fixed or removable appliances ( FA or RA ) and to relate the costs to the effects , using cost-minimization analysis . DESIGN , SETTING , AND PARTICIPANTS Sixty-two patients with anterior crossbite and functional shift were r and omized in blocks of 10 . Thirty-one patients were r and omized to be treated with brackets and arch wire ( FA ) and 31 with an acrylic plate ( RA ) . Duration of treatment and number and estimated length of appointments and cancellations were registered . Direct costs ( premises , staff salaries , material , and laboratory costs ) and indirect costs ( the accompanying parents ' loss of income while absent from work ) were calculated and evaluated with reference to successful outcome alone , to successful and unsuccessful outcomes and to re-treatment when required . Societal costs were defined as the sum of direct and indirect costs . INTERVENTIONS Treatment with FA or RA . RESULTS There were no significant differences between FA and RA with respect to direct costs for treatment time , but both indirect costs and direct costs for material were significantly lower for FA . The total societal costs were lower for FA than for RA . LIMITATIONS Costs depend on local factors and should not be directly extrapolated to other locations . CONCLUSION The analysis disclosed significant economic benefits for FA over RA . Even when only successful outcomes were assessed , treatment with RA was more expensive . TRIAL REGISTRATION This trial was not registered . PROTOCOL The protocol was not published before trial commencement OBJECTIVES The Access to Baby and Child Dentistry ( ABCD ) Program addresses the needs of families in obtaining dental care . In this study , the program was evaluated in rural Stevens County , Washington . Aims were to assess utilization of dental services , average dental expenditures per child , and oral health status . METHODS Medicaid-enrolled children aged 1 - 4 years were r and omly assigned to the ABCD program ( n=216 ) or to regular benefits ( n=221 ) . An outreach worker contacted each ABCD family and provided an orientation . Dental care utilization and expenditures were calculated from cl aims . A posttest-only design was used to evaluate oral health status . RESULTS An enrollment effect was seen in ABCD , but the difference between groups was not sustained . There was a doubling of utilization between groups for the youngest cohort , while the others showed no differences . In the first year the rate was higher for the entire ABCD group than for the children not in ABCD ( 34.0 % vs 24.7 % ) . Thirty-three percent of ABCD children ( 70/212 ) who had visited the dentist had > 1 appointment compared to 21.5 percent ( 47/219 ) for the children not in ABCD who had visited the dentist . There was no overall difference in expenditures , while expenditures for preventive services were greater for ABCD . ABCD children had fewer teeth with initial caries . The average incremental cost per child per initial lesion prevented was 31.44 dollars . CONCLUSION ABCD most benefited the youngest cohort of children and improved health OBJECTIVE A growing number of studies have investigated the prevalence of Molar Incisor Hypomineralization ( MIH ) around the world . The aim of this study was to systematic ally estimate the pooled prevalence of MIH . METHODS A comprehensive literature research was completed in English and Chinese data bases . R and om effect models were used to calculate the pooled prevalence . To address the heterogeneity , meta-regression , and sensitivity analyzes were conducted . Publication bias was estimated by trim and fill method . RESULTS Seventy eligible studies were included . The pooled prevalence of MIH was 14.2 % globally . In subgroup analysis , South America ( 18.0 % , 95 % CI : 13.8 - 22.2 ) and Spain ( 21.1 % , 95 % CI : 17.7 - 24.6 ) had the highest prevalence . There was no significant difference between males ( 14.3 % , 95 % CI : 12.0 - 16.6 ) and females ( 14.4 % , 95 % CI : 12.8 - 15.9 ) . The prevalence of MIH among children 10 years of age or younger ( 15.1 % , 95 % CI : 12.1 - 18.2 ) was much higher than the prevalence of MIH among older children ( 12.1 % , 95 % CI : 8.0 - 16.3 ) . Sample size explained 15.7 % heterogeneity . CONCLUSION MIH has a high incidence globally , especially among children < 10 years old . It is , therefore , imperative to develop more appropriate dental healthcare strategies to care for these children and to identify the etiology of MIH to prevent it occurring BACKGROUND Dental caries is the most common disease of childhood . The NHS guidelines promote preventative care in dental practice s , particularly for young children . However , the cost-effectiveness of this policy has not been established . OBJECTIVE To measure the effects and costs of a composite fluoride intervention design ed to prevent caries in young children attending dental services . DESIGN The study was a two-arm , parallel-group , r and omised controlled trial , with an allocation ratio of 1 : 1 . R and omisation was by clinical trials unit , using r and omised permuted blocks . Children/families were not blinded ; however , outcome assessment was blinded to group assessment . SETTING The study took place in 22 NHS dental practice s in Northern Irel and , UK . PARTICIPANTS The study participants were children aged 2 - 3 years , who were caries free at baseline . INTERVENTIONS The intervention was composite in nature , comprising a varnish containing 22,600 parts per million ( p.p.m . ) fluoride , a toothbrush and a 50-ml tube of toothpaste containing 1450 p.p.m . fluoride ; plus st and ardised , evidence -based prevention advice provided at 6-monthly intervals over 3 years . The control group received the prevention advice alone . MAIN OUTCOME MEASURES The primary outcome measure was conversion from caries-free to caries-active states . Secondary outcome measures were the number of decayed , missing or filled tooth surfaces in primary dentition ( dmfs ) in caries-active children , the number of episodes of pain , the number of extracted teeth and the costs of care . Adverse reactions ( ARs ) were recorded . RESULTS A total of 1248 children ( 624 r and omised to each group ) were recruited and 1096 ( 549 in the intervention group and 547 in the control group ) were included in the final analyses . A total of 87 % of the intervention children and 85 % of control children attended every 6-month visit ( p = 0.77 ) . In total , 187 ( 34 % ) children in the intervention group converted to caries active , compared with 213 ( 39 % ) in the control group [ odds ratio ( OR ) 0.81 , 95 % confidence interval ( CI ) 0.64 to 1.04 ; p = 0.11 ] . The mean number of tooth surfaces affected by caries was 7.2 in the intervention group , compared with 9.6 in the control group ( p = 0.007 ) . There was no significant difference in the number of episodes of pain between groups ( p = 0.81 ) . However , 164 out of the total of 400 ( 41 % ) children who converted to caries active reported toothache , compared with 62 out of 696 ( 9 % ) caries-free children ( OR 7.1 95 % CI 5.1 to 9.9 ; p < 0.001 ) . There was no statistically significant difference in the number of teeth extracted in caries-active children ( p = 0.95 ) . Ten children in the intervention group had ARs of a minor nature . The average direct dental care cost was £ 155.74 for the intervention group and £ 48.21 for the control group over 3 years ( p < 0.05 ) . The mean cost per carious surface avoided over the 3 years was estimated at £ 251.00 . LIMITATIONS The usual limitations of a trial such as generalisability and underst and ing the underlying reasons for the outcomes apply . There is no mean willingness-to-pay threshold available to enable assessment of value for money . CONCLUSIONS A statistically significant effect could not be demonstrated for the primary outcome . Once caries develop , pain is likely . There was a statistically significant difference in dmfs in caries-active children in favour of the intervention . Although adequately powered , the effect size of the intervention was small and of question able clinical and economic benefit . FUTURE WORK Future work should assess the caries prevention effects of interventions to reduce sugar consumption at the population and individual levels . Interventions design ed to arrest the disease once it is established need to be developed and tested in practice . TRIAL REGISTRATION Current Controlled Trials IS RCT N36180119 and EudraCT 2009 - 010725 - 39 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 20 , No. 71 . See the NIHR Journals Library website for further project information The aim of this study was to assess the cost-effectiveness of an experimental caries-control regimen in a r and omized clinical trial ( RCT ) conducted in Pori , Finl and , in 2001 - 2005 . Children ( n = 497 ) who were 11 - 12 yr of age and had at least one active initial caries lesion at baseline were studied . The children in the experimental group ( n = 250 ) were offered an individually design ed patient-centered regimen for caries control . The children in the control group ( n = 247 ) received st and ard dental care . Furthermore , the whole population was exposed to continuous community-level oral health promotion . Individual costs of treatment procedures and outcomes ( DMFS increment score ) for the follow-up period of 3.4 yr were calculated for each child in both groups . The incremental cost-effectiveness ratio was euro 34.07 per averted DMF surface . The experimental regimen was more effective , and also more costly . However , the total costs decreased year after year , and for the last 2 yr the experimental regimen was less expensive than the st and ard dental care . The experimental regimen would probably have been more cost-effective than st and ard dental care if the follow-up period had been longer , the regimen less comprehensive , and /or if dental nurses had conducted the preventive procedures OBJECTIVE Paediatric dental care under general anaesthesia among preschool children in Western Australia is increasing and costly . This study assessed cost-effectiveness of the atraumatic restorative treatment-based ( ART-based ) approach against the st and ard care ( SC ) approach to managing early childhood caries in a primary care setting based on a 1-year pragmatic r and omized controlled trial . METHODS Cost-effectiveness analysis , from the service provider perspective , was conducted . Outcomes include number of referral to specialists and dental treatments . One-way and probabilistic sensitivity analyses were undertaken to test the robustness of the cost-effectiveness estimates . RESULTS Six children in the ART-based group and 62 children in the SC group ( n = 127 each group ) were referred for paediatric dental specialist care . Children in the ART-based group received more dental services than those allocated to the SC group ( mean = 3.8 , SD 2.0 and mean = 1.8 , SD 1.8 , respectively , Wilcoxon rank-sum test , P < 0.01 ) . Total costs of the ART-based approach and the SC group were $ 137 860 and $ 178 217 , respectively . Based on probabilistic sensitivity analysis , $ 654 was saved per referral to specialist avoided and $ 36 was saved per additional dental treatment . The probability that the ART-based approach is cost-saving was 63 % . Specialist dental treatment fees had a big impact on the cost-effectiveness estimates . CONCLUSION The ART-based approach appears to be a worthwhile intervention because it result ed in fewer referred cases and enabled more treatments to be provided with cost-savings OBJECTIVES A total of 3373 12-year-olds agreed to participate in an intervention study evaluating different caries preventive measures . The study , titled ' Evaluation of caries preventive measures ' , was performed between 1995 and 1999 at 26 dental health clinics throughout Sweden . At the start of the study , the subjects were classified as individuals at high or low risk of developing caries . The high-risk group consisted of 1165 subjects . The children in the high-risk group were r and omly assigned to one of four preventive programs . The programs represent a step-wise increase in fluoride content , contact with dental personnel and cost . The aim of the present cost-effectiveness analysis ( CEA ) study performed from a societal perspective is to compare costs and consequences of caries preventive programs in a caries high-risk population . By ' costs ' is meant both treatment costs and costs contributed by the patient and the patient 's family . Costs contributed by patients and their families consist of out-of-pocket expenses , transportation costs , and time . Conclusions are that it is important to consider the perspective from which a study is carried out . Costs contributed by the patient and the patient 's family have a high impact on total costs for children and younger adolescents but decrease with time as the adolescents get older . The present study shows an incremental cost-effectiveness of 2043 SEK ( 8.54 SEK = 1 US dollar , December 1999 ) per averted decayed enamel and dentine missing and filled surface ( DeMFS ) , of which treatment costs represent 1337 SEK using the unit cost for a nurse . This means a yearly cost of approximately 334 SEK OBJECTIVE To assess the cost effectiveness of a postal toothpaste programme to prevent caries in 5-year-old children in the north west of Engl and . PARTICIPANTS Birth cohorts of children aged 12 months were recruited from high caries risk population s in nine health districts . DESIGN The results of a r and omised controlled trial to measure the effects of a postal toothpaste programme are used and related to the costs of running a similar programme . Children in the trial received free toothpaste on four occasions a year and a toothbrush once a year for four years from age 12 months to 5 years . When aged 5 - 6 years children were examined by trained , calibrated examiners using BASCD st and ards . Those who received toothpaste containing 1450 ppm F were found to have a significantly lower mean dmft than those who had not . The costs that would be incurred by a public dental service running such a postal toothpaste programme are identified , measured and related to the likely health improvement that could be achieved . MAIN OUTCOME MEASURES The cost per tooth saved and the cost per child saved from caries experience and extraction experience . RESULTS The estimated cost per tooth saved from carious attack was pounds sterling 80.83 and the cost per child of preventing caries experience was pounds sterling 424.38 and avoiding any extraction s was pounds sterling 679.01 . Analysis result ed in an overestimation of costs and underestimation of benefits . CONCLUSION The programme achieved a significant caries reduction in children who received the 1450 ppm F toothpaste and the costs are now available to those considering provision of treatment services in areas where children are at high caries risk BACKGROUND Cost-utility analysis using the quality -adjusted life years ( QALY ) as an outcome measure to inform healthcare re source allocation is becoming more common . The Child Health Utility 9D ( CHU9D ) enables the calculation of utility values in children . Children were involved throughout its development to ensure it is child centred . AIM To determine whether the CHU9D is responsive to the changing components of the dmfs+DMFS index score in children receiving dental care over a 1-year period . DESIGN The study sample comprised children aged 6 to 9 years old who were enrolled in a split-mouth , placebo-controlled r and omised controlled trial . All children had a comprehensive clinical examination including radiographs and health-related quality of life ( HRQoL ) was measured using the CHU9D at baseline and 1 year . Descriptive statistics was followed by bivariate analyses before effect sizes were calculated . A negative binomial model was fitted to assess whether the utility score predicted the components of decayed and filled teeth ( combined primary and permanent teeth ) . RESULTS Eighty ( 92 % ) children completed the CHU9D at baseline and follow-up . They presented with a mean baseline d3mfs+D3MFS of 6.7 ( SD = 7.1 ) , which rose to 7.3 ( SD = 7.0 ) at follow-up . The mean CHU9D score improved from 0.88 to 0.90 from baseline to follow-up . No statistically significant relationships were found between caries status and the CHU9D score . CONCLUSION The CHU9D was found to be unresponsive to the changing components of dental caries experience This study presents the results of a cost-effectiveness analysis in a controlled clinical trial on the effectiveness of a modified glass ionomer resin sealant ( Vitremer , 3 M ESPE ) and the application of fluoride varnish ( Duraphat , Colgate ) on occlusal surfaces of first permanent molars in children 6 - 8 years of age ( N = 268 ) , according to caries risk ( high versus low ) . Children were examined semiannually by the same calibrated dentist for 24 months after allocation in six groups : high and low risk controls ( oral health education every three months ) ; high and low risk with varnish ( oral health education every three months + varnish biannually ) ; and high and low risk with sealant ( oral health education every three months + a single application of sealant ) . Economic analysis showed that sealing permanent first molars of high-risk schoolchildren showed a C/E ratio of US$ 119.80 per saved occlusal surface and an incremental C/E ratio of US$ 108.36 per additional saved occlusal surface . The study concluded that sealing permanent first molars of high-risk schoolchildren was the most cost-effective intervention A cost-effectiveness analysis was conducted during a 3-year r and omized controlled clinical trial in a general dental practice in the Netherl and s in which 230 6-year-old children ( ± 3 months ) were assigned to either regular dental care , an increased professional fluoride application ( IPFA ) programme or a non-operative caries treatment and prevention ( NOCTP ) programme . Information on re source use during the 3-year period was documented by the dental nurse at every patient visit , such as treatment time , travel time and travel distance . Caries increment scores ( at D3MFS level ) were used to assess effectiveness . Cost calculations were performed using bottom-up micro-costing . Incremental cost-effectiveness ratios ( ICERs ) were expressed as additional average costs per prevented DMFS . The ICERs compared with regular dental care from a health care system perspective and societal perspective were , respectively , EUR 269 and EUR 1,369 per prevented DMFS in the IPFA programme , and EUR 30 and EUR 100 in the NOCTP programme . The largest investments for the NOCTP group were made in the first year of the study ; they decreased in the second and equalled the costs of control group in third year of the study . From both medical and economic points of view , the NOCTP strategy may be considered the preferred strategy for caries prevention |
10,961 | 26,872,590 | Knees with ACLD showed less peak knee flexion compared with that on contralateral sides during stair ascent , with minimal heterogeneity .
External knee flexion moments were lower for ACLR compared with those in controls and contralateral sides during ascent and descent , whereas these moments were decreased for the ACLD compared with controls only during ascent .
Differences for kinematics and kinetics for the ACL-injured knees indicate long-term compensatory and asymmetric movement patterns while ascending and descending stairs . | OBJECTIVE Biomechanical changes have been reported for patients with anterior cruciate ligament deficiency ( ACLD ) and anterior cruciate ligament ( ACL reconstruction ) ( ACLR ) , likely due to loss of stability and changes in proprioception and neuromotor control .
This review evaluated kinematics and kinetics of ACLD and ACLR knees , compared with those on the contralateral uninjured sides , as well as and those in asymptomatic controls during stair navigation . | Background The effectiveness of anterior cruciate ligament reconstruction for restoring normal knee kinematics is largely unknown , particularly during sports movements generating large , rapidly applied forces . Hypothesis Under dynamic in vivo loading , significant differences in 3-dimensional kinematics exist between anterior cruciate ligament-reconstructed knees and the contralateral , uninjured knees . Study Design Prospect i ve , in vivo laboratory study . Methods Kinematics of anterior cruciate ligament-reconstructed and contralateral ( uninjured ) knees were evaluated for 6 subjects during downhill running 4 to 12 months after anterior cruciate ligament reconstruction , using a 250 frame/s stereoradiographic system . Anatomical reference axes were determined from computed tomography scans . Kinematic differences between the uninjured and reconstructed limbs were evaluated with a repeated- measures analysis of variance . Results Anterior tibial translation was similar for the reconstructed and uninjured limbs . However , reconstructed knees were more externally rotated on average by 3.8 ± 2.3 ° across all subjects and time points ( P = .0011 ) . Reconstructed knees were also more adducted , by an average of 2.8 ± 1.6 ° ( P = .0091 ) . Although differences were small , they were consistent in all subjects . Conclusions Anterior cruciate ligament reconstruction failed to restore normal rotational knee kinematics during dynamic loading . Clinical Relevance Although further study is required , these abnormal motions may contribute to long-term joint degeneration associated with anterior cruciate ligament injury/reconstruction STUDY DESIGN Prospect i ve descriptive study . OBJECTIVE To determine the extent of bone mineral density ( BMD ) interlimb differences at several hip locations in the involved versus noninvolved lower extremity following anterior cruciate ligament ( ACL ) surgery . BACKGROUND Disuse following ACL reconstruction can be extensive . This disuse not only affects the soft tissue , but may also affect the skeletal structure . The extent of this disuse specific to the proximal femur has not been previously determined . METHODS AND MEASURES BMD was assessed in 15 subjects , 17 to 51 years old , who were between 6 and 32 months post-ACL reconstruction surgery . Bone mineral content ( BMC ) and BMD of the femoral neck , trochanteric region , intertrochanteric region , and entire hip were measured as a primary emphasis of this study . BMD and BMC of the entire lower extremities were also measured bilaterally . RESULTS BMD was significantly less in the involved lower extremity compared to noninvolved lower extremity at several hip sites : 6.6 % less ( P<.001 ) for the trochanteric region , 4.0 % less ( P<.001 ) for the entire hip , and 3.4 % less ( P = .004 ) for the intertrochanteric region . No significant differences were noted comparing the entire lower extremities for either BMD ( 0.9 % , P = .48 ) or BMC ( 3.7 % , P= .09 ) . CONCLUSION BMD differences at the hip are significant in patient 's postoperative ACL reconstruction , especially in the trochanteric region Anterior cruciate ligament ( ACL ) injury can result in failure to return to pre-injury activity levels and future osteoarthritis predisposition . Single leg hop is used in late rehabilitation to evaluate recovery and inform treatment but biomechanical underst and ing of this activity is insufficient . This study investigated single leg hop for distance aim ing to evaluate if ACL patients had recovered : ( 1 ) l and ing strategies and ( 2 ) medio-lateral knee control . We hypothesized that patients with reconstructive surgery ( ACLR ) would have more similar l and ing strategies and knee control to healthy controls than patients treated conservatively ( ACLD ) . 16 ACLD and 23 ACLR subjects were compared to 20 healthy controls ( CONT ) . Kinematic and ground reaction force data were collected while subjects hopped their maximum distance . The main output parameters were hop distance , peak knee flexor angles and extensor moments and Fluency ( a measure introduced to represent medio-lateral knee control ) . Statistical differences between ACL and control groups were analyzed using a general linear model univariate analysis , with COM velocity prior to l and ing as covariate . Hop distance was the smallest for ACLD and largest for CONT ( p<0.001 ; ACLD 57.1±14.1 ; ACLR 75.1±17.8 ; CONT 77.7±14.07 % height ) . ACLR used a similar kinematic strategy to CONT , but had a reduced peak knee extensor moment ( p<0.001 ; ACLD 0.32±0.14 ; ACLR 0.31±0.16 ; CONT 0.42±0.13 BW.height ) . Fluency was reduced in both ACLD and ACLR ( p=0.006 ; ACLD 0.13±0.34 ; ACLR 0.14±0.34 ; CONT 0.17±0.41 s ) . Clinical practice uses hopping distance to evaluate ACL patients ' recovery . This study demonstrated that aspects such as movement strategies and knee control need to be evaluated Thirty-seven patients who had undergone anterior cruciate ligament reconstruction were tested in a gait analysis laboratory at 2 and 6 weeks after surgery . Between test sessions , patients were r and omly assigned to a course of either closed or open kinetic chain resistance exercises ( 3 sessions per week for 4 weeks ) . Gait analysis consisted of bilateral calculations of knee joint angle , moment , and power during level walking , stair ascent , and stair descent . An analysis of variance on the effects of training group and test session indicated that the only variable to be significantly affected by the type of exercise program was the amount of knee flexion at the beginning of step-up ( P<0.05 ) . All other measures of knee angle , moment , and power ( 16 total variables ) showed no significant difference between the exercise groups . All variables measured on the injured side showed significant improvement from test 1 to test 2 ( P<0.05 ) , but the injured leg remained functionally deficient when compared with the uninjured leg . These data suggest that there are no clinical ly significant differences in the functional improvement result ing from the choice of open or closed kinetic chain exercises in the early period after this surgery 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 OBJECTIVE The adduction moment at the knee during gait is the primary determinant of medial-to-lateral load distribution . If the adduction moment contributes to progression of osteoarthritis ( OA ) , then patients with advanced medial tibiofemoral OA should have higher adduction moments . The present study was undertaken to investigate the hypothesis that the adduction moment normalized for weight and height is associated with medial tibiofemoral OA disease severity after controlling for age , sex , and pain level , and to examine the correlation of serum hyaluronan ( HA ) level with disease severity and with the adduction moment in a subset of patients . METHODS Fifty-four patients with medial tibiofemoral OA underwent gait analysis and radiographic evaluation . Disease severity was assessed using the Kellgren-Lawrence ( K-L ) grade and medial joint space width . In a subset of 23 patients with available sera , HA was quantified by s and wich enzyme-linked immunosorbent assay . Pearson correlations , a r and om effects model , and multivariate regression models were used . RESULTS The adduction moment correlated with the K-L grade in the left and right knees ( r = 0.68 and r = 0.60 , respectively ) , and with joint space width in the left and right knees ( r = -0.45 and r = -0.47 , respectively ) . The relationship persisted after controlling for age , sex , and severity of pain . The partial correlation between K-L grade and adduction moment was 0.71 in the left knees and 0.61 in the right knees . For every 1.0-unit increase in adduction moment , there was a 0.63-mm decrease in joint space width . In the subset of patients in whom serum HA levels were measured , HA levels correlated with medial joint space width ( r = -0.55 ) , but not with the adduction moment . CONCLUSION There is a significant relationship between the adduction moment and OA disease severity . Serum HA levels correlate with joint space width but not with the adduction moment . Longitudinal studies will be necessary to determine the contribution of the adduction moment , and its contribution in conjunction with metabolic markers , to progression of medial tibiofemoral OA OBJECTIVE To establish the gait adaptations of patients with anterior cruciate ligament deficiency during stair ascent . DESIGN Joint kinematics and kinetics during stair climbing were measured in both knees of normal subjects and unilateral anterior cruciate ligament deficient patients . BACKGROUND As there is limited research pertaining to activities other than level walking , the purpose of the current study was to eluci date the gait of patients with anterior cruciate ligament deficiency during stair climbing to determine the effects of the deficiency on knee joint motion and moments as compared with normal knee function . METHODS A motion analysis system was used to measure and calculate kinematic and kinetic data for six normal subjects and nine patients with unilateral anterior cruciate ligament deficiency during stair ascent on a specially constructed staircase . Left and right leg data were analysed to reveal between-limb differences for each subject . RESULTS Patients with anterior cruciate ligament deficiency displayed a significant ( P < 0.05 ) reduction of up to 50 % in peak knee flexion moments in their involved knee . In the present study where a step height of 15.5 cm was used , peak flexion moments in all subjects ' limbs occurred at knee flexion angles of about 40 degrees during single limb support . CONCLUSION The current study showed that most patients with an anterior cruciate deficient knee adapted their gait during stair ascent . RELEVANCE As stair climbing is a common activity , its effect on gait is relevant to better underst and appropriate treatment and management strategies of patients with anterior cruciate ligament deficient knees Background Athletes who return to sport participation after anterior cruciate ligament reconstruction ( ACLR ) have a higher risk of a second anterior cruciate ligament injury ( either reinjury or contralateral injury ) compared with non — anterior cruciate ligament— injured athletes . Hypotheses Prospect i ve measures of neuromuscular control and postural stability after ACLR will predict relative increased risk for a second anterior cruciate ligament injury . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-six athletes underwent a prospect i ve biomechanical screening after ACLR using 3-dimensional motion analysis during a drop vertical jump maneuver and postural stability assessment before return to pivoting and cutting sports . After the initial test session , each subject was followed for 12 months for occurrence of a second anterior cruciate ligament injury . Lower extremity joint kinematics , kinetics , and postural stability were assessed and analyzed . Analysis of variance and logistic regression were used to identify predictors of a second anterior cruciate ligament injury . Results Thirteen athletes suffered a subsequent second anterior cruciate ligament injury . Transverse plane hip kinetics and frontal plane knee kinematics during l and ing , sagittal plane knee moments at l and ing , and deficits in postural stability predicted a second injury in this population ( C statistic = 0.94 ) with excellent sensitivity ( 0.92 ) and specificity ( 0.88 ) . Specific predictive parameters included an increase in total frontal plane ( valgus ) movement , greater asymmetry in internal knee extensor moment at initial contact , and a deficit in single-leg postural stability of the involved limb , as measured by the Biodex stability system . Hip rotation moment independently predicted second anterior cruciate ligament injury ( C = 0.81 ) with high sensitivity ( 0.77 ) and specificity ( 0.81 ) . Conclusion Altered neuromuscular control of the hip and knee during a dynamic l and ing task and postural stability deficits after ACLR are predictors of a second anterior cruciate ligament injury after an athlete is released to return to sport BACKGROUND Currently there is a limited underst and ing of the factors influencing range of motion by comparing patellar resurfacing vs non-resurfacing in total knee arthroplasty during activities of daily living . A recent meta- analysis of patellar replacement confirms better outcome with patella resurfacing ; however , the result can be influenced by many other factors , such as : component design , surgeon experience , and technical aspects of the surgery . This study compares the biomechanics of the knee in patients after total knee arthroplasty with and without patellar resurfacing during stair climbing . METHODS Forty-seven patients with total knee arthroplasty were assessed at the mean follow-up of 24 months . In all of them a posterior stabilised fixed bearing prosthesis ( Optetrak PS , Exactech ) was implanted . Twenty-six patients were treated without patellar resurfacing and 21 with patellar resurfacing . Clinical evaluations were performed using the International Knee Society and the Hospital for Special Surgery scores . Ten patients with patellar resurfacing and 10 patients without patellar resurfacing were also studied with motion analysis during stair climbing ; 10 healthy subjects were studied for statistical comparison . FINDINGS Clinical passive knee flexion , International Knee Society Function and Hospital for Special Surgery scores were significantly higher in the patellar resurfacing group . During stair climbing , active knee joint range of motion during the stance phase was greater in patients with patellar resurfacing . The maximum adduction moment was significantly higher in the group without patellar resurfacing . INTERPRETATION Patients with patellar resurfacing demonstrated better clinical scores , and kinematic and kinetic data while ascending stairs |
10,962 | 16,456,206 | There is relatively weak evidence to indicate that pharmacist-led medication review s are effective in reducing hospital admissions .
There is currently no evidence for the effectiveness of other interventions which aim at reducing admissions or preventable drug related morbidity . | OBJECTIVE To identify and evaluate studies of interventions in primary care aim ed at reducing medication related adverse events that result in morbidity , hospital admission , and /or mortality . | OBJECTIVE To assess the effectiveness of psychotropic medication withdrawal and a home-based exercise program in reducing falls in older people . DESIGN A r and omized controlled trial with a two by two factorial design . SETTING Seventeen general practice s in Dunedin , New Zeal and . PARTICIPANTS Women and men aged 65 years registered with a general practitioner and currently taking psychotropic medication ( n = 93 ) . INTERVENTIONS Two interventions : ( 1 ) gradual withdrawal of psychotropic medication versus continuing to take psychotropic medication ( double blind ) and ( 2 ) a home-based exercise program versus no exercise program ( single blind ) . MEASUREMENTS Number of falls and falls risk during 44 weeks of follow-up . Analysis was on an intent to treat basis . RESULTS After 44 weeks , the relative hazard for falls in the medication withdrawal group compared with the group taking their original medication was .34 ( 95 % CI , .16-.74 ) . The risk of falling for the exercise program group compared with those not receiving the exercise program was not significantly reduced . CONCLUSIONS Withdrawal of psychotropic medication significantly reduced the risk of falling , but permanent withdrawal is very difficult to achieve OBJECTIVE To determine whether a new model of primary care , Chronic Care Clinics , can improve outcomes of common geriatric syndromes ( urinary incontinence , falls , depressive symptoms , high risk medications , functional impairment ) in frail older adults . DESIGN R and omized controlled trial with 24 months of follow-up . Physician practice s were r and omized either to the Chronic Care Clinics intervention or to usual care . SETTING Nine primary care physician practice s that comprise an ambulatory clinic in a large staff-model HMO in western Washington State . PARTICIPANTS Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline . INTERVENTION Intervention practice s ( 5 physicians , 96 patients ) held half-day Chronic Care Clinics every 3 to 4 months . These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management ; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications ; and a patient self-management/support group . Control practice s ( 4 physicians , 73 patients ) received usual care . MEASUREMENTS Changes in self-reported urinary incontinence , frequency of falls , depressive symptoms , physical function , and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences , covariates , and practice -level variation . Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed . RESULTS After 24 months , no significant improvements in frequency of incontinence , proportion with falls , depression scores , physical function scores , or prescriptions for high risk medications were demonstrated . Costs of medical care including frequency of hospitalization , hospital days , emergency and ambulatory visits , and total costs of care were not significantly different between intervention and control groups . A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients ( 40.0 % vs 25.3 % , P = .10 ) . CONCLUSIONS Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics , improved outcomes for selected geriatric syndromes were not demonstrated . These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system BACKGROUND Noncompliance is a major factor in the morbidity and unnecessary hospital readmissions for patients with heart failure . Several studies have aim ed to reduce rehospitalizations in heart failure patients through a comprehensive , multidisciplinary approach . Medication compliance was rarely measured in these studies or , when it was measured , the method employed was seldom valid . We aim ed at determining the effect of a pharmacist-led intervention on medication compliance in patients with heart failure . METHODS We conducted a r and omized controlled trial into the effect of a pharmacist-led intervention on medication compliance in patients with heart failure ( predominantly New York Heart Association [ NYHA ] II and III ) treated with loop diuretics , presenting to a cardiology outpatient clinic or admitted to hospitals in The Netherl and s. Patients in the intervention group received monthly consultations from their community pharmacist during a 6-month period . Patients in the control group received usual care . Primary endpoint was medication compliance , assessed with a medication event monitoring system , an electronic pill bottle that registers time of opening . Secondary endpoints were the number of rehospitalizations , death , and quality of life . RESULTS A total of 152 patients were r and omized : 74 patients to the intervention arm and 78 patients to the usual care arm . Over the 6-month study period , patients in the intervention group had 140/7656 days without use of loop diuretics compared with 337/6196 days in the usual care group ( relative risk 0.33 [ confidence interval ( CI ) 95 % 0.24 - 0.38 ] ) . Two consecutive days of nondosing occurred on 18/7656 days in the intervention group compared with 46/6196 days in the usual care group ( relative risk 0.32 [ CI 95 % 0.19 - 0.55 ] ) . There were no significant differences in rehospitalizations , mortality , or disease-specific quality of life between groups . CONCLUSIONS A pharmacy-led intervention can improve medication compliance in patients with moderate to severe heart failure , even in those with relatively high compliance . Future interventions should also focus at less compliant patients Abstract Objective : To assess the effect of a multifaceted intervention directed at general practitioners on six year mortality , morbidity , and risk factors of patients with newly diagnosed type 2 diabetes . Design : Pragmatic , open , controlled trial with r and omisation of practice s to structured personal care or routine care ; analysis after 6 years . Setting : 311 Danish practice s with 474 general practitioners ( 243 in intervention group and 231 in comparison group ) . Participants : 874 ( 90.1 % ) of 970 patients aged ≥40 years who had diabetes diagnosed in 1989 - 91 and survived until six year follow up . Intervention : Regular follow up and individualised goal setting supported by prompting of doctors , clinical guidelines , feedback , and continuing medical education . Main outcome measures : Predefined clinical non-fatal outcomes , overall mortality , risk factors , and weight . Results : Predefined non-fatal outcomes and mortality were the same in both groups . The following risk factor levels were lower for intervention patients than for comparison patients ( median values ) : fasting plasma glucose concentration ( 7.9 v 8.7 mmol/l , P=0.0007 ) , glycated haemoglobin ( 8.5 % v 9.0 % , P<0.0001 ; reference range 5.4 - 7.4 % ) , systolic blood pressure ( 145 v 150 mm Hg , P=0.0004 ) , and cholesterol concentration ( 6.0 v 6.1 mmol/l , P=0.029 , adjusted for baseline concentration ) . Both groups had lost weight since diagnosis ( 2.6 v 2.0 kg ) . Metformin was the only drug used more frequently in the intervention group ( 24 % ( 110/459 ) v 15 % (61/415)).Intervention doctors arranged more follow up consultations , referred fewer patients to diabetes clinics , and set more optimistic goals . Conclusions : In primary care , individualised goals with educational and surveillance support may for at least six years bring risk factors of patients with type 2 diabetes to a level that has been shown to reduce diabetic complications but without weight gain . What is already known on this topic Evidence is increasing that control of hyperglycaemia , hypertension , and dyslipidaemia may postpone the development of diabetic complications in patients with type 2 diabetes Maintaining good control over a long period can be difficult What this study adds Structured individualised personal care with educational and surveillance support for general practitioners reduced levels of risk factors in type 2 diabetic patients after six years Risk factors were reduced to a level that has been shown to have a beneficial effect on diabetic complications Participants also showed modest weight Abstract Objective : To determine whether a pharmacist can effectively review repeat prescriptions through consultations with elderly patients in general practice . Design : R and omised controlled trial of clinical medication review by a pharmacist against normal general practice review . Setting : Four general practice s. Participants : 1188 patients aged 65 or over who were receiving at least one repeat prescription and living in the community . Intervention : Patients were invited to a consultation at which the pharmacist review ed their medical conditions and current treatment . Main outcome measures : Number of changes to repeat prescriptions over one year , drug costs , and use of healthcare services . Results : 590 ( 97 % ) patients in the intervention group were review ed compared with 233 ( 44 % ) in the control group . Patients seen by the pharmacist were more likely to have changes made to their repeat prescriptions ( mean number of changes per patient 2.2 v 1.9 ; difference=0.31 , 95 % confidence interval 0.06 to 0.57 ; P=0.02 ) . Monthly drug costs rose in both groups over the year , but the rise was less in the intervention group ( mean difference £ 4.72 per 28 days , −£7.04 to -£2.41 ) ; equivalent to £ 61 per patient a year . Intervention patients had a smaller rise in the number of drugs prescribed ( 0.2 v 0.4 ; mean difference −0.2 , −0.4 to −0.1 ) . There was no evidence that review of treatment by the pharmacist affected practice consultation rates , outpatient consultations , hospital admissions , or death rate . Conclusions : A clinical pharmacist can conduct effective consultations with elderly patients in general practice to review their drugs . Such review results in significant changes in patients ' drugs and saves more than the cost of the intervention without affecting the workload of general practitioners . What is already known on this topic Review of patients on long term drug treatment is important but is done inadequately Evidence from the United States shows that pharmacists can improve patient care by review ing drug treatment What this study adds Consultations with a clinical pharmacist are an effective method of review ing the drug treatment of older patients Review by a pharmacist results in more drug changes and lower prescribing costs than normal care plus a much higher review rate Use of healthcare services by patients is not Twenty-seven independent community pharmacies that were preferred providers for a health maintenance organization ( HMO ) were enrolled in a study to determine the effect of increased intervention activities on the cost of a drug benefit in a managed care environment . Pharmacists from nine pharmacies were trained to initiate changes in medication prescriptions to contain costs , to enhance communication with patients and prescribers , and to intervene in drug-related problems . Their intervention activities during the nine-month study period were compared with activities of nine pharmacies assigned to a control group and nine pharmacies assigned to a comparison group . Patients who visited the intervention pharmacies had a 6.5 % lower prescription mean ingredient cost ; a 6.0 % higher generic substitution rate ; an 8.3 % lower average patient drug cost per month ; and no difference in the days supply , the average number of prescriptions per patient , or the aggregate hospital admission rate . The pharmacists in the intervention group spent more time with patients before preparing prescriptions ( 2.4-fold increase ) ; initiated more requests for prescribers to change prescriptions ( 2.5-fold increase ) ; intervened more often to reduce the cost of drug therapy ( 3.7-fold increase ) ; and suggested medication changes more often for better quality of care ( 1.9-fold increase ) . In this study , community pharmacists altered their practice procedures and setting s to foster communication with patients and prescribers . Also , the prospect i ve drug regimen review changed prescribing patterns : physicians permitted increased use of generic medications , which reduced monthly prescription expenditures Abstract Objective : To evaluate whether a programme of multifactorial home visits reduces falls and impairments in mobility in elderly people living in the community . Design : R and omised controlled trial with 18 months of follow up . Setting : Six general practice s in Hoensbroek , the Netherl and s. Participants : 316 people aged 70 and over living in the community , with moderate impairments in mobility or a history of recent falls . Intervention : Five home visits by a community nurse over a period of one year . Visits consisted of screening for medical , environmental , and behavioural factors causing falls and impairments in mobility , followed by specific advice , referrals , and other actions aim ed at dealing with the observed hazards . Main outcome measures : Falls and impairments in mobility . Results : No differences were found in falls and mobility outcomes between the intervention and usual care groups . Conclusion : Multifactorial home visits had no effects on falls and impairments in mobility in elderly people at risk who were living in the community . Because falls and impairments in mobility remain a serious problem among elderly people , alternative strategies should be developed and evaluated BACKGROUND regular medication review has been recommended for those over 75 and those on multiple drug therapy . Pharmacists are a potential source of assistance in review ing medication . Evidence of the benefits of this process is needed . OBJECTIVE to study the effect of medication review led by a pharmacist on resolution of pharmaceutical care issues , medicine costs , use of health and social services and health-related quality of life . DESIGN r and omized , controlled trial . SETTING general medical practice s in the Grampian region of Scotl and . SUBJECTS patients aged at least 65 years , with at least two chronic disease states who were taking at least four prescribed medicines regularly . METHODS pharmacists review ed the drug therapy of 332 patients , using information obtained from the practice computer , medical records and patient interviews . In 168 patients , a pharmaceutical care plan was then drawn up and implemented . The 164 control patients continued to receive normal care . All outcome measures were assessed at baseline and after 3 months . RESULTS all patients had at least two pharmaceutical care issues at baseline . Half of these were identified from the prescription record , the rest from notes and patient interview . Of all the issues , 21 % were resolved by information found in notes and 8.5 % by patient interview . General practitioners agreed with 96 % of all care issues documented on the care plans in the intervention group . At the time of follow-up , 70 % of the remaining care issues had been resolved in the intervention group , while only 14 % had been resolved in the control group . There were no changes in medicine costs or health-related quality of life in either group . There were small increases in contacts with health-care professionals and slightly fewer hospital admissions among the intervention group than the control group . CONCLUSIONS pharmacist-led medication review has the capacity to identify and resolve pharmaceutical care issues and may have some impact on the use of other health services BACKGROUND Traditional systems of managing repeat prescribing have been criticised for their lack of clinical and administrative controls . AIM To compare a community pharmacist-managed repeat prescribing system with established methods of managing repeat prescribing . METHOD A r and omised controlled intervention study ( 19 general medical practice s , 3074 patients , 62 community pharmacists ) . Patients on repeat medication were given sufficient three-monthly scripts , endorsed for monthly dispensing , to last until their next clinical review consultation with their general practitioner ( GP ) . The scripts were stored by a pharmacist of the patient 's choice . Each monthly dispensing was authorised by the pharmacist , using a st and ard protocol . The cost of the drugs prescribed and dispensed was calculated . Data on patient outcomes were obtained from pharmacist-generated patient records and GP notes . RESULTS A total of 12.4 % of patients had compliance problems , side-effects , adverse drug reactions , or drug interactions identified by the pharmacist . There were significantly more problems identified in total in the intervention group . The total number of consultations , deaths , and non-elective hospital admissions was the same in both groups . Sixty-six per cent of the study patients did not require their full quota of prescribed drugs , representing 18 % of the total prescribed costs ( estimated annual drug cost avoidance of 43 Pounds per patient ) . CONCLUSION This system of managing repeat prescribing has been demonstrated to be logistically feasible , to identify clinical problems , and to make savings in the drugs bill 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 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 The impacts of three alternative models of pharmacist consultation on the use and cost of health care services were studied . Two studies were conducted concurrently in an HMO over two years . In one , 6000 patients were r and omly assigned to one of three consultation models ; in the other , the three models were implemented in six geographic regions of California ( 4600 patients ) . The models were ( 1 ) consultation about new or changed prescriptions as m and ated by state law ( state model ) , ( 2 ) consultation focused on selected high-risk ambulatory care patients ( Kaiser Permanente [ KP ] model ) , and ( 3 ) a control model . The patients were surveyed three times about their health status and satisfaction , and computerized data on health care use and cost were collected . The effect of the consultation models on the use and cost of health care services was examined across five risk groups that were based on drug-use profiles . An additional 37,750 patients ( 10 % of the patients residing in the areawide study sites ) were included in a supplemental analysis of the use and cost of health care services . There was no indication in the r and om-assignment study that pharmacist consultations affected either drug costs or the cost of office visits . Similar results were found in the areawide study , with the exception that the KP model was associated with lower drug costs than the control model . In the 10 % sample , the KP model appeared to be associated with lower office visit costs but higher drug costs . Both models were associated with a lower likelihood of a hospital admission and with lower total health care costs for some high-risk patients compared with the control model . Counseling patients about their medications may be unlikely to reduce medication costs or the cost of office visits but may reduce the likelihood of hospital admissions and the overall costs of health care services ; a combination of counseling patients at high risk for drug-related problems and counseling all patients about any new or changed prescription should be considered Clinical pharmacists , under the supervision of a family practitioner physician , assumed responsibility for drug management of geriatric patients in a Los Angeles skilled nursing facility . In a quasi-experimental , pretest-post-test control group design , outcome criteria were measured . Compared with the control group which received traditional patient care , the prescribing clinical pharmacists ' group had a significantly lower number of deaths ( P = 0.05 ) , a significantly higher number of patients being discharged to lower levels of care ( P = 0.03 ) , and a significantly lower average number of drugs per patient ( P = 0.04 ) . The lower number of patients hospitalized approached significance ( P = 0.06 ) in the prescribing clinical pharmacists ' group . The practice of having clinical pharmacists prescribe drug therapy and render general care , under the supervision of a physician , has the potential for saving the health care system approximately $ 70,000 per year per 100 skilled nursing facility beds Community pharmacists are in a position to assume increased responsibility for preventing and resolving drug-related problems in ambulatory patients . Such an exp and ed role is m and ated under provisions of the Omnibus Budget Reconciliation Act of 1990 . The need for pharmacist oversight of drug therapy may be most acute in elderly patients . This study reports on a program to teach community pharmacists a process of assessing drug therapy of elderly patients and intervening to correct problems . Community pharmacists ( N = 102 ) were assigned to treatment and control conditions . Both groups targeted patients meeting criteria and enrolled them into the study . Treatment group pharmacists , who participated in a training program , also assessed the medication use of enrolled patients to identify and resolve medication-related problems . Patients ( N = 762 ) were telephoned by research ers 1 month after enrollment for an interview . Comparisons between treatment and control group patients were made on reports of pharmacist activities , knowledge of regimens , compliance , and potential drug therapy problems , such as interactions and side effects . Treatment patients were more likely to report that pharmacists provided information and assessed for problems than were control patients . These differences were maintained on 3-month follow-up question naires . No differences were found on the odds that patients indicated misunderst and ing of regimens , noncompliance , or potential therapeutic problems The Diabetes Control and Complications Trial ( DCCT ) and the Kumamoto study [ 1 , 2 ] showed that near-normal glycemic control reduces the development and progression of microvascular and neuropathic complications by approximately 50 % in type 1 and type 2 diabetes mellitus . Additional analyses [ 3 - 5 ] indicate that therapy to achieve near normalization of blood glucose levels is cost-effective compared with other treatments . Thus , the American Diabetes Association has recommended that all persons with diabetes attempt to achieve near normalization of blood glucose levels [ 6 ] . This recommendation is not routinely followed in medical practice . In a 1989 national survey of physician practice behaviors in the United States , 64 % of physicians agreed that achieving target HbA1c values is very important but only 18 % reported that they ordered HbA1c tests every 2 to 3 months for patients with type 1 diabetes [ 7 ] . Although 98 % agreed that patient education improves glucose control , only 55 % reported that they routinely used a dietitian or a diabetes educator in patient care . Studies indicate that bringing clinical practice into line with scientific knowledge can be difficult . Methods used to achieve diabetes control in clinical trials are re source intensive . The American Diabetes Association currently recommends that patients with diabetes see their primary care physicians two to four times per year . Data from the National Health Interview Survey , a nationally representative survey [ 8 ] , indicate that most patients with diabetes are seen by nonspecialists and that 69 % of physician visits last less than 15 minutes . Algorithms for diabetes care exist but may be complex and difficult for physicians to follow , given patient load , diversity of patients seen , lack of information systems , and time constraints . Simple , low-cost methods of translating guidelines into clinical care are required . One solution may be to make greater use of personnel other than physicians . Nurse case management was an integral part of intensive therapy in the DCCT and has proven to be effective in reducing smoking and cholesterol levels after acute myocardial infa rct ion [ 3 , 9 ] . A nonr and omized study [ 10 ] of more than 700 patients with diabetes in a health maintenance organization suggests that nurse case management may be effective in improving metabolic control . Other studies [ 11 , 12 ] show a strong association between algorithm-directed nurse interventions and improved glycemic control . To our knowledge , no r and omized , controlled clinical trial of nurse case management in diabetes has yet been published . In a 12-month r and omized , controlled trial , we compared a nurse case management model of diabetes care with usual diabetes management in a primary care setting . Methods Patients Our study was approved by the institutional review board of the Prudential Center for Health Care Research , and all patients gave written informed consent . Participants were recruited from two of the largest clinics within the Jacksonville Health Care Group , which is the largest provider of primary care services for the Prudential HealthCare HMO plan of Jacksonville , Florida . The Jacksonville Health Care Group is a group of 43 primary care physicians who provide care in eight clinics to more than 75 000 Prudential HealthCare plan members . Potential study participants were identified through a data base used to support quality -improvement activities . Prudential HealthCare HMO members who had diabetes were included in the data base if they had visited a physician for diabetes ( International Classification of Diseases , 9th Revision , codes 250.0 to 250.9 ) , had had a hospital cl aim processed for diabetes , had been seen by the utilization management nurse , or had been referred to an ophthalmologist for a diabetic retinal examination . This data base is up date d regularly . A list with each member 's name , address , telephone number , medical record number , member identification number , age , sex , physician , and clinic was generated by merging the data from the data base with enrollment information . In addition , a list of members who may have had diabetes was created by using pharmacy data . Adult members with diabetes who were potential study participants each received a recruitment call and were invited to schedule an appointment with a research assistant to discuss participation in the study . We made a total of 14 calls at different times and on different days before coding a member as unavailable . After consent was given and the eligibility assessment was completed , baseline information was obtained and an HbA1c test was ordered if the result of one given within the previous 60 days was not available . Patients were ineligible for the study if they had a recent HbA1c value less than 7.0 % ; had uncontrolled hypertension ( blood pressure > 180/110 mm Hg ) ; had unstable angina ( class 4 ) ; had had a myocardial infa rct ion in the past 3 months ; had had two or more episodes of seizures ; had alcoholism or drug abuse documented in the chart ; had late-stage complications of diabetes or other chronic conditions , such as severe immunodeficiency or cirrhosis ; were pregnant or were planning to become pregnant in the next 12 months ; or were unable to perform self-management . Patients were r and omly assigned in blocks to either the nurse case management ( intervention ) group or the usual care group . R and omization was based on a 1:1 allocation ratio and a block size of three . Each block contained six patients , three in each study group . This r and omization scheme ensured that the desired allocation ratio-one intervention patient to one usual care patient-was maintained after sequential enrollment of every sixth patient . Outcome Measures Change in HbA1c value was the primary outcome measure . Decreased HbA1c values correlate directly with reduced risk for diabetes-related microvascular and neuropathic complications in type 1 and type 2 diabetes [ 1 , 3 ] . We also assessed health-related quality of life by using four generic questions developed by the Centers for Disease Control and Prevention for the Behavioral Risk Factor Surveillance System ( BRFSS ) [ 13 , 14 ] . These questions evaluate key conceptual domains of health-related quality of life : 1 ) patient-perceived general health status , 2 ) patient-perceived physical dysfunction during the previous 30 days , 3 ) patient-perceived mental dysfunction during the previous 30 days , and 4 ) patient-perceived functional incapacity during the previous 30 days for either mental or physical reasons . The BRFSS quality -of-life measures have been vali date d in a national sample of adults in the United States [ 15 ] . Patient-perceived health was found to be a good proxy indicator for chronic disease conditions . The other three domains further characterize general health functioning and quality of life [ 15 ] . In this analysis , we report findings related to the patient-perceived general health status domain . Intervention and Follow-up The nurse case manager was a registered nurse and a certified diabetes educator . She was trained to follow a set of detailed management algorithms under the direction of a board-certified family medicine physician and an endocrinologist who were responsible for all diabetes management decisions for patients in the intervention group but were not primary care providers for these patients . The algorithms were specific for type of diabetes and were developed by a multidisciplinary team on which endocrinology , family medicine , nursing , pharmacy , health services research , and epidemiology were represented . The algorithms progressively moved a patient toward improvement of glycemic control through adjustments in medication , meal planning , and reinforcement of exercise ( Figure 1 ) . Figure 1 . Algorithm for management of type 2 diabetes mellitus . Patients assigned to receive nurse case management met with the nurse for an initial assessment , were instructed about a blood glucose monitoring schedule , and returned for a follow-up visit 2 weeks later . The initial visit with the nurse averaged 45 minutes . At the 2-week follow-up visit , the nurse review ed the patient 's blood glucose log ; explained the algorithm step to which the patient had been assigned ; and used this information as the baseline for subsequent medication adjustments , meal planning , and exercise reinforcement . Patients receiving nurse case management were also referred to a 5-week , 12-hour diabetes education program that included individual counseling by a dietitian , individual counseling by an exercise therapist , and group diabetes education classes . Subsequent in-person follow-up visits occurred quarterly . Patients in the nurse case management group who were taking insulin received weekly follow-up telephone calls . After the nurse review ed the blood glucose log and discussed glucose values with the patient , medication regimens were adjusted as needed and meal planning and exercise were reinforced . Patients treated with oral agents or diet and exercise received follow-up telephone calls every 2 weeks . The nurse case manager met at least biweekly with the family medicine physician and the endocrinologist to review patient progress , medication adjustments , and other issues related to diabetes care . All medication adjustments or changes were communicated to the patients ' regular primary care physicians . Patients assigned to receive usual care were given blood glucose meters and strips , were encouraged to discuss enrollment in the diabetes education class with their physicians if they had not done so in the past year , and continued to receive diabetes care and follow-up from their primary care physicians . The 5-week diabetes education program is a st and ard , free-of-charge benefit for all HMO members with diabetes . All Jacksonville Health Care Group primary care physicians participate in an annual diabetes care seminar and undergo regular peer review of their adherence to published diabetes care st and ards . Tests to STUDY OBJECTIVE To determine if clinical pharmacists could affect economic re source use and humanistic outcomes in an ambulatory , high-risk population . DESIGN Prospect i ve , r and omized , controlled study . SETTING Nine Veterans Affairs medical centers . PATIENTS Patients who were at high risk for medication-related problems . INTERVENTION Patients were r and omized to usual medical care with input from a clinical pharmacist ( intervention group ) or just usual medical care ( control group ) . MEASUREMENTS AND MAIN RESULTS Of 1,054 patients enrolled , 523 were r and omized to the intervention group and 531 to the control group . The number of clinic visits increased in the intervention group ( p=0.003 ) , but there was no difference in clinic costs . Mean increases in total health care costs were $ 1,020 for the intervention group and $ 1,313 for the control group ( p=0.06 ) . CONCLUSION Including the cost of pharmacist interventions , overall health care expenditures were similar for patients r and omized to see a clinical pharmacist versus usual medical care BACKGROUND Older people in nursing and residential homes often have complex disabilities and behavioural disturbances . Recent publicity has highlighted the dangers of medication in this group , and controls over prescribing have been suggested . AIMS To investigate the effect of a review of medication by a pharmacist . METHOD An 8-month prospect i ve trial of an active medication review by a pharmacist was carried out on 330 residents in nursing homes in Manchester . RESULTS The intervention group experienced greater deterioration in cognitive function and behavioural disturbance than the control group , but the changes in depression and quality of life were similar for both groups . The number of drugs prescribed fell in the intervention group , but not in the control group , with a corresponding saving in drug costs . The number of deaths was significantly smaller in the intervention homes during the intervention period ( 4 v. 14 ) but not overall during the study period as a whole ( 26 v. 28 ) . CONCLUSION This clinical intervention reduced the number of medicines prescribed to elderly people in nursing homes , with minimal impact on their morbidity and mortality OBJECTIVES --To assess whether intervention by a health visitor could reduce the number of fractures , over a four year period , in those aged 70 and over . DESIGN --R and omised , controlled trial ; r and omisation by household . SETTING --General practice in a market town . SUBJECTS -- Of 863 patients aged 70 and over on the practice records , 674 were traced and successfully interviewed ; 350 were assigned to the intervention group , 324 as controls . INTERVENTION -- The people in the intervention group were allocated to the care of a health visitor . The approach was four pronged : assessment and correction of nutritional deficiencies , including reducing smoking and alcohol intake ; assessment and referral of medical conditions such as heart block or inappropriate medication ; assessment and correction of environmental hazards in the home such as poor lighting ; assessment and improvement of fitness -- for example , exercise classes for the moderately fit . The intervention continued for four years . MAIN OUTCOME MEASURE -- Fracture rate over four years . RESULTS --The incidence of fractures was 5 % ( 16/350 ) in the intervention group and 4 % ( 14/324 ) in the control group ( difference not significant ) . CONCLUSIONS --A health visitor visiting a group of people aged 70 and over and using simple preventive measures had no effect on the incidence of fractures OBJECTIVE To evaluate the effects of a therapeutic outcomes monitoring ( TOM ) program on selected process and outcome measures . DESIGN Prospect i ve , controlled , multicenter study . SETTING Community pharmacies throughout Denmark ( 16 intervention , 15 control ) . PATIENTS Five hundred patients with asthma aged 16 to 60 years and treated in primary care . INTERVENTION TOM is a community-based program for pharmaceutical care . Using a structured , seven-step , cyclical outcome improvement process , TOM pharmacists identify and resolve ( or refer ) problems with drug therapy that , if not addressed , might result in therapeutic failure or adverse effects . Equal emphasis is placed on the patient 's perspective ( e.g. , coping , control , and empowerment ) and the professional 's perspective ( e.g. , adherence , patient knowledge , and therapeutic problems ) . TOM requires cooperation among pharmacists , patients , and physicians . MAIN OUTCOME MEASURES Asthma symptom status , days of sickness , health-related and asthma-specific quality of life , use of health care services and re sources , and satisfaction with health care and pharmacy . INTERMEDIATE OUTCOME AND PROCESS MEASURES : Peak expiratory flow rate ( PEFR ) , knowledge of asthma and asthma medications , inhalation errors , and drug therapy problems in the TOM group . RESULTS The mean individual differences for TOM and control patients were tested . Beneficial effects were found for the following outcome measures : asthma symptom status , days of sickness , and health-related and asthma-related quality of life . Satisfaction with health care and pharmacy varied throughout the course of the project , with no significant difference between groups at the final evaluation . Although not statistically significant , differences in use of services were considered to be clinical ly significant and encouraging . Beneficial effects were found for knowledge of asthma and medications , inhalation errors , drug use and drug therapy problems . No significant differences were found for PEFR . CONCLUSION The project demonstrated that therapeutic outcomes monitoring by community pharmacists is an effective strategy for improving the quality of drug therapy for asthma patients in primary health care PURPOSE We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes . SUBJECTS AND METHODS We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system . Patients were r and omly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator . Outcomes measured at 12 months included survey-reported self-care , perceived glycemic control , and symptoms , as well as glycosylated hemoglobin ( Hb A1c ) and serum glucose levels . RESULTS We collected follow-up data for 89 % of enrollees ( 248 patients ) . Compared with usual care patients , intervention patients reported more frequent glucose monitoring , foot inspection , and weight monitoring , and fewer problems with medication adherence ( all P -0.03 ) . Follow-up Hb A , , levels were 0.3 % lower in the intervention group ( P = 0.1 ) , and about twice as many intervention patients had Hb A1c levels within the normal range ( P = 0.04 ) . Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients ( P = 0.002 ) . Intervention patients also reported better glycemic control ( P = 0.005 ) and fewer diabetic symptoms ( P < 0.0001 ) , including fewer symptoms of hyperglycemia and hypoglycemia . CONCLUSIONS Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control , and for decreasing symptoms among vulnerable patients with diabetes PURPOSE To evaluate the effect of sustained clinical pharmacist interventions involving elderly out patients with polypharmacy and their primary physicians . PATIENTS AND METHODS R and omized , controlled trial of 208 patients aged 65 years or older with polypharmacy ( > or = 5 chronic medications ) from a general medicine clinic of a Veterans Affairs Medical Center . A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians . Outcome measures were prescribing appropriateness , health-related quality of life , adverse drug events , medication compliance and knowledge , number of medications , patient satisfaction , and physician receptivity . RESULTS Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months ( decrease 24 % versus 6 % , respectively ; P = 0.0006 ) and was sustained at 12 months ( decrease 28 % versus 5 % , respectively ; P = 0.0002 ) . There was no difference between groups at closeout in health-related quality of life ( P = 0.99 ) . Fewer intervention than control patients ( 30.2 % ) versus 40.0 % ; P = 0.19 ) experienced adverse drug events . Measures for most other outcomes remained unchanged in both groups . Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients ( 55.1 % versus 19.8 % ; P < 0.001 ) . CONCLUSIONS This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life Abstract Objective : To assess the impact of teaching general practitioners to carry out structured assessment s of their long term mentally ill patients . Design : R and omised controlled trial . Setting : Sixteen group general practice s in South Thames ( west ) region . Subjects : 440 adults disabled by long term mental illness . Interventions : Patients were identified by using practice data with help from local psychiatric and social services . In eight practice s the practitioners were taught a structured assessment schedule to use with patients every six months for two years . Main outcome measures : Changes in drug treatments , referrals , consultation rates , and recording of preventive health data in the two years after intervention . Results : Follow up data were available on 373 patients ( 84.7 % ) . At least one structured assessment was recorded for 127 patients in the intervention group but only 29 had four assessment s recorded . Participating practitioners considered the structured assessment to be time consuming and reported that it did not often lead directly to changes in treatment or referrals . Changes in treatment with neuroleptic drugs and referrals to community psychiatric nurses , however , were significantly more frequent in the intervention group ( differences for intervention group minus control group adjusted for activity in two years before intervention were 14.3 % ( 95 % confidence interval 4.3 % to 24.33 % ; P<0.01 ) for neuroleptic drugs and 13.3 % ( 2.0 % to 24.6%;P<0.05 ) for referrals ) . There were no significant differences in psychiatric admissions , use of the Mental Health Act , drug overdoses , prescriptions , referrals or admissions for physical problems , consultation rates , continuity of care , or recording of preventive data . Conclusions : Teaching general practitioners about the problems of long term mentally ill patients may increase their involvement in patients ' psychiatric care . Regular structured assessment s do not seem feasible in routine surgery appointments . More training for general practitioners and increased re sources such as more nurse time may be necessary if improvements in care of long term mentally ill patients in general practice are to be generalised CONTEXT Falls are a major health problem in nursing homes , but no interventions have been shown to prevent falls in nursing home residents . OBJECTIVE To evaluate an intervention program design ed to prevent falls and associated injuries in high-risk nursing home residents . DESIGN R and omized controlled trial . SETTING AND PARTICIPANTS Seven pairs of middle Tennessee nursing homes with 1 facility in each pair r and omly assigned to the intervention . Facilities had 482 ( 261 control , 221 intervention ) residents who qualified for the study because they had high risk of falls and a potential safety problem that could be addressed by the intervention . INTERVENTION Comprehensive structured individual assessment with specific safety recommendations that targeted suboptimal practice s for environmental and personal safety , wheelchair use , psychotropic drug use , and transferring and ambulation . Facility staff were encouraged to implement the individual recommendations and to improve overall facility safety . MAIN OUTCOME MEASURES The mean proportion of recurrent fallers and incidence rate of injurious falls in the facility in the year following the intervention . RESULTS The mean proportion of recurrent fallers in intervention facilities ( 43.8 % ) was 19.1 % ( 95 % confidence interval , 2.4%-35.8 % ) lower than that in control facilities ( 54.1 % , P=.03 ) . Intervention facilities had a nonsignificant trend toward a lower mean rate of injurious falls ( 13.7 vs 19.9 per 100 person-years , reduction of 31.2 % , P=.22 ) . Subgroup analyses suggested greatest benefits for residents for whom the recommended interventions were carried out or who had 3 or more falls in the preceding year . CONCLUSION The high rate of falls and related injuries in nursing homes should not be viewed as inevitable , but as outcomes that can be substantially improved through structured safety programs OBJECTIVES Because preventing disability and falls in older adults is a national priority , a r and omized controlled trial was conducted to test a multicomponent intervention program . METHODS From a r and om sample of health maintenance organization ( HMO ) enrollees 65 years and older , 1559 ambulatory seniors were r and omized to one of three groups : a nurse assessment visit and follow-up interventions targeting risk factors for disability and falls ( group 1 , n = 635 ) ; a general health promotion nurse visit ( group 2 , n = 317 ) ; and usual care ( group 3 , n = 607 ) . Data collection consisted of a baseline and two annual follow-up surveys . RESULTS After 1 year , group 1 subjects reported a significantly lower incidence of declining functional status and a significantly lower incidence of falls than group 3 subjects . Group 2 subjects had intermediate levels of most outcomes . After 2 years of follow-up , the differences narrowed . CONCLUSIONS The results suggest that a modest , one-time prevention program appeared to confer short-term health benefits on ambulatory HMO enrollees , although benefits diminished by the second year of follow-up . The mechanisms by which the intervention may have improved outcomes require further investigation BACKGROUND Since falling is associated with serious morbidity among elderly people , we investigated whether the risk of falling could be reduced by modifying known risk factors . METHODS We studied 301 men and women living in the community who were at least 70 years of age and who had at least one of the following risk factors for falling : postural hypotension ; use of sedatives ; use of at least four prescription medications ; and impairment in arm or leg strength or range of motion , balance , ability to move safely from bed to chair or to the bathtub or toilet ( transfer skills ) , or gait . These subjects were given either a combination of adjustment in their medications , behavioral instructions , and exercise programs aim ed at modifying their risk factors ( intervention group , 153 subjects ) or usual health care plus social visits ( control group , 148 subjects ) . RESULTS During one year of follow-up , 35 percent of the intervention group fell , as compared with 47 percent of the control group ( P = 0.04 ) . The adjusted incidence-rate ratio for falling in the intervention group as compared with the control group was 0.69 ( 95 percent confidence interval , 0.52 to 0.90 ) . Among the subjects who had a particular risk factor at base line , a smaller percentage of those in the intervention group than of those in the control group still had the risk factor at the time of re assessment , as follows : at least four prescription medications , 63 percent versus 86 percent , P = 0.009 ; balance impairment , 21 percent versus 46 percent , P = 0.001 ; impairment in toilet-transfer skills , 49 percent versus 65 percent , P = 0.05 ; and gait impairment , 45 percent versus 62 percent , P = 0.07 . CONCLUSIONS The multiple-risk-factor intervention strategy result ed in a significant reduction in the risk of falling among elderly persons in the community . In addition , the proportion of persons who had the targeted risk factors for falling was reduced in the intervention group , as compared with the control group . Thus , risk-factor modification may partially explain the reduction in the risk of falling Context In frail older people living in residential care facilities , hip protectors reduce fall-related femoral and pelvic injuries . In older people living in the community , prevention programs that target exercise and fall-related risk factors reduce falls and injuries . In older people living in residential care facilities , fall prevention programs , other than the use of hip protectors , have had mixed results . Contribution This r and omized trial shows that a multidisciplinary fall prevention program reduces falls and femoral fractures in older people living in residential care facilities . The program included general as well as resident-specific , tailored strategies . Editors ' Note The Cochrane Library ( Issue 3 , 2001 ) has two systematic review s that summarize r and omized trial evidence about interventions to prevent falls . The Editors Falls are a major problem in older people ( 1 , 2 ) . Hip fractures result ing from falls are particularly common in elderly persons living in residential care facilities ( 3 , 4 ) ; they account for a substantial proportion of dependency and mortality ( 5 ) . During the past decade , r and omized , controlled trials study ing fall prevention have shown both positive and negative results ( 6 - 8 ) . Differences in target groups , interventions , and outcome measures may explain the inconsistent results . In residential care facilities and nursing homes , only one trial demonstrated that intervention programs may help prevent falls ; however , this trial studied only people who fell repeatedly ( 9 ) . Other trials have not shown reductions in falls or injuries ( 10 - 13 ) but have shown fewer hospital admissions ( 11 ) and improvements in mobility ( 12 ) , visual acuity , and hypotension ( 13 ) . The use of hip protectors has consistently proved effective in preventing hip fractures in selected high-risk population s ( 14 ) . Some trials that have included cognitively healthier older people in the community have shown reduced falls and injuries when specific risk factors are targeted ( 15 - 18 ) . However , evidence is lacking for older people living in institutions ( 19 ) . We hypothesized that an intervention program that targeted multiple risk factors for falls in older people living in residential care facilities , in particular those with a high risk for falling , would reduce falls and fall-related injuries . We therefore conducted a cluster r and omized trial for preventing falls in nine residential care facilities . Methods Design Study participants were older people living in residential care facilities located in Ume , a city in northern Sweden . The selected facilities had to have more than 25 residents . The nine that met this criterion were divided into group A and group B. The distribution was based on the age and number of residents , type of setting ( care and service offered as well as corridor or private home design ) , and record of previous falls as routinely reported to the local authority . To keep the groups distinct from one another , the physicians , registered nurses , physical therapists , and occupational therapists who were responsible for working with the residents in group A could not also work with group B residents . Group A consisted of four facilities that accommo date d 224 residents ; the facilities had 29 to 74 residents each , and the median age by facility ranged from 82 to 85 years . Group B consisted of five facilities with a total of 215 residents ; there were 31 to 66 residents per facility , and the median age by facility ranged from 79 to 85 years . The number of falls reported to the local authorities in the 2.5 years preceding the trial was similar for both groups : 1.26 per resident per year for group A and 1.29 for group B. After baseline assessment of all residents , groups A and B were r and omly assigned by lots to an intervention or a control group ( Figure 1 ) . The r and om allocation was conducted by a person with no knowledge of the study . Two sealed , dark envelopes were used . In each envelope , a letter specified one of the groups . Before the lot was drawn , the first envelope drawn was design ated as the intervention group . The local authorities , residents , staff of the nine facilities , and the research group were then informed of the results of the r and omization . Figure 1 . Study design . All residents in the study received written and oral information . All participants ( or the relatives and guardians of participants with severe cognitive dysfunction ) gave informed consent . The administrators and staff of the nine facilities involved also received information about the study and agreed to participate . The Ethics Committee of the Medical Faculty of Ume University approved the study . Definition of a Fall and an Injury A fall was defined as an event in which the resident unintentionally came to rest on the ground or floor , regardless of whether an injury was sustained . Thus , this definition also includes falls that result ed from acute illness or epileptic seizure and incidents that result ed in a resident 's falling and being found on the floor by staff or another resident . An injury was defined according to the Abbreviated Injury Scale ( 20 ) . Classifications were minor for injuries limited to superficial wounds and bruises ; moderate for intermediate-level injuries , such as vertebral and wrist fractures ; and serious for major fractures , such as hip fractures and other femoral fractures . Participants and Setting s All residents in the nine facilities who were 65 years of age or older were selected in a cross-sectional manner . Thirty-seven of these residents declined to participate , were admitted to hospitals , or died before r and omization . Sex and age of the 37 non participants were similar to those of the remaining 402 residents . In Sweden , older people living in residential care facilities are disabled by cognitive or physical impairment and thus require supervision , functional support , or nursing care . In this study , some residents lived in private apartments and others had private rooms but shared dining and living rooms . In all facilities , residents had 24-hour daily access to assistance with activities of daily living , household issues , and medical care . The median age was 83 years ( range , 65 to 100 years ) , and most residents were female ( 72 % ) . Few residents could walk outdoors without a walking aid ( 14 % ) or shower without assistance ( 18 % ) ; few were nonambulatory ( 19 % ) or entirely dependent when eating ( 8 % ) . Additional baseline characteristics are presented in the Table . Table . Baseline Characteristics of the 402 Residents Participating in the Study All members of the permanent staff , regardless of profession , participated in the study . In addition , eight physiotherapists were employed part-time ( a total of 200 h/wk ) until the end of the intervention period , and three physiotherapists were employed part-time ( a total of 10 h/wk ) during the follow-up period . A total of 273 nurses ' aides or licensed practical nurses and 20 registered nurses worked at the nine facilities . Baseline Assessment Each resident 's physician completed a question naire regarding clinical characteristics and drugs prescribed . A registered nurse reported delirium episodes ( Table ) . Physiotherapists interviewed and assessed all residents . Hearing was rated as impaired if the resident could not hear normal speech from a distance of 1 meter or used a hearing aid . Vision was rated as impaired when the resident , with or without glasses , could not read a word written in 5-mm capital letters at reading distance . Global cognitive function was screened by using the Mini-Mental State Examination ( MMSE ) ( 21 ) . Licensed practical nurses or nurses ' aides were interviewed to determine the number of falls that had occurred during the 6 months preceding the study and the extent of use of physical restraints . Activities of daily living were assessed according to the Barthel index ( 22 , 23 ) . All residents were screened for the risk for falling . First , by using the Mobility Interaction Fall Chart ( 24 ) , a resident was classified to be at higher risk for falling if he or she stopped walking when talking to an accompanying person ( 25 ) , walked more slowly when carrying a glass of water ( 26 ) , or had impaired vision or difficulty concentrating . Second , a physiotherapist globally rated the fall risk as higher if the resident showed risk-taking behavior considered to jeopardize balance . If the residents were not classified to be at higher risk for falling by any of these described measures , they were considered to be at lower risk for falling . Residents at higher risk were likely to be older than those at lower risk ( median age , 84 years [ range , 65 to 98 years ] vs. 83 years [ range , 65 to 100 years ] ) , to have lower MMSE scores ( median score , 17 [ range , 0 to 30 ] vs. 21 [ range , 0 to 30 ] ) , and to have more medical diagnoses ( median , 4 vs. 3 ) . The main areas of each facility were also screened according to a checklist for environmental hazards , such as lighting , flooring , obstacles inside the facility , and dangerous areas outside the facility ( for example , icy areas ) . Twelve residents in the control group and six in the intervention group died or moved during the 11-week intervention period ( Figure 1 ) . Intervention Program The intervention program comprised strategies that targeted both general and resident-specific risk factors for falling . The strategies were design ed to be meaningful to the residents without compromising mobility . The 89 residents screened as being at higher risk as well as the 19 residents at lower risk who fell during the 11-week intervention period were the focus of the individualized intervention program . Increasing the staff 's knowledge about fall prevention was believed to be the starting point of a process that would produce long-term results . Staff Education All staff were invited to a 4-hour educational session , and more than half attended . The sessions were led by a physician and a physiotherapist and covered risk factors for falls and intervention Background : Falls are a major cause of morbidity in old age . A small number of fall prevention trials in cognitively intact community-dwelling older people have been effective . This study set out to examine the preventability of falls in older people living in institutional care . Objective : To evaluate the effectiveness of falls risk factor assessment /modification and seated balance exercise training in reducing falls among elderly people living in residential care . Methods : 133 residents with a mean age of 84± ( SD ) 6.8 years were allocated at r and om by home to receive either a 6-month falls risk factor assessment /modification and seated balance exercise training programme ( n = 77 ) or 6 months of reminiscence therapy ( n = 56 ) . The risk factors targeted were postural hypotension , polypharmacy , visual acuity , and ambient lighting levels . Falls risk factor assessment s and recommendation for modifications were performed at baseline in the intervention group and assessment s repeated at 6 months . Functional reach , reaction time , timed up- and - go , grip strength , spinal flexibility , and Philadelphia Geriatric Centre Morale Scale and Mini-Mental State Examination scores were determined at baseline and at 6 months by a ‘ blind ’ observer . Falls and fractures were then monitored in both groups during a 7- to 12-month falls-monitoring follow-up period . Results : Only 90 of 133 ( 67.7 % ) residents completed the 6-month intervention period , and 84 ( 63.2 % ) completed the 7- to 12-month falls-monitoring follow-up period . Both prevalence of postural hypotension ( p = 0.0005 ) and poor visual acuity ( p = 0.04 ) were reduced in the intervention group . There was no difference between the groups in the number of falls sustained , the risk of falling [ odds ratio 0.45 ( 95 % CI 0.19–1.14 ) ] , or in the risk of recurrent falling [ odds ratio 1.07 ( 95 % CI 0.40–2.97 ) ] . No significant differences were found between the groups with regard to change in other outcome measures . Conclusions : The high drop-out rate reduced the power of this study to detect any effect of the interventions used . It is possible that either the exercises were not sufficiently vigorous or that to improve balance exercises must be performed st and ing . Further research is required to identify effective fall prevention strategies for elderly people in residential setting Objective This study aim ed to measure the outcomes of a harmonised , structured pharmaceutical care programme provided to elderly patients ( ≥65 years of age ) by community pharmacists in a multicentre international study performed in 7 European countries . Design and setting The study was a r and omised , controlled , longitudinal , clinical trial with repeated measures performed over an 18-month period . A total of 104 intervention and 86 control pharmacy sites participated in the research and 1290 intervention patients and 1164 control patients were recruited into the study .Main outcome measures and results A general decline in health-related quality of life over time was observed in the pooled data ; however , significant improvements were achieved in patients involved in the pharmaceutical care programme in some countries . Intervention patients reported better control of their medical conditions as a result of the study and cost savings associated with pharmaceutical care provision were observed in most countries . The new structured service was well accepted by intervention patients and patient satisfaction with the services improved during the study . The pharmacists involved in providing pharmaceutical care had a positive opinion on the new approach , as did the majority of general practitioners surveyed . The positive effects appear to have been achieved via social and psychosocial aspects of the intervention , such as the increased support provided by community pharmacists , rather than via biomedical mechanisms . Conclusions This study is the first large-scale , multicentre study to investigate the effects of pharmaceutical care provision by community pharmacists to elderly patients . Future research methodology and implementation will be informed by the experience gained from this challenging trial This pilot study demonstrated the feasibility of providing practice nurse support as an adjunct to st and ard general practitioner treatment to patients with depressive disorders prescribed antidepressant medication . With respect to the measures used and pilot study objectives identified , there were no statistically significant differences between the study groups in treatment adherence to the prescription of antidepressant medication or in the incidence and severity of adverse events to medication . Large-scale r and omized controlled trials are in progress to assess the effectiveness of practice nurse interventions in the management of depressive illness in general practice |
10,963 | 26,519,952 | Hence , nonaffective psychosis is characterized by a hasty decision-making style , which is linked to an increased probability of delusions | We did a systematic review and meta- analysis to investigate the magnitude and specificity of the " jumping to conclusions " ( JTC ) bias in psychosis and delusions .
We examined the extent to which people with psychosis , and people with delusions specifically , required less information before making decisions .
We examined ( 1 ) the average amount of information required to make a decision and ( 2 ) numbers who demonstrated an extreme JTC bias , as assessed by the " beads task . " | Background : Given the evidence that reasoning biases contribute to delusional persistence and change , several research groups have made systematic efforts to modify them . The current experiment tested the hypothesis that targeting reasoning biases would result in change in delusions . Methods : One hundred and one participants with current delusions and schizophrenia spectrum psychosis were r and omly allocated to a brief computerized reasoning training intervention or to a control condition involving computer-based activities of similar duration . The primary hypotheses tested were that the reasoning training intervention , would improve ( 1 ) data gathering and belief flexibility and ( 2 ) delusional thinking , specifically paranoia . We then tested whether the changes in paranoia were mediated by changes in data gathering and flexibility , and whether working memory and negative symptoms moderated any intervention effects . Results : On an intention-to-treat analysis , there were significant improvements in state paranoia and reasoning in the experimental compared with the control condition . There was evidence that changes in reasoning mediated changes in paranoia , although this effect fell just outside the conventional level of significance after adjustment for baseline confounders . Working memory and negative symptoms significantly moderated the effects of the intervention on reasoning . Conclusion : The study demonstrated the effectiveness of a brief reasoning intervention in improving both reasoning processes and paranoia . It thereby provides proof-of-concept evidence that reasoning is a promising intermediary target in interventions to ameliorate delusions , and thus supports the value of developing this approach as a longer therapeutic intervention The present study aim ed to investigate whether a brief reasoning training module changes the “ jumping to conclusions ” data gathering bias in people with delusions . A secondary aim was to examine whether improvements in reasoning would lead to greater flexibility in thinking about delusions . It was found that people with delusions and a diagnosis of schizophrenia ( n = 34 ) requested less information on a reasoning task compared with a non clinical control group ( n = 34 ) . The clinical group was then r and omly allocated to a session of reasoning training or to an attention control condition . Following training , participants showed a significant increase in data gathering , and a small number reported more flexibility and less conviction in their delusions , although this finding was not significant . The presence at baseline of an extreme reasoning bias moderated the effect of training . The study provides further confirmation of the jumping to conclusions bias and shows that data gathering can be improved , though the severest form of the bias is resistant to change . It is recommended that lengthier , delusion-related reasoning packages be developed and evaluated BACKGROUND A consistent body of studies suggests that schizophrenia patients are extremely hasty when making decisions , and generally opt for the strongest response alternative . This pattern of results is primarily based on studies conducted with the beads task , which requires participants to determine from which of two possible jars a series of beads has been drawn . We have recently proposed a liberal acceptance ( LA ) bias to account for decision-making biases in schizophrenia , which cl aims that under heightened ambiguity the jump to conclusions ( JTC ) bias is abolished in schizophrenia . METHODS A total of 37 schizophrenia patients were compared with 37 healthy controls on different versions of the beads paradigm . For the first task , participants were required to rate the probability that a bead was being drawn from one of two jars , and had to evaluate after each bead whether the amount of presented information would justify a decision . The second task was a classical draws to decision experiment with two jars . The third task confronted participants with four possible jars . If JTC was ubiquitous in schizophrenia hasty convergence on one alternative would be predicted for all three tasks . In contrast , the LA account predicts an abolishment of the JTC effect in the final task . RESULTS Tasks 1 and 2 provide further evidence for the well-replicated JTC pattern in schizophrenia patients . In accordance with the LA hypothesis , no group differences were detected for task 3 . DISCUSSION The present results confirm that JTC is not ubiquitous in schizophrenia : in line with the LA account a JTC bias in schizophrenia occurred under low but not high ambiguity . LA may partly explain the emergence of fixed , false beliefs People with delusions have been shown to have both generalized ( Huq , Garety & Hemsley , 1988 ) and content-specific biases in reasoning ( Bentall , 1994 ) . Our concern here was whether the hastiness that has been found when people with delusions reason on relatively abstract tasks would be present on a more realistic task . A second concern was whether reasoning with salient or emotional material would increase the hastiness bias in people with delusions . Two versions of a probabilistic reasoning task were used to study the data gathering of people with delusions . The first version employed realistic but emotionally neutral material . People with delusions requested less evidence before making a decision than psychiatric and normal comparison groups . Therefore , the hastiness found previously with abstract material s was seen to generalize to a more realistic task . In the second version participants were required to reason with material that had an emotional content and may have been regarded as being personally meaningful . In this condition all groups reduced the amount of evidence requested before making a decision Biases in cognition such as Jumping to Conclusions ( JTC ) and Verbal Self-Monitoring ( VSM ) are thought to underlie the formation of psychotic symptoms . This prospect i ve study in people with an At Risk Mental State ( ARMS ) for psychosis examined how these cognitive biases changed over time , and predicted clinical and functional outcomes . Twenty-three participants were assessed at clinical presentation and a mean of 31 months later . Performance on a JTC and VSM tasks were measured at both time points . Relationships to symptom severity , level of function and the incidence of psychotic disorder were then examined . The levels of symptoms , function and VSM all improved over time , while JTC was stable . Five participants ( 22 % ) developed a psychotic disorder during the follow-up period , but the risk of transition was not related to performance on either task at baseline , or to longitudinal changes in task performance . JTC performance correlated with symptom severity at baseline and follow-up . Similarly , performance on the two tasks was not related to the level of functioning at follow-up . Thus , while the ARMS is associated with both VSM and JTC biases , neither predict the onset of psychosis or the overall functional outcome |
10,964 | 25,196,412 | These results suggest that interventions in African American FBOs can successfully improve weight and related behaviours .
However , not all of the findings about the success of certain approaches were as expected . | African Americans , especially women , have higher obesity rates than the general US population .
Because of the importance of faith to many African Americans , faith-based organizations ( FBOs ) may be effective venues for delivering health messages and promoting adoption of healthy behaviours . | Purpose This study developed and tested a culturally appropriate , church-based intervention to improve diabetes self-management . Research Design and Methods This was a r and omized trial conducted at 24 African American churches in central North Carolina . Churches were r and omized to receive the special intervention ( SI ; 13 churches , 117 participants ) or the minimal intervention ( MI ; 11 churches , 84 participants ) . The SI included an 8-month intensive phase , consisting of 1 individual counseling visit , 12 group sessions , monthly phone contacts , and 3 encouragement postcards , followed by a 4-month reinforcement phase including monthly phone contacts . The MI received st and ard educational pamphlets by mail . Outcomes were assessed at 8 and 12 months ; the primary outcome was comparison of 8-month A1C levels . Results At baseline , the mean age was 59 years , A1C 7.8 % , and body mass index 35.0 kg/m2 ; 64 % of participants were female . For the 174 ( 87 % ) participants returning for 8-month measures , mean A1C ( adjusted for baseline and group r and omization ) was 7.4 % for SI and 7.8 % for MI , with a difference of 0.4 % ( 95 % confidence interval [ CI ] , 0.1 - 0.6 , P = .009 ) . In a larger model adjusting for additional variables , the difference was 0.5 % ( 95 % CI , 0.2 - 0.7 , P < .001 ) . At 12 months , the difference between groups was not significant . Diabetes knowledge and diabetes-related quality of life significantly improved in the SI group compared with the MI group . Among SI participants completing an acceptability question naire , intervention components and material s were rated as highly acceptable . Conclusions The church-based intervention was well received by participants and improved short-term metabolic control Colorectal cancer screening has clear benefits in terms of mortality reduction ; however , it is still underutilized and especially among medically underserved population s , including African Americans , who also suffer a disproportionate colorectal cancer burden . This study consisted of a theory-driven ( health belief model ) spiritually based intervention aim ed at increasing screening among African Americans through a community health advisor-led educational series in 16 churches . Using a r and omized design , churches were assigned to receive either the spiritually based intervention or a nonspiritual comparison , which was the same in every way except that it did not contain spiritual/religious content and themes . Trained and certified peer community health advisors in each church led a series of two group educational sessions on colorectal cancer and screening . Study enrollees completed a baseline , 1-month , and 12-month follow-up survey at their churches . The interventions had significant pre – post impact on awareness of all four screening modalities , and self-report receipt of fecal occult blood test , flexible sigmoidoscopy , and colonoscopy . There were no significant study group differences in study outcomes , with the exception of fecal occult blood test utilization , whereas those in the nonspiritual intervention reported significantly greater pre – post change . Both of these community-engaged , theory-driven , culturally relevant approaches to increasing colorectal cancer awareness and screening appeared to have an impact on study outcomes . Although adding spiritual/religious themes to the intervention was appealing to the audience , it may not result in increased intervention efficacy OBJECTIVES Body and Soul was a collaborative effort among two research universities , a national voluntary agency ( American Cancer Society ) , and the National Institutes of Health to disseminate and evaluate under real-world conditions the impact of previously developed dietary interventions for African Americans . METHODS Body and Soul was constructed from two successful research -based interventions conducted in African-American churches . Components deemed essential from the prior interventions were combined , and then tested in a cluster r and omized-effectiveness trial . The primary outcome was fruit and vegetable intake measured with two types of food frequency question naires at baseline and 6-month follow-up . RESULTS At the 6-month follow-up , intervention participants showed significantly greater fruit and vegetable ( F&V ) intake relative to controls . Post-test differences were 0.7 and 1.4 servings for the 2-item and 17-item F&V frequency measures , respectively . Statistically significant positive changes in fat intake , motivation to eat F&V , social support , and efficacy to eat F&V were also observed . CONCLUSIONS The results suggest that research -based interventions , delivered collaboratively by community volunteers and a health-related voluntary agency , can be effectively implemented under real-world conditions OBJECTIVE The purpose of this study was to examine a church-based intervention employing a 6-month pilot weight loss program as a strategy to improve health of African-American adults . DESIGN A r and omized trial design was used without a control group . Eligible church members were r and omized into two groups : an intervention delivered in the group setting and an intervention delivered in the individual setting . SETTING The study was conducted at an African-American church in Baton Rouge , Louisiana . PARTICIPANTS Forty church members were enrolled in the study . Two trained church members without specialization in obesity treatment conducted the study . MAIN OUTCOME MEASURES The primary outcome measure was weight loss . RESULTS The program retention rate was 90 % . After six months , a modest but significant mean weight loss was seen in all participants of 3.3 kg . The mean weight losses in the individual and group interventions were 3.4 kg and 3.1 kg , respectively . The mean body fat loss was 2.1 kg and 1.9 kg , respectively . The difference in weight loss and fat loss between the individual and group interventions was not statistically significant . An improvement in the quality of life and an increase in physical activity were reported by the program participants . CONCLUSIONS A church setting may provide an effective delivery mechanism for a health and nutrition program . Church members may be trained to conduct a weight control program . Both interventions ( individual and group ) were effective in inducing weight loss OBJECTIVES This study assessed the effects of the Black Churches United for Better Health project on increasing fruit and vegetable consumption among rural African American church members in North Carolina . METHODS Ten counties comprising 50 churches were pair matched and r and omly assigned to either intervention or delayed intervention ( no program until after the follow-up survey ) conditions . A multicomponent intervention was conducted over approximately 20 months . A total of 2519 adults ( 77.3 % response rate ) completed both the baseline and 2-year follow-up interviews . RESULTS The 2 study groups consumed similar amounts of fruits and vegetables at baseline . AT the 2-year follow-up , the intervention group consumed 0.85 ( SE = 0.12 ) servings more than the delayed intervention group ( P < .0001 ) . The largest increases were observed among people 66 years or older ( 1 serving ) , those with education beyond high school ( 0.92 servings ) , those widowed or divorced ( 0.96 servings ) , and those attending church frequently ( 1.3 servings ) . The last improvement occurred among those aged 18 to 37 years and those who were single . CONCLUSIONS The project was a successful model for achieving dietary change among rural African Americans Background Despite a significant decrease in smoking prevalence over the past ten years , cigarette smoking still represents the leading cause of preventable morbidity and mortality in the United States . Moreover , smoking prevalence is significantly higher among those with low levels of education and those living at , or below , the poverty level . These groups tend to be confronted with significant barriers to utilizing more traditional smoking cessation intervention approaches . The purpose of the study , Project ACTION ( Adult smoking Cessation Treatment through Innovative Outreach to Neighborhoods ) , is to utilize a mobile clinic model , a network of community sites ( i.e. , community centers and churches ) and an interactive mobile messaging system to reach and deliver smoking cessation treatment to underserved , low-income communities . Methods / Design We are using a group-r and omized design , with the community site as the sampling unit , to compare the efficacy of three smoking cessation interventions : 1 ) St and ard Care - brief advice to quit smoking , nicotine replacement therapy ( NRT ) , and self-help material s ; 2 ) Enhanced Care - st and ard care components plus a cell phone-delivered text/graphical messaging component ; and 3 ) Intensive Care - enhanced care components plus a series of 11 cell phone-delivered proactive counseling sessions . An economic evaluation will also be performed to evaluate the relative cost effectiveness of the three treatment approaches . We will recruit 756 participants ( 252 participants in each of the 3 intervention groups ) . At the time of r and omization , participants complete a baseline assessment , consisting of smoking history , socio-demographic , and psychosocial variables . Monthly cell phone assessment s are conducted for 6 months-post enrollment , and a final 12-month follow-up is conducted at the original neighborhood site of enrollment . We will perform mixed-model logistic regression to compare the efficacy of the three smoking cessation intervention treatment groups . Discussion It is hypothesized that the intensive care approach will most successfully address the needs of the target population and result in the highest smoking cessation rates . In addition to increasing cessation rates , the intervention offers several features ( including neighborhood outreach and use of mHealth technology ) that are likely to reduce treatment barriers while enhancing participant engagement and retention to treatment . Trial registration This r and omized controlled trial is registered with clinical trials.gov registration number NCT00948129 Introduction Physical activity participation is low among blacks , and strategies are needed to successfully create immediate and sustained behavior change related to physical activity . Churches can play an important role in health promotion efforts among blacks because of their central role in spiritual guidance , communication , social support , and networking . This pilot study evaluated the feasibility and acceptability of implementing a physical activity program for sedentary black adults in churches . Methods We used a preintervention/postintervention single-group design to evaluate the effect of a 3-month faith-based physical activity intervention on daily walking and moderate- and vigorous-intensity physical activity among sedentary blacks . Eighty-seven black adults participated in eight group sessions that included discussion of physical activity-related topics , an instructor-led physical activity session , and weekly incentives to promote physical activity . We used a question naire to assess moderate and vigorous physical activity in minutes per week at baseline and after 3 months . Walking was assessed weekly in steps per day by using a pedometer . Results Participants ( mean age , 52 yrs ; mean body mass index , 35 kg/m2 ) reported 27 ± 54 and 10 ± 25 minutes per week in moderate-intensity and vigorous-intensity physical activity , respectively , and walked 4822 ± 2351 steps per day at baseline . After 12 weeks , moderate- and vigorous-intensity physical activity increased by 67 ± 78 and 44 ± 66 minutes per week , respectively ( P ≤ .01 ) , and daily walking increased by 1373 ± 728 steps per day ( P < .001 ) . Conclusion These data suggest that a faith-based physical activity intervention may be an appropriate strategy for increasing physical activity among sedentary black adults . Future research will determine the impact of this program in a r and omized , controlled design Objective . The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies : a st and ard behavioral group intervention , the st and ard intervention supplemented with spiritual strategies , or self-help strategies . Methods . Women were screened at baseline and after one year of participation . The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering . Because spiritual strategies were added to the st and ard intervention by participants themselves , the results from both active groups were similar and , thus , combined for comparisons with the self-help group . Results . A total of 529 women from 16 churches enrolled . Intervention participants exhibited significant improvements in body weight ( −1.1 lbs ) , waist circumference ( −0.66 inches ) , systolic blood pressure ( −1.6 mmHg ) , dietary energy ( −117 kcal ) , dietary total fat ( −8 g ) , and sodium intake ( −145 mg ) . The self-help group did not . In the active intervention group , women in the top decile for weight loss at one year had even larger , clinical ly meaningful changes in risk outcomes ( −19.8 lbs ) . Conclusions . Intervention participants achieved clinical ly important improvements in cardiovascular disease risk profiles one year after program initiation , which did not occur in the self-help group . Church-based interventions can significantly benefit the cardiovascular health of African American women OBJECTIVES This study reports on Eat for Life , a multicomponent intervention to increase fruit and vegetable consumption among African Americans that was delivered through Black churches . METHODS Fourteen churches were r and omly assigned to 3 treatment conditions : ( 1 ) comparison , ( 2 ) self-help intervention with 1 telephone cue call , and ( 3 ) self-help with 1 cue call and 3 counseling calls . The telephone counseling in group 3 was based on motivational interviewing . The primary outcome , assessed at baseline and 1-year follow-up , was fruit and vegetable intake as assessed by 3 food frequency question naires . RESULTS Change in fruit and vegetable intake was significantly greater in the motivational interviewing group than in the comparison and self-help groups . The net difference between the motivational interviewing and comparison groups was 1.38 , 1.03 , and 1.21 servings of fruits and vegetables per day for the 2-item , 7-item , and 36-item food frequency question naires , respectively . The net difference between the motivational interviewing and self-help groups was 1.14 , 1.10 , and 0.97 servings for the 2-item , 7-item , and 36-item food frequency question naires , respectively . CONCLUSIONS Motivational interviewing appears to be a promising strategy for modifying dietary behavior , and Black churches are an excellent setting to implement and evaluate health promotion programs OBJECTIVE To evaluate whether the evidence -based Body & Soul program , when disseminated and implemented without research er or agency involvement and support , would achieve results similar to those of earlier efficacy and effectiveness trials . DESIGN Prospect i ve group r and omized trial . SETTING Churches with predominantly African American membership . PARTICIPANTS A total of 1,033 members from the 15 churches completed baseline surveys . Of these participants , 562 ( 54.4 % ) completed the follow-up survey 6 months later . INTERVENTION Church-based nutrition program for African Americans that included pastoral involvement , educational activities , church environmental changes , and peer counseling . MAIN OUTCOME MEASURE Daily fruit and vegetable ( FV ) intake was assessed at pre- and posttest . ANALYSIS Mixed-effects linear models . RESULTS At posttest , there was no statistically significant difference in daily servings of FVs between the early intervention group participants compared to control group participants ( 4.7 vs 4.4 , P = .38 ) . Process evaluation suggested that added re sources such as technical assistance could improve program implementation . CONCLUSIONS AND IMPLICATION S The disseminated program may not produce improvements in FV intake equal to those in the earlier efficacy and effectiveness trials , primarily because of a lack of program implementation . Program dissemination may not achieve public health impact unless support systems are strengthened for adequate implementation at the church level OBJECTIVES To evaluate a faith-based intervention ( Sisters in Motion ) intended to increase walking in older , sedentary African-American women . DESIGN R and omized controlled trial using within-church r and omization . SETTING Three Los Angeles churches . PARTICIPANTS Sixty-two African-American women aged 60 and older who reported being active less than 30 minutes three times per week and walked less than 35,000 steps per week as measured using a baseline pedometer reading . INTERVENTION Intervention participants received a multicomponent curriculum including scripture readings , prayer , goal - setting , a community re source guide , and walking competitions . Intervention and control participants both participated in physical activity sessions . MEASUREMENTS The primary outcome was change in weekly steps walked as measured using the pedometer . Secondary outcomes included change in systolic blood pressure ( SBP ) . Outcomes were assessed at baseline and 6 months after the intervention . RESULTS Eighty-five percent of participants attended at least six of eight sessions . Intervention participants averaged 12,727 steps per week at baseline , compared with 13,089 steps in controls . Mean baseline SBP was 156 mmHg for intervention participants and 147 mmHg for controls ( P=.10 ) . At 6 months , intervention participants had increased their weekly steps by 9,883 on average , compared with an increase of 2,426 for controls ( P=.02 ) ; SBP decreased on average by 12.5 mmHg in intervention participants and only 1.5 mmHg in controls ( P=.007 ) . CONCLUSION The Sisters in Motion intervention led to an increase in walking and a decrease in SBP at 6 months . This is the first r and omized controlled trial of a faith-based physical activity program to increase physical activity in older African-American women and represents an attractive approach to stimulate lifestyle change in this population Healthy Body Healthy Spirit was a multicomponent intervention to increase fruit and vegetable ( F & V ) consumption and physical activity ( PA ) delivered through Black churches . Sixteen churches were r and omly assigned to 3 intervention conditions . At baseline , 1,056 individuals were recruited across the 16 churches , of which 906 ( 86 % ) were assessed at 1-year follow-up . Group 1 received st and ard educational material s , Group 2 received culturally targeted self-help nutrition and PA material s , and Group 3 received the same intervention as did Group 2 as well as 4 telephone counseling calls based on motivational interviewing ( MI ) delivered over the course of 1 year . At 1-year follow-up , Groups 2 and 3 showed significant changes in both F & V intake and PA . Changes were somewhat larger for F & V. For F & V , but not PA , there was a clear additive effect for the MI intervention OBJECTIVE This study was carried out to test the effectiveness of PATHWAYS , a weight loss program design ed specifically for urban African-American women , when administered in urban churches by trained lay facilitators . RESEARCH DESIGN AND METHODS Thirty-nine obese women were recruited from three urban African-American churches . After r and omization and the collection of baseline data on weight and lifestyle practice s , subjects in the experimental group ( n = 19 ) were assigned to receive a 14-week weight loss program ( PATHWAYS ) conducted by trained lay volunteers ; control group subjects ( n = 20 ) were put on a waiting list to receive the program at the conclusion of the study period . RESULTS Of the 39 women enrolled , 15 experimental group subjects and 18 control group subjects were available for posttreatment data collection . After completing the program , PATHWAYS participants lost an average of 10.0 lb , and the control group subjects gained an average of 1.9 lb . Posttreatment difference in weight loss between the groups was statistically significant ( P < 0.0001 ) . Waist circumference among PATHWAYS participants decreased 2.5 inches , while waist circumference among control group subjects remained relatively the same . This difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS A weight loss program administered by trained lay volunteers was effective in producing significant and clinical ly meaningful weight loss among African-American women who often do not benefit from typical weight loss programs . Ongoing research is focusing on whether the weight loss can be maintained or enhanced through monthly reinforcement sessions This article provides an overview of the development , implementation , and baseline findings from a statewide faith-based physical activity ( PA ) initiative . The 3-year program is training African Method ist Episcopal volunteers across South Carolina to implement programs to increase PA in their congregations . To date , 98 churches have been trained . Interviews done with a r and om sample ( n = 39 ) indicated that 54 % are implementing at least one PA program . The baseline telephone survey ( N = 571 ) estimates that 27.8 % of the population is regularly active , 54.9 % underactive , and 17.3 % sedentary . Baseline rates of regular PA were higher in those who were younger , healthier , and nonsmokers . Challenges to date have included obtaining rosters and implementing a large-scale program with limited re sources . Interest in the program has been strong and supported by church leaders . Current efforts are on training additional churches and working with those already trained to support sustainability OBJECTIVE Go Girls was a church-based nutrition and physical activity program design ed for overweight African-American ( AA ) adolescent females . RESEARCH METHODS AND PROCEDURES Ten predominantly middle-socioeconomic churches were r and omized to either a high-intensity ( 20 to 26 sessions ) or moderate-intensity ( six sessions ) culturally tailored behavioral group intervention delivered over 6 months . Each session included an experiential behavioral activity , approximately 30 minutes of physical activity , and preparation and tasting of healthy foods . In the high-intensity group , girls also received four to six telephone counseling calls . From the 10 churches , 123 girls completed baseline and 6-month post-test assessment s. The primary outcome was BMI ; secondary outcomes included waist and hip circumferences , percentage body fat estimated by bioimpedance , serum insulin , glucose , and lipids , and cardiovascular fitness at 6-month follow-up . Selected measures were also collected at 1-year follow-up . RESULTS At 6-month follow-up , the net difference between the high- and moderate-intensity groups was 0.5 BMI units . This difference was not statistically significant ( p = 0.20 ) . There were no significant group differences in secondary outcomes . Girls in the high-intensity condition , however , who attended more than three-quarters of the sessions had significantly lower BMI and percentage body fat relative to girls in the high-intensity group who attended fewer sessions . Findings at 1-year follow-up mirrored those at 6 months . DISCUSSION We concluded that the intervention was not effective in reducing adiposity , although there were some positive findings among high attenders . Despite the null result , the intervention was generally well received by participants . Future interventions may require greater dose and a more structured dietary change program OBJECTIVES The purpose of this study was to determine the feasibility of implementing a diabetes prevention program ( DPP ) in a rural African-American church . METHODS A six-session DPP , modeled after the successful National Institutes of Health ( NIH ) DPP , was implemented in a rural African-American church . Adult members of the church identified as high risk for diabetes , based on results of a risk question naire , were screened with a fasting glucose . Persons with prediabetes , a fasting glucose of 100 - 125 mg/dL , participated in the six-session , Lifestyle Balance Church DPP . The primary outcomes were attendance rates and changes in fasting glucose , weight and body mass index measured at baseline , six- and 12-month follow-up . RESULTS Ninety-nine adult church members were screened for diabetes risk . Eleven had impaired fasting glucose . Ten of 11 participated in the six-session intervention , for an attendance rate of 78 % . After the intervention and 12-month follow-up , there was a mean weight loss of 7.9 lbs and 10.6 lbs , respectively . CONCLUSIONS This pilot project suggests that a modified six-session DPP can be translated to a group format and successfully implemented in a church setting . Further r and omized studies are needed to determine the effectiveness of such an intervention The design of a large-scale research project ( The Health and Religion Project ) in which church volunteers deliver behavior change programming on major cardiovascular risk factors ( smoking , elevated blood pressure , elevated serum cholesterol , excess weight , and physical inactivity ) is described . A total of 20 churches ( Roman Catholic , Baptist , and Episcopal ) were recruited throughout Rhode Isl and and r and omly assigned to five experimental conditions . These conditions were design ed to test the necessity of training special task forces to coordinate efforts within each church and to test the relative efficacy of high or low levels of professional ( paid staff ) involvement . Churches have many characteristics that are compatible with behavior change programming for primary prevention of chronic diseases . However , there have been very few research studies of churches engaging in primary prevention activities . Thus , the first step was to test the churches ' receptivity to participation in this type of project . To do this , all churches in Rhode Isl and were surveyed by mail and phone . Those that met several eligibility criteria were r and omly selected for recruitment into the study . The high receptivity of the churches was demonstrated by a response rate of 65 percent ( 20 of 31 ) . This readiness is bolstered by the fact that all of the 20 churches that originally began the study have remained involved for at least 2 1/2 years BACKGROUND Faith-based interventions using a community-based participatory approach hold promise for eliminating ethnic health disparities . This study evaluated the effects of a volunteer-led statewide program to increase physical activity among members of African-American churches . METHODS African Method ist Episcopal churches within six regions ( Conferences ) were r and omly assigned to receive training in the program immediately or 1 year later . A cohort of 20 r and omly selected churches and 571 members within them took part in telephone surveys at baseline ( May-September 2003 ) and 1 year ( May-August 2004 ) and 2 years later ( June-September 2005 ) . Primary outcomes were physical activity participation , meeting physical activity recommendations , and stage of readiness for physical activity change . Statistical analyses were completed in April 2006 . RESULTS Volunteers ( N=889 ) from 303 churches were trained . Among survey respondents , physical activity did not increase significantly over time , although 67 % were aware of the program . Program awareness was significantly related to all three physical activity outcomes and to fruit and vegetable consumption . Pastoral support was significantly associated with physical activity . CONCLUSIONS Although this intervention reached a large number of churches and created awareness of intervention components , no effects on physical activity behaviors were found . Potential reasons for the lack of significant effects are discussed Despite multidisciplinary efforts to control the nation 's obesity epidemic , obesity has persisted as one of the U.S. 's top public health problems , particularly among African Americans . Innovative approaches to address obesity that are sensitive to the unique issues of African Americans are needed . Thus , a faith-based weight-loss intervention using a community-based participatory research approach was developed , implemented , and evaluated with a rural African American faith community . A two-group , quasi-experimental , delayed intervention design was used , with church as the unit of assignment ( treatment n = 2 , control n = 2 ) and individual as the unit of observation ( treatment n = 36 , control n = 37 ) . Weekly small groups led by trained community members met for 8 weeks and emphasized healthy nutrition , physical activity , and faith 's connection with health . The mean weight loss of the treatment group was 3.60 ± 0.64 lbs . compared to the 0.59 ± 0.59-lb loss of the control group This trial evaluated a 6-month , church-based aerobic exercise intervention to increase physical activity among African American women relative to a health lecture and stretching condition . Participants were 196 women from 11 churches . Churches were r and omized to an Aerobic Exercise or Health N Stretch intervention . Results indicated that physical activity was not different in Aerobic Exercise and Stretch N Health , although attendance in both interventions was low . Both groups reduced physical inactivity prevalence from baseline ( 26 % and 18 % decline , respectively ) . Higher baseline social support predicted change in physical activity , regardless of treatment assignment . Research ers must continue to work to identify successful intervention strategies to increase physical activity in African American women who are at disproportionate risk of chronic diseases associated with physical inactivity BACKGROUND Eat for Life , a multicomponent intervention to increase fruit and vegetable ( F & V ) consumption among African Americans , is delivered through African American churches . METHODS Fourteen churches were r and omly assigned to one of three treatment conditions : 1 ) comparison ; 2 ) culturally-sensitive multicomponent intervention with one phone call ; and 3 ) culturally-sensitive multicomponent intervention with four phone calls . The intervention included an 18-minute video , a project cookbook , printed health education material s , and several " cues " imprinted with the project logo and a 5 A Day message . A key element of the telephone intervention was the use of motivational interviewing , a counseling technique originally developed for addictive behaviors . Major outcomes for the trial included total F & V intake , assessed by food-frequency question naires ( FFQs ) and 24-hour recalls , and serum carotenoids . Psychosocial variables assessed included outcome expectations , barriers to F & V intake , preference for meat meals , neophobia , social support to eat more F & V , self-efficacy to eat more F & V , and nutrition knowledge . RESULTS Baseline mean F & V intakes across the three FFQs ranged from 3.45 to 4.28 servings per day . Intake based on a single 24-hour recall was 3.0 servings . Variables positively correlated with F & V intake included self-efficacy , outcome expectations , and a belief that F & V contain vitamins . Factors negatively correlated with intake include perceived barriers , meat preference , neophobia , and high-fat cooking practice s. The completion rate for the first telephone counseling call was 90 % . Completion rates for the remaining three calls ranged from 79 % to 86 % . CONCLUSION The recruitment and intervention methods of the Eat for Life study appear promising . The telephone intervention based on motivational interviewing is potentially useful for delivering dietary counseling BACKGROUND Faith-based interventions hold promise for promoting health in ethnic minority population s. To date , however , few of these interventions have used a community-based participatory research ( CBPR ) approach , have targeted both physical activity and healthy eating , and have focused on structural changes in the church . PURPOSE To report the results of a group r and omized CBPR intervention targeting physical activity and healthy eating in African-American churches . DESIGN Group RCT . Data were collected from 2007 to 2011 . Statistical analyses were conducted in 2012 . SETTING / PARTICIPANTS Seventy-four African Method ist Episcopal ( AME ) churches in South Carolina and 1257 members within them participated in the study . INTERVENTION Churches were r and omized to an immediate ( intervention ) or delayed ( control ) 15-month intervention that targeted organizational and environmental changes consistent with the structural ecologic model . A CBPR approach guided intervention development . Intervention churches attended a full-day committee training and a full-day cook training . They also received a stipend and 15 months of mailings and technical assistance calls to support intervention implementation . MAIN OUTCOME MEASURES Primary outcomes were self-reported moderate- to vigorous-intensity physical activity ( MVPA ) , self-reported fruit and vegetable consumption , and measured blood pressure . Secondary outcomes were self-reported fat- and fiber-related behaviors . Measurements were taken at baseline and 15 months . Intent-to-treat repeated measures ANOVA tested group X time interactions , controlling for church clustering , wave , and size , and participant age , gender , and education . Post hoc ANCOVAs were conducted with measurement completers . RESULTS There was a significant effect favoring the intervention group in self-reported leisure-time MVPA ( d=0.18 , p=0.02 ) , but no effect for other outcomes . ANCOVA analyses showed an intervention effect for self-reported leisure-time MVPA ( d=0.17 , p=0.03 ) and self-reported fruit and vegetable consumption ( d=0.17 , p=0.03 ) . Trainings were evaluated very positively ( training evaluation item means of 4.2 - 4.8 on a 5-point scale ) . CONCLUSIONS This faith-based structural intervention using a CBPR framework showed small but significant increases in self-reported leisure-time MVPA . This program has potential for broad-based dissemination and reach . TRIAL REGISTRATION This study is registered at www . clinical trials.gov NCT00379925 |
10,965 | 27,829,443 | Conclusion Our meta- analysis suggests an association of the DRD2 gene and the risk for schizophrenia , given that TaqI and C957 T polymorphisms presented a protective effect against schizophrenia , and in the sub-analyses the C957 T variant increased the risk for this disorder in the Chinese population | Background The association between the dopamine D2 receptor ( DRD2 ) gene and schizophrenia has been studied though no conclusive outcomes have been attained .
The aim of this study was to perform a systematic review and meta- analysis to explore the relation between three polymorphisms of the DRD2 gene ( C957 T , TaqI and Ser311Cys ) and schizophrenia . | A functional polymorphism in the promoter region of the dopamine D2 receptor gene , the -141C Del allele , which may be associated with schizophrenia susceptibility , has previously been described in a Japanese sample . The present study was done in order to examine whether such an association would also be found in a North American schizophrenia patient population . However , analysis of the -141C Del allele frequency in the present group of schizophrenia patients ( n = 50 ) and control subjects ( n = 51 ) did not identify any significant differences . These data support the recent reports on German and British subjects that this genetic variation in the 5'-flanking region of the dopamine D2 receptor gene does not play a major role in the genetic predisposition to schizophrenia Previous studies have demonstrated that subjects with one or two A1 alleles of dopamine D2 receptor ( DRD2 ) polymorphism at the Taq1 A locus have lower DRD2 density than those with no A1 allele . The present study aim ed to examine whether the Taq1 A DRD2 genotypes are related to therapeutic response to nemonapride , a selective dopamine antagonist , in schizophrenic patients . The subjects were 25 acutely exacerbated schizophrenic in patients who had received no medication for at least 1 month before the study . The fixed dose ( 18 mg/day ) of nemonapride was administered to each patient for 3 weeks . The clinical status was prospect ively monitored by the Brief Psychiatric Rating Scale ( BPRS ) before , and 3 weeks after , the treatment . The Taq1 A genotypes ( A1 and A2 alleles ) were determined by the polymerase chain reaction method . Three patients were homozygous for the A1 allele , 11 were heterozygous for the A1 and A2 alleles , and 11 were homozygous for the A2 allele . The patients with one or two A1 alleles ( n = 14 ) showed significantly higher percentage improvement in total BPRS and positive symptoms than those with no A1 allele ( n = 11 ) after 3-week treatment while the percentage improvement in other subgrouped symptoms ( negative , anxiety-depression , excitement and cognitive symptoms ) was similar between the two genotype groups . The present results suggest that the Taq1 A DRD2 polymorphism is related to early therapeutic response to nemonapride in schizophrenic patients , possibly by modifying the efficiency of DRD2 antagonism of the drug in the central nervous system The relationship between Taq1 A polymorphism of dopamine D(2 ) receptor ( DRD(2 ) ) gene and extrapyramidal adverse effects of bromperidol and nemonapride , which are both antipsychotic drugs with selective and potent DRD(2 ) antagonistic property , was investigated in Japanese schizophrenic in patients . Twenty-seven patients were treated with bromperidol at 6 or 12 or 18 mg/day , while 25 patients were treated with nemonapride at 18 mg/day . The duration of treatment was 3 weeks . The A1 and A2 alleles were determined by PCR . The extrapyramidal adverse effects were assessed by the Udvalg for Kliniske Unders¿ogelser side effects rating scale . Six patients were homozygous for the A1 allele , 27 were heterozygous for the A1 and A2 alleles , and 19 were homozygous for the A2 allele . There were no significant differences in the incidences or severity of extrapyramidal adverse effects between the patients with one or two A1 alleles and those with no A1 allele . The present study suggests that Taq1 A polymorphism is not related to the development of extrapyramidal adverse effects during acute phase of bromperidol and nemonapride treatments Neuroleptic drugs have a high affinity for the dopamine D2 receptor ( DRD2 ) ; therefore DRD2 is thought to be a c and i date gene for schizophrenia . Arinami et al. have reported a positive association between schizophrenia and the Cys311 variant of the DRD2 gene . We determined the allele frequency of this polymorphism in 78 Okinawan schizophrenic patients and 112 control subjects . The patients and controls did not differ significantly in allele frequencies of Cys311 The result of most association studies and linkage analyses have suggested a negative association between schizophrenia and D2-like ( D2 , D3 , and D4 ) receptor polymorphisms . Although the polymorphisms of the D2-like receptor in themselves may not account for the etiology of schizophrenia , they can contribute to the severity of the symptoms . Thus , we studied the associations between the polymorphisms and their combinations , and the vulnerability of schizophrenics . Fragments of the D2-like receptor genes were amplified by means of the polymerase chain reaction , and the polymorphisms were identified by the restriction fragment length polymorphism and single-str and ed conformation polymorphism methods . There were no statistically significant differences in the polymorphisms and their combinations between schizophrenics and controls . Schizophrenics with D4E1(A1/A2 ) , which contains 2 and 1 t and em repeats of a 12-base-pair sequence in exon 1 , had a lower total positive symptom score before medication than schizophrenics with D4E1(A1/A1 ) . There was no association between the polymorphisms and negative symptoms |
10,966 | 9,718,245 | Due to their sophisticated design s , these studies probably provide the best evidence that placebo analgesia exists .
They also indicate that placebo analgesia is mediated by endogenous opiates . | null | null |
10,967 | 17,709,759 | In a series of univariate meta-regression sensitivity analyses , none of the covariates we examined ( duration of follow-up , primary vs. secondary prevention , ischemic cause , presence of cardiac resynchronization therapy , NYHA class , mean age , mean LVEF , or mean QRS duration ) contributed to the moderate statistical heterogeneity observed in our meta- analysis of all-cause mortality . | Left ventricular ( LV ) systolic dysfunction carries a high risk for sudden cardiac death ( 1 ) .
Implantable cardioverter defibrillators ( ICDs ) can potentially mitigate this risk by delivering rapid life-saving therapy and have been substantially refined since their initial development in the late 1970s ( 2 ) .
R and omized , controlled trials ( RCTs ) have tested the efficacy of ICDs in high-risk individuals .
We previously reported a systematic review of 8 RCTs ( 3 RCTs of secondary prevention in survivors of sudden cardiac death ; 5 RCTs of primary prevention in patients without a history of ventricular arrhythmias ) demonstrating a 26 % reduction in all-cause mortality and a 57 % reduction in sudden cardiac death with ICDs ( 3 ) .
Since then , additional RCTs of primary prevention have been published , and questions have arisen about the generalizability of the RCT results for ICDs to clinical practice .
In particular , it is uncertain whether the benefits of ICDs seen in the trials extend to nontrial population s and whether the risks associated with ICDs may be higher in clinical practice than reported in trials .
In addition , we exp and ed the review to include data from observational studies to determine the effectiveness ( that is , the risks and benefits of a therapy when tested under usual clinical practice conditions ) and safety of ICDs when used in clinical practice . | AIMS This multicentre prospect i ve r and omised trial was undertaken to evaluate the usefulness of an electrophysiological study (EPS)-guided/implantable cardioverter defibrillator ( ICD ) strategy in patients at high risk of sudden death ( SD ) early after myocardial infa rct ion ( MI ) . Previous studies have shown the benefits of such a strategy only in high-risk patients late after MI . METHODS AND RESULTS We enrolled 143 survivors of acute MI ( < 1 month ) with left ventricular ejection fraction < or = 35 % and either frequent ( > or = 10/h ) premature ventricular complexes ( PVCs ) , or depressed heart rate variability ( SDNN < 70 ms ) or abnormal signal-averaged ECG , who were able to tolerate optimised beta-blocker therapy ( 68 + /- 40 mg/day of metoprolol ) . Of these , 138 were r and omised , in a 2:3 ratio , to two therapeutic strategies : conventional ( CONV ) strategy ( n = 59 ) or EPS-guided/ICD strategy ( n = 79 ) . The latter result ed in ICD implantation in 24 inducible patients and in CONV therapy in the remaining 55 . During a mean follow-up of 540 + /- 378 days , 26 patients ( 19 % ) died : nine ( 6.5 % ) SD , nine ( 6.5 % ) non-SD , and four ( 3 % ) non-cardiac death ; in four patients ( 3 % ) the cause of death was unknown . The actuarial overall mortality for the CONV and EPS-guided/ICD arms was 18 % vs 14 % after 1 year and 29.5 % vs 20 % after 2 years , respectively ( P = 0.3 and 0.2 ) . CONCLUSIONS Despite optimal therapy , mortality remains significant in high-risk patients following MI . Although there is a trend in favour of EPS-guided/ICD , our data are insufficient to demonstrate a survival benefit of this strategy early after MI STUDY OBJECTIVES Pocket hematoma is a common complication after pacemaker or implantable cardioverter defibrillator ( ICD ) implantation . Thus , we investigated the influence of patient comorbidity , implantation strategy , operator experience , antiplatelet therapy , and anticoagulation therapy on hematoma rate . DESIGN Between 1990 and 2002 , a total of 3,164 devices ( pectoral pacemakers , 2,792 ; ICDs , 372 ) were implanted at our institution . Predictors of hematoma occurrence were determined prospect ively and were analyzed by multivariate regression analysis . Operator experience was grade d by individual implantation number , as follows : low , < 50 ; medium , 50 to 100 ; and high , > 100 . RESULTS The incidence of pocket hematoma was 4.9 % , leading to prolonged hospitalization in 2.0 % of all patients . Reoperation for pocket hematoma was required in 1.0 % of patients . High-dose heparinization ( hazard ratio [ HR ] , 4.2 ) , combined acetylsalicylic acid (ASA)/thienopyridine treatment after coronary stenting ( HR , 5.2 ) , and low operator experience ( HR , 1.6 ) were independently predictive of hematoma development . Therapy with ASA alone did not increase the hematoma rate compared to patients who did receive antiplatelet or anticoagulation therapy ( 3.1 % vs 2.5 % , respectively ; difference not significant ) . In patients with nonvalvular atrial fibrillation , postoperative high-dose heparinization substantially increased the hematoma rate ( 10.7 % vs 2.9 % , respectively ; p < 0.001 ) without reducing the rate of arterial embolism within the first month after implantation ( 0.18 % vs 0.21 % , respectively ; difference not significant ) . The infection rate ( 0.28 % within 3 months after implantation ) was not influenced by the presence of the pocket hematoma . CONCLUSIONS The use of high-dose heparinization and combined ASA/thienopyridine treatment are highly predictive for the occurrence of intraoperative bleeding and pocket hematoma in patients who have undergone pacemaker and ICD surgery . We propose recommendations for the management of antiplatelet and anticoagulation therapy in patients undergoing these interventions AIMS Electrical storm ( ES ) is a life-threatening arrhythmia complication affecting patients treated with an implantable cardioverter defibrillator ( ICD ) . Despite its increasing importance , existing data on prognosis and management of ICD patients affected by ES are limited and conflicting . METHODS We prospect ively studied 169 consecutive patients receiving an ICD . Thirty-two patients presented with at least one episode of ES during the period of observation ( 33+/-26 months ) . ES patients were older ( 64+/-9 vs. 59+/-13 years , P=0.013 ) with more advanced congestive heart failure ( CHF ) but a similar incidence of an underlying organic heart disease . RESULTS Long-term total and cardiac mortality were both increased among ES patients . Seventeen of the 32 ES patients died as opposed to 19 of the 137 ICD patients without ES ( 53 vs. 14 % , P<0.001 ) . In multivariate Cox regression analysis adjusted for the main confounders , history of ES was significantly and independently associated with total and cardiac mortality ( risk ratio (RR)=2.13 , P=0.031 and RR=2.59 , P=0.019 , respectively ) . CONCLUSION ES is a relatively frequent complication affecting ICD patients treated for secondary prevention of sudden cardiac death ( SCD ) . Although the acute management of this serious arrhythmia complication is usually successful , occurrence of ES is a strong independent predictor of poor outcome in ICD patients BACKGROUND Implantable cardioverter-defibrillators ( ICDs ) have been shown in primary prevention efficacy trials to reduce mortality in patients with ischemic heart disease and left ventricular dysfunction . To investigate the generalizabilty of this mortality reduction , we examined the effectiveness of ICDs in clinical practice . METHODS We developed a prospect i ve multicenter cohort of 770 patients with ischemic left ventricular dysfunction ( ejection fraction < or = 35 % ) and without a history of ventricular arrhythmia , of whom 395 ( 52 % ) received ICDs . Mean + /- SD follow-up was 27 + /- 12 months . We assessed the degree to which ICDs decreased mortality risk using Cox proportional hazards analyses that controlled for clinical predictors of death , receipt of ICD ( a propensity score analysis ) , and predictors of arrhythmic death ( including electrophysiologic variables ) . RESULTS Multivariate Cox analyses showed that those with ICDs had significantly lower all-cause mortality ( hazard ratio [ HR ] , 0.53 ; 95 % confidence interval [ CI ] , 0.33 - 0.86 ) . This mortality reduction was mediated through dramatically lower arrhythmia-related mortality ( HR , 0.35 ; 95 % CI , 0.17 - 0.73 ) , with no significant effect on cardiovascular nonarrhythmic ( HR , 0.81 ; 95 % CI , 0.34 - 1.96 ) and noncardiovascular ( HR , 0.76 ; 95 % CI , 0.29 - 2.05 ) mortality . No differences were found between the ICD and non-ICD groups for a composite outcome of all-cause mortality , appropriate ICD shocks , or documented symptomatic ventricular arrhythmia , which suggests that the 2 groups had similar baseline risk for life-threatening arrhythmic events ( HR , 0.96 ; 95 % CI , 0.63 - 1.45 ) . CONCLUSION In clinical practice , ICDs appear to reduce all-cause and arrhythmic rates of mortality at levels similar to those found in primary prevention trials Monitoring of atrial rhythm in patients implanted with ICDs may improve accuracy in identifying supraventricular arrhythmias and , therefore , prevent inappropriate therapies . Since difficulties were found in dual chamber ICDs with separate leads , a new design ed single lead dual chamber ICD system was tested . Twenty-five patients implanted with a Deikos A+ ( single coil defibrillation lead with two atrial sensing rings combined with a dual chamber ICD with a high amplifying atrial channel ) were tested . Atrial and ventricular signals were analyzed during sinus rhythm ( SR ) and sinus tachycardias ( STs ) , atrial flutter and AF , and VT or VF . Follow-ups were performed after 1 , 3 , 6 , 9 , and 12 months after implantation . Analysis of EGM amplitudes of stored episodes revealed that atrial signals during atrial flutter ( 2.1 + /- 0.51 mV ) were comparable to those of ST ( 2.2 + /- 0.5 mV ) . Atrial amplitudes during AF were significantly lower ( 0.81 + /- 0.5 mV , P<0.01 ) . During VF atrial " sinus " signals ( 2 + /- 0.8 mV ) were stable . Ventricular parameters did not differ from a st and ard ICD lead ; defibrillation threshold was 11.4 + /- 4.5 J ( 16 patients ) . During intraoperative and prehospital discharge measurements , 97.1 % of SR-P waves and 99.2 % of atrial flutter waves were detected correctly . In AF 91.11 % of atrial signals were detected . Analysis of 505 stored episodes showed that 96.8 % of ST and 100 % of atrial flutter and 100 % of AF episodes have been classified correctly and no underdetection of VT/VF was found . The first experiences with the new VDD-ICD system show an increase of the specificity to detect ventricular tachycardias to a level comparable to dual chamber ICDs with two leads . The reliability of this system has to be proven in a prospect i ve r and omized study OBJECTIVES The purpose of this multicenter r and omized trial was to compare total mortality during therapy with amiodarone or an implantable cardioverter-defibrillator ( ICD ) in patients with nonischemic dilated cardiomyopathy ( NIDCM ) and nonsustained ventricular tachycardia ( NSVT ) . BACKGROUND Whether an ICD reduces mortality more than amiodarone in patients with NIDCM and NSVT is unknown . METHODS One hundred three patients with NIDCM , left ventricular ejection fraction < or = 0.35 , and asymptomatic NSVT were r and omized to receive either amiodarone or an ICD . The primary end point was total mortality . Secondary end points included arrhythmia-free survival , quality of life , and costs . RESULTS The study was stopped when the prospect i ve stopping rule for futility was reached . The percent of patients surviving at one year ( 90 % vs. 96 % ) and three years ( 88 % vs. 87 % ) in the amiodarone and ICD groups , respectively , were not statistically different ( p = 0.8 ) . Quality of life was also similar with each therapy ( p = NS ) . There was a trend with amiodarone , as compared to the ICD , towards improved arrhythmia-free survival ( p = 0.1 ) and lower costs during the first year of therapy ( $ 8,879 US dollars vs. $ 22,039 US dollars , p = 0.1 ) . CONCLUSIONS Mortality and quality of life in patients with NIDCM and NSVT treated with amiodarone or an ICD are not statistically different . There is a trend towards a more beneficial cost profile and improved arrhythmia-free survival with amiodarone therapy Background — Delivery of inappropriate shocks caused by misdetection of supraventricular tachycardia ( SVT ) remains a substantial complication of implanted cardioverter/defibrillator ( ICD ) therapy . Whether use of optimally programmed dual-chamber ICDs lowers this risk compared with that in single-chamber ICDs is not clear . Methods and Results — Subjects with a clinical indication for ICD ( n=400 ) at 27 participating centers received dual-chamber ICDs and were r and omly assigned to strictly defined optimal single- or dual-chamber detection in a single-blind manner . Programming minimized ventricular pacing . The primary end point was the proportion of SVT episodes inappropriately detected from the time of programming until crossover or end of study . On a per-episode basis , 42 % of the episodes in the single-chamber arm and 69 % of the episodes in the dual-chamber arm were due to SVT . Mortality ( 3.5 % in both groups ) and early study withdrawal ( 14 % single-chamber , 11 % dual-chamber ) were similar in both groups . The rate of inappropriate detection of SVT was 39.5 % in the single-chamber detection arm compared with 30.9 % in the dual-chamber arm . The odds of inappropriate detection were decreased by almost half with the use of the dual-chamber detection enhancements ( odds ratio , 0.53 ; 95 % confidence interval , 0.30 to 0.94 ; P=0.03 ) . Conclusions — Dual-chamber ICDs , programmed to optimize detection enhancements and to minimize ventricular pacing , significantly decrease inappropriate detection BACKGROUND End-stage heart failure ( HF ) patients are at high risk of sudden cardiac death . This study evaluates the role of implantable cardiac defibrillators ( ICDs ) in HF patients awaiting cardiac transplantation . METHODS We identified 194 consecutive patients ( age 51 + /- 12 years ) with New York Heart Association Class 3 or 4 HF ( ejection fraction 22 + /- 9 % ) listed for cardiac transplantation , 35 of whom underwent ICD implantation . Of the implanted patients , 16 ( Group A ) had an established indication for ICD implantation ( cardiac arrest , n = 10 ; sustained ventricular tachycardia [ VT ] , n = 3 ; and positive electrophysiology study , n = 3 ) . Nineteen patients ( Group B ) underwent ICD implantation for non-established indications ( syncope with non-ischemic cardiomyopathy , n = 4 ; non-sustained VT , n = 15 ) . There were no procedural complications from ICD implantation . RESULTS During follow-up of 9.2 + /- 10.1 months , there were 3 deaths in the ICD groups ( A and B ) , and 40 in the control group ( 8.6 % vs 25.2 % , p = 0.032 ) . Five patients in Group A and 6 in Group B ( 31 % ) received appropriate ICD therapy . The number of therapies per patient and the time to the first shock were similar between Groups A and B. Four of 6 Group B patients on outpatient inotropic therapy ( 67 % ) received appropriate ICD therapy . CONCLUSIONS Selected end-stage heart failure patients awaiting heart transplantation , including those without established ICD indications , are at high risk for malignant arrhythmias and may benefit from ICD implantation . Patients with ICD seem to have improved survival compared to those without ICD . R and omized prospect i ve studies are needed to confirm these findings INTRODUCTION Supraventricular tachyarrhythmias are the main cause of inappropriate therapies in patients with conventional single chamber implantable cardioverter defibrillators ( VVI-ICD ) . It was anticipated that dual chamber cardioverter defibrillators ( DDD-ICD ) , with their capacity to analyze atrial and ventricular rhythm , could substantially reduce inappropriate therapies . METHODS AND RESULTS Our prospect i ve study included 92 patients ( 87 men ; mean age 61 + /- 12.7 years ) who were r and omly assigned to a VVI-ICD ( 45 patients ) or a DDD-ICD ( 47 patients ) . Both groups were followed for 7.5 + /- 3.5 and 7.6 + /- 4.1 months , respectively . During the follow-up period , overall 725 ventricular tachycardia (VT)/ventricular fibrillation ( VF ) episodes were recorded in 45 ( 49 % ) of 92 patients . Of these episodes , 404 ( 56 % ) occurred in the VVI-ICD group and 321 ( 44 % ) episodes occurred in the DDD-ICD group . Twenty-three ( 51 % ) patients in the VVI-ICD group and 22 ( 47 % ) patients in the DDD-ICD group ( P = 0.8 ) developed VT/VF . Overall , 73 ( 10 % ) of 725 treated episodes were inappropriate in 6 ( 13 % ) patients in the VVI group and in 10 ( 21 % ) patients in the DDD-ICD group ( P = 0.2 ) . There were 22 ( 31 % ) inappropriately treated episodes in the VVI-ICD group and 51 ( 69 % ) in the DDD-ICD group . Thirty-two of the 51 inappropriate episodes in the DDD-ICD patients result ed from intermittent atrial sensing problems that led to failure of the respective dual chamber algorithms . Nonfatal complications occurred in 6 ( 13 % ) patients in the VVI-ICD group and in 3 ( 6 % ) patients in the DDD-ICD group ( P = 0.7 ) . CONCLUSION We conclude that the implanted DDD-ICD and conventional VVI-ICD are equally safe and effective for therapy of life-threatening ventricular tachyarrhythmias . Although DDD-ICDs allow better rhythm classification , the applied detection algorithms do not offer benefits in avoiding inappropriate therapies during supraventricular tachyarrhythmias Background —Sudden Unexplained Death Syndrome ( SUDS ) is the leading cause of death in young , healthy , Southeast Asian men . The role of an implantable cardioverter defibrillator ( ICD ) for mortality reduction in these patients remains unclear . Methods and Results —The Defibrillator Versus & bgr;-Blockers for Unexplained Death in Thail and ( DEBUT ) study is a r and omized , clinical trial conducted in 2 phases ( pilot study followed by the main trial ) to compare the annual all-cause mortality rates among SUDS patients treated with & bgr;-blockers versus that among those treated with an ICD . A total of 86 patients who were SUDS survivors and probable SUDS survivors were r and omized to receive an ICD or propranolol ( 20 patients were in the pilot study and 66 were in the main trial ) . The primary end point was death from all causes . The secondary end point was recurrent ventricular tachycardia/ventricular fibrillation ( VF ) or cardiac arrest . During the 3-year follow-up period of the main trial , there were 4 deaths ; all occurred in the & bgr;-blocker group ( P = 0.02 ) . Seven subjects in the ICD arm had recurrent VF , and all were effectively treated by the ICD . On the basis of the main trial results , the Data Safety Monitoring Board stopped the study . In total ( both from the Pilot study and the main trial ) , there were 7 deaths ( 18 % ) in the & bgr;-blocker group and no deaths in the ICD group , but there were a total of 12 ICD patients receiving ICD discharges due to recurrent VF . Conclusions —ICD treatment provides full protection from death related to primary VF in a SUDS population and is superior to & bgr;-blockade treatment OBJECTIVES The purpose of this r and omized study was to investigate the performance of single- and dual-chamber tachyarrhythmia detection algorithms . BACKGROUND A proposed benefit of dual-chamber implantable cardioverter-defibrillators ( ICDs ) is improved specificity of tachyarrhythmia detection . METHODS All ICD c and i date s received a dual-chamber ICD and were r and omized to programmed single- or dual-chamber detection . Of 60 patients ( 47 male , age 58 + /- 14 years , left ventricular ejection fraction 30 % ) , 29 had single-chamber and 31 had dual-chamber setting s. The detection results were corrected for multiple episodes within a patient with the generalized estimating equations method . RESULTS A total of 653 spontaneous arrhythmia episodes ( 39 patients ) were classified by the investigators ; 391 episodes were ventricular tachyarrhythmia ( 32 patients ) . All episodes of ventricular tachyarrhythmias were appropriately detected in both setting s. In 25 patients , 262 episodes of atrial tachyarrhythmias were recorded . Detection was inappropriate for 109 atrial tachyarrhythmia episodes ( 42 % , 18 patients ) . Rejection of atrial tachyarrhythmias was not significantly different between both groups ( p = 0.55 ) . Episodes of atrial flutter/tachycardia were significantly more misclassified ( p = 0.001 ) . Overall , no significant difference in tachyarrhythmia detection ( atrial and ventricular ) between both setting s was demonstrated ( p = 0.77 ) . CONCLUSIONS The applied detection criteria in dual-chamber devices do not offer benefits in the rejection of atrial tachyarrhythmias . Discrimination of atrial tachyarrhythmias with a stable atrioventricular relationship remains a challenge BACKGROUND A newly developed classification system relates adverse events to the surgical procedure or the function of the implantable defibrillator . METHODS AND RESULTS Adverse events were monitored during prospect i ve clinical evaluation of the Medtronic model 7219 Jewel ICD and were classified according to the definitions of the ISO 14155 st and ard for device clinical trials into 3 groups : severe and mild device-related and severe non-device-related adverse events . In addition , events were related to the surgical procedure , treatment with the device , or cardiac function . Seven hundred seventy-eight patients were followed up for an average of 4.0 months after ICD implantation . In total , 356 adverse events were observed in 259 patients . At 1 , 3 , and 12 months after ICD implantation , 99 % , 98 % , and 97 % of the patients , respectively , survived ; 95 % , 93 % , and 92 % , respectively , were free of surgical reintervention ; and 79 % , 68 % , and 51 % , respectively , were free of any adverse event . Twenty patients died : 6 deaths were related to the surgical procedure , 12 deaths were considered unrelated to ICD treatment , and 2 patients died of an unknown cause . Of 111 nonlethal severe adverse device effects , 47 required surgical intervention , 19 times for correction of a dislodged lead . Inappropriate delivery of therapy was observed 128 times in 111 patients , and the events were typically resolved by reprogramming or drug adjustment . Nine of these required rehospitalization . CONCLUSIONS Approximately 50 % of patients experience an adverse event within the first year after ICD implantation . The observed adverse event rate depends on the definitions and the prospect i ve monitoring . The incidence of inappropriate therapy emphasizes the need for improved detection algorithms and for quality -of-life evaluations , especially when considering ICD treatment in high-risk but arrhythmia-free patients Although the total number of deaths attributed to cardiovascular disease has decreased during recent decades , an increase in the percentage of cardiac deaths occurring suddenly ( from 56 % in 1989 to 63 % in 1998 ) has actually result ed in an increase in the total number of sudden deaths in the United States.1 The problem of sudden death spans all racial and cultural groups and is equally important in men and women . It is now 40 years since continuous ECG monitoring revealed that ventricular tachycardia and ventricular fibrillation ( VT/VF ) are responsible for the majority of sudden deaths . Dissemination of this information result ed in a marked change in practice . Until the 1970s , physicians treated only symptomatic VTs . Therapeutic options were limited to a few antiarrhythmic drugs , administered empirically . With the advent of telemetric ECG monitoring and continuous ambulatory ( Holter ) ECG monitoring came the recognition that frequent and multiform ventricular ectopy often preceded episodes of VF in the acute phase of myocardial infa rct ion ( MI ) . Ventricular ectopy and nonsustained VT was documented 1 to 2 weeks after MI in many patients . The presence of frequent ventricular premature complexes and runs of nonsustained VT in patients with significant left ventricular dysfunction were then demonstrated to be an independent predictor of sudden cardiac death late after MI . This information then led to the practice of administering antiarrhythmic drugs to suppress ventricular ectopy under the presumption that suppression of asymptomatic ectopy would prevent sudden death . This fashion lasted almost 20 years , until the results of the Cardiac Arrhythmia Suppression Trial ( CAST ) trial demonstrated the harm caused by this approach.2 Thus , a sea change in the practice of cardiology had occurred , from treating only symptomatic patients to therapy aim ed at primary prevention of sudden death . The initial efforts using antiarrhythmic drugs failed to reduce mortality . While many physicians in the 1970s were administering prophylactic drugs to survivors of MI , Michel Mirowski was developing the implantable cardioverter-defibrillator ( ICD ) , introduced to clinical medicine in 1980.3 It took more than a decade before r and omized , controlled trials evaluating the ability of ICDs to reduce mortality in survivors of cardiac arrest or sustained VT appeared in print . These studies demonstrated the superiority of ICDs over amiodarone and other pharmacological agents for secondary prevention of sudden death in survivors of cardiac arrest.4–7 After publication of the secondary -prevention studies , 3 trials were published demonstrating that ICDs could reduce mortality in patients with chronic coronary disease CONTEXT Implantable cardioverter defibrillator ( ICD ) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias . Most currently implanted ICD devices provide dual-chamber pacing therapy . The most common comorbid cause for mortality in this population is congestive heart failure . OBJECTIVE To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with st and ard indications for ICD implantation but without indications for antibradycardia pacing . DESIGN The Dual Chamber and VVI Implantable Defibrillator ( DAVID ) Trial , a single-blind , parallel-group , r and omized clinical trial . SETTING AND PARTICIPANTS A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers . All patients had a left ventricular ejection fraction ( LVEF ) of 40 % or less , no indication for antibradycardia pacemaker therapy , and no persistent atrial arrhythmias . INTERVENTIONS All patients had an ICD with dual-chamber , rate-responsive pacing capability implanted . Patients were r and omly assigned to have the ICDs programmed to ventricular backup pacing at 40/min ( VVI-40 ; n = 256 ) or dual-chamber rate-responsive pacing at 70/min ( DDDR-70 ; n = 250 ) . Maximal tolerated medical therapy for left ventricular dysfunction , including angiotensin-converting enzyme inhibitors and beta-blockers , was prescribed to all patients . MAIN OUTCOME MEASURE Composite end point of time to death or first hospitalization for congestive heart failure . RESULTS One-year survival free of the composite end point was 83.9 % for patients treated with VVI-40 compared with 73.3 % for patients treated with DDDR-70 ( relative hazard , 1.61 ; 95 % confidence interval [ CI ] , 1.06 - 2.44 ) . The components of the composite end point , mortality of 6.5 % for VVI-40 vs 10.1 % for DDDR-70 ( relative hazard , 1.61 ; 95 % CI , 0.84 - 3.09 ) and hospitalization for congestive heart failure of 13.3 % for VVI-40 vs 22.6 % for DDDR-70 ( relative hazard , 1.54 ; 95 % CI , 0.97 - 2.46 ) , also trended in favor of VVI-40 programming . CONCLUSION For patients with st and ard indications for ICD therapy , no indication for cardiac pacing , and an LVEF of 40 % or less , dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure BACKGROUND The value of an implantable cardioverter defibrillator ( ICD ) for primary prevention in dilated cardiomyopathy ( DCM ) is unclear , as r and omized trials could not show a survival benefit compared to drug therapy . It has not been investigated if patients with a very poor left ventricular function ( LVEF ) could profit from an ICD . METHODS Consecutive patients with DCM who received an ICD between December 1996 and November 2003 were included in this analysis . Patients were divided in group A ( secondary prevention ) and group B ( primary prevention ) . Both groups were stratified in subgroups with left ventricular ejection fraction ( LVEF ) below and above 20 % . RESULTS Fifty eight patients were included ( male 50 , age 56.4+/-12.7 years ) . Follow-up was 34+/-19 months . There was no difference regarding death ( 18 % vs. 11 % ) , but significant differences ( p value < 0.05 ) regarding any adverse events ( 55 % vs. 22 % ) , any ICD intervention ( 48 % vs. 17 % ) and ICD interventions for life-threatening arrhythmias ( 27 % vs. 0 % ) between group A and B. LVEF was not predictive for events in group A , whereas in group B only patients with a LVEF < 20 % had events ( p value 0.02 ) . Over time there was an increase of the LVEF of more than 15 % determined by echocardiography in 36 % of patients , significantly more often in group B. CONCLUSIONS Indication for primary prevention with an ICD in DCM should be made with caution . Larger studies are needed to determine if patients with LVEF of < 20 % might benefit from an ICD Background — Patients with idiopathic dilated cardiomyopathy ( DCM ) and impaired left ventricular ejection fraction have an increased risk of dying suddenly . Methods and Results — Patients with recent onset of DCM ( ≤9 months ) and an ejection fraction ≤30 % were r and omly assigned to the implantation of an implantable cardioverter-defibrillator ( ICD ) or control . The primary end point of the trial was all-cause mortality at 1 year of follow-up . The trial was terminated after the inclusion of 104 patients because the all-cause mortality rate at 1 year did not reach the expected 30 % in the control group . In August 2000 , the vital status of all patients was up date d by contacting patients , relatives , or local registration offices . One hundred four patients were enrolled in the trial : Fifty were assigned to ICD therapy and 54 to the control group . Mean follow-up was 22.8±4.3 months , on the basis of investigators ’ follow-up . After 1 year , 6 patients were dead ( 4 in the ICD group and 2 in the control group ) . No sudden death occurred during the first and second years of follow-up . In August 2000 , after a mean follow-up of 5.5±2.2 years , 30 deaths had occurred ( 13 in the ICD group and 17 in the control group ) . Cumulative survival was not significantly different between the two groups ( 93 % and 80 % in the control group versus 92 % and 86 % in the ICD group after 2 and 4 years , respectively ) . Conclusions —This trial did not provide evidence in favor of prophylactic ICD implantation in patients with DCM of recent onset and impaired left ventricular ejection fraction BACKGROUND Patients surviving ventricular fibrillation ( VF ) or sustained ventricular tachycardia ( VT ) are at a high risk of death due to a recurrence of arrhythmia . The implantable cardioverter defibrillator ( ICD ) terminates VT or VF , but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone . METHODS AND RESULTS A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were r and omly assigned to treatment with the ICD or with amiodarone . The primary outcome measure was all-cause mortality , and the secondary outcome was arrhythmic death . A total of 328 patients were r and omized to receive an ICD . A thoracotomy was done in 33 , no ICD was implanted in 18 , and the rest had a nonthoracotomy ICD . All 331 patients r and omized to amiodarone received it initially . At 5 years , 85.4 % of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day , 28.1 % of ICD patients were also receiving amiodarone , and 21.4 % of amiodarone patients had received an ICD . A nonsignificant reduction in the risk of death was observed with the ICD , from 10.2 % per year to 8.3 % per year ( 19.7 % relative risk reduction ; 95 % confidence interval , -7.7 % to 40 % ; P=0.142 ) . A nonsignificant reduction in the risk of arrhythmic death was observed , from 4.5 % per year to 3.0 % per year ( 32.8 % relative risk reduction ; 95 % confidence interval , -7.2 % to 57.8 % ; P=0.094 ) . CONCLUSIONS A 20 % relative risk reduction occurred in all-cause mortality and a 33 % reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone ; this reduction did not reach statistical significance INTRODUCTION Biventricular cardiac pacemakers provide important hemodynamic benefit in selected patients with heart failure and severe left ventricular ( LV ) dysfunction . Nevertheless , these patients remain at high mortality risk . To address this issue , we examined mortality outcome in patients with heart failure treated with biventricular pacemakers alone and those treated with biventricular implantable cardioverter defibrillators ( ICDs ) . METHODS AND RESULTS The study population consisted of 126 consecutive patients with LV dysfunction and heart failure who received either a biventricular ICD ( n = 62 ) or a biventricular pacemaker ( n = 64 ) between January 1998 and December 2002 . A minimum 12 months of follow-up was obtained in all survivors . ICD indications were conventional in all patients . Kaplan-Meier actuarial method and log rank statistics were used to calculate and compare survival rates in both groups . Comparison of mortality rates utilized Chi-square test . The two groups had similar clinical and demographic features , LV ejection fraction , and medication use . Average follow-up times were 13 + /- 11.8 months ( range 4 - 60 ) and 18 + /- 13.2 months ( range 0.5 - 53 ) for biventricular ICD and pacemaker groups , respectively . Overall mortality rate was significantly lower in the biventricular ICD group ( 13 % , 8 deaths ) compared to the pacemaker group ( 41 % , 26 deaths ) ( P = 0.01 ) . Further , the predominant survival benefit for ICD-treated patients becomes evident after the first 12 months of follow-up . CONCLUSION The findings in this study , although necessarily limited in their interpretation by the absence of treatment r and omization , suggest that biventricular ICDs offer a survival benefit compared to biventricular pacing alone . Furthermore , this benefit may be most apparent if other clinical factors do not preclude patient survival > 1 year postimplant Background —The tachycardia detection interval ( TDI ) in implantable cardioverter/defibrillators ( ICDs ) is conventionally programmed according to the slowest documented ventricular tachycardia ( VT ) , with a safety margin of 30 to 60 ms . With this margin , VTs above the TDI may occur . However , longer TDIs are associated with an increased risk of inappropriate therapy . We hypothesized that patients with slow VTs ( < 200 bpm ) may benefit from a long TDI and a dual-chamber detection algorithm compared with a conventionally programmed single-chamber ICD . Methods and Results — Patients with VTs < 200 bpm were implanted with a dual-chamber ICD that was r and omly programmed to a dual-chamber algorithm and a TDI of ≥469 ms or to a single-chamber algorithm with a TDI 30 to 60 ms above the slowest documented VT cycle length and the enhancement criteria of cycle length variation and acceleration . The primary combined end point was the number of all inappropriate therapies , VTs above the TDI , and VTs with significant therapy delay ( > 2 minutes ) . After 6 months , a crossover analysis was performed . Total follow-up was 1 year . One hundred two patients were included in the study . The programmed TDI was 500±36 ms during the dual-chamber phase and 424±63 ms during the single-chamber phase . For the primary end point ( inappropriate therapies , VTs above the TDI , or VTs with detection delay ) , a moderate superiority of the dual-chamber mode was found : Mann-Whitney estimator=0.6661 ; 95 % CI , 0.5565 to 0.7758 ; P=0.0040 . Conclusions —Dual-chamber detection with a longer TDI improves VT detection and does not increase the rate of inappropriate therapies despite a considerable increase in tachycardia burden Background —The implantable cardioverter defibrillator ( ICD ) is superior to amiodarone for secondary prophylaxis of sudden cardiac death . However , the magnitude of this benefit over long-term follow-up is not known . Thus , our objective was to evaluate the long-term consequences of using amiodarone versus an ICD as first-line monotherapy in patients with a prior history of sustained ventricular tachycardia/ventricular fibrillation or cardiac arrest . Methods and Results —A total of 120 patients were enrolled at St Michael ’s Hospital in the Canadian Implantable Defibrillator Study ( CIDS ) and were r and omly assigned to receive either amiodarone ( n=60 ) or an ICD ( n=60 ) . The treatment strategy was not altered after the end of CIDS unless the initial assigned therapy was not effective or was associated with serious side effects . After a mean follow-up of 5.6±2.6 years , there were 28 deaths ( 47 % ) in the amiodarone group , compared with 16 deaths ( 27 % ) in the ICD group ( P = 0.0213 ) . Total mortality was 5.5 % per year in the amiodarone group versus 2.8 % per year in the ICD group ( hazard ratio of amiodarone : ICD , 2.011 ; 95 % confidence interval , 1.087 to 3.721 ; P = 0.0261 ) . In the amiodarone group , 49 patients ( 82 % of all patients ) had side effects related to amiodarone , of which 30 patients ( 50 % of all patients ) required discontinuation or dose reduction ; 19 patients crossed over to ICD because of amiodarone failure ( n=7 ) or side effects ( n=12 ) . Conclusions —In a subset of CIDS , the benefit of the ICD over amiodarone increases with time ; most amiodarone-treated patients eventually develop side effects , have arrhythmia recurrences , or die PURPOSE Clinical trials with the implantable cardioverter defibrillator ( ICD ) have demonstrated desirable outcomes in terms of mortality and morbidity among patients with potentially lethal arrhythmias . This study examined the " resilience factors " of positive health expectations and global optimism prospect ively using the general quality -of-life ( QOL ) scores of newly implanted ICD patients . METHODS The study enrolled 88 newly implanted ICD patients ( mean age , 65.3 + /- 13.2 years ; 83 % male ; 92 % white ) assessed 8 and 14 months after ICD implantation . A series of 2 x 2 factorial multivariate analyses of covariance were performed to examine the differences between baseline low versus high positive health expectations and baseline low versus high optimism in short- and long-term general QOL scores . RESULTS After control was used for ejection fraction ( mean , 31 % ) , the patients with baseline high positive health expectations reported better general health at a long-term follow-up assessment ( P = .002 ) . The patients with high optimism reported better mental health and social functioning at a short-term follow-up assessment ( P = . 056 ) , and this finding approached significance at a long-term follow-up assessment ( P = .061 ) . CONCLUSIONS Positive health expectations and optimism are differentially related to various components of QOL . Collectively , these two resilience factors may be targeted in future studies of interventions to improve QOL for ICD patients 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 Patients with coronary heart disease , left ventricular dysfunction , and abnormalities on signal-averaged electrocardiograms have an increased risk sudden death . We evaluated the effect on survival of the prophylactic implantation of cardioverter-defibrillators in such patients at the time of coronary-artery bypass surgery . METHODS Over the course of five years , 37 clinical centers screened all patients who were scheduled for elective coronary bypass surgery . Patients were eligible for the trial if they were less than 80 years old , had a left ventricular ejection fraction of less than 0.36 , and had abnormalities on signal-averaged electrocardiograms . We identified 1422 eligible patients , enrolled 1055 , and r and omly assigned 900 to therapy with an implantable cardioverter-defibrillator ( 446 patients ) or to the control group ( 454 patients ) . The primary end point of the study was overall mortality , and the two groups were compared in an intention-to-treat analysis . RESULTS The base-line characteristics of the two groups were similar . During an average follow-up of 32+/-16 months , there were 101 deaths in the defibrillator group ( 71 from cardiac causes ) and 95 in the control group ( 72 from cardiac causes ) . The hazard ratio for death from any cause was 1.07 ( 95 percent confidence interval , 0.81 to 1.42 ; P=0.64 ) . There was no statistically significant interaction between defibrillator therapy and any of 10 preselected base-line covariates . CONCLUSIONS We found no evidence of improved survival among patients with coronary heart disease , a depressed left ventricular ejection fraction , and an abnormal signal-averaged electrocardiogram in whom a defibrillator was implanted prophylactically at the time of elective coronary bypass surgery This article addresses the feasibility and safety of ICD therapy in patients > 80 years of age . Recent trials have exp and ed the indication for ICD implantation to include an increasing number and variety of patients . The feasibility of ICD implantation in elderly patients has not been adequately studied . A prospect ively collected single center ICD data base was analyzed to assess the safety and feasibility of ICD implantation in elderly patients . Patients were divided based on age into two groups ( group 1 : 70 - 79 years of age , n = 183 ; group 2 : > or=80 years of age , n = 29 ) . The two groups were similar in gender distribution , NYHA class , and indication for implantation . The actuarial survival was not significantly different between groups 1 and 2 ( P > 0.05 ; primary endpoint ) , with a 1-year survival of 91 % and 93 % in groups 1 and 2 , respectively , ( P = NS ) . The complication rates at the time of ICD implantation were similar in groups 1 and 2 ( 6.6 % and 13.1 % , respectively , P = 0.16 ) . Age alone may not be sufficient criteria to exclude ICD implantation . The current consensus guidelines for ICD implantation appear to be generalizable to treating octogenarians who are otherwise medically fit OBJECTIVES The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator ( ICD ) , to discriminate ventricular tachycardia from supraventricular tachycardia . BACKGROUND ICDs are highly effective in treating ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) . However , they frequently deliver inappropriate therapy during supraventricular tachycardia ( SVT ) . METHODS We conducted a r and omized clinical trial of detection enhancements in a dual-chamber ICD compared to control ( rate-only ) detection to discriminate VT from SVT . Detection enhancements included a specific st and ardized protocol identical for all patients for programming rate stability , sudden onset , atrial-to-ventricular relationship ( sudden onset = 9 % and rate stability = 10 ms ; V > A " on " ) , and " sustained rate duration " ( 3 minutes ) . The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee . RESULTS One hundred forty-nine patients had a history of sustained VT or VF . Mean age ( + /- SD ) was 60 + /- 13 years ; 83 % were male , and mean ejection fraction was 35 + /- 15 % . Control ( n = 70 ) and " enhanced " ( n = 79 ) groups did not differ with regard to age , sex , ejection fraction , or primary arrhythmia . The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group ( hazard ratio = 0.47 , P = .011 ) . High-energy shocks were reduced from 0.58 + /- 4.23 shocks/patient/month in the control group to 0.04 + /- 0.15 shocks/patient/month in the enhanced group ( P = .0425 ) . No patient programmed per protocol failed to receive therapy for VT detected by the ICD ( 422 VT episodes ) . CONCLUSIONS St and ardized programming in a dual-chamber ICD leads to a significant and clinical ly important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT INTRODUCTION Recent trials have demonstrated benefit of prophylactic defibrillator ( ICD ) implantation compared to conventional treatment in high-risk patients . However , many patients have rare or no sustained arrhythmias following implantation . Our study addresses the question , whether patients with prophylactic defibrillator implantation have a lower risk for life-threatening ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) compared to sudden cardiac death ( SCD ) survivors . METHODS AND RESULTS Over 7 years we enrolled 245 patients . Occurrence of spontaneous sustained VT/VF result ing in adequate ICD treatment was the endpoint . Incidence , type , and treatment of sustained arrhythmia in 43 previously asymptomatic ICD recipients ( group B ) were compared to data of 202 survivors of imminent SCD ( group A ) . All patients had severely impaired left ventricular ejection fraction ( < 45 % ) . Group B patients had long runs ( > 6 cycles , < 30 s ) of VT during Holter monitoring and inducible sustained arrhythmia . Incidence of rapid VT and VF ( cycle length < 240 ms/heart rate > 250 bpm ) after 4 years ( 35 % in both groups , P = ns ) and adequate defibrillator therapies ( 57 % vs 55 % , P = ns ) were similar in both groups after univariate and multivariate analysis . Cumulative mortality tended to be lower in group B compared to group A , but the difference was not statistically significant . CONCLUSION During long-term follow-up , incidence of sustained rapid ventricular arrhythmia in prophylactically treated patients is as high as that of SCD survivors . Benefit from defibrillator implantation for primary prevention ( group B ) appears to be comparable to that for survived cardiac arrest ( group A ) BACKGROUND Empirical antiarrhythmic therapy has not reduced mortality among patients with coronary artery disease and asymptomatic ventricular arrhythmias . Previous studies have suggested that antiarrhythmic therapy guided by electrophysiologic testing might reduce the risk of sudden death . METHODS We conducted a r and omized , controlled trial to test the hypothesis that electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease , a left ventricular ejection fraction of 40 percent or less , and asymptomatic , unsustained ventricular tachycardia . Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were r and omly assigned to receive either antiarrhythmic therapy , including drugs and implantable defibrillators , as indicated by the results of electrophysiologic testing , or no antiarrhythmic therapy . Angiotensin-converting-enzyme inhibitors and beta-adrenergic-blocking agents were administered if the patients could tolerate them . RESULTS A total of 704 patients with inducible , sustained ventricular tachyarrhythmias were r and omly assigned to treatment groups . Five-year Kaplan-Meier estimates of the incidence of the primary end point of cardiac arrest or death from arrhythmia were 25 percent among those receiving electrophysiologically guided therapy and 32 percent among the patients assigned to no antiarrhythmic therapy ( relative risk , 0.73 ; 95 percent confidence interval , 0.53 to 0.99 ) , representing a reduction in risk of 27 percent ) . The five-year estimates of overall mortality were 42 percent and 48 percent , respectively ( relative risk , 0.80 ; 95 percent confidence interval , 0.64 to 1.01 ) . The risk of cardiac arrest or death from arrhythmia among the patients who received treatment with defibrillators was significantly lower than that among the patients discharged without receiving defibrillator treatment ( relative risk , 0.24 ; 95 percent confidence interval , 0.13 to 0.45 ; P<0.001 ) . Neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to electrophysiologically guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy . CONCLUSIONS Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators , but not with antiarrhythmic drugs , reduces the risk of sudden death in high-risk patients with coronary disease BACKGROUND Patients with advanced heart disease are at risk from sudden death ; however , benefit from implantable cardioverter defibrillators ( ICDs ) may be limited as a result of early mortality from other causes . The objective of this study was to develop a model to predict mortality within the first year after ICD implantation . METHODS AND RESULTS A retrospective analysis was performed of 469 consecutive patients who underwent ICD implantation at a single tertiary-care center from 1999 to 2002 . Vital status was determined from the Social Security Death Index . Patients were r and omized into prediction and validation cohorts . A risk score was derived from the prediction cohort by multivariate logistic regression and applied to the validation cohort . One point was assigned for each variable in the risk score ( age > 80 years , history of atrial fibrillation , creatinine > 1.8 mg/dL , New York Heart Association class III or IV ) . One-year mortality significantly increased with increasing risk score in both the prediction and validation cohorts . Validation cohort mortality was 3.4 % for 0 points , 4.3 % for 1 point , 17 % for 2 points , and 33 % for > or = 3 points ( P for trend < .0001 ) . A risk score > or = 2 predicted a 1-year mortality rate of 21 % , whereas a risk score < 2 predicted a mortality rate of 4 % at 1 year ( P < .0001 ) . CONCLUSION A risk score using simple clinical criteria may identify patients at high risk of early mortality after ICD implantation . This may be helpful in consideration of ICD risk/benefit for individual patients . Further studies conducted in a prospect i ve manner using these clinical criteria are warranted AIMS Identification of risk factors for ventricular tachycardia/ventricular fibrillation ( VT/VF ) occurrence in patients with implantable cardioverter-defibrillators ( ICD ) is reasonable , because ICD patients with multiple risk factors might benefit from more aggressive anti-arrhythmic therapy for the prevention of arrhythmic events . Furthermore , in the era of prophylactic ICD therapy and limited healthcare re sources , additional markers are needed for improved patient selection . METHODS AND RESULTS Thus , in Prospect i ve Analysis of Risk Factor for Appropriate ICD Therapy ( PROFIT ) , we prospect ively analyzed the role of ejection fraction ( EF ) , N-terminal probrain natriuretic peptide ( NT-proBNP ) , New York Heart Association ( NYHA ) class , atrial fibrillation , and QRS- duration as independent predictors for VT/VF occurrence in 250 ICD patients . Kaplan-Meier analysis showed that EF<40 % ( log-rank P=0.001 ) , NT-proBNP levels higher than median ( > or=405 ng/L ; log-rank P=0.04 ) , QRS- duration > or=150 ms ( log-rank P=0.016 ) , permanent atrial fibrillation ( log-rank P=0.008 ) , and higher NYHA class ( log-rank P=0.029 ) were associated with VT/VF occurrence . By multivariate Cox regression analysis EF , QRS- duration and atrial fibrillation remained significantly associated with appropriate VT/VF therapy , whereas there was no relationship among NT-proBNP , NYHA class , and VT/VF occurrence . Stratifying patients according to the number of their independent risk factors ( EF<40 % , AF , QRS-width > or=150 ms ) showed that patients with greater than or equal to two risk factors had a 100 % 2-year risk of VT/VF occurrence , whereas patients with no or one risk factor had a 19.3 and 25 % 2-year risk , respectively . CONCLUSIONS EF<40 % , permanent atrial fibrillation , and QRS > or=150 ms are independent predictors for VT/VF occurrence in predominantly secondary prophylactic ICD patients . Combining all independent predictors , we developed a risk score for VT/VF occurrence identifying a subgroup of patients with two or more risk factors who had a 100 % 2-year risk . Future studies will reveal if this risk score helps to identify ICD patients suitable for empirical anti-arrhythmic therapy and to improve patient selection for prophylactic ICD therapy BACKGROUND The primary aim of this study was to compare quality -of-life outcome between patients r and omized to implantable cardioverter defibrillator ( ICD ) therapy and patients r and omized to amiodarone treatment in the Canadian Implantable Defibrillator Study ( CIDS ) . A secondary aim was to evaluate the effects on quality -of-life outcomes of receiving shocks from the device . METHODS Quality of life was assessed in 317 English-speaking participants by use of the R and Corporation 's 38-item Mental Health Inventory ( MHI ) and the Nottingham Health Profile ( NHP ) . Assessment s were done in the hospital at baseline and with mailed question naires after 2 , 6 , and 12 months of follow-up . Sixty-two percent of patients completed the follow-up assessment s at 6 and 12 months . RESULTS Repeated measures analysis of variance revealed significant time by treatment group interaction effect on total MHI and the psychological distress and psychological well-being sub-scales , and on 5 of the 7 NHP scales ( energy , physical mobility , emotional reactions , sleep disturbance , and lifestyle impairment ) ( P < .05 ) . Emotional and physical health scores were shown to improve significantly in the ICD group and were either unchanged ( emotional health ) or deteriorated ( energy and physical mobility ) in the amiodarone-treated group by means of post-hoc comparisons . Quality of life did not improve in the subgroup of patients in the ICD-treated group who received > or = 5 shocks from their device . CONCLUSION Quality of life is better with ICD therapy than with amiodarone therapy . The beneficial quality -of-life effects from an ICD are not evident in patients who receive numerous shocks from their device Various techniques are used to establish defibrillation efficacy and to evaluate defibrillation safety margins in patients with an ICD . In daily practice a safety margin of 10 J is generally accepted . However , this is based on old clinical data and there are no data on safety margins using current ICD technology with unipolar , active pectoral defibrillators . Therefore , a r and omized study was performed to test if the likelihood of successful defibrillation at defibrillation energy requirement ( DER ) + 5 J and + 10 J is equivalent . Ninety-six patients ( 86 men ; age 61.0 + /- 10.3 years ; ejection fraction 0.341 + /- 0.132 ; coronary artery disease [ n = 65 ] , dilated cardiomyopathy [ n = 18 ] , other [ n = 13 ] ) underwent implantation of an active pectoral ICD system with unidirectional current pathway and a truncated , fixed tilt biphasic shock waveform . The defibrillation energy requirement ( DER ) was determined with the use of a step-down protocol ( delivered energy 15 , 10 , 8 , 6 , 4 , 3 , 2 J ) . The patients were then r and omized to three inductions of ventricular fibrillation at implantation and three at predischarge testing with shock strengths programmed to DER + 5 J at implantation and + 10 J at predischarge testing or vice versa . The mean DER in the total study population was 7.88 + /- 2.96 J. The number of defibrillation attempts was 288 for + 5 J and 288 for + 10 J. The rate of successful defibrillation was 94.1 % ( DER + 5 J ) and 98.9 % ( DER + 10 J ; P < 0.01 for equivalence ) . Charge times for DER + 5 J were significantly shorter than for DER + 10 J ( 3.65 + /- 1.14 vs 5.45 + /- 1.47 s ; P < 0.001 ) . A defibrillation safety margin of DER + 5 J is associated with a defibrillation probability equal to the st and ard DER + 10 J. In patients in whom short charge times are critical for avoidance of syncope , a safety margin of DER + 5 J seems clinical ly safe for programming of the first shock energy OBJECTIVES We sought to evaluate the cost implication s of the implantable cardioverter-defibrillator ( ICD ) , using utilization , cost , and survival data from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II . BACKGROUND This trial showed that prophylactic implantation of a defibrillator reduces the rate of mortality in patients who experienced a previous myocardial infa rct ion and low left ventricular ejection fraction . Given the size of the eligible population , the cost effectiveness of the ICD has substantial implication s. METHODS Our research comprises the cost-effectiveness component of the r and omized controlled trial , MADIT-II , based on utilization , cost , and survival information from 1,095 U.S. patients who were assigned r and omly to receive an ICD or conventional medical care . Utilization data were converted to costs using a variety of national and hospital-specific data . The incremental cost-effectiveness ratio ( iCER ) was calculated as the difference in discounted costs divided by the difference in discounted life expectancy within 3.5 years . Secondary analyses included projections of survival ( using three alternative assumptions ) , corresponding cost assumptions , and the result ing cost-effectiveness ratios until 12 years after r and omization . RESULTS During the 3.5-year period of the study , the average survival gain for the defibrillator arm was 0.167 years ( 2 months ) , the additional costs were 39,200 dollars , and the iCER was 235,000 dollars per year-of-life saved . In three alternative projections to 12 years , this ratio ranged from 78,600 dollars to 114,000 dollars . CONCLUSIONS The estimated cost per life-year saved by the ICD in the MADIT-II study is relatively high at 3.5 years but is projected to be substantially lower over the course of longer time horizons In patients with chronic heart failure and reduced systolic function , an implantable cardioverter-defibrillator ( ICD ) improves the prognosis , but morbidity and mortality remain high . We attempted to identify the prognostic impact of Doppler echocardiography and QRS duration in such patients . We prospect ively enrolled 84 patients with chronic heart failure , an ICD , and impaired systolic function ( mean ejection fraction 29 + /- 10 % ) . Echocardiographic measurements included left ventricular dimensions/volumes , ejection fraction , mitral E/A ratio , deceleration time , and tissue Doppler analysis of mitral annular velocities ( S ' , E ' , A ' ) . A cardiac event ( death from pump failure or appropriate ICD therapy , i.e. , antitachycardia pacing/shock due to sustained ventricular tachycardia or ventricular fibrillation ) was defined as the study end point . During a follow-up of 373 + /- 254 days , 22 patients ( 26 % ) had an event ( death from pump failure , n = 7 ; patients who received an appropriate ICD therapy , n = 16 ) . In patients with an event , the QRS duration was longer ( 169 + /- 41 vs 146 + /- 37 ms , p = 0.023 ) , the mitral E/E ' ratio was higher ( 16.0 + /- 6.5 vs 12.8 + /- 5.9 , p = 0.044 ) , and a restrictive filling pattern was more frequent ( 44 % vs 9 % , p = 0.017 ) . Stepwise multivariate Cox regression analysis identified a restrictive filling pattern as the only independent predictor of an event ( hazard ratio 3.65 , 95 % confidence interval 1.54 to 8.64 , p = 0.003 ) . For patients with a restrictive filling pattern , the outcome was markedly poorer than that for patients with a nonrestrictive pattern ( event-free survival rate 38 % vs 72 % , p = 0.005 ) . In conclusion , in patients with chronic heart failure , an ICD , and systolic dysfunction , a restrictive filling pattern is an independent predictor of adverse cardiac events CONTEXT Clinical studies of omega-3 polyunsaturated fatty acids ( PUFAs ) have shown a reduction in sudden cardiac death , suggesting that omega-3 PUFAs may have antiarrhythmic effects . OBJECTIVE To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) . DESIGN AND SETTING R and omized , double-blind , placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003 . PATIENTS Two hundred patients with an implantable cardioverter defibrillator ( ICD ) and a recent episode of sustained VT or VF . INTERVENTION Patients were r and omly assigned to receive fish oil , 1.8 g/d , 72 % omega-3 PUFAs , or placebo and were followed up for a median of 718 days ( range , 20 - 828 days ) . MAIN OUTCOME MEASURES Time to first episode of ICD treatment for VT/VF , changes in red blood cell concentrations of omega-3 PUFAs , frequency of recurrent VT/VF events , and predetermined subgroup analyses . RESULTS Patients r and omized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7 % to 8.3 % ( P<.001 ) , with no change observed in patients receiving placebo . At 6 , 12 , and 24 months , 46 % ( SE , 5 % ) , 51 % ( 5 % ) , and 65 % ( 5 % ) of patients r and omized to receive fish oil had ICD therapy for VT/VF compared with 36 % ( 5 % ) , 41 % ( 5 % ) , and 59 % ( 5 % ) for patients r and omized to receive placebo ( P = .19 ) . In the subset of 133 patients whose qualifying arrhythmia was VT , 61 % ( SE , 6 % ) , 66 % ( 6 % ) , and 79 % ( 6 % ) of patients in the fish oil group had VT/VF at 6 , 12 , and 24 months compared with 37 % ( 6 % ) , 43 % ( 6 % ) , and 65 % ( 6 % ) of patients in the control group ( P = .007 ) . Recurrent VT/VF events were more common in patients r and omized to receive fish oil ( P<.001 ) . CONCLUSION Among patients with a recent episode of sustained ventricular arrhythmia and an ICD , fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients OBJECTIVES We sought to compare the long-term survival rates of patients with sustained ventricular tachyarrhythmia after myocardial infa rct ion ( MI ) who were treated according to the results of electrophysiological ( EP ) study either with amiodarone or an implantable cardioverter-defibrillator ( ICD ) . BACKGROUND Patients with sustained ventricular tachyarrhythmias after MI are at high risk of sudden cardiac death ( SCD ) . However , data comparing the long-term survival rates of patients treated with amiodarone or ICD , according to the results of EP testing , are lacking . METHODS Patients underwent a first EP study at baseline and a second one after a loading dose of amiodarone of 14 + /- 2.9 g. According to the results of the second EP study , patients were classified either as responders or non-responders to amiodarone ; non-responders were eventually treated with an ICD . RESULTS Eighty-four consecutive patients with MI ( 78 men ; 21 - 77 years old ; mean left ventricular ( LV ) ejection fraction 36 + /- 11 % ) were consecutively included . Forty-three patients ( 51 % ) were responders , and 41 patients ( 49 % ) were non-responders to amiodarone therapy . During a mean follow-up period of 63 + /- 30 months , SCD and total mortality rates were significantly higher in the amiodarone-treated patients ( p = 0.03 and 0.02 , respectively ) . CONCLUSIONS The long-term survival of patients with sustained ventricular tachyarrhythmias after MI , with depressed LV function , is significantly better with an ICD than with amiodarone therapy , even when stratified according to the results of the EP study . These patients should benefit from early ICD placement , and any previous amiodarone treatment seems to have no additional value INTRODUCTION A major drawback of therapy with an implantable defibrillator is the nonspecificity of detection . Theoretically , adding atrial sensing information to a decision algorithm could improve specificity of detection . METHODS AND RESULTS This open-label nonr and omized study compares the detection algorithm of the Ventak AV and the Ventak Mini implantable defibrillators . The Ventak AV ( n = 39 ) uses dual chamber detection as opposed to single chamber detection ( with rate stability ) in the Ventak Mini ( n = 55 ) . Programmed zone configurations , rate thresholds , and stability criteria were identical in all patients . In the Ventak AV group , 235 ventricular tachyarrhythmias were adequately detected and treated by the device . In the Mini group , 699 episodes of ventricular fibrillation/tachycardia occurred . All but six of the latter episodes were correctly identified and treated : one patient with incessant ventricular tachycardia had five episodes not terminated by the device , another episode occurred in a patient with a device/lead defect . In the Ventak AV group , 33 episodes of sinus tachycardia and 166 episodes of atrial fibrillation/flutter activated the device ; inappropriate therapy was applied to 41 % of atrial fibrillation/flutter episodes . In the Ventak Mini group , 226 supraventricular tachyarrhythmias activated the device , eight of which were sinus tachycardia and 218 were atrial fibrillation or flutter ; of the atrial fibrillation/ flutter episodes 24 % were treated inappropriately ( fewer vs Ventak AV , P < 0.001 ) . CONCLUSION The new detection algorithm incorporated in the Ventak AV did not inadvertently withhold therapy for ventricular tachyarrhythmias , but at the same time the number of inappropriate therapies for atrial fibrillation was not decreased in comparison to a single chamber device INTRODUCTION Defibrillation testing of the implantable cardioverter-defibrillator ( ICD ) is considered a st and ard and required practice at the time of implantation . How much testing , if any in some cases , should be performed , however , remains unknown . METHODS AND RESULTS Included in this retrospective analysis were 835 patients ( 77 % men ; age 65 + /- 13 years ) who received transvenous ICDs between January 1996 and December 2003 . One hundred twenty-nine ( 15.5 % ) had intraoperative defibrillation threshold ( DFT ) testing , 503 ( 60.2 % ) had limited defibrillation safety margin testing , and 203 ( 24.3 % ) had no defibrillation testing . We compared the outcome ( success of ICD therapies against spontaneous VT/VF events and survival ) of the three groups of patients , who in some respects had important clinical differences . The success of the first delivered shocks against VT/VF was similar for DFT ( 91 % ) , safety margin testing ( 91 % ) , and no-testing ( 92 % ) groups ; and the second shocks terminated the remaining episodes in all three groups . Sudden-death-free survival rates were similar in the three groups , however , the overall long-term survival rate was significantly lower in the no-testing group ( 58 % ) than in the DFT ( 74 % ) and safety margin testing ( 69 % ) groups ( P < 0.0005 ) . Multivariate analysis found no strong predictors of sudden death , but there were several independent predictors of overall mortality including lack of ICD testing ( HR : 2.031 , CI : 1.253 - 3.290 , P = 0.004 ) . CONCLUSION In this select patient cohort , success of ICD therapies and sudden-death-free survival were similar in patients who had DFT , safety margin testing , and no testing , but overall survival was significantly lower in the no-testing group . Thus in the absence of prospect i ve mortality data , a minimum of safety margin ICD testing should remain st and ard practice The DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) was a multi-center , r and omized , investigator-initiated trial . Patients enrolled in the trial had non-ischemic cardiomyopathy ( LVEF < or=35 % ) , a history of symptomatic heart failure and spontaneous arrhythmia ( > 10 PVCs/hr or non-sustained ventricular tachycardia defined as 3 to 15 beats at a rate of > 120 bpm ) on Holter monitor or telemetry within the past 6 months . All patients received st and ard oral medical therapy for heart failure including angiotensin converting enzyme inhibitors and beta-blockers . Patients were r and omized to implantable cardioverter defibrillator ( ICD ) versus no ICD . Patients were followed for 2 to 3 years . The primary endpoint was total mortality . Quality of life and pharmacoeconomics analysis was also performed . A registry tracked patients who met basic inclusion criteria but were not r and omized . We estimated an annual total mortality of 15 % at 2 years in the treatment arm that did not receive an ICD . The ICD was expected to reduce mortality by 50 % . Approximately 229 patients were required in each treatment group . Forty-five centers were included in this trial that was design ed to last an estimated 4 years . Enrollment was projected to occur over 2 1/2 years with a post enrollment follow-up of 1 1/2 years BACKGROUND Although more than 150,000 implantable cardioverter defibrillators ( ICDs ) are implanted yearly worldwide , only few studies systematic ally examined complications of ICD therapy in large patient cohorts . METHODS We prospect ively analyzed ICD-related complications in 440 consecutive patients who underwent first implantation of an ICD system for primary or secondary prevention of sudden cardiac death within the last 10 years at our institution . All study patients received pectoral nonthoracotomy ICD lead systems with the exception of one patient who had an artificial tricuspid valve . RESULTS During 46 + /- 37 months follow-up , 136 of 440 patients ( 31 % ) experienced at least one complication including implant procedure-related complications in 43 patients ( 10 % ) , ICD generator-related complications in 28 patients ( 6 % ) , lead-related complications in 52 patients ( 12 % ) , and inappropriate shocks in 54 patients ( 12 % ) . The most serious complications included one perioperative death due to heart failure ( 0.2 % ) , two ICD system infections necessitating device removal ( 0.5 % ) and two perioperative cerebrovascular strokes ( 0.5 % ) . CONCLUSIONS We conclude that more than one quarter of ICD patients experience complications during a mean follow-up of almost 4 years , although serious complications such as intraoperative death or ICD system infections are rare in patients with nonthoracotomy ICD systems . Recognition of these complications is the prerequisite for advances in ICD technology and management strategies to avoid their recurrence BACKGROUND Pacing leads with a small electrode surface for high-impedance stimulation have been shown to prolong pacemaker longevity , but no sufficient data is available on the safety and feasibility of a defibrillation lead with this novel design . METHODS We evaluated the clinical performance of a tined , steroid-eluting defibrillation lead with a small electrode surface area ( model 6944 ) in a prospect i ve multicenter study . A total of 542 patients with conventional indications for an implantable cardioverter defibrillator were r and omized 1:1 to receive either the model 6944 or a tined , steroid-eluting defibrillation lead with a conventional sized electrode surface area ( model 6942 ) . Device performance and electrical parameters were evaluated at implant and 1 , 3 , 6 , and 12 months thereafter ( mean follow-up 11.3 + /- 5.6 months ) . RESULTS Baseline characteristics , lead implant success rates , and defibrillation thresholds did not differ significantly between the 2 groups . While pacing thresholds did not differ significantly during follow-up , pacing impedance was approximately twice as high in the model 6944 as in the model 6942 lead ( P < .0001 ) . Mean R-wave amplitudes were smaller in patients with a 6944 ( 9.1 + /- 3.1 mV vs 9.8 + /- 3.6 mV for model 6942 , P < .05 ) , but remained stable within both groups throughout the observation period . The total number of ventricular lead-related adverse events and patient survival did not differ significantly between the 2 groups . CONCLUSIONS The use of a defibrillation lead with a small electrode surface for high-efficiency pacing is safe and feasible and increases pacing impedance without significantly compromising clinical performance Background : Implantable cardioverter defibrillators ( ICDs ) improve survival and extend lives of patients with severe heart disease . Objective : We sought to evaluate the impact of ICDs on health-related quality of life ( HRQOL ) during the first 3 years after implantation . Subjects : A total of 1089 patients from the Multicenter Automatic Defibrillator Implantation Trial II ( MADIT II ) were r and omized to an ICD or medical treatment only . Measures : Health Utility Index ( HUI3 ) at baseline , 3 , 12 , 24 , and 36 months following r and omization ; survival data . Research Design : We constructed mean profiles of HRQOL for living patients , estimated overall quality -adjusted life years ( QALYs ) , separately by treatment arm , and calculated cumulative QALY gains/losses as the difference between the areas under the treatment specific HRQOL profiles . Multivariate fixed effect regression models were developed to impute the missing HRQOL data using baseline patient characteristics ( age , gender , treatment , HUI3 score , diabetes , diuretics use , and NYHA class ) . Bootstrapped st and ard errors were calculated for the estimated differences in HRQOL gains/losses between treatment arms . Similarly , we performed subgroup analyses ( by gender , age , and baseline NYHA class , blood urine nitrogen , ejection fraction , and QRS ) . Results : There were no differences in QALYs loss for living patients by treatment group ( −0.037 , P = 0.64 ) or in overall QALYs loss by treatment group ( 0.043 , P = 0.37 ) over 3 years . In subgroup analysis , female subjects demonstrated a trend towards greater survival benefit ( 0.298 , P = 0.07 ) and overall QALYs ( 0.261 , P = 0.14 ) . Conclusions : Adverse effects of the ICD on HRQOL together with lower HRQOL among survivors may offset the 3-year survival benefits of ICDs BACKGROUND Since its introduction , the implantable cardioverter defibrillator ( ICD ) has evolved to its present status as the dominant therapeutic modality for patients with life-threatening arrhythmias . Several r and omized studies have shown the benefit of ICD implantation as the first choice of treatment for primary as well as secondary indications for ventricular arrhythmias . Therefore , it is expected that the use of ICDs will increase further . The main objectives of this study were to analyze the Israeli experience with ICD implantation from 1993 to 1999 , to examine the diffusion of ICD therapy in Israel and the evolution of implantation patterns and indications . METHODS We conducted a retrospective review and analysis of an ICD registry for the period of January 1993-December 1999 . Data collected included demographic , administrative , clinical and survival data . RESULTS A total of 732 new implantations were identified and review ed . The mean length of follow up of all patients was 30.7+/-21.1 months . 86 % of patients were males and the mean age at implantation was 62.6+/-12.4 years . 79 % of patients had CAD and the mean EF of all patients was 29.2+/-11.2 % . 135 patients ( 18.4 % ) died during follow-up . One , two and three-year survival rates were calculated and were 92.7 % , 87.8 % and 82.0 % respectively . A steady increase in implantation rate and in implanting centers was observed over the years . CONCLUSIONS ICD therapy is relatively expensive ; therefore a national registry which is continuously monitored may be the most expedient method to follow clinical and economic aspects of the utilization of this therapeutic modality ICDs are the therapy of choice in patients with life-threatening ventricular arrhythmias . Mortality , morbidity , and complication rates including appropriate and inappropriate therapies are unknown when ICDs are used in routine medical care and not in well-defined patients included in multicenter trials . Therefore , the data of 3,344 patients ( 61.1 + /- 12.1 years ; 80.2 % men ; CAD 64.6 % , dilated cardiomyopathy 18.9 % ; NYHA Class I-III : 19.1 % , 54.3 % , 20.1 % , respectively ; LVEF > 0.50 : 0.234 , LVEF 0.30 - 0.50 : 0.472 , LVEF < 0.30 : 0.293 , respectively ) implanted in 62 German hospitals between January 1998 and October 2000 were prospect ively collected and analyzed as a part of the European Registry of Implantable Defibrillators ( EURID Germany ) . The 1-year survival rate was 93.5 % . Patients in NYHA Class III and aLVEF < 0.30 had a lower survival rate than patients in NYHA Class I and a preserved LVEF ( 0.852 vs 0.975,P = 0.0001 ) . Including the 1-year follow-up , 49.5 % of patients had an intervention by the ICD , 39.8 % had appropriate ICD therapies , 16.2 % had inappropriate therapies . Overall , 1,691 hospital readmissions were recorded . The main causes for hospital readmissions were ventricular arrhythmias ( 61.3 % ) and congestive heart failure symptoms ( 12.9 % ) . Thus , demographic data and mortality of patients treated with an ICD in conditions of st and ard medical care seems to be comparable and based on , or congruent with , the large secondary preventions trials . When ICDs are used in st and ard medical care , the 1-year survival rate is high , especially in patients with NYHA Class I and preserved LVEF . However , nearly half of all patients suffer from ICD intervention Eighty-nine patients with a documented history of atrial tachyarrhythmias or fibrillation ( AF ) received a cardioverter defibrillator design ed to selectively differentiate and treat atrial and ventricular arrhythmias . Twenty-two patients received a coronary sinus lead and , therefore , could use a separate shock vector for selective treatment of atrial tachyarrhythmias/AF . The device is design ed to treat tachyarrhythmias with antitachycardia pacing ( ATP ) and /or shock therapy using an atrial and /or a ventricular shock vector . Patients underwent induction and shock termination of atrial or dual tachyarrhythmias ( AF/VF ) to verify proper device function and to measure the arrhythmia detection time with enhancements and preventive algorithms programmed On and Off , respectively . Detection time for 329 VF inductions was 2.41 + /- 0.64 seconds with enhancements On and 2.29 + /- 0.47 with enhancements Off ( NS ) . At implant or predischarge , 283 AF and /or AF/VF ( 121 atrial and 162 atrial/ventricular fibrillation ) were induced . Shock conversion efficacy was 89.8 % with AF conversion energies ranging from 0.9 to 27 J. Thirteen of the 23 patients had atrial shock conversions using the separate shock vector with an average conversion energy of 1.9 + /- 1.4 J. ( range 0.5 - 5 J ) . During follow-up the efficacy of ATP on atrial tachyarrhythmias was 59 % and the efficacy of delivered shocks on AF was 85 % . This new dual chamber cardioverter defibrillator appropriately detected and classified atrial arrhythmias , and shock therapy for AF was highly effective . The detection algorithm differentiated atrial tachyarrhythmia/AF and did not delay VF detection . The separate shock vector converted induced AF with energies ranging from 0.6 to 5 BACKGROUND Unsustained ventricular tachycardia in patients with previous myocardial infa rct ion and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent . We studied whether prophylactic therapy with an implanted cardioverter-defibrillator , as compared with conventional medical therapy , would improve survival in this high-risk group of patients . METHODS Over the course of five years , 196 patients in New York Heart Association functional class I , II , or III with prior myocardial infa rct ion ; a left ventricular ejection fraction < or = 0.35 ; a documented episode of asymptomatic unsustained ventricular tachycardia ; and inducible , nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were r and omly assigned to receive an implanted defibrillator ( n = 95 ) or conventional medical therapy ( n=101 ) . We used a two-sided sequential design with death from any cause as the end point . RESULTS The base-line characteristics of the two treatment groups were similar . During an average follow-up of 27 months , there were 15 deaths in the defibrillator group ( 11 from cardiac causes ) and 39 deaths in the conventional-therapy group ( 27 from cardiac causes ) ( hazard ratio for overall mortality , 0.46 ; 95 percent confidence interval , 0.26 to 0.82 ; P=0.009 ) . There was no evidence that amiodarone , beta-blockers , or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio . CONCLUSIONS In patients with a prior myocardial infa rct ion who are at high risk for ventricular tachyarrhythmia , prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy BACKGROUND Implantable cardioverter-defibrillators ( ICD ) are increasingly used for prevention of sudden cardiac death ( SCD ) . Although mortality risk reduction is about the same in primary and secondary prevention trials ( ~30 % ) , we hypothesised that the incidence and the nature of ventricular arrhythmias is different in high risk ICD recipients without prior arrhythmias compared to patients who presented with life threatening arrhythmias . METHODS A hundred consecutive ICD recipients were allocated to 2 groups : 1 ) secondary prevention : an ICD was implanted for secondary prevention of episodes of ventricular tachycardia ( VT ) or ventricular fibrillation ( VF ) . 2 ) primary prevention : patients at high risk of SCD without prior arrhythmias . They were prospect ively followed and the incidence of appropriate ICD therapies was determined by review ing stored electrograms . RESULTS During a mean follow-up of 20 ( 10 ) months , the overall mortality was 5 % and 5 % of the patients underwent heart transplantation . Of the 67 secondary prevention patients , 40 % ( n = 27 ) had VT/VF triggering ICD therapy , whereas only 15 % ( n = 5 ) of the 33 primary prevention patients had VT/VF triggering ICD therapy ( p < 0.05 ) . The adjusted hazard ratio for arrhythmias triggering ICD interventions in the primary prevention group was 0.345 ( 95 % confidence interval 0.132 to 0.902 , p = 0.03 ) . CONCLUSIONS The risk of developing arrhythmias triggering appropriate ICD intervention was 65 % lower among the primary prevention patients than in secondary prevention patients . Importantly , ICD therapies are not correlated with lives saved , and efficacy of ICD therapy in primary and secondary prevention can not be drawn from these data . However , the low incidence of ICD use in primary prevention patients emphasises that efforts should be made to develop better instruments for stratification INTRODUCTION Important sex differences in the incidence and outcome of patients with ischemic heart disease , the leading cause of ventricular tachyarrhythmias , have been identified . Implantable cardioverter defibrillator ( ICD ) therapy has become the treatment of choice for patients with ventricular tachycardia ( VT ) and ventricular fibrillation ( VF ) , but little is known about gender differences in the outcome of ICD-treated patients . METHODS AND RESULTS In this retrospective study , we compared arrhythmic events and survival of 376 women and 1,654 men treated with an ICD as part of prospect i ve evaluations of transvenous devices or lead systems . Women were younger ( 62+/-14 years vs 65+/-12 years , P = 0.0005 ) , had higher left ventricular ejection fraction ( 0.36+/-0.15 vs 0.32+/-0.13 , P < 0.0001 ) , were more likely to present with VF ( 34 % vs 19 % , P < 0.001 ) , and had lower implantation defibrillation threshold ( 11+/-6 vs 13+/-6 J , P < 0.0001 ) . Implant complication rates were similar in men and women ( 2.6 % vs 3.5 % , P = 0.46 ) . The 1-year and 2-year cumulative rates of appropriate ICD therapies were 31.4 % and 38.4 % for men and 32.6 % and 40.8 % for women , respectively ( P = 0.63 ) . The unadjusted 1-year and 2-year cumulative survival rates were 95.6 % and 93.7 % for men and 95.7 % and 94.3 % for women , respectively ( P = 0.98 ) . Adjusted total ( P = 0.61 ) , sudden ( P = 0.82 ) , and cardiac ( P = 0.34 ) death-free survivals also were similar in men and women . CONCLUSION Despite clinical differences suggesting women are at lower risk than men , men and women with VT/VF who are treated with an ICD have similar arrhythmic event and survival rates . These factors should be considered when determining risk and prescription of ICD therapy for women |
10,968 | 10,796,300 | There was considerable heterogeneity in length of stay and cost data .
There is a trend to effectiveness when combined outcome variables ( death and institutional care , death and deterioration in function ) are considered . | BACKGROUND Hip fracture is a major cause of morbidity in older people and its impact , both on the individual and to society , is substantial .
OBJECTIVES To examine the effects of co-ordinated multidisciplinary inpatient rehabilitation , compared with usual orthopaedic care , for older patients with hip fracture . | Abstract Objective : To evaluate the effect of intensive geriatric rehabilitation on demented patients with hip fracture . Design : Preplanned sub analysis of r and omised intervention study . Settting : Jyväskylä Central Hospital , Finl and . Participants : 243 independently living patients aged 65 years or older admitted to hospital with hip fracture . Intervention : After surgery patients in the intervention group ( n=120 ) were referred to the geriatric ward whereas those in the control group were discharged to local hospitals . Main outcome measures : Length of hospital stay , mortality , and place of residence three months and one year after surgery for hip fracture . Results : The median length of hospital stay of hip fracture patients with moderate dementia ( mini mental state examination score 12 - 17 ) was 47 days in the intervention group ( n=24 ) and 147 days in the control group ( n=12 , P=0.04 ) . The corresponding figures for patients with mild dementia ( score 18 - 23 ) were 29 days in the intervention group ( n=35 ) and 46.5 days in the control group ( n=42 , P=0.002 ) . Three months after the operation , in the intervention group 91 % ( 32 ) of the patients with mild dementia and 63 % ( 15 ) of the patients with moderate dementia were living independently . In the control group , the corresponding figures were 67 % ( 28 ) and 17 % ( 2 ) . There were no significant differences in mortality or in the lengths of hospital stay of severely demented patients and patients with normal mini mental state examination scores . Conclusions : Hip fracture patients with mild or moderate dementia can often return to the community if they are provided with active geriatric rehabilitation Background : An orthopaedic management/patient‐focused care unit ( OMPFCU ) involving a dedicated orthopaedic – geriatrics liaison team was established at the Royal Brisbane Hospital in 1994 in an effort to safely accelerate rehabilitation of patients with proximal femoral fractures Des vieillards atteints de fracture du femur sont suivis pendant 1 an , avec ou sans traitement de reeducation specialisee . Survie a 1 an : 67 % des temoins , 81 % des malades reeduques . 69 % des malades reeduques peuvent vivre de nouveau dans leur ancien domicile , contre 39 % seulement des OBJECTIVES Delirium ( or acute confusional state ) affects 35 % to 65 % of patients after hip-fracture repair , and has been independently associated with poor functional recovery . We performed a r and omized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture . DESIGN Prospect i ve , r and omized , blinded . SETTING Inpatient academic tertiary medical center . PARTICIPANTS 126 consenting patients 65 and older ( mean age 79 + /- 8 years , 79 % women ) admitted emergently for surgical repair of hip fracture . MEASUREMENTS Detailed assessment through interviews with patients and design ated proxies and review of medical records was performed at enrollment to ascertain prefracture status . Subjects were then r and omized to proactive geriatrics consultation , which began preoperatively or within 24 hours of surgery , or " usual care . " A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol . To ascertain study outcomes , all subjects underwent daily , blinded interviews for the duration of their hospitalization , including the Mini-Mental State Examination ( MMSE ) , the Delirium Symptom Interview ( DSI ) , and the Memorial Delirium Assessment Scale ( MDAS ) . Delirium was diagnosed using the Confusion Assessment Method ( CAM ) algorithm . RESULTS The 62 patients r and omized to geriatrics consultation were not significantly different ( P>.1 ) from the 64 usual-care patients in terms of age , gender , prefracture dementia , comorbidity , type of hip fracture , or type of surgical repair . Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively . A mean of 10 recommendations were made throughout the duration of the hospitalization , with 77 % adherence by the orthopedics team . Delirium occurred in 20 /62 ( 32 % ) intervention patients , versus 32 / 64 ( 50 % ) usual-care patients ( P = .04 ) , representing a relative risk of 0.64 ( 95 % confidence interval ( CI ) = 0.37 - 0.98 ) for the consultation group . One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group . There was an even greater reduction in cases of severe delirium , occurring in 7/ 60 ( 12 % ) of intervention patients and 18 / 62 ( 29 % ) of usual-care patients , with a relative risk of 0.40 ( 95 % CI = 0.18 - 0.89 ) . Despite this reduction in delirium , length of stay did not significantly differ between intervention and usual-care groups ( median + /- interquartile range = 5 + /- 2 days in both groups ) , likely because protocol s and pathways predetermined length of stay . In subgroup analyses , geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living ( ADL ) functional impairment . CONCLUSIONS Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair . Geriatrics consultation reduced delirium by over one-third , and reduced severe delirium by over one-half . Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients A r and omised controlled trial comparing an accelerated rehabilitation program after proximal femoral fracture with conventional care and rehabilitation was conducted with 252 elderly patients treated at an Australian general hospital in 1989/1990 . This paper presents a cost-effectiveness analysis of the accelerated rehabilitation program . The measure of cost was all direct costs of treatment and subsequent care ( medical and non-medical ) incurred during the 4 months after fracture . Effectiveness was defined as whether the patient returned to semi-independent living ; or if moderately or severely disabled prior to the fracture to the premorbid level of physical independence . The cost for treatment up to 4 months after fracture was estimated at A$ 10,600 per accelerated rehabilitation patient and A$ 12,800 per conventional care patient ( 1990 Australian dollars , A$ ) . Thus , accelerated rehabilitation releases re sources equivalent to approximately 17 % of costs for treatment per patient . When cost effectiveness is considered , the potential cost savings rise to 38 % per recovered patient We tested the hypothesis that since the implementation of the prospect i ve payment system ( PPS ) , elderly patients hospitalized for hip fractures receive shorter , less care-intensive hospitalizations and are more frequently institutionalized . In blinded fashion , we review ed the charts of elderly patients with hip fractures admitted to a municipal hospital from 1981 through 1985 . Demographic and clinical characteristics of patients treated before implementation of the PPS were similar to patients treated thereafter . After implementation of the PPS , the mean length of hospitalization fell from 16.6 to 10.3 days , and the mean number of physical therapy sessions received decreased from 9.7 to 4.9 . Concomitantly , the proportion of patients discharged to a nursing home increased ( 21 % to 48 % ) , as did the proportion receiving nursing home care at six months after discharge ( 13 % to 39 % ) . This increase in long-term nursing home placement suggests that the quality of care for elderly patients with hip fractures may have deteriorated A r and omised controlled trial of two management regimens was carried out in women patients over 65 years of age with hip fractures . Ninety seven patients were admitted to a design ated orthopaedic geriatric unit and 125 to orthopaedic wards . No difference was observed in mortality , length of stay , or placement of patients between the two groups . More medical conditions were recognised and treated in patients in the orthopaedic geriatric unit group . It is concluded that design ated orthopaedic geriatric units can provide medical care to these patients and should be administered without additional cost Orthopaedic geriatric care has become widely accepted despite relatively little formal evaluation . In the East Dorset health authority all patients with fractured neck of femur initially share common orthopaedic facilities but only those from one geographical sector have subsequent access to an orthopaedic geriatric unit , patients from the other sector receiving st and ard care . We have carried out a prospect i ve population -based comparison of the outcome of 155 consecutive incident cases of fractured neck of femur aged over 65 years . On admission to hospital the two population s were similar in respect of age , sex , fracture type , social status , medical and orthopaedic problems , mental status and dependency ( Clifton assessment procedure for the elderly ) . Multiple regression analysis showed that the mean length of stay was 9.5 days shorter in patients from the sector with access to orthopaedic geriatric care ( p less than 0.05 , 95 % confidence interval 0.6 to 18.4 days ) . This reduction was not due to any difference between the two groups as regards dependency or the level of support provided on discharge . There was no difference in outcome at 6 months post-operatively in terms of mortality , functional outcome ( pain and mobility ) , change in dependency or social status . We conclude that in the East Dorset health authority this combined approach has result ed in a significant reduction in the length of inpatient stay without any other apparent effect on patient outcome OBJECTIVE To assess outcomes of using a clinical pathway for managing patients with fractured neck of femur . DESIGN Prospect i ve , pseudor and omised , controlled trial . SETTING St Vincent 's Hospital , Melbourne , Victoria ( a tertiary referral , university teaching hospital ) , 1 October 1997 to 30 November 1998 . PARTICIPANTS 111 patients ( 80 women and 31 men ; mean age , 81 years ) admitted via the emergency department with a primary diagnosis of fractured neck of femur . INTERVENTIONS Management guided by a clinical pathway ( 55 patients ) or established st and ard of care ( control group , 56 patients ) . MAIN OUTCOME MEASURES Timing of referrals and discharge planning ; total length of stay ; and complication and readmission rates within 28 days of discharge . RESULTS Patients managed according to the clinical pathway had a shorter total stay ( 6.6 versus 8.0 days ; P = 0.03 ) , even if assessment for placement by the Aged Care Assessment Service was required ( 9.5 versus 13.6 days ; P = 0.03 ) . There were no significant differences in complication and readmission rates between pathway and control patients ( complication rates , 24 % versus 36 % ; P = 0.40 ; readmission rates , 4 % versus 11 % ; P = 0.28 ) . CONCLUSION Coordinated multidisciplinary care of patients with fractured neck of femur reduces length of stay without increasing complications Objective : To compare hospital and home setting s for the rehabilitation of patients following hip fracture . Design : R and omized controlled trial comparing accelerated discharge and home-based rehabilitation ( n = 34 ) with conventional hospital care ( n = 32 ) for patients admitted to hospital with hip fracture . Setting : Three metropolitan hospitals in Adelaide , Australia . Subjects : Sixty-six patients with fractured hip . Interventions : Patients assigned to the home-based rehabilitation group were discharged within 48 hours of r and omization . The project team therapists made visits to the patient ’s home and negotiated a set of realistic , short-term and measurable treatment goals with both the patient and carer . Those r and omized to usual care remained in hospital for conventional rehabilitation . Main outcome measures : Physical and social dependence , balance con”dence , quality of life , carer strain , patient and carer satisfaction , use of community services and incidence of adverse events such as re-admission and falls . Results : While there was no difference between the groups for all measures of quality of life , patients in the accelerated discharge and home-based rehabilitation group recorded a greater improvement in MBI from r and omization ( p < 0.05 ) and scored higher on the Falls Ef”cacy Scale ( p < 0.05 ) at four months . There was no difference in falls rates . Patients in the home-based rehabilitation group had a shorter stay in hospital ( p < 0.05 ) but a longer stay in rehabilitation overall ( p < 0.001 ) . The groups were comparable on the rate and length of admissions after discharge , use of community services , need for carer input and contact with general practitioner ( GP ) after discharge 1 . Although there are sophisticated surgical procedures for hip fracture repair , a substantial proportion of patients never return to pre-fracture levels of physical function . Factors that influence the recovery of older hip fracture patients represent important areas to study in order to more precisely predict outcome . 2 . Research findings suggest that elevated depressive symptoms and cognitive impairment may negatively affect recovery , while mental alertness , emotional stability , and social involvement positively affect recovery . Thus , hip fracture and its subsequent disability must be studied as a biopsychosocial phenomenon , rather than merely as a physiological event . 3 . Older hip fracture patients may be at higher risk for psychological problems related to the traumatic nature of the injury . A comprehensive psychological assessment at admission can assist the nursing staff to determine which patients are at higher risk for emotional distress This carer study forms part of a wider study which compares accelerated rehabilitation after proximal femoral fracture with conventional care . Two measures of burden on family caregivers were used ; social worker 's assessment of overall burden and an index of disruption to carers ' lives . Participants were carers of 200 patients interviewed at five periods up to 12 months after fracture . Carer burden prior to the fracture was the strongest predictor of subsequent burden , with carers of patients in nursing homes and patients with a cognitive or physical disability being more burdened . Carer burden may increase or decrease after the patient 's injury , irrespective of r and omization group . There is no simple relationship between burden and r and omized group . Accelerated rehabilitation does not impact greatly on carer burden , but already severely burdened carers may benefit from additional counselling/information . Specific ways in which carers ; lives were disrupted are reported The effectiveness of providing additional community re sources to enable early discharge following hip fracture surgery has been prospect ively evaluated in a consecutive series of 645 patients . For those discharged under the scheme , the average hospital stay was 9.3 days , and this result ed in a substantial saving of hospital bed days OBJECTIVE To determine the effect of an early intervention program in an acute care setting on the length of stay in hospital of elderly patients with proximal femoral fractures . SETTING Acute orthopaedic ward of a large teaching hospital . DESIGN AND PARTICIPANTS A r and omised controlled trial comparing 38 Intervention patients with 33 St and ard Care patients . INTERVENTION Early surgery , minimal narcotic analgesia , intense daily therapy and close monitoring of patient needs via a multidisciplinary approach versus routine hospital management . MAIN OUTCOME MEASURES Length of stay ( LOS ) ; deaths ; level of independent functioning . RESULTS Mean LOS was shorter in the Intervention group than in the St and ard Care group ( 21 days v. 32.5 days ; P < 0.01 ) . After adjusting for other factors that could affect LOS ( eg , age , sex , pre-trauma functional levels , pre-trauma comorbidity and postsurgical complications ) , the Intervention program was significantly predictive of shorter LOS ( P = 0.01 ) . The Intervention group did not experience greater numbers of deaths , deterioration in function or need for social support than the St and ard Care group . CONCLUSION This early intervention program in an acute care setting results in significantly shorter length of hospital stay for elderly patients with femoral fractures OBJECTIVE To assess the cost savings associated with a patient education and high-intensity strength intervention to improve rehabilitation after hip fracture . METHODS Economic analysis conducted alongside a r and omized controlled trial , using cost-benefit ratios and net present value statistics . Study subjects were aged over 64 years and were followed for 18 months postsurgery . Re source utilization data were gathered by telephone question naire . Medicare reimbursement rates and prevailing costs for services not covered by Medicare were used to convert utilization patterns into costs . Intervention costs were obtained from program records . RESULTS The cost of the intervention was $ 722 per patient . Over the followup period , median costs were $ 11,941 and $ 21,577 for the intervention and control groups , respectively , yielding an average program benefit of $ 9,636 . Cost-benefit ratios exceeded 4.5 , and net present value exceeded $ 150,974 . CONCLUSION The results indicate that the benefits of the intervention exceeded its costs This r and omized controlled trial compared accelerated rehabilitation after surgical treatment of proximal femoral fracture with conventional care and was conducted in a general hospital in an outer urban area . Participating were 261 sequentially admitted patients over the age of 50 years who met predetermined inclusion criteria and all were followed up until death or 4 months after fracture . Patients who were treated with the accelerated rehabilitation programme had a 20 % reduction in length of hospital stay . Improved physical independence ( as measured by Barthel Index ) was observed after fracture in accelerated rehabilitation programme patients with limited pre-existing disability . Non-nursing-home patients receiving accelerated rehabilitation were also less likely to be discharged to nursing-home care or die in hospital . Accelerated rehabilitation led to a substantial reduction in length of hospital stay with a modest short-term improvement in level of physical independence and accommodation status after discharge We determined the effect of geriatric rehabilitation of hip fracture patients on mortality , length of hospital stay , and functional recovery . In a r and omized , controlled intervention study , 243 community dwelling hip fracture patients over 64 years of age were r and omly assigned to 2 rehabilitation groups . The intervention group ( n = 120 ) was referred to a geriatric ward for team rehabilitation , and the controls ( n = 123 ) to local hospital wards for st and ard care . The median length of total hospital stay after a hip fracture operation was 34 ( 95 % CI 28 - 38 ) days in the intervention group and 42 ( 95 % CI 35 - 48 ) days in the control group ( p = 0.05 ) . The intervention group recovered instrumental activities of daily living faster ( p = 0.05 ) . Direct costs of medical care during the first year did not differ remarkably BACKGROUND Hip fractures in elderly people are associated with impaired function and ambulation and high rates of death and admission to institutions . Interventions design ed to improve the outcomes of hip fracture ( e.g. , mobility and discharge to own home ) that have incorporated interdisciplinary care have had mixed results . We compared the effectiveness of postoperative interdisciplinary care with that of usual care for elderly patients with hip fracture . METHODS The study population consisted of 279 patients at least 70 years of age from the community and from nursing homes who underwent surgical repair of hip fracture at a university-affiliated acute care hospital . The subjects were r and omly assigned to receive postoperative interdisciplinary care ( n = 141 ) or usual care ( n = 138 ) during their hospital stay . Interdisciplinary care included routine assessment and care by an internist-geriatrician , physiotherapist , occupational therapist , social worker and clinical nurse specialist , as well as twice-weekly interdisciplinary rounds to set goals for the patients and to monitor their progress . The primary outcome measure was the proportion of patients alive with no decline in ambulation or transfers in and out of a chair or bed and no change in place of residence at 6 months after surgery . RESULTS At 6 months , 56 patients ( 39.7 % ) in the interdisciplinary care group and 47 ( 34.1 % ) in the usual care group were alive and had no decline from baseline in terms of ambulation , chair and bed transfers or place of residence ( difference 5.6 % , 95 % confidence interval -5.6 % to 17.0 % ) . Multiple logistic regression analysis with adjustment for baseline factors showed no significant difference between treatment groups for the primary outcome measure at 3 months ( p = 0.44 ) or at 6 months ( p = 0.67 ) . The initial length of stay in hospital was longer for patients receiving interdisciplinary care : 29.2 ( st and ard deviation [ SD ] 22.6 ) v. 20.9 ( SD 18.8 ) days ( p < 0.001 ) . However , the mean number of days spent in an institution ( including hospital , inpatient rehabilitation and nursing home ) over the 6-month follow-up period was similar in the 2 groups ( p = 0.84 ) . A subgroup analysis suggested a trend to benefit from interdisciplinary care in patients with mild to moderate cognitive impairment . INTERPRETATION Postoperative inpatient interdisciplinary care did not result in significantly better 3- or 6-month outcomes in elderly patients with hip fracture OBJECTIVE --To compare postoperative collaborative care between orthopaedic surgeons and physicians in geriatric medicine with routine orthopaedic care in elderly women with proximal femoral fracture . DESIGN --Exclusion of patients dying before fit enough to enter trial , those with pathological fractures , those likely to be discharged within seven days of entering the trial , and those remaining unfit for transfer to a peripheral hospital . Remainder allocated to two groups : treatment group and control group . SETTING --District hospital acute admission ward and rehabilitation ward . PATIENTS --144 sequentially admitted elderly women with proximal fracture of the femur ; 36 excluded on above criteria and remainder entered into trial . INTERVENTION -- Both treatment and control groups ( n = 54 in each ) received physiotherapy and other services . The treatment group also received thrice weekly supervision by a geriatrician . END POINTS -- Physical independence , residence after discharge , and length of hospital stay . MEASUREMENTS AND MAIN RESULTS --At discharge significantly more patients in treatment group were independent in terms of activities of daily living than controls ( 41 v 25 ) and their median stay was 24 days ( range 8 - 197 ) compared with 41 ( 9 - 365 ) ( 95 % confidence intervals for difference 2 to 25 ) . Significantly fewer treatment patients were discharged to institutional care ( 10 % v 32 % ; 95 % confidence interval for difference 6 % to 37 % ) and more to their own homes ( 63 % v 38 % ; 95 % confidence interval for difference 6 % to 44 % ) . These beneficial effects were consistent across a range of ages and mental state . CONCLUSIONS --Both hospital and patient benefited when postoperative rehabilitation was provided in a setting specialising in such care for elderly patients with trauma |
10,969 | 27,820,528 | An example of this potential difficulty , from a healthcare provider perspective , is identifying the potential conflict that may develop when a patient 's preference is different from clinical practice guidelines .
Both patients and health care providers have noted improvement in relationships and improved interactions when shared decision-making is in evidence .
Along with this improved relationship and | REVIEW QUESTION / OBJECTIVE The objective of this review is to identify and synthesize the best available evidence related to the meaningfulness of internal and external influences on shared-decision making for adult patients and health care providers in all health care setting s .
The specific questions to be answered are : BACKGROUND : Patient-centered care is emphasized in today 's healthcare arena .
This emphasis is seen in the works of the International Alliance of Patients ' Organizations ( IAOP ) who describe patient-centered healthcare as care that is aim ed at addressing the needs and preferences of patients .
These five principles are further described as : Within the description of these five principles the idea of shared decision-making is clearly evident .
The concept of shared decision-making began to appear in the literature in the 1990s .
It is defined as a " process jointly shared by patients and their health care provider .
It aims at helping patients play an active role in decisions concerning their health , which is the ultimate goal of patient-centered care . "
This information may include the disease , potential treatments , consequences of those treatments , and any alternatives , which may include the decision to do nothing .
Without knowing this information the patient will not be able to participate in the shared decision-making process .
Depending on the results of this assessment the health care provider then must communicate the information to the patient .
Shared decision-making has been associated with autonomy , empowerment , and effectiveness and efficiency . | BACKGROUND Important barriers to the wider implementation of shared decision making remain . The experiences of professionals who are skilled in this approach may identify how to overcome these barriers . AIMS To identify the experiences and views of professionals skilled in shared decision making and risk communication , exploring the opportunities and challenges for implementation . DESIGN OF STUDY Qualitative study . SETTING Gwent Health Authority . METHOD Exit interviews using focus group methodology with 20 GPs who had been in practice between 1 and 10 years , and participated in an explanatory trial lasting 6 months . The trial interventions comprised training in shared decision-making skills and the use of risk communication material s. The doctors consulted with up to 48 patients each ( mean = 40 , half of them audiotaped ) for the study . RESULTS The GPs indicated positive attitudes towards involving patients and described positive effects on their consultations . However , the frequency of applying the new skills and tools was limited outside the trial . Doctors were selective about when they felt greater patient involvement was appropriate and feasible , rather than seeking to apply the approaches to the majority of consultations . They felt they often responded to consumer preferences for low levels of involvement in decision making . Time limitations were important in not implementing the approach more widely . CONCLUSION The promotion of ' patient involvement ' appears likely to continue . Professionals appear receptive to this , and willing to acquire the relevant skills . Strategies for wider implementation of patient involvement could address how consultations are scheduled in primary care , and raise consumers ' expectations or desires for involvement OBJECTIVE Fibromyalgia syndrome ( FMS ) is a condition of chronic widespread pain that is difficult to control and is associated with strains in physician-patient interaction . Shared decision making ( SDM ) can be a potential solution to improve interaction . We evaluated the effects of an SDM intervention , including an SDM communication training program for physicians , in a r and omized controlled trial with FMS patients . The main objective was to assess whether SDM improves the quality of physician-patient interaction from patients ' perspective . METHODS Patients were r and omized to either an SDM group or an information-only group . The SDM group was treated by physicians trained in SDM communication and had access to a computer-based information package ; the information-only group received only the information package and was treated by st and ard physicians . All patients were offered the same evidence -based treatment options for FMS . Patients were assessed with question naires on physician-patient interaction ( main outcome criteria ) and decisional processes . Physicians filled out a question naire on interaction difficulties . Assessment took place immediately after the initial consultation . RESULTS Data from 85 FMS patients ( 44 in the SDM group and 41 in the information-only group ) were analyzed . The mean age was 49.9 years ( S.D.=10.2 ) , and 91.8 % of patients were female . The quality of physician-patient interaction was significantly higher in the SDM group than in the information-only group ( P<.001 ) . We found no differences in secondary outcome measures . CONCLUSIONS SDM with FMS patients might be a possible means to achieve a positive quality of physician-patient interaction . A specific SDM communication training program teaches physicians to perform SDM and reduces frustration in patients BACKGROUND AND PURPOSE Shared decision-making ( SDM ) as a model in physician-patient interaction is gaining relevance in the German health system . By applying this model , mid- and long-term improvements are expected especially in the outcomes of chronic diseases . Up to now , there has hardly been any empirical data available in German health services research regarding the state and development of SDM . This study establishes a baseline and provides actual data on this subject based on a German-wide survey of end-stage renal disease ( ESRD ) patients . METHODS St and ardized German-wide survey of 6,614 patients with ESRD . The question naire included an instrument to measure the patients ' perceived involvement in care ( PICS ) which had been translated and vali date d before . RESULTS 82 % of the question ed patients feel their physicians facilitated involvement in decision making . 81 % of the patients actively inform themselves concerning their disease and treatment options . 69 % state that SDM has taken place . Age , years on dialysis and gender correlate with perceived involvement . CONCLUSION This paper provides a valid baseline for the prospect i ve research of SDM in ESRD . The results indicate that dialysis patients are willing to participate in the process of medical decision-making . Characteristics and preferences of the patients should be taken into account not only in everyday clinical interactions . They could be monitored systematic ally within the framework of quality management and used as potential for quality improvement |
10,970 | 26,447,819 | Effect sizes remained highly significant for medication-free patients compared to controls across all disorders .
Smaller and significant reductions in HRV were observed for specific antidepressants and antipsychotics .
Combined findings confirm substantial reductions in HRV across psychiatric disorders , and these effects remained significant even in medication-free individuals .
Reductions in HRV may therefore represent a significant mechanism contributing to elevated cardiovascular risk in individuals with psychiatric disorders . | BACKGROUND Autonomic nervous system ( ANS ) dysfunction is a putative underlying mechanism for increased cardiovascular disease risk in individuals with psychiatric disorders .
Previous studies suggest that this risk may be related to psychotropic medication use .
In the present study we systematic ally review ed and analyzed published studies of heart rate variability ( HRV ) , measuring ANS output , to determine the effect of psychiatric illness and medication use . | Background —High levels of phobic anxiety have been associated with elevated risks of coronary heart disease ( CHD ) death and sudden cardiac death ( SCD ) among men . To the best of our knowledge , no studies have looked at this association among women . Anxiety may influence CHD mortality by increasing the risk of ventricular arrhythmia and SCD . Methods and Results —We prospect ively examined the relationship between phobic anxiety , as measured by the Crown-Crisp index ( CCI ) , and CHD among women participating in the Nurses ' Health Study . Among 72 359 women with no history of cardiovascular disease or cancer in 1988 , 97 SCDs , 267 CHD deaths , and 930 nonfatal myocardial infa rct ions ( MI ) were documented over 12 years of follow-up . A higher score on the CCI was associated with an increased risk of SCD and fatal CHD but not of nonfatal MI in age-adjusted ( P , trend ≤0.008 ) and in multivariable models excluding possible biological intermediaries ( P , trend ≤0.03 ) . Multivariable adjustment appeared to attenuate the relations ; women who scored 4 or greater on the CCI were at a 1.59-fold ( 95 % CI , 0.97 to 2.60 ) marginally increased risk of SCD and a 1.31-fold ( 95 % CI , 0.97 to 1.75 ) marginally increased risk of fatal CHD compared with those who scored 0 or 1 . After control for possible intermediaries ( hypertension , diabetes , and elevated cholesterol ) , a trend toward an increased risk persisted for SCD ( P=0.06 ) . Conclusions —These prospect i ve data suggest that high levels of phobic anxiety are associated with an increased risk of fatal CHD , particularly from SCD . Some but not all of this risk can be accounted for by CHD risk factors associated with phobic anxiety Background Antipsychotic-induced subjective inner restlessness is one of the common and distressing adverse effects associated with antipsychotics ; however , its underlying neurobiological basis is not well understood . We examined the relationship between antipsychotic-induced subjective inner restlessness and autonomic neurocardiac function . Methods Twenty-two schizophrenia patients with antipsychotic-induced subjective restlessness , 28 schizophrenia patients without antipsychotic-induced subjective restlessness , and 28 matched healthy control subjects were evaluated . Assessment s of the linear and nonlinear complexity measures of heart rate dynamics were performed . Multivariate analysis of variance and correlation analysis were conducted . Results The mean interbeat ( RR ) interval value was significantly higher in control subjects than in patients with and without antipsychotic-induced subjective restlessness ( P < 0.05 ) . The low frequency/high frequency ratio was significantly higher in patients with antipsychotic-induced subjective restlessness than in control subjects and in patients without antipsychotic-induced subjective restlessness ( P < 0.05 ) , while the approximate entropy value was significantly lower in patients with antipsychotic-induced subjective restlessness than in control subjects and in patients without antipsychotic-induced subjective restlessness ( P < 0.05 ) . Correlation analyses controlling for psychotic symptom severity showed that the degree of antipsychotic-induced restlessness had a significant negative correlation with the value of approximate entropy ( P < 0.05 ) . Conclusion The results indicate that antipsychotic-induced subjective restlessness is associated with altered heart rate dynamics parameters , particularly the nonlinear complexity measure , suggesting that it might adversely affect autonomic neurocardiac integrity . Further prospect i ve research is necessary to eluci date the precise interrelationships and causality Background — Cardiac mortality and electrophysiological dysfunction both increase with age . Heart rate variability ( HRV ) provides indices of autonomic function and electrophysiology that are associated with cardiac risk . How habitual physical activity among older adults prospect ively relates to HRV , including nonlinear indices of erratic sinus patterns , is not established . We hypothesized that increasing the levels of both total leisure-time activity and walking would be prospect ively associated with more favorable time-domain , frequency-domain , and nonlinear HRV measures in older adults . Methods and Results — We evaluated serial longitudinal measures of both physical activity and 24-hour Holter HRV over 5 years among 985 older US adults in the community-based Cardiovascular Health Study . After multivariable adjustment , greater total leisure-time activity , walking distance , and walking pace were each prospect ively associated with specific , more favorable HRV indices , including higher 24-hour st and ard deviation of all normal-to-normal intervals ( Ptrend=0.009 , 0.02 , 0.06 , respectively ) and ultralow-frequency power ( Ptrend=0.02 , 0.008 , 0.16 , respectively ) . Greater walking pace was also associated with a higher short-term fractal scaling exponent ( Ptrend=0.003 ) and lower Poincaré ratio ( Ptrend=0.02 ) , markers of less erratic sinus patterns . Conclusions — Greater total leisure-time activity , and walking alone , as well , were prospect ively associated with more favorable and specific indices of autonomic function in older adults , including several suggestive of more normal circadian fluctuations and less erratic sinoatrial firing . Our results suggest potential mechanisms that might contribute to lower cardiovascular mortality with habitual physical activity later in life Background —The predictive value of heart rate variability ( HRV ) in chronic heart failure ( CHF ) has never been tested in a comprehensive multivariate model using short-term laboratory recordings design ed to avoid the confounding effects of respiration and behavioral factors . Methods and Results —A multivariate survival model for the identification of sudden ( presumably arrhythmic ) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF ( age 52±9 years , left ventricular ejection fraction 24±7 % , New York Heart Association class 2.3±0.7 ; the derivation sample ) . Time- and frequency-domain HRV parameters obtained from an 8′ recording of ECG at baseline and during controlled breathing ( 12 to 15 breaths/min ) were challenged against clinical and functional parameters . This model was then vali date d in 242 consecutive patients referred between 1996 and 2001 ( validation sample ) . In the derivation sample , sudden death was independently predicted by a model that included low-frequency power ( LFP ) of HRV during controlled breathing ≤13 ms2 and left ventricular end-diastolic diameter ≥77 mm ( relative risk [ RR ] 3.7 , 95 % CI 1.5 to 9.3 , and RR 2.6 , 95 % CI 1.0 to 6.3 , respectively ) . The derivation model was also a significant predictor in the validation sample ( P = 0.04 ) . In the validation sample , LFP ≤11 ms2 during controlled breathing and ≥83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death ( RR 3.0 , 95 % CI 1.2 to 7.6 , and RR 3.7 , 95 % CI 1.5 to 9.0 , respectively ) . Conclusions —Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients with CHF that is independent of many other variables . These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator OBJECTIVES Cardiac mortality is known to be increased in depressive patients . However , the underlying mechanisms remain elusive to date . Decreased heart rate variability ( HRV ) has been discussed as contributing to increased cardiac mortality , but studies examining patients suffering from major depressive disorder ( MDD ) have revealed inconsistent results . This study aim ed to investigate long-term and broad b and parameters of heart rate regulation in MDD , which have been shown to be more sensitive for the assessment of autonomic dysfunction . METHODS A total of 18 non-medicated patients suffering from MDD and 18 matched control subjects without cardiac disease were recruited and 24-h ambulatory electrocardiograms were recorded . Data were recorded during three distinct time intervals linear and nonlinear parameters as well as autonomic information flow ( AIF ) were calculated . RESULTS The power law slope was significantly reduced in the patient group for all intervals investigated and correlated with symptom severity , whereas st and ard deviation of the 5-min NN intervals ( SDANN ) and area under the AIF curve ( INT(NN ) ) showed significant differences between groups in the morning hours only . Analysis of st and ard HRV parameters in the time and frequency domain revealed no significant differences between groups . CONCLUSIONS The evidence for decreased complexity of cardiac regulation in depressed patients presented here might be useful as an indicator of the increased cardiac mortality known in depression , especially since these parameters are capable of predicting cardiac mortality in other diseases . The importance of these parameters for patients at risk should be evaluated in future prospect i ve studies BACKGROUND Several studies have suggested an increased risk of fatal coronary heart disease ( CHD ) among patients with panic disorder , phobic anxiety , and other anxiety disorders . We prospect ively examined this association in the Normative Aging Study . METHODS AND RESULTS An anxiety symptoms scale was constructed out of five items from the Cornell Medical Index , which was administered to the cohort at baseline . During 32 years of follow-up , we observed 402 cases of incident coronary heart disease ( 137 cases of nonfatal myocardial infa rct ion , 134 cases of angina pectoris , and 131 cases of fatal CHD : made up of 26 cases of sudden cardiac death and 105 cases of nonsudden death ) . A nested case-control design ( involving 1869 control subjects who remained free of diagnosed CHD ) was used to assess the association between anxiety and risk of CHD . Compared with men reporting no symptoms of anxiety , men reporting two or more anxiety symptoms had elevated risks of fatal CHD ( age-adjusted odds ratio [ OR ] = 3.20 , 95 % confidence interval [ CI ] : 1.27 to 8.09 ) , and sudden death ( age-adjusted OR = 5.73 , 95 % CI : 1.26 to 26.1 ) . The multivariate OR after adjusting for a range of potential confounding variables was 1.94 ( 95 % CI : 0.70 - 5.41 ) for fatal CHD and 4.46 ( 95 % CI : 0.92 - 21.6 ) for sudden death . No excess risks were found for nonfatal myocardial infa rct ion or angina . CONCLUSIONS These data suggest an association between anxiety and fatal coronary heart disease , in particular , sudden cardiac death BACKGROUND Low heart rate variability has been implicated as a risk factor for sudden death . However , no large epidemiological studies using sudden death as an outcome event have been reported . METHODS AND RESULTS A total of 6,693 consecutive patients who underwent 24-hour ambulatory ECG were followed up for 2 years ; of these , 245 patients died suddenly . Clinical data at the time of 24-hour ambulatory ECG were collected for all patients who died suddenly and for a r and om sample of 268 patients from the study cohort . In all patients in sinus rhythm with or without occasional supraventricular arrhythmias at the 24-hour ECG ( 193 patients who died suddenly and 230 patients from the sample ) , heart rate variability parameters were derived . Patients with low short-term RR interval variability ( mean during 24 hours of per-minute st and ard deviations [ SD ] of RR intervals < 25 msec ) had a 4.1-fold higher risk ( 95 % confidence interval [ CI ] , 2.6 , 8.1 ) for sudden death than patients with high short-term variability ( > or = 40 msec ) ; after adjustment for age , evidence of cardiac dysfunction , and history of myocardial infa rct ion , the relative risk was 2.6 ( 95 % CI , 1.4 , 5.1 ) . The crude relative risk of long-term RR interval variability ( SD during 24 hours of per-minute means of RR intervals < 8 msec ) was 4.4 ( 95 % CI , 2.6 , 7.7 ) ; after adjustment for the same risk factors , it was 2.2 ( 95 % CI , 1.2 , 4.1 ) . Patients with a minimum heart rate > or = 65 beats per minute had a double risk of sudden death compared with those with a minimum heart rate < 65 beats per minute ( adjusted relative risk , 2.1 ; 95 % CI , 1.3 , 3.6 ) . CONCLUSIONS These findings support the theory that patients with low parasympathetic activity ( low short-term RR interval variability ) have an increased risk for sudden death independent of other risk factors OBJECTIVES Alarming somatic symptoms and in particular the cardiovascular symptoms , are the characteristic features of panic attacks . Increased cardiac mortality and morbidity have been proposed in these patients . Power spectral analysis of electrocardiogram R-R intervals is known to be a particularly successful tool in the detection of autonomic instabilities in various clinical disorders . Heart rate variability ( HRV ) has been found to be the outcome of rapidly reacting cardiovascular control systems . The aim of our study is to measure very low frequency b and ( VLF ) , low frequency b and ( LF ) and high frequency b and ( HF ) components of R-R interval during orthostatic experiment in patients with panic disorder before and after treatment and compares it with healthy controls . METHODS We assessed heart rate variability in 19 patients with panic disorder before and after 6-weeks treatment with antidepressants combined with cognitive behavioral therapy ( CBT ) and in 18 healthy controls . Diagnosis was done according to the ICD-10 research diagnostic criteria confirmed with MINI ( MINI international neuropsychiatric interview ) . Patients were treated with CBT and psychotropics . They were regularly every week assessed using CGI ( Clinical Global Impression ) , BAI ( Beck Anxiety Inventory ) and BDI ( Beck Depression Inventory ) . Heart rate variability was assessed during 3 positions ( 1st - 5 min supine ; 2nd - 5 min st and ing ; 3rd - 5 min supine ) before and after the treatment . Power spectra were computed for very low frequency - VLF ( 0.0033 - 0.04 Hz ) , low-frequency - LF ( 0.04 - 0.15 Hz ) and high frequency - HF ( 0.15 - 0.40 Hz ) b and s using fast Fourier transformation . RESULTS Nineteen panic disorder patients resistant to pharmacological treatment entered a 6-week open-label treatment study with combination of SSRI and CBT . The combination of CBT and pharmacotherapy proved to be an effective treatment in these patients . The patients significantly improved during the study period in all rating scales . There were highly statistical significant differences between panic patients and control group in all components of power spectral analysis in 2nd ( VLF , LF and H in st and ing ) and in two component of 3rd ( LF and HF in supine ) positions . There was also a statistically significant difference between these two groups in LF/HF ratio in st and ing position ( 2nd ) . During therapy there was a tendency increasing values in all three positions in components of HRV power spectra , but HF in 1st supine position was the only component where the increase reached the level os statistical significance . CONCLUSIONS These findings demonstrate a lower autonomic activity in panic disorder patients measured during the changes of postural position in comparison with healthy controls and tendency to increase this autonomic power during the treatment Exposure to combat experiences is associated with increased risk of developing Post Traumatic Stress Disorder . Prolonged exposure therapy and cognitive processing therapy have garnered a significant amount of empirical support for PTSD treatment ; however , they are not universally effective with some patients continuing to struggle with residual PTSD symptoms . Heart rate variability ( HRV ) is a measure of the autonomic nervous system functioning and reflects an individual ’s ability to adaptively cope with stress . A pilot study was undertaken to determine if veterans with PTSD ( as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist ) would show significantly different HRV prior to an intervention at baseline compared to controls ; specifically , to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD . The study also aim ed at assessing the feasibility , acceptability , and potential efficacy of providing HRV biofeedback as a treatment for PTSD . The findings suggest that implementing an HRV biofeedback as a treatment for PTSD is effective , feasible , and acceptable for veterans . Veterans with combat-related PTSD displayed significantly depressed HRV as compared to subjects without PTSD . When the veterans with PTSD were r and omly assigned to receive either HRV biofeedback plus treatment as usual ( TAU ) or just TAU , the results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD . However , the TAU had no significant effect on either HRV or symptom reduction . A larger r and omized control trial to vali date these findings appears warranted Objective : Heart rate variability ( HRV ) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system , abnormalities of which have both figured prominently in various etiological models of schizophrenia , particularly those that address patients ’ vulnerability to stress in connection to psychosis onset and exacerbation . This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics , as well as cardiac data on matched healthy controls . We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness ( or psychosis ) itself . Method : We collected 24-hour ECGs on 19 patients and 24 controls . Of the patients , 9 were medication free and 10 were on atypical antipsychotics . All subject groups were matched for age and gender . Patient groups showed equivalent symptom severity and type , as well as duration of illness . We analyzed the data using nonlinear complexity ( symbolic dynamic ) HRV analyses as well as st and ard and relative spectral analyses . Results : For the medication-free patients as compared to the healthy controls , our data show decreased R – R intervals during sleep , and abnormal suppression of all frequency ranges , but particularly the low frequency range , which persisted even after adjusting the spectral data for the mean R – R interval . This effect was exacerbated for patients on atypical antipsychotics . Likewise , nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics . Conclusions : Altogether , the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls , apart from and beyond any differences due to medication side effects . The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV , which may exacerbate an underlying vulnerability in patients . These results support previous evidence that autonomic abnormalities may be a core feature of the illness ( or psychosis ) , and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinical ly appropriate Twenty-four unmedicated patients with episodes of major depression ( DSM-III-R ) and an age- and sex-matched group of 24 normal subjects underwent a heart rate analysis . The battery of cardiovascular reflex tests included the coefficient of variation while resting ( CVr ) and during deep breathing ( CVdr ) , a spectral analysis of heart rate variability , the Valsalva test , and the posture index . The depressed patients showed no significant abnormalities in any of the tests as compared to the healthy subjects . The 24 patients were r and omly allocated for treatment with either amitriptyline or paroxetine . During treatment with 20 mg paroxetine per day , patients showed no changes in cardiovascular autonomic function tests after 14 days . However , treatment with 150 mg amitriptyline per day decreased all heart rate parameters significantly due to anticholinergic side effects , except heart rate , which increased significantly . As autonomic side effects are a potential hazard of antidepressant therapy , the data suggest that paroxetine is an appropriate antidepressant for cases with pre-existing cardiovascular autonomic neuropathy Decreased heart rate variability ( HRV ) is a cardiovascular predictor of mortality . Recent debate has focused on whether reductions in HRV in major depressive disorder ( MDD ) are a consequence of the disorder or a consequence of pharmacotherapy . Here we report on the impact of transcranial direct current stimulation ( tDCS ) , a non-pharmacological intervention , vs. sertraline to further investigate this issue . The employed design was a double-blind , r and omized , factorial , placebo-controlled trial . One hundred and eighteen moderate-to-severe , medication-free , low-cardiovascular risk depressed patients were recruited for this study and allocated to either active/sham tDCS ( 10 consecutive sessions plus two extra sessions every other week ) or placebo/sertraline ( 50 mg/d ) for 6 wk . Patients were age and gender-matched to healthy controls from a concurrent cohort study [ the Brazilian Longitudinal Study of Adult Health ( ELSA-Brasil ) ] . The impact of disorder , treatment and clinical response on HRV ( root mean square of successive differences and high frequency ) was examined . Our findings confirmed that patients displayed decreased HRV relative to controls . Furthermore , HRV scores did not change following treatment with either a non-pharmacological ( tDCS ) or pharmacological ( sertraline ) intervention , nor did HRV increase with clinical response to treatment . Based on these findings , we discuss whether reduced HRV is a trait-marker for MDD , which may predispose patients to a host of conditions and disease even after response to treatment . Our findings have important implication s for our underst and ing of depression pathophysiology and the relationship between MDD , cardiovascular disorders and mortality Heart rate variability ( HRV ) provides reliable tools to assess the integrity and reactivity of autonomic nervous function . Our aim was to examine HRV in the resting condition and during different mental loads in acute psychosis compared to healthy controls . HRV was measured in 17 first-episode drug-naive patients with psychosis and 21 healthy controls during oddball tasks and while performing the Wisconsin Card Sorting Test . A discrete event series was constructed by an adaptive QRS detector algorithm and power spectrum estimation was carried out . The RMSSD ( representing interval differences of successive heartbeats ) and the amount of high frequency ( HF ) power were significantly reduced in patients . Moreover , the patients ' HRV remained unaltered during the tasks , whereas in controls the HRV diminished with increasing mental load of the task . Patients with psychosis displayed less short-term HR reactivity than healthy controls . They also failed to adapt HRV according to the task-connected strain . Acute psychosis is characterized by a limited capacity to respond to external dem and s at the level of autonomic nervous system It remains unclear if diminished high frequency heart rate variability ( HF-HRV ) can be found across anxiety disorders . HF-HRV and heart rate ( HR ) were examined in panic ( PD ) , generalized anxiety ( GAD ) , social anxiety ( SAD ) , and obsessive-compulsive disorder ( OCD ) relative to healthy controls at baseline and during anxiety stressors . All disorders evidence d diminished baseline HF-HRV relative to controls . Baseline HRV differences were maintained throughout relaxation . For hyperventilation , PD and GAD demonstrated greater HR than controls . Psychotropic medication did not account for HF-HRV differences except in OCD . Age and sex evidence d multiple main effects . Findings suggest that low baseline HF-HRV represents a common index for inhibitory deficits across PD , GAD , and SAD , which is consistent with the notion of autonomic inflexibility in anxiety disorders . Elevated HR responses to hyperventilation , however , are specific to PD and GAD Panic disorder has been widely hypothesized to be associated with dysfunction of the autonomic nervous system . In this study , 24 patients with panic disorder and 26 healthy control subjects took part in a broad battery of autonomic function tests , each design ed to stress the autonomic nervous system in a particular fashion . Testing consisted of postural challenge , isometric exercise , cold pressor , and Valsalva maneuver . Dependent measures included heart rate , vagal tone , blood pressure , respiratory frequency , end-tidal CO2 levels , and plasma norepinephrine and epinephrine levels . The testing procedures reliably produced changes in autonomic output in the expected directions , but patients with panic disorder were not found to differ from healthy controls in their cardiorespiratory or plasma catecholaminergic responses . This pattern of normal autonomic responsivity in the patients with panic disorder was evident across multiple test conditions with varying autonomic dem and characteristics , thereby supporting the integrity of autonomic regulatory systems in this illness . These data run counter to a simple notion of autonomic dysfunction in panic disorder OBJECTIVE St and ardized mortality rates are elevated in schizophrenia compared to the general population . The incidence of coronary heart disease ( CHD ) and the relative contribution of CHD to increased mortality in schizophrenia patients are not clear , despite recent concerns about metabolic complications of certain atypical antipsychotics . METHOD Ten-year risk for CHD was calculated for 689 subjects who participated in the Clinical Trials of Antipsychotic Treatment Effectiveness ( CATIE ) Schizophrenia Trial at baseline using the Framingham CHD risk function and were compared with age- , race- and gender-matched controls from the National Health and Nutrition Examination Survey ( NHANES ) III . RESULTS Ten-year CHD risk was significantly elevated in male ( 9.4 % vs. 7.0 % ) and female ( 6.3 % vs. 4.2 % ) schizophrenia patients compared to controls ( p = 0.0001 ) . Schizophrenia patients had significantly higher rates of smoking ( 68 % vs. 35 % ) , diabetes ( 13 % vs. 3 % ) , and hypertension ( 27 % vs. 17 % ) and lower HDL cholesterol levels ( 43.7 vs. 49.3 mg/dl ) compared to controls ( p < 0.001 ) . Only total cholesterol levels did not differ between groups . Ten-year CHD risk remained significantly elevated in schizophrenia patients after controlling for body mass index ( p = 0.0001 ) . CONCLUSIONS These results are consistent with recent evidence of increased cardiac mortality in schizophrenia patients . While the impact of cigarette smoking is clear , the relative contributions to cardiac risk of specific antipsychotic agents , diet , exercise , and quality of medical care remain to be clarified BACKGROUND Experimental evidence suggests that autonomic markers such as heart-rate variability and baroreflex sensitivity ( BRS ) may contribute to postinfa rct ion risk stratification . There are clinical data to support this concept for heart-rate variability . The main objective of the ATRAMI study was to provide prospect i ve data on the additional and independent prognostic value for cardiac mortality of heart-rate variability and BRS in patients after myocardial infa rct ion in whom left-ventricular ejection fraction ( LVEF ) and ventricular arrhythmias were known . METHODS This multicentre international prospect i ve study enrolled 1284 patients with a recent ( < 28 days ) myocardial infa rct ion . 24 h Holter recording was done to quantify heart-rate variability ( measured as st and ard deviation of normal to normal RR intervals [ SDNN ] ) and ventricular arrhythmias . BRS was calculated from measurement of the rate-pressure response to intravenous phenylephrine . FINDINGS During 21 ( SD 8) months of follow-up , the primary endpoint , cardiac mortality , included 44 cardiac deaths and five non-fatal cardiac arrests . Low values of either heart-rate variability ( SDNN < 70 ms ) or BRS ( < 3.0 ms per mm Hg ) carried a significant multivariate risk of cardiac mortality ( 3.2 [ 95 % CI 1.42 - 7.36 ] and 2.8 [ 1.24 - 6.16 ] , respectively ) . The association of low SDNN and BRS further increased risk ; the 2-year mortality was 17 % when both were below the cut-offs and 2 % ( p<0.0001 ) when both were well preserved ( SDNN > 105 ms , BRS > 6.1 ms per mm Hg ) . The association of low SDNN or BRS with LVEF below 35 % carried a relative risk of 6.7 ( 3.1 - 14.6 ) or 8.7 ( 4.3 - 17.6 ) , respectively , compared with patients with LVEF above 35 % and less compromised SDNN ( > or = 70 ms ) and BRS ( > or = 3 ms per mm Hg ) . INTERPRETATION ATRAMI provides clinical evidence that after myocardial infa rct ion the analysis of vagal reflexes has significant prognostic value independently of LVEF and of ventricular arrhythmias and that it significantly adds to the prognostic value of heart-rate variability Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a st and ardized heart rate analysis ( HRA ) before therapy and after 14 days . The battery of cardiovascular reflex tests included the determination of the coefficient of variation ( CV ) while resting and during deep respiration , a spectral analysis of heart rate , the heart rate response to st and ing , and the Valsalva manoeuvre . The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex . On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests ( P<0.0001 ) , probably due to the anticholinergic side effects of amitriptyline . Heart rate increased form 78.1 to 93.6 bpm on average ( P<0.0001 ) . Abnormal CV at rest was registered in 96 % of the patients ; during deep respiration 29 % showed abnormal CV results . An abnormal spectral analysis was found in 100 % of the cases ( low frequency peak : 42 % , mid-frequency peak : 100 % , high frequency peak : 79 % ) . The heart rate response to st and ing was abnormal in 75 % and the Valsalva test in 33 % of the cases . Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy . As yet , the consequences of these changes for the patients have not been sufficiently eluci date Clinical evidence indicates that parasympatholytic effects of tricyclic antidepressants increase with age . The aim of the present study was to determine the possible physiological reason for this phenomenon . Subjects included 23 patients ( 14 female ) with major depression , melancholic type , and 23 age- and sex-matched healthy control subjects . Cardiac vagal tone was measured at rest using both spectral analysis and a time domain beat-to-beat method . Results of the spectral and time domain methods for the estimation of vagal tone used in this study were highly correlated in control subjects as well as in medicated depressed subjects . Both patients and control subjects showed an age-related decline in cardiac vagal tone . Tricyclic antidepressants decreased vagal tone significantly by 25 - 49 % depending on age ( 20 - 60 years ) , although the age difference was not significant . The greater effect of tricyclic antidepressants on parasympathetic activity typically seen in older age groups may reflect the fact that predrug levels of vagal tone are already low in older patients . Measurement of vagal tone prior to drug administration may therefore be of prognostic value for anticholinergic side effects C ingestion has been found to increase sympathetic nervous system activity ( SNSA ) . This observation may underlie the finding of short-term increases in systolic blood pressure and arterial stiffness after caffeine ingestion . There have been few studies on the effects of caffeine on the cardiac parasympathetic nervous system activity ( PNSA ) . PNSA is an independent risk factor for future cardiovascular events , in particular sudden cardiac death , at least in patients with existing disease . The present study therefore sought to determine the effect of acute caffeine ingestion on PNSA in nonhabitual caffeine users . Because of putative direct effects of caffeine on the autonomic nervous system , we hypothesised that , in addition to increased SNSA , acute caffeine ingestion would be associated with reduced PNSA . • • • Nonhabitual caffeine users ( 1 dose/day ) aged 18 years were studied . Any clinical ly relevant medical condition , need for regular medication , current cigarette smoking , or alcohol abuse was an exclusion to entry . The study was approved by the Institutional Ethics Committee of the Alfred Hospital . All subjects provided written informed consent before commencing the study . Ten subjects ( 6 men and 4 women , mean age 26 years [ range 23 to 32 ] ) were r and omized in a 3-way , single-blind , crossover study design to receive single oral doses of placebo or 100 or 200 mg of caffeine dissolved in honey . A minimum 4-day washout period was m and ated to minimize any carryover effects as well as the potential for effects of caffeine withdrawal . On each study day , heart rate , blood pressure , alertness , and PNSA were measured before administration of caffeine/placebo as well as during the period 60 to 90 minutes after ingestion . This time point was chosen based on the known pharmacokinetics and pharmodynamics of caffeine . Blood pressure was measured by a Dinamap ( Critikon , Arlington , Texas ) semiautomated blood pressure monitor . Three measurements were averaged for each blood pressure determination . PNSA was determined from analysis of heart rate variability ( HRV ) . HRV is a simple , noninvasive method of assessing cardiac PNSA , as previously described in detail . Computerized electrocardiographic recordings were converted into a scatter plot of the current cardiac cycle length ( RR interval ) against the immediately preceding RR interval ( Poincare plot ) . Artifact and ectopic beats were filtered , with time and frequency-domain parameters of HRV calculated using customized software . The time-domain parameters of HRV evaluated were SD of RR intervals , rootmean-squared difference in successive RR intervals , and percentage of successive RR intervals 50 ms different from one another . The frequency domain parameter of HRV evaluated was high-frequency power ( 0.15 to 0.40 Hz ) . The above HRV measures are generally accepted as reflecting cardiac PNSA . Sympathovagal balance was assessed by low-frequency power/high-frequency power ratio . Alertness was assessed by visual analog scale . Subjects were asked to draw a vertical line through a 10-cm-wide horizontal bar with 0 cm representing “ very awake ” and 10 cm “ very sleepy ” compared with baseline level of alerteness . The sample size for the study was based on the primary end point of high-frequency power as a measure of cardiac PNSA . Blood pressure , HRV , and alertness values for changes in 100 and 200 mg of caffeine from baseline were compared with placebo by 1-way analysis of variance . All values are expressed as mean SEM . A 2-tailed p value 0.05 was considered statistically significant . Baseline blood pressure values measured before drug ingestion were similar on all 3 study days ( coefficient of variation , systolic blood pressure 2.3 % , diastolic blood pressure 2.9 % ) . Systolic and diastolic blood pressures were significantly increased acutely 90 minutes after acute caffeine ingestion ( Table 1 ) . Baseline heart rate and HRV values measured before drug ingestion were similar on all 3 study days ( coefficient of variation , 3.6 % to 12.1 % ) . Placebocorrected changes at 90 minutes compared with baseline for heart rate and during 60 to 90 minutes for HRV measures are summarized in Table 1 . There was no significant difference in heart rate after caffeine ingestion . However , HRV measures of PNSA measured 60 to 90 minutes after ingestion were significantly decreased with caffeine compared with placebo . This is reflected by the decreases in the SD of RR intervals , root-mean-squared difference in successive RR intervals , and percentage of successive RR intervals 50 ms different from one another in the time domain , and in high-frequency power in the frequency domain . Furthermore , the low/high-frequency power ratio was increased with high-dose caffeine compared with placebo , supporting a shift in sympathovagal balance toward sympathetic predominance . Alertness was increased with caffeine ingestion , as expected . By visual analog scale , alertness 90 minutes From the Clinical Pharmacology Unit , Department of Epidemiology & Preventive Medicine , Department of Medicine , Monash University/ Alfred Hospital , Prahran Victoria , Australia ; and University of Leiden , Leiden , The Netherl and s. Dr. Krum ’s address is : Clinical Pharmacology Unit , Department of Epidemiology & Preventive Medicine/Department of Medicine , Monash University/Alfred Hospital , Prahran Victoria 3181 , Australia . E-mail : [email protected] . Manuscript received April 8 , 2002 ; revised manuscript received and accepted June 10 , 2002 BACKGROUND Cardiac autonomic dysfunction has been proposed as an important contributing factor to the increased cardiovascular risk observed in major depression ( MDD ) . However , the evidence regarding alterations in heart rate variability ( HRV ) in otherwise healthy depressed subjects has been inconclusive . METHODS A case-control study in 50 treatment-naïve young adults with a first MDD episode without comorbid psychiatric disorders and 50 healthy control subjects was conducted . Time- and frequency-domain indexes of HRV were determined at baseline supine and after 5-min of orthostatic stress at 60 ° . RESULTS There were no significant differences in the time- or frequency-domain variables of HRV between depressed patients and controls . However , a r and om-effect ANOVA model showed that during orthostatic stress depressed men had a reduced HRV and decreased parasympathetic activity compared to control subjects , while no differences were found between depressed women and controls . CONCLUSION These results suggest a sex-dependent relationship between major depression and cardiac autonomic dysfunction and provide one potential explanation for sex differences in the association of depressive symptoms with cardiovascular morbidity Abstract Previous studies have suggested the utility of nonlinear complexity measures of heart rate variability ( HRV ) in evaluating the regulatory capacity of the neuroautonomic system . The purpose of the present study was to investigate the effects of clozapine on the nonlinear complexity measures of HRV in patients with treatment-resistant schizophrenia to find novel electrophysiological markers that indicate response to clozapine treatment . Forty patients with treatment-resistant schizophrenia were evaluated during 8 weeks of clozapine monotherapy . For nonlinear complexity measures of HRV , the approximate entropy ( ApEn ) and sample entropy ( SampEn ) values were obtained . The response rate to clozapine was 37.5 % . The results of multivariate analysis of covariance revealed that the ApEn and the SampEn values of HRV at week 8 were significantly higher in the responders than in the nonresponders . Repeated- measures analysis of covariance showed a significant group by time interaction effect in the ApEn and SampEn indices . The responder group showed an increasing pattern of change in these complexity measures after administration of clozapine , whereas the nonresponder group showed a decreasing pattern of change . These results suggest that the nonlinear dynamic complexity measures of HRV , which indicate the irregularity and complexity of the biosystem , may be useful in evaluating the therapeutic changes of neuroautonomic function in schizophrenia . The response to clozapine treatment is expected to be more favorable when the plasticity of the neuroautonomic system reflected in the nonlinear complexity measures is high We investigated cardiac autonomic function in 16 patients with panic disorder before and after treatment with paroxetine using Holter ECG records . Our previous data suggest a relative increase in sympathetic activity in patients with panic disorder , especially during sleep . Data for 20 h and awake and sleep periods were analyzed using spectral analysis to quantify absolute and relative heart period variability in ultra low ( ULF : < 0.0033 Hz ) , very low ( VLF : 0.0033–0.04 Hz ) , low ( LF : 0.04–0.15 Hz ) and high ( HF : 0.15–0.5 Hz ) frequency b and s. We also obtained fractal dimensions ( FD ) for the 20-hour , awake and sleep time series of RR intervals . Paroxetine treatment ( 19.7 ± 4.7 mg/day for 105 ± 37 days ) result ed in a significant improvement in the frequency and intensity of panic attacks and also on the state anxiety inventory . Paroxetine treatment produced a significant decrease of 20-hour absolute HF power , awake absolute LF power and sleep absolute HF power . There was also a significant decrease of FDs after treatment with paroxetine for the sleep period . The decrease in LF and HF powers , and sleep FD is likely due to the antimuscarinic effect of paroxetine . The decrease in day-time LF power may also be due to a decrease in relative cardiac sympathetic activity after paroxetine treatment St and ardized investigations on resting heart rate variability ( HRV ) should provide more information on acamprosate 's human pharmacodynamic properties because acamprosate interacts with several neurotransmitter systems which are also involved in maintaining autonomic neurocardiac balance . We performed HRV measurements prospect ively in 69 healthy controls and 19 chronic alcoholics to prove the hypotheses that : ( 1 ) compared to healthy controls , chronic alcoholics show disturbances in neurocardiac vagal function ; and ( 2 ) in alcoholics , acamprosate treatment ( 6 - 8 days ) should further decrease parasympathetic activity if acamprosate interacts with central gamma-aminobutyric acidA receptors in vivo . Cardiovagal dysfunction was initially present in 21 % of the alcoholics . After treatment . however , their neurocardiac sympathetic-parasympathetic balance improved significantly Objective : To assess the 24-hour temporal-domain heart-rate variability correlates of treatment with fluoxetine or doxepinfor depression . Method : A r and omized evaluation of fluoxetine and doxepin measured a 50 % change in the Hamilton Depression Rating Scale ( HDRS ) score as a response to therapy and was correlated with measures of st and ard deviation of the mean of all 5-minute segments of normal electrocardiographic R-R intervals ( SDANN ) , st and ard deviation of all normal R-R intervals ( SDNN ) , root mean square of successive differences in R-R intervals ( r-MSSD ) , and percentage difference between adjacent normal R-R intervals that are greater than 50 msec (pNN50)from 24-hour electrocardiogram ( ECG ) tapes . Results : Ten out of 14 patients responded . Response was associated with an increase in SDANN of 17 % ( P < 0.05 ) . Nonresponse was associated with a 17 % decrease in SDANN and a 22 % decrease in SDNN ( both P < 0.05 ) . No other measures correlated with therapeutic response . No heart-rate variability ( HRV ) differences between the 2 drug therapies were observed . Conclusion : Twenty-four-hour HRV measures may be useful in assessing response to antidepressant therapy INTRODUCTION The vast majority of work on the physiological effects of nicotine in humans has been done in smokers or smokers trying to quit . Such studies can be confounded by tolerance , desensitization of receptors , or withdrawal . Because of these difficulties , there is still some dispute as to whether nicotine is proparasympathetic or prosympathetic in humans . To circumvent these difficulties , we assessed the effect of nicotine on autonomic function by measuring changes in heart rate variability ( HRV ) in nicotine-naive healthy subjects . METHODS Twenty males and 20 females aged between 18 and 25 years received 4 mg oral nicotine lozenge or placebo . HRV was assessed in 15-min periods before , during , and after ingestion . RESULTS There were no significant changes in any measure after placebo administration . During and after nicotine ingestion , heart rate increased to 78 ± 2 beats per minute ( bpm ) from a baseline level of 75 ± 2 bpm ( p < .01 ) . Nicotine significantly increased low frequency ( LF ; normalized units ) from 66 ± 2 at baseline to 70 ± 2 at 15 - 30 min postingestion ( p < .01 ) and decreased high frequency ( HF ; normalized units ) from 28 ± 2 to 24 ± 1 ( p < .01 ) . LF/HF ratio was therefore substantially increased from 2.9 ± 0.3 to 3.7 ± 0.3 ( p < .01 ) . CONCLUSIONS A single dose of 4 mg oral nicotine produces a significant reduction in HRV ( i.e. , a proportional decrease in high-frequency variability ) in healthy young nonsmokers consistent with a reduced vagal activity . This has implication s for nicotine replacement treatments aim ed at cessation of smoking A total of 32 unmedicated patients with episodes of major depression ( DSM-III-R ) and 32 normal control subjects matched for age and sex were tested for heart rate variability ( R-R variation ) while resting and during deep breathing . Compared with the group of healthy subjects , the depressed patients showed no abnormalities before therapy . The patients were r and omly allocated for treatment with 150 mg of amitriptyline per day ( N = 8) , 150 mg of doxepin per day ( N = 8) , 150 mg of fluvoxamine per day ( N = 8) , and 20 mg of paroxetine per day ( N = 8) . During treatment with either amitriptyline or doxepin , the coefficients of variation at rest and during deep breathing , which are largely independent of heart rate , had significantly decreased after 14 days ( p = 0.012 ) , whereas patients treated with fluvoxamine or paroxetine showed no significant changes of heart rate variability parameters after 14 days . The implication s of these findings are discussed Cardiac patients often have sinus arrhythmia of nonrespiratory origin ( erratic sinus rhythm [ ESR ] ) . ESR was quantified using hourly Poincaré and power spectral heart rate variability plots from normal-to-normal interbeat intervals and hourly values of the short-term fractal scaling exponent and correlations of normal-to-normal intervals in n = 60 nonsurvivors and n = 66 r and omly selected survivors in the Cardiac Arrhythmia Suppression Trial . Hours were coded ( ABN ) as normal ( 0 ) , borderline ( 0.5 ) , or ESR ( 1 ) . t Tests compared ABN for n = 2413 paired hours at baseline and on therapy . ABN was higher in nonsurvivors ( 0.38 + /- 0.44 vs 0.28 + /- 0.40 , baseline , and 0.51 + /- 0.45 vs 0.34 + /- 0.43 , on therapy , P < .001 ) . Increased ABN with treatment were greater in nonsurvivors . Normal hours at baseline ( relative risk = 0.77 ; 095 % confidence interval , 0.62 - 0.96 , P = .018 ) and on treatment ( relative risk = 0.47 ; 95 % confidence interval , 0.39 - 0.58 ) were significantly associated with decreased mortality compared with ESR . Quantification of ESR may identify more vulnerable patients or help monitor the effects of pharmacologic treatment There exists a growing body of evidence linking depression with cardiovascular events , although the mechanisms responsible remain unknown . We investigated the role of the autonomic nervous system and inflammation in the link between coronary heart disease and major depressive disorder ( MDD ) , and examined the cardiac risk modification following pharmacological treatment of depression . We measured cardiac baroreflex function , heart rate variability , pulse pressure and high sensitivity C-reactive protein ( hsCRP ) , all of which have an impact on cardiac risk , pre- and post-treatment in 25 patients with MDD , with no history of coronary heart disease , and in 15 healthy subjects . Treatment consisted of selective serotonin reuptake inhibitors for approximately 12 weeks . No significant differences were observed between untreated MDD patients and healthy subjects in blood pressure , heart rate , baroreflex sensitivity or heart rate variability . Pulse pressure and hsCRP , however , were significantly elevated in patients with MDD prior to treatment ( p=0.023 and p=0.025 , respectively ) . Moreover , while pharmacotherapy was effective in alleviating depression , surprisingly , each of cardiac baroreflex function , heart rate variability , pulse pressure and hsCRP was modified ( p<0.05 ) in a manner likely to increase cardiac risk . In conclusion , this study demonstrated higher pulse pressure and hsCRP plasma levels in patients with MDD , which might contribute to increased cardiac risk . Following treatment vagal activity was reduced , as indicated by reductions in baroreflex sensitivity and heart rate variability , accompanied by increases in pulse pressure and plasma hsCRP levels . Mechanisms potentially responsible for generating cardiac risk in patients treated with selective serotonin reuptake inhibitors may need to be therapeutically targeted to reduce the incidence of coronary heart disease in this population Spectral analysis of fluctuations in heart rate ( HR ) and blood pressure ( BP ) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine ( IMI ) or mirtazapine ( MIR ) . In a double-blind r and omized study , 10 patients received treatment with IMI and 10 patients received treatment with MIR . Cardiovascular parameters were studied before and after 4 weeks of treatment : HR and BP ( Finapres ) were recorded continuously during supine rest ( SR ) and orthostatic challenge ( OC ; 60-degrees head-up tilting ) . During SR and OC , power spectra were calculated for HR and systolic BP . Spectral density was assessed for three frequency b and s : low ( 0.02 - 0.06 Hz ) , mid ( 0.07 - 0.14 Hz ) , and high ( 0.15 - 0.50 Hz ) . Before treatment , the depressed patients ( N = 20 ) differed from age-matched controls ( N = 20 ) only in their response to OC : the depressed patients showed more suppression of HR variability ( both mid- and high-frequency b and fluctuations ) , indicating stronger vagal inhibition , and a reduced increase of BP variability ( mid-frequency b and fluctuations ) , indicating reduced sympathetic activation . After 4 weeks of treatment , patients treated with either antidepressant drug showed significant changes of HR ( increase ) and HR variability ( decrease ) during SR and OC ; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR . The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI ( strong ) and MIR ( weak ) , result ing in cardiac vagal inhibition . Whereas MIR had no effect on BP or BP variability , IMI specifically reduced mid-frequency b and fluctuations of BP as the result of a suppression of central sympathetic activity . Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients : spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved , specifically during OC . The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs . In fact , some of the components of the cardiovascular autonomic dysfunction were further aggravated , depending on the pharmacologic profile of the drug under investigation BACKGROUND Patients with depression have higher rates of cardiac morbidity and mortality . Alterations of cardiac autonomic functions associated with depression may partly explain this . Prospect i ve studies comparing the effects of antidepressants on these abnormalities are limited due to confounding factors and co-morbidities . METHODS Cardiac autonomic functions were studied in antidepressant naïve patients with major depression ( without co-morbid medical or psychiatric disorders ) before and after treatment with repetitive transcranial magnetic stimulation ( rTMS ; n=30 ) , specific serotonin reuptake inhibitors ( SSRIs ; n=32 ) and tricyclic antidepressants ( TCAs ; n=32 ) . Conventional autonomic function tests and time- and frequency-domain measures of heart rate variability ( HRV ) were measured using st and ard procedures . Changes in autonomic functions were compared across the three treatment groups using repeated measures analysis of variance ( ANOVA ) using sex and age as covariates . RESULTS Depression improved by comparable extent across patients treated with the three treatments . Overall , there was no change in cardiac autonomic functions . However , significant group × occasion interactions were noted for HRV measures . Both time- and frequency-domain HRV measures showed increase with rTMS and decrease with TCAs ; they remained virtually unchanged with SSRIs . LIMITATIONS One of the major limitations of our work being we could not r and omize the treatment groups . CONCLUSIONS The effects of antidepressant treatments on cardiac autonomic function abnormalities found in depression vary with the mode of treatment used . Long-term clinical implication s of these effects on cardiac health of patients with depression need further studies In contrast to diabetic autonomic neuropathy , cardiovascular autonomic neuropathy ( CAN ) in long-term alcoholics has been studied rarely . Using both st and ardized bedside tests and computer-assisted analysis of heart rate variability ( HRV ) , we prospect ively compared autonomic neurocardial function between 35 strictly selected , detoxified alcoholics ( DSM-III-R ) , and 80 well matched healthy controls . Evidence for a potential CAN was found in 25.7 % of all the alcoholics studied and in 41 % of those with clinical ly manifest PNP ( n=22 ) . Overall , our results demonstrated a significant association between the presence of a CAN and peripheral neuropathy ( PNP ) amongst chronic alcoholics ( chi-square test P<0.05 ) ; there was no evidence of a CAN in any of the alcoholics without a clinical ly manifest PNP . The CAN was characterized by a dissociated appearance of parasympathetic and sympathetic disorders . Our findings provide reason to suspect that the total lifetime dose of alcohol and the duration of alcohol dependence are the most important factors contributing to the pathogenesis of both PNP and sympathetic dysfunction . As is the case with diabetics , computer-assisted measurements of HRV including spectral analysis appear to be far superior to conventional bedside tests for detecting evidence of cardiovagal dysfunction in long-term alcoholics Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability . This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients . However , the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated , applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias . We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls . New nonlinear parameters ( approximate entropy , compression entropy , fractal dimension ) of heart rate variability and also the QT-variability index were calculated . In accordance with previous results , we have observed reduced complexity of heart rate regulation in untreated patients . Furthermore , the QT-variability index was significantly increased in unmedicated patients , indicating increased repolarization lability . Reduction of the heart rate regulation complexity after olanzapine treatment was seen , as measured by compression entropy of heart rate . No change in QT variability was observed after treatment . This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction . Olanzapine treatment seems to have very little additional impact in regard to the QT variability . However , the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function , which may increase the risk for cardiac mortality . Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics The analysis of heart rate variability ( HRV ) has proven to be useful in evaluating the neuroautonomic dysfunctions associated with various clinical conditions . The purpose of this study was to investigate the linear and non-linear dynamic measures of HRV , and to evaluate their relationship with the psychotic symptom severity , in clozapine-treated schizophrenic subjects . Fifty schizophrenic patients treated with clozapine as monotherapy and 50 normal control subjects were evaluated for HRV analysis . The HRV measurements were obtained from a 30-min resting electrocardiogram ( ECG ) . The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale ( PANSS ) . In the patient group , the complexity and symbolic dynamics measures as well as the time and frequency domain measures of HRV were significantly lower than in the control group ( P<0.01 ) . The intermediate-term fractal scaling component value was significantly higher in the patient group ( P<0.01 ) . The PANSS total score and the positive symptom subscale score had significant negative correlations with the sample entropy ( SampEn ) value ( P<0.01 ) . In conclusion , schizophrenic patients treated with clozapine had markedly different heart rate dynamics compared to normal control subjects . The severity of psychotic symptoms was associated with the SampEn value , suggesting that the non-linear complexity measure might be useful in assessing the neuroautonomic dysfunction in schizophrenia BACKGROUND Panic disorder ( PD ) patients have been shown to have reduced heart rate variability ( HRV ) . Low HRV has been associated with elevated risk for cardiovascular disease . Our aim was to investigate the effects of treatment on heart rate ( HR ) in patients with PD through a hyperventilation challenge . METHODS We studied 54 participants , 43 with Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV ) PD and 11 controls . Subjects lay supine with their heads in a plastic canopy chamber , resting for 15 min and then breathing at a rate of 30 breaths per minute for 10 min . HRV was sample d for spectral analysis . Clinical and behavioral measures of anxiety were assessed . Treatment was chosen by patients : either 12 weeks of CBT alone or CBT with sertraline . RESULTS All patients showed significant decrease on clinical measures from baseline and 31 were treatment responders , 8 dropped out of the study before completion of the 12-week treatment phase and 4 were deemed nonresponders after 12 weeks of treatment . Although both treatments led to significant clinical improvement , only CBT alone demonstrated a significant reduction in HR and increase in HRV . CONCLUSIONS Our study replicated the finding that increased HR and decreased HRV occur in PD patients . Given the evidence of cardiac risk related to HRV , CBT appears to have additional benefits beyond symptom reduction . The mechanisms of this difference between CBT and sertraline are unclear and require further study PURPOSE Heart rate variability ( HRV ) reflects a healthy autonomic nervous system and is increased with physical training . Methamphetamine dependence ( MD ) causes autonomic dysfunction and diminished HRV . We compared recently abstinent methamphetamine-dependent participants with age-matched , drug-free controls ( DF ) and also investigated whether HRV can be improved with exercise training in the methamphetamine-dependent participants . METHODS In 50 participants ( MD = 28 ; DF = 22 ) , resting heart rate ( HR ; R-R intervals ) was recorded over 5 min while seated using a monitor affixed to a chest strap . Previously reported time domain ( SDNN , RMSSD , pNN50 ) and frequency domain ( LFnu , HFnu , LF/HF ) parameters of HRV were calculated with customized software . MD were r and omized to thrice-weekly exercise training ( ME = 14 ) or equal attention without training ( MC = 14 ) over 8 wk . Groups were compared using paired and unpaired t-tests . Statistical significance was set at P ≤ 0.05 . RESULTS Participant characteristics were matched between groups ( mean ± SD ) : age = 33 ± 6 yr ; body mass = 82.7 ± 12 kg , body mass index = 26.8 ± 4.1 kg·min . Compared with DF , the MD group had significantly higher resting HR ( P < 0.05 ) , LFnu , and LF/HF ( P < 0.001 ) as well as lower SDNN , RMSSD , pNN50 , and HFnu ( all P < 0.001 ) . At r and omization , HRV indices were similar between ME and MC groups . However , after training , the ME group significantly ( all P < 0.001 ) increased SDNN ( + 14.7 ± 2.0 ms , + 34 % ) , RMSSD ( + 19.6 ± 4.2 ms , + 63 % ) , pNN50 ( + 22.6 % ± 2.7 % , + 173 % ) , HFnu ( + 14.2 ± 1.9 , + 60 % ) , and decreased HR ( -5.2 ± 1.1 bpm , -7 % ) , LFnu ( -9.6 ± 1.5 , -16 % ) , and LF/HF ( -0.7 ± 0.3 , -19 % ) . These measures did not change from baseline in the MC group . CONCLUSIONS HRV , based on several conventional indices , was diminished in recently abstinent , methamphetamine-dependent individuals . Moreover , physical training yielded a marked increase in HRV , representing increased vagal modulation or improved autonomic balance Abstract : Depressed patients may exhibit reduced heart rate variability ( HRV ) , and antidepressants which block norepinephrine uptake may also lower HRV . This study compared paroxetine ( PAR ) and venlafaxine XR ( VEN-XR ) on HRV . Out patients were r and omly assigned to double-blind treatment with PAR up to 40 mg or VEN-XR up to 225 mg daily . HRV measures of parasympathetic control consisted of change in R-R interval during forced 10-second breaths and respiratory sinus arrhythmia ( RSA ) during paced breathing . Ex vivo estimates of serotonin and norepinephrine transporter occupancy were obtained before and after treatment , as were measures of depression , anxiety , and resilience . Plasma drug concentrations were measured at end point . Forty-nine patients entered treatment ; 44 of whom were evaluable ( n = 22 per group ) . Significant within-group reductions were noted in R-R interval variation and in RSA after VEN-XR only . Between-group analyses showed significant group-by-time interaction , with greater reduction in R-R interval variation and in RSA for VEN-XR compared with PAR . Improvement in resiliency correlated significantly with norepinephrine transporter occupancy for VEN-XR . Further comparisons of selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor drugs on HRV are warranted As part of a prospect i ve clinical study investigating the effects of atypical neuroleptics on autonomic neurocardiac function ( ANF ) , serial st and ardized recordings of conventional electrocardiograms and computer-calculated measurements of 5-minute resting heart rate variability ( HRV ) were obtained from 51 medication-free in patients with schizophrenia ( DSM-III-R-diagnosed ) before and after an average of 14.1 days of treatment with amisulpride 400 mg/day ( N = 12 ) , olanzapine 20 mg/day ( N = 13 ) , sertindole 12 mg/day ( N = 13 ) , or clozapine 100 mg/day ( N = 13 ) . Reference values for the HRV data were obtained from a large group of well-matched healthy controls ( N = 70 ) . The most important findings were the following : ( 1 ) clozapine , olanzapine , and sertindole all prolonged mean frequency-corrected QTc times , which , in the case of sertindole , proved to be significant ( Wilcoxon test p < 0.05 ) ; ( 2 ) sertindole and clozapine significantly increased the mean resting heart rate ; and ( 3 ) only clozapine significantly reduced the parasympathetic resting tone . The results of the HRV studies are discussed considering the in vitro receptor profiles of the atypical neuroleptics under study . Potential implication s for the cardiac safety and tolerance of these drugs are also discussed BACKGROUND The link between depression and autonomic dysfunction has attracted more attention since epidemiological studies have revealed that depressed patients have an augmented risk of cardiovascular morbidity and mortality . Former studies of autonomic dysfunction in major depression have shown inconclusive results . AIMS To further eluci date the effect of depression and medication on autonomic function , 18 patients and 18 matched control subjects were comprehensively assessed once medicated and once non-medicated as well as after full clinical recovery . METHODS Cardiac autonomic function was evaluated by measuring heart rate variability ( HRV ) parameters , and central autonomic tone was investigated by obtaining parameters of the pupillary light reflex ( PLR ) . RESULTS Acutely depressed patients who had not taken antidepressant medication for 8 weeks prior to the investigation differed significantly neither in heart rate parameters nor in parameters of the PLR from their controls . However , after 2 days of antidepressant treatment ( SSRI and NaSSRI ) , parameters of heart rate analysis and PLR ( except relative amplitude ) changed significantly and remained significantly different after clinical recovery . LIMITATIONS The study needs to be repeated using larger patient groups . Long-term studies are absolutely essential . CONCLUSION The state of depression did not influence autonomic parameters significantly . In fact , treatment influenced autonomic function far more than the disease itself . Other branches of the autonomic nervous system ( ANS ) , as well as new techniques should be applied to eluci date whether small changes in autonomic function exist . This might clarify whether disease or treatment might influence cardiac mortality in depression Evidence from previous studies suggests autonomic dysregulation in patients with major depressive disorder ( MDD ) . Antidepressant treatment may also affect central autonomic function . We investigated whether the type of antidepressant might be associated with the pattern of cardiorespiratory coordination in non-depressed women with recurrent MDD . Resting electrocardiograms and respiratory signals were simultaneously recorded from 38 euthymic women with recurrent MDD who were treated with either escitalopram ( n=19 ) or venlafaxine ( n=19 ) monotherapy and from 38 healthy women . Linear measures of heart rate variability were extracted to assess cardiac autonomic control . Sample entropy ( SampEn ) was computed to assess the complexity of heart rate and respiratory signals , and cross-SampEn was calculated to measure the nonlinear interaction of both signals . Significant decreases in the cardiovagal tone and cardiorespiratory coupling of women with recurrent MDD receiving venlafaxine , and tendencies toward lower cardiovagal tone and cardiorespiratory coupling in women with recurrent MDD receiving escitalopram were observed when compared with healthy controls . Effect sizes for these differences were large between women receiving venlafaxine and healthy controls . We found a positive association between cardiorespiratory decoupling and venlafaxine dose . Norepinephrine-enhancement , within a therapeutic dose range , seems to be closely associated with decreased vagal tone and reduced nonlinear coupling between heart rate and respiration in euthymic women with recurrent MDD . However , the effects of serotonin enhancement on cardiovagal tone should be considered . Our results suggest that the pharmacodynamic properties of antidepressants may affect autonomic regulation of women with recurrent MDD even in euthymic state |
10,971 | 30,728,053 | Barriers that influenced the implementation or acceptability of the toolkit intervention for physicians included time and staff constraints , Internet access , patient volume , and inadequate underst and ing of the quality improvement toolkit intervention . | Background The ACS QUIK trial showed that a multicomponent quality improvement toolkit intervention result ed in improvements in processes of care for patients with acute myocardial infa rct ion in Kerala but did not improve clinical outcomes in the context of background improvements in care .
We describe the development of the ACS QUIK intervention and evaluate its implementation , acceptability , and sustainability . | AIMS There are limited contemporary data on the presentation , management , and outcomes of acute coronary syndrome ( ACS ) admissions in India . We aim ed to develop a prospect i ve registry to address treatment and health systems gaps in the management of ACSs in Kerala , India . METHODS AND RESULTS We prospect ively collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125 hospitals in Kerala . We evaluated data on presentation , management , and in-hospital mortality and major adverse cardiovascular events ( MACE ) . We created r and om-effects multivariate regression models to evaluate predictors of outcomes while accounting for confounders . Mean ( SD ) age at presentation was 60 ( 12 ) years and did not differ among ACS types [ ST-segment myocardial infa rct ion ( STEMI ) = 37 % ; non-STEMI = 31 % ; unstable angina = 32 % ] . In-hospital anti-platelet use was high ( > 90 % ) . Thrombolytics were used in 41 % of STEMI , 19 % of non-STEMI , and 11 % of unstable angina admissions . Percutaneous coronary intervention rates were marginally higher in STEMI admissions . Discharge medication rates were variable and generally suboptimal ( < 80 % ) . In-hospital mortality and MACE rates were highest for STEMI ( 8.2 and 10.3 % , respectively ) . After adjustment , STEMI diagnosis ( vs. unstable angina ) [ odds ratio ( OR ) ( 95 % confidence interval = 4.06 ( 2.36 , 7.00 ) ] , symptom-to-door time > 6 h [ OR = 2.29 ( 1.73 , 3.02 ) ] , and inappropriate use of thrombolysis [ OR = 1.33 ( 0.92 , 1.91 ) ] were associated with higher risk of in-hospital mortality and door-to-needle time < 30 min [ OR = 0.44 ( 0.27 , 0.72 ) ] was associated with lower mortality . Similar trends were seen for risk of MACE . CONCLUSION These data represent the largest ACS registry in India and demonstrate opportunities for improving ACS care Background —Organizational and wider health system factors influence the implementation and success of interventions . Clinical Pathways in Acute Coronary Syndromes 2 is a cluster r and omized trial of a clinical pathway – based intervention to improve acute coronary syndrome care in hospitals in China . We performed a qualitative evaluation to examine the system-level barriers to implementing clinical pathways in the dynamic healthcare environment of China . Methods and Results —A qualitative descriptive analysis of 40 in-depth interviews with health professionals conducted in a sample of 10 hospitals purposively selected to explore barriers to implementation of the intervention . Qualitative data were analyzed using the Framework method . In-depth interviews identified 5 key system-level barriers to effective implementation : ( 1 ) leadership support for implementing quality improvement , ( 2 ) variation in the capacity of clinical services and quality improvement re sources , ( 3 ) fears of patient disputes and litigation , ( 4 ) healthcare funding constraints and high out-of-pocket expenses , and ( 5 ) patient-related factors . Conclusions —System-level barriers affect the ability of acute coronary syndrome clinical pathways to change practice . Addressing these barriers in the context of current and planned national health system reform will be critical for future improvements in the management of acute coronary syndromes , and potentially other hospitalized conditions , in China . Clinical Trial Registration —URL : http://www.anzctr.org.au/default.aspx . Register . Unique identifier : ACTRN12609000491268 BACKGROUND Acute coronary syndromes ( ACSs ) are a major cause of morbidity and mortality , yet effective ACS treatments are frequently underused in clinical practice . R and omized trials including the CPACS-2 study suggest that quality improvement initiatives can increase the use of effective treatments , but whether such programs can impact hard clinical outcomes has never been demonstrated in a well-powered r and omized controlled trial . DESIGN The CPACS-3 study is a stepped-wedge cluster-r and omized trial conducted in 104 remote level 2 hospitals without PCI facilities in China . All hospitalized ACS patients will be recruited consecutively over a 30-month period to an anticipated total study population of more than 25,000 patients . After a 6-month baseline period , hospitals will be r and omized to 1 of 4 groups , and a 6-component quality improvement intervention will be implemented sequentially in each group every 6months . These components include the following : establishment of a quality improvement team , implementation of a clinical pathway , training of physicians and nurses , hospital performance audit and feedback , online technical support , and patient education . All patients will be followed up for 6months postdischarge . The primary outcome will be the incidence of in-hospital major adverse cardiovascular events comprising all-cause mortality , myocardial infa rct ion or reinfa rct ion , and nonfatal stroke . CONCLUSIONS The CPACS-3 study will be the first large r and omized trial with sufficient power to assess the effects of a multifaceted quality of care improvement initiative on hard clinical outcomes , in patients with ACS Background —Substantial evidence - practice gaps exist in the management of acute coronary syndromes ( ACS ) in China . Clinical pathways are tools for improving ACS quality of care but have not been rigorously evaluated . Methods and Results —Between October 2007 and August 2010 , a quality improvement program was conducted in 75 hospitals throughout China with mixed methods evaluation in a cluster r and omized , controlled trial . Eligible hospitals were level 2 or level 3 centers routinely admitting > 100 patients with ACS per year . Hospitals were assigned immediate implementation of the American Heart Association/American College of Cardiology guideline based clinical pathways or commencement of the intervention 12 months later . Outcomes were several key performance indicators reflecting the management of ACS . The key performance indicators were measured 12 months after commencement in intervention hospitals and compared with baseline data in control hospitals , using data collected from 50 consecutive patients in each hospital . Pathway implementation was associated with an increased proportion of patients discharged on appropriate medical therapy , with nonsignificant improvements or absence of effects on other key performance indicators . Conclusions —Among hospitals in China , the use of a clinical pathway for the treatment of ACS compared with usual care improved secondary prevention treatments , but effectiveness was otherwise limited . An accompanying process evaluation identified several health system barriers to more successful implementation . Clinical Trial Registration —URL : http://www.anzctr.org.au/default.aspx . Unique identifier : ACTRN12609000491268 CONTEXT Studies have found that patients with acute coronary syndromes ( ACS ) often do not receive evidence -based therapies in community practice . This is particularly true in low- and middle-income countries . OBJECTIVE To evaluate whether a multifaceted quality improvement ( QI ) intervention can improve the use of evidence -based therapies and reduce the incidence of major cardiovascular events among patients with ACS in a middle-income country . DESIGN , SETTING , AND PARTICIPANTS The BRIDGE-ACS ( Brazilian Intervention to Increase Evidence Usage in Acute Coronary Syndromes ) trial , a cluster-r and omized ( concealed allocation ) trial conducted among 34 clusters ( public hospitals ) in Brazil and enrolling a total of 1150 patients with ACS from March 15 , 2011 , through November 2 , 2011 , with follow-up through January 27 , 2012 . INTERVENTION Multifaceted QI intervention including educational material s for clinicians , reminders , algorithms , and case manager training , vs routine practice ( control ) . MAIN OUTCOME MEASURES Primary end point was the percentage of eligible patients who received all evidence -based therapies ( aspirin , clopidogrel , anticoagulants , and statins ) during the first 24 hours in patients without contraindications . RESULTS Mean age of the patients enrolled was 62 ( SD , 13 ) years ; 68.6 % were men , and 40 % presented with ST-segment elevation myocardial infa rct ion , 35.6 % with non-ST-segment elevation myocardial infa rct ion , and 23.6 % with unstable angina . The r and omized clusters included 79.5 % teaching hospitals , all from major urban areas and 41.2 % with 24-hour percutaneous coronary intervention capabilities . Among eligible patients ( 923/1150 [ 80.3 % ] ) , 67.9 % in the intervention vs 49.5 % in the control group received all eligible acute therapies ( population average odds ratio [ OR(PA ) ] , 2.64 [ 95 % CI , 1.28 - 5.45 ] ) . Similarly , among eligible patients ( 801/1150 [ 69.7 % ] ) , those in the intervention group were more likely to receive all eligible acute and discharge medications ( 50.9 % vs 31.9 % ; OR(PA ) , , 2.49 [ 95 % CI , 1.08 - 5.74 ] ) . Overall composite adherence scores were higher in the intervention clusters ( 89 % vs 81.4 % ; mean difference , 8.6 % [ 95 % CI , 2.2%-15.0 % ] ) . In-hospital cardiovascular event rates were 5.5 % in the intervention group vs 7.0 % in the control group ( OR(PA ) , 0.72 [ 95 % CI , 0.36 - 1.43 ] ) ; 30-day all-cause mortality was 7.0 % vs 8.4 % ( ORPA , 0.79 [ 95 % CI , 0.46 - 1.34 ] ) . CONCLUSION Among patients with ACS treated in Brazil , a multifaceted educational intervention result ed in significant improvement in the use of evidence -based therapies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00958958 & NA ; Ischemic heart disease is the leading cause of death in India , and there are likely more myocardial infa rct ions in India than in any other country in the world . We have previously reported heterogeneous care for patients with myocardial infa rct ion in Kerala , a state in southern India , including both gaps in optimal care and inappropriate care . Based on that prior work , limitations from previous nonr and omized quality improvement studies and promising gains in process of care measures demonstrated from previous r and omized trials , we and the Cardiological Society of India — Kerala chapter sought to develop , implement , and evaluate a quality improvement intervention to improve process of care measures and clinical outcomes for these patients . In this article , we report the rationale and study design for the ACS QUIK cluster‐r and omized stepped‐wedge clinical trial ( NCT02256657 ) in which we aim to enroll 15,750 participants with acute coronary syndromes across 63 hospitals . To date , most participants are men ( 76 % ) and have ST‐segment elevation myocardial infa rct ion ( 63 % ) . The primary outcome is 30‐day major adverse cardiovascular events defined as death , recurrent infa rct ion , stroke , or major bleeding . Our secondary outcomes include health‐related quality of life and individual‐ and household‐level costs . We also describe the principal features and limitations of the stepped‐wedge study design , which may be important for other investigators or sponsors considering cluster‐r and omized stepped‐wedge trials Background The burden of cardiovascular diseases ( CVDs ) remains unclear in many regions of the world . Objectives The GBD ( Global Burden of Disease ) 2015 study integrated data on disease incidence , prevalence , and mortality to produce consistent , up-to- date estimates for cardiovascular burden . Methods CVD mortality was estimated from vital registration and verbal autopsy data . CVD prevalence was estimated using modeling software and data from health surveys , prospect i ve cohorts , health system administrative data , and registries . Years lived with disability ( YLD ) were estimated by multiplying prevalence by disability weights . Years of life lost ( YLL ) were estimated by multiplying age-specific CVD deaths by a reference life expectancy . A sociodemographic index ( SDI ) was created for each location based on income per capita , educational attainment , and fertility . Results In 2015 , there were an estimated 422.7 million cases of CVD ( 95 % uncertainty interval : 415.53 to 427.87 million cases ) and 17.92 million CVD deaths ( 95 % uncertainty interval : 17.59 to 18.28 million CVD deaths ) . Declines in the age-st and ardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries . Ischemic heart disease was the leading cause of CVD health lost globally , as well as in each world region , followed by stroke . As SDI increased beyond 0.25 , the highest CVD mortality shifted from women to men . CVD mortality decreased sharply for both sexes in countries with an SDI > 0.75 . Conclusions CVDs remain a major cause of health loss for all regions of the world . Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI , but only a gradual decrease or no change in most regions . Future up date s of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD Background —In-hospital and postdischarge treatment rates for acute coronary syndrome ( ACS ) remain low in India . However , little is known about the prevalence and associations of the package of optimal ACS medical care in India . Our objective was to define the prevalence , associations , and impact of optimal in-hospital and discharge medical therapy in the Kerala ACS Registry of 25 718 admissions . Methods and Results —We defined optimal in-hospital ACS medical therapy as receiving the following 5 medications : aspirin , clopidogrel , heparin , & bgr;-blocker , and statin . We defined optimal discharge ACS medical therapy as receiving all of the above therapies except heparin . Comparisons by optimal versus nonoptimal ACS care were made via Student t test for continuous variables and & khgr;2 test for categorical variables . We created r and om effects logistic regression models to evaluate the association between Global Registry of Acute Coronary Events risk score variables and optimal in-hospital or discharge medical therapy . Optimal in-hospital and discharge medical care were delivered in 40 % and 46 % of admissions , respectively . Wide variability in both in-hospital and discharge medical care was present , with few hospitals reaching consistently high ( > 90 % ) levels . Patients receiving optimal in-hospital medical therapy had an adjusted odds ratio ( 95 % confidence interval)=0.93 ( 0.71 , 1.22 ) for in-hospital death and an adjusted odds ratio ( 95 % confidence interval)=0.79 ( 0.63 , 0.99 ) for major adverse cardiovascular event rates . Patients who received optimal in-hospital medical care were far more likely to receive optimal discharge care ( adjusted odds ratio [ 95 % confidence interval ] = 10.48 [ 9.37 , 11.72 ] ) . Conclusions —Strategies to improve in-hospital and discharge medical therapy are needed to improve local process-of-care measures and ACS outcomes in Kerala |
10,972 | 30,762,815 | Results : This systematic review will assess the effectiveness of ES on AEs caused by chemotherapy in patients with CC .
Conclusion : The findings of this study may summarize the latest evidence for the ES on AEs following chemotherapy for CC . | Background : This protocol of systematic review aims to investigate the effectiveness of electrical stimulation ( ES ) on adverse events ( AEs ) caused by chemotherapy in patients with cervical cancer ( CC ) . | OBJECTIVE This multicenter phase II Japanese Gynecologic Oncology Group study ( JGOG1067 ) was design ed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer . METHODS Patients with stage IB-IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study . The patients postoperatively received irinotecan ( CPT-11 ; 60mg/m2 intravenously on days 1 and 8) and nedaplatin ( NDP ; 80mg/m2 intravenously on day 1 ) . Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles . The primary endpoint of this study was the 2-year recurrence-free survival ( RFS ) rate . The secondary endpoints were the 5-year overall survival ( OS ) rate , 5-year RFS rate , and adverse events such as complications of chemotherapy and lower-limb edema . RESULTS Sixty-two patients were analyzed according to our protocol , among whom 55 ( 88.7 % ) completed 5cycles of scheduled treatment . The median follow-up period was 66.1months ( range , 16.8 - 96.6months ) . The 2-year and 5-year RFS rates were 87.1 % ( 95 % confidence interval [ CI ] : 75.9 - 99.3 ) and 77.2 % ( 95 % CI : 64.5 - 85.8 ) , respectively . Fourteen patients ( 22.5 % ) experienced recurrence during the follow-up period , 8 of whom died of the disease . The 5-year OS rate in this study was 86.5 % ( 95 % CI : 74.8 - 93.0 ) . Only 9.7 % of the patients experienced lymphedema in their legs . CONCLUSION Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer BACKGROUND To evaluate the efficacy of a miniaturized portable transcutaneous electrical nerve stimulation ( TENS ) unit ( ReliefB and ) as an adjunct to st and ard antiemetic therapy for controlling nausea and vomiting induced by cisplatin-based chemotherapy in gynecologic oncology patients . METHODS Forty-two patients were enrolled in a r and omized , double-blind , placebo-controlled parallel-subjects trial with a follow-up crossover trial . All patients received a st and ardized antiemetic protocol , then wore the ReliefB and continuously for 7 days . RESULTS Thirty-two patients were evaluable for the parallel-subjects component , 16 in each group . The percentage of patients with absent or minimal nausea was 59 % overall , which was similar to that for both the active ( 56 % ) and placebo ( 62 % ) groups . The incidence and severity of nausea and vomiting was similar for each group . Eighteen patients completed two consecutive cycles and were evaluable for the crossover component . The average age of the crossover patients and their dose intensity were comparable with those of the overall study population ( 56.3 versus 58.6 years and 22.7 versus 22.7 mg/m2/week , respectively ) . The percentage of cycles with absent or minimal nausea was 47 % overall , which was similar to that of the active ( 50 % ) and placebo ( 44 % ) cycles . However , the severity of nausea was significantly lower in the active cycles during days 2 to 4 . Patients averaged less than one episode of vomiting daily in each cycle . CONCLUSIONS The ReliefB and is an effective adjunct to st and ard antiemetic agents for controlling nausea induced by cisplatin-based chemotherapy in gynecologic oncology patients OBJECTIVES . The aim of this study was to compare 4 versus 6 courses of adjuvant chemotherapy after neoadjuvant chemotherapy plus radical surgery in terms of overall survival ( OS ) , disease-free survival ( DFS ) , recurrence rate and toxicity profile . METHODS . We r and omly assigned 200 patients with IB2-IIB cervical cancer to receive 4 ( Group A ) or 6 ( Group B ) courses of cisplatin 100 mg/mq and paclitaxel 175 mg/mq every 21 days . RESULTS . At 4-years follow-up , the comparison of recurrence rate ( p = 1 ; RR = 1.005 ; 95 % CI = 0.87 to 1.161 ) , OS ( p = 0.906 ) and DFS ( p = 0.825 ) did not show statistically significant differences between the two groups . Data analysis showed statistically significant differences between the two groups in term of episodes of leukopenia ( p = 0.0072 ; RR = 1.513 ; 95 % CI = 1.127 - 2.03 ) , anemia ( p = 0.048 ; RR = 1.188 ; CI = 1.012 - 1.395 ) and febrile neutropenia ( p = 0.042 ; RR = 1.119 ; 95 % CI = 1.014 - 1.235 ) , in favor of Group A. As regards non-hematological toxicities , there were no statistically significant differences in terms of gastrointestinal symptoms ( p = 0.49 ; RR = 1.046 ; CI = 0.948 - 1.153 . On the contrary , there was a statistically significant difference regarding neurological symptoms ( p=0.014 ; RR=1.208 ; CI=1.046 - 1.395 ) , that were less frequent in Group A ( 13 % ) than in Group B ( 28 % ) . CONCLUSIONS . Adjuvant treatment with 4 or 6 courses of platinum-based chemotherapy showed similar results in terms of OS and DSF , with a favorable toxicity profile in favor of the first regimen CONTEXT Chemotherapy-induced peripheral neuropathy ( CIPN ) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents , affecting up to 30%-40 % of patients . To date , there is no effective prevention or therapy . An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse . OBJECTIVES To evaluate the impact on CIPN associated with the MC5-A Calmare ® therapy device . METHODS The MC5-A Calmare ® therapy device is design ed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity . Sixteen patients from one center received one-hour interventions daily over 10 working days . RESULTS Of 18 patients , 16 were evaluable . The mean age of the patients was 58.6 years-four men and 14 women- and the duration of CIPN was three months to eight years . The most common drugs were taxanes , platinums , and bortezomib ( Velcade , Millenium Pharmaceuticals , Cambridge MA ) . At the end of the study ( Day 10 ) , a 20 % reduction in numeric pain scores was achieved in 15 of 16 patients . The pain score fell 59 % from 5.81±1.11 before treatment to 2.38±1.82 at the end of 10 days ( P<0.0001 by paired t-test ) . A daily treatment benefit was seen with a strong statistically significant difference between the pre- and post-daily pain scores ( P<0.001 ) . Four patients had their CIPN reduced to zero . A repeated- measures analysis using the scores from all 10 days confirmed these results . No toxicity was seen . Some responses have been durable without maintenance . CONCLUSION Patient-specific cutaneous electrostimulation with the MC5-A Calmare ® device appears to dramatically reduce pain in refractory CIPN patients with no toxicity . Further studies are underway to define the benefit , mechanisms of action , and optimal schedule Background Many patients experience nausea and vomiting during chemotherapy treatment . Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting ( CINV ) . However , the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified . Methods / Design This study consists of a r and omized controlled trial ( RCT ) with four parallel arms : a control group and three electroacupuncture groups ( one with Neiguan ( PC6 ) , one with Zhongwan ( CV12 ) , and one with both PC6 and CV12 ) . The control group received st and ard antiemetic only , while the other three groups received electroacupuncture stimulation with different acupoints besides the st and ard antiemetic . The intervention is done once daily from the first day ( day 1 ) to the fourth day ( day 4 ) during chemotherapy treatment . The primary outcome measures include frequency of nausea , vomiting and retching . The secondary outcome measures are the grade of constipation and diarrhea , electrogastrogram , assessment of quality of life , assessment of anxiety and depression , and other adverse effects during the chemotherapy . Assessment s are scheduled from one day pre-chemotherapy ( day 0 ) to the fifth day of chemotherapy ( day 5 ) . Follow-ups are done from day 6 to day 21 . Discussion The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV.Trial registration The register number of r and omized controlled trial is NCT02195908 . The date of registration was 21 July 2014 PURPOSE The aim of this Phase II , non-r and omized study was to assess activity and safety of neoadjuvant chemotherapy ( NACT ) before chemoradiation ( CT/RT ) followed by radical surgery ( RS ) in locally advanced cervical cancer ( LACC ) patients . METHODS AND MATERIAL S The primary end point was rate of pathologic complete response ( pCR ) . FIGO Stage IB2-IVA patients were administered NACT chemotherapy ( paclitaxel 80 mg/m2 , carboplatin AUC 2 ) , for 6 weeks , followed by Intensity Modulated Radiotherapy plus simultaneous boost ( total dose of 50.4 Gy to CTV1 , and 39.6 Gy to CTV2 ) . Clinical response was assessed according to RECIST criteria . Responsive patients were triaged to RS . The regimen would be considered active if > 20 pCRs were registered in 39 patients . RESULTS 45 patients were enrolled into the study ; 25 patients ( 55.5 % ) were FIGO stage IIB , 9 cases ( 20.0 % ) had stage III disease . At work up , pelvic lymph node involvement was documented in 38 ( 84.4 % ) patients ; pCR was documented in 18 out of 40 patients ( 45.0 % ) . Grade 3 - 4 hematological toxicity after NACT occurred in 4 patients ; CT/RT associated grade 3 toxicity was found in 7 patients . Early and late postoperative complications were detected in 16 , and 11 cases , respectively . Three-year PFS and OS were 66.0 % and 86.0 % , respectively . CONCLUSIONS NACT followed by CT/RT by IMRT and RS , is feasible and safe ; failure to achieve the primary endpoint has to be recognized ; however , enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size , could have result ed in reduced activity A prospect i ve phase 2 study was conducted to evaluate the clinical utility of acupuncture-like transcutaneous nerve stimulation ( ALTENS ) for the treatment of chemotherapy-induced peripheral neuropathy ( CIPN ) . Eligible cancer patients had a < 2 ECOG performance score , received neurotoxic chemotherapy , and developed CIPN symptoms for > two months . R and omization was used to eliminate bias in patient selection for ALTENS and was not to compare the effectiveness between the two treatments . ALTENS treatments were delivered using Codetron units . Bilateral acupuncture points included LI4 and LIV3 , plus LI11 or ST36 were stimulated . Acupuncture treatments were administered to CV6 , SP6 , ST6 , LI11 , Bafeng , Baxie and selective Jing points bilaterally . Twelve treatments were delivered twice weekly over 6 to 8 weeks . The Modified Total Neuropathy Score ( mTNS ) , Numbness Score , and Edmonton Symptom Assessment Score ( ESAS ) were assessed at baseline , treatment completion , plus at 3 and 6 months follow-up . The primary study endpoint was mTNS score at 6 months . We planned to recruit 23 patients into each group . After 30 patients were recruited , 2 were lost to follow-up at 3 months in the ALTENS group and 3 in the acupuncture group . The research team decided to recruit all remaining consecutive patients only to the ALTENS group to ensure an adequate evaluation of ALTENS , the primary object of evaluation . There were 27 patients in the ALTENS group , with an average symptom duration of 10 months after chemotherapy . Twenty four and 23 patients completed the 3 and 6 month follow-up respectively . The median mTNS scores were 7.1 , 4.0 , 3.6 and 3.1 at baseline , treatment completion , 3 and 6 months follow-up , respectively . One-way ANOVA analysis showed a significant improvement in mTNS scores ( p<0.001 ) at 6 months . Numbness scores were also significantly improved at 6 months . ESAS pain scores and perception of well-being scores analyses were inconclusive . There were no significant reported side effects of ALTENS . There were only 13 patients in the acupuncture group and the number was insufficient for either an independent or a comparative analysis . The results of this study suggests that ALTENS significantly reduces the mTNS scores and numbness in patients suffering from CIPN symptoms The beneficial effects of transcutaneous electrical stimulation of the P6 antiemetic point ( Neiguan ) as an adjuvant to st and ard antiemetics was studied in over 100 patients in whom chemotherapy-induced sickness was not adequately controlled by antiemetics alone . Although the results were not quite as good as with invasive acupuncture , more than 75 % patients achieved considerable benefit from what was a nontoxic procedure . The use of large diffuse low impedence electrodes simplifies the technique . The 2 hourly application of Sea B and s prolongs the antiemetic action . Best results were obtained from the 2 hourly self-administration of 5 min of transcutaneous electrical stimulation of P6 using a simple battery-operated TENS machine ( 15 Hz ) to activate a large , easy-to-place surface electrode and increasing current until Qi is elicited OBJECTIVE To compare the clinical effects between electroacupuncture at Zusanli ( ST 36 ) combined with intravenous drip of Granisetron and intravenous drip of Granisetron only for treatment of nausea and vomiting caused by the chemotherapy of the malignant tumor . METHODS The methods of multi central , r and omized controlled trial were used , the observation group ( 127 cases ) was treated with electroacupuncture at Zusanli ( ST 36 ) combined with intravenous drip of Granisetron , and the control group ( 119 cases ) was treated with intravenous drip of Granisetron only . RESULTS The total effective rate of 90.5 % in observation group was superior to that of 84.0 % in control group ( P < 0.01 ) ; the nausea and vomiting scores of two groups were obviously decreased after treatment ( both P < 0.001 ) , and the decreased degree of the observation group was superior to that of control group ( P < 0.001 ) . CONCLUSION Electroacupuncture at Zusanli ( ST 36 ) can significantly alleviate the symptoms such as nausea and vomiting caused by the chemotherapy of the patients Cervical cancer is one of the leading causes of cancer-related deaths among women and it is caused by the human papillomavirus ( HPV ) . High variation has been reported in the attribution of specific HPV genotypes to cervical neoplasia among various geographic regions . For effective control of cervical cancer through HPV vaccination , it is essential to estimate the cost-effectiveness of vaccination , to monitor the potential transition into other HPV genotypes , and to underst and the distribution of specific HPV genotypes across a specific geographic region . In this study , the distribution of HPV genotypes was investigated in southeast China , from 2011 to 2016 . The 12,816 cervical swabs collected from women ( age 18–78 years , median 43.6 years ) out patients were analyzed . HPV prevalence among 12,816 cervical swabs analyzed was 22.3 % ( 2,856/12,816 ) . Among these positive cases , 2,216 had only one HPV genotype while 640 had multiple HPV genotypes . The cases with multiple types revealed 23 different HPV genotypes with the five most prevalent being HPV18 ( 18.2 % ) , HPV52 ( 14.1 % ) , HPV16 ( 11.9 % ) , HPV58 ( 10.6 % ) , and HPV33 ( 5.5 % ) . The rates of HPV infection in patients with cervical inflammation , CIN-1 , CIN-2 , CIN-3 , squamous carcinoma , and adenocarcinoma were 38.4 % , 80.5 % , 82.6 % , 92.3 % , 97.5 % , and 93.4 % , respectively . Four HPV genotypes , HPV18 , HPV16 , HPV52 , and HPV58 , were more prevalent in patients with CIN-2-CIN-3 and invasive cervical cancer . A comparison of HPV genotypes attribution to cervical cancer between southeast China and global incidences revealed distinct differences . Due to this unique prevalence , it is essential to streamline the vaccination development protocol prior to administering vaccines based on global data |
10,973 | 28,146,603 | The effects of the various regimens on lung function were non-significant .
People with cystic fibrosis could be encouraged to inhale hypertonic saline before or during airway clearance techniques to maximise perceived efficacy and satisfaction , even though these timing regimens may not have any better effect on lung function than inhalation after airway clearance techniques . | BACKGROUND Inhalation of hypertonic saline improves sputum rheology , accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis .
OBJECTIVES To determine whether the timing of hypertonic saline inhalation ( in relation to airway clearance techniques or in relation to time of day ) has an impact on its clinical efficacy in people with cystic fibrosis . | BACKGROUND Beneficial effects of hypertonic saline on lung function in cystic fibrosis patients are well documented . However , the effects of various concentrations of hypertonic saline are not well studied . We , therefore , compared the effects of 3 and 7 % hypertonic saline administered by nebulization on lung function in children with cystic fibrosis . METHOD In a double-blind r and omized controlled trial , 31 children with cystic fibrosis were r and omized to receive either 3 % saline or 7 % saline nebulization twice daily for 28 days . Spirometry was performed and functional status was measured on Day 14 and 28 . RESULTS Of 31 children enrolled in the study , 30 completed the 28 days follow up ( 15 in each group ) . Percentage change in Forced Expiratory Volume during first second ( FEV(1 ) ) from baseline to Day 14 and on Day 28 was significantly higher in the group receiving 3 % saline as compared with those receiving 7 % saline inhalation . There was some decrease in FEV(1 ) ( percentage predicted ) immediately after 7 % saline inhalation unlike 3 % saline . The functional status remained comparable between the two groups . CONCLUSION The results suggest that 3 % hypertonic saline nebulization was better than 7 % saline inhalation . There is a need for studies with larger sample size and longer duration to confirm our results Background The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis ( CF ) . Objectives To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay , lung function , symptoms , oxygenation , exercise tolerance , quality of life , bacterial load and time to next hospitalisation . Methods 132 adults with an exacerbation of CF were r and omised to inhale three nebulised doses a day of either 4 mL 7 % saline or a taste-masked control of 0.12 % saline , throughout the hospital admission . The primary outcome measure was length of hospital stay . Results All participants tolerated their allocated saline solution . There was no significant difference in length of stay , which was 12 days in the hypertonic saline group and 13 days in controls , with a mean between-group difference ( MD ) of 1 day ( 95 % CI 0 to 2 ) . The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group ( 75 % vs 57 % ) , and the number needed to treat was 6 ( 95 % CI 3 to 65 ) . On a 0–100 scale , the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep ( MD=13 , 95 % CI 4 to 23 ) , congestion ( MD=10 , 95 % CI 3 to 18 ) and dyspnoea ( MD=8 , 95 % CI 1 to 16 ) . No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups ( HR=0.86 ( CI 0.57 to 1.30 ) , p=0.13 ) . Other outcomes did not significantly differ . Conclusions Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay . Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution . Trial registration number ACTRN12605000780651 Our goal was to assess the role of early childhood vaccination in the occurrence of respiratory symptoms and allergic sensitization in 7 - 8-year-old Dutch and German children . A nested case-control study was conducted among children participating in a large longitudinal study on respiratory health , to study the relationship between vaccination ( bacille Calmette-Guérin ( BCG ) , pertussis , measles/mumps , rubella , and Haemophilus influenza type b ( Hib ) ) and respiratory symptoms and allergic sensitization . Parents of 510 7 - 8-year-old children with respiratory complaints and an equal number of r and omly selected children without respiratory complaints were asked to complete a question naire . Blood sample s were collected for specific serum IgE analysis . Vaccination status was assessed through the records of the participating Municipal Health Services . No association between vaccination against pertussis , measles , rubella , or Hib and respiratory symptoms or allergic sensitization was found . For sensitization against house dust mite , BCG vaccination result ed in an increased risk ( OR , 2.28 ; 95 % CI , 1.05 - 4.96 ) . Birth order was inversely associated with allergic sensitization , but was not related to respiratory symptoms . We found an association between BCG vaccination and the subsequent risk for sensitization against house dust mite . No evidence was found for an association between vaccination and respiratory symptoms . Earlier reports of an association of birth order with atopic disease were supported by the results of the present study BACKGROUND Chronic rhinosinusitis is a hallmark of Cystic fibrosis ( CF ) impairing the patients ' quality of life and overall health . However , therapeutic options have not been sufficiently evaluated . Bronchial inhalation of mucolytic substances is a gold st and ard in CF therapy . Previously , we found that sinonasal inhalation of dornase alfa as vibrating aerosol reduces symptoms of chronic rhinosinusitis more effectively than NaCl 0.9 % ( net treatment benefit : -5.87±2.3 points , p=0.017 ; SNOT-20 total score ) . This multicenter study compares the effect of NaCl 6.0 % vs. NaCl 0.9 % following the protocol from our preceding study with dornase alfa . METHODS Sixty nine CF patients with chronic rhinosinusitis in eleven German CF centers were r and omized to receive sinonasal vibrating inhalation of either NaCl 6.0 % or NaCl 0.9 % for 28days . After 28days of wash-out , patients crossed over to the alternative treatment . The primary outcome parameter was symptom score in the disease-specific quality of life Sino-Nasal Outcome Test-20 ( SNOT-20 ) . Additionally , pulmonary function was assessed , as well as rhinomanometry and inflammatory markers in nasal lavage ( neutrophil elastase , interleukin (IL)-1β , IL-6 , and IL-8 ) in a subgroup . RESULTS Both therapeutic arms were well tolerated and showed slight improvements in SNOT-20 total scores ( NaCl 6.0 % : -3.1±6.5 points , NaCl 0.9 % : -5.1±8.3 points , ns ) . In both treatment groups , changes of inflammatory parameters in nasal lavage from day 1 to day 29 were not significant . We suppose that the irritating properties of NaCl 6.0 % reduced the suitability of the SNOT-20 scores as an outcome parameter . Alternative primary outcome parameters such as MR-imaging or the quantity of sinonasal secretions mobilized with both saline concentrations were , however , not feasible . CONCLUSION Sinonasal inhalation with NaCl 6.0 % did not lead to superior results vs. NaCl 0.9 % , whereas dornase alfa had been significantly more effective than NaCl 0.9 % Background Streamlining the timing of treatments in cystic fibrosis ( CF ) is important to optimise adherence while ensuring efficacy . The optimal timing of treatment with hypertonic saline ( HTS ) and airway clearance techniques ( ACT ) is unknown . Objectives This study hypothesised that HTS before ACT would be more effective than HTS during ACT as measured by Lung Clearance Index ( LCI ) . Methods Adults with CF providing written informed consent were r and omised to a crossover trial of HTS before ACT or HTS during ACT on consecutive days . ACT treatment consisted of Acapella Duet . Patients completed LCI and spirometry at baseline and 90 min post treatment . Mean difference ( MD ) and 95 % CIs were reported . Results 13 subjects completed the study ( mean ( SD ) age 33 ( 12 ) years , forced expiratory volume in 1second % ( FEV1 % ) predicted 51 % ( 22 ) , LCI ( no. turnovers ) 14 ( 4 ) ) . Comparing the two treatments ( HTS before ACT vs HTS during ACT ) , the change from baseline to 90 min post treatment in LCI ( MD ( 95 % CI ) −0.02 ( −0.63 to 0.59 ) ) and FEV1 % predicted ( MD ( 95 % CI ) −0.25 ( −2.50 to 1.99 ) ) was not significant . There was no difference in sputum weight ( MD ( 95 % CI ) −3.0 ( −14.9 to 8.9 ) ) , patient perceived ease of clearance ( MD ( 95 % CI ) 0.4 ( −0.6 to 1.3 ) or satisfaction ( MD ( 95 % CI ) 0.4 ( −0.6 to 1.5 ) ) . The time taken for HTS during ACT was significantly shorter ( MD ( 95 % CI ) 14.7 ( 9.8 to 19.6 ) ) . Conclusions In this pilot study , HTS before ACT was no more effective than HTS during ACT as measured by LCI . Trial registration number NCT01753869 ; Pre- results BACKGROUND Inhaled hypertonic saline acutely increases mucociliary clearance and , in short-term trials , improves lung function in people with cystic fibrosis . We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial . METHODS In this double-blind , parallel-group trial , 164 patients with stable cystic fibrosis who were at least six years old were r and omly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent ( control ) saline twice daily for 48 weeks , with quinine sulfate ( 0.25 mg per milliliter ) added to each solution to mask the taste . A bronchodilator was given before each dose , and other st and ard therapies were continued during the trial . RESULTS The primary outcome measure , the rate of change ( slope ) in lung function ( reflected by the forced vital capacity [ FVC ] , forced expiratory volume in one second [ FEV1 ] , and forced expiratory flow at 25 to 75 percent of FVC [ FEF25 - 75 ] ) during the 48 weeks of treatment , did not differ significantly between groups ( P=0.79 ) . However , the absolute difference in lung function between groups was significant ( P=0.03 ) when averaged across all post-r and omization visits in the 48-week treatment period . As compared with the control group , the hypertonic-saline group had significantly higher FVC ( by 82 ml ; 95 percent confidence interval , 12 to 153 ) and FEV1 ( by 68 ml ; 95 percent confidence interval , 3 to 132 ) values , but similar FEF25 - 75 values . The hypertonic-saline group also had significantly fewer pulmonary exacerbations ( relative reduction , 56 percent ; P=0.02 ) and a significantly higher percentage of patients without exacerbations ( 76 percent , as compared with 62 percent in the control group ; P=0.03 ) . Hypertonic saline was not associated with worsening bacterial infection or inflammation . CONCLUSIONS Hypertonic saline preceded by a bronchodilator is an inexpensive , safe , and effective additional therapy for patients with cystic fibrosis . ( Clinical Trials.gov number , NCT00271310 . BACKGROUND : Positive expiratory pressure ( PEP ) is used for airway clearance in cystic fibrosis ( CF ) patients . Hypertonic saline ( HTS ) aerosol increases sputum expectoration volume and may improve respiratory secretion properties . CPAP may also be used to maintain airway patency and mobilize secretions . To evaluate if CPAP would increase the beneficial clearance effect of HTS in subjects with CF , we investigated the effects of CPAP alone and CPAP followed by HTS on sputum physical properties and expectoration volume in CF subjects . METHODS : In this crossover study , 15 CF subjects ( mean age 19 y old ) were r and omized to interventions , 48 hours apart : directed coughs ( control ) , CPAP at 10 cm H2O , HTS 7 % , and both CPAP and HTS ( CPAP+HTS ) . Sputum collection was performed at baseline and after interventions . Expectorated volume was determined and in vitro sputum properties were analyzed for contact angle and cough clearability . RESULTS : There were no significant differences between any treatment in arterial blood pressure , heart rate , or pulse oximetry , between the 2 time points . HTS and CPAP+HTS improved cough clearability by 50 % ( P = .001 ) and expectorated volume secretion by 530 % ( P = .001 ) . However , there were no differences between control and CPAP on sputum contact angle , cough clearability , or volume of expectorated secretion . CONCLUSIONS : CPAP alone had no effect on mucus clearance , sputum properties , or expectorated volume , and did not potentiate the effect of HTS alone in CF subjects BACKGROUND Cystic fibrosis ( CF ) airways are nitric oxide ( NO ) deficient . We studied safety and efficacy of repeated inhalations of nebulized L-arginine , the substrate for NO synthase ( NOS ) , in patients with CF . METHODS Double-blind , r and omized , placebo-controlled crossover treatment trial of twice daily inhalation of 500 mg L-arginine for two weeks compared to inhalation of saline in 19 CF patients ( Clinical Trials.gov Identifier : NCT00405665 ) . RESULTS L-arginine inhalation was well tolerated and result ed in a significant increase in exhaled NO . FEV1 increased by an average of 56 ml compared to -8 ml after saline solution ; but this difference did not reach statistical significance . Sputum concentrations of L-ornithine , the product of arginase activity , increased significantly while the L-ornithine derived polyamines did not . There was no change in inflammatory markers in sputum . CONCLUSION Repeated inhalation of L-arginine in CF patients was safe and well tolerated . Inhaled L-arginine increased NO production without evidence for changes in airway inflammation It has been postulated that hypertonic saline ( HS ) might impair the antimicrobial effects of defensins within the airways . Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance ( BMC ) in patients with cystic fibrosis ( CF ) . This study reports the effect of inhalation of another osmotic agent , dry powder Mannitol ( 300 mg ) , compared with its control ( empty capsules plus matched voluntary cough ) and a 6 % solution of HS on BMC in 12 patients with cystic fibrosis ( CF ) . Mucus clearance was measured using a radioaerosol/gamma camera technique . Post-intervention clearance was measured for 60 min , followed by cough clearance for 30 min . Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls . However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol ( 8.7+/-3.3 % versus 2.8+/-0.7 % ) and HS ( 10.0+/-2.3 % versus 3.5+/-0.8 % ) . There was also a significant improvement in cough clearance with the Mannitol ( 9.7+/-2.4 % ) compared with its control ( 2.5+/-0.8 % ) . Despite premedication with a bronchodilator , a small fall in forced expiratory volume in one second ( FEV1 ) was seen immediately after administration of both the mannitol ( 7.3+/-2.5 % ) and HS ( 5.8+/-1.2 % ) . Values of FEV1 returned to baseline by the end of the study . Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients . Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol Background Little is known of how mucociliary clearance ( MCC ) in children with cystic fibrosis ( CF ) and normal pulmonary function compares with healthy adults , or how an acute inhalation of 7 % hypertonic saline ( HS ) aerosol affects MCC in these same children . Methods We compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12 % saline ( placebo ) , or HS , admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind , r and omized , cross-over study . Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy , non-CF adults . Mucociliary clearance was quantified over a 90 min period , using gamma scintigraphy , and is reported as MCC at 60 min ( MCC60 ) and 90 min ( MCC90 ) . Results Median [ interquartile range ] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4 - 24.5]% and 19.3 [17.3 - 27.8%]% , respectively , which were similar to the adults with 17.8 [6.4 - 28.7]% and 29.6 [16.1 - 43.5]% , respectively . There was no significant improvement in MCC60 ( 2.2 [-6.2 - 11.8]% ) or MCC90 ( 2.3 [-1.2 - 10.5]% ) with HS , compared to placebo . In addition , 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90 , respectively , after inhalation of HS . A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 ( p = 0.045 ) . Conclusions These data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions , with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values . In addition , although MCC did not improve in all children after inhalation of HS , improvement did occur in children with relatively low MCC values after placebo . This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC values . Trial Registration Clinical Trials.gov : Background and aims Sensitive outcome measures to assess the efficacy of therapeutic interventions in patients with cystic fibrosis ( CF ) with mild lung disease are currently lacking . Our objective was to study the ability of the lung clearance index ( LCI ) , a measure of ventilation inhomogeneity , to detect a treatment response to hypertonic saline inhalation in paediatric patients with CF with normal spirometry . Methods In a crossover trial , 20 patients with CF received 4 weeks of hypertonic saline ( HS ) and isotonic saline ( IS ) in a r and omised sequence separated by a 4 week washout period . The primary end point was the change in the LCI due to HS versus IS . Results Baseline characteristics including the LCI were not significantly different between both study periods . Four weeks of twice-daily HS inhalation significantly improved the LCI compared with IS ( 1.16 , 95 % CI 0.26 to 2.05 ; p=0.016 ) , whereas other outcome measures such as spirometry and quality of life failed to reach statistical significance . R and omisation order had no significant impact on the treatment effect . Conclusions The LCI , but not spirometry was able to detect a treatment effect from HS inhalation in patients with CF with mild disease and may be a suitable tool to assess early intervention strategies in this patient population . Clinical trial number NCT00635141 QUESTION Among adults with cystic fibrosis , does the timing of hypertonic saline relative to airway clearance techniques affect lung function , perceived efficacy , tolerability , or satisfaction with the entire airway clearance regimen , and is the preferred timing regimen stable over time ? DESIGN A r and omised crossover trial with concealed allocation , intention-to-treat analysis , and blinded assessors . PARTICIPANTS 50 adults with cystic fibrosis and stable lung function at the end of a hospital admission . INTERVENTION Participants performed 3 sessions of airway clearance techniques per day for 3 days . On each day , participants were r and omised to inhale hypertonic saline either before , during , or after the airway clearance techniques . Participants readmitted within one year repeated the 3-day study . OUTCOME MEASURES The primary outcome was the change in forced expiratory volume in one second ( FEV(1 ) ) from before to 2 hours after an entire airway clearance session . Secondary outcomes were change in forced vital capacity , perceived efficacy , tolerability , satisfaction , adverse events , and adherence . RESULTS All 50 participants completed the study . The effects on lung function were non-significant or were of borderline statistical significance favouring inhalation of hypertonic saline before airway clearance techniques . Satisfaction was rated significantly worse on a 100 mm scale when hypertonic saline was inhaled after the airway clearance techniques : mean differences 20 mm ( 95 % CI 12 to 29 ) compared to before the airway clearance techniques and 15 mm ( 95 % CI 6 to 24 ) compared to during the techniques . Perceived effectiveness showed similar effects but other outcomes were unaffected . All 14 participants who were readmitted repeated the study and most preferred the same timing regimen . Conclusion People with cystic fibrosis could be encouraged to time hypertonic saline before or during airway clearance techniques to maximise perceived efficacy and satisfaction , even though lung function may not be better with these timing regimens . TRIAL REGISTRATION ACTRN12611000673943 HYPOTHESIS We hypothesized that aerosol distribution in the lungs of patients with cystic fibrosis changes with positive expiratory pressure ( PEP ) . METHODS Eight patients were r and omized to one of 2 conditions . On one study day , patients inhaled saline aerosol containing 99mtechnetium generated by a Pari LC Plus nebulizer and exhaled through a Pari PEP device . On another day , the same patients exhaled through a low-resistance Pari filter ( no PEP ) . Afterwards , they underwent gamma-camera lung imaging . Images were analyzed for lung deposition fraction , expressed as a percent of the initial nebulizer activity , and deposition pattern , expressed in terms of inner-outer and apical-basal ratios . RESULTS Lung deposition fraction was significantly lower with the Pari PEP device ; the mean + SD deposition fraction was 6.10 + 3.05 % ( median 6.20 % ) with PEP , compared to 10.76 + 4.52 % ( median 10.32 % ) ( p = 0.0078 ) without PEP . The inner-outer ratio was 2.01 + 0.69 ( median 2.23 ) with PEP , which was significantly lower than without PEP ( 2.76 + 1.33 , median 2.55 ) ( p = 0.004 ) . The apical-basal ratio was 0.82 + 0.31 ( median 0.80 ) with PEP , which was not significantly different from no PEP ( 1.00 + 0.49 , median 0.90 ) . CONCLUSION These results indicate that less aerosol is deposited in the lungs of patients with cystic fibrosis when the Pari LC Plus nebulizer is used with the Pari PEP device , as described in these experiments . Nevertheless , aerosol administration with this nebulizer and PEP device also results in a proportional redistribution of aerosol to the peripheral airways , compared to nebulization without the PEP device . The clinical relevance of this subtle redistribution of aerosol in cystic fibrosis patients will probably depend on the drug administered and disease severity Cystic fibrosis ( CF ) is the most frequent lethal autosomal recessive disease among Caucasians . In more than 90 % of all patients the pulmonary involvement is the life-limiting factor . In the lung , the production of viscous sputum is a main and early clinical feature of CF . To help clear the lungs from this material mucolytic active drugs were used . Recombinant human DNase ( rhDNase ) w1x and hypertonic ( 5.85 % ) saline ( HS ) w2x both were mucolytic active and improved FEV1 in the same range in patients with CF . Besides this similarity there are differences such as the modulation of rheological parameters and costs . To determine whether these treatments can replace each other , we compared effect and acceptance in the same group of patients BACKGROUND Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense . Through osmotic forces , hypertonic saline may increase the volume of airway surface liquid , restore mucus clearance , and improve lung function . METHODS A total of 24 patients with cystic fibrosis were r and omly assigned to receive treatment with inhaled hypertonic saline ( 5 ml of 7 percent sodium chloride ) four times daily with or without pretreatment with amiloride . Mucus clearance and lung function were measured during 14-day baseline and treatment periods . RESULTS Long-term inhalation of hypertonic saline without pretreatment with amiloride ( i.e. , with placebo pretreatment ) result ed in a sustained ( > or = 8 hours ) increase in 1-hour rates of mucus clearance , as compared with those with amiloride pretreatment ( 14.0+/-2.0 vs. 7.0+/-1.5 percent , respectively ; P=0.02 ) and increased 24-hour rates of mucus clearance over baseline . Furthermore , inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second ( FEV1 ) between the baseline period and the treatment period ( mean difference , 6.62 percent ; 95 percent confidence interval , 1.6 to 11.7 ; P=0.02 ) , whereas hypertonic saline with amiloride did not improve FEV1 ( mean difference , 2.9 percent ; 95 percent confidence interval , -2.2 to 8.0 ; P=0.23 ) . Forced vital capacity ( FVC ) , the forced expiratory flow between 25 and 75 percent of FVC ( FEF25 - 75 ) , and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo , whereas the residual volume as a proportion of total lung capacity ( RV : TLC ) did not change in either group . A comparison of the changes in lung function in the two groups showed no significant difference . In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance , whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit . CONCLUSIONS In patients with cystic fibrosis , inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function . This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease OBJECTIVES This study compared the relative cost-effectiveness of daily recombinant human deoxyribonuclease ( rhDNase ) , with alternate day rhDNase and hypertonic saline ( HS ) for treating children with cystic fibrosis ( CF ) . METHODS A r and omized controlled trial with a crossover design allocated 40 CF children consecutively to 12 weeks of daily rhDNase , alternate day rhDNase , or HS . The primary outcome measure was forced expiratory volume in 1 second ( FEV1 ) , a measure of lung function . All health re source use was prospect ively documented for each patient and multiplied by unit costs to give a total health service cost for each 12-week treatment period . The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics for each treatment comparison , for various hypothetical levels of the decision maker 's ceiling ratio . RESULTS Compared with HS , there was a 14 % improvement in FEV1 for daily rhDNase ( 95 % Cl , 5 % to 23 % ) , and a 12 % improvement ( 95 % Cl , 2 % to 22 % ) for alternate day rhDNase . For a ceiling ratio of 200 pounds sterling per 1 % gain in FEV1 , the mean net benefits of daily and alternate day rhDNase compared with HS were 1,158 pounds sterling ( 95 % Cl , -621pounds sterling to 2,842 ) and 1,188 pounds sterling ( 95 % Cl , -847 to 3,343 ) , respectively ; the mean net benefit of daily compared with alternate day rhDNase was -30 pounds sterling ( 95 % Cl , -2,091 pounds sterling to 1,576 ) . CONCLUSIONS If decision makers are prepared to pay 200 pounds sterling for a 1 % gain in FEV1 over a 12-week period , then on average either rhDNase strategy is cost-effective The objective of this study was to test the inter-rater reproducibility of the Portuguese version of the PEDro Scale . Seven physiotherapists rated the method ological quality of 50 reports of r and omized controlled trials written in Portuguese indexed on the PEDro data base . Each report was also rated using the English version of the PEDro Scale . Reproducibility was evaluated by comparing two separate ratings of reports written in Portuguese and comparing the Portuguese PEDro score with the English version of the scale . Kappa coefficients ranged from 0.53 to 1.00 for individual item and an intraclass correlation coefficient ( ICC ) of 0.82 for the total PEDro score was observed . The st and ard error of the measurement of the scale was 0.58 . The Portuguese version of the scale was comparable with the English version , with an ICC of 0.78 . The inter-rater reproducibility of the Brazilian Portuguese PEDro Scale is adequate and similar to the original English version Objectives To evaluate the risk of bias tool , introduced by the Cochrane Collaboration for assessing the internal validity of r and omised trials , for inter-rater agreement , concurrent validity compared with the Jadad scale and Schulz approach to allocation concealment , and the relation between risk of bias and effect estimates . Design Cross sectional study . Study sample 163 trials in children . Main outcome measures Inter-rater agreement between review ers assessing trials using the risk of bias tool ( weighted κ ) , time to apply the risk of bias tool compared with other approaches to quality assessment ( paired t test ) , degree of correlation for overall risk compared with overall quality scores ( Kendall ’s τ statistic ) , and magnitude of effect estimates for studies classified as being at high , unclear , or low risk of bias ( metaregression ) . Results Inter-rater agreement on individual domains of the risk of bias tool ranged from slight ( κ=0.13 ) to substantial ( κ=0.74 ) . The mean time to complete the risk of bias tool was significantly longer than for the Jadad scale and Schulz approach , individually or combined ( 8.8 minutes ( SD 2.2 ) per study v 2.0 ( SD 0.8 ) , P<0.001 ) . There was low correlation between risk of bias overall compared with the Jadad scores ( P=0.395 ) and Schulz approach ( P=0.064 ) . Effect sizes differed between studies assessed as being at high or unclear risk of bias ( 0.52 ) compared with those at low risk ( 0.23 ) . Conclusions Inter-rater agreement varied across domains of the risk of bias tool . Generally , agreement was poorer for those items that required more judgment . There was low correlation between assessment s of overall risk of bias and two common approaches to quality assessment : the Jadad scale and Schulz approach to allocation concealment . Overall risk of bias as assessed by the risk of bias tool differentiated effect estimates , with more conservative estimates for studies at low risk BACKGROUND Daily recombinant human deoxyribonuclease ( rhDNase ) is an established but expensive treatment in cystic fibrosis . Alternate-day treatment , if equally effective , would reduce the drug cost . Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies . We compared the effectiveness of daily rhDNase , hypertonic saline , and alternate-day rhDNase in children with cystic fibrosis . METHODS In an open cross-over trial , 48 children were allocated in r and om order to 12 weeks of once-daily rhDNase ( 2.5 mg ) , alternate-day rhDNase ( 2.5 mg ) , and twice-daily 5 mL 7 % hypertonic saline . The primary outcome was forced expiratory volume in 1 s ( FEV(1 ) ) . Secondary outcomes were forced vital capacity , number of pulmonary exacerbations , weight gain , quality of life , exercise tolerance , and the total costs of hospital and community care . FINDINGS Mean FEV(1 ) increased by 16 % ( SD 25 % ) , 14 % ( 22 % ) , and 3 % ( 21 % ) with daily rhDNase , alternate-day rhDNase , and hypertonic saline , respectively . There was no difference between daily and alternate-day rhDNase ( 2 % [ 95 % CI -4 to 9 ] , p=0.55 ) . However , daily rhDNase showed a significantly greater increase in FEV(1 ) than hypertonic saline ( 8 % [ 2 to 14 ] , p=0.01 ) . The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 ( 95 % CI -546 to 1510 ) and that between daily rhDNase and hypertonic saline was pound1409 ( 440 to 2318 ) . None of the secondary clinical outcomes showed significant differences between treatments . INTERPRETATION Hypertonic saline , delivered by jet nebuliser , is not as effective as daily rhDNase , although there is variation in individual response . There is no evidence of a difference between daily and alternate-day rhDNase Recombinant human DNase ( rhDNase ) is an established treatment in cystic fibrosis ( CF ) , but it may liberate cationic mediators bound to DNA in the airways . An alternative mucolytic therapy is hypertonic saline ( HS ) ; however , HS may potentiate neutrophilic inflammation . We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum . In a r and omized , crossover trial , 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase , alternate-day 2.5 mg rhDNase , and twice-daily 7 % HS . Sputum levels of total interleukin-8 ( IL-8 ) , free IL-8 , myeloperoxidase , eosinophil cationic protein , and neutrophil elastase ( NE ) activity were measured before and after each treatment . The change in mediator levels from baseline with daily rhDNase and HS was not significant ; however , with alternate-day rhDNase , there was an increase in free IL-8 . When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS , no significant differences were detected . Only changes in NE activity were associated with changes in lung function . In summary , we were unable to show that rhDNase or HS promote airway inflammation in CF BACKGROUND Outcome measures that can evaluate treatment efficacy are important to enhance development of new therapeutic agents for Cystic Fibrosis ( CF ) . We investigated whether the lung clearance index ( LCI ) measured by multiple breath washout ( MBW ) can detect a treatment effect of hypertonic saline ( HS ) inhalation after single dosing within a 24 h period . METHODS In this r and omized controlled cross-over trial , CF patients received inhalation of HS and isotonic saline ( IS ) . MBW and spirometry were performed at 5 time points over 24 h. LCI was measured using both a nitrogen washout technique ( LCIN2 ) and sulfur hexafluoride as a tracer gas ( LCISF6 ) . The primary endpoint was the change in the LCIN2 between baseline and 24 h. Secondary endpoints included change in LCISF6 and spirometry outcomes . RESULTS Twenty-one patients were r and omized . Sixteen completed all study visits and all time point measurements . Eighteen patients contributed to the intention to treat analysis . Significant changes were not detected for either LCI or the spirometry outcomes . However , the primary outcome parameter ( change in LCI between the baseline visits and 24 h after inhalation ) demonstrated a trend towards improved LCI , in the HS treatment arm compared with the IS treatment arm , -0.60 LCIN2 ( SE 0.32 ) , p = 0.08 ) ; similar trends were not observed for spirometric measures . The overall effect size of HS was smaller than in previous studies of longer duration . CONCLUSIONS These data suggest that LCI may potentially be used as an outcome measure in early phase trials with therapeutic agents that have a larger treatment effects than a single inhalation of HS 1 . Mucociliary clearance has been measured over a 6 h period by using the radioaerosol technique in seven normal male subjects lying supine , both during the day when awake , and during the night when asleep . 2 . The percentage of radioaerosol cleared during the night , when asleep , was significantly less than during the day when awake ( P less than 0.02 ) . 3 . A comparison of radioaerosol clearance before and after the time of onset of sleep demonstrates that reduced clearance occurred during sleep , indicating that this is probably a sleep-related phenomenon and not merely a result of diurnal variation . 4 . This finding has important implication s for patients with chronic bronchitis or asthma , in whom early morning cough or wheeze may be a predominant feature Background : Daily recombinant human deoxyribonuclease ( rhDNase ) is an established but expensive treatment in cystic fibrosis ( CF ) . An alternative lower cost therapy is hypertonic saline ( HS ) , which has been shown to improve lung function in short term studies . This study compares the costs and consequences of daily rhDNase with alternate day rhDNase and HS in children with CF . Methods : In an open , r and omised , crossover trial , 48 children with CF were allocated consecutively to 12 weeks of once daily 2.5 mg rhDNase , alternate day 2.5 mg rhDNase , and twice daily 5 ml 7 % HS . Outcomes assessed included forced expiratory volume in 1 second ( FEV1 ) and quality of life . All healthcare re source use was prospect ively recorded for each patient . Unit costs were collected and combined with re source use data to give the total health service costs per patient for each treatment strategy . Results : Daily rhDNase result ed in a significantly greater increase in mean FEV1 than HS ( 8 % , 95 % CI 2 to 14 ) but there was no significant difference in FEV1 between daily and alternate day rhDNase ( 2 % , 95 % CI –4 to 9 ) . Over a 12 week period the mean incremental costs of daily rhDNase compared with HS was £ 1409 ( 95 % CI £ 440 to £ 2318 ) , and the incremental cost of using daily rather than alternate day rhDNase was £ 513 ( 95 % CI –£546 to £ 1510 ) . Conclusions : Daily rhDNase is more effective than 5 ml 7 % HS twice daily delivered by jet nebuliser , but significantly increases healthcare costs . Administering rhDNase on an alternate day rather than a daily basis is as effective , with a potential for cost savings Progressive lung disease in patients with cystic fibrosis ( CF ) is caused by thick secretions , which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms . Recently , recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function . Ultrasonically nebulized hypertonic saline ( HS ) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions , and may therefore provide a low cost alternative . We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease . The patients were evaluated following 2 weeks of treatment with HS in an open-label study . Subjects were r and omly allocated to receive 10 ml of either 0.9 % NaCl ( IS ) or 6 % NaCl ( HS ) . Twice daily , prior to physiotherapy , treatments were delivered by a portable ultrasonic nebulizer . To prevent bronchoconstriction , 600 mg of salbutamol was administered prior to the nebulized solutions . A symptom score was recorded and spirometry was performed on day 0 before therapy was started , on day 14 ( the last day of therapy ) , and on day 28 ( 14 days after the last treatment with either IS or HS ) . Fifty-two patients ( 32 males ) , with a mean age of 16.2 ( range 7 - 36 ) years completed the study . There was no difference in baseline characteristics between the two groups . Following 2 weeks of treatment , there was a significant improvement from baseline in FEV1 of 15.0 + /- 16.0 % ( mean + /- SD ) in patients treated with HS , compared with a change of 2.8 + /- 13 % in those on IS therapy ( P = 0.004 ) . Furthermore , there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS ( P = 0.02 ) . The treatment was well tolerated . We conclude that in patients with CF , ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period . Nebulized saline also enhances the perception of effectiveness of chest physiotherapy 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 . Background This crossover , r and omized , double-blind study ( conducted over a 32-week period ) was performed to determine , in clinical ly stable Cystic fibrosis ( CF ) preschool children : the effects of 7 % inhaled hypertonic saline on spirometry and interrupter resistance technique ( Rint ) , and the possible side effects . Methods Twelve CF children ( 6 M , mean age ± SD : 5.7 ± 0.8 yrs ) were enrolled and r and omly assigned to receive hypertonic saline ( HS-4 ml 7 % sodium chloride ) , or normal saline ( NS-0.9 % sodium chloride ) twice a day . After a 16 weeks period , therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments . Monitoring visits , spirometry ( COSMED Quark PFT4 ergo ) and Rint were scheduled at 0,4,16,20,32 weeks . At T0 , spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy . Salbutamol ( 400 mcg ) was administered before the drug at each visit . Results After a 16-weeks treatment with HS an improvement of FVC ( p = 0.02 ) and a favorable trend of FEV1 were registered . A worsening of FEV1 ( p < 0.0001 ) and of FEF25 - 75 ( p = 0.019 ) were found in NS group . No differences were found in expiratory and inspiratory Rint in both groups . No serious adverse events occurred . Conclusions Seven percent hypertonic saline therapy proved to be a useful and safe treatment in young CF children with clinical ly stable conditions . Trial registration IS RCT N12345678 CONTEXT Inhaled hypertonic saline is recommended as therapy for patients 6 years or older with cystic fibrosis ( CF ) , but its efficacy has never been evaluated in patients younger than 6 years with CF . OBJECTIVE To determine if hypertonic saline reduces the rate of protocol -defined pulmonary exacerbations in patients younger than 6 years with CF . DESIGN , SETTING , AND PARTICIPANTS The Infant Study of Inhaled Saline in Cystic Fibrosis ( ISIS ) , a multicenter , r and omized , double-blind , placebo-controlled trial conducted from April 2009 to October 2011 at 30 CF care centers in the United States and Canada . Participants were aged 4 to 60 months and had an established diagnosis of CF . A total of 344 patients were assessed for eligibility ; 321 participants were r and omized ; 29 ( 9 % ) withdrew prematurely . INTERVENTION The active treatment group ( n = 158 ) received 7 % hypertonic saline and the control group ( n = 163 ) received 0.9 % isotonic saline , nebulized twice daily for 48 weeks . Both groups received albuterol or levalbuterol prior to each study drug dose . MAIN OUTCOME MEASURES Rate during the 48-week treatment period of protocol -defined pulmonary exacerbations treated with oral , inhaled , or intravenous antibiotics . RESULTS The mean pulmonary exacerbation rate ( events per person-year ) was 2.3 ( 95 % CI , 2.0 - 2.5 ) in the active treatment group and 2.3 ( 95 % CI , 2.1 - 2.6 ) in the control group ; the adjusted rate ratio was 0.98 ( 95 % CI , 0.84 - 1.15 ) . Among participants with pulmonary exacerbations , the mean number of total antibiotic treatment days for a pulmonary exacerbation was 60 ( 95 % CI , 49 - 70 ) in the active treatment group and 52 ( 95 % CI , 43 - 61 ) in the control group . There was no significant difference in secondary end points including height , weight , respiratory rate , oxygen saturation , cough , or respiratory symptom scores . Infant pulmonary function testing performed as an exploratory outcome in a subgroup ( n = 73 , with acceptable measurements at 2 visits in 45 participants ) did not demonstrate significant differences between groups except for the mean change in forced expiratory volume in 0.5 seconds , which was 38 mL ( 95 % CI , 1 - 76 ) greater in the active treatment group . Adherence determined by returned study drug ampoules was at least 75 % in each group . Adverse event profiles were also similar , with the most common adverse event of moderate or severe severity in each group being cough ( 39 % of active treatment group , 38 % of control group ) . CONCLUSION Among infants and children younger than 6 years with cystic fibrosis , the use of inhaled hypertonic saline compared with isotonic saline did not reduce the rate of pulmonary exacerbations over the course of 48 weeks of treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00709280 BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application OBJECTIVE To determine whether inhalation of hypertonic saline ( HS ) increases sputum expectoration in patients with cystic fibrosis ( CF ) . METHODOLOGY Ten adolescents with CF , who were receiving inpatient treatment for a pulmonary exacerbation , were enrolled in a controlled cross-over clinical trial . After inhalation of beta adrenergic drug to prevent possible broncho-constriction , each patient inhaled for 10 min either 0.9 % isotonic saline ( IS ) or 6 % HS prior to routine physiotherapy . The following day the patient received the alternative solution . Seven patients undertook a second block after 1 - 5 days . Outcome measures included weight of sputum , a visual analogue score to assess the subjective feeling of a cleared chest after physiotherapy , and spirometry . RESULTS Sputum expectoration ( median ; Q1,Q3 ) from the beginning of the inhalation of HS or IS to the final spirometry measure 60 min post-physiotherapy was significantly greater after HS than IS [ 17.2 g ( 11.7 , 34.8 ) vs 11.3 g ( 6.5 , 16.1 ) : P = 0.006 ] . A clinical score of the patient 's own judgement of a cleared chest was significantly better after HS than IS . Spirometry results did not change following either of the two inhalations . CONCLUSIONS These data show that the inhalation of 6 % HS prior to physiotherapy can increase sputum expectoration in patients with CF and suggest that HS might be an effective , safe and cheap adjunct to regular physiotherapy in patients with CF BACKGROUND Patients with cystic fibrosis are known to have decreased mucociliary clearance . It has previously been shown that inhalation of a 7.0 % solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis . The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline . METHODS Ten patients ( seven men ) of mean ( SE ) age 22 ( 4 ) years and mean forced expiratory volume in one second ( FEV1 ) 52.0 (6.7)% predicted completed the study . Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9 % NaCl + voluntary cough ( control ) , 3.0 % NaCl , 7.0 % NaCl , and 12 % NaCl . RESULTS There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline ( HS ) compared with control . The amount cleared at 90 minutes on the control day was 12.7 % ( 95 % confidence interval ( CI ) 9.8 to 17.2 ) compared with 19.7 % ( 95 % CI 13.6 to 29.5 ) for 3 % HS , 23.8 % ( 95 % CI 15.9 to 36.7 ) for 7 % HS and 26.0 % ( 95 % CI 19.8 to 35.9 ) for 12 % HS . The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day . The hypertonic saline did not induce a clinical ly significant change in FEV1 . CONCLUSIONS Within the range of concentrations examined in this study , the effect of hypertonic saline appears to be dose dependent . Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis Treatment with recombinant human deoxyribonuclease I ( rhDNase ) is currently used as therapy for cystic fibrosis ( CF ) lung disease . Hypertonic saline ( HS ) acts as an expectorant promoting mucus secretion and augmenting the volume of sputum . We evaluated the individual and combined effects of HS and rhDNase in vitro on the viscoelasticity of CF sputum . Sputum sample s were collected from nine CF patients to use for in vitro testing . Aliquots of CF sputum ( 0.20 to 0.40 g ) were subjected to the following protocol s : ( 1 ) negative control sample without any treatment ; ( 2 ) positive control sample , adding 10 % volume of normal saline ( 0.9 % NaCl ) ; ( 3 ) application of hypertonic saline ( HS-3 % NaCl ) ; ( 4 ) combining approximately 100 nM concentration of rhDNase with protocol s 2 and 3 . The sample s in protocol s 2 through 4 were incubated for 30 min at 37 degrees C. For each protocol , CF sputum was analyzed at baseline and at 30 min for spinnability by filancemeter and viscoelasticity by magnetic microrheometry . Spinnability decreased for the sputum sample s that were treated with rhDNase , in combination with either HS or normal saline . Treatment with HS alone and combined treatment with rhDNase and HS decreased log G * ( the principal viscoelasticity index ) to the same degree . Saline alone and rhDNase in normal saline both increased the predicted cough clearability of the sputum ; however , the combined treatment with rhDNase and hypertonic saline had the best overall effect on cough clearability . The change in predicted mucociliary clearability , although greatest after HS , was not significant . These in vitro results suggest that combined treatment with rhDNase and HS should be evaluated further as a potential mucotropic approach to augment the clearance of purulent sputum in CF lung disease OBJECTIVES To assess the reliability of the Cochrane Risk of Bias ( ROB ) tool between individual raters and across consensus agreements of pairs of review ers and examine the impact of study -level factors on reliability . STUDY DESIGN AND SETTING Two review ers assessed risk of bias for 154 r and omized controlled trials ( RCTs ) . For 30 RCTs , two review ers from each of four centers assessed risk of bias and reached consensus . We assessed interrater agreement using kappas and the impact of study -level factors through subgroup analyses . RESULTS Reliability between two review ers was fair for most domains ( κ=0.24 - 0.37 ) , except sequence generation ( κ=0.79 , substantial ) . Reliability results across review er pairs : sequence generation , moderate ( κ=0.60 ) ; allocation concealment and " other sources of bias , " fair ( κ=0.37 - 0.27 ) ; and other domains , slight ( κ=0.05 - 0.09 ) . Reliability was influenced by the nature of the outcome , nature of the intervention , study design , trial hypothesis , and funding source . Variability result ed from different interpretation of the tool rather than different information identified in the study reports . CONCLUSION Low agreement has implication s for interpreting systematic review s. These findings suggest the need for detailed guidance in assessing the risk of bias 1 Respiratory Unit , Great Ormond Street Hospital for Children NHS Trust , London , UK 2 Department of Respiratory Paediatrics , Royal Brompton and Harefield NHS Trust , London , UK 3 Medical Research Council Biostatistics Unit , Institute of Public Health , Cambridge , UK 4 Department of Epidemiology and Population Health , London School of Hygiene and Tropical Medicine , UK 5 Clinical Trials and Evaluation Unit , Royal Brompton and Harefield NHS Trust , London , UK 6 Department of Public Health and Policy , London School of Hygiene and Tropical Medicine , UK Daily recombinant human deoxyribonuclease ( rhDNase ) is an established but expensive treatment in cystic fibrosis ( CF ) . Alternate-day rhDNase and hypertonic saline ( HS ) represent potential cheaper alternative therapies . However , not all patients improve on treatment . To assess response , many CF centers have developed formal n-of-1 trials of treatment to find out who benefits . Response to daily rhDNase at 3 months has been shown to be a good predictor of response at 1 year . There are no data correlating individual response at a shorter time period with 3-month response . We assessed whether individual responses to daily rhDNase , alternate-day rhDNase , and HS could be predicted from lung function response at 6 weeks , thus shortening the n-of-1 trial , or from baseline patient characteristics , therefore avoiding the need for an n-of-1 trial . In a r and omized crossover trial , 48 CF children were allocated consecutively to 12 weeks of once-daily 2.5-mg rhDNase , alternate-day 2.5-mg rhDNase , and twice-daily 5 ml of 7 % HS . Forced expiratory volume in 1 sec ( FEV1 ) and forced vital capacity ( FVC ) were measured at baseline and then at 6 and 12 weeks into each treatment period . Lung function response to the drugs at 6 weeks was highly predictive of response at 3 months . There was some evidence that response to HS was worse in patients with lower baseline lung function . However , there was no association between response to alternate-day or daily rhDNase and baseline characteristics . In conclusion , response to rhDNase and HS at 6 weeks was highly predictive of response at 3 months . For daily and alternate-day rhDNase , at least , the drug needs to be administered for at most 6 weeks initially to assess long-term response to treatment . Response to treatment could not be reliably predicted from baseline characteristics RATIONALE Lung clearance index ( LCI ) , measured by multiple breath washout ( MBW ) , is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis ( CF ) . OBJECTIVES To study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers . METHODS The Infant Study of Inhaled Saline trial was a multicenter , r and omized , controlled trial of hypertonic ( 7 % ) versus isotonic ( 0.9 % ) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age . LCI measurements were performed in a single-center pilot sub study at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas . LCI measurements were st and ardized using published normative data ( zLCI ) to account for height-related changes in LCI during early childhood . A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect . MEASUREMENTS AND MAIN RESULTS A total of 27 participants were r and omized ; 25 participants , aged ( median [ range ] ) 2.6 ( 0.34 - 4.95 ) years , had acceptable baseline and follow-up LCI measures . On average , LCI decreased in the hypertonic saline group ( n = 12 ) by 1.19 z-scores units ( 95 % confidence interval [ CI ] = -2.46 to 0.06 ) , and remained stable in the isotonic saline group ( n = 13 ) at 0.81 ( 95 % CI = -0.40 to 2.02 ) . A significant treatment effect was observed for zLCI ( 2.01 ; 95 % CI = 0.26 to 3.76 ; P = 0.025 ) . CONCLUSIONS MBW testing is feasible in an interventional study in infants and preschool children with CF . These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF , and provide estimates for sample size calculations for future studies Background : Hypertonic saline inhalation has been shown to be effective in patients with cystic fibrosis and lung disease . However , adverse events including marked airway narrowing are reported and a bronchodilator must be given before the administration of the product . Methods : We carried out a prospect i ve , r and omized , double-blind , parallel-group , controlled study of a hypertonic saline solution containing hyaluronic acid ( Hyaneb ) versus st and ard hypertonic saline therapy to assess whether the presence of hyaluronic acid would improve the tolerability of hypertonic saline . Results and conclusions : The results showed that nebulized Hyaneb was more effective in reducing the need for β2 bronchodilators and caused a significant reduction in the incidence of adverse effects compared with nebulized hypertonic saline solution alone . Its safety profile indicates that Hyaneb can be used for the treatment of lung disease in cystic fibrosis Background Many bibliographic data bases index research studies evaluating the effects of health care interventions . One study has concluded that the Physiotherapy Evidence Data base ( PEDro ) has the most complete indexing of reports of r and omized controlled trials of physical therapy interventions , but the design of that study may have exaggerated estimates of the completeness of indexing by PEDro . Objective The purpose of this study was to compare the completeness of indexing of reports of r and omized controlled trials of physical therapy interventions by 8 bibliographic data bases . Design This study was an audit of bibliographic data bases . Methods Prespecified criteria were used to identify 400 reports of r and omized controlled trials from the reference lists of systematic review s published in 2008 that evaluated physical therapy interventions . Eight data bases ( AMED , CENTRAL , CINAHL , EMBASE , Hooked on Evidence , PEDro , PsycINFO , and PubMed ) were search ed for each trial report . The proportion of the 400 trial reports indexed by each data base was calculated . Results The proportions of the 400 trial reports indexed by the data bases were as follows : CENTRAL , 95 % ; PEDro , 92 % ; PubMed , 89 % ; EMBASE , 88 % ; CINAHL , 53 % ; AMED , 50 % ; Hooked on Evidence , 45 % ; and PsycINFO , 6 % . Almost all of the trial reports ( 99 % ) were found in at least 1 data base , and 88 % were indexed by 4 or more data bases . Four trial reports were uniquely indexed by a single data base only ( 2 in CENTRAL and 1 each in PEDro and PubMed ) . Limitations The results are only applicable to search ing for English- language published reports of r and omized controlled trials evaluating physical therapy interventions . Conclusions The 4 most comprehensive data bases of trial reports evaluating physical therapy interventions were CENTRAL , PEDro , PubMed , and EMBASE . Clinicians seeking quick answers to clinical questions could search any of these data bases knowing that all are reasonably comprehensive . PEDro , unlike the other 3 most complete data bases , is specific to physical therapy , so studies not relevant to physical therapy are less likely to be retrieved . Research ers could use CENTRAL , PEDro , PubMed , and EMBASE in combination to conduct exhaustive search es for r and omized trials in physical therapy |
10,974 | 26,465,274 | In the CHAT trial , at seven months , neurocognitive performance and attention and executive function had not improved with surgery : scores were similar in both groups .
In otherwise healthy children , without a syndrome , of older age ( five to nine years ) , and diagnosed with mild to moderate OSAS by PSG , there is moderate quality evidence that adenotonsillectomy provides benefit in terms of quality of life , symptoms and behaviour as rated by caregivers and high quality evidence that this procedure is beneficial in terms of PSG parameters .
At the same time , high quality evidence indicates no benefit in terms of objective measures of attention and neurocognitive performance compared with watchful waiting .
Furthermore , PSG recordings of almost half of the children managed non-surgically had normalised by seven months , indicating that physicians and parents should carefully weigh the benefits and risks of adenotonsillectomy against watchful waiting in these children . | BACKGROUND Obstructive sleep-disordered breathing ( oSDB ) is a condition that encompasses breathing problems when asleep , due to an obstruction of the upper airways , ranging in severity from simple snoring to obstructive sleep apnoea syndrome ( OSAS ) .
It affects both children and adults .
In children , hypertrophy of the tonsils and adenoid tissue is thought to be the commonest cause of oSDB .
As such , tonsillectomy - with or without adenoidectomy - is considered an appropriate first-line treatment for most cases of paediatric oSDB .
OBJECTIVES To assess the benefits and harms of tonsillectomy with or without adenoidectomy compared with non-surgical management of children with oSDB . | BACKGROUND AND OBJECTIVES : Data from a r and omized , controlled study of adenotonsillectomy for obstructive sleep apnea syndrome ( OSAS ) were used to test the hypothesis that children undergoing surgery had greater quality of life ( QoL ) and symptom improvement than control subjects . The objectives were to compare changes in vali date d QoL and symptom measurements among children r and omized to undergo adenotonsillectomy or watchful waiting ; to determine whether race , weight , or baseline OSAS severity influenced changes in QoL and symptoms ; and to evaluate associations between changes in QoL or symptoms and OSAS severity . METHODS : Children aged 5 to 9.9 years with OSAS ( N = 453 ) were r and omly assigned to undergo adenotonsillectomy or watchful waiting with supportive care . Polysomnography , the Pediatric Quality of Life inventory , the Sleep-Related Breathing Scale of the Pediatric Sleep Question naire , the 18-item Obstructive Sleep Apnea QoL instrument , and the modified Epworth Sleepiness Scale were completed at baseline and 7 months . Changes in the QoL and symptom surveys were compared between arms . Effect modification according to race and obesity and associations between changes in polysomnographic measures and QoL or symptoms were examined . RESULTS : Greater improvements in most QoL and symptom severity measurements were observed in children r and omized to undergo adenotonsillectomy , including the parent-completed Pediatric Quality of Life inventory ( effect size [ ES ] : 0.37 ) , the 18-item Obstructive Sleep Apnea QoL instrument ( ES : –0.93 ) , the modified Epworth Sleepiness Scale score ( ES : –0.42 ) , and the Sleep-Related Breathing Scale of the Pediatric Sleep Question naire ( ES : –1.35 ) . Effect modification was not observed by obesity or baseline severity but was noted for race in some symptom measures . Improvements in OSAS severity explained only a small portion of the observed changes . CONCLUSIONS : Adenotonsillectomy compared with watchful waiting result ed in significantly more improvements in parent-rated generic and OSAS-specific QoL measures and OSAS symptoms BACKGROUND The relative importance of obesity and adenotonsillar hypertrophy in the pathogenesis of obstructive sleep-disordered breathing ( SDB ) in childhood is unclear . Adenotonsillectomy ( AT ) for SDB is not always curative , and obese children are at increased risk for residual disease postoperatively . OBJECTIVE The aim of this investigation was to assess the efficacy of AT as treatment for SDB in obese and nonobese children . METHODS Children with adenoidal and /or tonsillar hypertrophy who underwent AT for the treatment of SDB underwent polysomnography preoperatively and postoperatively . A body mass index ( BMI ) z score of > 1.645 was used to define obesity . The achievement of a postoperative obstructive apnea-hypopnea index ( OAHI ) of less than one episode per hour ( ie , the cure of SDB ) was the primary outcome measure . RESULTS Twenty-two obese children ( mean [ + /- SD ] age , 5.8 + /- 1.8 years ; mean BMI z score , 2.6 + /- 0.8 ; mean OAHI , 9.5 + /- 9.7 episodes per hour ) and 48 nonobese children ( mean age , 6.9 + /- 2.6 years ; mean BMI z score , 0.09 + /- 1.1 ; OAHI , 6 + /- 5.4 episodes per hour ) were recruited . After surgery , obese and nonobese subjects did not differ in the efficacy of AT ( postoperative OAHI of less than one episode per hour , 22.7 % vs 25 % of subjects , respectively ; p > 0.05 ) . The presence of obesity , adenoidal or tonsillar hypertrophy , gender , and postoperative BMI change were not significant predictors of SDB cure . CONCLUSIONS Obesity does not necessarily predict an unfavorable outcome of AT as treatment for SDB OBJECTIVE To evaluate the efficacy of adenotonsillectomy ( AT ) in the treatment of children with obstructive sleep apnea ( OSA ) in a 3-y prospect i ve , longitudinal study with analysis of risk factors of recurrence of OSA . STUDY DESIGN An investigation of children ( 6 to 12 y old ) with OSA documented at entry and followed posttreatment at 6 , 12 , 24 , and 36 mo with examination , question naires , and polysomnography . Multivariate generalized linear modeling and hierarchical linear models analysis were used to determine contributors to suboptimal long-term resolution of OSA , and Generalized Linear Models were used for analysis of risk factors of recurrence . RESULTS Of the 135 children , 88 terminated the study at 36 months post-AT . These 88 children ( boys = 72 , mean age = 8.9 ± 2.7 yersus boys 8.9 ± 2.04 y , girls : 8.8 ± 2.07 y ; body mass index [ BMI ] = 19.5 ± 4.6 kg/m(2 ) ) had a preoperative mean apnea-hypopnea index ( AHI0 ) of 13.54 ± 7.23 and a mean postoperative AHI at 6 mo ( AHI6 ) of 3.47 ± 8.41 events/h ( with AHI6 > 1 = 53.4 % of 88 children ) . A progressive increase in AHI was noted with a mean AHI36 = 6.48 ± 5.57 events/h and AHI36 > 1 = 68 % of the studied group . Change in AHI was associated with changes in the OSA-18 question naire . The residual pediatric OSA after AT was significantly associated with BMI , AHI , enuresis , and allergic rhinitis before surgery . From 6 to 36 mo after AT , recurrence of pediatric OSA was significantly associated with enuresis , age ( for the 24- to 36-mo period ) , postsurgery AHI6 ( severity ) , and the rate of change in BMI and body weight . CONCLUSIONS Adenotonsillectomy leads to significant improvement in apnea-hypopnea index , though generally with incomplete resolution , but a worsening over time was observed in 68 % of our cases BACKGROUND AND OBJECTIVES : Adenotonsillectomy for obstructive sleep apnea syndrome ( OSAS ) may lead to weight gain , which can have deleterious health effects when leading to obesity . However , previous data have been from nonr and omized uncontrolled studies , limiting inferences . This study examined the anthropometric changes over a 7-month interval in a r and omized controlled trial of adenotonsillectomy for OSAS , the Childhood Adenotonsillectomy Trial . METHODS : A total of 464 children who had OSAS ( average apnea/hypopnea index [ AHI ] 5.1/hour ) , aged 5 to 9.9 years , were r and omized to Early Adenotonsillectomy ( eAT ) or Watchful Waiting and Supportive Care ( WWSC ) . Polysomnography and anthropometry were performed at baseline and 7-month follow-up . Multivariable regression modeling was used to predict the change in weight and growth indices . RESULTS : Interval increases in the BMI z score ( 0.13 vs 0.31 ) was observed in both the WWSC and eAT intervention arms , respectively , but were greater with eAT ( P < .0001 ) . Statistical modeling showed that BMI z score increased significantly more in association with eAT after considering the influences of baseline weight and AHI . A greater proportion of overweight children r and omized to eAT compared with WWSC developed obesity over the 7-month interval ( 52 % vs 21 % ; P < .05 ) . Race , gender , and follow-up AHI were not significantly associated with BMI z score change . CONCLUSIONS : eAT for OSAS in children results in clinical ly significant greater than expected weight gain , even in children overweight at baseline . The increase in adiposity in overweight children places them at further risk for OSAS and the adverse consequences of obesity . Monitoring weight , nutritional counseling , and encouragement of physical activity should be considered after eAT for OSAS BACKGROUND Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome , yet its usefulness in reducing symptoms and improving cognition , behavior , quality of life , and polysomnographic findings has not been rigorously evaluated . We hypothesized that , in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation , early adenotonsillectomy , as compared with watchful waiting with supportive care , would result in improved outcomes . METHODS We r and omly assigned 464 children , 5 to 9 years of age , with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting . Polysomnographic , cognitive , behavioral , and health outcomes were assessed at baseline and at 7 months . RESULTS The average baseline value for the primary outcome , the attention and executive-function score on the Developmental Neuropsychological Assessment ( with scores ranging from 50 to 150 and higher scores indicating better functioning ) , was close to the population mean of 100 , and the change from baseline to follow-up did not differ significantly according to study group ( mean [ ±SD ] improvement , 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group ; P=0.16 ) . In contrast , there were significantly greater improvements in behavioral , quality -of-life , and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group . Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group ( 79 % vs. 46 % ) . CONCLUSIONS As compared with a strategy of watchful waiting , surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior , quality of life , and polysomnographic findings , thus providing evidence of beneficial effects of early adenotonsillectomy . ( Funded by the National Institutes of Health ; CHAT Clinical Trials.gov number , NCT00560859 . ) OBJECTIVES : Children with nonsevere obstructive sleep apnea ( OSA ) benefit from alternative therapeutic interventions such as leukotriene modifiers . We hypothesized that montelukast might improve OSA in children . We tested this hypothesis in a double-blind , r and omized , placebo-controlled fashion . METHODS : Of 50 possible c and i date s , we recruited 46 children with polysomnographically diagnosed OSA . In this prospect i ve , double-blind , r and omized trial , children received daily oral montelukast at 4 or 5 mg ( < 6 or > 6 years of age , respectively ) or placebo for 12 weeks . Polysomnographic assessment s , parent question naires , and radiographs to assess adenoid size were performed before and after therapy . RESULTS : Compared with the 23 children that received placebo , the 23 children that received montelukast showed significant improvements in polysomnographic measures of respiratory disturbance ( obstructive apnea index ) , children 's symptoms , and adenoid size . The obstructive apnea index decreased by > 50 % in 65.2 % of treated children . No attrition or side effects occurred . CONCLUSIONS : A 12-week treatment with daily , oral montelukast effectively reduced the severity of OSA and the magnitude of the underlying adenoidal hypertrophy in children with nonsevere OSA Objectives : To evaluate the impact of adenotonsillectomy ( T&A ) on quality -of-life ( QOL ) and behavior in obese versus normal-weight children with Obstructive Sleep Apnea ( OSA ) . Design : Prospect i ve , non-r and omized , controlled study . Methods : Children with an apnea-hypopnea index ( AHI ) ≥2 were studied . Polysomnography was performed before and after T&A. An age- and gender-specific body mass index ( BMI -for-age ) percentile was determined preoperatively . Children who were obese ( > 95th percentile ) were compared to normal-weight children ( BMI -for-age > 5th–85th percentile ) . Caregivers completed the OSA-18 QOL survey and the Behavioral Assessment Survey for Children ( BASC ) before surgery and 3–6 months postoperatively . Pre- and postoperative scores were compared using paired t-tests , and the impact of covariants was analyzed using ANOVA . Results : The study population consisted of 89 children , 40 of whom were obese ( 45 % ) . Postoperative scores for AHI , OSA-18 total and domain scores , and BASC scales and composites were significantly lower ( improved ) compared to pre-operative values in all children ( p < .001 ) . All mean OSA-18 and BASC scores were higher ( indicating worse quality -of-life and behavior ) pre- and postoperatively in obese than in normal-weight children . Postoperatively , the majority of OSA-18 total scores and domain scores were significantly higher in obese children . A comparison of the total OSA-18 scores between children with a postoperative AHI < 2 and AHI ≥ 2 in obese children and a similar comparison in normal-weight children was not statistically significant . There was no significant difference for BASC scores pre- and postoperatively between obese and normal-weight children . The pre- and postoperative scores for the AHI had a poor correlation with the pre- and postoperative Behavioral Symptoms Index ( BSI ) and total OSA-18 scores ( r = .09 ) , respectively . Conclusions : Following T&A all children have improvements in AHI , QOL , and behavior . Obese children are more likely to have persistent OSA and poor QOL scores after T&A. Behavior improves postoperatively to a similar extent in all children regardless of obesity QUESTION A 4-year-old child was diagnosed by polysomnography as experiencing mild obstructive sleep apnea ( OSA ) . Despite the child being inattentive and distracted during the day at school , his parents prefer to avoid surgical treatment ( adenotonsillectomy ) . Are there any non-surgical treatments for mild OSA in young children ? ANSWER Obstructive sleep apnea in children is caused mainly by adenotonsillar hypertrophy and can lead to considerable morbidities , including neurocognitive and behavioural disturbances . Surgical removal of the tonsils and adenoids is the treatment of choice . In recent years , however , a new underst and ing of the inflammatory components of OSA has led to the assumption that anti-inflammatory treatment can reduce adenotonsillar size and improve OSA symptoms . Evidence from a few studies suggests that intranasal steroids and oral leukotriene receptor antagonists have beneficial effects , but data from r and omized controlled trials are still lacking OBJECTIVES /HYPOTHESIS To vali date a clinical assessment score for pediatric sleep-disordered breathing . STUDY DESIGN Prospect i ve instrument validation . METHODS One hundred children scheduled for overnight polysomnography were evaluated by a st and ardized history and physical examination and assigned a clinical assessment score . Parents completed the Obstructive Sleep Apnea (OSA)-18 , the Pediatric Quality of Life Inventory ( PedsQL ) 4.0 , and the Child Behavior Checklist question naires . Children with positive polysomnography underwent adenotonsillectomy or adenoidectomy . The identical assessment s were performed at a mean follow-up of 8 months . RESULTS Item reduction yielded a score of 15 items ( Clinical Assessment Score-15 [ CAS-15 ] ) that demonstrated the best internal consistency and predictive utility ( Cronbach α = .80 ) . Intraclass correlation ( ICC ) demonstrated good intrarater ( ICC , 0.78 ; 95 % confidence interval [ CI ] , 0.58 to 0.89 ) and inter-rater agreement ( ICC , 0.65 ; 95 % CI , 0.26 to 0.84 ) . All change scores were significantly improved after surgery . Effect sizes were large for the CAS-15 ( 2.6 ) , OSA-18 ( 2.4 ) , and apnea-hypopnea index ( 1.4 ) , and moderate for the Child Behavior Checklist ( 0.7 ) and PedsQL 4.0 ( -0.5 ) . Moderate to strong correlation was found between the initial CAS-15 scores and the external measures ( |r| between 0.32 and 0.65 ) . Receiver operating characteristic curves were constructed to determine the optimal initial CAS-15 score for predicting positive polysomnography . The area under the curve was 0.77 ( 95 % CI , 0.67 to 0.87 ) ; and a score ≥32 yielded a sensitivity of 77.3 % ( 95 % CI , 65.3 to 86.7 ) and a specificity of 60.7 % ( 95 % CI , 40.6 to 78.5 ) . CONCLUSIONS The CAS-15 proved useful in an office setting and correctly diagnosed 72 % of referred children when compared to polysomnography . It correlated well with external measures and demonstrated a good response to clinical change INTRODUCTION Obstructive Sleep Apnea ( OSA ) is a common medical problem in adults that is becoming increasingly recognized in children . It occurs in the pediatric age group , from newborns to teens . More recently , many specialists have estimated OSA prevalence to be between 5 and 6 % . However , in syndromic children , the prevalence of OSA can be from 50 to 100 % , having a significant effect on their Quality -of-Life . As they are a challenging population for management , it is essential to evaluate them thoroughly before planning appropriate intervention . OBJECTIVE To compare the efficacy of Adenotonsillectomy ( T&A ) and Continuous Positive Airway Pressure ( CPAP ) in syndromic children [ Down syndrome ( DS ) and Mucopolysaccharidoses ( MPS ) ] with Obstructive Sleep Apnea ( OSA ) . MATERIAL S AND METHODS In a prospect i ve , r and omized , cohort comparative study , 124 syndromic children ( DS and MPS ) aged between 6 and 12 years were recruited from a private MPS support group and the Down Syndrome Society , Chennai . A st and ard assessment was performed on all children who entered the study including a full overnight Polysomnogram ( PSG ) , Epworth Sleepiness Scale-Children ( ESS-C ) and Quality -of-Life ( QOL ) tool OSA-18 . The children with positive PSG who consented for the study ( n = 80 ) were r and omly distributed to two groups , T&A group & CPAP group . The children were followed up with repeat PSG , clinical evaluation , ESS-C and Quality -of-Life ( QOL ) tool OSA-18 for a period of 1 year . OBSERVATION AND RESULTS Follow-up was available for 73 syndromic children . Both the groups , T&A group and CPAP group , showed statistically significant ( p < 0.05 ) improvement in Apnea-Hypoapnea Index ( AHI ) , ESS-C , QOL from the intervention . In our study , T&A showed equal outcome compared to CPAP . The contrasting feature between the two groups was that CPAP use gave immediate sustained improvement while T&A gave gradual progressive improvement of symptoms over a period of 1 year . CONCLUSION On average , T&A gives equal outcomes as CPAP and it can be suggested as a first-line treatment in this group of syndromic children Objectives Prior research has demonstrated poor correlation between the obstructive apnea-hypopnea index ( AHI ) on full-night polysomnogram ( PSG ) and quality -of-life ( QOL ) scores . We aim to examine the association between rapid eye movement ( REM ) AHI and QOL scores in children with sleep-disordered breathing ( SDB ) . Study Design Prospect i ve trial . Setting Two tertiary children ’s hospitals . Subjects and Methods Children between 3 and 16 years of age with suspected SDB who were undergoing PSG were eligible . Children with craniofacial anomalies were excluded . Subjects ’ caregivers completed the Obstructive Sleep Apnea–18 ( OSA-18 ) , a vali date d QOL survey . Power analysis determined a group size of 34 . Results One hundred twenty-seven patients were enrolled . The mean ( SD ) age was 6.3 ( 3.3 ) years . Most subjects ( 52 % ) were black and 26 % were obese . The mean ( SD ) obstructive AHI of the subject population was 5.4 ( 11.9 ) , while the mean ( SD ) REM AHI was 13.1 ( 23.7 ) . The mean total OSA-18 score was 65.2 , indicating a moderate impact of SDB on QOL . Neither the obstructive AHI ( P = .73 ) nor the REM AHI ( P = .49 ) correlated with total OSA-18 scores . However , lower nadir oxygen saturation was associated with significantly poorer QOL ( P = .02 ) . The sleep disturbance OSA-18 subset score significantly correlated with both the obstructive AHI ( r 2 = 0.22 ; P = .01 ) and the REM AHI ( r 2 = 0.22 ; P = .01 ) ; the remaining 4 subset scores did not correlate with either factor . Conclusion Neither obstructive AHI nor REM AHI correlates with total OSA-18 QOL scores . With the exception of nadir oxygen saturation , PSG parameters do not reflect the burden of SDB on QOL in children Objective To determine the impact of adenotonsillectomy vs observation on quality of life ( QOL ) in children with mild obstructive sleep apnea ( OSA ) . Study Design Prospect i ve , nonr and omized trial . Setting Tertiary children ’s hospital . Subjects and Methods Sixty-four children ( ages 3 - 16 years ) with mild OSA ( apnea hypopnea index between 1 and 5 on polysomnogram ) completed the study . Caregivers chose between management options of adenotonsillectomy and observation and completed vali date d QOL instruments ( OSA-18 and Children ’s Health Question naire ) at baseline , early , and late follow-ups . The primary outcome measure was QOL . Results Thirty patients chose adenotonsillectomy , while 34 were observed . Total OSA-18 scores at baseline were significantly poorer ( P = .01 ) in the surgery group ( 72.3 ) compared with the observation group ( 58.5 ) . Four months following surgery , OSA-18 scores improved by 39.1 points over baseline ( P = .0001 ) , while there was no change for the observation group ( P = .69 ) . After 8 months , OSA-18 scores remained improved in the surgery group , and observation group scores improved by 13.4 points over baseline ( P = .005 ) . While OSA-18 scores at the late follow-up visit were poorer in the observation group , the difference was not statistically significant ( P = .05 ) . Six observation patients opted for adenotonsillectomy during the study . Conclusion Quality of life significantly improves in children with mild OSA after adenotonsillectomy . In children with mild OSA who are observed , QOL improvements at early follow-up are less pronounced , but significant improvements in QOL are evident after 8 months . QOL instruments may be useful tools to help providers determine which children with mild OSA may benefit from early intervention This study aim ed to evaluate the effect of adenotonsillectomy on visual attention and daytime sleepiness in children with sleep‐disordered breathing Abstract Conclusion : Persistent obstructive sleep apnoea syndrome ( OSAS ) occurs in approximately 20 % of normal-weight children after adenotonsillectomy ( T&A ) and , in nearly 70 % of them , it is caused by adenoid regrowth . Patients with severe or moderate OSAS showed a high incidence of persistent disease even after T&A. Allergic disease , severity and large adenoid size are associated with adenoid regrowth and persistent disease . Objectives : To investigate factors contributing to persistent OSAS and adenoid regrowth after T&A in normal-weight children . Methods : This was a prospect i ve , observational study at a single institute and involved 49 normal-weight children with severe or moderate OSAS ( apnoea – hypopnoea index , AHI , ≥ 5 ) who underwent T&A. Background information , nasal endoscopic data and pre- and postoperative polysomnographic data were collected . A third polysomnography ( PSG ) was performed 1.5 year postoperatively in children who subsequently developed symptoms of sleep disturbance . Results : Thirteen children ( 27 % , 13/49 ) were symptomatic 1.5 years after T&A. Allergic rhinitis ( 38.5 % vs 11.1 % , p = 0.03 ) and allergic disease ( 69.2 % vs 30.6 % , p = 0.02 ) were seen more frequently in these children . A third PSG confirmed persistent disease ( AHI ≥ 5 ) in nine children ( 18.4 % , 9/49 ) . Six children ( 12.2 % , 6/49 ) were diagnosed as having adenoid regrowth and three ( 6.1 % , 3/49 ) underwent revision adenoidectomy OBJECTIVE To evaluate the effect of adenotonsillectomy on the oxygen saturation measures by nocturnal pulse oximetry in children with sleep breathing disorders ( SBD ) . METHODS A non-controlled clinical trial was performed . Thirty-one children with suspected SBD and a clinical indication for adenotonsillectomy were recruited . All of them underwent overnight oxygen saturation monitoring before and after surgery . RESULTS Twenty-seven patients completed the study . The mean age was 5.2+/-1.8 years . Eighteen ( 66.7 % ) were male . The most prevalent symptoms were : snoring ( 100 % ) , respiratory pauses ( 96.8 % ) , nocturnal mouth breathing ( 96.8 % ) , restless sleep ( 80 % ) and drooling ( 74.1 % ) . Twenty-three children ( 85.2 % ) presented grade 3 or 4 tonsillar hyperplasia . There was a significant improvement in the postoperative oxygen desaturation index ( ODI ) ( 0.65 ; 0.5 - 1.3 ) compared with the preoperative index ( 1.63 ; 1.1 - 2.4 ) ( p<0.001 ) . CONCLUSION Adenotonsillectomy improved the oxygen saturation measures by nocturnal pulse oximetry in children with sleep breathing disorders OBJECTIVE To determine whether children with a clinical assessment suggestive of obstructive sleep apnea ( OSA ) but with negative polysomnography ( PSG ) have improvement in their clinical assessment score after tonsillectomy and adenoidectomy ( T&A ) as compared with similar children who do not undergo surgery . METHODS In a prospect i ve , r and omized , investigator-blinded , controlled trial , 59 otherwise healthy children ( mean age : 6.3 years [ 3.0 ] ; 31 boys , 28 girls ) with a clinical diagnosis of OSA ( clinical assessment score 40 ) were recruited from the pediatric otolaryngology and pediatric pulmonary private offices and clinics of a tertiary care , academic medical center . A st and ardized assessment was performed on all patients , including history , physical examination , voice recording , tape recording of breathing during sleep , lateral neck radiograph , echocardiogram , and PSG . A clinical assessment score was assigned . Children with positive PSG ( n = 27 ) were scheduled for T&A , whereas children with negative PSG ( n = 29 ) were r and omized to T&A ( n = 15 ) or no surgery ( n = 14 ) . Children were reassessed in an identical manner at a planned 6-month follow-up . RESULTS Follow-up was available for 21 patients with positive PSG , 11 patients with negative PSG r and omized to T&A , and 9 nonsurgery patients . In the r and omized subjects , the median reduction in clinical assessment score was 49 ( range : 32 - 61 ) for the T&A patients as compared with 8 ( range : -9 to 29 ) for the nonsurgery patients . Nine ( 82 % ) of the T&A patients were asymptomatic ( clinical assessment score < 20 ) compared with 2 ( 22 % ) of the nonsurgery patients . CONCLUSION Children with a positive clinical assessment of OSA but negative PSG have significant improvement after T&A as compared with observation alone , thus validating the clinician 's role in diagnosing upper airway obstruction OBJECTIVE We tested the hypothesis that a 6-week course of a nasal glucocorticoid spray would decrease the severity of obstructive sleep apnea in children with adenotonsillar hypertrophy . STUDY DESIGN We conducted a r and omized , triple-blind , placebocontrolled , parallel-group trial of nasal fluticasone propionate versus placebo in 25 children aged 1 to 10 years with obstructive sleep apnea proven on polysomnography . The primary outcome was the change from baseline in the frequency of mixed and obstructive apneas and hypopneas . RESULTS Thirteen children received fluticasone , and 12 received placebo . The mixed/obstructive apnea/hypopnea index decreased from 10.7 + /- 2.6 ( SE ) to 5.8 + /- 2.2 in the fluticasone group but increased from 10.9 + /- 2.3 to 13.1 + /- 3.6 in the placebo group , P = .04 . The mixed/obstructive apnea/hypopnea index decreased in 12 of 13 subjects treated with fluticasone versus 6 of 12 treated with placebo , P = .03 . The frequencies of hemoglobin desaturation and respiratory movement/arousals also decreased more in the fluticasone group . Changes from baseline in tonsillar size , adenoidal size , and symptom score were not significantly different between groups . CONCLUSION Nasal fluticasone decreased the frequency of mixed and obstructive apneas and hypopneas , suggesting that topical corticosteroids may be helpful in ameliorating pediatric obstructive sleep apnea Each year , over 500,000 adenotonsillectomies ( AT ) , mostly for the treatment of pediatric obstructive sleep apnea ( OSA ) are performed in the US in children under 15 years of age . No definitive study , however , has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing , but also for improving clinical ly relevant outcomes , such as neurocognitive function , behavior , and quality of life . The Childhood Adenotonsillectomy Trial ( CHAT ) was design ed to assess neuropsychological and health outcomes in children r and omized to receive early AT ( eAT ) as compared to Watchful Waiting with Supportive Care ( WWSC ) . Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race . This paper addresses key elements in the design and implementation of a controlled trial for a widely used " st and ard practice " surgical intervention in a pediatric population , that include establishment of st and ardized data collection procedures across sites for a wide variety of data types , establishment of equipoise , and approaches for minimizing unblinding of selected key personnel . The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions |
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10,976 | 24,612,748 | From this review , non-face-to-face physical activity interventions effectively promote physical activity in older adults . | Physical activity is effective in preventing chronic diseases , increasing quality of life and promoting general health in older adults , but most older adults are not sufficiently active to gain those benefits .
A novel and economically viable way to promote physical activity in older adults is through non-face-to-face interventions .
These are conducted with reduced or no in-person interaction between intervention provider and program participants .
The aim of this review was to summarize the scientific literature on non-face-to-face physical activity interventions targeting healthy , community dwelling older adults ( ≥ 50 years ) . | OBJECTIVE We evaluate the 6-month efficacy of Keep Active Minnesota , a phone- and mail-based physical activity maintenance intervention design ed for use with adults age 50 to 70 years who have increased their physical activity within the past year . METHOD Participants ( N=1049 ) recruited in 2004 and 2005 from one large managed-care organization in Minnesota were r and omly assigned to either treatment ( N=523 ) or usual care ( N=526 ) with physical activity assessed using the Community Healthy Activities Model Program for Seniors question naire , and expressed as kcal/week expenditures . RESULTS Total physical activity at baseline was similar for treatment and usual care participants ( p<0.44 ) as was moderate/vigorous physical activity ( p<0.21 ) . Maintenance of physical activity was higher among treatment participants whose mean 6-month change in total kcal/week energy expenditure was -91 , compared to -683 for usual care participants ( p<0.002 ) . Mean 6-month change in kcal/week expenditure in moderate or vigorous activities was -49 for treatment participants , compared to -612 for usual care participants ( p<0.001 ) . CONCLUSIONS This phone- and mail-based physical activity maintenance intervention is efficacious at maintaining physical activity at 6 months Although telephone and mail are often used to promote physical activity adoption , their ability to produce long-term maintenance is unclear . In this study , 140 men and women aged 50 - 65 years received 1 year of telephone counseling to adopt higher ( i.e. , more vigorous ) versus lower intensity ( i.e. , moderate ) exercise . After 1 year , participants were rer and omized to a 2nd year of contact via ( a ) telephone and mail or ( b ) predominantly mail . Participants who were prescribed higher intensity exercise and received predominantly mail had better exercise adherence during the maintenance year than those who received telephone and mail . Both strategies were similarly effective in promoting maintenance in the lower intensity condition . Results suggest that after successful adoption of physical activity with the help of telephone counseling , less intensive interventions are successful for physical activity maintenance in older adults OBJECTIVE To evaluate the efficacy at 6- , 12- , and 24-month follow-up of Keep Active Minnesota ( KAM ) , a telephone and mail-based intervention design ed to promote physical activity ( PA ) maintenance among currently active adults age 50 to 70 . METHOD Participants who reported having recently increased their MVPA to a minimum of 2d/wk , 30 min/bout , ( N=1049 ) were recruited in 2004 and 2005 from one large managed care organization in Minnesota , and r and omly assigned to either treatment ( KAM ; N=523 ) , or Usual Care ( UC ; N=526 ) with PA assessed using the CHAMPS question naire , and expressed as kcal/wk energy expenditure . RESULTS We find a sustained , significant benefit of the intervention at 6 , 12 and 24 months . kcal/wk expenditure in moderate or vigorous activities was higher at 6 ( p<.03 , Cohen 's d(6m)=.16 ) , 12 ( p<.04 , d(12 m)=.13 ) and 24 months ( p<.01 , d(24 m)=.16 ) for KAM participants , compared to UC participants . CONCLUSIONS The KAM telephone- and mail-based PA maintenance intervention was effective at maintaining PA in both the short-term ( 6 months ) and longer-term ( 12 and 24 months ) relative to usual care Background Important health benefits can be derived when low-cost ( e.g. , computer-tailored ) physical activity interventions for older adults demonstrate sustained effects . Purpose The purpose of the study was to conduct in-depth analysis on the long-term efficacy of two tailored physical activity interventions for older adults . Methods A r and omized controlled trial ( n = 1,971 ) with two computer-tailored interventions and a no-intervention control group was conducted . The two tailored interventions consisted of three tailored letters , delivered during 4 months . The basic tailored intervention targeted psychosocial determinants alone , while the environmentally tailored intervention additionally targeted environmental determinants , by providing tailored environmental information . Self-reported behaviors ( i.e. , total physical activity , transport walking and cycling , leisure walking and cycling , and sports ) were measured at baseline and 12 months . Additionally , potential personal , health-related , and psychosocial moderators of the intervention effects were examined . Results The environmentally tailored intervention was effective in changing total physical activity , leisure cycling , and sports compared with the basic intervention and control group . No intervention effects were found for the basic intervention . Moderation analysis revealed that participants with a higher age , lower body mass index , and higher intention were unresponsive to the interventions . Conclusions Providing environmental information is an effective intervention strategy for increasing physical activity behaviors among older adults , especially among certain “ at-risk ” subgroups such as lower educated , overweight , or insufficiently active participants . Moderation analysis was perceived as a promising method for identifying meaningful subgroups that are unaffected by an intervention , which should receive special attention in future interventions Background : Attempts to study the translation of evidence -based physical activity interventions in community setting s are scarce . Purpose : This project was an investigation of whether 13 diverse local lead agencies could effectively implement a choice-based , telephone-assisted physical activity promotion program for older adults based on intervention models proven efficacious in research setting s. Methods : At baseline , participants developed their own physical activity programs through an individualized planning session based on preference , health status , readiness to change , and available community re sources . Thereafter , participants received regular telephone calls over a 1-year period from a trained staff member or volunteer support buddy . Additional program components consisted of health education workshops , newsletters , and group-based physical activities . Self-report data on caloric expenditure due to all and moderate or greater intensity physical activities were collected from 447 participants ( M age = 68 ± 8.6 years ) . Results : A significant increase ( p ≤ .0001 ) from baseline to midintervention and intervention endpoint was observed for total weekly caloric expenditure ( Mdn change = 644–707 kcal/week ) and moderate or greater weekly caloric expenditure ( Mdn change = 149–265 kcal/week ) , as well as for weekly physical activity duration and frequency . These changes were observed in participants across all sites . Conclusions : The increases in weekly caloric expenditure were commensurate with findings from several previous r and omized clinical trials . The utilization of community agency staff and volunteers receiving basic training to implement essential program components proved feasible . Very favorable levels of program satisfaction expressed by community staff , volunteer support buddies , and participants , combined with the significant increases in physical activity , warrant further dissemination of the intervention model Background Physical activity ( PA ) for older adults has well-documented physical and cognitive benefits , but most seniors do not meet recommended guidelines for PA , and interventions are lacking . Objectives This study evaluated the efficacy of a 12-week Internet intervention to help sedentary older adults over 55 years of age adopt and maintain an exercise regimen . Methods A total of 368 sedentary men and women ( M=60.3 ; SD 4.9 ) were recruited , screened , and assessed online . They were r and omized into treatment and control groups and assessed at pretest , at 12 weeks , and at 6 months . After treatment group participants rated their fitness level , activity goals , and barriers to exercise , the Internet intervention program helped them select exercise activities in the areas of endurance , flexibility , strengthening , and balance enhancement . They returned to the program weekly for automated video and text support and education , with the option to change or increase their exercise plan . The program also included ongoing problem solving to overcome user-identified barriers to exercise . Results The multivariate model indicated significant treatment effects at posttest ( P=.001 ; large effect size ) and at 6 months ( P=.001 ; medium effect size ) . At posttest , intervention participation showed significant improvement on 13 of 14 outcome measures compared to the control participants . At 6 months , treatment participants maintained large gains compared to the control participants on all 14 outcome measures . Conclusions These results suggest that an online PA program has the potential to positively impact the physical activity of sedentary older adult participants . More research is needed to replicate the study results , which were based on self-report measures . Research is also needed on intervention effects with older population BACKGROUND The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition . METHODS Fifty-nine healthy but sedentary community-dwelling volunteers , aged 60 - 79 years , participated in the 6-month r and omized clinical trial . Half of the older adults served in the aerobic training group , the other half of the older adults participated in the toning and stretching control group . Twenty young adults served as controls for the magnetic resonance imaging ( MRI ) , and did not participate in the exercise intervention . High spatial resolution estimates of gray and white matter volume , derived from 3D spoiled gradient recalled acquisition MRI images , were collected before and after the 6-month fitness intervention . Estimates of maximal oxygen uptake ( VO2 ) were also obtained . RESULTS Significant increases in brain volume , in both gray and white matter regions , were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning ( nonaerobic ) control group . As predicted , no significant changes in either gray or white matter volume were detected for our younger participants . CONCLUSIONS These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans . Furthermore , these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults PURPOSE Given the prevalence of physical inactivity among American adults , convenient , low-cost interventions are strongly indicated . This study determined the 6- and 12-month effectiveness of telephone interventions delivered by health educators or by an automated computer system in promoting physical activity . DESIGN Initially inactive men and women age 55 years and older ( N = 218 ) in stable health participated . Participants were r and omly assigned to human advice , automated advice , or health education control . MEASURES The vali date d 7-day physical activity recall interview was used to estimate minutes of moderate to vigorous physical activity . Physical activity differences by experimental arm were verified on a r and om sub sample via accelerometry . RESULTS Using intention-to-treat analysis , at 6 months , participants in both interventions , although not differing from one another , showed significant improvements in weekly physical activity compared with controls . These differences were generally maintained at 12 months , with both intervention arms remaining above the target of 150 min per week of moderate to vigorous physical activity on average . CONCLUSION Automated telephone-linked delivery systems represent an effective alternative for delivering physical activity advice to inactive older adults OBJECTIVE This study compared a motivational intervention based on protection motivation theory ( PMT , Rogers , 1975 , 1983 ) with the same motivational intervention augmented by a volitional intervention based on implementation intentions ( Gollwitzer , 1993 ) . DESIGN The study had a longitudinal design , involving three waves of data collection over a 2-week period , incorporating an experimental manipulation of PMT variables at Time 1 and a volitional , implementation intention intervention at Time 2 . METHOD Participants ( N=248 ) were r and omly allocated to a control group or one of two intervention groups . Cognitions and exercise behaviour were measured at three time-points over a 2-week period . RESULTS The motivational intervention significantly increased threat and coping appraisal and intentions to engage in exercise but did not bring about a significant increase in subsequent exercise behaviour . In contrast , the combined protection motivation theory/implementation intention intervention had a dramatic effect on subsequent exercise behaviour . This volitional intervention did not influence behavioural intention or any other motivational variables . CONCLUSIONS It is concluded that supplementing PMT with implementation intentions strengthens the ability of the model to explain behaviour . This has implication s for health education programmes , which should aim to increase both participants ' motivation and their volition The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function Objective . To evaluate the effectiveness of a 12-week home-based postal and telephone physical activity and nutrition pilot program for seniors . Methods . The program was delivered by mailed material and telephone calls . The main intervention consisted of a booklet tailored for seniors containing information on dietary guidelines , recommended physical activity levels , and goal setting . Dietary and walking activity outcomes were collected via a self-administered postal question naire pre- and postintervention and analysed using linear mixed regressions . Of the 270 seniors recruited , half were r and omly selected for the program while others served as the control group . Results . The program elicited favourable responses . Postintervention walking for exercise/recreation showed an average gain of 27 minutes per week for the participants in contrast to an average drop of 5 minutes for the controls ( P < .01 ) . Little change was evident in err and walking for both groups . The intervention group ( n = 114 ) demonstrated a significant increase in fibre intake ( P < .01 ) but no reduction in fat intake ( P > .05 ) compared to controls ( n = 134 ) . Conclusions . The participants became more aware of their health and wellbeing after the pilot program , which was successful in increasing time spent walking for recreation and improving fibre intake BACKGROUND Regular physical activity is generally associated with psychological well-being , although there are relatively few prospect i ve studies in older adults . We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population . METHODS In this nested case-control study , subjects aged 60 years or more were identified from r and omly selected cohorts being followed prospect ively in the Geelong Osteoporosis Study . Cases were individuals with incident depressive or anxiety disorders , diagnosed using the Structured Clinical Interview for DSM-IV-TR ( SCID-I/NP ) ; controls had no history of these disorders . Habitual physical activity , measured using a vali date d question naire , and other exposures were documented at baseline , approximately four years prior to psychiatric interviews . Those with depressive or anxiety disorders that pre- date d baseline were excluded . RESULTS Of 547 eligible subjects , 14 developed de novo depressive or anxiety disorders and were classified as cases ; 533 controls remained free of disease . Physical activity was protective against the likelihood of depressive and anxiety disorders ; OR = 0.55 ( 95 % CI 0.32 - 0.94 ) , p = 0.03 ; each st and ard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders . Leisure-time physical activity contributed substantially to the overall physical activity score . Age , gender , smoking , alcohol consumption , weight and socioeconomic status did not substantially confound the association . CONCLUSION This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders BACKGROUND Both self-help print material s and telephone-assisted counseling have generally proved useful strategies to increase physical activity . This study examined their effectiveness in an intervention aim ed specifically at promoting walking for specific purpose s. METHODS Participants ( n = 399 ) were r and omly allocated to one of two 3-week intervention programs . The Print program comprised multiple mailing of brochures that emphasized walking within the local community environments . The Print plus Telephone program received the same brochures plus three telephone calls . Data collected via mailed self-completed surveys were analyzed by exploring outcomes related to walking for specific purpose s. RESULTS There were no significant differences between the two programs in any of the walking measures . Both groups significantly increased time reported walking for exercise per week [ Print : t(1,277 ) = -3.50 , P < 0.001 ; Print plus telephone : t(1,106 ) = -2.44 , P < 0.016 ] . Significantly , more participants in the Print plus Telephone group reported receiving and reading the material s ( chi2 = 20.11 , P < 0.0001 ) . CONCLUSIONS The intervention programs were more successful at increasing walking for exercise than for any other purpose . The addition of brief telephone support was successful in focusing participants ' attention on the print material s , but did not result in any additional increase in walking PURPOSE We examined the efficacy of an intervention tailored to the individual 's stage of change for exercise adoption on exercise stage of change , physical activity , and physical function in community-dwelling older adults . DESIGN AND METHODS We r and omized participants to a print and telephone intervention or a contact comparison group . Through the use of longitudinal analyses we examined the intervention 's effectiveness in promoting stage progression , altering decisional balance and the processes of change , increasing self-efficacy and physical activity , and improving physical function among older adults who completed the 24-month study ( N = 966 ) . We conducted similar analyses that excluded individuals who were in maintenance at baseline and 24 months . RESULTS At the end of the study , there were no differences in stage progression , self-efficacy , decisional balance , the processes of change , physical activity , or physical function by intervention assignment . When the analyses excluded those participants ( n = 358 ) who were in the maintenance stage for exercise throughout the intervention , we found that , compared with the comparison group , a greater proportion of individuals who received the exercise intervention progressed in stage by 24 months . Conversely , more individuals in the comparison group remained stable or regressed in stage compared with the intervention group . IMPLICATION S Results indicate that a tailored intervention is effective in increasing motivational readiness for exercise in individuals who were in stages of change other than maintenance Background : Unhealthy diet and lack of physical activity increase rural midlife and older women 's risk of chronic diseases and premature death , and they are behind urban residents in meeting Healthy People 2010 objectives . Objectives : The objective of this study was to compare a tailored intervention based on the Health Promotion Model with a generic intervention to increase physical activity and healthy eating among rural women . Methods : In a r and omized-by-site , community-based , controlled , clinical trial , Wellness for Women , 225 women aged 50 to 69 years were recruited in two similar rural areas . Over 12 months , women received by mail either 18 generic newsletters or 18 newsletters computer tailored on Health Promotion Model behavior-specific cognitions ( benefits , barriers , self-efficacy , and interpersonal support ) , activity , and eating . Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating . Data were analyzed by repeated- measures analysis of variance and chi-square tests ( & agr ; < .05 ) . Results : Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased percentage of calories from fat , whereas only the tailored group increased moderate or greater intensity activity and decreased percentage of calories from saturated fat from baseline to 6 months . Both groups increased stretching and strengthening exercise , whereas only the tailored group increased moderate or greater intensity activity and fruit and vegetable servings and decreased percentage of calories from fat from baseline to 12 months . Both groups had several changes in biomarkers over the study . A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for moderate or greater intensity activity , fruit and vegetable servings , and percentage of calories from fat at 12 months . Discussion : Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months . Tailored newsletters were more efficacious in facilitating change over 12 months BACKGROUND Efforts to achieve population -wide increases in walking and similar moderate-intensity physical activities potentially can be enhanced through relevant applications of state-of-the-art interactive communication technologies . Yet few systematic efforts to evaluate the efficacy of h and -held computers and similar devices for enhancing physical activity levels have occurred . The purpose of this first-generation study was to evaluate the efficacy of a h and -held computer ( i.e. , personal digital assistant [ PDA ] ) for increasing moderate intensity or more vigorous ( MOD+ ) physical activity levels over 8 weeks in mid-life and older adults relative to a st and ard information control arm . DESIGN R and omized , controlled 8-week experiment . Data were collected in 2005 and analyzed in 2006 - 2007 . SETTING / PARTICIPANTS Community-based study of 37 healthy , initially underactive adults aged 50 years and older who were r and omized and completed the 8-week study ( intervention=19 , control=18 ) . INTERVENTION Participants received an instructional session and a PDA programmed to monitor their physical activity levels twice per day and provide daily and weekly individualized feedback , goal setting , and support . Controls received st and ard , age-appropriate written physical activity educational material s. MAIN OUTCOME MEASURE Physical activity was assessed via the Community Healthy Activities Model Program for Seniors ( CHAMPS ) question naire at baseline and 8 weeks . RESULTS Relative to controls , intervention participants reported significantly greater 8-week mean estimated caloric expenditure levels and minutes per week in MOD+ activity ( p<0.04 ) . Satisfaction with the PDA was reasonably high in this largely PDA-naive sample . CONCLUSIONS Results from this first-generation study indicate that h and -held computers may be effective tools for increasing initial physical activity levels among underactive adults OBJECTIVES To assess the long-term effectiveness of a telephone counseling intervention on physical activity and health-related quality of life in low-active older adults recruited through their primary care physician . DESIGN R and omized , controlled trial . SETTING Three primary care practice s from different socioeconomic regions of Auckl and , New Zeal and . PARTICIPANTS One hundred and eighty-six low-active adults ( aged 65 ) recruited from their primary care physicians ' patient data bases . INTERVENTION Eight telephone counseling sessions over 12 weeks based on increasing physical activity . Control patients received usual care . MEASUREMENTS Change in physical activity ( as measured using the Auckl and Heart Study Physical Activity Question naire ) and quality of life ( as measured using the Short Form-36 Health Survey ( SF-36 ) ) over a 12-month period . RESULTS Moderate leisure physical activity increased by 86.8 min/wk more in the intervention group than in the control group ( P=.007 ) . More participants in the intervention group reached 2.5 hours of moderate or vigorous leisure physical activity per week after 12 months ( 42 % vs 23 % , odds ratio=2.9 , 95 % confidence interval=1.33 - 6.32 , P=.007 ) . No differences on SF-36 measures were observed between the groups at 12 months . CONCLUSION Telephone-based physical activity counseling is effective at increasing physical activity over 12 months in previously low-active older adults BACKGROUND Better underst and ing the impact of changes in physical activity behavior on short-term health care charges may inform re source allocation decisions to increase population levels of physical activity . This study examines the prospect i ve relationship of changes in physical activity status on short-term changes in health care charges for older adults . METHODS A prospect i ve cohort study was done on a stratified r and om sample of 2,393 adults aged 50 and older enrolled in a Minnesota health plan , predicting changes in re source use between two periods ( September 1994 to August 1995 and September 1996 to August 1997 ) based on billed health care charges . RESULTS After adjustment for age , gender , comorbidity , smoking status , and body mass index , all physical activity states had declining health care charges , relative to those who were consistently inactive . Subjects who increased their physical activity from 0 - 1 to 3 + days/week had significant declines in their mean annualized total charges ( -2,202 dollars , P < 0.01 ) relative to those who remained inactive . CONCLUSIONS Increased physical activity among older adults is associated with lower health care charges within 2 years , relative to charges for those who were persistently inactive . These cost savings may justify investments in effective interventions to increase physical activity in older adults OBJECTIVE To examine the contribution of social-cognitive factors ( self-efficacy and affect ) in predicting long-term physical activity in a sample of older adults ( N=174 ) . DESIGN A prospect i ve design assessed physical activity and psychosocial variables at 2 and 5 years following a 6-month r and omized , controlled exercise trial . MAIN OUTCOME MEASURES The primary outcome variable was self-reported physical activity , with previous behavior , self-efficacy , and affect assessed as determinants of physical activity . RESULTS Covariance modeling analyses indicated that physical activity at Year 2 was the strongest predictor of physical activity at 5-year follow-up . Both self-efficacy and affect at Year 2 were also associated with physical activity at Year 5 , as was original treatment condition . Variables accounted for 35 % of the variance in Year 5 activity . CONCLUSION Older adults with higher levels of physical activity , more positive affect , and higher self-efficacy at Year 2 were more likely to continue to be active at Year 5 . This study is one of the longest follow-ups of exercise behavior in older adults and has implication s for structuring environments to maximize the maintenance of physical activity This study examined the feasibility and effectiveness for increasing physical activity of a print-based intervention , and a print- plus telephone-mediated intervention among mid-life and older Australian adults . A r and omised controlled trial study design was used . In mid-2002 , 66 adults ( 18 men , 48 women ) aged 45 - 78 years , who identified themselves as underactive , were recruited through advertisements and word-of-mouth at two sites ( Melbourne and Brisbane ) , and r and omised to either the print or print-plus-telephone mediated intervention group . Participants in both groups attended an initial briefing session , and over the 12-week intervention period received an instructional newsletter and use of a pedometer ( both groups ) , and individualised telephone calls ( print-plus-telephone group only ) . Self-reported physical activity data were collected at baseline , 12 and 16 weeks . Measures of self-reported global physical activity , moderate-vigorous intensity activity and walking all showed increases between baseline and 12 weeks for both intervention groups . These increases were generally maintained by 16 weeks , although participants in the print-plus-telephone group maintained slightly higher levels of global reported activity and walking ( by approximately 30 mins/wk ) than those in the print group . These interventions show potential for promoting initial increases in physical activity among mid-life and older Australian adults , and should be evaluated across more extended time periods Purpose : While substantial evidence demonstrates physical activity is effective at reducing risk for cardiovascular and other diseases , the percentage of older women participating in regular activity is low . The Internet offers an alternative method for delivery of a primary prevention intervention . This preliminary study examined the feasibility and effectiveness of using the Internet to deliver behavior change interventions for promoting physical activity in women ages 50‐69 years . Methods : Thirty‐one healthy women ( 56.1 ± 4.9 years ) were r and omly assigned to either tailored or st and ard newsletter groups . Both groups received 3 Internet‐delivered newsletters at baseline , 1 month , and 2 months . Behavioral markers and biomarkers were measured at baseline and postintervention . Post‐testing occurred at 3 months ( 1 month after delivery of the third newsletter ) . Results : Repeated measures ANOVAs revealed improvement in measures of flexibility and perceived barriers to exercise for both groups . For the st and ard group , improvement occurred in % body fat while VO2max declined . Women indicated the newsletters were helpful in influencing behavior change . Conclusion : Internet‐delivered newsletters appeared feasible and promising for favorably influencing perceptions about barriers to physical activity in these women . Selfreported physical activity did not increase although selected biomarkers did improve . Whether tailored or st and ard messaging was more effective was inconclusive OBJECTIVE The authors investigated the associations of medical and lifestyle factors with the mental health of men in their 80s . METHODS This was a prospect i ve study of a community-representative cohort of older men . Successful mental health aging was defined as reaching age 80 years with Mini-Mental State Examination score ( MMSE ) of 24 or more and Geriatric Depression Scale-15 items ( GDS-15 ) score of 5 or less . RESULTS Of 601 men followed for 4.8 years , 76.0 % enjoyed successful mental health aging . Successful mental health aging was inversely associated with age ( hazard ratio [ HR ] = 0.87 ; 95 % confidence interval [ CI ] : 0.81 - 0.94 ) , non-English-speaking background ( HR = 0.42 ; 95 % CI : 0.21 - 0.85 ) , and the consumption of full-cream milk ( HR = 0.63 ; 95 % CI : 0.45 - 0.89 ) , and directly associated with high school or university education ( HR = 1.92 ; 95 % CI : 1.34 - 2.75 ) and vigorous ( HR = 1.89 ; 95 % CI : 1.17 - 3.05 ) and nonvigorous physical activity ( HR = 1.50 ; 95 % CI : 1.05 - 2.14 ) . Marital status , smoking and alcohol use , weekly consumption of meat or fish , and a medical history of hypercholesterolemia , hypertension , diabetes , myocardial infa rct ion , and stroke were not associated with mental health outcomes in men aged 80 years or over . CONCLUSION Three in four men who reach age 80 years undergo successful mental health aging . Factors associated with successful mental health aging include education and lifestyle behaviors such as physical activity . Lifestyle modification by means of increasing physical activity and reducing saturated fat intake may prove to be a safe , inexpensive , and readily available strategy to help maximize the successful mental health aging of the population |
10,977 | 24,032,995 | No trend was observed regarding relative utility of the various commonly employed techniques .
Cross-matched PLTs are useful in increasing PLT counts in alloimmunized , transfusion-refractory HT patients , but data about their impact on hemorrhage and mortality are lacking | BACKGROUND Multiply transfused hypoproliferative thrombocytopenic ( HT ) patients with alloimmune transfusion refractoriness require specially selected platelets ( PLTs ) .
Cross-matching apheresis PLTs is a popular support option , avoiding requirements for large panels of typed donors for HLA-based selection .
We undertook a systematic review of the utility of various cross-matching techniques on mortality reduction , prevention of hemorrhage , alloimmunization and refractoriness , and improvement in PLT utilization or count increments . | Summary . Refractoriness to r and om‐donor platelets as a result of alloimmunization remains a major problem in long‐term platelet transfusion therapy despite the use of HLA‐matched platelets . We have therefore studied the use of two methods for detection of platelet associated IgG as platelet crossmatch tests for the selection of platelet donors . These methods use radiolabelled staphylococcal protein A ( 125I‐SPA ) and peroxidase anti‐peroxidase ( PAP ) , respectively Seventy-nine platelet transfusions to 73 thrombocytopenic patients with cancer were analyzed to determine whether a platelet count obtained one hour after transfusion could help differentiate between alloimmunization and other clinical factors that result in rapid platelet destruction . These transfusions were selected because 18- to 24-hour increments were inadequate in response to fresh , r and om donor platelets . A corrected count increment ( Cl ) ( Cl=[posttransfusion count-pretransfusion count]Xbody surface area [ sq m]/platelets transfusedX10 ' ' ) at one hour of 10X103/microliter or greater was associated with absence of lymphocytotoxic antibody , whereas increments of less than 10X103/microliter were generally associated with high levels of strongly cytotoxic antibody . HLA-matched transfusions produced no improvement in increments when the previous one-hour Cl had been 10X103/microliter or greater , whereas in the other group significantly better increments were obtained . A one-hour posttransfusion count is a simple test that correlates well with the presence of antibody against HLA antigens , is valuable in predicting the need for HLA-matched platelets , and helps avoid wasteful , empirical use of such transfusions A latex agglutination assay was evaluated for the purpose of identifying compatible platelet donors for alloimmunized recipients . Assay reagents were prepared by adsorbing detergent-solubilized , donor-specific platelets to polystyrene latex beads . Semiquantitative results for up to 30 donors can be completed in less than 1 hour . These reagents retained their immunoreactivity for at least 3.5 months . A retrospective study has established the assay 's upper limit of compatibility . The prospect i ve study evaluated transfusions to a group of multiply transfused patients . Part I evaluated 143 crossmatched , single-donor platelet transfusions given to 50 patients . In 96 percent of the cases , a positive crossmatch was associated with an unsuccessful transfusion outcome ; in 84 percent of the transfusions , a negative crossmatch predicted a satisfactory platelet increment . The overall predictability , sensitivity , and specificity were 87 , 62 , and 99 percent , respectively . Part II evaluated 105 transfusions given to the 43 patients ( of 50 ) in whom no incidence of fever , sepsis , or bleeding could be documented . A positive crossmatch was 96-percent efficient in predicting an unsuccessful transfusion , whereas a negative crossmatch was associated with an adequate platelet increment following 89 percent of the transfusions . The overall predictability was 91 percent , the sensitivity was 72 percent , and the specificity was 99 percent . Within-run and between-run variations were 6.3 and 6.2 percent , respectively . These results demonstrate that detergent-solubilized platelet antigens , immobilized on latex particles , can be used in a cost-effective crossmatching procedure Although the value of HLA matching for the selection of platelet donors for patients refractory to r and om platelets is beyond doubt , even perfectly matched combinations sometimes fail to give a satisfactory transfusion response . With HLA typing and negative lymphocytotoxicity crossmatches , 35 % of the platelet transfusions administered to 15 patients gave disappointing results ( 29 of 82 ) . Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7 % ( 6 of 82 ) . Five of these failures were observed in one patient . The target of the antibodies detected with this platelet fluorescence test is not yet fully specified . It seems probable that both HLA and platelet-specific non-HLA antibodies were detected . No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found A variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets ( TRAP ) . Responses measured were platelet increments , interval between platelet transfusions , and platelet refractoriness . Patient factors that improved platelet responses were splenectomy and increasing patient age . In contrast , at least 2 prior pregnancies , male gender , splenomegaly , bleeding , fever , infection , disseminated intravascular coagulation , increasing height and weight , lymphocytotoxic antibody positivity , an increasing number of platelet transfusions , or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses . Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets , platelets stored for 48 hours or less , and giving large doses of platelets while ultraviolet B ( UV-B ) or gamma irradiation decreased platelet responses . However , in alloimmunized lymphocytoxic antibody-positive patients , the immediate increment to UV-B-irradiated platelets was well maintained , whereas all other products showed substantial reductions . Refractoriness to platelet transfusions developed in 27 % of the patients . Platelet refractoriness was associated with lymphocytotoxic antibody positivity , heparin administration , fever , bleeding , increasing number of platelet transfusions , increasing weight , at least 2 pregnancies , and male gender . The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets R and omized controlled trials have shown a reduction in platelet alloimmunization and refractoriness in patients with acute leukemia ( AL ) with the use of poststorage leukoreduction of blood products . Universal prestorage leukoreduction ( ULR ) of red cell and platelet products has been performed in Canada since August 1999 . We conducted a retrospective analysis of 13 902 platelet transfusions in 617 patients undergoing chemotherapy ( CT ) for AL or stem cell transplantation ( SCT ) before ( n = 315 ) and after ( n = 302 ) the introduction of ULR . Alloimmunization was significantly reduced ( 19 % to 7 % , P < .001 ) in the post-ULR group . Alloimmune platelet refractoriness was similarly reduced ( 14 % to 4 % , P < .001 ) . Fewer patients in the post-ULR group received HLA-matched platelets ( 14 % vs 5 % , P < .001 ) . Alloimmunization and alloimmune refractoriness in the 318 patients who were previously pregnant and /or transfused were also reduced after ULR ( P = .023 and P = .005 , respectively ) . In a Cox regression model , the 3 independent factors that predicted for alloimmune refractoriness were nonleukoreduced blood products ( relative risk [ RR ] , 2.2 [ 95 % CI , 1.2 - 4.3 ] ) , a history of pregnancy and /or transfusion ( RR , 2.3 [ 95 % CI , 1.3 - 4.2 ] ) , and receipt of 13 or more platelet transfusions ( RR , 6.0 [ 95 % CI , 2.4 - 15.3 ] ) . In conclusion , ULR reduces alloimmunization , refractoriness , and requirements for HLA-matched platelets when applied as routine transfusion practice to patients receiving CT or SCT Four platelet compatibility assays were performed on serum and platelet or lymphocyte sample s from 38 closely HLA-matched donor/recipient pairs involved in 55 single-donor platelet transfusions . The 22 patients studied were refractory to transfusions of pooled r and om-donor platelets . Of the four assays ( platelet suspension immunofluorescence , PSIFT ; 51Cr release ; microlymphocytotoxicity ; and a monoclonal anti-IgG assay , MAIA ) , the MAIA was most predictive of platelet transfusion outcome ( predictability , 74 % for one-hour posttransfusion platelet recovery and 76 % for 24-hour recovery ) . The only other assay to reach statistical significance was the PSIFT ( 63 % predictability for one-hour posttransfusion recovery ) . The degree of HLA compatibility between donor and recipient ( exact matches v those utilizing cross-reactive associations ) was unrelated to the ability of the MAIA to predict transfusion results . The MAIA may be capable of differentiating HLA antibodies , ABO antibodies , and platelet-specific antibodies responsible for failure of HLA-matched and selectively mismatched single-donor platelet transfusions BACKGROUND HLA-matched platelets and crossmatch-compatible platelets are used to support thrombocytopenic patients who are refractory to r and omly selected platelets . Data supporting the effectiveness of crossmatch-compatible platelets are limited , being essentially restricted to the subset of refractory patients previously shown to be alloimmunized . The authors ' hospital does not test for alloimmunization . To determine the effectiveness of crossmatch-compatible platelets in an unselected group of refractory patients , the use of such platelets for all patients who are refractory to r and om-donor platelets was review ed . STUDY DESIGN AND METHODS All patients who received crossmatch-compatible platelets between January 1991 and May 1994 were retrospectively review ed . All study patients were refractory to r and om-donor platelets , having two consecutive corrected count increments ( CCIs ) of < 10,000 . A solid-phase red cell adherence method was used for platelet crossmatching , and CCI was used to monitor the effectiveness of each platelet transfusion . RESULTS A total of 475 crossmatch-compatible platelet components were administered to 66 evaluable patients who were refractory to r and om-donor platelets . A significant improvement was found in the mean CCI when crossmatch-compatible platelets were compared with r and omly selected platelets ( p < 0.0001 ) : an increase of 8000 + /- 6100 ( mean + /- SD ) . In 59 percent ( 39/ 66 ) of the patients , the mean CCI improved to at least 7,500 and in 41 percent ( 27/66 ) to at least 10,000 . If the 10 patients for whom crossmatch-compatible platelets were not identified are included , the mean CCI in 51 percent ( 37/76 ) of the refractory patients improved to at least 7,500 ; in 36 percent ( 27/76 ) , it improved to at least 10,000 . The effectiveness of crossmatch-compatible platelets did not decline with continued use . CONCLUSION Crossmatch-compatible platelet components significantly improve the mean CCI for approximately one-half of patients who are refractory to r and om-donor platelets , even when the patients are not preselected for having alloimmunization to explain their refractory state BACKGROUND The use of crossmatch-compatible platelets ( PLTs ) improves posttransfusion corrected count increments ( CCIs ) in patients with alloimmune PLT refractoriness . However , few reports address the efficacy of utilizing this strategy for patients requiring intensive PLT transfusion therapy lasting several weeks to months . STUDY DESIGN AND METHODS Medical records of patients with two or more PLT crossmatch assays performed between 2002 and 2010 were review ed . All patients were refractory to r and om single-donor apheresis PLT units , defined as two consecutive 1-hour posttransfusion CCIs of less than 7500 . A commercial solid-phase adherence assay was used for crossmatching . RESULTS Seventy-one patients were included . A median of four crossmatch assays were performed per patient ( range , 2 - 17 ) . Mean percent reactivity in initial ( 58.6 % ) versus last ( 55.3 % ) crossmatch assay for each patient demonstrated no trend toward progressive alloimmunization ( p = NS ) . A total of 738 crossmatched PLT units were administered with a mean ± st and ard deviation CCI of 7000 ± 7900 ( n = 443 units with adequate 1-hr posttransfusion counts ) , a significant improvement over r and om PLTs ( p < 0.001 ) . Patients with an initial crossmatch reactivity of greater than 66 % were significantly more likely to demonstrate at least one panreactive crossmatch assay , impacting the availability of compatible PLTs for optimum transfusion support . One patient ( 1.4 % ) developed WHO Grade IV bleeding . CONCLUSIONS Progressive alloimmunization to mismatched antigens does not impact medium-term transfusion support with crossmatched PLTs . Increased reactivity in the initial crossmatch assay can serve as a trigger to initiate workup for HLA-matched PLTs as a second-line approach . However , for most patients , medium-term transfusion support with crossmatched PLTs offers an effective and rapid first-line approach to management of PLT transfusion refractoriness Despite the use of HLA-matched platelets for alloimmunized recipients , transfusion failures occur . In order to reduce these failures , we investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching . The principle of the test is that of an indirect Coombs test using 125I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test ( RAGT ) index . Using this technique , we performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to r and om donor platelets and receiving varying degrees of HLA-matched platelets . Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment ( CCI ) determined at 1 and 20 hr . When the RAGT index was 1.9 or less , the mean CCI at 1 lhr was 17,570 + /- 7003/cu mm , n = 55 . When the RAGT index was 2.0 or greater , the mean CCI was 4237 + /- 4100/cu mm , n = 34 . At 20 hr when the RAGT index was 1.9 or less , the mean CCI was 8722 + /- 3143/cu mm , n = 33 , and when the index was 2.0 or greater , the mean CCI was 571 + /- 1286/cu mm , n = 23 . Using this technique , one false negative result ed . Nine positive crossmatches with good increments at 1 hr were found ; at 20 hr , however , the survival of these units was zero . These data suggest that this method is a useful adjunct in the selection of platelets in the refractory patient Fifty-three patients receiving long-term platelet transfusions were regularly screened for platelet-associated antibodies by a platelet suspension immunofluorescence test ( PSIFT ) and a lymphocytotoxicity test ( LCT ) . Subsequently , 24 patients became alloimmunized ; all of their antibodies were of HLA specificity . Eighty-two single-donor platelet transfusions were given , and the clinical responses were considered satisfactory if the 18-hour corrected count increment was 7.5 x 10(3 ) per microL or higher . In the meantime , 82 pairs of patient sera and donor lymphocytes were crossmatched . Among 63 crossmatched transfusions , 53 ( 84 % ) result ed in a satisfactory increment , with a mean ( + /- SEM ) of 17.71 + /- 1.96 ( x 10(3)/microL ) , and 10 did not result in a satisfactory increment . The increments after 19 unmatched transfusions and 25 r and om-donor ( uncrossmatched ) transfusions were 0.7 + /- 0.3 and 2.39 + /- 0.66 , respectively . The difference was not significant ( p greater than 0.05 ) . The agreement between the LCT results and clinical response was 88 percent . Retrospectively , the corrected count increments showed no significant differences ( p greater than 0.05 ) among three groups of HLA grading : the increments for A/BU/BX , C/D , and r and om HLA matches were 22.97 + /- 4.07 , 15.1 + /- 1.97 , and 14.85 + /- 2.04 , respectively . These results suggest that platelet crossmatching by LCT is an effective method for use in alloimmunized patients , especially Chinese patients Sample s obtained from bag segments of stored platelet concentrates ( PCs ) were crossmatched with sera from alloimmunized patients to identify potentially compatible donors . Sera from 41 patients who were refractory to r and om-donor platelet transfusions were tested . All sera had lymphocytotoxic antibody ( LCTAb ) , and 37 patients had LCTAb that reacted strongly against greater than 75 percent of the cells in the panel . At least 18 units of PCs were tested per patient . Sera from 33 patients were tested by microenzyme-linked immunosorbent assay ( microELISA ) . Crossmatches with 703 ( 74 percent ) of 944 PCs were positive , 23 percent were negative , 3 percent were indeterminant . Eight additional patients were also tested with a solid-phase system ; 352 ( 85 percent ) of 417 crossmatches were positive and 15 percent were negative . Patients with more reactive LCTAb had very few ( often 0 - 2 ) in vitro compatible units . Thirty-four transfusions of pooled compatible PCs , all stored less than 3 days , were administered to clinical ly evaluable patients . Six of 20 transfusions selected by microELISA produced satisfactory increases ( corrected count increments [ CCIs ] greater than 7500 ) 10 minutes after transfusion in 4 of 14 patients . Eight of 14 transfusions selected by solid-phase produced CCIs greater than 7500 in 5 of 8 patients . Although it is difficult to select large numbers of compatible units for heavily alloimmunized patients by these techniques , some transfusions were successful in patients who had very few HLA-compatible donors . This approach may be of particular value in emergency situations Platelet crossmatching may provide a useful way of selecting donors for effective platelet transfusions in patients refractory to r and om donor platelet concentrates due to alloimmunization . We assessed the predictive value of a flow cytometric platelet immunofluorescence crossmatch test for the outcome of HLA matched platelet transfusions in a group of alloimmunized patients . Platelet immunofluorescence ( PIFT ) crossmatches were performed for 104 HLA‐matched platelet transfusions administered to 30 patients . A negative PIFT crossmatch correctly predicted a successful platelet transfusion ( 1 h post‐transfusion platelet recovery > 20 % ) in 56/75 ( 75 % ) cases . We also considered non‐immunological factors that , in combination with alloimmunization , might have contributed to an unsuccessful transfusion result , i.e. fever , septicaemia , splenomegaly , disseminated intravascular coagulation and bleeding . The predictive value of a negative PIFT crossmatch was better when these non‐immunological factors were absent [ 48/59 ( 81 % ) correct predictions ] than when these factors were present [ 8/16 ( 50 % ) correct predictions ] ( P=0.01 ; chi‐square test ) . The effect of ABO incompatibility between donor and recipient on the predictive value of the PIFT crossmatch was also analysed . Positive PIFT crossmatches occurred more frequently in ABO incompatible donor – recipient combinations [ in 18/28 ( 64 % ) cases ] than in ABO‐compatible donor – recipient combinations [ in 11/76 cases ( 14 % ) ] ( P<0.001 , chi‐square test ) . Successful platelet transfusions were observed on 53/76 ( 70 % ) occasions in ABO compatible transfusions as compared to 16/28 ( 57 % ) in ABO incompatible transfusions . This difference was not statistically significant ( P=0.23 ; chi‐square test ) . Consequently , a negative PIFT crossmatch appeared to be non‐predictive for the transfusion outcome in cases of ABO incompatibility between donor and recipient . We conclude that the PIFT crossmatch for platelet donor selection in addition to matching for HLA antigens , is predictive for the outcome of ABO compatible transfusions in alloimmunized recipients and prediction levels are increased when non‐immunological causes for platelet refractoriness are absent Selection of platelets for alloimmunized , thrombocytopenic patients has traditionally been based on HLA matching . This approach is indirect and may not adequately recognize incompatibility between the recipient and the platelet donor . The authors evaluated the usefulness of directly showing donor-recipient compatibility by crossmatching the patient 's serum with prospect i ve platelet donors who were not preselected on the basis of their HLA type . Eleven alloimmunized patients were chosen for study , and crossmatching was done by a radiolabeled antiglobulin test . These patients had high levels of HLA alloantibody , and their unusual HLA types made the provision of HLA-matched platelets difficult . When the crossmatch was compatible , the mean one-hour corrected count increment was 18,379 + /- 4,670 ( 1 st and ard deviation ) , n = 22 , and at 18 - 24 hours , 7,318 + /- 3,317 . If the crossmatch was positive , the mean one-hour corrected increment was 2,536 + /- 3,057 , and at 18 - 24 hours , 227 + /- 657 , n = 16 . There were two false negative crossmatches and one false positive crossmatch . One hundred forty-eight crossmatches were done to find 48 potential donors , who , by conventional selection using HLA matching , would not have been considered appropriate donors . These results show that successful platelet transfusions for alloimmunized thrombocytopenic patients can be prospect ively selected by platelet crossmatching without the need of doing expensive HLA typing of a large population of platelet donors . Although it may be difficult to find compatible platelets for some patients with broadly reactive HLA antibodies , platelet crossmatching may detect compatible donors who are ordinarily excluded on the basis of their HLA phenotype A multi-site clinical study compared platelets chosen for refractory patients by prospect i ve platelet crossmatching using stored donor platelets and HLA-based selection . Seventy-three patients who were refractory to r and om-donor platelets received two plateletpheresis components , one chosen by HLA-based criteria and the other by crossmatching . Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results . Each of the five study sites used a crossmatch procedure with which it had experience . Results from this study indicate the following : 1 ) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grade s of matching and mismatching was compared to a crossmatch-based method of donor selection . 2 ) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone . Donor selection based on HLA matching ( grade s A or BU ) was also superior to selection based on any degree of HLA mismatching ( grade s BX , C , or D ) . 3 ) Selection of donors based on HLA-cross-reactive groups ( defined by in vitro serologic crossreactivity ) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone . 4 ) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients , even though patients demonstrating nonimmune factors were eliminated from the study . It can be concluded that HLA-compatible ( grade s A and BU ) platelets provide optimal support for refractory patients , but that crossmatch-selected platelets are acceptable as an alternative component Effective platelet support for alloimmunized refractory thrombocytopenic patients may be provided by several potential strategies , the most common being HLA-matched single-donor platelets or crossmatch-compatible , pooled r and om- or single-donor platelets . This study used a detailed economic analysis to compare the cost-effectiveness of several techniques for platelet crossmatching and that of HLA-matched single-donor platelets . The crossmatch methods evaluated were a microlymphocytotoxicity test ( LCT ) , an immunofluorescence technique ( PSIFT ) , a radioactive antiglobulin test ( PRAT ) , and an enzyme-linked immunosorbent assay ( ELISA ) . The analysis was based on the need to support 100 refractory patients with acute leukemia with a presumed requirement of 500 transfusions . The relative costs for a successful crossmatch were : PRAT less than LCT less than LCT + PRAT less than PSIFT less than ELISA . In the comparison of the crossmatch methods , an increase in costs was generally associated with an increase in the number of successful transfusion episodes . However , decreasing marginal gains were seen . The HLA-matched single-donor platelets were relatively cost-inefficient in comparison to the crossmatch-compatible platelets . A theoretic sequence of tests for cost-effective provision of optimal platelet support in refractory patients was evaluated . Such considerations of cost are important in the selection of an optimal program for the management of alloimmunized refractory thrombocytopenic patients Summary An indirect platelet radioactive antiglobulin test was used in a prospect i ve crossmatch study in 29 patients for selecting compatible r and om donors for platelet transfusion . Patients received crossmatch‐compatible , crossmatch‐incompatible and uncrossmatched platelets . A successful outcome for transfusion was defined as a 24 h post‐transfusion corrected platelet increment of greater than 4·5 × 109/I. Of 47 predictions based on crossmatch results , the technique successfully predicted the outcome of the transfusion in 90 % of cases . In all patients , transfusion of crossmatch‐compatible platelets result ed in a significantly higher 24 h corrected platelet increment than was obtained following transfusion of incompatible platelets . The mean±SEM 24 h corrected post‐transfusion increment ( × 109/1 ) was 17·79±2·01 in 26 patients who received crossmatch‐compatible pooled r and om donor platelets ; in 21 patients who received crossmatch‐incompatible platelets , it was 1·19 ±0·56 ; and in 25 patients who received uncrossmatched platelets , 4·42 ±0·97 . The differences were highly significant . There was an 83 % correlation of results with those obtained using an indirect platelet suspension immunofluorescence technique BACKGROUND Despite supportive care with platelet ( PLT ) transfusions , bleeding complications occur in a substantial number of patients with thrombocytopenia due to cytotoxic therapy . Moreover , refractoriness to PLT transfusions remains a frequently encountered problem . The clinical impact of PLT transfusion failure was investigated in 117 patients , part of a r and omized PLT transfusion trial , which excluded patients with HLA and /or HPA alloantibodies . STUDY DESIGN AND METHODS Between October 2003 and April 2005 , a multicenter r and omized controlled trial , testing the clinical efficacy of PLTs stored in plasma compared to PLT additive solution ( PAS II ) , was performed . Using multiple regression analysis of observational data of patients r and omized in one of the participating centers , the occurrence of PLT transfusion refractoriness was analyzed for a relation with bleeding complications and patient survival . RESULTS PLT transfusion failure occurred at least once in 49.6 percent of the patients . Mild to moderate bleeding complications occurred in 19 percent of the patients . PLT transfusion failure was , independently from thrombocytopenia , positively associated with bleeding complications ( odds ratio , 3.4 ; 95 % confidence interval , 1.1 - 11 ) . Moreover , patients experiencing one or more 24-hour PLT transfusion failures had , compared to patients always showing a sufficient 24-hour increment , a significantly reduced median survival of 491 days ( interquartile range [ IQR ] , 156 - 858 days ) versus 825 days ( IQR , 355 - 996 days ) , respectively . In a Cox regression model , the effect on survival was independent of therapy , diagnosis , and age . CONCLUSION Our results suggest that PLT transfusion failure might be a sensitive clinical marker for the occurrence of bleeding and impaired patient survival . PLT transfusion failure , bleeding complications , and decreased survival could be manifestations of a more severe degree of endothelial damage BACKGROUND Patients who are refractory to platelet transfusion as a result of HLA alloimmunization are generally given HLA-matched or crossmatched platelets . However , HLA-matched platelets that are matched at HLA-A and -B loci ( A-matched ) or those without any mismatched or cross-reactive antigens ( BU-matched ) are frequently unavailable . A disadvantage of crossmatching is that crossmatched platelets have a shelf life of only 5 days , so that crossmatch tests must be performed frequently for patients requiring long-term platelet transfusions . An alternative method is the selection of platelets according to the patient 's HLA antibody specificity , called the antibody specificity prediction ( ASP ) method . STUDY DESIGN AND METHODS An anti-human globulin-enhanced microlymphocytotoxicity test modified by a double addition of serum and a computer program were used to determine the specificity of patients ' HLA antibodies . Platelet crossmatching was performed with a solid-phase adherence assay . The percentage of platelet recovery ( PPR ) was determined in 1621 platelet transfusions in an observational study in 114 patients , and the PPR of platelets selected by the ASP method was compared with the PPR of those that were HLA-matched , crossmatched , or r and omly selected . The numbers of potential donors in files of HLA-typed donors as identified by HLA matching vs. the ASP method were determined . RESULTS After adjustments for covariates , the mean + /- SEM PPR was similar for HLA-matched ( 21 + /-4 % ) , cross-matched ( 23+/-4 % ) , and ASP-selected ( 24+/-3 % ) platelets and was significantly lower for r and omly selected ( 15+/-1.4 % ) platelets . For 29 alloimmunized HLA-typed patients , the mean number of potential donors found in a file of 7247 HLA-typed donors was 6 who were an HLA-A match ( median = 1 ) , 33 who were an HLA-BU match ( median = 20 ) , and 1426 who were identified by the ASP method ( median = 1365 ) . CONCLUSION The ASP method of donor selection for refractory alloimmunized patients appears as effective as HLA matching or crossmatching . Far more donors are identified in a file of HLA-typed donors by the ASP method than by HLA matching , and this indicates that the ASP method provides important advantages regarding the availability of compatible platelet components BACKGROUND We conducted a multi-institutional , r and omized , blinded trial to determine whether the use of platelets from which leukocytes had been removed by a filter or that had been treated with ultraviolet B irradiation would prevent the formation of antiplatelet alloantibodies and refractoriness to platelet transfusions . METHODS Patients who were receiving induction chemotherapy for acute myeloid leukemia were r and omly assigned to receive one of four types of platelets transfusions : unmodified , pooled platelet concentrates from r and om donors ( control ) ; filtered , pooled platelet concentrates from r and om donors ( F-PC ) ; ultraviolet B-irradiated , pooled platelet concentrates from r and om donors ( UVB-PC ) ; or filtered platelets obtained by apheresis from single r and om donors ( F-AP ) . All patients received transfusions of filtered , leukocyte-reduced red cells . RESULTS Of 530 patients with no alloantibodies at base line , 13 percent of those in the control group produced lymphocytotoxic antibodies and their thrombocytopenia became refractory to platelet transfusions , as compared with 3 percent in the F-PC group , 5 percent in the UVB-PC group , and 4 percent in the F-AP group ( P < or = 0.03 for each treated group as compared with the controls ; there were no significant differences among the treated groups ) . Lymphocytotoxic antibodies were found in 45 percent of the controls , as compared with 17 to 21 percent in the treated groups ( P<0.001 for each treated group as compared with the controls ; there were no significant differences among the treated groups ) . Antibodies against platelet glycoproteins developed in 6 to 11 percent of the patients , with no significant differences among the four groups . CONCLUSIONS Reduction of leukocytes by filtration and ultraviolet B irradiation of platelets are equally effective in preventing alloantibody-mediated refractoriness to platelets during chemotherapy for acute myeloid leukemia . Platelets obtained by apheresis from single r and om donors provided no additional benefit as compared with pooled platelet concentrates from r and om donors BACKGROUND AND OBJECTIVES Alloantibodies against platelets can be detected by using different laboratory tests . Most of these tests , which use panel cells or antigens as a target , perform poorly in non-selected haematological patients . In relation to these tests , a crossmatch test of transfused platelets and patient 's serum may be viewed as the st and ard and may be superior in predicting donor platelet destruction by alloimmunization . MATERIAL S AND METHODS In 95 r and omly selected thrombocytopenic patients with haematological malignancies , who were receiving leucodepleted blood products , 184 serum sample s were studied in an in vitro crossmatch test by using the technique of the platelet immunofluorescence test ( crossmatch-PIFT ) , in an in vivo crossmatch test detecting in vivo binding of immunoglobulins to transfused platelets according to the PIFT technique ( in vivo-PIFT ) , in the indirect PIFT using five r and om donors as a target ( panel-PIFT ) and in an enzyme linked immunosorbent assay using immobilized human leucocyte antigens ( HLAs ) of 100 st and ardized donors ( ELIHLA ) . The results of all these methods were related to the recovery at 1 and 16 h post-transfusion . RESULTS The results of the crossmatch-PIFT were not associated with platelet recovery at 1 and 16 h after transfusion . Even in a subgroup of patients , in whom predefined clinical factors were excluded , no association with platelet recovery was found . The results of the crossmatch-PIFT correlated with those of the in vivo-PIFT ( P = 0.02 ) ; however , 35 ( 19 % ) discrepant results were identified between these tests . The results of the crossmatch-PIFT were not related to the panel-PIFT ( P = 0.25 ) , but did relate to those of the ELIHLA ( P = 0.02 ) , still revealing 36 ( 20 % ) discrepant results . None of the in vivo-PIFT , the panel-PIFT or the ELIHLA was associated with platelet recovery after 1 h , whilst only a positive panel-PIFT was associated with poor platelet recovery at 16 h after transfusion ( P = 0.03 ) . CONCLUSIONS In a population at low risk for alloimmunization , the correlation of test outcome and platelet recovery is poor . None of these crossmatch tests or screening tests was identified as superior to any other in this population In this prospect i ve study , 26 consecutive patients being treated for haematological malignancies receiving st and ard ( i.e. non-leucocyte-depleted ) blood components were observed for the development of refractoriness to platelet transfusions . One hundred and sixteen of the 266 ( 44 % ) platelet transfusions failed to produce a satisfactory response . In 102/116 ( 88 % ) , the poor response was in the presence of non-immune factors known to be associated with platelet refractoriness . Non-immune factors were present alone in 78/116 ( 67 % ) , and in combination with immune factors in a further 24/116 ( 21 % ) . Immune factors ( HLA and platelet-specific antibodies ) were present during 29/116 ( 25 % ) of unsuccessful platelet transfusions . Statistical analysis confirmed that platelet refractoriness was significantly associated with the presence of non-immune factors . The non-immune factors associated with refractoriness were often multiple , most frequently a combination of fever , infection and antibiotic therapy . This study provides evidence that immune mechanisms were not the predominant cause of platelet refractoriness in the patient population studied . It also suggests that measures for the prevention of HLA alloimmunisation , such as leucocyte depletion , may have a limited impact in reducing the incidence of refractoriness to platelet transfusions The st and ard lymphocytotoxicity assay ( LCT ) , a biotin‐avidin enzyme immunoassay ( ELISA ) , platelet suspension immunofluorescence test ( PSIFT ) , and platelet radioactive antiglobulin test ( PRAT ) were examined in prospect i ve crossmatching for selection of compatible r and om donor platelets for refractory patients . One hundred seven episodes of pooled r and om donor platelet transfusions were evaluated in 26 patients . There was good reproducibility of results by individual techniques . Concordance of results by the different methods was 40–60 % . One‐hour and 24 hr posttransfusion corrected count increments ( CCI ) were compared as parameters for assessing success or failure of the transfusion . Using a rank scoring system , the relative efficiency of predictiveness for all transfusions was PRAT > LCT > PSIFT > ELISA . Combination of PRAT and LCT afforded the best predictability and sensitivity was higher than for either PRAT or LCT alone ( 93 vs. 79 and 62 % , respectively ) . Mean posttransfusion CCI ( x 108/L ) following PRAT‐compatible platelets was 13.9 ± 12.7 at 1 hr and 7.3 ± 6.9 at 24 hr ; following PRAT‐incompatible 5.7 ± 7.8 ( 1 hr ) and 2.1 ± 4.1 ( 24 hr ) . Results were similar for LCT‐tested platelets . A radioimmunofiltration modification of the PRAT developed and used in selected cases was simple , fast , efficient , and inexpensive . The study indicated that the techniques evaluated are practical and feasible for routine use in the provision of compatible r and om donor platelets to the refractory patient who has no other cause for increased platelet destruction In 1999 , we implemented an automated platelet cross‐matching ( XM ) programme to select compatible platelets from the local inventory for patients refractory to r and om donor platelets . In this study , we evaluated platelet count increments in 40 consecutive refractory patients ( 8·3 % of 480 consecutive platelet recipients ) given 569 cross‐match‐negative platelets between April 1999 and December 2001 . XM was performed automatically with a commercially available immunoadherence assay . Pre‐ , 1‐ and 24‐h post‐transfusion platelet counts ( mean ± SD ) for the 569 XM‐negative platelet transfusions containing 302 ± 71 × 109 platelets were 7·7 ± 5·5 , 32·0 ± 21·0 and 16·8 ± 15·5 × 109/l respectively . Increments were significantly higher ( P < 0·05 , t‐test ) than those observed in the same patients given 303 r and om platelet pools ( dose = 318 ± 52 × 109 platelets ) during the month before refractoriness was detected , when pre‐ , 1‐ and 24‐h post‐transfusion counts were 7·0 ± 8·6 , 15·9 ± 16·1 and 9·6 ± 12·8 × 109/l respectively . The cost of the platelet XM disposable kit per transfusion to produce 1‐h post‐transfusion platelet count increments > 10 × 109/l was euro 447 . This programme enabled the rapid selection of effective platelets for refractory patients , from the local inventory BACKGROUND For HLA-alloimmunized patients , platelet ( PLT ) concentrations are provided either at matched HLA-A and HLA-B loci or by serologic cross-reactivity groups ( CREG ) matching strategy . However , this method has some limitations . STUDY DESIGN AND METHODS In this study , the epitope-based matching ( EBM ) method was evaluated for selecting proper HLA-typed PLTs for patients with PLT transfusion refractoriness . Bead-based single-antigen HLA antibody detection method and HLAMatchmaker software were used to define the epitopes recognized by HLA-specific antibodies and to select compatible PLTs for nine patients with alloimmunized refractoriness . Corrected count increments ( CCIs ) were prospect ively determined to compare successful transfusion rates among different matching methods in 142 PLT transfusions . In addition , HLA antibodies were serially detected to see whether any emerging antibodies appeared after receiving the EBM-matched PLTs . RESULTS The transfusion success rates evaluated with 1-hour CCIs for perfect matching or lacking any mismatching at HLA-A and -B locus (A/BU)-matched , CREG-matched , and EBM-matched PLTs were 85.2 , 63.2 , and 83.7 % , respectively . Compared to CREG-matched PLTs , EBM-matched PLTs showed better transfusion results ( p = 0.035 ) . In the follow-up study ( 7 months ; range , 3 - 13 months ) , no emerging HLA-specific antibodies were detected after receiving EBM-matched PLTs . CONCLUSIONS EBM performed on the basis of bead-based single-antigen HLA antibody detection coupled with the HLAMatchmaker program is recommended in choosing proper PLTs for refractory patients when A/BU-matched PLTs were not available |
10,978 | 21,760,525 | Factors that were associated with medication adherence were self-efficacy , depression , patient-provider communication , and healthcare system related . | BACKGROUND Rates of medication adherence are low among hypertensive blacks despite numerous interventions to increase their adherence .
PURPOSE The aim of the study was to conduct a systematic review of the literature to underst and the factors associated with medication adherence in hypertensive blacks . | Relationships between depression , alcohol and illicit drug use , adherence behaviors , and blood pressure ( BP ) were examined in 190 urban hypertensive Black men enrolled in an ongoing hypertension control clinical trial . More than one fourth ( 27.4 % ) of the sample scored greater than 16 on the Center for Epidemiological Studies - Depression Scale ( CES-D ) , indicating a high risk of clinical depression . Depression was significantly associated with an increased likelihood of meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ) criteria for alcohol abuse or dependence ( odds ratio = 5.2 ; 95 % confidence interval = 1.897–14.214 ) . The level of depression was significantly correlated with poor medication ( r = .301 ) and poor dietary compliance ( r = .164 ) . Both alcohol intake and illicit drug use were significantly correlated with poor dietary compliance ( r = .195 and .185 , respectively ) and smoking ( r = .190 and .269 , respectively ) . Although no direct relationship between depression and the level of BP was substantiated by multivariate analysis , findings of descriptive analyses revealed statistically significant associations among depression , substance use , poor adherence , and poor BP outcomes . Given the harsh environment in which a large number of young urban Black men live , the high prevalence of substance abuse might be an attempt to fight off depression . Further in- depth investigation is needed to identify the role of depression and BP control in urban young Blacks in order to construct effective interventions that address their unique needs BACKGROUND The prevalence , morbidity and mortality of hypertension are strikingly higher for African Americans than for Whites . Poor adherence to the antihypertensive medication regimen is a major cause of inadequate blood pressure control . In this study , we assess the relationship of antihypertensive medication adherence to sociodemographic , clinical and cognitive characteristics of urban African American adults . METHOD Data were drawn from a larger r and omized controlled trial assessing the effect of a behavioral intervention to improve medication adherence and blood pressure control among hypertensive African American patients followed in an urban primary care network . Medication adherence was assessed at baseline using the Medication Event Monitoring System (MEMS)--a method regarded as the gold st and ard for assessing medication adherence in clinical research . Information on potential correlates of medication adherence ( sociodemographic , clinical and cognitive ) was obtained at baseline by computer-assisted interview . We assessed the cross sectional association of these factors to medication adherence in baseline data . RESULTS Medication adherence was significantly associated with systolic blood pressure ( r=.253 , P<.04 ) and self-reported medication adherence ( r=.285 , P<.03 ) . The relationship of education to medication adherence varied significantly by sex ( P<.05 for interaction ) . Specifically , lower educational attainment was related to higher adherence among men , but lower adherence among women . CONCLUSION Identifying correlates of low antihypertensive medication adherence and their interactions , as in this study , will help health providers to better recognize patients at higher risk for worse hypertension-related outcomes . This knowledge can also inform interventions which target a higher-risk subset of hypertensive patients Barriers to high blood pressure ( HBP ) care and control have been reported in the literature for > 30 years . Few reports on barriers , however , have focused on the young black man with HBP , the age/sex/race group with the highest rates of early severe and complicated HBP and the lowest rates of awareness , treatment , and control . In a r and omized clinical trial of comprehensive care for hypertensive young urban black men , factors potentially associated with care and control were assessed at baseline for the 309 enrolled men . A majority of the men encountered a variety of barriers including economic , social , and lifestyle obstacles to adequate BP care and control , including no current HBP care ( 49 % ) , risk of alcoholism ( 62 % ) , use of illicit drugs ( 45 % ) , social isolation ( 47 % ) , unemployment ( 40 % ) , and lack of health insurance ( 51 % ) . Having health insurance ( odds ratio = 7.20 , P = .00 ) and a negative urine drug screen ( odds ratio = .56 , P = .04 ) were significant predictors of being in HBP care . Low alcoholism risk and employment were identified as significant predictors of compliance with HBP medication-taking behavior . Men currently using illicit drugs were 2.64 times less likely to have controlled BP compared with their counterparts who did not use illicit drugs , and men currently taking HBP medication were 63 times more likely have controlled BP compared with men not taking HBP medication . Comprehensive interventions are needed to address socioeconomic and lifestyle issues as well as other barriers to care and treatment , if HBP care is to be salient and effective in this high risk group Many studies have documented the negative effects of depression on adherence to recommended treatment ; however , little is known about the mechanism underlying this relationship . Using the Kenny and Baron analytic framework of mediation , the authors assessed whether self-efficacy mediated the relationship between depression and medication adherence in 167 hypertensive African Americans followed in a primary care practice . Depressive symptoms are associated with poor medication adherence ( β = .013 , p = .036 ) and low self-efficacy ( β = —.008 , p = .023 ) . Self-efficacy is negatively associated with medication adherence at follow-up ( β = —.612 , p < .001 ) . The relationship between depressive symptoms and medication adherence becomes nonsignificant when controlling for self-efficacy ( β = .010 , p = .087 ) . Implication s for further examination into the mediating role of self-efficacy and the deleterious effect of depression on medication adherence are discussed BACKGROUND Poor medication adherence is a significant problem in hypertensive African Americans . Although motivational interviewing ( MINT ) is effective for adoption and maintenance of health behaviors in patients with chronic diseases , its effect on medication adherence remains untested in this population . METHODS This r and omized controlled trial tested the effect of a practice -based MINT counseling vs. usual care ( UC ) on medication adherence and blood pressure ( BP ) in 190 hypertensive African Americans ( 88 % women ; mean age 54 years ) . Patients were recruited from two community-based primary care practice s in New York City . The primary outcome was adherence measured by electronic pill monitors ; the secondary outcome was within-patient change in office BP from baseline to 12 months . RESULTS Baseline adherence was similar in both groups ( 56.2 and 56.6 % for MINT and UC , respectively , P = 0.94 ) . Based on intent-to-treat analysis using mixed-effects regression , a significant time x group interaction with model-predicted posttreatment adherence rates of 43 and 57 % were found in the UC and MINT groups , respectively ( P = 0.027 ) , with a between-group difference of 14 % ( 95 % confidence interval , -0.2 to -27 % ) . The between-group difference in systolic and diastolic BP was -6.1 mm Hg ( P = 0.065 ) and -1.4 mm Hg ( P = 0.465 ) , respectively , in favor of the MINT group . CONCLUSIONS A practice -based MINT counseling led to steady maintenance of medication adherence over time , compared to significant decline in adherence for UC patients . This effect was associated with a modest , nonsignificant trend toward a net reduction in systolic BP in favor of the MINT group |
10,979 | 25,652,550 | The use of external peer review , audit and feedback had no significant effect on VBAC rates .
An educational strategy delivered by an opinion leader significantly increased VBAC rates .
The use of XRP significantly increased CS rates .
An opinion leader educational strategy confers benefit for increasing VBAC rates . | Background The number of caesarean sections ( CS ) is increasing globally , and repeat CS after a previous CS is a significant contributor to the overall CS rate .
Vaginal birth after caesarean ( VBAC ) can be seen as a real and viable option for most women with previous CS .
To achieve success , however , women need the support of their clinicians ( obstetricians and midwives ) .
The aim of this study was to evaluate clinician-centred interventions design ed to increase the rate of VBAC . | The data about the safety of vaginal birth after caesarean section are conflicting . This study in a referral hospital in Sana'a , Yemen investigated the outcome of vaginal birth after caesarean section in 357 women who had one prior caesarean section and were admitted to hospital at term with spontaneous onset of labour . A control group ( n = 155 ) was matched from women without previous caesarean section . The success rate of vaginal birth after caesarean section was 311/357 ( 87.1 % ) . The mean duration of the first and second stages of labour were not significantly different in the study group ( 146.2 and 30.7 min respectively ) compared with the control group ( 146.7 and 29.8 min ) . There were infrequent complications ; only 1 woman ( 0.3 % ) had ruptured uterus and 3 women ( 1.0 % ) suffered uterine dehiscence . There was 1 stillbirth after the uterine rupture but no maternal deaths Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery . Design Prospect i ve cohort study within the 2005 WHO global survey on maternal and perinatal health . Setting 410 health facilities in 24 areas in eight r and omly selected Latin American countries ; 123 were r and omly selected and 120 participated and provided data Participants 106 546 deliveries reported during the three month study period , with data available for 97 095 ( 91 % coverage ) . Main outcome measures Maternal , fetal , and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery , adjusted for clinical , demographic , pregnancy , and institutional characteristics . Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.5 ) for intrapartum caesarean and 2.3 ( 1.7 to 3.1 ) for elective caesarean ) . The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries . With cephalic presentation , there was a trend towards a reduced odds ratio for fetal death with elective caesarean , after adjustment for possible confounding variables and gestational age ( 0.7 , 0.4 to 1.0 ) . With breech presentation , caesarean delivery had a large protective effect for fetal death . With cephalic presentation , however , independent of possible confounding variables and gestational age , intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care ( 2.1 ( 1.8 to 2.6 ) and 1.9 ( 1.6 to 2.3 ) , respectively ) and the risk of neonatal mortality up to hospital discharge ( 1.7 ( 1.3 to 2.2 ) and 1.9 ( 1.5 to 2.6 ) , respectively ) , which remained higher even after exclusion of all caesarean deliveries for fetal distress . Such increased risk was not seen for breech presentation . Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery , but rupturing of membranes may be protective . Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations A r and omized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section . The guideline recommended clinical actions to increase trial of labor and vaginal birth rates . Charts for all 3552 cases in the study groups were audited . After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group , but rates were 46 % and 85 % higher , respectively , among physicians educated by an opinion leader . Duration of hospital stay was lower in the opinion leader education group than in the other two groups . The overall cesarean section rate was reduced only in the opinion leader education group . There were no adverse clinical outcomes attributable to the interventions . The use of opinion leaders improved the quality of care Objective To determine whether antepartum X‐ray pelvimetry ( XRP ) reliably identified women suitable for a trial labour or repeat elective caesarean section after one previous section In response to a Western Australian Ministerial enquiry into the levels of intervention in childbirth , a 2‐year prospect i ve audit was undertaken of the indication and timing of all public Caesarean section deliveries at King Edward Memorial hospital . During the study period , a total of 9,138 deliveries were performed at the hospital , of which 1,624 were by Caesarean section , an overall rate of 17.8 % . Of these , 633 ( 39 % ) were elective and 911 ( 61 % ) were nonelective . The most common primary indication for elective Caesarean section was maternal choice , largely due to a refusal of the patient to consent to a trial of scar following a single previous Caesarean section or a refusal to attempt a trial of vaginal breech delivery . The most common indications for nonelective Caesarean section birth were an intrapartum diagnosis of suspected fetal distress or failure to progress in labour . Strategies to reduce the incidence of Caesarean section birth need to focus on the pathways involved with maternal decision‐making in the birth process , and on improving the diagnosis of intrapartum fetal compromise |
10,980 | 29,144,030 | Conclusions Synergistic suppression of fasting glucagon and insulin resistance may act together to restore normoglycaemia following weight loss .
Whether suppression of plasma glucagon may contribute to increased hunger after weight loss and gradual weight regain is not yet known | Aims This meta- analysis aim ed to investigate the role of glucagon suppression in regulating glucose homeostasis following diet or bariatric surgery . | Marked improvement in glycemic control occurs in patients with type 2 diabetes mellitus shortly after Roux-en-Y gastric bypass surgery ( RYGB ) and before there is major weight loss . The objective of this study was to determine whether the magnitude of this change is primarily due to caloric restriction or is unique to the surgical procedure . We studied eleven subjects who underwent RYGB and fourteen subjects mean-matched for BMI , HbA1c , and diabetes duration who were admitted to our inpatient research unit and given a very low – calorie diet ( VLCD ) of 500 kcal/day with a macronutrient content similar to that consumed by patients after RYGB . Frequently sample d intravenous glucose tolerance tests were performed before and after interventions . Both groups lost an equivalent amount of weight over a mean study period of 21 days . Insulin sensitivity , acute insulin secretion after intravenous glucose administration , and β-cell function as determined by disposition index improved to a similar extent in both groups . Likewise , changes in fasting glucose and fructosamine levels were similar . Based on these data , VLCD improves insulin sensitivity and β-cell function just as well as RYGB in the short term Although moderate weight loss improves glycemic control in obese NIDDM patients , quite often it is not normalized . To determine whether the response to weight loss can be improved by altering the macronutrient composition of hypocaloric diets , 17 obese NIDDM patients were studied at 1 ) baseline , 2 ) after dieting for 6 weeks on a formula diet enriched in either monounsaturated fatty acids ( MUFAs , n = 9 ) or carbohydrates ( CHOs , n = 8) at a 50 % caloric deficit , and 3 ) after 4 weeks of postdiet refeeding on the respective formulas with caloric intake titrated to achieve weight maintenance . Fasting , 24-h , and oral glucose tolerance test ( OGTT ) blood glucose , plasma insulin , and C-peptide levels were measured . All prediet parameters were similar between groups . After dieting , although weight loss was similar between groups , the fasting glucose level decreased significantly more in the MUFA group ( −4.6 ± 0.7 mmol/l ) than in the CHO group ( −2.4 ± 1.0 mmol/l ; P < 0.05 ) . Twenty-four – hour glycemia decreased in both groups after dieting , but the MUFA group had a greater decrease than the CHO group ( P < 0.05 , analysis of variance [ ANOVA ] ) . Although decreases in fasting glycemia were maintained in both groups after refeeding , postpr and ial glycemia deteriorated after refeeding with the CHO- but not the MUFA-enriched formula ( P < 0.05 ) . After dieting and refeeding , fasting C-peptide increased 204 ± 47 pmol/l in the MUFA group , but the CHO group remained at prediet levels ( P < 0.05 ) . Twenty-four-hour C-peptide levels were similar between groups after dieting and refeeding , despite the lower glycemia and CHO content of the MUFA formula . However , when equal amounts of CHO were consumed during the OGTT , the MUFA group had significantly higher C-peptide levels after both dieting and refeeding ( P < 0.05 ) . Fasting , 24-h , and OGTT insulin levels were similar between groups throughout the study . These results indicate that macronutrient composition is an important determinant of the glycemic response to weight-loss therapy in obese NIDDM patients . Based on the C-peptide response during the OGTT , increased CHO-induced insulin secretion is one possible mechanism by which this occurs There has been interest in the effect of various types and amounts of dietary carbohydrates and proteins on blood glucose . On the basis of our previous data , we design ed a high-protein/low-carbohydrate , weight-maintaining , nonketogenic diet . Its effect on glucose control in people with untreated type 2 diabetes was determined . We refer to this as a low-biologically-available-glucose ( LoBAG ) diet . Eight men were studied using a r and omized 5-week crossover design with a 5-week washout period . The carbohydrate : protein : fat ratio of the control diet was 55:15:30 . The test diet ratio was 20:30:50 . Plasma and urinary beta-hydroxybutyrate were similar on both diets . The mean 24-h integrated serum glucose at the end of the control and LoBAG diets was 198 and 126 mg/dl , respectively . The percentage of glycohemoglobin was 9.8 + /- 0.5 and 7.6 + /- 0.3 , respectively . It was still decreasing at the end of the LoBAG diet . Thus , the final calculated glycohemoglobin was estimated to be approximately 6.3 - 5.4 % . Serum insulin was decreased , and plasma glucagon was increased . Serum cholesterol was unchanged . Thus , a LoBAG diet ingested for 5 weeks dramatically reduced the circulating glucose concentration in people with untreated type 2 diabetes . Potentially , this could be a patient-empowering way to ameliorate hyperglycemia without pharmacological intervention . The long-term effects of such a diet remain to be determined Rapid glycemic improvements following Roux-en-Y gastric bypass ( RYGB ) are frequently attributed to the enhanced GLP-1 response , but causality remains unclear . To determine the role of GLP-1 in improved glucose tolerance after surgery , we compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification ( ILM ) ( n = 10 per group ) before and after equivalent short-term weight reduction . The GLP-1 receptor antagonist exendin(9–39)-amide ( Ex-9 ) was administered , in r and om order and in double-blinded fashion , with saline during two separate visits after equivalent weight loss . Despite the markedly exaggerated GLP-1 response after RYGB , changes in postpr and ial glucose and insulin responses did not significantly differ between groups , and glucagon secretion was paradoxically augmented after RYGB . Hepatic insulin sensitivity also increased significantly after RYGB . With Ex-9 , glucose tolerance deteriorated similarly from the saline condition in both groups , but postpr and ial insulin release was markedly attenuated after RYGB compared with ILM . GLP-1 exerts important insulinotropic effects after RYGB and ILM , but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery . Instead , enhanced hepatic metabolism , independent of GLP-1 receptor activation , may be more important for early postsurgical glycemic improvements BACKGROUND Biliopancreatic diversion ( BPD ) is the most effective bariatric procedure in terms of weight loss and remission of diabetes type 2 ( T2DM ) , but it is accompanied by nutrient deficiencies . Sleeve gastrectomy ( SG ) is a relatively new operation that has shown promising results concerning T2DM resolution and weight loss . The objective of this study was to evaluate and compare prospect ively the effects of BPD long limb ( BPD ) and laparoscopic SG on fasting , and glucose-stimulated insulin , glucagon , ghrelin , peptide YY ( PYY ) , and glucagon-like peptide-1 ( GLP-1 ) secretion and also on remission of T2DM , hypertension , and dyslipidemia in morbidly obese patients with T2DM . METHODS Twelve patients ( body mass index [ BMI ] 57.6 ± 9.9 kg/m(2 ) ) underwent BPD and 12 ( BMI 43.7 ± 2.1 kg/m(2 ) ) underwent SG . All patients had T2DM and underwent an oral glucose tolerance test ( OGTT ) before and 1 , 3 , and 12 months after surgery . RESULTS BMI decreased more after BPD , but percent excess weight loss ( % EWL ) was similar in both groups ( P = .8 ) and T2DM resolved in all patients at 12 months . Insulin sensitivity improved more after BPD than after SG ( P = .003 ) . Blood pressure , total and LDL cholesterol decreased only after BPD ( P<.001 ) . Triglycerides decreased after either operation , but HDL increased only after SG ( P<.001 ) . Fasting ghrelin did not change after BPD ( P = .2 ) , but decreased markedly after SG ( P<.001 ) . GLP-1 and PYY responses during OGTT were dramatically enhanced after either procedure ( P = .001 ) . CONCLUSIONS SG was comparable to BPD in T2DM resolution but inferior in improving dyslipidemia and blood pressure . SG and BPD enhanced markedly PYY and GLP-1 responses but only SG suppressed ghrelin levels 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 OBJECTIVE Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet . Improvement typically occurs soon after diet implementation . This rapid response could result from low fuel supply ( calories ) , lower carbohydrate content of the weight-loss diet , and /or weight loss per se . To differentiate these effects , glucose , insulin , C-peptide and glucagon were determined during the last 24 h of a 3-day period without food ( severe calorie restriction ) and a calorie-sufficient , carbohydrate-free diet . RESEARCH DESIGN Seven subjects with untreated type 2 diabetes were studied . A r and omized-crossover design with a 4-week washout period between arms was used . METHODS Results from both the calorie-sufficient , carbohydrate-free diet and the 3-day fast were compared with the initial st and ard diet consisting of 55 % carbohydrate , 15 % protein and 30 % fat . RESULTS The overnight fasting glucose concentration decreased from 196 ( st and ard diet ) to 160 ( carbohydrate-free diet ) to 127 mg/dl ( fasting ) . The 24 h glucose and insulin area responses decreased by 35 % and 48 % on day 3 of the carbohydrate-free diet , and by 49 % and 69 % after fasting . Overnight basal insulin and glucagon remained unchanged . CONCLUSIONS Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations . Carbohydrate restriction per se could account for 71 % of the reduction . Insulin could not entirely explain the glucose responses . In the absence of carbohydrate , the net insulin response was 28 % of the st and ard diet . Glucagon did not contribute to the metabolic adaptations observed Objective : To evaluate the physiologic importance of the satiety gut hormones . Background : Controversy surrounds the physiologic role of gut hormones in the control of appetite . Bariatric surgery remains the most effective treatment option for obesity , and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass . Methods : We correlated peptide YY ( PYY ) and glucagon-like peptide 1 ( GLP-1 ) changes within the first week after gastric bypass with changes in appetite . We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass . Finally , we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake . Results : Postpr and ial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass ( P < 0.05 ) . Changes in appetite are evident within days after gastric bypass surgery ( P < 0.05 ) , and unlike other operations , the reduced appetite continues . However , in patients with poor weight loss after gastric bypass associated with increased appetite , the postpr and ial PYY and GLP-1 responses are attenuated compared with patients with good weight loss ( P < 0.05 ) . Inhibiting gut hormone responses , including PYY and GLP-1 after gastric bypass , results in return of appetite and increased food intake ( P < 0.05 ) . Conclusion : The attenuated appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations , and appetite returns when the release of gut hormones is inhibited . The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implication s for the treatment of obesity The gastrointestinal hormone , glucagon-like peptide-1(7 - 36)amide ( GLP-1 ) is released after a meal . The potency of synthetic GLP-1 in stimulating insulin secretion and in inhibiting glucagon secretion indicates the putative physiological function of GLP-1 . In vitro , the nonmammalian peptide , exendin(9 - 39)amide [ ex(9 - 39)NH2 ] , is a specific and competitive antagonist of GLP-1 . This in vivo study examined the efficacy of ex(9 - 39)NH2 as an antagonist of exogenous GLP-1 and the physiological role of endogenous GLP-1 . Six healthy volunteers underwent 10 experiments in r and om order . In each experiment , a 30-min period of euglycemia was followed by an intravenous infusion of glucose for 150 min that established a stable hyperglycemia of 8 mmol/liter . There was a concomitant intravenous infusion of one of the following : ( 1 ) saline , ( 2 ) GLP-1 ( for 60 min at 0.3 pmol . kg-1 . min-1 that established physiological postpr and ial plasma levels , and for another 60 min at 0.9 pmol . kg-1 . min-1 to induce supraphysiological plasma levels ) , ( 3 - 5 ) ex(9 - 39)NH2 at 30 , 60 , or 300 pmol . kg-1 . min-1 + GLP-1 , ( 6 - 8 ) ex(9 - 39)NH2 at 30 , 60 , or 300 pmol . kg-1 . min-1 + saline , ( 9 and 10 ) GIP ( glucose-dependent insulinotropic peptide ; for 60 min at 0.8 pmol . kg-1 . min-1 , with saline or ex(9 - 39)NH2 at 300 pmol . kg-1 . min-1 ) . Each volunteer received each of these concomitant infusions on separate days . ex(9 - 39)NH2 dose-dependently reduced the insulinotropic action of GLP-1 with the inhibitory effect declining with increasing doses of GLP-1 . ex(9 - 39)NH2 at 300 pmol . kg-1 . min-1 blocked the insulinotropic effect of physiological doses of GLP-1 and completely antagonized the glucagonostatic effect at both doses of GLP-1 . Given alone , this load of ex(9 - 39)NH2 increased plasma glucagon levels during euglycemia and hyperglycemia . It had no effect on plasma levels of insulin during euglycemia but decreased plasma insulin during hyperglycemia . ex(9 - 39)NH2 did not alter GIP-stimulated insulin secretion . These data indicate that in humans , ex(9 - 39)NH2 is a potent GLP-1 antagonist without any agonistic properties . The pancreatic A cell is under a tonic inhibitory control of GLP-1 . At hyperglycemia , the B cell is under a tonic stimulatory control of GLP-1 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 OBJECTIVE Obesity and aging increase the risk of type 2 diabetes ( T2D ) . We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults . METHODS AND PROCEDURES Twenty-four obese ( BMI : 38 + /- 2 kg/m(2 ) ) older ( age : 70 + /- 2 years ) adults completed a 6-month r and omized , controlled trial . Participants were r and omized to diet and exercise ( treatment group ) or no therapy ( control group ) . beta-Cell function ( assessed using the C-peptide minimal model ) , alpha-cell function ( assessed by the glucagon response to an oral glucose load ) , insulin sensitivity ( assessed using the glucose minimal model ) , and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test . RESULTS Body weight decreased in the treatment group , but did not change in the control group ( -9 + /- 1 % vs. 0 + /- 1 % ; P < 0.001 ) . Insulin sensitivity doubled in the treatment group and did not change in the control group ( 116 + /- 49 % vs. -11 + /- 13 % ; P < 0.05 ) . Even though indices of beta-cell responsivity to glucose did not change ( P > 0.05 ) , the disposition index ( DI ) , which adjusts beta-cell insulin response to changes in insulin sensitivity , improved in the treatment group compared with the control group ( 100 + /- 47 % vs. -22 + /- 9 % ; P < 0.05 ) . The glucagon response decreased in the treatment but not in the control group ( -5 + /- 2 % vs. 4 + /- 4 % ; P < 0.05 ) . Insulin secretion rate did not change ( P > 0.05 ) , but insulin clearance rate increased ( 51 + /- 25 % ; P < 0.05 ) , result ing in lower plasma insulin concentrations . DISCUSSION Weight loss therapy concomitantly improves beta-cell function , lowers plasma glucagon concentrations , and improves insulin action in obese older adults . These metabolic effects are likely to reduce the risk of developing T2D in this population |
10,981 | 21,824,382 | Conclusions Some CCDSSs can modify practitioner test-ordering behavior . | Background Underuse and overuse of diagnostic tests have important implication s for health outcomes and costs .
Decision support technology purports to optimize the use of diagnostic tests in clinical practice .
The objective of this review was to assess whether computerized clinical decision support systems ( CCDSSs ) are effective at improving ordering of tests for diagnosis , monitoring of disease , or monitoring of treatment .
The outcome of interest was effect on the diagnostic test-ordering behavior of practitioners . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions We developed a computer-stored medical record system containing a limited set of the total clinical data base -- primarily diagnostic studies and treatments . This system responds to its own content according to physician-authored reminder rules . To determine the effect of the reminder messages generated by 1490 rules on physician behavior , we r and omly assigned practitioners in a general medicine clinic to study or control groups . The computer found indications for six different actions per patient in 12 467 patients during a 2-year study : 61 study group residents who received computer reminders responded to 49 % of these indications ; 54 control group residents , to only 29 % ( p less than 0.0001 ) . Preventive care ( occult blood testing , mammographic screening , weight reduction diets , influenza and pneumococcal vaccines ) was affected . The intentions of the study group to use a given action for an indication predicted their response to the indications ( p less than 0.03 , r2 = 0.33 ) . The intentions of the control residents did not To determine whether clinical errors can be reduced by prospect i ve computer suggestions about the management of simple clinical events , I studied the responses of nine physicians to computer suggestions generated by 390 protocol s in a controlled crossover design . These protocol s dealt primarily with conditions managed ( e.g. , elevated blood pressure ) or caused ( e.g. , liver toxicity ) by drugs . Physicians responded to 51 per cent of 327 events when given , and 22 per cent of 385 events when not given computer suggestions . Neither level of postgraduate training ( first-year postgraduate or third-year post-graduate ) nor the order in which physicians served as study and control subjects had statistically significant overall effect on the results . It appears that the prospect i ve reminders do reduce errors , and that many of these errors are probably due to man 's limitations as a data processor rather than to correctable human deficiencies OBJECTIVE —The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practice s. RESEARCH DESIGN AND METHODS —This was a group-r and omized , controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention ( TRANSLATE ) in 24 practice s. The intervention included implementation of an electronic diabetes registry , visit reminders , and patient-specific physician alerts . A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion . The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure ( SBP ) < 130 mmHg , LDL cholesterol < 100 mg/dl , and A1C < 7.0 % at baseline and 12 months . Six process measures were also followed . RESULTS —Over 24 months , 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practice s from 17 health systems . Diabetes process measures increased significantly more in intervention than in control practice s , giving net increases as follows : foot examinations 35.0 % ( P < 0.0.001 ) ; annual eye examinations 25.9 % ( P < 0.001 ) ; renal testing 28.5 % ( P < 0.001 ) ; A1C testing 8.1%(P < 0.001 ) ; blood pressure monitoring 3.5 % ( P = 0.05 ) ; and LDL testing 8.6 % ( P < 0.001 ) . Mean A1C adjusted for age , sex , and comorbidity decreased significantly in intervention practice s ( P < 0.02 ) . At 12 months , intervention practice s had significantly greater improvement in achieving recommended clinical values for SBP , A1C , and LDL than control clinics ( P = 0.002 ) . CONCLUSIONS — Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes Purpose : Physicians and patients frequently miss opportunities to improve the quality of care of diabetes , primarily because of the complexity of managing many risk factors over many years with many other providers . Electronic decision support is a potential way to improve prescribing and quality of care . Shared care , meaning patients and physicians sharing access to the patient ’s status compared to recommended targets , is thought to improve outcomes as are supportive reminders . Our objective was to rigorously evaluate whether an electronic medical record (EMR)-linked , individualized electronic diabetes tracker with automated telephone reminders could improve the quality of diabetes management in primary care . Methods : Community-based family physicians across Ontario who were already using EMRs in their practice , were recruited . Patient and physician versions of a Web-based diabetes tracker , the ( COMPETE II Diabetes Tracker ( CIIDT ) system , were developed . The main tracker page showed all 13 monitoring variables – the patient ’s recent values , both process ( when last checked ) and outcome ( the result ) , target values for process and outcome , and short advisory messages , with red/yellow/green highlighting to indicate urgency of review . Links to best evidence guidelines and patient re sources were provided . The physician view appeared as an overlay in a corner of their own electronic medical record ( N = 6 EMR products ) . Intervention patients were linked to a voice biometric-enabled automated telephone reminder system ( ATRS ) for medications , labs and visits . Consenting patients with diabetes were r and omized to the CIIDT-ATRS intervention or usual care ( neither ) . Since the study was relatively short ( 6 months follow-up ) , the primary outcome was a composite score of process quality – the quality of monitoring the variables compared to target . Secondary outcomes included clinical outcomes plus evaluations of the tracker and ATRS , and impact on health information privacy . Results : Forty-eight physicians ( mean age ( SD ) = 45.2 ( 10.0 ) , 38.2 % female ) were recruited and 511 patients ( mean age ( SD ) = 60.3 ( 12.4 ) , 49.6 % female , 78 % completed high school ) were r and omized . Only 46.1 % of patients used the Internet at least monthly so print versions of their recent information were sent to them prior to their physician visits . There were frequent technical problems with the Web-based tracker and a lack of data integration between the various EMRs and the tracker . Despite problems , the primary outcome of composite score of physician visits , and checks of blood pressure ( BP ) , LDL cholesterol , HbA1C , microalbuminuria , BMI , feet and eyes , showed a highly statistically significant improvement in the intervention group compared to control ( p<0.0001 ) . There were also highly statistically significant improvements in actual blood pressure ( -2.68 mm diastolic BP , p=0.007 ) and in HbA1C ( -.2 % , p=0.001 ) . 75.9 % of intervention patients were as satisfied or more satisfied with their care since the use of the tracker system and 62.5 % voted to continue to receive ATRS reminders . 22.4 % of patients felt that , in general , the risk of possible loss of confidentiality outweighed the benefits that computers could bring to their health . Over the course of the study , physicians developed a more favourable attitude towards the benefits vs risks of computerized systems in healthcare . Discussion : Despite considerable technical challenges for both patients and physicians , we have demonstrated that the care of a complex chronic disease can be improved with electronic tracking and decision support for both physician and patient . This is one of the first r and omized trial to demonstrate success in routine , community-based primary care . Funding Source : Grant from the Canada Health Infostructure Partnerships Program , Health Canada . References : 1 . Branger PJ . van't Hooft A. van der Wouden JC . Moorman PW . van Bemmel JH . Shared care for diabetes : supporting communication between primary and secondary care . International Journal of Medical Informatics 1999 ; 53:133 - 42 . 2 . Jerant AF . Hill DB . Does the use of electronic medical records improve surrogate patient outcomes in outpatient setting s ? Journal of Family Practice 2000;49:349 - 57 . * Dr Lee is deceased BACKGROUND A cluster r and omized trial of tailored interventions to support the implementation of guidelines for sore throat and urinary tract infection found little or no change in the main outcomes , which were antibiotic prescriptions , use of laboratory tests and use of telephone consultations . There was great variation between the practice s in the change in these outcomes . OBJECTIVES Our aim was to evaluate how the interventions were received and to underst and why practice s did or did not change . METHODS The trial was conducted in general practice s in Norway . Data for this process evaluation were collected from the 120 practice s that completed the trial . Multiple methods were used : observations , semi-structured telephone interviews , a postal survey and data extracted from electronic medical records . We investigated factors that might explain a lack of change , including : agreement with the guidelines ; communication within each practice ; degree of participation in the project ; taking time to discuss the guidelines and their implementation ; use of the components of the interventions ; and routines for telephone consultations . Possible explanatory factors were explored in relation to variation in change and the overall extent of change in rates of use of antibiotics , laboratory tests and telephone consultations . RESULTS Sixty-three per cent of practice s agreed with the guidelines . Only 35 % reported having regular meetings , and 33 % discussed the project before its start , although 75 % reported agreement about participating within the practice . Only 33 % reported meeting to discuss the guidelines . Use of the components of the interventions ranged from 11 % for the increased fee for telephone consultations to 48 % for the computerized decision support . Forty-four per cent reported problems with telephone routines . No single factor explained the observed variation in the extent of change across practice s. CONCLUSIONS Inadequate time , re sources and support were the most salient factors that might explain a lack of change . Problems with internal communication and telephone routines were important contributing factors in many practice OBJECTIVE To assess the effects on health care re source utilization of a network of microcomputer workstations for writing all inpatient orders . DESIGN R and omized controlled clinical trial . SETTING Inpatient internal medicine service of an urban public hospital . SUBJECTS A total of 5219 internal medicine patients and the 68 teams of house officers , medical students , and faculty internists who cared for them . INTERVENTION Microcomputer workstations , linked to a comprehensive electronic medical record system , for writing all inpatient orders . MAIN OUTCOME MEASURES Total inpatient charges for each admission and charges for specific categories of orders . A time-motion study of selected interns assessed the ordering system 's time consumption . RESULTS Intervention teams generated charges that were $ 887 ( 12.7 % ) lower per admission than did control teams ( P = .02 ) . Significant reductions ( P < .05 ) were demonstrated separately for bed charges , diagnostic test charges , and drug charges . Reductions of similar proportion and statistical significance were found for hospital costs . The mean length of stay was 0.89 day shorter for intervention resident teams ( P = .11 ) . Interns in the intervention group spent an average of 33 minutes longer ( 5.5 minutes per patient ) during a 10-hour observation period writing orders than did interns in the control group ( P < .0001 ) . CONCLUSIONS A network of microcomputer workstations for writing all inpatient orders significantly lowered patient charges and hospital costs . This would amount to savings of more than $ 3 million in charges annually for this hospital 's medicine service and potentially tens of billions of dollars nationwide . However , the system required more physician time than did the paper charts . Research at other sites and system advances to reduce time requirements are warranted Abstract Objective To test the effectiveness of educational interventions in improving detection rates and management of dementia in primary care . Design Unblinded , cluster r and omised , before and after controlled study . Setting General practice s in the United Kingdom ( central Scotl and and London ) between 1999 and 2002 . Interventions Three educational interventions : an electronic tutorial carried on a CD Rom ; decision support software built into the electronic medical record ; and practice based workshops . Participants 36 practice s participated in the study . Eight practice s were r and omly assigned to the electronic tutorial ; eight to decision support software ; 10 to practice based workshops ; and 10 to control . Electronic and manual search es yielded 450 valid and usable medical records . Main outcome measures Rates of detection of dementia and the extent to which medical records showed evidence of improved concordance with guidelines regarding diagnosis and management . Results Decision support software ( P = 0.01 ) and practice based workshops ( P = 0.01 ) both significantly improved rates of detection compared with control . There were no significant differences by intervention in the measures of concordance with guidelines . Conclusions Decision support systems and practice based workshops are effective educational approaches in improving detection rates in dementia BACKGROUND Medication errors are frequently related to failure to appropriately select medications or adjust for laboratory parameters . Differences between guideline recommendations and actual frequency of therapeutic laboratory monitoring are substantial . This study evaluated interventions to improve laboratory monitoring at initiation of medication therapy . METHODS This cluster-r and omized trial compared 3 interventions to usual care for 10 medications in 15 primary care clinics in a health maintenance organization with an electronic medical record system . Eligible patients , identified from electronic data bases , had not received recommended laboratory monitoring within 5 days after new dispensing of a study medication . Interventions were an electronic medical record reminder to the prescribing health care professional , an automated voice message to the patient , and a pharmacy team outreach to the patient . Primary outcome was completion of all recommended baseline laboratory monitoring . RESULTS A total of 961 patients participated in the study . At 25 days , 95 ( 48.5 % ) of 196 patients in the electronic medical record reminder group , 177 ( 66.3 % ) of 267 in the automated voice message group , 214 ( 82.0 % ) of 261 in the pharmacy team outreach group , and 53 ( 22.4 % ) of 237 in the usual care group had completed all recommended baseline laboratory monitoring ( P<.001 ) . After adjustments , the hazard ratios for completing laboratory monitoring compared with usual care were 2.5 ( 95 % confidence interval , 1.8 - 3.5 ) for electronic medical record reminder , 4.1 ( 95 % confidence interval , 3.0 - 5.6 ) for automated voice message , and 6.7 ( 95 % confidence interval , 4.9 - 9.0 ) for pharmacy team outreach . CONCLUSIONS All 3 interventions were effective in increasing laboratory monitoring when initiating new medications in primary care . Further work is necessary to determine if these interventions improve patient outcomes Although absolute risk of death associated with raised blood pressure increases with age , the benefits of treatment are greater in elderly patients . Despite this , the ' rule of halves ' particularly applies to this group . We conducted a r and omised controlled trial to evaluate different levels of feedback design ed to improve identification , treatment and control of elderly hypertensives . Fifty-two general practice s were r and omly allocated to either : Control ( n=19 ) , Audit only feedback ( n=16 ) or Audit plus Strategic feedback , prioritising patients by absolute risk ( n=17 ) . Feedback was based on electronic data , annually extracted from practice computer systems . Data were collected for 265,572 patients , 30,345 aged 65 - 79 . The proportion of known hypertensives in each group with BP recorded increased over the study period and the numbers of untreated and uncontrolled patients reduced . There was a significant difference in mean systolic pressure between the Audit plus Strategic and Audit only groups and significantly greater control in the Audit plus Strategic group . Providing patient-specific practice feedback can impact on identification and management of hypertension in the elderly and produce a significant increase in control BACKGROUND Optimal care for patients with diabetes is difficult to achieve in clinical practice . OBJECTIVE To evaluate the impact of a registry and decision support system on processes of care , and physiologic control . PARTICIPANTS R and omized trial with clustering at the practice level , involving 7,412 adults with diabetes in 64 primary care practice s in the Northeast . INTERVENTIONS Provider decision support ( reminders for overdue diabetes tests , alerts regarding abnormal results , and quarterly population reports with peer comparisons ) and patient decision support ( reminders and alerts ) . MEASUREMENTS AND MAIN RESULTS Process and physiologic outcomes were evaluated in all subjects . Functional status was evaluated in a r and om patient sample via question naire . We used multiple logistic regression to quantify the effect , adjusting for clustering and potential confounders . Intervention subjects were significantly more likely to receive guideline -appropriate testing for cholesterol ( OR = 1.39 ; [ 95%CI 1.07 , 1.80 ] P = 0.012 ) , creatinine ( OR = 1.40 ; [ 95%CI 1.06 , 1.84 ] P = 0.018 ) , and proteinuria ( OR = 1.74 ; [ 95%CI 1.13 , 1.69 ] P = 0.012 ) , but not A1C ( OR = 1.17 ; [ 95 % CI 0.80 , 1.72 ] P = 0.43 ) . Rates of control of A1C and LDL cholesterol were similar in the two groups . There were no differences in blood pressure , body mass index , or functional status . CONCLUSIONS A chronic disease registry and decision support system based on easily obtainable laboratory data was feasible and acceptable to patients and providers . This system improved the process of laboratory monitoring in primary care , but not physiologic control Abstract Objective : To underst and the factors influencing the adoption of a computerised clinical decision support system for two chronic diseases in general practice . Design : Practice based , longitudinal , qualitative interview study . Setting : Five general practice s in north east Engl and . Participants : 13 respondents ( two practice managers , three nurses , and eight general practitioners ) gave a total of 19 semistructured interviews . 40 people in practice s included in the r and omised controlled trial ( 34 doctors , three nurses ) and interview study ( three doctors , one previously interviewed ) gave feedback . Results : Negative comments about the decision support system significantly outweighed the positive or neutral comments . Three main areas of concern among clinicians emerged : timing of the guideline trigger , ease of use of the system , and helpfulness of the content . Respondents did not feel that the system fitted well within the general practice context . Experience of “ on-dem and ” information sources , which were generally more positively viewed , informed the comments about the system . Some general practitioners suggested that nurses might find the guideline content more clinical ly useful and might be more prepared to use a computerised decision support system , but lack of feedback from nurses who had experienced the system limited the ability to assess this . Conclusions : Significant barriers exist to the use of complex clinical decision support systems for chronic disease by general practitioners . Key issues include the relevance and accuracy of messages and the flexibility to respond to other factors influencing decision making in primary care . What is already known on this topic R and omised controlled trials of complex computerised decision support systems have found low rates of use and no effects on process and outcomes of care What this study adds Clinicians found a computerised decision support system for chronic disease in general practice to be difficult to use and unhelpful clinical ly It did not fit well into a general practice consultation and compared unfavourably with “ on-dem and ” information “ Active ” decision support can make clinicians aware of gaps between their own practice and “ best ” practice , but computer prompts need to be relevant and CONTEXT Computerized systems to remind physicians to provide appropriate care have not been widely evaluated in large numbers of patients in multiple clinical setting s. OBJECTIVE To examine whether a computerized reminder system operating in multiple Veterans Affairs ( VA ) ambulatory care clinics improves resident physician compliance with st and ards of ambulatory care . DESIGN , SETTING , AND PARTICIPANTS A total of 275 resident physicians at 12 VA medical centers were r and omly assigned in firms or half-day clinic blocks to either a reminder group ( n = 132 ) or a control group ( n = 143 ) . During a 17-month study period ( January 31 , 1995-June 30 , 1996 ) , the residents cared for 12,989 unique patients for whom at least 1 of the studied st and ards of care ( SOC ) was applicable . MAIN OUTCOME MEASURES Compliance with 13 SOC , tracked using hospital data bases and encounter forms completed by residents , compared between residents in the reminder group vs those in the control group . RESULTS Measuring compliance as the proportion of patients in compliance with all applicable SOC by their last visit during the study period , the reminder group had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 58.8 % vs 53.5 % ; odds ratio [ OR ] , 1.24 ; 95 % confidence interval [ CI ] , 1.08 - 1.42 ; P = .002 ) and for 5 of the 13 st and ards examined individually . Measuring compliance as the proportion of all visits for which care was indicated in which residents provided proper care , the reminder group also had statistically significantly higher rates of compliance than the control group for all st and ards combined ( 17.9 % vs 12.2 % ; OR , 1.57 ; 95 % CI , 1.45 - 1.71 ; P<.001 ) and for 9 of the 13 st and ards examined individually . The benefit of reminders , however , declined throughout the course of the study , even though the reminders remained active . CONCLUSIONS Our data indicate that reminder systems installed at multiple sites can improve residents ' compliance to multiple SOC . The benefits of such systems , however , appear to deteriorate over time . Future research needs to explore methods to better sustain the benefits of reminders . JAMA . 2000;284:1411 - 1416 OBJECTIVE To evaluate the implementation of clinical guidelines for hypertension in general practice by use of a computer-based clinical decision support system ( CDSS ) and a specific implementation strategy . Evaluation of patient outcome . DESIGN R and omised study with health centres as units . The intervention group had the CDSS installed and made ready for use , doctors and assistants were trained and received a user-manual , the doctors were offered telephone repetitions , a seminar in risk intervention and , at the same seminar , further demonstration of the CDSS . The doctors received baseline registration s with information of how they treated their own hypertensive patients , and use of the CDSS was checked repeatedly . SETTING General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . PARTICIPANTS Seventeen health centres with 24 doctors and 984 patients in the intervention group . Data from 879 patients used in the final analyses . Twelve health centres with 29 doctors and 1255 patients in the control group . Data from 1119 patients used in the final analyses . MAIN OUTCOME MEASURES After an intervention period of 18 months , group differences in level of systolic and diastolic blood pressure , serum cholesterol , body mass index , and risk score for myocardial infa rct ion were calculated , as well as group differences in fractions of smokers . RESULTS Significant group difference in favour of intervention group : diastolic blood pressure 1 mmHg ( 95 % CI -1.89 , -0.17 ) . However , a significant baseline difference in systolic blood pressure in favour of control group of 2.7 mmHg ( 95 % CI 1.0 , 4.5 ) had been reduced to 1.2 mmHg ( 95 % CI -0.6 , 3.0 ) after intervention . CONCLUSION Implementation of clinical guidelines in the treatment of hypertensive patients in general practice by means of a CDSS and several other procedures for implementation did not affect patient outcome in any clinical ly significant way Information Technology ( IT ) enables health care providers to manage patients with chronic conditions through identification , follow up and administration of specific interventions . In our setting , we developed a surveillance system for chronic diseases . The aim of this study was to show its efficacy on monitoring blood pressure throughout a cluster r and omized controlled trial . Patients without blood pressure registries ( condition 1 ) or with high blood pressure measurements ( condition 2 ) were r and omized to be detected by the surveillance system or to receive usual care . The proportion of patients with at least one blood pressure measurement within three months of follow up was 49.9 % ( 207 patients ) in the intervention group and 37 % ( 195 ) in the control group ( p<0.001 ) for condition 1 . And 61 % ( 224 ) vs. 50 % ( 239 ) respectively ( p=0.002 ) for condition 2 . Patients under the surveillance system have higher proportion of blood pressure measurements , showing this study an improvement on the process of care with this IT tool OBJECTIVE Errors of omission are a common cause of systems failures . Physicians often fail to order tests or treatments needed to monitor/ameliorate the effects of other tests or treatments . The authors hypothesized that automated , guideline -based reminders to physicians , provided as they wrote orders , could reduce these omissions . DESIGN The study was performed on the inpatient general medicine ward of a public teaching hospital . Faculty and housestaff from the Indiana University School of Medicine , who used computer workstations to write orders , were r and omized to intervention and control groups . As intervention physicians wrote orders for 1 of 87 selected tests or treatments , the computer suggested corollary orders needed to detect or ameliorate adverse reactions to the trigger orders . The physicians could accept or reject these suggestions . RESULTS During the 6-month trial , reminders about corollary orders were presented to 48 intervention physicians and withheld from 41 control physicians . Intervention physicians ordered the suggested corollary orders in 46.3 % of instances when they received a reminder , compared with 21.9 % compliance by control physicians ( p < 0.0001 ) . Physicians discriminated in their acceptance of suggested orders , readily accepting some while rejecting others . There were one third fewer interventions initiated by pharmacists with physicians in the intervention than control groups . CONCLUSION This study demonstrates that physician workstations , linked to a comprehensive electronic medical record , can be an efficient means for decreasing errors of omissions and improving adherence to practice guidelines Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake Abstract Objective : To assess the effectiveness of tailored interventions to implement guidelines for urinary tract infections in women and sore throat Design : Unblinded , cluster r and omised pretest-post-test trial Setting : 142 general practice s in Norway Participants : 72 practice s received interventions to implement guidelines for urinary tract infection and 70 practice s received interventions to implement guidelines for sore throat , serving as controls for each other . 59 practice s in the urinary tract infection group and 61 practice s in the sore throat group completed the study . Outcomes were measured in 16 939 consultations for sore throat and 9887 consultations for urinary tract infection . Interventions : Interventions were developed to overcome identified barriers to implementing the guidelines . The main components of the tailored interventions were patient educational material , computer based decision support and reminders , an increase in the fee for telephone consultations , and interactive courses for general practitioners and practice assistants Main outcome measures : Changes in rates of use of antibiotics , laboratory tests , and telephone consultations Results : Patients in the sore throat group were 3 % less likely to receive antibiotics after the intervention . Women with symptoms of urinary tract infection in the intervention group were 5.1 % less likely to have a laboratory test ordered . No significant differences were found between the groups for the other outcomes . Large variation was found across the included practice sin the rates of antibiotic prescription , use of laboratory tests and telephone consultations , and in the extent of change for all three outcome measures Conclusions : Passively delivered , complex interventions targeted at identified barriers to change had little effect in changing OBJECTIVE To assess compliance with a clinical decision support system ( CDSS ) for diagnostic management of children with fever without apparent source and to study the effects of application of the CDSS on time spent in the emergency department ( ED ) and number of laboratory tests . DESIGN The CDSS was used by ED nursing staff to register children presenting with fever . The CDSS identified children that met inclusion criteria ( 1 - 36 months and fever without apparent source ( FWS ) ) and provided patient-specific diagnostic management advice . Children at high risk for serious bacterial infection were r and omized for the ' intervention ' ( n = 74 ) or the ' control ' ( n = 90 ) group . In the intervention group , the CDSS provided the advice to immediately order laboratory tests and in the control group the ED physician first assessed the children and then decided on ordering laboratory tests . RESULTS Compliance with registration of febrile children was 50 % ( 683/1,399 ) . Adherence to the advice to order laboratory tests was 82 % ( 61/74 ) . Children in the intervention group had a median ( 25(th)-75(th ) percentile ) length of stay at the ED of 138 ( 104 - 181 ) minutes . The median length of stay at the ED in the control group was 123 ( 83 - 179 ) minutes . Laboratory tests were significantly more frequently ordered in the intervention group ( 82 % ) than in the control group ( 44 % , p < 0.001 , chi(2 ) test ) . CONCLUSION Implementation of a CDSS for diagnostic management of young children with fever without apparent source was successful regarding compliance and adherence to CDSS recommendations , but had unexpected effects on patient outcome in terms of ED length of stay and number of laboratory tests . The use of the current CDSS was discontinued BACKGROUND Dyslipidemia remains underdiagnosed and undertreated in patients with coronary artery disease . The Computer-based Clinical Decision Support System provides an opportunity t close these gaps . OBJECTIVES To study the impact of computerized intervention on secondary prevention of CAD . METHODS The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an up date d lipoprotein profile and treatment with lipid-lowering drugs . The program produced automatic computer-generated monitoring and treatment recommendations . Adjusted primary clinics were r and omly assigned to intervention ( n=56 ) or st and ard care arms ( n=56 ) . Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment . Compliance and lipid levels were monitored . The study group comprised all patients with CAD who were alive at least 3 months after hospitalization . RESULTS Follow-up was available for 7448 patients ( median 19.8 months , range 6 - 36 months ) . Overall , 51.7 % of patients were adequately screened , and 55.7 % of patients were compliant with treatment to lower lipid level . In patients with initial low density lipoprotein > 120 mg/dl , a significant decrease in LDL levels was observed in both arms , but was more pronounced in the intervention arm : 121.9 + /- 34.2 vs. 124.3 + /- 34.6 mg/dl ( P < 0.02 ) . A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs , 37 % vs. 40.9 % ( P < 0.001 ) . CONCLUSIONS This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines , presenting a major obstacle to implementing effective secondary prevention . Our automatic computerized reminders system substantially facilitates adherence to guidelines and supports wide-range implementation OBJECTIVE Recommendations for routine laboratory monitoring to reduce the risk of adverse medication events are not consistently followed . We evaluated the impact of electronic reminders delivered to primary care physicians on rates of appropriate routine medication laboratory monitoring . DESIGN We enrolled 303 primary care physicians caring for 1,922 patients across 20 ambulatory clinics that had at least one overdue routine laboratory test for a given medication between January and June 2004 . Clinics were r and omized so that physicians received either usual care or electronic reminders at the time of office visits focused on potassium , creatinine , liver function , thyroid function , and therapeutic drug levels . MEASUREMENTS Primary outcomes were the receipt of recommended laboratory monitoring within 14 days following an outpatient clinic visit . The effect of the intervention was assessed for each reminder after adjusting for clustering within clinics , as well as patient and provider characteristics . RESULTS Medication-laboratory monitoring non-compliance ranged from 1.6 % ( potassium monitoring with potassium-supplement use ) to 6.3 % ( liver function monitoring with HMG CoA Reductase Inhibitor use ) . Rates of appropriate laboratory monitoring following an outpatient visit ranged from 14 % ( therapeutic drug levels ) to 64 % ( potassium monitoring with potassium-sparing diuretic use ) . Reminders for appropriate laboratory monitoring had no impact on rates of receiving appropriate testing for creatinine , potassium , liver function , renal function , or therapeutic drug level monitoring . CONCLUSION We identified high rates of appropriate laboratory monitoring , and electronic reminders did not significantly improve these monitoring rates . Future studies should focus on setting s with lower baseline adherence rates and alternate drug-laboratory combinations OBJECTIVE to compare the ability of computer-aided diagnosis and contrast radiography for the diagnosis of acute mechanical small bowel obstruction . DESIGN Prospect i ve r and omised trial . SETTING Kaunas University of Medicine , Lithuania . SUBJECTS 80 patients with small bowel obstruction with no clinical evidence of strangulation who were r and omised into two groups ( n = 40 in each ) to be investigated by computer-aided diagnosis and contrast radiography . INTENVENTIONS : 37 patients required operation ( 46 % ) . MAIN OUTCOME MEASURES specificity , sensitivity , false positive and negative predictive values of the 2 methods ; time necessary to make the diagnosis ; and morbidity and mortality . RESULTS The specificity , sensitivity , positive and negative predictive values in the diagnosis of complete acute small bowel obstruction for the computer-aided group were 100 % , 87.5 % , 100 % and 92.3 % , and for the contrast radiography group 100 % , 76.9 % , 100 % and 90 % , respectively . The mean time period for making the diagnosis was 1 hour in the computer-aided group and 16 hours in the radiography group ( p < 0.001 ) . The overall mortality was 3 % and morbidity 9 % . CONCLUSION Computer-aided diagnosis had no significant advantage over contrast radiography in the accuracy of diagnosis of the character of small bowel obstruction . However , significantly less time was needed to make the diagnosis in the computer-aided group BACKGROUND The influence of non-medical factors on physicians ' decision-making has been documented in many observational studies , but rarely in an experimental setting capable of demonstrating cause and effect . We conducted a controlled factorial experiment to assess the influence of non-medical factors on the diagnostic and treatment decisions made by practitioners of internal medicine in two common medical situations . METHOD One hundred and ninety-two white male internists individually viewed professionally produced video scenarios in which the actor-patient , presenting with either chest pain or dyspnea , possessed various balanced combinations of sex , race , age , socioeconomic status , and health insurance coverage . Physician subjects were r and omly drawn from lists of internists in private practice , hospital-based practice , and HMO 's , at two levels of experience . RESULTS The most frequent diagnoses for both chest pain and dyspnea were psychogenic origin and cardiac problems . Smoking cessation was the most frequent treatment recommendation for both conditions . Younger patients ( all other factors being the same ) were significantly more likely to receive the psychogenic diagnosis . Older patients were more likely to receive the cardiac diagnosis for chest pain , particularly if they were insured . HMO-based physicians were more likely to recommend a follow-up visit for chest pain . Several interactions of patient and physician factors were significant in addition to the main effects . CONCLUSIONS The variability in decision-making evidence d by physicians in this experiment was not entirely accounted for by strictly rational Bayesian inference ( the common prescriptive model for medical decision-making ) , in-as-much as non-medical factors significantly affected the decisions that they made . There is a need to supplement idealized medical schemata with considerations of social behavior in any comprehensive theory of medical decision-making We studied the effect of informing physicians of the charges for outpatient diagnostic tests on their ordering of such tests in an academic primary care medical practice . All tests were ordered at microcomputer workstations by 121 physicians . For half ( the intervention group ) , the charge for the test being ordered and the total charge for tests for that patient on that day were displayed on the computer screen . The remaining physicians ( control group ) also used the computers but received no message about charges . The primary outcomes measured were the number of tests ordered and the charges for tests per patient visit . In the 14 weeks before the study , the number of tests ordered and the average charge for tests per patient visit were similar for the intervention and control groups . During the 26-week intervention period , the physicians in the intervention group ordered 14 percent fewer tests per patient visit than did those in the control group ( P less than 0.005 ) , and the charges for tests were 13 percent ( $ 6.68 per visit ) lower ( P less than 0.05 ) . The differences were greater for scheduled visits ( 17 percent fewer tests and 15 percent lower charges for the intervention group ; P less than 0.01 ) than for unscheduled ( urgent ) visits ( 11 percent fewer tests and 10 percent lower charges ; P greater than 0.3 ) . During the 19 weeks after the intervention ended , the number of tests ordered by the physicians in the intervention group was only 7.7 percent lower than the number ordered by the physicians in the control group , and the charges for tests were only 3.5 percent lower ( P greater than 0.3 ) . Three measures of possible adverse outcomes --number of hospitalizations , emergency room visits , and outpatient visits during the study period and the following six months -- were similar for the patients seen by the physicians in both groups . We conclude that displaying the charges for diagnostic tests significantly reduced the number and cost of tests ordered , especially for patients with scheduled visits . The effects of this intervention did not persist after it was discontinued OBJECTIVE : Suboptimal treatment of hyperlipidemia in patients with coronary artery disease ( CAD ) is well documented . We report the impact of a computer-assisted physician-directed intervention to improve secondary prevention of hyperlipidemia . DESIGN AND SETTING : Two hundred thirty-five patients under the care of 14 primary care physicians in an academically affiliated practice with an electronic health record were enrolled in this proof-of-concept physician-blinded r and omized , controlled trial . Each patient with CAD or risk equivalent above National Cholesterol Education Program-recommended low-density lipoprotein ( LDL ) treatment goal for greater than 6 months was r and omized , stratified by physician and baseline LDL . Physicians received a single e-mail per intervention patient . E-mails were visit independent , provided decision support , and facilitated “ one-click ” order writing . MEASUREMENTS : The primary outcomes were changes in hyperlipidemia prescriptions , time to prescription change , and changes in LDL levels . The time spent using the system was assessed among intervention patients . RESULTS : A greater proportion of intervention patients had prescription changes at 1 month ( 15.3 % vs 2 % , P=.001 ) and 1 year ( 24.6 % vs 17.1 % , P=.14 ) . The median interval to first medication adjustment occurred earlier among intervention patients ( 0 vs 7.1 months , P=.005 ) . Among patients with baseline LDLs > 130 mg/dL , the first postintervention LDLs were substantially lower in the intervention group ( 119.0 vs 138.0 mg/dL , P=.04 ) . Physician processing time was under 60 seconds per e-mail . CONCLUSION : A visit-independent disease management tool result ed in significant improvement in secondary prevention of hyperlipidemia at 1-month postintervention and showed a trend toward improvement at 1 year A computer was used to prospect ively detect and suggest responses to simple , medication-related events as reflected in a computerized record in a prospect i ve , r and omized study of a diabetes clinic with primary -care responsibility . There were two categories of event/suggestions : when the last observation of a test required for medication control was too old , the computer suggested a repeat ; and when an abnormality with therapeutic implication s was detected , the computer suggested a specific change in therapeutics . Clinicians responded to 36 % of events in the first category with computer reminders and 11 % without ( P less than 0.0001 ) ; they responded to 28 % of events in the second category with computer assistance and 13 % without ( P less than 0.026 ) . For the most clinical ly significant of these second category events , the difference was even greater : 47 % with and 4 % without computer assistance ( P less than 0.0004 ) . I believe that computer detection and response ( in the form of reminders ) to simple clinical events will change clinician behavior A computerized medical record system was design ed to detect and remind the responsible clinician about clinical events that might need corrective action . These reminders significantly increased the clinician response rate ( in terms of test orders and treatment changes ) to the events in question . The addition of relevant medical literature citations to the reminders did not significantly change the clinician response rate as compared with that with reminders alone , nor did it stimulate the physicians to read any of the cited articles kept in an immediately available " library " of reprints We developed statistical equations to predict abnormalities on eight commonly ordered diagnostic tests and we gave the predictions to 112 physicians practicing in an academic internal medicine practice . Half of each physician 's patients were r and omized to intervention status . All diagnostic tests were ordered by microcomputer , and when a physician ordered one of the eight study tests for an intervention patient , the computer displayed the probability ( 0 % to 100 % ) that the test would be positive for the main abnormality being tested for . The physician could then cancel the test if desired . During a six-month controlled trial , when there were more than 15,000 scheduled patient visits , patient charges for the eight study tests were 8.8 % less for the intervention patients . The largest reductions ( greater than 10 % ) were for serum electrolyte level tests and complete blood cell counts , the two most commonly ordered tests . Physicians ordered fewer low-probability tests for intervention patients than for controls , suggesting that with timely predictive information , physicians can target tests to higher-risk patients STUDY OBJECTIVE To determine the effect of displaying previous results of diagnostic tests on the ordering of selected outpatient tests . DESIGN Sixteen-week controlled trial with a 13-week pre-intervention and 8-week post-intervention observation periods . Patients were r and omly assigned to intervention or control groups so that each physician was his or her own control . Only scheduled visits were included . R and omization occurred before the pre-intervention observation period . SETTING Academic primary care general medicine clinic affiliated with an urban general hospital . SUBJECTS Pre-intervention period : 111 physicians ( 97 internal medicine residents , 14 faculty internists ) , 4683 patients , 5942 scheduled visits . INTERVENTION period : same 111 physicians , 5946 patients , 8148 visits . Post-intervention period : 76 physicians ( 62 residents , 14 faculty ) , 2571 patients , 2858 scheduled visits . INTERVENTION With an order for one of eight selected diagnostic tests through microcomputer workstations , a window was opened on the screen and previous test results were displayed along with the time interval between the first and last result . Tests were ordered for control patients into the same workstations without previous results displayed . MEASUREMENTS AND MAIN RESULTS Previous results of one or more study tests were available for display for 96 % of scheduled patients . Significantly lower results ( p less than 0.05 by paired t-test ) for the selected tests were found for intervention patient visits than for control visits : charges per visit ( mean + /- SE ) for intervention patients $ 12.17 + /- 0.62 , compared with $ 13.99 + /- 0.77 for controls , a 13.0 % difference ; tests per visit were 0.51 + /- 0.03 , compared with 0.56 + /- 0.03 , an 8.5 % difference . The number of study tests ordered decreased significantly for intervention patients ( 16.8 % ) and for controls ( 10.9 % ) . During the post-intervention period , ordering of study tests increased for both groups , but the increase from the intervention period was not significant . CONCLUSIONS Presenting physicians with previous test results reduced the ordering of those tests . The actual effect may have been greater than 13 % , because there were reductions in study tests ordered for both intervention and control patients during the intervention period when compared with the pre-intervention period , and both tended to rise after the intervention , or display , was turned off OBJECTIVES To evaluate the implementation of clinical guidelines for diabetes mellitus in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . METHODS R and omized study with health center as unit . General practice in Sør- and Nord-Trøndelag counties in Norway , 380,000 inhabitants . Seventeen health centers with 24 doctors and 499 patients with diabetes mellitus were in the intervention group and 12 health centers with 29 doctors and 535 patients were in the control group . Main outcome measures were group differences in fractions of patients without registration s ( process evaluation ) and mean group differences for the same variables ( patient outcome evaluation ) . RESULTS Statistically significant group differences were experienced for fractions of patients without registration of cigarette smoking ( intervention group , 82.6 % ; control group 94.5 % ) , body mass index ( 78.2 % vs. 93.0 % ) , and sufficient registration s for calculation of risk score for myocardial infa rct ion ( 91.1 % vs. 98.3 % ) ; all during 18 months . Large center variations were shown for all variables . The only statistically significant group difference was -2.3 mm Hg ( 95 % CI , -3.8 , -0.8 ) in diastolic blood pressure in favor of the intervention group . Statistically insignificant differences in favor of the intervention group were HbA1c , -0.1 % ( 95 % CI , -0.4 , 0.1 ) , systolic blood pressure , -1.2 mm Hg ( 95 % CI , -4.4 , 2.0 ) . Statistically insignificant differences in favor of the control group were fractions of smokers , + 3.0 % ( 95 % CI , -4.0 , 10.0 ) , body mass index , + 0.3 kg/m2 ( 95 % CI , -0.8 , 1.4 ) , risk score in female + 0.1 ( 95 % CI , -5.1 , 5.2 ) , and risk score in male + 2.6 ( 95 % CI , -14.2 , 19.5 ) . CONCLUSIONS Implementation of clinical guidelines for diabetes mellitus in general practice , by means of a CDSS and several procedures for implementation , did not result in a clinical ly significant change in doctors ' behavior or in patient outcome PURPOSE Clinical guidelines are design ed to assist in the management of specific diseases ; however , these guidelines are often neglected in the delivery of care . The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having , at the patient visit , a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient 's electronic medical record . SUBJECTS AND METHODS In a 6-month controlled trial at a primary care clinic , 58 primary care clinicians were r and omized to receive either a special encounter form with the computer-generated guideline recommendations or a st and ard encounter form . The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations . Data from 30 clinicians were analyzed ; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care . RESULTS Availability of patient management recommendations generated by the decision support system result ed in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus ( P = 0.01 ) . Median compliance for the group receiving the recommendations was 32.0 % versus 15.6 % for the control group . CONCLUSION Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients . This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care st and ards . Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p < 0.001 ) ; 61.7 % ( 156/253 ) of patients in the intervention group , compared with 42.6 % ( 110/258 ) of control patients , showed improvement ( difference 19.1 % , p < 0.001 ) . The clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 . UNLABELLED OBJECTIVE To determine whether a computerized clinical decision support system providing patient-specific recommendations in real-time improves the quality of prescribing for long-term care residents with renal insufficiency . DESIGN R and omized trial within the long-stay units of a large long-term care facility . R and omization was within blocks by unit type . Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units . Measurement The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories : ( 1 ) recommended medication doses ; ( 2 ) recommended administration frequencies ; ( 3 ) recommendations to avoid the drug ; ( 4 ) warnings of missing information . RESULTS The rates of alerts were nearly equal in the intervention and control units : 2.5 per 1,000 resident days in the intervention units and 2.4 in the control units . The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units ( relative risk 0.95 , 95 % confidence interval 0.83 , 1.1 ) for the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units : relative risk 2.4 for maximum frequency ( 1.4 , 4.4 ) ; 2.6 for drugs that should be avoided ( 1.4 , 5.0 ) ; and 1.8 for alerts to acquire missing information ( 1.1 , 3.4 ) . Overall , final drug orders were appropriate significantly more often in the intervention units-relative risk 1.2 ( 1.0 , 1.4 ) . CONCLUSIONS Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions . TRIAL REGISTRATION http:// clinical trials.gov Identifier : NCT00599209 OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P<.001 ) . The effect of provider advice combined with patient education was not significantly different from provider advice alone ( P=.88 ) . Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients Interventions that have proven effective in the management of chronic illness have often been difficult to establish in widespread practice . The Chronic Care Model provides a framework for implementing interventions , but it is expensive and difficult to implement . We developed a decision support system based on this model to improve the care of adults who have diabetes and receive primary care in Vermont or adjacent New York . The Vermont Diabetes Information System uses a network of community laboratories for providing data to produce flowsheets , reminders , action alerts , and population reports that are sent to primary care providers by fax and to patients by mail . Currently , 7295 patients are cared for by 124 primary care providers in 62 practice s and are enrolled in a r and omized controlled trial to study its effects OBJECTIVE To demonstrate the potential effect of deploying a sentinel system that scans administrative cl aims information and clinical data to detect and mitigate errors in care and deviations from best medical practice s. METHODS Members ( n = 39 462 ; age range , 12 - 64 years ) of a midwestern managed care plan were r and omly assigned to an intervention or a control group . The sentinel system was programmed with more than 1000 decision rules that were capable of generating clinical recommendations . Clinical recommendations triggered for subjects in the intervention group were relayed to treating physicians , and those for the control group were deferred to study end . RESULTS Nine hundred eight clinical recommendations were issued to the intervention group . Among those in both groups who triggered recommendations , there were 19 % fewer hospital admissions in the intervention group compared with the control group ( P < .001 ) . Charges among those whose recommendations were communicated were dollar 77.91 per member per month ( pmpm ) lower and paid cl aims were dollar 68.08 pmpm lower than among controls compared with the baseline values ( P = .003 for both ) . Paid cl aims for the entire intervention group ( with or without recommendations ) were dollar 8.07 pmpm lower than those for the entire control group . In contrast , the intervention cost dollar 1.00 pmpm , suggesting an 8-fold return on investment . CONCLUSION Ongoing use of a sentinel system to prompt clinical ly actionable , patient-specific alerts generated from administratively derived clinical data was associated with a reduction in hospitalization , medical costs , and morbidity BACKGROUND AND OBJECTIVE To assess the cost-effectiveness of an intervention based on the Global INitiative for Asthma ( GINA ) recommendations as compared to usual care . SUBJECTS AND METHOD Pragmatic , cluster-r and omised trial . Ten pneumologists and 10 general practitioners were r and omised to an intervention or control group , recruiting 98 and 100 asthma patients , respectively . The intervention consisted of an education program and a clinical decision support system ( CDSS ) providing recommendations based on the GINA . The control group was characterized by usual care . Effectiveness was assessed by the health related quality of life as measured by the St. George 's Respiratory Question naire ( SGRQ ) . Costs were computed from the re source consumption recorded during a 12 months follow-up period , and the cost-effectiveness of the intervention was investigated in an incremental analysis . RESULTS The intervention effect on the SGRQ total score was estimated as a 6.8 point reduction ( 95 % confidence interval , 2.5 - 11.1 ; p = 0.0021 ) , and a significant improvement in the SGRQ subscores and in the symptoms-free periods were also observed . From the social perspective , the mean total costs showed savings of -1,022 Euros ( 95 % confidence interval , -2,165 to 122 ; p = 0.0795 ) in intervention group as compared to usual care . The incremental analysis confirmed that the intervention was cost-effective . CONCLUSIONS The implementation of an asthma management program based in GINA recommendations improved the patient 's health related quality of life and was cost-effective as compared to usual care PURPOSE To determine the impact of giving physicians computerized reminders about apparently redundant clinical laboratory tests . SUBJECTS AND METHODS We performed a prospect i ve r and omized controlled trial that included all in patients at a large teaching hospital during a 15-week period . The intervention consisted of computerized reminders at the time a test was ordered that appeared to be redundant . Main outcome measures were the proportions of clinical laboratory orders that were canceled and the proportion of the tests that were actually performed . RESULTS During the study period , there were 939 apparently redundant laboratory tests among the 77,609 study tests that were ordered among the intervention ( n = 5,700 patients ) and control ( n = 5,886 patients ) groups . In the intervention group , 69 % ( 300 of 437 ) of tests were canceled in response to reminders . Of 137 overrides , 41 % appeared to be justified based on chart review . In the control group , 51 % of ordered redundant tests were performed , whereas in the intervention group only 27 % of ordered redundant tests were performed ( P < 0.001 ) . However , the estimated annual savings in laboratory charges was only $ 35,000 . This occurred because only 44 % of redundant tests performed had computer orders , because only half the computer orders were screened for redundancy , and because almost one-third of the reminders were overridden . CONCLUSIONS Reminders about orders for apparently redundant laboratory tests were effective when delivered . However , the overall effect was limited because many tests were performed without corresponding computer orders , and many orders were not screened for redundancy We describe the design and implementation of a clinical decision support system for ambulatory hyperlipidemia management . Despite readily available and evidence -based guidelines , cholesterol control remains persistently sub-optimal in clinical practice . " FastTrack " is an integrated , multi-faceted informatics tool to reduce barriers to effective cholesterol management by proactively integrating pertinent clinical information , evidence -based decision support and a simple means to act via a single FastTrack e-mail . We tested the intervention in a r and omized , controlled trial involving 14 physicians and 276 patients . In an interim analysis , we found that physicians on average were able to review and act upon 9 patient e-mails in less than 15 minutes . Significantly more intervention patients were initiated on a statin therapy or had their dose increased ( 15.3 % vs. 2.3 % , p < 0.001 ) . Impact of the intervention on LDL levels will be assessed at trial completion Despite recommendations for voluntary HIV screening , few medical centres have implemented screening programmes . The objective of the study was to determine whether an intervention with computer-based reminders and feedback would increase screening for HIV in a Department of Veterans Affairs ( VA ) health-care system . The design of the study was a r and omized controlled trial at five primary care clinics at the VA Palo Alto Health Care System . All primary care providers were eligible to participate in the study . The study intervention was computer-based reminders to either assess HIV risk behaviours or to offer HIV testing ; feedback on adherence to reminders was provided . The main outcome measure was the difference in HIV testing rates between intervention and control group providers . The control group providers tested 1.0 % ( n = 67 ) and 1.4 % ( n = 106 ) of patients in the preintervention and intervention period , respectively ; intervention providers tested 1.8 % ( n = 98 ) and 1.9 % ( n = 114 ) , respectively ( P = 0.75 ) . In our r and om sample of 753 untested patients , 204 ( 27 % ) had documented risk behaviours . Providers were more likely to adhere to reminders to test rather than with reminders to perform risk assessment ( 11 % versus 5 % , P < 0.01 ) . Sixty-one percent of providers felt that lack of time prevented risk assessment . In conclusion , in primary care clinics in our setting , HIV testing rates were low . Providers were unaware of the high rates of risky behaviour in their patient population and perceived important barriers to testing . Low-intensity clinical reminders and feedback did not increase rates of screening BACKGROUND Laboratory services play an important part in screening , diagnosis , and management of patients within primary care . However , unnecessary use of laboratory tests is increasing . Our aim was to assess the effect of two interventions on the number of laboratory tests requested by primary -care physicians . METHODS We did a cluster r and omised controlled trial using a 2x2 factorial design , involving 85 primary -care practice s ( 370 family practitioners ) that request all laboratory tests from one regional centre . The interventions were quarterly feedback of practice requesting rates for nine laboratory tests , enhanced with educational messages , and brief educational reminder messages added to the test result reports for nine laboratory tests . The primary outcome was the number of targeted tests requested by primary -care practice s during the 12 months of the intervention . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N06490422 . FINDINGS Practice s that received either or both the enhanced feedback and the reminder messages were significantly less likely than the control group to request the targeted tests in total ( enhanced feedback odds ratio 0.87 , 95 % CI 0.81 - 0.94 ; reminder messages 0.89 , 0.83 - 0.93 ) . The effect of the interventions varied across the targeted tests individually , although the number of tests requested for both interventions was generally reduced . Neither intervention was consistently better than the other . INTERPRETATION Enhanced feedback of requesting rates and brief educational reminder messages , alone and in combination , are effective strategies for reducing test requesting in primary care . Both strategies are feasible within most laboratory setting OBJECTIVE To test the efficiency and cost-effectiveness of interventions aim ed at enhancing laboratory monitoring of medication . STUDY DESIGN Cost-effectiveness analysis . METHODS Patients of a not-for-profit , group-model HMO were r and omized to 1 of 4 interventions : an electronic medical record reminder to the clinician , an automated voice message to patients , pharmacy-led outreach , or usual care . Patients were followed for 25 days to determine completion of all recommended baseline laboratory monitoring tests . We measured the rate of laboratory test completion and the cost-effectiveness of each intervention . Direct medical care costs to the HMO ( repeated testing , extra visits , and intervention costs ) were determined using trial data and a mix of other data sources . RESULTS The average cost of patient contact was $ 5.45 in the pharmacy-led intervention , $ 7.00 in the electronic reminder intervention , and $ 4.64 in the automated voice message reminder intervention . The electronic medical record intervention was more costly and less effective than other methods . The automated voice message intervention had an incremental cost-effectiveness ratio ( ICER ) of $ 47 per additional completed case , and the pharmacy intervention had an ICER of $ 64 per additional completed case . CONCLUSIONS Using the data available to compare strategies to enhance baseline monitoring , direct clinician messaging was not an efficient use of re sources . Depending on a decision maker 's willingness to pay , automated voice messaging and pharmacy-led efforts can be efficient choices to prompt therapeutic baseline monitoring , but direct clinician messaging is probably a less efficient use of re sources BACKGROUND Errors involving medication use are common . Computerized physician order entry ( CPOE ) can improve prescribing practice s. Few studies have examined the effect of CPOE in combination with decision support tools on prescribing practice s in the outpatient setting . Less is known about prescribers ' adherence to laboratory monitoring recommendations . OBJECTIVE To evaluate if reminders presented during CPOE for medications would increase physicians ' compliance with guidelines for laboratory monitoring at initiation of therapy . STUDY DESIGN R and omized prospect i ve intervention study . METHODS Two hundred seven primary care physicians in a group-model managed care organization were r and omized to receive or not receive drug laboratory monitoring alerts within the CPOE system . Adherence to laboratory monitoring recommendations for patients prescribed selected medications was compared between physician groups . RESULTS There was no significant difference between the control and intervention group physicians in the overall rate of compliance with ordering the recommended laboratory monitoring for patients prescribed study medications . Laboratory monitoring was performed as recommended 56.6 % of the time in the intervention group compared with 57.1 % of the time in the control group ( P = .31 ) . In cases in which a statistically significant difference was demonstrated , improved compliance favored the intervention group ( eg , 71.2 % vs 62.3 % [ P = .003 ] for gemfibrozil and 75.7 % vs 73.9 % [ P = .05 ] for statins ) . CONCLUSIONS As CPOE becomes more prevalent , additional research is needed to determine effective decision support tools . These findings then should be communicated to the developers and users of computerized medical record systems BACKGROUND The importance of laboratory monitoring for drugs is reflected in product labeling and published guidelines , but monitoring recommendations are followed inconsistently . Opportunity exists to improve monitoring , with the potential to decrease therapy complications . METHODS The objective of this r and omized trial was to determine whether computerized alerts were effective at increasing the percentage of ambulatory patients with laboratory monitoring at initiation of drug therapy . Physicians and pharmacists teamed up to develop organization-specific guidelines for monitoring selected drugs . In collaboration with physicians , pharmacists were alerted to missing laboratory test results , ordered missing tests , reminded patients to obtain tests , assessed test completion , review ed test results , and managed abnormal results . Eligible individuals included patients with therapy initiated for any of 15 drugs among 400,000 health plan members . RESULTS In the intervention group , 79.1 % ( n = 4076 ; 95 % confidence interval [ CI ] , 78.0%-80.2 % ) of dispensings were monitored compared with 70.2 % ( n = 3522 ; 95 % CI , 68.9%-71.5 % ) in the usual-care group ( P < .001 ) . For example , 78.6 % of amiodarone ( 95 % CI , 73.1%-83.5 % ) dispensing was monitored in the intervention group vs 51.4 % ( 95 % CI , 44.4%-58.4 % ) in the group receiving usual care ( P < .001 ) . CONCLUSIONS This study demonstrates the effectiveness of a computerized tool plus collaboration among health care professionals at increasing the percentage of patients receiving laboratory monitoring at initiation of therapy . Coupling data available from information systems with the knowledge and skills of physicians and pharmacists can result in improved patient monitoring This study describes the influence of a computerized medical record summary system in three disease areas ( hypertension , obesity and renal disease ) observed in the course of a controlled , r and omized and prospect i ve study of 479 Northwestern University Clinic patients . Experimental patients , who had available automated record summaries , and control patients , who had available only the manual record , were compared on several medical tests and procedures whose yearly occurrence was considered good medical practice for this patient population , and were compared as well on several measures of outcome of medical care . Evidence suggesting better care and outcome of care among patients with computerized record summaries available is presented Discrepancies between clinical guidelines and clinical practice call for practical implementation strategies . This study evaluates the implementation of clinical guidelines for hypertension in general practice with a specific computer-based clinical decision support system ( CDSS ) as part of the intervention . We carried out a r and omized study of general practice health centres in Sør- and Nord-Trøndelag counties in Norway ( population 380000 ) . A total of 17 health centres were included , with 24 doctors and 984 patients in the intervention group . Data from 887 patients was used in the analyses . There were 12 health centres with 29 doctors and 1255 patients in the control group . Data from 1127 control patients was used in the analyses . The main outcome measures were doctor 's behaviour , measured by adherence to registration of recommended variables in the Norwegian clinical guidelines for hypertension . The aim of the intervention was to lower the fractions of patients without registration s. However , there were no clinical ly significant differences between the intervention group and the control group for fractions of patients without registration of blood pressure ( intervention group 14.3 % , control group 14.2 % ) or serum cholesterol ( 62.3 % vs. 56.8 % ) during 12 months , nor , during 18 months , for fractions of patients without a registration of cigarette smoking ( 82.9 % vs. 87.1 % ) , cardiovascular inheritance ( 79.5 % vs. 73.4 % ) and body mass index ( 81.5 % vs. 89.2 % ) . One or several variables necessary for calculation of risk score for myocardial infa rct ion were missing in 91.7 % of patients in the intervention group and 91.9 % of patients in the control group . Large centre variations were shown for all variables . Implementation of clinical guidelines in the treatment of hypertensive patients in general practice , by means of a CDSS and several procedures for implementation did not result in clinical ly significant changes in the doctors ' behaviour . Of importance are both the lack of user-friendliness of the specific CDSS and problems in performing time-consuming multidimensional procedures The present study examined the influence of a computerized medical record summary system on incidence and length of hospitalization . Additional indicators of process of care were also considered . A prospect i ve , r and omized design was used where 241 experimental patients had a computerized medical record summary and 238 control patients had the traditional medical record . All patients were followed and compared over a two-year period . Although no difference in incidence of hospitalization was found between patients with and without the summary , during the second year , patients with summaries spent fewer days in the hospital . Patients with summaries also had more completed referrals for consultation , assigned diets , detected new problems and diagnostic tests on record than patients without the summary AIM To assess the impact of two modes of spirometry expert support on Family physicians ' ( FPs ' ) diagnoses and planned management in patients with apparent respiratory disease . METHOD A cluster-r and omised trial was performed with family practice s as the unit of r and omisation . FPs from 44 family practice s recorded their diagnosis and planned management before and after spirometry for 868 patients . Intervention consisted of spirometry interpretation support by either a chest physician or expert software . Both interventions were compared with usual care ( i.e. no additional interpretation support ) . Change in FPs ' diagnoses after spirometry served as the primary outcome . Secondary outcomes were referral rate , additional diagnostic tests , and disease management changes . Effects were expressed as percentages and Odds Ratios ( OR ) with 95 % confidence intervals . RESULTS Diagnoses changed after intervention in all groups : 47.8 % ( 95 % CI 41.8 to 53.9 ) for chest physician support ; 45.0 % ( 95 % CI 39.5 to 50.6 ) for software support ; and 53.3 % ( 95 % CI 47.2 to 59.4 ) for usual care . Differences in the proportions of changed diagnosis were not statistically significant : chest physician support versus usual care OR 0.79 ( 95%CI 0.49 to 1.30 ) ; software support versus usual care OR 0.72 ( 95 % CI 0.45 - 1.15 ) . There were no differences in secondary outcomes . CONCLUSION Neither chest physician spirometry support nor expert software spirometry support had a significant impact on FPs ' diagnosis of respiratory conditions or management decisions . TRIAL NUMBER http://www . clinical trials.gov/ct/show/NCT00131157?order=1 |
10,982 | 25,788,000 | Meta- analysis results ( limited to the MA , the recommended population assessment method ) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677 T genotypes .
Lower blood folate concentrations associated with this polymorphism could have implication s for a population -level risk of neural tube defects | BACKGROUND The methylenetetrahydrofolate reductase ( MTHFR ) 677C > T polymorphism is a risk factor for neural tube defects .
The T allele produces an enzyme with reduced folate-processing capacity , which has been associated with lower blood folate concentrations . | We have studied the effect of common mutations ( 677C-->T and 1298A-->C ) of the methylenetetrahydrofolate reductase ( MTHFR ) gene in sixty-six healthy French subjects , aged 27 - 47 years . Serum folate , vitamin B12 , and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes . The frequency of subjects homozygous for the 677TT genotype was 18 % , and that of those homozygous for the 1298CC genotype was 12.5 % . The frequency of individuals heterozygous for both mutations was 23.5 % . The 1298A-->C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes . This activity was 60 % for the 677CC/1298AC genotype and 52 % for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype . Heterozygotes for both mutations ( 677CT/1298AC genotype ) had 36 % of the reference specific activity . Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes , no significant differences were observed among different genotypes . This may be due to high serum folate level in our sample s , and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects BACKGROUND Methylenetetrahydrofolate reductase ( MTHFR ; EC 1.7.99.5 ) supplies the folate needed for the metabolism of homocysteine . A reduction in MTHFR activity , as occurs in the homozygous state for the 677C-->T ( so-called thermolabile ) enzyme variant ( TT genotype ) , is associated with an increase in plasma total homocysteine ( tHcy ) . OBJECTIVE In vitro studies suggest that the reduced activity of thermolabile MTHFR is due to the inappropriate loss of its riboflavin cofactor . We investigated the hypothesis that MTHFR activity in the TT genotype group is particularly sensitive to riboflavin status . DESIGN We studied tHcy and relevant B-vitamin status by MTHFR genotype in a cross-sectional study of 286 healthy subjects aged 19 - 63 y ( median : 27 y ) . The effect of riboflavin status was examined by dividing the sample into tertiles of erythrocyte glutathionine reductase activation coefficient , a functional index of riboflavin status . RESULTS Lower red blood cell folate ( P = 0.0001 ) and higher tHcy ( P = 0.0082 ) concentrations were found in the TT group than in the heterozygous ( CT ) or wild-type ( CC ) groups . However , these expected relations in the total sample were driven by the TT group with the lowest riboflavin status , whose mean tHcy concentration ( 18.09 micromol/L ) was almost twice that of the CC or CT group . By contrast , adequate riboflavin status rendered the TT group neutral with respect to tHcy metabolism . CONCLUSIONS The high tHcy concentration typically associated with homozygosity for the 677C-->T variant of MTHFR occurs only with poor riboflavin status . This may have important implication s for governments considering new fortification policies aim ed at the prevention of diseases for which this genotype is associated with increased risk The effectiveness of additional food folate in improving folate status in humans is uncertain particularly in people with the common genetic variant ( 677 C-->T ) in the methylenetetrahydrofolate reductase ( MTHFR ) gene . To examine the effect of a doubling of food folate consumption on folate status response variables , women ( n=32 ; 18 - 46 years ) with the MTHFR 677 CC or TT genotype consumed either 400 ( n=15 ; 7 CC and 8 TT ) or 800 ( n=17 ; 8 CC and 9 TT ) microg/day of dietary folate equivalents ( DFE ) derived exclusively from naturally occurring food folate for 12 weeks . A repeated measures two-factor ANOVA was used to examine the effect of the dietary treatment , the MTHFR C677 T genotype and their interactions on serum folate , RBC folate and plasma total homocysteine ( tHcy ) during the last 3 weeks of the study . Consumption of 800 microg DFE/day result ed in serum folate concentrations that were 67 % ( P=.005 ) higher than consumption of 400 microg DFE/day ( 18.6+/-2.9 vs. 31.0+/-2.7 nmol/L , respectively ) and RBC folate concentrations that were 33 % ( P=.001 ) higher ( 1172+/-75 vs. 1559+/-70 nmol/L , respectively ) . Serum folate ( P=.065 ) and RBC folate ( P=.022 ) concentrations were lower and plasma tHcy was higher ( P=.039 ) in women with the MTHFR 677 TT genotype relative to the CC genotype . However , no genotype by dietary treatment interaction was detected . These data suggest that a doubling of food folate intake will lead to marked improvements in folate status in women with the MTHFR 677 CC or TT genotype Objective To determine an optimal population red blood cell ( RBC ) folate concentration for the prevention of neural tube birth defects . Design Bayesian model . Setting Data from two population based studies in China . Participants 247 831 participants in a prospect i ve community intervention project in China ( 1993 - 95 ) to prevent neural tube defects with 400 μg/day folic acid supplementation and 1194 participants in a population based r and omized trial ( 2003 - 05 ) to evaluate the effect of folic acid supplementation on blood folate concentration among Chinese women of reproductive age . Intervention Folic acid supplementation ( 400 μg/day ) . Main outcome measures Estimated RBC folate concentration at time of neural tube closure ( day 28 of gestation ) and risk of neural tube defects . Results Risk of neural tube defects was high at the lowest estimated RBC folate concentrations ( for example , 25.4 ( 95 % uncertainty interval 20.8 to 31.2 ) neural tube defects per 10 000 births at 500 nmol/L ) and decreased as estimated RBC folate concentration increased . Risk of neural tube defects was substantially attenuated at estimated RBC folate concentrations above about 1000 nmol/L ( for example , 6 neural tube defects per 10 000 births at 1180 ( 1050 to 1340 ) nmol/L ) . The modeled dose-response relation was consistent with the existing literature . In addition , neural tube defect risk estimates developed using the proposed model and population level RBC information were consistent with the prevalence of neural tube defects in the US population before and after food fortification with folic acid . Conclusions A threshold for “ optimal ” population RBC folate concentration for the prevention of neural tube defects could be defined ( for example , approximately 1000 nmol/L ) . Population based RBC folate concentrations , as a biomarker for risk of neural tube defects , can be used to facilitate evaluation of prevention programs as well as to identify sub population s at elevated risk for a neural tube defect affected pregnancy due to folate insufficiency INTRODUCTION Methylenetetrahydrofolate reductase ( MTHFR ) C677 T is involved in folate and homocysteine metabolism . Disruption in the activity of this enzyme will alter their levels in the body . METHODOLOGY This study assessed MTHFR C677 T polymorphism and its relationship with serum homocysteine and B-vitamins levels in a sample of Chinese and Malays subjects in UPM , Serdang . One hundred subjects were r and omly selected from among the university population . Folate , vitamin B12 , B6 , and homocysteine levels were determined using MBA , ECLIA , and HPLC , respectively . PCR coupled with HinfI digestion was used for detection of MTHFR C677 T polymorphism . RESULTS The frequency of T allele was higher in the Chinese subjects ( 0.40 ) compared to the Malay ( 0.14 ) . Folate , vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups . Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels . The serum folate and homocysteine were mainly affected by homozygous genotype . CONCLUSION MTHFR C677 T polymorphism plays an important role in influencing the folate and homocysteine metabolism BACKGROUND The association between blood homocysteine concentration and the risk of cardiovascular disease ( CVD ) remains controversial , but few studies have examined the association between MTHFR C677 T ( a proxy for high homocysteine concentration ) and death from CVD . OBJECTIVE The objective was to examine associations of MTHFR C677 T , a proxy for high homocysteine concentrations , with CVD mortality and with all-cause mortality in a national representative prospect i ve cohort of the US adult population before the introduction of m and atory folic acid fortification of flour . DESIGN We used Mendelian r and omization to examine the association of MTHFR C677 T with cause-specific mortality in 5925 participants by accessing the NHANES III ( 1991 - 1994 ) Linked Mortality File ( through 2006 ) . RESULTS A comparison of homozygotes at baseline showed that individuals with a TT genotype had a 2.2-μmol/L higher homocysteine and a 1.4-ng/mL lower folate concentration , respectively , than did those with a CC genotype . The TT genotype frequency varied from 1.2 % ( 95 % CI : 0.7 , 2.0 ) in non-Hispanic blacks and 11.6 % ( 95 % CI : 9.6 , 14.0 ) in non-Hispanic whites to 19.4 % ( 95 % CI : 16.7 , 22.3 ) in Mexican Americans . After adjustment for ethnic group and other CVD risk factors , the MTHFR C677 T TT genotype was associated with significantly lower CVD mortality ( HR : 0.69 ; 95 % CI : 0.50 , 0 . 95 ) but had no significant effect on all-cause mortality ( HR : 0.79 ; 95 % CI : 0.59 , 1.05 ) . After stratification by period of follow-up , the inverse association of MTHFR with CVD mortality was significant only in the period after introduction of m and atory folic acid fortification . CONCLUSION The inverse association of MTHFR with CVD mortality was unexpected and highlights the need for caution in interpretation of Mendelian r and omization studies , which , like other observational studies , can be influenced by chance , bias , or confounding BACKGROUND The methylenetetrahydrofolate reductase ( MTHFR ) genotype is associated with modification of disease and risk of neural tube defects . Plasma and red blood cell ( RBC ) folate and plasma homocysteine concentrations change in response to daily intakes of folic acid supplements , but no large-scale or population -based r and omized trials have examined whether the MTHFR genotype modifies the observed response . OBJECTIVE We sought to determine whether the MTHFR 677C→T genotype modifies the response to folic acid supplementation during and 3 mo after discontinuation of supplementation . DESIGN Northern Chinese women of childbearing age were enrolled in a 6-mo supplementation trial of different folic acid doses : 100 , 400 , and 4000 μg/d and 4000 μg/wk . Plasma and RBC folate and plasma homocysteine concentrations were measured at baseline ; after 1 , 3 , and 6 mo of supplementation ; and 3 mo after discontinuation of supplementation . MTHFR genotyping was performed to identify a C→T mutation at position 677 ( n = 932 ) . RESULTS Plasma and RBC folate and homocysteine concentrations were associated with MTHFR genotype throughout the supplementation trial , regardless of folic acid dose . MTHFR TT was associated with lower folate concentrations , and the trend of TT < CC was maintained at even the highest doses . Folic acid doses of 100 μg/d or 4000 μg/wk did not reduce high homocysteine concentrations in those with the MTHFR TT genotype . CONCLUSION MTHFR genotype was an independent predictor of plasma and RBC folate and plasma homocysteine concentrations and did not have a significant interaction with folic acid dose during supplementation . This trial was registered at clinical trials.gov as NCT00207558 |
10,983 | 29,187,249 | Intervention effect was only moderate .
Most adherence measures in studies on educational and behavioral interventions showed statistically significant differences .
Studies that combined educational and behavioral intervention components showed larger effects .
Studies that included an individualized component and more intensive interventions showed larger effects .
Conclusion Educational and behavioral AEI can increase adherence .
In particular , multimodal and individualized interventions seem promising .
However , because of the small effect , the high risk of bias , and the invalidity of adherence measures , the actual benefit of adherence interventions for an unselected patient population ( i.e. , including also adherent patients ) seems limited .
No conclusion is possible for interventions combining adherence-enhancing components that address intentional ( behavioral ) as well as unintentional adherence ( reminder ) | Background Immunosuppressive drugs have to be taken through the whole duration of kidney transplant survival to avoid rejection .
Low adherence can increase the risk of allograft rejection .
The objective was to evaluate the effectiveness of adherence-enhancing interventions ( AEI ) in kidney transplantation recipients taking immunosuppressive drugs . | The objective of this r and omized controlled trial was to assess the effects of a 1‐year behavioral contract intervention on immunosuppressant therapy ( IST ) adherence and healthcare utilizations and costs among adult renal transplant recipients ( RTRs ) . The sample included adult RTRs who were at least 1 year posttransplant , taking tacrolimus or cyclosporine and served by a specialty pharmacy . Pharmacy refill records were used to measure adherence and monthly question naires were used to measure healthcare utilizations . Direct medical costs were estimated using the 2009 Medicare Expenditure Panel Survey . Adherence was analyzed using the GLM procedure and the MIXED procedure of SAS . Rate ratios and 95 % confidence intervals were estimated to quantify the rate of utilizing healthcare services relative to treatment assignment . One hundred fifty RTRs were enrolled in the study . Intervention group RTRs ( n = 76 ) had higher adherence than control group RTRs ( n = 74 ) over the study period ( p < 0.01 ) . And 76.1 % of the intervention group compared with 42.7 % of the control group was not hospitalized during the 1‐year study period ( RR = 1.785 ; 95 % CI : 1.314 , 2.425 ) , result ing in cost savings . Thus , evidence supports using behavioral contracts as an effective adherence intervention that may improve healthcare outcomes and lower costs Russell C , Conn V , Ashbaugh C , Madsen R , Wakefield M , Webb A , Coffey D , Peace L. Taking immunosuppressive medications effectively ( TIMELink ) : a pilot r and omized controlled trial in adult kidney transplant recipients . Clin Transplant 2011 : 25 : 864–870 . © 2010 John Wiley & Sons 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 Scientific background Poor compliance or adherence in drug therapy can cause increased morbidity , mortality and enormous costs in the healthcare system ( in Germany annually approximately 10 billion euros ) . Different methods are used for enhancing the compliance or adherence . Research questions The evaluation addresses the questions about existence , efficacy , cost-benefit relation as well as ethical-social and juridical implication s of strategies for enhancing compliance or adherence in drug therapy with concomitant improvements in treatment outcomes . Methods A systematic literature search was conducted in the medical , also health economic relevant , literature data bases in January 2007 , beginning from 2002 . Systematic review s on the basis of ( r and omised controlled trials ( RCT ) concerning interventions to enhance compliance or adherence with regard to treatment outcomes as well as systematic review s of health economic analyses were included in the evaluation . Additionally , it was also search ed for publications which primarily considered ethical-social and juridical aspects of these interventions for the German context . Results One systematic review with data for 57 RCT was included in the medical evaluation and one systematic review with data for six studies into the health economic evaluation . No publication primary concerning ethical-social or juridical implication s could be identified . A significant positive effect on the treatment outcome was reported for 22 evaluated interventions . For many interventions the results can be classified as reliable : counseling with providing an information leaflet and compliance diary chart followed by phone consultation for helicobacter pylori positive patients , repeated counseling for patients with acute asthma symptoms , telephone calls to establish the level of compliance and to make recommendations based on that for the therapy of cardiovascular diseases , calls of an automated telephone system with phone counseling in problem cases for diabetics , different family based interventions including repeated family counseling , education and " culturally modified family therapy " in patients with schizophrenia , repeated " compliance therapy " sessions for patients with acute psychosis . For other interventions the results should be viewed with more concern ( because of the poor method ical quality of the underlying studies ) . The effect size of the interventions can not be estimated from the available data . From the available data , no reliable results can be provided concerning the cost-benefit relation of these strategies . Discussion Many of the reported studies had a poor reporting and method ological quality . The reliability of the conclusions of the studies is restricted because of method ical shortcomings . Efficacy and cost estimates determined in the health economic studies are not transferable to the current situation in Germany . It has been discussed recently that the compliance or adherence enhancing interventions can restrict the autonomy and the privacy of the patients . Conclusions In drug therapy some compliance or adherence enhancing interventions with concomitant positive effect on the treatment outcome may be used . The cost-benefit relation of these interventions is to be estimated . Using these interventions the patient ’s autonomy and privacy are to be restricted as few as possible Background Unintentional non-adherence has been characterized as passively inconsistent medication-taking behavior ( forgetfulness or carelessness ) . Our objectives were to : ( 1 ) study the prevalence and predictors of unintentional non-adherence ; and ( 2 ) explore the interrelationship between intentional and unintentional non-adherence in relation to patients ’ medication beliefs . Methods We conducted a cross-sectional survey of adults with asthma , hypertension , diabetes , hyperlipidemia , osteoporosis , or depression from the Harris Interactive Chronic Illness Panel . The analytic sample for this study included 24,017 adults who self-identified themselves as persistent to prescription medications for their index disease . They answered three questions on unintentional non-adherence ( forgot , ran out , being careless ) , 11 questions on intentional non-adherence , and three multi-item scales assessing perceived need for medication ( k = 10 ) , perceived medication concerns ( k = 6 ) , and perceived medication affordability ( k = 4 ) . Logistic regression was used to model predictors of each unintentional non-adherence behavior . Baron and Kenny ’s regression approach was used to test the mediational effect of unintentional non-adherence on the relationship between medication beliefs and intentional non-adherence . Bootstrapping was employed to confirm the statistical significance of these results . Results For the index disease , 62 % forgot to take a medication , 37 % had run out of the medication , and 23 % were careless about taking the medication . Common multivariate predictors ( p < .001 ) of the three behaviors were : ( 1 ) lower perceived need for medications ; ( 2 ) more medication affordability problems ; ( 3 ) worse self-rated health ; ( 4 ) diabetes or osteoporosis ( relative to hypertension ) ; and ( 5 ) younger age . Unique statistically-significant predictors of the three behaviors were : ( a ) ‘ forgot to take medications ’ - greater concerns about the index medication and male gender ; ( b ) ‘ run out of medications ’ - non-white race , asthma , and higher number of total prescription medications ; ( c ) ‘ being careless ’ - greater medication concerns . Mediational tests confirmed the hypothesis that the effect of medication beliefs ( perceived need , concerns , and affordability ) on intentional non-adherence is mediated through unintentional non-adherence . Conclusions For our study sample , unintentional non-adherence does not appear to be r and om and is predicted by medication beliefs , chronic disease , and sociodemographics . The data suggests that the importance of unintentional non-adherence may lie in its potential prognostic significance for future intentional non-adherence . Health care providers may consider routinely inquiring about unintentional non-adherence in order to proactively address patients ’ suboptimal medication beliefs before they choose to discontinue therapy all together Background Outcome after renal transplantation depends on patient compliance and adherence for early detection of complications and identification of intervention opportunities . Compliance describes the degree to which patients follow medical advice and take their medications . Adherence has been defined as the extent to which a patients ' behavior coincides with clinical prescriptions . Material s and Methods Patients were r and omized 7 to 14 days after transplantation into groups with ( n = 40 ) and without ( n = 40 ) an electronic medication dispenser ( EMD ) . The EMD , which was used for the 1-year study period , recorded the date and time the patient took their medications and was monitored via a web-based application . Patients were monitored for 1 year regarding outpatient follow-up visits , emergency hospitalizations , renal biopsies , rejection episodes , renal function , and blood concentration of medications . Results Compliance in the intervention group was 97.8 % ( the control group was not assessed ) . Number of missed doses varied significantly by weekday ( P = 0.033 ) ; patients were most likely to miss doses on Saturdays and Thursdays . Patients missed a total of 11 follow-up visits . During the study , 92 biopsies were performed on 55 patients ( intervention group : 32 [ 17 ] ; control group , 60 [ 38 ] ) . Biopsy-verified rejection was three times more common among controls ( 13 patients vs 4 ; P = 0.054 , not significant ) . Average P-creatinine level was slightly lower in the intervention group than the control group ( 131 vs 150 & mgr;mol/L , not significant ) , whereas mean tacrolimus was similar ( 7.32 vs 7.22 ng/mL , n.s . ) . Conclusions The EMD is associated with high compliance , and there are also indications of a lower rejection rate Background : Non‐compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post‐transplant care . This r and omized , controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients ’ compliance with immunosuppressive agents . Methods : Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were r and omized in the intervention or control group provided they met study criteria . In addition to routine clinic services at each clinic visit , patients in the intervention group received clinical pharmacy services , which included medication histories and review of patients ’ medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events . The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes . To promote medication compliance by using compliance enhancement strategies , the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications . Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction . Compliance rate ( CR ) was calculated and patient 's compliance status was determined from the CR . The CR , the fraction of patients remaining compliant for each month , and the mean time patients were compliant were compared between groups . Whether there was a difference in the frequency of patients achieving ‘ target ’ immunosuppressive levels in the control and study groups was evaluated . Results : The mean CR for patients who had clinical pharmacist intervention ( n=12 ) was statistically higher than the control group 's ( n=12 ) mean CR ( p<0.001 ) . During the 12‐month post‐transplant study period , patients in the intervention group had a longer duration of compliance than patients in the control group ( p<0.05 ) . Additionally , patients who had clinical pharmacy services had a greater achievement of ‘ target ’ levels than patients who did not receive these services ( p<0.05 ) . Conclusions : Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services . Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post‐transplant patients is beneficial for enhancing medication compliance Abstract : Background : Although non‐adherence to an immunosuppressive regimen ( NAH ) is a major risk factor for poor outcome after renal transplantation ( RTx ) , very few studies have examined non‐adherence intervention in this context . This pilot r and omized controlled trial ( RCT ) tested the efficacy of an educational – behavioural intervention to increase adherence in non‐adherent RTx patients . We also assessed how NAH evolves over time OBJECTIVES Improving treatment adherence to immunosuppressive agents could have positive effects on the morbidity and mortality of kidney transplant recipients . Our objective was to determine whether psychoeducational intervention aim ed at improving treatment adherence also could improve 10-year kidney allograft survival rates . MATERIAL S AND METHODS A r and omized open-label study compared a group who received psychoeducational intervention ( n = 55 ) with a control group ( n = 55 ) , with all patients being kidney transplant recipients in the Department of Nephrology and Organ Transplantation ( University Hospital , Toulouse , France ) . Psychoeducational intervention comprised 8 weekly sessions provided by multidisciplinary teams . Patients were included between 2002 and 2003 . The primary endpoint was allograft survival at 10 years ( ie , by 2012 ) . A failed allograft or death with a functioning allograft was considered an event . RESULTS Mean overall allograft survival rate at 10 years was 78.2 % ( 95 % confidence interval , 70.5 - 25.3 ) . In the control group , 48 patients ( 43.6 % ) still had a functioning graft at 10 years versus 38 patients ( 34.5 % ) in the psychoeducational intervention group ( P = .02 ) . However , a log-rank test did not find any significant difference in allograft survival between the groups ( P = .06 ) . In multivariate analyses ( Cox model ) , no factor was significantly associated with allograft survival at 10 years . CONCLUSIONS After an initial 6-month observational adherence survey , there was no benefit to kidney allograft survival at 10 years after the psychoeducational intervention , which had aim ed to improve patient adherence to treatment with immunosuppressive agents . This might be related to the fact that booster interventions are needed ( eg , on a yearly basis ) Purpose Solid-organ transplant recipients present a high rate of non-adherence to drug treatment . Few interventional studies have included approaches aim ed at increasing adherence . The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients . Methods In a r and omized prospect i ve study , incident renal transplant patients ( n = 111 ) were divided into two groups : control group ( received usual transplant patient education ) and treatment group ( usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes ) . Treatment adherence was assessed using ITAS adherence question naire after 3 months . Renal function at 3 , 6 , and 12 months , and the incidence of transplant rejection were evaluated . Results The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups ( p = 0.001 ) , respectively . The relative risk for non-adherence was 2.59 times ( CI 1.38–4.88 ) higher in the control group . Multivariate analysis demonstrated a 5.84 times ( CI 1.8–18.8 , p = 0.003 ) higher risk of non-adherence in the control group . There were no differences in renal function and rejection rates between groups . Conclusions A behavioral and educational strategy addressing the patient ’s perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy Abstract Background : The economic impact of therapeutic non-adherence in chronic diseases has rarely been examined using qualitative st and ards for economic evaluation . This study illustrates the impact of non-adherence on the cost utility of renal transplantation versus haemodialysis from the societal perspective and examines the scope for adherence-enhancing interventions . Methods : Long-term costs and outcomes in adherent and non-adherent renal transplant patients were simulated in a Markov model . The cost ( euros , year 2000 values ) and outcome data that were imputed in the model were derived from a prospect i ve study in renal transplantation c and i date s performed in 2002 . Probabilities of adverse events , graft rejection , graft loss and death in adherent and non-adherent renal transplant patients were derived from literature . Results : Compared with dialysis , renal transplantation offers a better outcome in both adherent and non-adherent patients . Lifetime costs after transplantation in the adherent patient group are higher than lifetime dialysis costs and lifetime costs in the non-adherent patient group , mainly because adherent patients live longer after transplantation . Long-term outcomes after transplantation are better for adherent than for non-adherent patients . The mean cost per QALY gained in adherent patients relative to non-adherent patients was € 35 021 per QALY ( 95 % CI 26 959 , 46 620 ) . Conclusion : Compared with established healthcare interventions , such as haemodialysis , renal transplantation can be considered a cost-effective therapy for patients with end-stage renal disease , even if patients are non-adherent after transplantation . The low incremental cost per QALY calculated in this model for adherent renal transplant patients , suggests there may be scope for adherenceenhancing interventions ( provided that such interventions with a sufficiently high effectiveness exist or can be developed ) . As the findings are based on simulated long-term costs and outcomes , they should not be considered as precise estimates of the impact of non-adherence . This study is rather meant as an illustration of how non-adherence may impact on the results of cost-effectiveness analyses BACKGROUND Medication adherence is critical for transplant patients because the consequences of non-adherence can result in allograft loss and may be life threatening . METHODS A prospect i ve study with 74 renal transplant recipients using a sequential control group design was performed to investigate the impact of a pharmaceutical intensified care programme led by a clinical pharmacist on daily drug adherence during the first year after renal transplantation . Thirty-nine patients of the control group received the already established st and ardized drug and transplant training , while 35 patients of the intensified care group ( ICG ) received additional inpatient and outpatient pharmaceutical care and counselling by a dedicated clinical pharmacist . Applied interventions were clustered and classified using the behaviour change technique taxonomy according to Michie . Adherence to immunosuppressive drug therapy was monitored up to 1 year using a medication event monitoring system , pill count ( PC ) , drug holiday ( DH ) occurrence , Morisky question naire and self-report . RESULTS Sixty-seven patients ( 35 of the st and ard care and 32 of the ICG ) were analysed . Implementation of DA was significantly ( P = 0.014 ) improved in patients of the ICG ( 91 % ) compared with SCG ( 75 % ) during the first year after transplantion . Daily adherence measures were already improved within 30 - 40 days after start of intensified patient care and continued throughout the study period . Intensified care patients also showed significantly better results for taking adherence ( P = 0.006 ) , PC ( P = 0.008 ) and DHs ( P = 0.001 ) . CONCLUSIONS The additional , intensified pharmaceutical care improved patients ' medication adherence remarkably , suggesting that the applied additional care programme has the potential to improve outcomes after organ transplantation |
10,984 | 23,190,360 | All phase II chemotherapy studies reported maintained HRQL or improved dysphagia combined with low level of toxicity . | BACKGROUND Patient-reported outcomes ( PROs ) and assessment s of treatment-related toxicity provide important information on the effect of palliative chemotherapy and /or radiotherapy .
The aim of this study was to review the effect of palliative radiotherapy and /or chemotherapy on symptoms and quality of life assessed by PROs and measurement of toxicity for patients with oesophageal cancer . | BACKGROUND This r and omised study compared protracted venous infusion ( PVI ) fluorouracil ( 5-FU ) with PVI 5-FU plus mitomycin C ( MMC ) in patients with advanced oesophago-gastric cancer . PATIENTS AND METHODS Two hundred and fifty-four patients with adenocarcinoma , squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus , oesophago-gastric junction or the stomach were r and omised . The major end points were tumour response , survival , toxicity and quality of life . RESULTS The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors . The overall response rate was 16.1 % [ 95 % confidence interval ( CI ) 9.5 % to 22.7 % ] in patients treated with PVI 5-FU alone compared with 19.1 % ( 95 % CI 12.0 % to 26.0 % ) for those treated with PVI 5-FU plus MMC ( P = 0.555 ) . Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC ( P = 0.195 ) . Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC ( P = 1.0 ) . Toxicity was mild for both treatments . Symptomatic benefit measured by improvement in pain control , weight loss , dysphagia and oesophageal reflux was observed in over 64 % of patients in each arm . Quality of life scores were comparable in each arm . CONCLUSIONS PVI 5-FU is a safe , effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit BACKGROUND We aim ed to establish the superiority ( or noninferiority if superiority was not achieved ) in terms of time to progression ( TTP ) of irinotecan/5-fluorouracil ( IF ) over cisplatin/5-fluorouracil ( CF ) in chemonaive patients with adenocarcinoma of the stomach/esophagogastric junction . PATIENTS AND METHODS Patients received either IF : i.v . irinotecan 80 mg/m(2 ) 30 min , folinic acid 500 mg/m(2 ) 2 h , 5-fluorouracil ( 5-FU ) 2000 mg/m(2 ) 22 h , for 6/7 weeks or CF : cisplatin 100 mg/m(2 ) 1 - 3 h , with 5-FU 1000 mg/m(2)/day 24 h , days 1 - 5 , every 4 weeks . RESULTS In all , 333 patients were r and omized and treated ( IF 170 , CF 163 ) . Patient characteristics were balanced except more IF patients had Karnofsky performance status 100 % . TTP for IF was 5.0 months [ 95 % confidence interval ( CI ) 3.8 - 5.8 ] and 4.2 months ( 95 % CI 3.7 - 5.5 ) for CF ( P = 0.088 ) . Overall survival ( OS ) was 9.0 versus 8.7 months , response rate 31.8 % versus 25.8 % , time to treatment failure ( TTF ) 4.0 versus 3.4 months for IF and CF , respectively . The difference in TTF was statistically significant ( P = 0.018 ) . IF was better in terms of toxic deaths ( 0.6 % versus 3 % ) , discontinuation for toxicity ( 10.0 % versus 21.5 % ) , severe neutropenia , thrombocytopenia and stomatitis , but not diarrhea . CONCLUSION IF did not yield a significant TTP or OS superiority over CF , and the results of noninferiority of IF were borderline . However , IF may provide a viable , platinum-free front-line treatment alternative for metastatic gastric cancer BACKGROUND Clinical data showed promising antitumour activity with feasible tolerability for matuzumab plus epirubicin , cisplatin and capecitabine ( ECX ) chemotherapy in untreated advanced oesophago-gastric ( OG ) cancer . The aim was to evaluate the efficacy of matuzumab plus ECX versus ECX alone . PATIENTS AND METHODS In this multicentre , r and omised open-label phase II study , 72 patients with metastatic OG cancer were r and omly assigned to either 800 mg matuzumab weekly plus epirubicin 50 mg/m² , cisplatin 60 mg/m² on day 1 and capecitabine 1250 mg/m² daily in a 21-day cycle ( ECX ) or the same ECX regimen alone . The primary end point was objective response . Secondary end points included progression-free survival ( PFS ) , overall survival ( OS ) , quality of life , safety and tolerability . RESULTS Following r and om assignment , 35 patients ( median age 59 years ) received ECX/matuzumab and 36 patients ( median age 64 years ) ECX . The addition of matuzumab to ECX did not improve objective response : 31 % for ECX/matuzumab [ 95 % confidence interval ( CI ) 17 - 49 ] compared with 58 % for the ECX arm ( 95 % CI 41 - 74 ) P = 0.994 ( one sided ) . There was no significant difference in median PFS : 4.8 months ( 95 % CI 2.9 - 8.1 ) for ECX/matuzumab versus 7.1 months ( 95 % CI 4.4 - 8.5 ) for ECX , or in median OS : 9.4 months ( 95 % CI 7.5 - 16.2 ) , compared with 12.2 months ( 95 % CI 9.8 - 13.8 months ) . Grade 3/4 treatment-related toxicity was observed in 27 and 25 patients in the ECX/matuzumab and ECX groups , respectively . CONCLUSION Matuzumab 800 mg weekly combined with ECX chemotherapy does not increase response or survival for patients with advanced OG cancer . Therefore , ECX/matuzumab should not be examined further in phase III 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 The purpose of the study was to establish the optimal dose of capecitabine ( X ) to be used within a multicentre , r and omised study evaluating the potential roles of oxaliplatin ( O ) and X in chemonaive patients ( pts ) with advanced oesophagogastric cancer . Two by two design was used , and pts were r and omised to one of four regimens and stratified for extent of disease , performance status ( PS ) and centre . The treatment regimens are epirubicin , cisplatin , 5-fluorouracil ( ECF ) , EOF , ECX or EOX . Doses : E 50 mg m−2 , C 60 mg m−2 and O 130 mg m−2 i.v . 3 weekly ; F 200 mg m−2 day−1 i.v . and X 500 mg m−2 b.i.d.−1 ( escalated to 625 mg m−2 b.i.d.−1 after results of first interim analysis ) p.o . , continuously . First interim analysis was performed when 80 pts had been r and omised . Dose-limiting fluoropyrimidine toxicities were stomatitis , palmar plantar erythema ( PPE ) and diarrhoea ; 5.1 % of X-treated pts experienced grade 3/4 toxicity . Protocol planned dose escalation of X to 625 mg m−2 b.i.d.−1 was instituted and a second interim analysis has been performed ; results are presented in this paper . A total of 204 pts were r and omised at the time of the protocol planned 2nd interim analysis . Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7 % pts receiving F , 8.4 % pts receiving X 500 mg m−2 b.i.d.−1 and 14.7 % pts receiving X 625 mg m−2 b.i.d.−1 . Combined complete and partial response rates were ECF 31 % ( 95 % CI 18.7–46.3 ) , EOF 39 % ( 95 % CI 25.9–53.1 ) , ECX 35 % ( 95 % CI 21.4–50.3 ) , EOX 48 % ( 95 % CI 33.3–62.8 ) . Grade 3/4 fluoropyrimidine toxicity affected 14.7 % of pts treated with X 625 mg m−2 b.i.d.−1 , which is similar to that observed with F , confirming this to be the optimal dose . The replacement of C by O and F by X does not appear to impair efficacy . The trial continues to total accrual of 1000 pts OBJECTIVES : A dramatic rise in incidence , an aging population , and expensive palliative treatments have led to an escalating burden on clinicians managing inoperable esophageal cancer with only limited evidence of effectiveness . This study compares the clinical effectiveness and cost-effectiveness of self-exp and ing metal stents ( SEMSs ) with other palliative therapies to aid clinicians in making an evidence -based treatment choice . METHODS : We conducted a prospect i ve , multicenter , r and omized , controlled , clinical trial with 215 patients followed until death or study closure . The primary outcome measures were dysphagia , quality of life ( QL ) 6 weeks following treatment , and total cost of treatment . Secondary outcome measures included treatment-associated morbidity , mortality , survival , and cost-effectiveness . An intention-to-treat analysis was carried out . RESULTS : There was a significant difference in mean dysphagia grade between treatment arms 6 weeks following treatment ( P=0.046 ) , with worse swallowing reported by rigid stent – treated patients ( mean dysphagia score difference=−0.49 ; 95 % confidence interval ( CI ) −0.10 to −0.89 , P=0.014 ) . Global QL scores were lower at both 1 and 6 weeks following treatment for patients treated by SEMSs ( mean difference QL index week 1=−0.66 ; 95 % CI : −0.02 to −1.30 , P=0.04 ; mean difference QL index week 6=−1.01 ; 95 % CI −0.30 to −1.72 , P=0.006 ) . These findings were associated with higher post-procedure pain scores in the SEMS patient group ( mean difference of the European Organisation for Research and Treatment of Cancer QLQ C-30 pain symptom score at week 1=11.13 ; 95 % CI : 2.89–19.4 ; P=0.01 ) . Although mean EQ-5D QL values differed between the treatments ( P<0.001 ) , this difference dissipated following generation of quality -adjusted life year values . Total costs varied between treatment arms but these findings canceled out when SEMSs were compared with non-SEMS therapies ( 95 % CI −845.15–1,332.62 ) . These results were robust to sensitivity analysis . There were no differences in the in-hospital mortality or early complication rates , but late complications were more frequent after rigid stenting ( risk ratio=2.47 ; 95 % CI 1.88–3.04 ) . There was a survival advantage for non-stent-treated patients ( log-rank statistic=4.21 , P=0.04 ) . CONCLUSIONS : The treatment choice for patients with inoperable esophageal cancer should be between a SEMS or a non-stent treatment after consideration has been given to both patient and tumor characteristics and clinician and patient preferences PURPOSE Between 1994 and 1997 , 22 patients with dysphagia from advanced incurable esophageal cancer were enrolled in a phase I/II prospect i ve study to assess the palliative benefit and toxicity of a short course of radiotherapy with chemotherapy . METHODS The study population included 17 men and five women with a median age of 69 ( range 43 - 84 ) . Patients were treated with 30 Gy in ten fractions to the mediastinum with a concurrent single course of chemotherapy ( 5-FU , 1000 mg/m(2 ) , days 1 - 4 and mitomycin-C 10 mg/m(2 ) , day 1 ) . Swallowing ability was recorded each day on a self-administered diary card using the five point dysphagia index of the MRC ( UK ) . The median baseline MRC swallowing score was 4 ( can not swallow solids ) . RESULTS Treatment was generally well tolerated , but seven ( 32 % ) patients had transient worsening of dysphagia scores immediately following treatment because of esophagitis ; fifteen ( 68 % ) achieved a complete response ( score 1 : no difficulty on swallowing ) with a median time to normalization of swallowing of 5 weeks . For these patients , the median dysphagia-free interval from time of onset of improvement was 11 weeks ( range 1 - 131 weeks ) and 11 ( 73 % ) remained dysphagia-free until death . The remaining patients had no or marginal improvement . Univariate analysis showed no difference between responders and non-responders with respect to age , gender , or histology . Median survival for the entire study population was 20 weeks ( range 3 - 135 weeks ) . CONCLUSIONS This prospect i ve trial shows that a short course of radiotherapy plus chemotherapy may produce complete relief of swallowing difficulties in a substantial proportion of patients with acceptable toxicity PURPOSE A phase II study was performed in patients with unresectable or metastatic gastric cancer evaluating the efficacy of a new chemotherapy schedule combining epirubicin and cisplatin with a continuous ambulatory infusion of 5-fluorouracil ( ECF ) . PATIENTS AND METHODS One hundred thirty-nine consecutive , previously untreated patients were given ECF . Of these , 128 had measurable disease . Epirubicin ( 50 mg/m2 i.v . ) and cisplatin ( 60 mg/m2 i.v . ) were administered every three weeks for 8 cycles during a 21 week continuous i.v . infusion of 5-fluorouracil ( 200 mg/m2/day ) . In total 773 cycles of chemotherapy were given . RESULTS Objective tumour responses was seen in 91 ( 71 % ) of the 128 patients with measurable disease , of which 15 ( 12 % ) had a complete response . Twenty patients with locally advanced disease responding to ECF had attempted resection of the primary --11 ( 55 % ) were completely removed , 4 of these had no residual tumour in the resected specimen . The overall median survival was 8.2 months with 1 and 2 year survivals of 30 % and 10 % respectively . Grade 3 or 4 emesis occurred in 13 % , stomatitis in 7 % , diarrhoea in 4 % , infection in 6 % , leucopenia in 21 % and thrombocytopenia in 8 % of patients . Myelosuppression delayed treatment in 39 ( 5 % ) of the 773 cycles . Six of the 139 patients ( 4.3 % ) had treatment related deaths . There was no measurable reduction in quality of life during chemotherapy , while 67 % of the 66 patients with dysphagia had complete resolution of this symptom . CONCLUSIONS The ECF regimen displays high anti-tumour activity with moderate toxicity in patients with gastric cancer and in some cases enabled resection of previously inoperable tumours This Phase II study assessed the response rate and toxicity profile of the combination CPT‐11 and cisplatin administered weekly to patients with untreated , advanced adenocarcinoma of the stomach or the gastroesophageal junction PURPOSE We report the results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin , and protracted venous infusion fluorouracil ( 5-FU ) ( ECF regimen ) with the st and ard combination of 5-FU , doxorubicin , and methotrexate ( FAMTX ) in previously untreated patients with advanced esophagogastric cancer . PATIENTS AND METHODS Two hundred seventy-four patients with adenocarcinoma or undifferentiated carcinoma were r and omized and analyzed for survival , tumor response , toxicity , and quality of life ( QL ) . RESULTS The overall response rate was 45 % ( 95 % confidence interval [ CI ] , 36 % to 54 % ) with ECF and 21 % ( 95 % CI , 13 % to 29 % ) with FAMTX ( P = .0002 ) . Toxicity was tolerable and there were only three toxic deaths . The FAMTX regimen caused more hematologic toxicity and serious infections , but ECF caused more emesis and alopecia . The median survival duration was 8.9 months with ECF and 5.7 months with FAMTX ( P = .0009 ) ; at 1 year , 36 % ( 95 % CI , 27 % to 45 % ) of ECF and 21 % ( 95 % CI , 14 % to 29 % ) of FAMTX patients were alive . The median failure-free survival duration was 7.4 months with ECF and 3.4 months with FAMTX ( P = .00006 ) . The global QL scores were better for ECF at 24 weeks , but the remaining QL data showed no differences between either arm of the study . Hospital-based cost analysis on a subset of patients was similar for each arm and translated into an increment cost of $ 975 per life-year gained . CONCLUSION The ECF regimen results in a survival and response advantage , tolerable toxicity , better QL and cost-effectiveness compared with FAMTX chemotherapy . This regimen should now be considered the st and ard treatment for advanced esophagogastric cancer Background : Many patients with advanced malignant dysphagia are not suitable for definitive treatment . The best option for palliation of dysphagia varies between patients . This paper looks at a simple technique for enhancing laser recanalisation . Aim : To assess the value of adjunctive brachytherapy in prolonging palliation of malignant dysphagia by endoscopic laser therapy . Patients : Twenty two patients with advanced malignant dysphagia due to adenocarcinoma of the oesophagus or gastric cardia , unsuitable for surgery or radical chemoradiotherapy . Methods : Patients able to eat a soft diet after laser recanalisation were r and omised to no further therapy or a single treatment with brachytherapy ( 10 Gy ) . Results were judged on the quality and duration of dysphagia palliation , need for subsequent intervention , complications , and survival . Results : The median dysphagia score for all patients two weeks after initial treatment was 1 ( some solids ) . The median dysphagia palliated interval from the end of initial treatment to recurrent dysphagia or death increased from five weeks ( control group ) to 19 weeks ( brachytherapy group ) . Three patients had some odynophagia for up to six weeks after brachytherapy . There was no other treatment related morbidity or mortality . Further intervention was required in 10 of 11 control patients ( median five further procedures ) compared with 7/11 brachytherapy patients ( median two further procedures ) . There was no difference in survival ( median 20 weeks ( control ) , 26 weeks ( brachytherapy ) ) . Conclusions : Laser therapy followed by brachytherapy is a safe , straightforward , and effective option for palliating advanced malignant dysphagia , which is complementary to stent insertion PURPOSE To evaluate the response , toxicity , survival , and quality of life in patients with unresectable or metastatic esophageal cancer treated with weekly irinotecan and cisplatin . PATIENTS AND METHODS Thirty-five patients with metastatic or unresectable esophageal adenocarcinoma ( 23 patients ) or squamous cell carcinoma ( 12 patients ) were treated . No prior chemotherapy was allowed . The majority of patients had metastatic and bidimensionally measurable disease ( 34 patients each [ 97 % ] ) . Patients were treated with cisplatin 30 mg/m(2 ) and irinotecan 65 mg/m(2 ) , repeated weekly for 4 weeks , followed by a 2-week rest period . Treatment was recycled every 6 weeks . Degree of dysphagia relief was monitored , and quality of life was measured prospect ively using the European Organization for Research and Treatment of Cancer Quality of Life Question naire C-30 and Functional Assessment of Cancer Therapy-General instruments . RESULTS Thirty-five patients were assessable for response and toxicity . Major objective responses were observed in 20 patients ( 57 % ; 95 % confidence interval , 41 % to 73 % ) , including two complete responses ( 6 % ) . Similar response rates were observed for adenocarcinoma ( 12 of 23 patients ; 52 % ) and squamous carcinoma ( eight of 12 patients ; 66 % ) . The median duration of response was 4.2 months ( range , 1 to 8.8 + months ) . Median actuarial survival was 14.6 months ( range , 1 to 15.2 + months ) . In 20 patients with dysphagia assessable at baseline , 18 ( 90 % ) noted either improvement or resolution of dysphagia on chemotherapy . Global quality of life improved in responding patients , primarily because of improvements in pain , emotional state , and relationships with family and friends . Toxicity was relatively mild and included only three patients ( 9 % ) with grade 4 neutropenia and four ( 11 % ) with grade 3 diarrhea . There were no treatment-related deaths . CONCLUSION The combination of weekly cisplatin plus irinotecan had significant activity in metastatic esophageal carcinoma and result ed in significant relief of dysphagia . The regimen was well tolerated , with acceptable myelosuppression and rare treatment-related diarrhea . Further evaluation of the combination of weekly irinotecan and cisplatin , including the addition of other agents to this regimen , is indicated Metal stent placement and single dose brachytherapy are commonly used treatment modalities for the palliation of inoperable oesophageal carcinoma . We investigated generic and disease-specific health-related quality of life ( HRQoL ) after these palliative treatments . Patients with dysphagia from inoperable oesophageal carcinoma were r and omised to placement of a covered Ultraflex stent ( n = 108 ) or single dose ( 12 Gy ) brachytherapy ( n = 101 ) . We obtained longitudinal data on disease-specific ( dysphagia score , European Organisation for Research and Treatment of Cancer ( EORTC ) OES-23 , visual analogue pain scale ) and generic ( EORTC Quality of Life-Core 30 Question naire ( QLQ-C30 ) , Euroqol (EQ)-5D ) HRQoL at monthly home visits by a specially-trained research nurse . We compared HRQoL between the two treatments and analysed changes in HRQoL during follow-up . Dysphagia improved more rapidly after stent placement than after brachytherapy , but long-term relief of dysphagia was better after brachytherapy . For generic HRQoL , there was an overall significant difference in favour of brachytherapy on four out of five functional scales of the EORTC QLQ-C30 ( role , emotional , cognitive and social ) ( P < 0.05 ) . Generic HRQoL deteriorated over time on all functional scales of the EORTC QLQ C-30 and EQ-5D , in particular physical and role functioning ( on average -23 and -24 on a 100 points scale during 0.5 years of follow-up ) . This decline was more pronounced in the stent group . Major improvements were seen on the dysphagia and eating scales of the EORTC OES-23 , in contrast to other scales of this disease-specific measure , which remained almost stable during follow-up . Reported levels of chest or abdominal pain remained stable during follow-up in both treatment groups , general pain levels increased to a minor extent . The effects of single dose brachytherapy on HRQoL compared favourably to those of stent placement for the palliation of oesophageal cancer . Future studies on palliative care for oesophageal cancer should at least include generic HRQoL scales , since these were more responsive in measuring patients ' functioning and well-being during follow-up than disease-specific HRQoL scales In a prospect i ve study of 69 patients being treated for oesophageal carcinoma , quality of life was assessed with the Rotterdam Symptom Checklist , a dysphagia score and an activities of daily living question naire . Significant correlations were found between the results of the Rotterdam Symptom Checklist , the dysphagia score and most aspects of the activities of daily living question naire . Eighteen patients underwent surgery , 43 radiotherapy or intubation , and eight a combination of surgery and other therapy . Patients undergoing surgery were significantly younger and had better scores in all parameters examined before operation , including significantly better scores in ‘ knowledge and communication ’ and ‘ mobility and fatigue ’ . The dysphagia score fell significantly after intervention both in patients undergoing surgery alone and in those receiving palliative therapy . The activities of daily living question naire showed significant improvements in two parameters in the surgical group ( ‘ self‐care ’ and ‘ eating and drinking ’ ) and in none of the parameters assessed in the palliation group in 16 weeks . Quality ‐of‐life assessment is useful in assessing quality of care and patient well‐being after the diagnosis and treatment of oesophageal carcinoma BACKGROUND The aim of therapy for advanced esophageal cancer is relief of dysphagia with minimal treatment-related morbidity . This study assessed the efficacy of endoscopic intratumoral injection of cisplatin/epinephrine gel to relieve obstruction and improve swallowing . The gel is design ed to minimize diffusion of active drug away from the tumor injection site . METHODS Patients with inoperable esophageal cancer and dysphagia caused by exophytic esophageal tumor underwent up to 6 weekly endoscopic injections of the gel . Response was documented objective ly ( exophytic tumor volume , lumen size , dysphagia grade ) and subjectively ( achievement of treatment goal ) . RESULTS Twenty-four patients were treated . Primary evaluation criteria for 18 evaluable patients were as follows : dysphagia grade improved in 4 ( duration 30 to 45 days ) and stabilized in 11 ; lumen patency improved in 6 ( duration 29 to 56 days ) and stabilized in 10 ; exophytic tumor volume decreased in 8 ( duration 29 to 114 days ) . Eight patients felt that their ability to swallow improved . One patient with intramural and exophytic tumor developed a tracheoesophageal fistula , possibly related to treatment . Other complications were tolerable and self-limited . No nephrotoxicty or severe nausea/vomiting typical of systemic administration of cisplatin occurred . CONCLUSIONS Endoscopic injection of cisplatin/epinephrine gel is a straightforward procedure with st and ard equipment and techniques , which can provide palliation for patients with exophytic malignant tumors of the esophagus . Assessment of this method in conjunction with other therapeutic options such as brachytherapy is warranted SUMMARY Esophageal cancer often presents as advanced stage disease with a dismal prognosis , with only 10 - 15 % of patients surviving 5 years . Therefore , in a large proportion of patients , palliative treatment is the only option available . The aim of this study was to prospect ively compare the palliative effect of self-exp and able stent placement with that of endoluminal brachytherapy regarding the effect on quality of life and on specific symptoms . Sixty-five patients with advanced cancer of the esophagus or gastroesophageal junction were r and omized to treatment with either an Ultraflex exp and able stent or high-dose-rate endoluminal brachytherapy with 7 Gy x 3 given in 2 - 4 weeks . Clinical assessment and health-related quality of life ( HRQL ) were measured at inclusion and 1 , 3 , 6 , 9 and 12 months later . The HRQL was measured with st and ardized question naires ( European Organization for Research and Treatment of Cancer Quality of Life Question naire Core 30 , European Organization for Research and Treatment of Cancer Quality of Life Question naire Oesophageal Module and Hospital Anxiety and Depression Scale ) . Twenty-eight patients completed the stent treatment and 24 patients the brachytherapy . The group of patients treated with stent reported significantly better HRQL scores for dysphagia ( P < 0.05 ) at the 1-month follow-up , but most other HRQL scores , including functioning and symptom scales , deteriorated . Among brachytherapy-treated patients , improvement was found for the dysphagia-related scores at the 3-months follow-up , whereas other significant changes of scores were few . The median survival time was comparable in the two groups ( around 120 days ) . In conclusion , insertion of self-exp and able metal stents offered a more instant relief of dysphagia compared to endoluminal brachytherapy , but HRQL was more stable in the brachytherapy group PURPOSE In the r and omized , multinational phase II/III trial ( V325 ) of untreated advanced gastric cancer patients , the phase II part selected docetaxel , cisplatin , and fluorouracil ( DCF ) over docetaxel and cisplatin for comparison against cisplatin and fluorouracil ( CF ; reference regimen ) in the phase III part . PATIENTS AND METHODS Advanced gastric cancer patients were r and omly assigned to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 ( day 1 ) plus fluorouracil 750 mg/m2/d ( days 1 to 5 ) every 3 weeks or cisplatin 100 mg/m2 ( day 1 ) plus fluorouracil 1,000 mg/m2/d ( days 1 to 5 ) every 4 weeks . The primary end point was time-to-progression ( TTP ) . RESULTS In 445 r and omly assigned and treated patients ( DCF = 221 ; CF = 224 ) , TTP was longer with DCF versus CF ( 32 % risk reduction ; log-rank P < .001 ) . Overall survival was longer with DCF versus CF ( 23 % risk reduction ; log-rank P = .02 ) . Two-year survival rate was 18 % with DCF and 9 % with CF . Overall response rate was higher with DCF ( chi2 P = .01 ) . Grade 3 to 4 treatment-related adverse events occurred in 69 % ( DCF ) v 59 % ( CF ) of patients . Frequent grade 3 to 4 toxicities for DCF v CF were : neutropenia ( 82 % v 57 % ) , stomatitis ( 21 % v 27 % ) , diarrhea ( 19 % v 8 % ) , lethargy ( 19 % v 14 % ) . Complicated neutropenia was more frequent with DCF than CF ( 29 % v 12 % ) . CONCLUSION Adding docetaxel to CF significantly improved TTP , survival , and response rate in gastric cancer patients , but result ed in some increase in toxicity . Incorporation of docetaxel , as in DCF or with other active drug(s ) , is a new therapy option for patients with untreated advanced gastric cancer PURPOSE Therapy of patients with advanced gastric or gastroesophageal junction cancer should provide symptom relief and improve quality of life ( QOL ) because most patients are symptomatic at baseline . Using vali date d instruments , we prospect ively assessed QOL ( even after completion of protocol treatment ) as one of the secondary end points of the V325 phase III trial . PATIENTS AND METHODS Four hundred forty-five patients r and omly received either docetaxel 75 mg/m(2 ) and cisplatin 75 mg/m(2 ) each on day 1 plus fluorouracil 750 mg/m(2)/d continuous infusion on days 1 to 5 every 3 weeks ( DCF ) or cisplatin 100 mg/m(2 ) on day 1 plus fluorouracil 1,000 mg/m(2)/d continuous infusion on days 1 to 5 every 4 weeks ( CF ) . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) and , where available , the EuroQOL EQ-5D question naire were administered every 8 weeks from baseline until progression and then every 3 months . Time to definitive deterioration of QOL parameters was analyzed . RESULTS The proportions of patients having assessable EORTC QLQ-C30 and EQ-5D question naires at baseline were 86.0 % and 78.7 % with DCF , respectively , and 89.7 % and 92.8 % with CF , respectively . Time to 5 % deterioration of global health status ( primary end point ) significantly favored DCF over CF ( log-rank test , P = .01 ) . QOL was preserved longer for patients on DCF than those on CF for all time to deterioration analyses , demonstrating the statistical superiority of DCF compared with CF . CONCLUSION V325 represents the largest trial with the longest prospect ively controlled evaluations of QOL during protocol chemotherapy and follow-up in patients with advanced gastric or gastroesophageal junction cancer . In V325 , advanced gastric or gastroesophageal junction cancer patients receiving DCF not only had statistically improved overall survival and time to tumor-progression , but they also had better preservation of QOL compared with patients receiving CF The results of chemotherapy for patients with esophagogastric carcinoma have generally been modest but regimens developed more recently have produced higher response rates , and rekindled interest in neoadjuvant chemotherapy . One such regimen is epirubicin , cisplatin , and 5‐fluorouracil ( ECF ) . This study evaluates its efficacy , toxicity , impact on quality of life ( QL ) , and impact on survival in a large consecutive series of patients with metastatic and locally advanced disease ( LAD ) The outcomes of treatment of oesophageal cancer include traditional biological and physical measures , such as mortality and morbidity data , disease free and overall survival , clinical and pathological response rates and symptom control . Such factors are essential and should be recorded prospect ively for clinical audit . Using this type of information alone to evaluate effectiveness of treatment is inadequate , however , because the diagnosis and treatment of oesophageal cancer has a major impact on functional well-being ( including psycho-social function ) , general health perceptions and overall quality of life (QL)/satisfaction with health and health care . These aspects of patients ' well-being need to be considered , in addition to st and ard outcomes in the evaluation of treatment of oesophageal cancer . Recent needs to judge the economic efficiency of health care by comparing health outcomes with costs may also be part of treatment appraisal . This article review s surgical , oncological , patient-based and economic outcomes in oesophageal cancer PURPOSE We report the results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin , and protracted venous-infusion fluorouracil ( PVI 5-FU ) ( ECF ) with the combination of mitomycin , cisplatin , and PVI 5-FU ( MCF ) in previously untreated patients with advanced esophagogastric cancer . PATIENTS AND METHODS Five hundred eighty patients with adenocarcinoma , squamous carcinoma , or undifferentiated carcinoma were r and omized to receive either ECF ( epirubicin 50 mg/m(2 ) every 3 weeks , cisplatin 60 mg/m(2 ) every 3 weeks and PVI 5-FU 200 mg/m(2)/d ) or MCF ( mitomycin 7 mg/m(2 ) every 6 weeks , cisplatin 60 mg/m(2 ) every 3 weeks , and PVI 5-FU 300 mg/m(2)/d ) and analyzed for survival , response , toxicity , and quality of life ( QOL ) . RESULTS The overall response rate was 42.4 % ( 95 % confidence interval [ CI ] , 37 % to 48 % ) with ECF and 44.1 % ( 95 % CI , 38 % to 50 % ) with MCF ( P = .692 ) . Toxicity was tolerable , and there were only two toxic deaths . ECF result ed in more grade 3/4 neutropenia and grade 2 alopecia , but MCF caused more thrombocytopenia and plantar-palmar erythema . Median survival was 9.4 months with ECF and 8.7 months with MCF ( P = .315 ) ; at 1 year , 40.2 % ( 95 % CI , 34 % to 46 % ) of ECF and 32.7 % ( 95 % CI , 27 % to 38 % ) of MCF patients were alive . Median failure-free survival was 7 months with both regimens . Global QOL scores were better with ECF at 3 and 6 months . CONCLUSION This study confirms response , survival , and QOL benefits of ECF observed in a previous r and omized study . The equivalent efficacy of MCF was demonstrated , but QOL was superior with ECF . ECF remains one of the reference treatments for advanced esophagogastric cancer |
10,985 | 15,452,400 | Conclusions : A systematic review and meta- analysis demonstrated that neonatal mortality is significantly reduced when depressed newly born infants are resuscitated with ambient air instead of pure oxygen .
For infants with low 1-min Apgar score ( < 4 ) , no significant difference in neonatal mortality was found .
Recovery was faster in infants resuscitated with 21 % O2 than 100 % O2 | Background : It is discussed whether depressed newborn infants should be resuscitated with room air or 100 % O2 .
Objective : To perform a systematic review and meta- analysis including studies that report resuscitation of depressed newly born infants with 21 or 100 % O2 . | Objective . Birth asphyxia represents a serious problem worldwide , result ing in ∼1 million deaths and an equal number of serious sequelae annually . It is therefore important to develop new and better ways to treat asphyxia . Resuscitation after birth asphyxia traditionally has been carried out with 100 % oxygen , and most guidelines and textbooks recommend this ; however , the scientific background for this has never been established . On the contrary , theoretic considerations indicate that resuscitation with high oxygen concentrations could have detrimental effects . We have performed a series of animal studies as well as one pilot study indicating that resuscitation can be performed with room air just as efficiently as with 100 % oxygen . To test this more thoroughly , we organized a multicenter study and hypothesized that room air is superior to 100 % oxygen when asphyxiated newborn infants are resuscitated . Methodology . In a prospect i ve , international , controlled multicenter study including 11 centers from six countries , asphyxiated newborn infants with birth weight > 999 g were allocated to resuscitation with either room air or 100 % oxygen . The study was not blinded , and the patients were allocated to one of the two treatment groups according to date of birth . Those born on even date s were resuscitated with room air and those born on odd date s with 100 % oxygen . Informed consent was not obtained until after the initial resuscitation , an arrangement in agreement with the new proposal of the US Food and Drug Administration 's rules governing investigational drugs and medical devices to permit clinical research on emergency care without the consent of subjects . The protocol was approved by the ethical committees at each participating center . Entry criterion was apnea or gasping with heart rate < 80 beats per minute at birth necessitating resuscitation . Exclusion criteria were birth weight < 1000 g , lethal anomalies , hydrops , cyanotic congenital heart defects , and stillbirths . Primary outcome measures were death within 1 week and /or presence of hypoxic – ischemic encephalopathy , grade II or III , according to a modification of Sarnat and Sarnat . Secondary outcome measures were Apgar score at 5 minutes , heart rate at 90 seconds , time to first breath , time to first cry , duration of resuscitation , arterial blood gases and acid base status at 10 and 30 minutes of age , and abnormal neurologic examination at 4 weeks . The existing routines for resuscitation in each participating unit were followed , and the ventilation techniques described by the American Heart Association were used as guidelines aim ing at a frequency of manual ventilation of 40 to 60 breaths per minute . Results . Forms for 703 enrolled infants from 11 centers were received by the steering committee . All 94 patients from one of the centers were excluded because of violation of the inclusion criteria in 86 of these . Therefore , the final number of infants enrolled in the study was 609 ( from 10 centers ) , with 288 in the room air group and 321 in the oxygen group . Median ( 5 to 95 percentile ) gestational ages were 38 ( 32.0 to 42.0 ) and 38 ( 31.1 to 41.5 ) weeks ( NS ) , and birth weights were 2600 ( 1320 to 4078 ) g and 2560 ( 1303 to 3900 ) g ( NS ) in the room air and oxygen groups , respectively . There were 46 % girls in the room air and 41 % in the oxygen group ( NS ) . Mortality in the first 7 days of life was 12.2 % and 15.0 % in the room air and oxygen groups , respectively ; adjusted odds ratio ( OR ) = 0.82 with 95 % confidence intervals ( CI ) = 0.50–1.35 . Neonatal mortality was 13.9 % and 19.0 % ; adjusted OR = 0.72 with 95 % CI = 0.45–1.15 . Death within 7 days of life and /or moderate or severe hypoxic – ischemic encephalopathy ( primary outcome measure ) was seen in 21.2 % in the room air group and in 23.7 % in the oxygen group ; OR = 0.94 with 95 % CI = 0.63–1.40 . Heart rates did not differ between the two groups at any time point and were ( mean ± SD ) 90 ± 31 versus 93 ± 33 beats per minute at 1 minute and 110 ± 27 versus 113 ± 30 beats per minute at 90 seconds in the room air and oxygen groups , respectively . Apgar scores at 1 minute ( median and 5 to 95 percentiles ) were significantly higher in the room air group ( 5 [ 1 to 6.7 ] ) than in the oxygen group ( 4 [ 1 to 7 ] ) ; however , at 5 minutes there were no significant differences , with 8 ( 4 to 9 ) versus 7 ( 3 to 9 ) . There were significantly more infants with very low 1-minute Apgar scores ( < 4 ) in the oxygen group ( 44.4 % ) than in the room air group ( 32.3 % ) . There also were significantly more infants with 5-minute Apgar score < 7 in the oxygen group ( 31.8 % ) than in the room air group ( 24.8 % ) . There were no differences in acid base status or Sao 2during the observation period between the two groups . Mean ( SD ) Pao 2 was 31 ( 17 ) versus 30 ( 22 ) mm Hg in cord blood in the room air and oxygen groups , respectively ( NS ) . At 10 minutes Pao 2 was 76 ( 32 ) versus 87 ( 49 ) mm Hg ( NS ) , and at 30 minutes , the values were 74 ( 29 ) versus 89 ( 42 ) mm Hg in the room air and oxygen groups , respectively . Median ( 95 % CI ) time to first breath was 1.1 ( 1.0–1.2 ) minutes in the room air group versus 1.5 ( 1.4 to 1.6 ) minutes in the oxygen group . Time to the first cry also was in mean 0.4 minute shorter in the room air group compared with the oxygen group . In the room air group , there were 25.7 % so-called resuscitation failures ( bradycardia and /or central cyanosis after 90 seconds ) that were switched to 100 % oxygen after 90 seconds . The percentage of resuscitation failures in the oxygen group was 29.8 % . Conclusions . This study with patients enrolled primarily from developing countries indicates that asphyxiated newborn infants can be resuscitated with room air as efficiently as with pure oxygen . In fact , time to first breath and first cry was significantly shorter in room air- versus oxygen-resuscitated infants . Resuscitation with 100 % oxygen may depress ventilation and therefore delay the first breath . More studies are needed confirming these results before resuscitation guidelines are changed ABSTRACT : To test the hypothesis that room air is superior to 100 % oxygen when asphyxiated newborns are resuscitated , 84 neonates ( birth weight > 999 g ) with heart rate < 80 and /or apnea at birth were allocated to be resuscitated with either room air ( n = 42 ) or 100 % oxygen ( n = 42 ) . Serial , unblinded observations of heart rates at 1 , 3 , 5 , and 10 min and Apgar scores at 1 min revealed no significant differences between the two groups . At 5 min , median ( 25th and 75th percentile ) Apgar scores were higher in the room air than in the oxygen group [ 8 ( 7–9 ) versus 7 ( 6–8 ) , p = 0.03 ] . After the initial resuscitation , arterial partial pressure of oxygen , pH , and base excess were comparable in the two groups . Assisted ventilation was necessary for 2.4 ( 1.5–3.4 ) min in the room air group and 3.0 ( 2.0–4.0 ) min in the oxygen group ( p = 0.14 ) . The median time to first breath was 1.5 ( 1.0–2.0 ) min in both the room air and oxygen groups ( p = 0.59 ) , and the time to first cry was 3.0 ( 2.0–4.0 ) min and 3.5 ( 2.5–5.5 ) min in the room air and oxygen groups , respectively ( p = 0.19 ) . Three neonates in the room air group and four in the oxygen group died in the neonatal period . At 28 d , 72 of the 77 surviving neonates were available for follow-up ( 36 in each group ) , and none had any neurologic sequelae . This preliminary study did not provide conclusive evidence that room air is superior to 100 % oxygen in the resuscitation of asphyxiated newborns , although it indicated that room air is as effective as 100 % oxygen . Additional trials with increased numbers of patients are necessary before deciding whether room air or oxygen should be used in clinical practice OBJECTIVE To follow-up children who had been resuscitated at birth with either 21 % or 100 % oxygen ( O2 ) . METHODS A multicenter study with 10 participating centers recruited 609 infants to the Resair 2 study where resuscitation was performed with either 21 % or 100 % O2 . A follow-up between ages 18 and 24 months was performed . However , during follow-up registration , it was found that 18 infants had been enrolled twice in the original Resair 2 study with different registration numbers , leaving 591 enrolled in the Resair 2 study and 410 enrolled in the 7 centers participating in the follow-up . Of these 410 infants , 79 died ( 76 in the neonatal and 3 in the postneonatal period ) . Furthermore , for 8 infants informed consent was not obtained , leaving 323 eligible for follow-up . Of these , 213 infants ( 66 % ) were followed-up : 91 ( 62 % ) had been resuscitated with 21 % O2 , and 122 ( 69 % ) with 100 % O2 . At a median age of 22 and 20 months ( not significant ) in the 21 % and 100 % groups , respectively , a simple question naire was filled out and neurologic assessment was performed in addition to measuring anthropometric data . RESULTS There were no significant differences in weight , height , or head circumference between the 2 groups . Cerebral palsy developed in 10 % and 7 % , respectively , in the 2 groups ( not significant ) . In total , 11 cases ( 12 % ) in the 21 % versus 11 cases ( 9 % ) in the 100 % O(2 ) group ( odds ratio : 1.39 , 95 % confidence interval : 0.57 - 3.36 ) developed cerebral palsy and /or mental or other delay . Furthermore , it was concluded that 14 ( 15 % ) in the 21 % group and 12 ( 10 % ) in the 100 % group were not normal ( odds ratio : 1.67 , 95 % confidence interval : 0.73 - 3.80 ) . CONCLUSIONS There were no significant differences in somatic growth or neurologic h and icap at an age of 18 to 24 months in infants resuscitated with either 21 % or 100 % O2 at birth . Based on these data , resuscitation with ambient air seems to be safe , at least in most cases . More studies are needed to settle this issue We describe a prospect i ve cross-sectional survey over a 12-month period in the principal maternity hospital of Kathm and u , Nepal , where over 50 % of the local population deliver . The study aim was to estimate the contribution of birth asphyxia to perinatal mortality in this setting . During 1995 , there were 14,371 livebirths and 400 stillbirths , a total stillbirth rate of 27 per 1000 total births . The fresh term ( 2000 g or more ) stillbirth rate was 8.5 per 1000 total births [ 95 % CI 7.1 , 10.1 ] . Ninety-two cases of neonatal encephalopathy ( NE ) affecting term infants were detected ( excluding those due to congenital malformations , hypoglycaemia and early neonatal sepsis ) . The birth prevalence of NE was 6.4 per 1000 livebirths [ 95 % CI 5.2 , 7.8 ] . There was evidence of intrapartum compromise in 63 ( 68 % ) of the cases of NE and 65 ( 76 % ) of the stillbirths , but only in 12 ( 12 % ) of controls . The cause-specific early neonatal mortality rate for NE was 2.1 per 1000 livebirths [ 95 % CI 1.4 , 3.0 ] . Combining the NE deaths and fresh stillbirths gives an upper estimate for term birth asphyxia perinatal mortality rate of 10.8 per 1000 total births [ 95 % CI 9.2 , 12.6 ] , 24 % of all perinatal deaths before hospital discharge . This study suggests that birth asphyxia remains an important cause of perinatal mortality in developing countries . The paper discusses the pros and cons of different strategies to reduce birth asphyxia in low-income countries Background . Traditionally , asphyxiated newborn infants have been ventilated using 100 % oxygen . However , a recent multinational trial has shown that the use of room air was just as efficient as pure oxygen in securing the survival of severely asphyxiated newborn infants . Oxidative stress markers in moderately asphyxiated term newborn infants resuscitated with either 100 % oxygen or room air have been studied for the first time in this work . Methods . Eligible term neonates with perinatal asphyxia were r and omly resuscitated with either room air or 100 % oxygen . The clinical parameters recorded were those of the Apgar score at 1 , 5 , and 10 minutes , the time of onset of the first cry , and the time of onset of the sustained pattern of respiration . In addition , reduced and oxidized glutathione concentrations and antioxidant enzyme activities ( superoxide dismutase , catalase , and glutathione peroxidase ) were determined in blood from the umbilical artery during delivery and in peripheral blood at 72 hours and at 4 weeks ' postnatal age . Results . Our results show that the room-air resuscitated ( RAR ) group needed significantly less time to first cry than the group resuscitated with 100 % oxygen ( 1.2 ± 0.6 minutes vs 1.7 ± 0.5 ) . Moreover , the RAR group needed less time undergoing ventilation to achieve a sustained respiratory pattern than the group resuscitated with pure oxygen ( 4.6 ± 0.7 vs 7.5 ± 1.8 minutes ) . The reduced-to-oxidized-glutathione ratio , which is an accurate index of oxidative stress , of the RAR group ( 53 ± 9 ) at 28 days of postnatal life showed no differences with the control nonasphyxiated group ( 50 ± 12 ) . However , the reduced-to-oxidized-glutathione ratio of the 100 % oxygen-resuscitated group ( OxR ) ( 15 ± 5 ) was significantly lower and revealed protracted oxidative stress . Furthermore , the activities of superoxide dismutase and catalase in erythrocytes were 69 % and 78 % higher , respectively , in the OxR group than in the control group at 28 days of postnatal life . Thus , this shows that these antioxidant enzymes , although higher than in controls , could not cope with the ongoing generation of free radicals in the OxR group . However , there were no differences in antioxidant enzyme activities between the RAR group and the control group at this stage . Conclusions . There are no apparent clinical disadvantages in using room air for ventilation of asphyxiated neonates rather than 100 % oxygen . Furthermore , RAR infants recover more quickly as assessed by Apgar scores , time to the first cry , and the sustained pattern of respiration . In addition , neonates resuscitated with 100 % oxygen exhibit biochemical findings reflecting prolonged oxidative stress present even after 4 weeks of postnatal life , which do not appear in the RAR group . Thus , the current accepted recommendations for using 100 % oxygen in the resuscitation of asphyxiated newborn infants should be further discussed and investigated OBJECTIVE To compare the short-term efficacy of room air versus 100 % oxygen for resuscitation of asphyxic newborns at birth . DESIGN Multicentric quasi r and omized controlled trial . SETTING Teaching hospitals . INCLUSION CRITERIA Asphyxiated babies weighing greater than 1000 grams , with heart rate less than 100 per min and /or apnea , unresponsive to nasopharyngeal suction and tactile stimuli and having no lethal abnormalities . INTERVENTION Asphyxiated neonates born on odd date s were given oxygen and those on even date s room air for resuscitation . OUTCOME MEASURES Primary : Apgar score at 5 minutes ; Secondary : Mortality and Hypoxic ischaemic encephalopathy ( HIE ) during first 7 days of life . RESULTS A total of 431 asphyxiated babies , 210 in the room air and 221 in 100 % oxygen group were enrolled for the study . Both the groups were comparable for maternal , intrapartum and neonatal characteristics . The heart rates in room air and 100 % oxygen groups were comparable at 1 minute ( 94 bpm and 88 bpm ) , 5 minutes ( 131 bpm and 131 bpm ) and 10 minutes ( 135 bpm and 136 bpm ) . Median apgar scores at 5 min [ 7 versus 7 ] and 10 minutes [ 8 versus 8 ] , in the room air and oxygen groups respectively , were found to be comparable . Median time to first breath ( 1.5 versus 1.5 minutes ) was similar in the room air and oxygen group . Median time to first cry ( 2.0 versus 3.0 minutes ) and median duration of resuscitation ( 2.0 versus 3 minutes ) were significantly shorter in the room air group . The number of babies with HIE during first seven days of life in the two treatment groups ( 35.7 % babies in room air and 37.1 % in the 100 % oxygen group ) were similar . There was also no statistically significant difference in the overall and asphyxia related mortality in the two treatment groups ( 12.4 % and 10.0 % in room air versus 18.1 % and 13.6 % in oxygen group ) . CONCLUSION Room air appears as good as 100 % oxygen for resuscitation of asphyxic newborn babies at birth The aim of this study was to investigate whether reoxygenation with 21 % O2 rather than 100 % O2 results in reduced hydrogen peroxide ( H2O2 ) concentrations in neutrophils ( PMN ) . Piglets ( 2–4 d old ) exposed to severe hypoxia ( inspired fraction of oxygen , 0.08 ) were r and omized to resuscitation with 21 ( n = 13 ) or 100 % O2 ( n = 12 ) . Five animals served as controls . H2O2 concentrations in PMN in terms of rhodamine 123 ( Rho 123 ) fluorescence intensity from arterial and superior sagittal sinus blood were quantified by flow cytometry . Laser Doppler flowmetry ( LDF ) was used to assess cortical blood perfusion . During hypoxia , Rho 123 increased in arterial PMN in both study groups by 15 and 32 % , respectively ( p < 0.05 ) . In cerebral venous PMN , the increase was less dominant ( p = 0.06 ) . Reoxygenation with 100 or 21 % O2 had no different effect on Rho 123 in arterial PMN . In cerebral venous PMN , Rho 123 was approximately 40 % higher after 60 min and 30 % higher after 120 min compared with corresponding data in the 21 % O2 group ( p < 0.05 ) , which were close to baseline levels . Further , O2 treatment in both groups induced PMN accumulation in arterial blood ( p < 0.05 ) . Laser Doppler flowmetry signals increased during transient hypoxia ( p < 0.0001 compared with baseline ) and were normalized after reoxygenation in both study groups . In conclusion , arterial and cerebral venous H2O2 concentration in PMN tended to increase during hypoxia . During reoxygenation , H2O2 concentration in PMN in the cerebral circulation was low with 21 % O2 but remained high with 100 % O2 ventilation . We speculate that oxygen should be reintroduced with more caution during neonatal resuscitation In this article we present results from the Resair 2 study in which we tested whether room air is more efficient than 100 % oxygen in newborn resuscitation . Eleven participating centres in Egypt , Estonia , India , Norway , Philippines , and Spain recruited 609 infants who needed resuscitation at birth ; of these , 288 were resuscitated with room air and 321 with 100 % oxygen . There were no differences between the two groups with regard to outcome . One minute Apgar scores were significantly lower in the oxygen group than in the room air group . Median time to first breath was significantly delayed with 24 seconds in the oxygen group compared with the room air group . It seems that 100 % oxygen depresses ventilation in newborn infants . Room air is as safe and efficient as 100 % oxygen at least in most cases of newborn resuscitation . Further studies confirming these results are needed before new resuscitation routines are implemented OBJECTIVE To test the hypothesis that resuscitation of asphyxiated infants with pure oxygen causes hyperoxemia and oxidative stress . Study design Asphyxiated term newborn infants ( n = 106 ) were r and omly resuscitated with room air ( RAR = 51 ) or 100 % oxygen ( OxR = 55 ) . The Apgar score , time of the first cry , and establishment of a sustained pattern of respiration were recorded . Assays performed included : blood gases ; reduced glutathione ( GSH ) and oxidized glutathione ( GSSG ) in whole blood ; glutathione-related enzyme activities ; and superoxide dismutase activity ( SOD ) in erythrocytes . RESULTS The RAR group needed less time of ventilation for resuscitation ( 5.3 + /- 1.5 vs 6.8 + /- 1.2 min ; P < .05 ) . Pure oxygen caused hyperoxemia ( PO(2 ) , 126.3 + /- 21.8 mm Hg ) that did not occur with the use of room air ( PO(2 ) , 72.2 + /- 6.8 mm Hg ) . GSH was decreased and GSSG , the glutathione cycle enzymes , and SOD activities were increased in both asphyxiated groups . However , the 100 % oxygen-resuscitated group showed significantly greater alterations that correlated positively with hyperoxemia . CONCLUSIONS Asphyxia causes oxidative stress in the perinatal period , and resuscitation with 100 % oxygen causes hyperoxemia and increased oxidative stress . Because there are no advantages to resuscitation with 100 % oxygen , room air may be preferred under certain circumstances for the resuscitation of asphyxiated neonates |
10,986 | 30,523,513 | The prophylactic use of carvedilol exerted no impact on the early asymptomatic LVEF decrease but seemed to attenuate the frequency of clinical ly overt cardiotoxicity and prevent ventricular remodeling | Some r and omized controlled trials ( RCTs ) have tested the efficacy of beta-blockers as prophylactic agents on cancer therapy-induced cardiotoxicity ; however , the quality of this evidence remains undetermined .
This systematic review and meta- analysis study aims to evaluate the prophylactic effects of beta-blockers , especially carvedilol , on chemotherapy-induced cardiotoxicity . | BACKGROUND Anthracycline ( ANT ) chemotherapy is associated with cardiotoxicity . Prevention with β-blockers remains controversial . OBJECTIVES This prospect i ve , r and omized , double-blind , placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity . METHODS The authors r and omized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction ( LVEF ) referred for ANT ( 240 mg/m2 ) to receive carvedilol or placebo until chemotherapy completion . The primary endpoint was prevention of a ≥10 % reduction in LVEF at 6 months . Secondary outcomes were effects of carvedilol on troponin I , B-type natriuretic peptide , and diastolic dysfunction . RESULTS Primary endpoint occurred in 14 patients ( 14.5 % ) in the carvedilol group and 13 patients ( 13.5 % ) in the placebo group ( p = 1.0 ) . No differences in changes of LVEF or B-type natriuretic peptide were noted between groups . A significant difference existed between groups in troponin I levels over time , with lower levels in the carvedilol group ( p = 0.003 ) . Additionally , a lower incidence of diastolic dysfunction was noted in the carvedilol group ( p = 0.039 ) . A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group ( 44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm ; p = 0.057 ) . CONCLUSIONS In this largest clinical trial of β-blockers for prevention of cardiotoxicity under contemporary ANT dosage , the authors noted a 13.5 % to 14.5 % incidence of cardiotoxicity . In this scenario , carvedilol had no impact on the incidence of early onset of LVEF reduction . However , the use of carvedilol result ed in a significant reduction in troponin levels and diastolic dysfunction . ( Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [ CECCY ] ; NCT01724450 ) Purpose The primary toxicity of trastuzumab therapy for human epidermal growth factor receptor 2-overexpressing ( HER2-positive ) breast cancer is dose-independent cardiac dysfunction . Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure . We hypothesized that angiotensin-converting enzyme inhibitors and β-blockers could prevent trastuzumab-related cardiotoxicity . Patients and Methods In this double-blinded , placebo-controlled trial , patients with HER2-positive early breast cancer were r and omly assigned to receive treatment with perindopril , bisoprolol , or placebo ( 1:1:1 ) for the duration of trastuzumab adjuvant therapy . Patients underwent cardiac magnetic resonance imaging at baseline and post-cycle 17 for the determination of left ventricular volumes and left ventricular ejection fraction ( LVEF ) . Cardiotoxicity was evaluated as the change in indexed left ventricular end diastolic volume and LVEF . Results Thirty-three patients received perindopril , 31 received bisoprolol , and 30 received placebo . Baseline demographic , cancer , and cardiovascular profiles were similar between groups . Study drugs were well tolerated with no serious adverse events . After 17 cycles of trastuzumab , indexed left ventricular end diastolic volume increased in patients treated with perindopril ( + 7 ± 14 mL/m2 ) , bisoprolol ( + 8 mL ± 9 mL/m2 ) , and placebo ( + 4 ± 11 mL/m2 ; P = .36 ) . In secondary analyses , trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated patients ( -1 ± 5 % ) relative to the perindopril ( -3 ± 4 % ) and placebo ( -5 ± 5 % ) groups ( P = .001 ) . Perindopril and bisoprolol use were independent predictors of maintained LVEF on multivariable analysis . Conclusion Perindopril and bisoprolol were well tolerated in patients with HER2-positive early breast cancer who received trastuzumab and protected against cancer therapy-related declines in LVEF ; however , trastuzumab-mediated left ventricular remodeling-the primary outcome -was not prevented by these pharmacotherapies BACKGROUND The use of antracycline ( ANT ) in breast cancer has been associated with adverse cardiac events . Two-dimensional ( 2D ) strain imaging ( SI ) can provide a more sensitive measure of altered left ventricular ( LV ) systolic function . We aim ed to evaluate the preventive effect of carvedilol administration assessed by SI in a patient with breast cancer treated with ANT . METHODS Patients receiving ANT were r and omly assigned to the carvedilol- or placebo-receiving group . Each received an echocardiographic examination with conventional 2D echocardiography , pulsed tissue Doppler , and 2D SI prior to and 6 months post ANT treatment . RESULTS During the 6-month follow-up period there were no patient deaths or interrupted chemotherapy treatments due to doxorubicin-induced cardiotoxicity . Both left ventricular ejection fraction ( LVEF ) and fractional shortening ( FS ) were within normal limits for all patients before and after ANT therapy . EF , FS and LV dimensions were measured using M-mode echocardiography and found to be similar in both groups before and after ANT therapy . The mean EF , FS , and LV echocardiograph baseline and control dimensions were similar in both groups after 6 months . Though baseline SI parameters were similar between the groups , there was a significant decrease in LV basal septal and basal lateral peak systolic strain in the control group compared to the carvedilol group . CONCLUSIONS These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT 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 : Anthracyclines ( ANTs ) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer . We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity . Methods : In this r and omized , single-blind , placebo-controlled study , 91 women with recently diagnosed breast cancer undergoing ANT therapy were r and omly assigned to groups treated with either carvedilol ( n = 46 ) or placebo ( n = 45 ) . Echocardiography was performed before and at 6 months after r and omization , and absolute changes in the mean left ventricular ejection fraction , left ventricular end diastolic volume , and left ventricular end systolic volume were determined . Furthermore , the percentage change in the left atrial ( LA ) diameter and other variables of left ventricular ( LV ) diastolic function , such as transmitral Doppler parameters , including early ( E wave ) and late ( A wave ) diastolic velocities , E/A ratio and E wave deceleration time , pulmonary venous Doppler signals , including forward systolic ( S wave ) and diastolic ( D wave ) velocities into LA , late diastolic atrial reversal velocity , and early diastolic tissue Doppler mitral annular velocity ( e ' ) were measured . In addition , tissue Doppler mitral annular systolic ( s ' ) velocity , as a marker of early stage of LV systolic dysfunction , E/e ' ratio , as a determinant of LV filling pressure , and troponin I level , as a marker of myocardial necrosis were measured . Results : At the end of follow-up period , left ventricular ejection fraction did not change in the carvedilol group . However , this parameter was significantly reduced in the control group ( P < 0.001 ) . Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group . In pulse Doppler studies , pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group . Moreover , a significant decrease in the mitral annuli early diastolic ( e ' ) and peak systolic ( s ' ) velocities and a significant increase in the E ( the peak early diastolic velocity)/e ' ratio in the control group were also observed . However , none of these variables were adversely changed at the end of follow-up in the carvedilol group . Furthermore , the TnI level was significantly higher in the control group than in the carvedilol group ( P = 0.036 ) at 30 days after the initiation of chemotherapy . Conclusions : Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity , even at low doses Abstract Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction . We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker c and esartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction ( LVEF ) associated with adjuvant , anthracycline-containing regimens with or without trastuzumab and radiation . Methods and results In a 2 × 2 factorial , r and omized , placebo-controlled , double-blind trial , we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker c and esartan cilexetil , the β-blocker metoprolol succinate , or matching placebos in parallel with adjuvant anticancer therapy . The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging . A priori , a change of 5 percentage points was considered clinical ly important . There was no interaction between c and esartan and metoprolol treatments ( P = 0.530 ) . The overall decline in LVEF was 2.6 ( 95 % CI 1.5 , 3.8 ) percentage points in the placebo group and 0.8 ( 95 % CI −0.4 , 1.9 ) in the c and esartan group in the intention-to-treat analysis ( P-value for between-group difference : 0.026 ) . No effect of metoprolol on the overall decline in LVEF was observed . Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation , concomitant treatment with c and esartan provides protection against early decline in global left ventricular function BACKGROUND We aim ed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients . METHODS In this small , prospect i ve , double-blind study , we r and omly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5 mg daily ( n=27 ) or placebo ( n=18 ) . Echocardiographic measurements and N-terminal pro-brain natriuretic peptide ( NT-pro-BNP ) levels were obtained at baseline and at 6-month of chemotherapy . RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline . At 6-month , the left ventricular ( LV ) end-systolic and end-diastolic diameters increased in the placebo group ( LVESD : 29.7 ± 3.4 to 33.4 ± 4.5 mm ; LVEDD : 47.2 ± 3.8 to 52.0 ± 4.6 mm , p=0.01 for both ) but remained unchanged in the nebivolol group ( LVESD : 30.4 ± 3.5 to 31.0 ± 3.6 mm , p=0.20 ; LVEDD : 47.0 ± 4.4 to 47.1 ± 4.0 mm , p=0.93 ) . The placebo group also had lower LVEF than the nebivolol group ( 57.5 ± 5.6 % vs. 63.8 ± 3.9 % , p=0.01 ) at 6-month . NT-pro-BNP level remained static in the nebivolol group ( 147 ± 57 to 152 ± 69 pmol/l , p=0.77 ) while it increased in the placebo group ( 144 ± 66 to 204 ± 73 pmol/l , p=0.01 ) . CONCLUSIONS Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients Background & objectives : Adriamycin though considered as an effective anticancer drug , leads to irreversible cardiomyopathy ( CMP ) and congestive heart failure ( CHF ) . The aim of this study was to determine the protective effect of carvedilol in adriamycin (ADR)-induced cardiomyopathy ( CMP ) in cancer patients . Methods : Patients with lymphoreticular malignancy in whom ADR therapy was planned were r and omized into two groups : carvedilol and control . Twenty seven patients each were enrolled in carvedilol and control groups . In the carvedilol group , 12.5 mg once daily oral carvedilol was given during six months . The patients were evaluated by echocardiography before and after chemotherapy . Left ventricular ejection fraction ( EF ) and systolic and diastolic diameters were calculated . Results : At six months of follow up , six patients in the carvedilol group and five in the control group had died . The mean EF ( 63.19 vs. 63.88 % ) and fraction shortening ( FS ) ( 34 vs. 34.6 ) of the carvedilol group were similar at follow up , but in the control group , the mean EF ( 67.27 vs. 60.82 % , P=0.003 ) and FS ( 38.48 vs. 34.6 , P<0.05 ) at control echocardiography were significantly lower . In carvedilol group , both systolic and diastolic diameters were not changed , but in control group , systolic diameters were significantly increased compared with basal measures ( left ventricular end systolic diameter = 28.26±5.50 mm vs. 31.25± 6.50 mm ; P < 0.05 ) . Interpretation & conclusions : Prophylactic use of carvedilol in patients receiving anthracycline protected systolic functions of the left ventricle . Carvedilol can be a potential drug which can ameliorate ADR-induced CMP OBJECTIVES The aim of this study was to determine the protective effect of carvedilol in anthracycline (ANT)-induced cardiomyopathy ( CMP ) . BACKGROUND Despite its broad effectiveness , ANT therapy is associated with ANT-induced CMP . Recent animal studies and experimental observations showed that carvedilol prevented development of CMP due to chemotherapeutics . However , there is no placebo-controlled clinical trial concerning prophylactic carvedilol use in preventing ANT-induced CMP . METHODS Patients in whom ANT therapy was planned were r and omized to administration of carvedilol or placebo . We enrolled 25 patients in carvedilol and control groups . In the carvedilol group , 12.5 mg once-daily oral carvedilol was given during 6 months . The patients were evaluated with echocardiography before and after chemotherapy . Left ventricular ejection fraction ( EF ) and systolic and diastolic diameters were calculated . RESULTS At the end of 6 months of follow-up , 1 patient in the carvedilol group and 4 in the control group had died . Control EF was below 50 % in 1 patient in the carvedilol group and in 5 in the control group . The mean EF of the carvedilol group was similar at baseline and control echocardiography ( 70.5 vs. 69.7 , respectively ; p = 0.3 ) , but in the control group the mean EF at control echocardiography was significantly lower ( 68.9 vs. 52.3 ; p < 0.001 ) . Both systolic and diastolic diameters were significantly increased compared with basal measures in the control group . In Doppler study , whereas E velocities in the carvedilol group decreased , E velocities and E/A ratios were significantly reduced in the control group . CONCLUSIONS Prophylactic use of carvedilol in patients receiving ANT may protect both systolic and diastolic functions of the left ventricle BACKGROUND Assessment of left ventricular systolic function is necessary during trastuzumab-based chemotherapy because of potential cardiotoxicity . Deformation indices have been proposed as an adjunct to clinical risk factors and ejection fraction ( EF ) , but the optimal parameter and optimal cutoffs are undefined . The aim of this study was to determine the best means of early detection of subsequent reduction of EF in patients with breast cancer treated with trastuzumab . METHODS Eighty-one consecutive women ( mean age , 50 ± 11 years ) receiving trastuzumab were prospect ively studied , 37 of whom received concurrent anthracyclines . Conventional echocardiographic indices ( mitral annular systolic [ s ' ] and diastolic [ e ' ] velocities ) and myocardial deformation indices ( global longitudinal peak systolic strain [ GLS ] , global longitudinal peak systolic strain rate [ GLSR-S ] , and global longitudinal early diastolic strain rate [ GLSR-E ] ) were measured at baseline and at 6 and 12 months . Cardiotoxicity was defined as a > 10 % decline as a percentage of baseline EF in 12 months . RESULTS In the 24 patients ( 30 % ) who later developed cardiotoxicity , myocardial deformation indices decreased at 6 months ( GLS , P < .001 ; GLSR-S , P = .009 ; GLSR-E , P = .002 vs baseline ) , but e ' was unchanged . The strongest predictor of cardiotoxicity was ΔGLS ( area under the curve , 0.84 ) ; an 11 % reduction ( 95 % confidence interval , 8.3%-14.6 % ) was the optimal cutoff , with sensitivity of 65 % and specificity of 94 % . In sequential models , the clinical model ( χ(2 ) = 10.2 ) was improved by GLSR-S ( χ(2 ) = 14.7 , P = .03 ) and even more so by GLSR-E ( χ(2 ) = 18.0 , P = .005 ) or GLS ( χ(2 ) = 21.3 , P = .0008 ) . Discrimination improvement by adding GLS was confirmed by an integrated discrimination improvement of 18.6 % ( 95 % confidence interval , 8.6%-28.6 % ; P = .0003 ) . A net 29 % of the patients without events were reclassified into lower risk categories , and a net 48 % of the patients with events were reclassified into higher risk categories , result ing in a total continuous net reclassification improvement ( > 0 ) of 0.77 ( 95 % confidence interval , 0.33 - 1.22 ; P = .036 ) . CONCLUSIONS GLS is an independent early predictor of later reductions in EF , incremental to usual predictors in patients at risk for trastuzumab-induced cardiotoxicity OBJECTIVE Anthracyclines can damage the left ventricle , causing cardiomyopathy . This study evaluated the protective effect of carvedilol in cardiomyopathy caused by anthracyclines in patients suffering from breast cancer and lymphoma . METHODS In this clinical trial , patients undergoing chemotherapy were r and omly divided into three groups . The first group received placebo and the second and third groups received , respectively , 12.5 mg and 25 mg of apo-carvedilol 24 hours before starting the study . The patients underwent echocardiography and tissue Doppler to look for cardiomyopathy . After four months the efficacy of carvedilol was evaluated . RESULTS Sixty-six patients were evaluated . No meaningful difference was observed among the groups in terms of mortality , age , gender , type of malignancy , chemotherapy regimen , and cumulative dose of doxorubicin and epirubicin . No statistically significant differences were observed between control and case groups considering the frequency of systolic cardiomyopathy ( p=0.284 ) or the frequency of diastolic cardiomyopathy ( p=0.284 ) . CONCLUSION Carvedilol at a daily dose of 12.5 mg has a protective effect against diastolic disorder and at a daily dose of 25 mg has a protective effect against both systolic and diastolic disorders Anthracyclines have contributed to a marked increase in survival in different types of cancer [ 1,2 ] . Unfortunately , they are associated with dose-dependent cardiotoxicity and heart failure ( HF ) [ 3–8 ] . Change to a weekly dosage schedule with slow infusions has been tested , a strategy that requires more frequent hospital visits and increased storage re sources [ 7,9 ] . Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [ 10 ] . Beta-blockers and angiotensin converting enzyme(ACE ) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity , but have not been tested in long-term prospect i ve , r and omized , controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [ 11–16 ] . We investigated doxorubicin-induced clinical or sub clinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment . We examined whether cardiotoxicity was related to the treatment or any other variable . We found that HF was less frequent under concomitant treatment than no treatment , especially in the metoprolol group , but the differences were not significant . No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact . The marginal benefit seen with metoprolol should be investigated further |
10,987 | 30,702,796 | CONCLUSION The current meta- analysis showed that in general , psychological interventions that used OT , CT , HBM and TPB were effective in enhancing oral health status , and interventions that used SCT did not have an effect on improving oral health status . | OBJECTIVE In the present study , we attempted to assess how psychological theories ( health belief model [ HBM ] , theory of planned behaviour [ TPB ] , social cognitive theory [ SCT ] , clinical theories [ CT ] and other theories [ OT ] ) influence oral health interventions . | Oral healthcare providers have a clinical opportunity for early detection of disordered eating behaviors because they are often the first health professionals to observe overt oral and physical signs . Curricula regarding early recognition of this oral/systemic medical condition are limited in oral health educational programs . Web-based learning can supplement and reinforce traditional learning and has the potential to develop skills . The study purpose was to determine the efficacy of a theory-driven Web-based training program to increase the capacity of oral health students to perform behaviors related to the secondary prevention of disordered eating behaviors . Using the Reach , Effectiveness , Adoption , Implementation and Maintenance evaluation framework , a longitudinal group-r and omized controlled trial involving 27 oral health classes from 12 oral health education programs in the United States was implemented to assess the efficacy of the Web-based training on attitudes , knowledge , self-efficacy and skills related to the secondary prevention of disordered eating behaviors . Mixed-model analysis of covariance indicated substantial improvements among students in the intervention group ( effect sizes : 0.51 - 0.83 ) on all six outcomes of interest . Results suggest that the Web-based training program may increase the capacity of oral healthcare providers to deliver secondary prevention of disordered eating behaviors . Implication s and value of using the Reach , Effectiveness , Adoption , Implementation and Maintenance framework are discussed OBJECTIVE To determine if mothers receiving a smoking cessation intervention emphasizing health risks of environmental tobacco smoke ( ETS ) for their children have a higher quit rate than 1 ) mothers receiving routine smoking cessation advice or 2 ) a control group . DESIGN R and omized , controlled trial . SETTING Primary care center in a large urban children 's hospital . INTERVENTION Four hundred seventy-nine mothers were r and omly assigned to a smoking cessation intervention either aim ed at their child 's health or their own health , or to a control group receiving safety information . OUTCOME MEASURES Smoking status , stage of change , cigarettes/day , location smoking occurred , and knowledge of ETS effects . RESULTS Complete data ( baseline and both follow-ups ) were available for 166 subjects . There was no impact of group assignment on the quit rate , cigarettes/day , or stage of change . The Child Health Group intervention had a sustained effect on location where smoking reportedly occurred ( usually outside ) and on improved knowledge of ETS effects . CONCLUSIONS Further research is needed to devise more effective methods of using the pediatric health care setting to influence adult smoking behaviors This study examined the value of SLT as a model for predicting levels of dental hygiene behaviors . The brushing and flossing frequency of 131 adults was measured both retrospectively ( via question naire ) and prospect ively ( via self-monitoring records ) . Two types of SLT variables -- expectations and environmental influences -- were reliably related to dental hygiene behaviors . Such variables ( for example , self-efficacy expectations and the dental behaviors of significant others ) accounted for up to 38 % of the variance in brushing frequency and 33 % of the variance in flossing frequency . Overall , a SLT model appears to hold promise for identifying psychosocial variables that are related to dental hygiene behaviors . The findings suggest that educational programs intended to increase the frequency of such behaviors should focus on increasing self-efficacy , reducing structural and life-style barriers to adherence , and involving significant others in educational efforts AIM Because patient adherence to oral hygiene is essential for periodontal treatment success , the aim of the study was to assess whether a motivational interview addressing the five dimensions of Leventhal 's theory performed better than conventional basic instruction on improving compliance with plaque control among patients with periodontitis . MATERIAL S AND METHODS A r and omized controlled clinical trial design was used in which a group of patients underwent a motivational interview in addition to classical consultation . A control group received only the st and ard consultation . The O'Leary Plaque Index was used to judge the oral hygiene at baseline and at 1 month follow-up . Patient satisfaction with the dental visit was scored using a specific question naire . RESULTS At baseline , the mean full mouth plaque score varied between 55 % ( experimental group ) and 58 % ( control group ) . Patients in the experimental group had a higher oral hygiene improvement ( 21 ± 20 % versus 4 ± 5 % , p < 0.001 ) 1 month post-treatment . The motivational interview result ed in greater satisfaction scores compared with those of patients in the control group : 10.55 ± 1.53 versus 8.82 ± 2.40 , p = 0.014 . CONCLUSIONS This new concept of motivational interview is a promising approach and can be useful for counselling-related periodontal disorders AIM To evaluate the effectiveness of an individually tailored oral health educational programme for oral hygiene self-care in patients with chronic periodontitis compared with the st and ard treatment . MATERIAL AND METHOD A r and omized , evaluator-blinded , controlled trial with two different active treatments were used with 113 subjects ( 60 females and 53 males ) r and omly allocated to an experimental or a control group . The individually tailored oral health educational programme was based on cognitive behavioural principles and the individual tailoring for each participant was based on participants ' thoughts , intermediate , and long-term goals , and oral health status . The effect of the programmes on gingivitis [ gingival index ( GI ) ] , oral hygiene [ plaque indices ( PlI ) and self-report ] , and participants ' global rating of treatment was evaluated 3 and 12 months after oral health education and non-surgical treatment . RESULTS Between baseline and the 12-month follow-up , the experimental group improved both GI and PlI more than the control group . The mean gain-score difference was 0.27 for global GI [ 99.2 % confidence interval ( CI ) : 0.16 - 0.39 , p<0.001 ] and 0.40 for proximal GI ( 99.2 % CI : 0.27 - 0.53 , p<0.001 ) . The mean gain-score difference was 0.16 for global PlI ( 99.2 % CI : 0.03 - 0.30 , p=0.001 ) , and 0.26 for proximal PlI ( 99.2 % CI : 0.10 - 0.43 , p<0.001 ) . The subjects in the experimental group reported a higher frequency of daily inter-dental cleaning and were more certain that they could maintain the attained level of behaviour change . CONCLUSION The individually tailored oral health educational programme was efficacious in improving long-term adherence to oral hygiene in periodontal treatment . The largest difference was for interproximal surfaces Parents and school staff play important roles in promoting children 's oral health . Our study goals were to investigate whether an intervention targeting parents and school staff can improve the oral-health behavior and oral-health status of schoolchildren . Three-hundred and ninety-two schoolchildren in six schools in Tehran participated in a group r and omized trial from September 2010 to March 2011 . Schools were r and omly allocated into three groups : comprehensive , student , and control . Intervention in the comprehensive group consisted of strategies to encourage children , their parents , and school staff to increase the frequency of toothbrushing and flossing . In the student group , the intervention targeted only children . The control group received no intervention . The primary outcome was change in oral-health behaviors ( brushing and flossing ) , while the secondary outcomes were changes in oral hygiene and Community Periodontal indices and in Health Belief Model components . Multilevel modeling was employed for data analyses . Students who were in the comprehensive intervention group brushed and flossed significantly more frequently compared with those in the student intervention group . Although students ' gingival health improved significantly in the comprehensive intervention group , such significant improvement was not seen in the student group . In conclusion , promising results are seen when the oral-health education targets both school and home setting Considerable re sources are expended in dealing with dental disease easily prevented with better oral hygiene . The study hypothesis was that an evidence -based intervention , framed with psychological theory , would improve patients ’ oral hygiene behavior . The impact of trial methodology on trial outcomes was also explored by the conducting of two independent trials , one r and omized by patient and one by dentist . The study included 87 dental practice s and 778 patients ( Patient RCT = 37 dentists/300 patients ; Cluster RCT = 50 dentists/478 patients ) . Controlled for baseline differences , pooled results showed that patients who experienced the intervention had better behavioral ( timing , duration , method ) , cognitive ( confidence , planning ) , and clinical ( plaque , gingival bleeding ) outcomes . However , clinical outcomes were significantly better only in the Cluster RCT , suggesting that the impact of trial design on results needs to be further explored OBJECTIVES This clinical trial study investigates whether a behavioural educational intervention based on the autoregulation theory can improve periodontitis patients ' compliance with proper dental care at a 1-month follow-up . MATERIAL AND METHODS Thirty patients matched for gender ( 20 men ) , age ( mean age=39 years ) and education were r and omly assigned to a control or an experimental treatment condition . In the control condition , patients received the regular treatment based on instruction of the proper prophylactic dental care . In the experimental treatment condition , patients received information about the symptoms of periodontitis , the causes , consequences and temporal course , and the types of effective strategy and they were requested to keep daily records of the effects of applying prophylactic dental care on their periodontitis symptoms . In both groups , plaque indices ( PIs ) ( Silness & Löe 1964 ) were measured prior to treatment and at a 1-month follow-up . A self-report question naire also assessed the representation of periodontitis in all patients . RESULTS A 2 ( time of measurement : baseline versus follow-up ) x 3 ( PI localization ) x 2 ( experimental group ) mixed- design anova computed on the PI reports a large effect of time , F(1 , 28)=267.10 , p<0.000 , indicating that both groups improved from baseline ( mean=1.73 , SD=0.08 ) to the 1-month follow-up ( mean=0.56 , SD=0.06 ) . It is important to point out that this analysis also revealed the expected Group x Time interaction , F(1 , 28)=7.09 , p<0.02 , partial eta(2)=0.19 , indicating that smaller PI were observed in the experimental group ( mean=0.24 , SD=0.14 ) than in the control group ( mean=0.88 , SD=0.38 ) at follow-up . Post hoc analyses showed that this pattern applies to the proximal and lingual PI but not to the vestibular PI . CONCLUSIONS The present data show that the behavioural education intervention is ( a ) more effective than a classical intervention based on information and training about prophylactic techniques and ( b ) that it is effective in bringing most patients to normal levels of PI . For clinical practice , it suggests that better results can be obtained if ( a ) patients are taught a correct representation about periodontitis and ( b ) patients ' sense of self-efficacy is developed through their own direct experience , by observing the effects of their behaviour on periodontitis symptoms AIMS / OBJECTIVES To determine the benefit of twice daily toothbrushing on newly erupted first permanent molars . To investigate , through the Health Belief Model , how parents ' beliefs influence the likelihood of their children brushing twice a day . To identify aspects of a toothbrushing intervention programme that can be used in general dental practice . DESIGN R and omised controlled trial . SETTING Schools in deprived communities in Scotl and . PARTICIPANTS 461 , 5-year-old children . INTERVENTIONS / METHODS Supervised toothbrushing on school-days with a 1,000 ppm chalk-based fluoride toothpaste for two years . A school and home-based incentive scheme including toothbrushing charts , 6-monthly dental examinations and parental question naires . MAIN OUTCOME MEASURES Caries increment and twice daily toothbrushing . RESULTS In the control group , children who brushed once a day or less had 64 % more caries than those who brushed at least twice a day ( P = 0.001 ) . In the intervention group this difference in caries was reduced to 16 % ( P > 0.05 ) . The most significant parental belief explaining variation in twice-daily brushing was whether parents feel strongly that there is time to check their child 's toothbrushing ( P = 0.0001 ) . The odds of these parents reporting that their child brushes twice daily are nearly three times greater . 95 % of parents felt that toothbrushing charts would be a good way for dentists in practice to encourage children to brush regularly . CONCLUSIONS The benefit of twice daily toothbrushing on caries development in newly erupted first permanent molar teeth is around 50 % compared to brushing once a day or less . Parents ' beliefs do influence the likelihood of their children brushing twice a day . Key parts of the intervention programme can be used when children attend general dental practice and would be welcomed by parents BACKGROUND Oral health education for the mothers of very young children is important in reducing the risk of early childhood caries . This study aim ed to evaluate the impact of an oral health intervention among mothers of 1 - 2 years old children . METHODS This cluster r and omized controlled trial ( 2012 ) was conducted among ninety mothers of 1 - 2 year old children . The setting of study was 10 child day-care centers out of 18 in Hamadan , western Iran . Day-care centers were r and omly allocated into two groups : an intervention group ( 5 day-care centers , 45 mothers ) and a control group ( 5 day-care centers , 45 mothers ) . Intervention consisted of three sessions , a booklet , and mobile phone text-message reminders . The primary outcome was change in cleaning the children ' teeth , while the secondary outcomes were changes in Theory of Planned Behavior ( TPB ) cognitions . Question naires at baseline , 10 days , and 3 months assessed intervention effects . Data were analyzed using SPSS v.16 . T tests , chi- square , and logistic and linear generalized estimating equations ( GEE ) regression were used to test intervention impact . RESULTS At 10-day assessment , mothers in intervention group reported a significant difference in knowledge ( P=0.001 ) , attitude ( P=0.004 ) , perceived behavioral control ( P=0.008 ) , and cleaning of children 's teeth ( P=0.011 ) . Also , at 3-month assessment compared to control group , the mothers in intervention group significantly improved in scores of knowledge ( P=0.001 ) , attitude ( P=0.001 ) , perceived behavioral control ( P=0.001 ) , and cleaning of children 's teeth ( P=0.001 ) . However , the effect sizes were small to medium and ranged from 0.1 to 0.4 for all cognitions except knowledge ( effect size>0.70 ) . Generalized estimating equations ( GEE ) showed that score of attitude and perceived behavioral control of intervention group improved between the two post-test assessment s. CONCLUSIONS A brief multicomponent theory-based intervention among mothers of 1 - 2 years old children was effective moderately in improving cognitions and self-reported cleaning children 's teeth OBJECTIVES Patient engagement in effective oral hygiene following periodontal therapy is essential to long-term success . Motivational interviewing ( MI ) is a behavioural counselling approach documented to positively influence behaviour change related to smoking , diabetes control and medication adherence . Emerging evidence suggests utility of MI to improve oral health . The objective of this study was to evaluate whether the use of brief motivational interviewing ( BMI ) is effective in improving internal motivation for oral hygiene behaviour . METHODS A convenience sample of fifty-six previously treated periodontal patients who were in maintenance yet presented with signs of clinical inflammation were recruited to participate in this single blind , r and omized controlled trial . Patients were r and omly assigned to receive either BMI in conjunction with traditional oral health education ( TOHE ) , ( n = 29 ) or TOHE alone ( n = 27 ) . Bleeding on probing scores ( BOP ) , plaque index ( PI ) , pocket depths ( PD ) , motivation ( M ) , autonomous regulation ( AR ) controlled regulation ( CR ) and oral health knowledge ( K ) were assessed at baseline , 6 weeks and 12 weeks . RESULTS Statistically significant decreases were found over time for BOP ( P = 0.001 ) , PI ( P = 0.001 ) and PD 4 - 6 mm ( P = 0.001 ) for both groups . Differences in clinical parameters between groups were not evident at either 6 or 12 weeks . CONCLUSION Results show that a one-time MI session is insufficient for improving oral hygiene in long-st and ing maintenance patients Sense of coherence ( SOC ) has been related to oral health behaviors and oral-health-related quality of life ( OHRQoL ) in observational studies . This cluster-r and omized trial aim ed to test the effect of an intervention to enhance SOC on OHRQoL in children . Twelve primary schools were r and omly allocated to intervention and control groups . The intervention was comprised of 7 sessions over 2 mos , focusing on child participation and empowerment . The first 4 sessions were classroom activities , and the last 3 involved working on healthy school projects . Trained teachers who received a one-day course delivered the intervention . Socio-demographic and clinical data , together with self-reported measures of OHRQoL , SOC , and oral health beliefs , were obtained from 261 total 10- to 12-year-olds ( 133 in the intervention and 128 in the control groups ) . Data were collected at baseline , 2 wks after the intervention , and at three-month follow-up . Mixed-effects models indicated that the intervention increased SOC and improved OHRQoL , together with oral health beliefs and gingival health . The findings offer experimental evidence that OHRQoL can be influenced by SOC . SOC may also provide an avenue for oral health promotion ( Australian New Zeal and Clinical Trials Registry ACTRN12612000547842 ) OBJECTIVE Determine whether a six-step behavioral cognitive method is more effective than traditional oral hygiene instruction . METHODS Thirty-eight patients with chronic periodontitis were r and omly assigned to two groups . The control group was given traditional oral hygiene instruction for 20 min . The intervention group received counseling by Farquhar 's six-step method for 10 min after traditional oral hygiene instruction . In both groups , oral hygiene instruction was given once a week , and performed three times in total for 3 weeks . Clinical characteristics , deposition of dental plaque , frequency and duration of brushing , frequency of interdental cleaning and scores based on scale of " self-efficacy for brushing of the teeth " were compared in both groups . RESULTS There were no differences between the two groups in clinical , demographic , behavioral and self-efficacy characteristics at the baseline examination . However after the third visit , the intervention group had a significantly higher self-efficacy , lower plaque index , longer brushing duration and higher frequency of inter-dental cleaning than those of the control group . Multiple regression analysis showed significant association of toothbrushing duration with self-efficacy for brushing of the teeth ( p<0.001 ) . CONCLUSION The six-step method might be more effective for enhancing self-efficacy and behavioral change of oral hygiene than traditional oral hygiene instruction alone . PRACTICE IMPLICATION S Dentists and dental hygienists can use the six-step method for effective oral hygiene instruction |
10,988 | 30,823,897 | Conclusions In patients with STEMI and MVD , FFR-guided CR is better than COR in terms of MACE and ischemia-driven repeat revascularization , while there are almost similar in all-cause mortality . | Background Approximately 30–50 % patients with acute ST-segment elevation myocardial infa rct ion ( STMEI ) were found to have non-infa rct -related coronary artery ( IRA ) disease , which was significantly associated with worse prognosis .
However , challenges still remain for these patients : which non-infa rct -related lesion should be treated and when should the procedure be performed ?
The present study aims to investigate Fractional flow reserve (FFR)-guided complete revascularization ( CR ) in comparison to culprit-only revascularization ( COR ) in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) and multi-vessel disease ( MVD ) . | Aim We assessed the management and outcomes of non-ST segment elevation myocardial infa rct ion ( NSTEMI ) patients r and omly assigned to fractional flow reserve (FFR)-guided management or angiography-guided st and ard care . Methods and results We conducted a prospect i ve , multicentre , parallel group , 1 : 1 r and omized , controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30 % of the lumen diameter assessed visually ( threshold for FFR measurement ) ( NCT01764334 ) . Enrolment took place in six UK hospitals from October 2011 to May 2013 . Fractional flow reserve was disclosed to the operator in the FFR-guided group ( n = 176 ) . Fractional flow reserve was measured but not disclosed in the angiography-guided group ( n = 174 ) . Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention ( PCI ) or coronary artery bypass surgery ( CABG ) . The median ( IQR ) time from the index episode of myocardial ischaemia to angiography was 3 ( 2 , 5 ) days . For the primary outcome , the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [ 40 ( 22.7 % ) vs. 23 ( 13.2 % ) , difference 95 % ( 95 % CI : 1.4 % , 17.7 % ) , P = 0.022 ] . Fractional flow reserve disclosure result ed in a change in treatment between medical therapy , PCI or CABG in 38 ( 21.6 % ) patients . At 12 months , revascularization remained lower in the FFR-guided group [ 79.0 vs. 86.8 % , difference 7.8 % ( −0.2 % , 15.8 % ) , P = 0.054 ] . There were no statistically significant differences in health outcomes and quality of life between the groups . Conclusion In NSTEMI patients , angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management . A larger trial is necessary to assess health outcomes and cost-effectiveness Background There are conflicting data regarding optimal treatment of non-culprit lesions detected during primary percutaneous coronary intervention ( PCI ) in patients with ST-elevation myocardial infa rct ion ( STEMI ) and multi-vessel disease ( MVD ) . We aim ed to investigate whether ischaemia-driven early invasive treatment improves the long-term outcome and prevents major adverse cardiac events ( MACE ) . Methods 121 patients with at least one non-culprit lesion were r and omised in a 2:1 manner , 80 were r and omised to early fractional flow reserve (FFR)-guided PCI ( invasive group ) , and 41 to medical treatment ( conservative group ) . The primary endpoint was MACE at 3 years . Results Three-year follow-up was available in 119 patients ( 98.3 % ) . There was no significant difference in all-cause mortality between the invasive and conservative strategy , 4 patients ( 3.4 % ) died , all in the invasive group ( P = 0.29 ) . Re-infa rct ion occurred in 14 patients ( 11.8 % ) in the invasive group versus none in the conservative group ( p = 0.002 ) . Re-PCI was performed in 7 patients ( 8.9 % ) in the invasive group and in 13 patients ( 32.5 % ) in the conservative group ( P = 0.001 ) . There was no difference in MACE between these two strategies ( 35.4 vs 35.0 % , p = 0.96 ) . Conclusions In STEMI patients with MVD , early FFR-guided additional revascularisation of the non-culprit lesion did not reduce MACE at three-year follow-up compared with a more conservative strategy . The rate of MACE in the invasive group was predominantly driven by death and re-infa rct ion , whereas in the conservative group the rate of MACE was only driven by repeat interventions OBJECTIVES The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention ( PCI ) guided by fractional flow reserve ( FFR ) in patients with multivessel coronary artery disease ( CAD ) . BACKGROUND In patients with multivessel CAD undergoing PCI , coronary angiography is the st and ard method for guiding stent placement . The FAME ( Fractional Flow Reserve Versus Angiography for Multivessel Evaluation ) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year . It is unknown if these favorable results are maintained at 2 years of follow-up . METHODS At 20 U.S. and European medical centers , 1,005 patients with multivessel CAD were r and omly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements . Before r and omization , lesions requiring PCI were identified based on their angiographic appearance . Patients r and omized to angiography-guided PCI underwent stenting of all indicated lesions , whereas those r and omized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was < or=0.80 . RESULTS The number of indicated lesions was 2.7+/-0.9 in the angiography-guided group and 2.8+/-1.0 in the FFR-guided group ( p=0.34 ) . The number of stents used was 2.7+/-1.2 and 1.9+/-1.3 , respectively ( p<0.001 ) . The 2-year rates of mortality or myocardial infa rct ion were 12.9 % in the angiography-guided group and 8.4 % in the FFR-guided group ( p=0.02 ) . Rates of PCI or coronary artery bypass surgery were 12.7 % and 10.6 % , respectively ( p=0.30 ) . Combined rates of death , nonfatal myocardial infa rct ion , and revascularization were 22.4 % and 17.9 % , respectively ( p=0.08 ) . For lesions deferred on the basis of FFR>0.80 , the rate of myocardial infa rct ion was 0.2 % and the rate of revascularization was 3.2 % after 2 years . CONCLUSIONS Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infa rct ion at 2 years when compared with st and ard angiography-guided PCI . ( Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [ FAME ] ; NCT00267774 ) Background — Magnetic resonance myocardial perfusion imaging ( MRMPI ) has a number of advantages over the other noninvasive tests used to detect reversible myocardial ischemia . The majority of previous studies have generally used quantitative coronary angiography as the gold st and ard to assess the accuracy of MRMPI ; however , only an approximate relationship exists between stenosis severity and functional significance . Pressure wire – derived fractional flow reserve ( FFR ) values < 0.75 correlate closely with objective evidence of reversible ischemia . Accordingly , we have compared MRMPI with FFR . Methods and Results — One hundred three patients referred for investigation of suspected angina underwent MRMPI with a 1.5-T scanner . The stress agent was intravenous adenosine ( 140 & mgr;g · kg−1 · min−1 ) , and the first-pass bolus contained 0.1 mmol/kg gadolinium . In the following week , coronary angiography with pressure wire studies was performed . FFR was recorded in all patent major epicardial coronary arteries , with a value < 0.75 denoting significant stenosis . MRMPI scans , analyzed by 2 blinded observers , identified perfusion defects in 121 of 300 coronary artery segments ( 40 % ) , of which 110 had an FFR < 0.75 . We also found that 168 of 179 normally perfused segments had an FFR ≥0.75 . The sensitivity and specificity of MRMPI for the detection of functionally significant coronary heart disease were 91 % and 94 % , respectively , with positive and negative predictive values of 91 % and 94 % . Conclusion — MRMPI can detect functionally significant coronary heart disease with excellent sensitivity , specificity , and positive and negative predictive values compared with FFR Background Few reports described outcomes of complete compared with infa rct -related artery (IRA)-only revascularisation in patients with ST-elevation myocardial infa rct ion ( STEMI ) and multivessel coronary artery disease ( CAD ) . Moreover , no studies have compared the simultaneous treatment of non-IRA with the IRA treatment followed by an elective procedure for the other lesions ( staged revascularisation ) . Methods The outcomes of 214 consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty were studied . Before the first angioplasty patients were r and omly assigned to three different strategies : culprit vessel angioplasty-only ( COR group ) ; staged revascularisation ( SR group ) and simultaneous treatment of non-IRA ( CR group ) . Results During a mean follow-up of 2.5 years , 42 ( 50.0 % ) patients in the COR group experienced at least one major adverse cardiac event ( MACE ) , 13 ( 20.0 % ) in the SR group and 15 ( 23.1 % ) in the CR group , p<0.001 . Inhospital death , repeat revascularisation and re-hospitalisation occurred more frequently in the COR group ( all p<0.05 ) , whereas there was no significant difference in re-infa rct ion among the three groups . Survival free of MACE was significantly reduced in the COR group but was similar in the CR and SR groups . Conclusions Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment . Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA AIMS To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention ( PCI ) and its association with 90-day outcomes . METHODS AND RESULTS We examined the incidence , propensity for , and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infa rct ion patients with multi-vessel coronary artery disease ( MVD ) . Of the 5373 patients who underwent primary PCI in the APEX-AMI trial , 2201 had MVD . Of those , 217 ( 9.9 % ) underwent non-infa rct -related arteries ( IRA ) PCI , whereas 1984 ( 90.1 % ) underwent PCI of the IRA alone . Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group ( 12.5 vs. 5.6 % , P ( log-rank ) < 0.001 and 17.4 vs. 12.0 % , P ( log-rank ) = 0.020 , respectively ) . After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI , this procedure remained independently associated with an increased hazard of 90-day mortality [ adjusted hazard ratio 2.44 , 95 % CI ( 1.55 - 3.83 ) , P < 0.001 ] . CONCLUSION Non-culprit coronary interventions were performed at the time of primary PCI in 10 % of MVD patients and were significantly associated with increased mortality . Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients . Prospect i ve r and omized study of this issue may be warranted BACKGROUND Non-infa rct -related artery ( non-IRA ) disease is prevalent in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . We aim ed to assess the impact of non-IRA disease on infa rct size and clinical outcomes in patients with acute STEMI . METHODS The Counterpulsation to Reduce Infa rct Size Pre-PCI Acute Myocardial Infa rct ion ( CRISP-AMI ) trial r and omized patients to intra-aortic balloon counterpulsation ( IABC ) vs no IABC prior to percutaneous coronary intervention in patients with acute STEMI . Infa rct size ( % left ventricular mass ) at 3 - 5 days post percutaneous coronary intervention and 6-month clinical outcomes were compared between patients with and without non-IRA disease ( defined as ≥50 % stenosis in at least one non-IRA ) . RESULTS A total of 324 ( 96.1 % ) patients had anterior STEMI , of whom 34.9 % had non-IRA disease . There was no difference in infa rct size ( % left ventricular mass ) between patients with and without non-IRA disease ( median 39 % vs 39 % ; P = .73 ) . At 6 months , there was no difference in rates of recurrent myocardial infa rct ion ( 0.9 % vs 0.9 % ; P = .78 ) , major Thrombolysis In Myocardial Infa rct ion bleeding ( 0.9 % vs 0.5 % ; P = .77 ) , or all-cause death ( 3.5 % vs 2.4 % ; P = .61 ) in patients with and without non-IRA disease , respectively . Patients with non-IRA disease had a higher rate of new/worsening heart failure with hospitalization ( 8.8 % vs 1.9 % ; P = .0050 ) . CONCLUSIONS More than one-third of patients with anterior STEMI in the CRISP-AMI study had non-IRA disease . These patients had similar infa rct sizes and rates of recurrent myocardial infa rct ion , major bleeding , and all-cause death . Patients with non-IRA disease did have a higher rate of new/worsening heart failure with hospitalization . Further study is needed to underst and the mechanisms of outcomes of patients with non-IRA disease OBJECTIVES We investigated the reliability of fractional flow reserve ( FFR ) of nonculprit coronary stenoses during percutaneous coronary intervention ( PCI ) in acute myocardial infa rct ion . BACKGROUND Assessing the hemodynamic severity of the nonculprit coronary artery stenoses at the acute phase of a myocardial infa rct ion could improve risk stratification and shorten the diagnostic work-up . METHODS One hundred one patients undergoing PCI for an acute myocardial infa rct ion ( n = 75 with ST-segment elevation myocardial infa rct ion [ STEMI ] , and n = 26 with non-ST-segment elevation myocardial infa rct ion ) were prospect ively recruited . The FFR measurements in 112 nonculprit stenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later . In addition , left ventricular ejection fraction , quantitative coronary angiographic measurements of the nonculprit stenoses , Thrombolysis In Myocardial Infa rct ion ( TIMI ) flow , corrected TIMI frame count ( cTFC ) , and the index of microcirculatory resistance ( n = 14 ) of the nonculprit vessels were assessed in the acute phase and at control angiogram . RESULTS The FFR value of the nonculprit stenoses did not change between the acute and follow-up ( 0.77 ± 0.13 vs. 0.77 ± 0.13 , respectively , p = NS ) . In only 2 patients , the FFR value was higher than 0.8 at the acute phase and lower than 0.75 at follow-up . The TIMI flow , cTFC , percentage diameter stenosis , minimum lumen diameter , and index of microcirculatory resistance did not change . Left ventricular ejection fraction increased significantly in patients with STEMI ( from 54 ± 13 % to 57 ± 13 % , p = 0.03 ) . CONCLUSIONS During the acute phase of acute coronary syndromes , the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR . This allows a decision about the need for additional revascularization and might contribute to a better risk stratification BACKGROUND Patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease . We aim ed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infa rct -related artery only . METHODS We undertook an open-label , r and omised controlled trial at two university hospitals in Denmark . Patients presenting with STEMI who had one or more clinical ly significant coronary stenosis in addition to the lesion in the infa rct -related artery were included . After successful percutaneous coronary intervention ( PCI ) of the infa rct -related artery , patients were r and omly allocated ( in a 1:1 ratio ) either no further invasive treatment or complete FFR-guided revascularisation before discharge . R and omisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI . All patients received best medical treatment . The primary endpoint was a composite of all-cause mortality , non-fatal reinfa rct ion , and ischaemia-driven revascularization of lesions in non-infa rct -related arteries and was assessed when the last enrolled patient had been followed up for 1 year . Analysis was on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT01960933 . FINDINGS From March , 2011 , to February , 2014 , we enrolled 627 patients to the trial ; 313 were allocated no further invasive treatment after primary PCI of the infa rct -related artery only and 314 were assigned complete revascularization guided by FFR values . Median follow-up was 27 months ( range 12–44 months ) . Events comprising the primary endpoint were recorded in 68 ( 22 % ) patients who had PCI of the infa rct -related artery only and in 40 ( 13 % ) patients who had complete revascularisation ( hazard ratio 0∙56 , 95 % CI 0∙38–0∙83 ; p=0∙004 ) . INTERPRETATION In patients with STEMI and multivessel disease , complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI . This effect is driven by significantly fewer repeat revascularisations , because all-cause mortality and non-fatal reinfa rct ion did not differ between groups . Thus , to avoid repeat revascularisation , patients can safely have all their lesions treated during the index admission . Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints . FUNDING Danish Agency for Science , Technology and Innovation and Danish Council for Strategic Research BACKGROUND In acute ST-segment elevation myocardial infa rct ion ( STEMI ) , the use of percutaneous coronary intervention ( PCI ) to treat the artery responsible for the infa rct ( infa rct , or culprit , artery ) improves prognosis . The value of PCI in noninfa rct coronary arteries with major stenoses ( preventive PCI ) is unknown . METHODS From 2008 through 2013 , at five centers in the United Kingdom , we enrolled 465 patients with acute STEMI ( including 3 patients with left bundle-branch block ) who were undergoing infa rct -artery PCI and r and omly assigned them to either preventive PCI ( 234 patients ) or no preventive PCI ( 231 patients ) . Subsequent PCI for angina was recommended only for refractory angina with objective evidence of ischemia . The primary outcome was a composite of death from cardiac causes , nonfatal myocardial infa rct ion , or refractory angina . An intention-to-treat analysis was used . RESULTS By January 2013 , the results were considered conclusive by the data and safety monitoring committee , which recommended that the trial be stopped early . During a mean follow-up of 23 months , the primary outcome occurred in 21 patients assigned to preventive PCI and in 53 patients assigned to no preventive PCI ( infa rct -artery-only PCI ) , which translated into rates of 9 events per 100 patients and 23 per 100 , respectively ( hazard ratio in the preventive-PCI group , 0.35 ; 95 % confidence interval [ CI ] , 0.21 to 0.58 ; P<0.001 ) . Hazard ratios for the three components of the primary outcome were 0.34 ( 95 % CI , 0.11 to 1.08 ) for death from cardiac causes , 0.32 ( 95 % CI , 0.13 to 0.75 ) for nonfatal myocardial infa rct ion , and 0.35 ( 95 % CI , 0.18 to 0.69 ) for refractory angina . CONCLUSIONS In patients with STEMI and multivessel coronary artery disease undergoing infa rct -artery PCI , preventive PCI in noninfa rct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events , as compared with PCI limited to the infa rct artery . ( Funded by Barts and the London Charity ; PRAMI Current Controlled Trials number , IS RCT N73028481 . ) AIMS Primary percutaneous coronary intervention ( PPCI ) is the preferred strategy for acute ST-segment elevation myocardial infa rct ion ( STEMI ) , with evidence of improved clinical outcomes compared to fibrinolytic therapy . However , there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI , with little robust data on best management of angiographically significant stenoses detected in non-infa rct -related ( N-IRA ) coronary arteries . CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI . METHODS AND RESULTS CVLPRIT ( Complete Versus culprit-Lesion only PRimary PCI Trial ) is an open-label , prospect i ve , r and omised , multicentre trial . STEMI patients undergo verbal " assent " on presentation . Patients are included when angiographic MVD has been detected , and r and omised to culprit (IRA)-only PCI ( n=150 ) or in-patient complete multivessel PCI ( n=150 ) . Cumulative major adverse cardiac events ( MACE ) - all-cause mortality , recurrent MI , heart failure , need for revascularisation ( PCI or CABG ) will be recorded at 12 months . Secondary endpoints include safety endpoints of confirmed ischaemic stroke , intracranial haemorrhage , major non-intracranial bleeding , and repair of vascular complications . A cardiac magnetic resonance ( CMR ) sub study will provide mechanistic data on infa rct size , myocardial salvage index and microvascular obstruction . A cost efficacy analysis will be undertaken . CONCLUSIONS The management of multivessel coronary artery disease in the setting of PPCI for STEMI , including the timing of when to perform non-culprit-artery revascularisation if undertaken , remains unresolved . CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infa rct period DESIGN : Prospect i ve r and omized , multicentre study . RATIONALE : Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infa rct ion . With the exception of cardiogenic shock , staged procedures are performed in the presence of multivessel disease . The study hypothesis is that with modern non-thrombogenic stents ( heparin coated ) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost . ENDPOINTS : PRIMARY : 12-month incidence of repeat revascularization ( any revascularization , infa rct related artery as well as non-infa rct -related artery ) . SECONDARY : ( 1 ) in hospital repeat revascularization , reinfa rct ion and death ; ( 2 ) total hospital cost ( including a 12 months follow-up period ) . METHODS : 69 patients with ST elevation Acute Myocardial Infa rct ion ( AMI ) , < 12 hours after symptoms onset , undergoing primary angioplasty , with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation . Unbalanced r and omization between culprit lesion treatment only ( n = 17 ) and complete multivessel treatment ( n = 52 , with 71 additional lesions treated ) . RESULTS : The two groups were well balanced in terms of clinical characteristics , number of diseased vessels and angiographic characteristics of the culprit lesion . In the complete multivessel treatment group 2.36 ± 0.64 lesions per patient were treated using 2.73 ± 0.78 heparin coated stents ( 1.00 lesions and 1.29 ± 0.61 stents in the culprit treatment group , bothp < 0.001 ) . The duration of the procedure increased from 53 ± 21 min ( culprit treatment group ) to 69 ± 32 min ( p = 0.032 ) and the amount of contrast used from 242 ± 102 ml ( culprit treatment group ) to 341 ± 163 ml ( multivessel complete treatment),p = 0.025 . A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups ( 0 and 3.8 % in culprit and multivessel treatment groups , p = 0.164 ) . The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant ( 35 vs 17%,p = 0.247 ) but was sufficient to compensate the initial higher in-hospital cost , with a similar 12 month hospital cost in the 2 groups ( € 22 330 ± € 13 653 vs € 20 382 ± € 11 671,p = 0.231 ) . CONCLUSION : Multivessel treatment during primary PTCA was safe in this controlled trial . However , when only the culprit lesion was initially treated , the need for subsequent clinical ly driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach . In clinical practice , a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinical ly relevant lesions . ( Int J Cardiovasc Intervent 2004 ; 6 : 128 - 133 Background : Previous studies found that percutaneous coronary intervention ( PCI ) does not improve outcome compared with medical therapy ( MT ) in patients with stable coronary artery disease , but PCI was guided by angiography alone . FAME 2 trial ( Fractional Flow Reserve Versus Angiography for Multivessel Evaluation ) compared PCI guided by fractional flow reserve with best MT in patients with stable coronary artery disease to assess clinical outcomes and cost-effectiveness . Methods : A total of 888 patients with stable single-vessel or multivessel coronary artery disease with reduced fractional flow reserve were r and omly assigned to PCI plus MT ( n=447 ) or MT alone ( n=441 ) . Major adverse cardiac events included death , myocardial infa rct ion , and urgent revascularization . Costs were calculated on the basis of re source use and Medicare reimbursement rates . Changes in quality -adjusted life-years were assessed with utilities determined by the European Quality of Life–5 Dimensions health survey at baseline and over follow-up . Results : Major adverse cardiac events at 3 years were significantly lower in the PCI group compared with the MT group ( 10.1 % versus 22.0 % ; P<0.001 ) , primarily as a result of a lower rate of urgent revascularization ( 4.3 % versus 17.2 % ; P<0.001 ) . Death and myocardial infa rct ion were numerically lower in the PCI group ( 8.3 % versus 10.4 % ; P=0.28 ) . Angina was significantly less severe in the PCI group at all follow-up points to 3 years . Mean initial costs were higher in the PCI group ( $ 9944 versus $ 4440 ; P<0.001 ) but by 3 years were similar between the 2 groups ( $ 16 792 versus $ 16 737 ; P=0.94 ) . The incremental cost-effectiveness ratio for PCI compared with MT was $ 17 300 per quality -adjusted life-year at 2 years and $ 1600 per quality -adjusted life-year at 3 years . The above findings were robust in sensitivity analyses . ConclusionS : PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable coronary artery disease . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01132495 Background The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention ( P-PCI ) for ST-segment elevation myocardial infa rct ion is uncertain . Objectives CvLPRIT ( Complete versus Lesion-only Primary PCI trial ) is a U.K. open-label r and omized study comparing complete revascularization at index admission with treatment of the infa rct -related artery ( IRA ) only . Methods After they provided verbal assent and underwent coronary angiography , 296 patients in 7 U.K. centers were r and omized through an interactive voice-response program to either in-hospital complete revascularization ( n = 150 ) or IRA-only revascularization ( n = 146 ) . Complete revascularization was performed either at the time of P-PCI or before hospital discharge . R and omization was stratified by infa rct location ( anterior/nonanterior ) and symptom onset ( ≤3 h or > 3 h ) . The primary endpoint was a composite of all-cause death , recurrent myocardial infa rct ion ( MI ) , heart failure , and ischemia-driven revascularization within 12 months . Results Patient groups were well matched for baseline clinical characteristics . The primary endpoint occurred in 10.0 % of the complete revascularization group versus 21.2 % in the IRA-only revascularization group ( hazard ratio : 0.45 ; 95 % confidence interval : 0.24 to 0.84 ; p = 0.009 ) . A trend toward benefit was seen early after complete revascularization ( p = 0.055 at 30 days ) . Although there was no significant reduction in death or MI , a nonsignificant reduction in all primary endpoint components was seen . There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding , contrast-induced nephropathy , or stroke between the groups . Conclusions In patients presenting for P-PCI with multivessel disease , index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA . In such patients , inpatient total revascularization may be considered , but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival . ( Complete Versus Lesion-only Primary PCI Pilot Study [ CvLPRIT ] ; IS RCT N70913605 |
10,989 | 31,482,229 | Nevertheless , among the investigated gene polymorphisms , it appears that the 1236C > T , 3435C > T and 2677 G > T/A SNPs of the drug transporter gene ABCB1 were the most promising determinants of clinical outcomes .
Therefore , using the haplotype ( 1236C > T , 2677G > T , and 3435C > T ) analysis rather than a single SNP may be a more useful approach for phenotype prediction .
Some of the patients with variants of CYP genes were associated with unsatisfactory treatment response ( efficacy and toxicity ) , suggesting that these variants may be associated with either reduction or absence of CYP enzyme activity . | Not all patients respond well to cancer chemotherapy .
One of the most important factors contributing to treatment response ( efficacy and toxicity ) is genetic determinant .
The current systematic review aims to provide current status of the information on the genetic contribution of genes encoding drug transport proteins and drug metabolizing enzyme , cytochrome P450 ( CYP ) , and relationship with clinical outcomes of cancer chemotherapy .
Although both 1236C > T and 3435C > T polymorphism are synonymous SNPs , several studies have demonstrated that not all synonymous SNPs are silent . | E7070 is a novel sulfonamide anticancer agent that disrupts the G1/S phase of the cell cycle . The objectives of this phase I study of E7070 were to estismate the maximal tolerated dose ( MTD ) , to determine the recommended dose for phase II , and to clarify the pharmacokinetic profile of E7070 and its relation to polymorphisms of CYP2C9 ( * 2 , * 3 ) and CYP2C19 ( * 2 , * 3 ) in Japanese patients . Patients received 1–2‐h i.v . infusions of E7070 ( 400 , 600 , 700 , 800 or 900 mg/m2 ) on day 1 of a 21‐day cycle . Twenty‐one patients received between one and eight cycles of E7070 . The dose‐limiting toxicities ( DLT ) comprised leukopenia , neutropenia , thrombocytopenia , elevation of aspartate aminotransferase , colitis , and ileus . The mean area under the plasma concentration – time curve ( AUC ) for successive dose levels increased in a non‐dose‐proportional manner . Two patients were heterozygous for the CYP2C9 mutation . For CYP2C19 , eight patients were wild type and the remainder had heterozygous ( n = 8) or homozygous mutations ( n = 5 ) . Regarding the CYP2C19 genotype , the AUC of patients with mutant alleles were higher than those of patients with wild type at a dose of 600 mg/m2 or more . The severity of toxic effects , such as myelosuppression , seemed to depend on the AUC . No partial responses were observed . One patient treated at a dose of 700 mg/m2 experienced a maximum tumor volume reduction of 22.5 % . The MTD was estimated to be 900 mg/m2 . A dose of 800 mg/m2 is recommended for further phase II studies . The pharmacokinetic/pharmacodynamic properties of E7070 seemed to be influenced by CYP2C19 genotype . The observed safety profile and preliminary evidence of antitumor activity warrant further investigation of this drug in monotherapy or in combination chemotherapy . ( Cancer Sci 2005 ; 96 : 721 –728 Background The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer ( CRPC ) patients . Functional polymorphisms within the cytochrome P450 1B1 ( CYP1B1 ) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen . Methods CYP1B1 genotyping was performed on blood sample s of 60 CRPC patients treated with docetaxel , using TaqMan probes-based assays . Association between CYP1B1 - 142C > G ( leading to the 48ArgGly transition ) , 4326C > G ( 432LeuVal ) , and 4390A > G ( 453AsnSer ) polymorphisms and treatment response , progression-free-survival ( PFS ) and overall-survival ( OS ) was estimated using Pearson χ2 test , Kaplan-Meier curves and Log-rank test . Results Patients carrying the CYP1B1 - 432ValVal genotype experienced a significantly lower response-rate ( P = 0.014 ) , shorter progression-free-survival ( P = 0.032 ) and overall-survival ( P < 0.001 ) . Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS . No significant associations were found among other polymorphisms and both response and clinical outcome . Conclusions CYP1B1 - 4326C > G ( 432LeuVal ) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization . Larger prospect i ve trials are warranted to vali date these findings , which might be applied to the future practice of CRPC treatment Introduction Aromatase inhibitor-associated arthralgia ( AIAA ) is a common and often debilitating symptom in breast cancer survivors . Since joint symptoms have been related to estrogen deprivation through the menopausal transition , we hypothesized that genetic polymorphisms in CYP19A1 , the final enzyme in estrogen synthesis , may be associated with the occurrence of AIAA . Methods We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor ( AI ) therapy . Patient-reported AIAA was the primary outcome . DNA was genotyped for c and i date CYP19A1 polymorphisms . Serum estrogen levels were evaluated by radioimmunoassay . Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders . Results Among 390 Caucasian participants , 50.8 % reported AIAA . Women carrying at least one 8-repeat allele had lower odds of AIAA ( adjusted odds ratio ( AOR ) 0.41 , 95 % confidence interval ( CI ) 0.21 to 0.79 , P = 0.008 ) after adjusting for demographic and clinical covariates . Estradiol and estrone were detectable in 47 % and 86 % of subjects on AIs , respectively . Although these post-AI levels were associated with multiple genotypes , they were not associated with AIAA . In multivariate analyses , women with more recent transition into menopause ( less than five years ) were significantly more likely to report AIAA than those greater than ten years post-menopause ( AOR 3.31 , 95 % CI 1.72 to 6.39 , P < 0.001 ) . Conclusions Functional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA , supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA . Prospect i ve investigation is needed to further delineate relationships between host genetics , changing estrogen levels and AIAA Introduction Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer . Even if most patients benefit from tamoxifen , many breast tumours either fail to respond or become resistant . Because tamoxifen is extensively metabolised by polymorphic enzymes , one proposed mechanism underlying the resistance is altered metabolism . In the present study we investigated the prognostic and /or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 ( * 3 ) , CYP2D6 ( * 4 ) , sulphotransferase 1A1 ( SULT1A1 ; * 2 ) and UDP-glucuronosyltransferase 2B15 ( UGT2B15 ; * 2 ) in tamoxifen-treated patients with breast cancer . Methods In all , 677 tamoxifen-treated postmenopausal patients with breast cancer , of whom 238 were r and omised to either 2 or 5 years of tamoxifen , were genotyped by using PCR with restriction fragment length polymorphism or PCR with denaturing high-performance liquid chromatography . Results The prognostic evaluation performed in the total population revealed a significantly better disease-free survival in patients homozygous for CYP2D6 * 4 . For CYP3A5 , SULT1A1 and UGT2B15 no prognostic significance was observed . In the r and omised group we found that for CYP3A5 , homozygous carriers of the * 3 allele tended to have an increased risk of recurrence when treated for 2 years with tamoxifen , although this was not statistically significant ( hazard ratio ( HR ) = 2.84 , 95 % confidence interval ( CI ) = 0.68 to 11.99 , P = 0.15 ) . In the group r and omised to 5 years ' tamoxifen the survival pattern shifted towards a significantly improved recurrence-free survival ( RFS ) among CYP3A5 * 3-homozygous patients ( HR = 0.20 , 95 % CI = 0.07 to 0.55 , P = 0.002 ) . No reliable differences could be seen between treatment duration and the genotypes of CYP2D6 , SULT1A1 or UGT2B15 . The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5 * 3 homozygotes was also seen in a multivariate Cox model ( HR = 0.13 , CI = 0.02 to 0.86 , P = 0.03 ) , whereas no differences could be seen for CYP2D6 , SULT1A1 and UGT2B15 . Conclusion The metabolism of tamoxifen is complex and the mechanisms responsible for the resistance are unlikely to be explained by a single polymorphism ; instead it is a combination of several mechanisms . However , the present data suggest that genetic variation in CYP3A5 may predict response to tamoxifen therapy Purpose : P-glycoprotein , encoded by the mdr-1 gene , confers multidrug resistance to a variety of antineoplastic agents , e.g. , paclitaxel . Recently , different polymorphisms in the mdr-1 gene have been identified and their consequences for the function of P-glycoprotein , as well as for the treatment response to P-glycoprotein substrates , are being clarified . We analyzed the allelic frequencies at polymorphic sites G2677T/A and C3435 T in ovarian cancer patients with good or poor response to treatment with paclitaxel in combination with carboplatin in order to evaluate their predictive values . Experimental Design : Fifty-three patients were included in the study ; 28 of them had been relapse-free for at least 1 year and 25 had progressive disease or relapsed within 12 months . A reference material consisting of 200 individuals was also analyzed . The genotypes of each single nucleotide polymorphism ( SNP ) were determined using Pyrosequencing . Results : The G2677T/A SNP was found to significantly correlate with treatment outcome . The probability of responding to paclitaxel treatment was higher in homozygously mutated patients ( T/T or T/A ; Fisher 's exact test ; P < 0.05 ) . The frequency of the T or A alleles was also higher in the group of patients who had a good response ( P < 0.05 ) . There was also a dose-dependent influence of the number of mutated alleles on the response to paclitaxel treatment ( χ2 test for linear-by-linear association ; P = 0.03 ) . However , the C3435 T SNP was not found to correlate to treatment outcome . Conclusions : The mdr-1 polymorphism G2677T/A in exon 21 correlates with the paclitaxel response in ovarian cancer and may be important for the function of P-glycoprotein and resistance to paclitaxel and provide useful information for individualized therapy For infants and very young children with brain tumors , chemotherapy after surgical resection is the main treatment due to neurologic and neuroendocrine adverse effects from whole brain irradiation . Topotecan , an anticancer drug with antitumor activity against pediatric brain tumors , can be given intravenous or orally . However , high interpatient variability in oral drug bioavailability is common in children less than 3 years old . Therefore , this study aim ed to determine the population pharmacokinetics of oral topotecan in infants and very young children , specifically evaluating the effects of age and ABCG2 and ABCB1 on the absorption rate constant ( Ka ) , as well as other covariate effects on all pharmacokinetic parameters . A nonlinear mixed effects model was implemented in Monolix 4.3.2 ( Lixoft , Orsay , France ) . A one-compartment model with first-order input and first-order elimination was found to adequately characterize topotecan lactone concentrations with population estimates as [ mean ( S.E. ) ] ; Ka = 0.61 ( 0.11 ) h−1 , apparent volume of distribution ( V/F ) = 40.2 ( 7.0 ) l , and apparent clearance ( CL/F ) = 40.0 ( 2.9 ) l/h . After including the body surface area in the V/F and CL/F as a power model centered on the population median , the ABCG2 rs4148157 allele was found to play a significant role in the value of Ka . Patients homozygous or heterozygous for G > A demonstrated a Ka value 2-fold higher than their GG counterparts , complemented with a 2-fold higher maximal concentration as well . These results demonstrate a possible role for the ABCG2 rs4148157 allele in the pharmacokinetics of oral topotecan in infants and very young children , and warrants further investigation Objective This study aim ed to explore the influence of SLC22A1 , PXR , ABCG2 , ABCB1 and CYP3A5 * 3 genetic polymorphisms on imatinib mesylate ( IM ) pharmacokinetics in Asian patients with chronic myeloid leukemia ( CML ) . Patients and Methods Healthy subjects belonging to three Asian population s ( Chinese , Malay , Indian ; n = 70 each ) and CML patients ( n = 38 ) were enrolled in a prospect i ve pharmacogenetics study . Imatinib trough ( C0h ) and clearance ( CL ) were determined in the patients at steady state . Haplowalk method was applied to infer the haplotypes and generalized linear model ( GLM ) to estimate haplotypic effects on IM pharmacokinetics . Association of haplotype copy numbers with IM pharmacokinetics was defined by Mann-Whitney U test . Results Global haplotype score statistics revealed a SLC22A1 sub-haplotypic region encompassing three polymorphisms ( rs3798168 , rs628031 and IVS7 + 850C > T ) , to be significantly associated with IM clearance ( p = 0.013 ) . Haplotype-specific GLM estimated that the haplotypes AGT and CGC were both associated with 22 % decrease in clearance compared to CAC [ CL ( * 10−2 L/hr/mg ) : CAC vs AGT : 4.03 vs 3.16 , p = 0.017 ; CAC vs CGC : 4.03 vs 3.15 , p = 0.017 ] . Patients harboring 2 copies of AGT or CGC haplotypes had 33.4 % lower clearance and 50 % higher C0h than patients carrying 0 or 1 copy [ CL ( * 10−2 L/hr/mg ) : 2.19 vs 3.29 , p = 0.026 ; C0h ( * 10−6 1/ml ) : 4.76 vs 3.17 , p = 0.013 , respectively ] . Further subgroup analysis revealed SLC22A1 and ABCB1 haplotypic combinations to be significantly associated with clearance and C0h ( p = 0.002 and 0.009 , respectively ) . Conclusion This exploratory study suggests that SLC22A1-ABCB1 haplotypes may influence IM pharmacokinetics in Asian CML patients Background This study aim ed to evaluate the efficacy of a high dose of oral tegafur-uracil ( 400 mg/m2 ) plus leucovorin with preoperative chemoradiation of locally advanced rectal cancer and to explore the impact of polymorphisms of cytochrome P 2A6 ( CYP2A6 ) , uridine monophosphate synthetase ( UMPS ) , and ATP-binding cassette B1 ( ABCB1 ) on clinical outcome . Methods Patients with cT3 or cT4 rectal cancer were enrolled and were given tegafur-uracil 400 mg/m2/day and leucovorin 90 mg/m2/day for 7 days a week during preoperative chemoradiation ( 50.4 Gy/28 fractions ) in this phase II trial . Primary endpoint was pathologic complete response rate , and the secondary endpoint was to explore the association between clinical outcomes and genetic polymorphisms CYP2A6 ( * 4 , * 7 , * 9 and * 10 ) , UMPS G638C , and three ABCB1 genotypes ( C1236 T , C3435 T , and G2677 T ) . Results Ninety-one patients were given study treatment , and 90 underwent surgery . Pathologic complete response was noted in 10 patients ( 11.1 % ) . There was no grade 4 or 5 toxicity ; 20 ( 22.0 % ) experienced grade 3 toxicities , including diarrhea ( 10 , 11.0 % ) , abdominal pain ( 2 , 2.2 % ) , and anemia ( 2 , 2.2 % ) . Relapse-free survival and overall survival at 5 years were 88.6 % and 94.2 % , respectively . Patients with the UMPS 638 CC genotype experienced significantly more frequent grade 2 or 3 diarrhea ( p for trend = 0.018 ) . Conclusions Preoperative chemoradiation with tegafur-uracil 400 mg/m2/day with leucovorin was feasible , but did not meet the expected pathologic complete response rate . The UMPS 638 CC genotype might be a c and i date biomarker predicting toxicity in patients receiving tegafur-uracil/leucovorin-based preoperative chemoradiation for locally advanced rectal cancer . Trial registration IS RCT N11812525 , registered on 25 July 2016 . Retrospectively registered Background A Phase I dose escalation first in man study assessed maximum tolerated dose ( MTD ) , dose-limiting toxicity ( DLT ) and recommended Phase II dose of TP300 , a water soluble prodrug of the Topo-1 inhibitor TP3076 , and active metabolite , TP3011 . Methods Eligible patients with refractory advanced solid tumors , adequate performance status , haematologic , renal , and hepatic function . TP300 was given as a 1-hour i.v . infusion 3-weekly and pharmacokinetic ( PK ) profiles of TP300 , TP3076 and TP3011 were analysed . Polymorphisms in CYP2D6 , AOX1 and UGT1A1 were studied and DNA str and -breaks measured in peripheral blood mononuclear cells ( P BMC s ) . Results 32 patients received TP300 at 1 , 2 , 4 , 6 , 8 , 10 , 12 mg/m2 . MTD was 10 mg/m2 ; DLTs at 12 ( 2/4 patients ) and 10 mg/m2 ( 3/12 ) included thrombocytopenia and febrile neutropenia ; diarrhoea was uncommon . Six patients ( five had received irinotecan ) , had stable disease for 1.5 - 5 months . TP3076 showed dose proportionality in AUC and Cmax from 1–10 mg/m2 . Genetic polymorphisms had no apparent influence on exposure . DNA str and -breaks were detected after TP300 infusion . Conclusions TP300 had predictable hematologic toxicity , and diarrhoea was uncommon . AUC at MTD is substantially greater than for SN38 . TP3076 and TP3011 are equi-potent with SN38 , suggesting a PK advantage . Trial registration EU-CTR2006 - 001345 - Purpose 3-AP is a ribonucleotide reductase inhibitor and has been postulated to act synergistically with other chemotherapeutic agents . This study was conducted to determine the toxicity and antitumor activity of 3-AP with irinotecan . Correlative studies included pharmacokinetics and the effects of ABCB1 and UGT1A1 polymorphisms . Methods The treatment plan consisted of irinotecan on day 1 with 3-AP on days 1–3 of a 21-day cycle . Starting dose was irinotecan 150 mg/m2 and 3-AP 85 mg/m2 per day . Polymorphisms of ABCB1 were evaluated by pyrosequencing . Drug concentrations were determined by HPLC . Results Twenty-three patients were enrolled , 10 men and 13 women . Tumor types included seven patients with pancreatic cancer , four with lung cancer , two with cholangiocarcinoma , two with mesothelioma , two with ovarian cancer , and six with other malignancies . Two patients experienced dose-limiting toxicity ( DLT ) at dose level 1 , requiring amendment of the dose-escalation scheme . Maximal tolerated dose ( MTD ) was determined to be 3-AP 60 mg/m2 per day and irinotecan 200 mg/m2 . DLTs consisted of hypoxia , leukopenia , fatigue , infection , thrombocytopenia , dehydration , and ALT elevation . One partial response in a patient with refractory non-small cell lung cancer was seen . Genotyping suggests that patients with wild-type ABCB1 have a higher rate of grade 3 or 4 toxicity than those with ABCB1 mutations . Conclusions The MTD for this combination was 3-AP 60 mg/m2 per day on days 1–3 and irinotecan 200 mg/m2 on day 1 every 21 days . Antitumor activity in a patient with refractory non-small cell lung cancer was noted at level 1 Background Pre clinical studies demonstrated antiproliferative synergy of 1,25-D3 ( calcitriol ) with cisplatin . The goals of this phase I/II study were to determine the recommended phase II dose ( RP2D ) of 1,25-D3 with cisplatin and docetaxel and its efficacy in metastatic non-small-cell lung cancer . Methods Patients were ≥18 years , PS 0–1 with normal organ function . In the phase I portion , patients received escalating doses of 1,25-D3 intravenously every 21 days prior to docetaxel 75 mg/m2 and cisplatin 75 mg/m2 using st and ard 3 + 3 design , targeting dose-limiting toxicity ( DLT ) rate <33 % . Dose levels of 1,25-D3 were 30 , 45 , 60 , and 80 mcg/m2 . A two-stage design was employed for phase II portion . We correlated CYP24A1 tagSNPs with clinical outcome and 1,25-D3 pharmacokinetics ( PK ) . Results 34 patients were enrolled . At 80 mcg/m2 , 2/4 patients had DLTs of grade 4 neutropenia . Hypercalcemia was not observed . The RP2D of 1,25-D3 was 60 mcg/m2 . Among 20 evaluable phase II patients , there were 2 confirmed , 4 unconfirmed partial responses ( PR ) , and 9 stable disease ( SD ) . Median time to progression was 5.8 months ( 95 % CI 3.4 , 6.5 ) , and median overall survival 8.7 months ( 95 % CI 7.6 , 39.4 ) . CYP24A1 SNP rs3787554 ( C > T ) correlated with disease progression ( P = 0.03 ) and CYP24A1 SNP rs2762939 ( C > G ) trended toward PR/SD ( P = 0.08 ) . There was no association between 1,25-D3 PK and CYP24A1 SNPs . Conclusions The RP2D of 1,25-D3 with docetaxel and cisplatin was 60 mcg/m2 every 21 days . Pre-specified endpoint of 50 % confirmed RR was not met in the phase II study . Functional SNPs in CYP24A1 may inform future studies individualizing 1,25-D3 BACKGROUND Adjuvant tamoxifen therapy is effective for postmenopausal women with endocrine-responsive breast cancer . Cytochrome P450 2D6 ( CYP2D6 ) enzyme metabolizes tamoxifen to clinical ly active metabolites , and CYP2D6 polymorphisms may adversely affect tamoxifen efficacy . In this study , we investigated the clinical relevance of CYP2D6 polymorphisms . METHODS We obtained tumor tissues and isolated DNA from 4861 of 8010 postmenopausal women with hormone receptor-positive breast cancer who enrolled in the r and omized , phase III double-blind Breast International Group ( BIG ) 1 - 98 trial between March 1998 and May 2003 and received tamoxifen and /or letrozole treatment . Extracted DNA was used for genotyping nine CYP2D6 single-nucleotide polymorphisms using polymerase chain reaction-based methods . Genotype combinations were used to categorize CYP2D6 metabolism phenotypes as poor , intermediate , and extensive metabolizers ( PM , IM , and EM , respectively ; n = 4393 patients ) . Associations of CYP2D6 metabolism phenotypes with breast cancer-free interval ( referred to as recurrence ) and treatment-induced hot flushes according to r and omized endocrine treatment and previous chemotherapy were assessed . Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS No association between CYP2D6 metabolism phenotypes and breast cancer-free interval was observed among patients who received tamoxifen monotherapy without previous chemotherapy ( P = .35 ) . PM or IM phenotype had a non-statistically significantly reduced risk of breast cancer recurrence compared with EM phenotype ( PM or IM vs EM , HR of recurrence = 0.86 , 95 % CI = 0.60 to 1.24 ) . CYP2D6 metabolism phenotype was associated with tamoxifen-induced hot flushes ( P = .020 ) . Both PM and IM phenotypes had an increased risk of tamoxifen-induced hot flushes compared with EM phenotype ( PM vs EM , HR of hot flushes = 1.24 , 95 % CI = 0.96 to 1.59 ; IM vs EM , HR of hot flushes = 1.23 , 95 % CI = 1.05 to 1.43 ) . CONCLUSIONS CYP2D6 phenotypes of reduced enzyme activity were not associated with worse disease control but were associated with increased hot flushes , contrary to the hypothesis . The results of this study do not support using the presence or absence of hot flushes or the pharmacogenetic testing of CYP2D6 to determine whether to treat postmenopausal breast cancer patients with tamoxifen Single nucleotide polymorphisms ( SNPs ) in the multiple drug resistance protein 1 ( MRP1 ) and P-glycoprotein 1 ( MDR1 ) genes modulate their ability to mediate drug resistance . We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and /or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin ( PLD ) . The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population , all of whom received PLD + bortezomib . Its presence was associated with a longer time to progression ( TTP ; median 330 vs. 129 days ; p = 0.0008 ) , progression-free survival ( PFS ; median 338 vs. 129 days ; p = 0.0006 ) , and overall survival ( p = 0.0045 ) . MDR1/3435(C > T ) , which was in Hardy – Weinberg equilibrium , showed a trend of association with PFS ( p = 0.0578 ) , response rate ( p = 0.0782 ) and TTP ( p = 0.0923 ) in PLD + bortezomib patients , though no correlation was found in the bortezomib arm . In a recessive genetic model , MDR1/3435 T was significantly associated with a better TTP ( p = 0.0405 ) and PFS ( p = 0.0186 ) in PLD + bortezomib patients . These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and /or refractory myeloma patients treated with PLD + bortezomib . Moreover , they support prospect i ve studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients Introduction Tamoxifen is one of the most effective adjuvant breast cancer therapies available . Its metabolism involves the phase I enzyme , cytochrome P4502D6 ( CYP2D6 ) , encoded by the highly polymorphic CYP2D6 gene . CYP2D6 variants result ing in poor metabolism of tamoxifen are hypothesised to reduce its efficacy . An FDA -approved pre-treatment CYP2D6 gene testing assay is available . However , evidence from published studies evaluating CYP2D6 variants as predictive factors of tamoxifen efficacy and clinical outcome are conflicting , querying the clinical utility of CYP2D6 testing . We investigated the association of CYP2D6 variants with breast cancer specific survival ( BCSS ) in breast cancer patients receiving tamoxifen . Methods This was a population based case-cohort study . We genotyped known functional variants ( n = 7 ; minor allele frequency ( MAF ) > 0.01 ) and single nucleotide polymorphisms ( SNPs ) ( n = 5 ; MAF > 0.05 ) tagging all known common variants ( tagSNPs ) , in CYP2D6 in 6640 DNA sample s from patients with invasive breast cancer from SEARCH ( Studies of Epidemiology and Risk factors in Cancer Heredity ) ; 3155 cases had received tamoxifen therapy . There were 312 deaths from breast cancer , in the tamoxifen treated patients , with over 18000 years of cumulative follow-up . The association between genotype and BCSS was evaluated using Cox proportional hazards regression analysis . Results In tamoxifen treated patients , there was weak evidence that the poor-metaboliser variant , CYP2D6 * 6 ( MAF = 0.01 ) , was associated with decreased BCSS ( P = 0.02 ; HR = 1.95 ; 95 % CI = 1.12 - 3.40 ) . No other variants , including CYP2D6 * 4 ( MAF = 0.20 ) , previously reported to be associated with poorer clinical outcomes , were associated with differences in BCSS , in either the tamoxifen or non-tamoxifen groups . Conclusions CYP2D6 * 6 may affect BCSS in tamoxifen-treated patients . However , the absence of an association with survival in more frequent variants , including CYP2D6 * 4 , questions the validity of the reported association between CYP2D6 genotype and treatment response in breast cancer . Until larger , prospect i ve studies confirming any associations are available , routine CYP2D6 genetic testing should not be used in the clinical setting ABSTRACT The purpose of this study is to investigate associations between allelic variations of ABCG2 and ABCB1 with skin toxicity , diarrhea , liver injury and interstitial lung disease ( ILD ) in gefitinib-treated patients . A prospect i ve clinical study of 83 Japanese patients with non – small – cell lung cancer was performed . Polymorphic loci in ABCG2 and ABCB1 were genotyped , and their effects on gefitinib toxicities were evaluated . ABCG2 34G > A was statistically associated with occurrence of skin rash ; 13 ( 42 % ) of the 32 patients with at least one variant ABCG2 34G > A allele ( G/A and A/A ) developed grade 2 or worse skin rash , whereas only 10 ( 19 % ) of 51 patients homozygous for the reference allele ( G/G ) for the wild-type sequence for both alleles did so ( P = 0.046 ) . There was no significant association between severe toxicities and polymorphisms of ABCG2 421C > A nor ABCB1 3435C > T. The results suggested that ABCG2 34G > A would be useful for predicting grade 2 or worse skin rash Lung cancer is one of the most common cancers and is the leading cause of death worldwide . Platinum-based chemotherapy is the main treatment method in lung cancer patients . Our previous studies indicated that single nucleotide polymorphisms ( SNPs ) in some transporter genes played important role in platinum-based chemotherapy efficacy . The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy . The main polymorphisms on transporters OCT2 , LRP , AQP2 , AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients . The rs195854 in genotypic model , rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response . In stratification analysis , TMEM205 rs896412 , OCT2 rs1869641 and rs195854 , AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response . In conclusion , the genetic polymorphisms in OCT2 , AQP2 , AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients Introduction Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types . The current study in children with B-cell non-Hodgkin 's lymphoma ( NHL ) was design ed to corroborate previous findings in a large prospect i ve study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology . Methods A total of 644 plasma sample s collected over a 5 year period , from 49 B-cell NHL patients ≤18 years receiving cyclophosphamide ( 250 mg/m2 ) , were used to characterise a population pharmacokinetic model . Polymorphisms in genes including CYP2B6 and CYP2C19 were analysed . Results A two-compartment model provided the best fit of the population analysis . The mean cyclophosphamide clearance value following dose 1 was significantly lower than following dose 5 ( 1.83 ± 1.07 versus 3.68 ± 1.43 L/h/m2 , respectively ; mean ± st and ard deviation from empirical Bayes estimates ; P < 0.001 ) . The presence of at least one CYP2B6 * 6 variant allele was associated with a lower cyclophosphamide clearance following both dose 1 ( 1.54 ± 0.11 L/h/m2 versus 2.20 ± 0.31 L/h/m2 , P = 0.033 ) and dose 5 ( 3.12 ± 0.17 L/h/m2 versus 4.35 ± 0.37 L/h/m2 , P = 0.0028 ) , as compared to homozygous wild-type patients . No pharmacokinetic parameters investigated were shown to have a significant influence on progression free survival . Conclusion The results do not support previous findings of a link between cyclophosphamide pharmacokinetics or metabolism and disease recurrence in childhood B-cell NHL . While CYP2B6 genotype was shown to influence pharmacokinetics , there was no clear impact on clinical outcome Pharmacogenetic studies in chronic myelogenous leukemia ( CML ) typically use a c and i date gene approach . In an alternative strategy , we analyzed the impact of single nucleotide polymorphisms ( SNPs ) in drug transporter genes on the molecular response to imatinib , using a DNA chip containing 857 SNPs covering 94 drug transporter genes . Two cohorts of CML patients treated with imatinib were evaluated : an exploratory cohort including 105 patients treated at 400 mg/d and a validation cohort including patients sample d from the 400 mg/d and 600 mg/d arms of the prospect i ve SPIRIT trial ( n=239 ) . Twelve SNPs discriminating patients according to cumulative incidence of major molecular response ( CI-MMR ) were identified within the exploratory cohort . Three of them , all located within the ABCG2 gene , were vali date d in patients included in the 400 mg/d arm of the SPIRIT trial . We identified an ABCG2 haplotype ( define as G-G , rs12505410 and rs2725252 ) as associated with significantly higher CI-MMR in patients treated at 400 mg/d . Interestingly , we found that patients carrying this ABCG2 “ favorable ” haplotype in the 400 mg arm reached similar CI-MMR rates that patients r and omized in the imatinib 600 mg/d arm . Our results suggest that response to imatinib may be influenced by constitutive haplotypes in drug transporter genes . Lower response rates associated with “ non-favorable ” ABCG2 haplotypes may be overcome by increasing the imatinib daily dose up to 600 mg/d Estrogen catabolism is a major function of CYP2C19 . The effect of CYP2C19 polymorphisms on tamoxifen sensitivity may therefore not only be mediated by a variation in tamoxifen metabolite levels but also by an effect on breast cancer risk and molecular subtype due to variation in lifelong exposure to estrogens . We determined the association between these polymorphisms and tamoxifen sensitivity in the context of a r and omized trial , which allows for the discernment of prognosis from prediction . We isolated primary tumor DNA from 535 estrogen receptor-positive , stages I – III , postmenopausal breast cancer patients who had been r and omized to tamoxifen ( 1–3 years ) or no adjuvant therapy . Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of CYP2C19 * 2 and CYP2C19 * 17 . Hazard ratios and interaction terms were calculated using multivariate Cox proportional hazard models , stratified for nodal status . Tamoxifen benefit was not significantly affected by CYP2C19 * 17 . Patients with at least one CYP2C19 * 2 allele derived significantly more benefit from tamoxifen ( HR 0.26 ; p = 0.001 ) than patients without a CYP2C19 * 2 allele ( HR 0.68 ; p = 0.18 ) ( p for interaction 0.04 ) . In control patients , CYP2C19 * 2 was an adverse prognostic factor . In conclusion , breast cancer patients carrying at least one CYP2C19 * 2 allele have an adverse prognosis in the absence of adjuvant systemic treatment , which can be substantially improved by adjuvant tamoxifen treatment Reliable biomarkers are required to predict the response to sorafenib . We investigated genomic variations associated with responsiveness to sorafenib for patients with unresectable hepatocellular carcinoma ( HCC ) . Blood sample s from 2 extreme , 2 strong and 3 poor responders to sorafenib were subjected to whole-genome analysis . Then , we vali date d c and i date genomic variations with another 174 HCC patients , and performed in vitro functional analysis and in silico analyses . Genomic data of > 96 gigabases/ sample was generated at average of ~34X sequencing depth . In total , 1813 genomic variations were matched to sorafenib responses in clinical data ; 708 were located within regions for sorafenib-target genes or drug absorption , distribution , metabolism , and excretion (ADME)-related genes . From them , 36 variants were within the coding regions and 6 identified as non-synonymous single-nucleotide variants from 4 ADME-related genes ( ABCB1 , FMO3 , MUSK , and SLC15A2 ) . Validation genotyping confirmed sequencing results and revealed patients genotype for rs2257212 in SLC15A2 showed longer progression-free survival ( HR = 2.18 ) . In vitro study displayed different response to sorafenib depending on the genotype of SLC15A2 . Structural prediction analysis revealed changes of the phosphorylation levels in protein , potentially affecting sorafenib-associated enzymatic activity . Our finding using extreme responder seems to generate robust biomarker to predict the response of sorafenib treatment for HCC The reduced folate carrier ( RFC ) is involved in the transport of methotrexate ( MTX ) across the cell membrane . The RFC gene ( SLC19A1 ) is located on chromosome 21 , and we hypothesized that the RFC80 G > A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone . A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocol s were included , and we found that the RFC AA variant was associated with a 50 % better chance of staying in remission compared with GG or GA variants ( P = .046 ) . Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant . In a subset of 182 children receiving 608 high-dose MTX courses , we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants ( platelet 73 vs 99/105 x 10(9)/L , P = .004 , hemoglobin 5.6 vs 5.9/6.0 mmol/L , P = .004 ) and a higher degree of liver toxicity in patients with RFC GG variant ( alanine aminotransferase 167 vs 127/124 U/L , P = .05 ) . In conclusion , the RFC 80G > A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX S‐1 is an oral anticancer agent composed of tegafur ( FT ) , 5‐chloro‐2,4‐dihydroxypyridine ( CDHP ) , and potassium oxonate . CDHP is added to prevent degradation of 5‐fluorouracil ( 5‐FU ) by inhibiting dihydropyrimidine dehydrogenase . CYP2A6 is involved in the biotransformation of FT to 5‐FU . Thus , we prospect ively analyzed the effects of the CYP2A6 genotype , plasma level of CDHP , and patient characteristics on the pharmacokinetic ( PK ) variability of FT and 5‐FU . Fifty‐four Japanese patients with metastatic or recurrent cancers who received S‐1 were enrolled . The CYP2A6 polymorphisms ( * 4A , * 7 , and * 9 ) with deficient or reduced activity were analyzed . All subjects were classified into three groups according to their CYP2A6 genotype : wild type ( * 1/*1 ) , one‐variant allele ( * 1/any ) , or two‐variant alleles ( combination other than * 1 ) . The PK of FT , 5‐FU , and CDHP were measured on day 1 of treatment . Multivariate regression analysis revealed that oral clearance of FT was associated with the CYP2A6 genotype ( analysis of variance [ ANOVA ] , P = 0.000838 ) . The oral clearance of FT seen in patients with the two‐variant alleles was significantly lower than those in wild type and the one‐variant allele ( 95 % confidence intervals 0.75–2.41 and 0.41–1.82 , respectively ; Tukey‐Kramer test ) . The area under the time – concentration curve ( AUC ) of 5‐FU was significantly correlated with the AUC of CDHP ( ANOVA , P = 0.00126 ) . The AUC of 5‐FU and CDHP were inversely correlated with creatinine clearance ( ANOVA , P = 0.0164 and P = 0.000762 , respectively ) . Although the CYP2A6 variants are the cause of the PK variability of FT , the AUC of CDHP affected by renal function is the key determinant of the variability in the PK of 5‐FU . ( Cancer Sci 2008 ; 99 : 1049–1054 PURPOSE To evaluate the efficacy and toxicity of pemetrexed combined with bevacizumab as second-line therapy for patients with advanced non-small-cell lung cancer ( NSCLC ) and to correlate allelic variants in pemetrexed-metabolizing genes with clinical outcome . PATIENTS AND METHODS Patients with previously treated NSCLC received pemetrexed ( 500 mg/m(2 ) intravenous ) combined with bevacizumab ( 15 mg/kg intravenous ) every 3 weeks . The primary end point , evaluated using a one-stage Fleming design for detecting a true success rate of at least 70 % , was the proportion of patients who were progression free and on treatment at 3 months . Polymorphisms in genes responsible for pemetrexed transport ( reduced folate carrier [ SLC19A1 ] ) and metabolism ( folylpolyglutamate synthase [ FPGS ] and gamma-glutamyl hydrolase [ GGH ] ) evaluated in germline DNA ( blood ) were correlated with treatment outcome . RESULTS Forty-eight evaluable patients ( 14 females and 34 males ) received a median of four cycles ( range , one to 20 cycles ) . The most common grade 3 or 4 nonhematologic adverse events ( AEs ) were fatigue ( 13 % ) , dyspnea ( 10 % ) , and thrombosis ( 10 % ) . Grade 3 or 4 hematologic AEs were neutropenia ( 19 % ) and lymphopenia ( 13 % ) . Twenty-four ( 57 % ; 95 % CI , 41 % to 72 % ) of the first 42 patients met the success criteria . Median overall survival ( OS ) and progression-free survival ( PFS ) times were 8.6 and 4.0 months , respectively . The exon 6 (2522)C-->T polymorphism in SLC19A1 correlated with 3-month progression-free status ( P = .01 ) and with PFS ( P = .05 ) . The IVS1(1307)C-->T polymorphism in GGH correlated with OS ( P = .04 ) . CONCLUSION The study did not meet its primary end point . However , the median PFS time of 4 months is promising . Pharmacogenetic studies in larger cohorts are needed to definitively identify polymorphisms that predict for survival and toxicity of pemetrexed Paclitaxel is one of the most frequently used chemotherapeutic agents for the treatment of breast cancer patients . Using a c and i date gene approach , we hypothesized that polymorphisms in genes relevant to the metabolism and transport of paclitaxel are associated with treatment efficacy and toxicity . Patient and tumor characteristics and treatment outcomes were collected prospect ively for breast cancer patients treated with paclitaxel-containing regimens in the neoadjuvant setting . Treatment response was measured before and after each phase of treatment by clinical tumor measurement and categorized according to RECIST criteria , while toxicity data were collected from physician notes . The primary endpoint was achievement of clinical complete response ( cCR ) and secondary endpoints included clinical response rate ( complete response + partial response ) and grade 3 + peripheral neuropathy . The genotypes and haplotypes assessed were CYP1B1 * 3 , CYP2C8 * 3 , CYP3A4 * 1B/CYP3A5 * 3C , and ABCB1 * 2 . A total of 111 patients were included in this study . Overall , cCR was 30.1 % to the paclitaxel component . CYP2C8 * 3 carriers ( 23/111 , 20.7 % ) had higher rates of cCR ( 55 % vs. 23 % ; OR = 3.92 [ 95 % CI : 1.46–10.48 ] , corrected p = 0.046 ) . In the secondary toxicity analysis , we observed a trend toward greater risk of severe neuropathy ( 22 % vs. 8 % ; OR = 3.13 [ 95 % CI : 0.89–11.01 ] , uncorrected p = 0.075 ) in subjects carrying the CYP2C8 * 3 variant . Other polymorphisms interrogated were not significantly associated with response or toxicity . Patients carrying CYP2C8 * 3 are more likely to achieve clinical complete response from neoadjuvant paclitaxel treatment , but may also be at increased risk of experiencing severe peripheral neurotoxicity OBJECTIVE Tumor cells that overexpress P-glycoprotein ( Pgp ) may be resistant to several anticancer agents due to altered pharmacokinetics and reduced intracellular concentrations of the anticancer agents . Pgp is encoded by the ATP binding cassette gene B1 ( ABCB1 ) . To our knowledge , only one previous report has evaluated the effect of ABCB1 gene polymorphisms on clinical outcomes of gastric cancer . The purpose of this analysis was to evaluate the impact of genetic polymorphisms of the ABCB1 gene on clinical outcomes in patients with advanced gastric cancer ( AGC ) treated with second-line chemotherapy . METHODS We retrospectively analyzed the impact of ABCB1 gene polymorphisms ( ABCB1 3435C > T ) on clinical outcomes in 100 patients with AGC who received second-line chemotherapy . RESULTS Median overall survival ( OS ) since the initiation of second-line chemotherapy was 6.0 months ( 95 % confidence interval [ CI ] , 4.8 to 8.0 months ) , and median progression-free survival ( PFS ) was 2.7 months ( 95 % CI , 2.1 to 3.4 months ) . In a multivariate analysis of PFS , a 3435 CC polymorphism ( n=45 ) was significantly associated with longer PFS compared with the CT/TT type polymorphism ( n=55 ) , with borderline significance ( PFS of 3.2 months vs. 2.2 months , respectively ; HR 1.50 ; 95 % CI , 0.98 - 2.30 ; P = 0.061 ) . ABCB1 3435 C > T polymorphisms were not associated with OS . No interaction was seen between ABCB1 polymorphisms and treatment regimens . CONCLUSION Genetic polymorphisms of ABCB1 3435C > T might have a possible impact on clinical outcomes of second-line chemotherapy in AGC . Further prospect i ve evaluation using a larger sample size is required AIM Lung carcinoma is the most common malignancy and the leading cause of cancer deaths worldwide . Although clinical factors including age , performance status and stage influence the likelihood of benefit from and tolerability of chemotherapy , the genetic profile of individual patients may be an independent predictor of response and toxicity . The present study aim ed to identify pharmacogenetic markers associated with clinical response and toxicity in patients with advanced non-small cell lung cancer ( NSCLC ) treated primarily with carboplatin and paclitaxel . MATERIAL S & METHODS Genomic DNA sample s from 90 adult male patients diagnosed with stage IIIB/IV NSCLC were genotyped for SNPs in c and i date genes of relevance to platinating agents and paclitaxel and analyzed for association with survival and toxicities in univariate and multivariate models . RESULTS After adjusting for performance status and stage , SNPs in the drug transporters ABCB1 and ABCC1 , as well as within NQO1 were associated with progression-free survival . With respect to hematological and nonhematological toxicities , SNPs in drug transporters ( ABCB1 and ABCG2 ) were associated with thrombocytopenia , nausea and neutropenia , whereas SNPs in the DNA repair pathway genes ERCC4 and XPC were significantly associated with neutropenia and sensory neuropathy , respectively . CONCLUSION Our study evaluated and identified SNPs in key c and i date genes in platinating agent and taxane pathways associated with outcome and toxicity in advanced NSCLC . If vali date d in large prospect i ve studies , these findings might provide opportunities to personalize therapeutic strategies Purpose : To retrospectively evaluate the effects of six known allelic variants in the CYP2C8 , CYP3A4 , CYP3A5 , and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel ( Taxol ) . Experimental Design : A cohort of 97 Caucasian patients with cancer ( median age , 57 years ) received paclitaxel as an i.v . infusion ( dose range , 80 - 225 mg/m2 ) . Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing . Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling . The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM . In addition , relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA . Results : The allele frequencies for the CYP2C8 * 2 , CYP2C8 * 3 , CYP2C8 * 4 , CYP3A4 * 3 , CYP3A5 * 3C , and ABCB1 3435C > T variants were 0.7 % , 9.2 % , 2.1 % , 0.5 % , 93.2 % , and 47.1 % , respectively , and all were in Hardy-Weinberg equilibrium . The population typical value of clearance of unbound paclitaxel was 301 L/h ( individual clearance range , 83.7 - 1055 L/h ) . The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel . Likewise , no statistically significant association was observed between the ABCB1 3435C > T variant and any of the studied pharmacokinetic variables . Conclusions : This study indicates that the presently evaluated variant alleles in the CYP2C8 , CYP3A4 , CYP3A5 , and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics Background : The large individual variability for anticancer drugs in both outcome and toxicity risk makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect . Aims : This work aim ed to evaluate the importance of genetic polymorphisms involved in drug detoxification to predict clinical outcomes of anthracycline-based neoadjuvant chemotherapy for breast cancer . Results : GSTP1 313 AA genotype was associated with a poor clinical response relative to G allele carrier ( 58.4 % vs 80.8 % ; p = 0.006 ) , and MDR1 3435 TT genotype had a worse response compared with C allele carrier ( 33.3 % vs 71.2 % p = 0.001 ) . Patients with both the adverse genotypes of GSTP1 314AA and MDR 3435TT showed the worst therapy efficacy in all ( 14.3 % ; p = 0.000 ) . Kaplan-Meier survival analysis showed that the patients with no adverse genotype were associated with decreased hazard of relapse ( p = 0.002 ) , compared with those with 1 or 2 adverse genotypes . Multivariate analysis demonstrated that clinical response and no adverse genotype was independent predictors of disease-free survival ( DFS ) . Methods : Genotyping was performed by allele-specific oligonucleotide ligation reaction ( MnSOD , CAT , GSTP1 ) , multiplex PCR ( GSTM1 , GSTT1 ) or PCR-RFLP ( MDR1 ) . Based on 153 patients received anthracycline-based neoadjuvant chemotherapy , these genotypes or their combinations in relation to treatment-related response , hematologic toxicity and DFS were investigated . Conclusions : These results suggest that polymorphisms in GSTP1 and MDR1 may help to predict clinical response and DFS of anthracycline-based chemotherapy , and a polygenic pathway approach should provide more useful information . The findings required independent prospect i ve confirmation Drug resistance is a clinical ly relevant problem in the treatment of acute myeloid leukaemia ( AML ) . We have previously reported a relationship between single nucleotide polymorphisms ( SNPs ) of ABCB1 , encoding the multi‐drug transporter P‐glycoprotein , and overall survival ( OS ) in normal karyotype (NK)‐AML . Here we extended this material , enabling subgroup analysis based on FLT3 and NPM1 status , to further eluci date the influence of ABCB1 SNPs . De novo NK‐AML patients ( n = 201 ) were analysed for 1199G > A , 1236C > T , 2677G > T/A and 3435C > T , and correlations to outcome were investigated . FLT3 wild‐type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele ; medians 20 vs. 49 months , respectively , P = 0·017 . There was also an inferior outcome in FLT3 wild‐type 2677G/G patients compared to patients carrying the variant allele , median OS 20 vs. 35 months , respectively , P = 0·039 . This was confirmed in Cox regression analysis . Our results indicate that ABCB1 1236C > T and 2677G > T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild‐type group , which may contribute to future individualizing of treatment strategies The authors investigated whether ABCB1 , ABCC2 , and ABCG2 genetic polymorphisms affect pharmacokinetics ( PK ) of irinotecan and treatment outcome of patients with advanced nonsmall cell lung cancer ( NSCLC ) BACKGROUND & AIMS Variants in the cytochrome P450 2C9 ( CYP2C9 ) gene are associated with impaired metabolism of celecoxib . We examined the influence of CYP2C9 * 2 ( R144C ) and CYP2C9 * 3 ( I359L ) variants on dose-related response or toxicity in a r and omized trial of celecoxib . METHODS We identified individuals with CYP2C9 * 2 and CYP2C9 * 3 genotypes ( > or=1 variant allele ) in the Adenoma Prevention with Celecoxib trial . Following adenoma removal , patients were assigned r and omly to groups given placebo or low-dose ( 200 mg twice daily ) or high-dose ( 400 mg twice daily ) celecoxib and underwent follow-up colonoscopies at 1 and /or 3 years . RESULTS Among 1660 patients , 21 % were CYP2C9 * 2 , and 12 % were CYP2C9 * 3 genotypes . Overall , celecoxib was associated with a dose-dependent reduction in adenoma , compared with placebo , with relative risks ( RR ) of 0.65 ( 95 % confidence interval [ CI ] : 0.56 - 0.76 ) for the low-dose and 0.54 ( 95 % CI : 0.46 - 0.63 ) for the high-dose groups . However , the additional protective effect of the high dose , compared with the low-dose , was observed only in those with CYP2C9 * 3 genotypes ( RR , 0.51 ; 95 % CI : 0.30 - 0.87 ) . The high dose , compared with low dose , was not associated with significant risk reduction among those with CYP2C9 * 2 ( RR , 0.83 ; 95 % CI : 0.57 - 1.21 ) or wild-type ( RR , 0.89 ; 95 % CI : 0.72 - 1.11 ) genotypes . Compared with placebo , a higher incidence of cardiovascular events was associated with both doses among patients with wild-type genotypes but only with the high dose among patients with variant genotypes . CONCLUSIONS The greater efficacy of high-dose celecoxib , compared with the low-dose , in preventing colorectal adenoma appears confined to individuals with slow metabolizer ( CYP2C9 * 3 ) genotypes . Genetic variability influences susceptibility to the potential benefits and hazards of celecoxib Purpose : To correlate polymorphisms in genes involved in the transport , activation , and inactivation of pemetrexed with the outcome of patients with advanced non-small cell lung cancer ( NSCLC ) treated with pemetrexed . Experimental Design : Data from a phase II NSCLC trial evaluating the optimal schedule of gemcitabine and pemetrexed were used . All patients with available DNA were genotyped for polymorphisms in FPGS , GGH , and SLC19A1 genes . Patients with various genotypes were compared for efficacy and adverse events result ing from pemetrexed . Results : Fifty-four patients had genotype results for all polymorphisms studied . Patients with the homozygous variant genotypes for SLC19A1 IVS4(2117 ) C > T , IVS5(9148 ) C > A , and wild-type genotype for exon6(2522 ) C > T had a significantly better overall survival compared with their counterparts ( median overall survival in months : 8.9 [ CC ] versus 14.0 [ CT ] versus 16.7 [ TT ] ; 9.4 [ CC ] versus 10.3 [ CA ] versus 22.7 [ AA ] ; and 22.7 [ CC ] versus 10.3 [ CT ] versus 9.4 [ TT ] respectively ; all log rank p = 0.03 ) . Patients with the heterozygous TC genotype for GGH IVS5(1042 ) T > C had greater rates of confirmed response + stable disease compared with the TT genotype ( 85 % versus 60 % ; odds ratio = 4.0 ; p = 0.06 ) . A greater risk for grade 3/4 SGPT ( ALT ) elevation was observed in patients heterozygous ( GA ) for the FPGS IVS1 ( 28 ) G > A polymorphism compared with the GG genotype ( 43 % versus 13 % ; odds ratio = 5.0 , p = 0.07 ) . All results were largely consistent within patients with nonsquamous ( n = 40 ) histology . Conclusion : Polymorphisms in SLC1A91 seem to predict for survival differences in pemetrexed-treated NSCLC . Additionally , polymorphisms in GGH and FPGS have marginal associations with response and adverse event . These results should be vali date d in larger prospect i ve studies using pemetrexed The aim of this study was to explore the impact of individual variation in drug elimination on imatinib disposition . Twenty‐two patients with gastrointestinal stromal tumor or chronic myeloid leukemia initially received imatinib 600 mg daily with dosage subsequently toxicity adjusted . Pharmacokinetic parameters on day 1 and at steady‐state were compared with elimination phenotype and single‐nucleotide polymorphisms of CYP3A5 and ABCB1 . A fivefold variation in estimated imatinib clearance ( CL/F ) was present on day 1 and mean CL/F had fallen by 26 % at steady state . This reduction in imatinib CL/F was associated with ABCB1 genotype , being least apparent in thymidine homozygotes at the 1236T > C , 2677G > T/A and 3435C > T loci . Toxicity‐related dose reduction also tended to be less common in these individuals . ABCB1 genotype was associated with steady‐state CL/F due to an apparent genotype‐specific influence of imatinib on elimination . Further evaluation of ABCB1 genotype and imatinib dosage is warranted OBJECTIVE To evaluate the impact of the multi-drug resistance 1(MDR1 ) C3435 T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy . METHODS From January 2005 to December 2008 , 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University . The polymorphism was tested using real time polymerase chain reaction ( RT-PCR ) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0 . RESULTS The CT/TT genotype of C3435 T was significantly associated with a shorter progression-free survival ( PFS ) and overall survival ( OS ) compared with the CC genotype [ PFS : adjusted hazard ratio ( HR ) = 2.01 , 95 % confidence intervals ( CI ) : 1.17 - 3.45 , P = 0.012 ; OS : adjusted HR = 2.37 , 95 % CI : 1.31 - 4.28 , P = 0.004 ] . TNM stage was also associated with PFS ( adjusted HR = 2.33 , 95 % CI : 1.34 - 4.05 , P = 0.003 ) and OS ( adjusted HR = 2.62 , 95 % CI : 1.44 - 4.76 , P = 0.002 ) in gastric cancer patients treated with postoperative adjuvant chemotherapy . CONCLUSION Our results suggest that the MDR1 gene C3435 T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy . This now needs to be confirmed by a r and omized prospect ively controlled study |
10,990 | 25,650,284 | Conclusions On the basis of our meta- analysis , we conclude that laparoscopic and open repair of incisional hernia is comparable . | Context The utility of laparoscopic repair in the treatment of incisional hernia repair is still contentious .
Objectives The aim was to conduct a meta- analysis of RCTs investigating the surgical and postsurgical outcomes of elective incisional hernia by open versus laparoscopic method . | BACKGROUND To analyze hospital re source utilization for laparoscopic vs open incisional hernia repair including the postoperative period . METHODS Prospect ively collected administrative data for incisional hernia repairs were examined . A total of 884 incisional hernia repairs were examined for trends in type of approach over time . Starting October 2001 , detailed records were available , and examined for operating room ( OR ) time , cost data , length of stay ( LOS ) , and 30-day postoperative hospital encounters . RESULTS Of the total , 469 incisional hernias were approached laparoscopically ( 53 % ) and 415 open ( 47 % ) . Laparoscopic repair had shorter LOS ( 1 + /- 0.2 days vs 2 + /- 0.6 days ) , longer OR time ( 149 + /- 4 min vs 89 + /- 4 min ) , higher supply costs ( 2,237 dollars + /- 71 dollars vs 664 dollars + /- 113 dollars ) , slightly lower total hospital cost ( 6,396 dollars + /- 477 dollars vs 7,197 dollars + /- 1,819 dollars ) , and slightly more postoperative hospital encounters ( 15 % vs 13 % ) . Use of laparoscopy increased over time ( 37 % in 2000 vs 68 % in 2004 ) . CONCLUSIONS Laparoscopic incisional hernia repair is becoming increasingly popular , and not at increased cost to the health care system Objective : The aim of the trial was to compare laparoscopic technique with open technique regarding short-term pain , quality of life ( QoL ) , recovery , and complications . Background : Laparoscopic and open techniques for incisional hernia repair are recognized treatment options with pros and cons . Methods : Patients from 7 centers with a midline incisional hernia of a maximum width of 10 cm were r and omized to either laparoscopic ( LR ) or open sublay ( OR ) mesh repair . Primary end point was pain at 3 weeks , measured as the bodily pain subscale of Short Form-36 ( SF-36 ) . Secondary end points were complications registered by type and severity ( the Clavien-Dindo classification ) , movement restrictions , fatigue , time to full recovery , and QoL up to 8 weeks . Results : Patients were recruited between October 2005 and November 2009 . Of 157 r and omized patients , 133 received intervention : 64 LR and 69 OR . Measurements of pain did not differ , nor did movement restriction and postoperative fatigue . SF-36 subscales favored the LR group : physical function ( P < 0.001 ) , role physical ( P < 0.012 ) , mental health ( P < 0.022 ) , and physical composite score ( P < 0.009 ) . Surgical site infections were 17 in the OR group compared with 1 in the LR group ( P < 0.001 ) . The severity of complications did not differ between the groups ( P < 0.213 ) . Conclusions : Postoperative pain or recovery at 3 weeks after repair of midline incisional hernias does not differ between LR and OR , but the LR results in better physical function and less surgical site infections than the OR does . ( Clinical Trials.gov Identifier : NCT00472537 Background The laparoscopic approach has emerged in the search for a surgical technique to decrease the morbidity associated with conventional repair of ventral hernias . In this study we aim ed to compare the results of our open and laparoscopic ventral hernia repairs prospect ively . Methods Between January 2001 and October 2005 , a total of 46 patients diagnosed with ventral hernias ( primary and incisional ) who were admitted to our surgical unit and accepted to be included in this study group were examined . All patients were divided into laparoscopic repair ( n = 23 ) and open repair ( n = 23 ) subgroups in a r and omized fashion . The patients ’ demographic characteristics , operation times , body mass indices , sizes of fascial defects , hernia locations , duration s of hospital stay , presence and degrees of postoperative pain , and postoperative minor and major complications were analysed and compared . All the data were expressed as means ± SDs . Chi-square and Wilcoxon tests were used for statistical analysis , and P < 0.05 was accepted as a significant statistical value ( SPSS 11.0 for Windows ) . Results The demographic characteristics of both groups were similar . Women predominated , especially in the laparoscopy group ( P < 0.05 ) . The comparison of the results revealed that the major advantage of laparoscopy was the shortened postoperative hospital stay and the reduced incidence of mesh infection ( P < 0.05 , P < 0.05 ) . On the other h and , operation time was significantly longer in the laparoscopy group ( P < 0.05 ) . The major complications encountered in the laparoscopy group were ileus and a missed enterotomy . The most frequent minor complication was seroma , which was significantly more frequent in the laparoscopy group ( P < 0.05 ) . Postoperative pain assessment revealed similar results in both groups ( P > 0.05 ) . Conclusions The laparoscopic approach appears to be as effective as open repairs in the treatment of ventral hernias . Advanced surgical skill , laparoscopic experience and high technology are m and atory factors for successful ventral hernia repair BACKGROUND The objective of this quasi experimental study was to compare the frequency of wound infection between open cholecystectomy ( OC ) and laparoscopic cholecystectomy ( LC ) conducted in Surgical Unit IV , Jinnah Hospital Lahore from June 2005 to January 2006 . METHODS 100 patients undergoing elective cholecystectomy for symptomatic gallstones were studied . The patients were allocated in the two groups of 50 each by simple r and om technique . Group-I underwent OC and Group-II underwent LC . The patients were then followed up for four weeks to pick up signs of wound infection . In case of infection , the degree of infection and the remedial measures done were documented and the results analysed . RESULTS In LC group there was only one case of Class-II wound infection i.e. 2 % . In case of OC there were three cases of wound infection i.e. 6 % . Out of these , two were of Class-IIl and one of Class-Il . CONCLUSION While there was no wound infection in cases of chronic Cholecystitis in both groups , the frequency of wound infection was three times as common in OC as compared to LC in Acute Cholecystitis/Empyema Objective : The objective of this study was to determine the best treatment of incisional hernia , taking into account recurrence , complications , discomfort , cosmetic result , and patient satisfaction . Background : Long-term results of incisional hernia repair are lacking . Retrospective studies and the midterm results of this study indicate that mesh repair is superior to suture repair . However , many surgeons are still performing suture repair . Methods : Between 1992 and 1998 , a multicenter trial was performed , in which 181 eligible patients with a primary or first-time recurrent midline incisional hernia were r and omly assigned to suture or mesh repair . In 2003 , follow-up was up date d. Results : Median follow-up was 75 months for suture repair and 81 months for mesh repair patients . The 10-year cumulative rate of recurrence was 63 % for suture repair and 32 % for mesh repair ( P < 0.001 ) . Abdominal aneurysm ( P = 0.01 ) and wound infection ( P = 0.02 ) were identified as independent risk factors for recurrence . In patients with small incisional hernias , the recurrence rates were 67 % after suture repair and 17 % after mesh repair ( P = 0.003 ) . One hundred twenty-six patients completed long-term follow-up ( median follow-up 98 months ) . In the mesh repair group , 17 % suffered a complication , compared with 8 % in the suture repair group ( P = 0.17 ) . Abdominal pain was more frequent in suture repair patients ( P = 0.01 ) , but there was no difference in scar pain , cosmetic result , and patient satisfaction . Conclusions : Mesh repair results in a lower recurrence rate and less abdominal pain and does not result in more complications than suture repair . Suture repair of incisional hernia should be ab and oned IMPORTANCE Incisional hernia is the most frequent surgical complication after laparotomy . Up to 30 % of all patients undergoing laparotomy develop an incisional hernia . OBJECTIVE To compare laparoscopic vs open ventral incisional hernia repair with regard to postoperative pain and nausea , operative results , perioperative and postoperative complications , hospital admission , and recurrence rate . DESIGN Multicenter r and omized controlled trial between May 1999 and December 2006 with a mean follow-up period of 35 months . SETTING All patients were operated on in a clinical setting at 1 of the 2 participating university medical centers or at the other 8 teaching hospitals . PARTICIPANTS Two hundred six patients from 10 hospitals were r and omized equally to laparoscopic or open mesh repair . Patients with an incisional hernia larger than 3 cm and smaller than 15 cm , either primary or recurrent , were included . Patients were excluded if they had an open abdomen treatment in their medical histories . INTERVENTION Laparoscopic or open ventral incisional hernia repair . MAIN OUTCOME MEASURES The primary outcome of the trial was postoperative pain . Secondary outcomes were use of analgesics , perioperative and postoperative complications , operative time , postoperative nausea , length of hospital stay , recurrence , morbidity , and mortality . RESULTS Median blood loss during the operation was significantly less ( 10 mL vs 50 mL ; P = .05 ) as well as the number of patients receiving a wound drain ( 3 % vs. 45 % ; P < .001 ) in the laparoscopic group . Operative time for the laparoscopic group was longer ( 100 minutes vs. 76 minutes ; P = .001 ) . Perioperative complications were significantly higher after laparoscopy ( 9 % vs. 2 % ) . Visual analog scale scores for pain and nausea , completed before surgery and 3 days and 1 and 4 weeks postoperatively , showed no significant differences between the 2 groups . At a mean follow-up period of 35 months , a recurrence rate of 14 % was reported in the open group and 18 % , in the laparoscopic group ( P = .30 ) . The size of the defect was found to be an independent predictor for recurrence ( P < .001 ) . CONCLUSIONS AND RELEVANCE During the operation , there was less blood loss and less need for a wound drain in the laparoscopic group . However , operative time was longer during laparoscopy . Perioperative complications were significantly higher in the laparoscopic group . Visual analog scores for pain and nausea did not differ between groups . The incidence of a recurrence was similar in both groups . The size of the defect was found to be an independent factor for recurrence of an incisional hernia BACKGROUND Laparoscopic repair of ventral incisional hernias has not been proved to be safer than open mesh repair . DESIGN Prospect i ve r and omized trial conducted between February 1 , 2004 , to January 31 , 2007 . SETTING Four Veterans Affairs medical centers . PARTICIPANTS One hundred sixty-two patients with ventral incisional hernias . INTERVENTIONS St and ardized laparoscopic or open repair . MAIN OUTCOME MEASURES Overall complication rates at 8 weeks and the odds of complications , adjusted for study site , body mass index , and hernia type . RESULTS Of the 162 r and omized patients , 146 underwent surgery ( 73 open and 73 laparoscopic repairs ) . Complications were less common in the laparoscopic group ( 23 patients [ 31.5 % ] ) compared with the open repair group ( 35 patients [ 47.9 % ] ; adjusted odds ratio [ AOR ] , 0.45 ; 95 % confidence interval [ CI ] , 0.22 - 0.91 ; P = .03 ) . Surgical site infection through 8 weeks was less common in the laparoscopic group ( 5.6 % vs 23.3 % ; AOR , 0.2 ; 95 % CI , 0.1 - 0.6 ) . The mean worst pain score in the laparoscopic group was 15.2 mm lower on a visual analog scale at 52 weeks ( 95 % CI , 1.0 - 29.3 ; P = .04 ) . Time to resume work activities was shorter for the laparoscopic group than for the open repair group ( median , 23.0 days vs 28.5 days ) , with an adjusted hazard ratio of 0.54 ( 95 % CI , 0.28 - 1.04 ; P = .06 ) . Overall recurrence at 2 years was 12.5 % in the laparoscopic group and 8.2 % in the open repair group ( AOR , 1.6 ; 95 % CI , 0.5 - 4.7 ; adjusted P = .44 ) . CONCLUSIONS Laparoscopic repair was associated with fewer , albeit more severe , complications and improved some patient-centered outcomes . Trial Registration clinical trials.gov Identifier : NCT00240188 The appearance of incisional hernia after laparotomy closure continues to be an important postoperative complication . Advances in anesthesia techniques , adequate prevention and treatment of infection during surgery , and the use of new suture material s have reduced the incidence of incisional hernia . Nevertheless , incisional hernia still occurs in 0.5 % to 11 % of all laparotomies performed . There are many different techniques currently in use for ventral incisional hernia ( VIH ) repair . Among these techniques , laparoscopic repair has been reported to be superior to open repair because of less pain , a lower recurrence rate , fewer complications , and earlier return to work . The lower rate of complications may be a major contributing factor to a reduced incidence of recurrence . However , laparoscopic repair requires expensive equipment and supplies , and it is not yet generally accepted . No conclusive r and omized trial of sufficient size and power has been done to establish the " gold st and ard " for VIH repair , and surgeons are calling for proper evaluation . This r and omized clinical trial conducted at 3 Veterans Affairs medical centers was design ed to compare open VIH repair with the laparoscopic technique with respect to postoperative complications at 8 weeks , health-related quality of life , postoperative pain , time to return to normal activities , patient satisfaction , and recurrence rate of the hernia at 1 and 2 years . The study design calls for r and omization of 314 men over a period of 32 months . This will allow > or = 80 % power to detect a 15 % difference in complication rates between the 2 surgical procedures at 8 weeks . R and omization is stratified by hospital , whether the hernia is recurrent and whether the patient 's body mass index is > or = 35 or < 35 . We report the design and beginning of a multicenter trial comparing open and laparoscopic VIH repair . When completed , this study will provide surgeons and their patients with information that will help guide their choice of surgical technique Background Incisional hernia is a common complication following abdominal surgery . Although the use of prosthetics has decreased recurrence rates , the st and ard open approach is still unsatisfactory . Laparoscopic techniques are an attempt to provide similar outcomes with the advantages of minimally invasive surgery . Methods Open r and omized controlled clinical trial with follow-up at 1 , 2 , 3 , 7 , and 15 days , and 1 , 3 , and 12 months from hernia repair . The study was carried out in the surgery departments of three general hospitals of the Valencia Health Agency . Objectives To compare laparoscopic with anterior open repair using health-related quality of life outcomes as main endpoints . Results Eighty-four patients with incisional hernia were r and omly allocated to an open group ( OG ) ( n = 39 ) or to a laparoscopic group ( LG ) ( n = 45 ) . Seventy-four patients completed 1-year follow up . Mean length of stay and time to oral intake were similar between groups . Operative time was 32 min longer in the LG ( p < 0.001 ) . Conversion rate was 11 % . The local complication rate was superior in the LG ( 33.3 % versus 5.2 % ) ( p < 0.001 ) . Recurrence rate at 1 year ( 7.9 % versus 9.7 % ) was similar in the two groups . There were no significant differences in the pain scores or the EQ5D tariffs between the two groups during follow-up . Conclusions Laparoscopic incisional hernia repair does not seem to be a better procedure than the open anterior technique in terms of operative time , hospitalization , complications , pain or quality of life Background Annually approximately 100.000 patients undergo a laparotomy in the Netherl and s. About 15,000 of these patients will develop an incisional hernia . Both open and laparoscopic surgical repair have been proven to be safe . However , the most effective treatment of incisional hernias remains unclear . This study , the ‘ INCH-trial ’ , comparing cost-effectiveness of open and laparoscopic incisional hernia repair , is therefore needed . Methods / Design A r and omized multi-center clinical trial comparing cost-effectiveness of open and laparoscopic repair of incisional hernias . Patients with a symptomatic incisional hernia , eligible for laparoscopic and open incisional hernia repair . Only surgeons , experienced in both open and laparoscopic incisional hernia repair , will participate in the INCH trial . During incisional hernia repair , a mesh is placed under or on top of the fascia , with a minimal overlap of 5 cm . Primary endpoint is length of hospital stay after an incisional hernia repair . Secondary endpoints are time to full recovery within three months after index surgery , post-operative complications , recurrences , mortality and quality of life . Our hypothesis is that laparoscopic incisional hernia repair comes with a significant shorter hospital stay compared to open incisional hernia repair . A difference of two days is considered significant . One-hunderd- and -thirty-five patients are enrolled in each treatment arm . The economic evaluation will be performed from a societal perspective . Primary outcomes are costs per patient related to time-to-recovery and quality of life . The main goal of the trial is to establish whether laparoscopic incisional hernia repair is superior to conventional open incisional hernia repair in terms of cost-effectiveness . This is measured through length of hospital stay and quality of life . Secondary endpoints are re-operation rate due to post-operative complications or recurrences , mortality and quality of life . Discussion The difference in time to full recovery between the two treatment strategies is thought to be in favor of laparoscopic incisional hernia repair . Laparoscopic incisional hernia repair is therefore expected to be a more cost-effective approach . Trial registration Netherl and s Trial register : Background : Postoperative pain control after laparoscopic ventral hernia repairs remains a significant clinical problem . We sought to determine the pain-sparing efficacy of local anesthetic infiltrated into the abdominal wall wounds created by the placement of transabdominal sutures used to ensure adequate fixation of the mesh during laparoscopic ventral hernia repair . Methods : Patients undergoing laparoscopic ventral/incisional hernia repair were r and omized to receive local anesthesia ( 0.25 % bupivacaine with epinephrine ) into all layers of the abdominal wall to the level of the parietal peritoneum at suture fixation sites immediately before suture placement ( Group I ; n=9 ) or no local anesthesia ( Group II , control ; n=9 ) . The anesthetic technique was otherwise st and ard for both groups . Postoperatively , pain was assessed with a 10-point visual analogue scale ( VAS ) at 1 , 2 , 4 , and 24 hours . Analgesic use and hospital stay were also recorded . Results : The groups were similar in age , sex , ASA , and size of hernia defect . The operative times were not statistically different between the 2 groups ( Group I , 118±12 minutes ; Group II , 144±21 minutes ; P>0.05 ) . Group I had a statistically significant decrease in the pain scores compared with Group II ( 2.2±0.8 vs. 6.4±0.9 ; P<0.05 ) at 1 hour postoperatively . At 2 and 4 hours , the mean pain scores were decreased but not statistically different . Similarly , the cumulative consumption of pain medication at 1 , 2 , and 4 hours postoperatively as well as the average hospital stay ( Group I , 2.0±0.4 ; Group II , 2.4±0.4 days ) were lower but not statistically significant in patients in Group I compared with those in Group II . Conclusion : This small , r and omized study demonstrates that infiltration of suture fixation sites is effective in reducing early postoperative pain but not analgesic consumption following laparoscopic incisional and ventral hernia repairs . A larger study is required to investigate this strategy on later postoperative pain and hospital stay To compare the early and intermediate results of the open and laparoscopic tension-free repair of incisional hernia , 24 patients were r and omized prospect ively to undergo laparoscopic or open repair of incisional hernia with retromuscular placement of the prosthesis using transabdominal sutures for mesh fixation . All the procedures were completed as planned . The mean duration of surgery was not significantly different between the 2 groups ( P=0.15 ) . Time to oral solid food intake was longer in the open group ( P=0.002 ) . The analgesic requirement was lower in the laparoscopic group ( P=0.05 ) . One patient after open surgery and 2 in the laparoscopic group suffered postoperative complications ( P=0.71 ) . Postoperative stay was shorter in the laparoscopic group ( P=0.006 ) . No readmission or recurrence was registered within 6 months from surgery in either group . Laparoscopic incisional hernia repair , based on the Rives-Stoppa technique , is a safe , feasible alternative to open techniques . However , larger studies and long-term follow-up are required to further evaluate the true effectiveness of this operation Background Incisional hernia is an important complication of abdominal surgery . Its repair has progressed from a primary suture repair to various mesh repairs and laparoscopic repair . Laparoscopic mesh repair is a promising alternative , and in the absence of consensus , needs prospect i ve r and omized controlled trials . Methods Between April 2003 and April 2005 , 66 patients with incisional , primary ventral and recurrent hernias were r and omized to receive either open retrorectus mesh repair or laparoscopic mesh repair . These patients were followed up at 1- , 3- , and 6-month intervals thereafter for a mean of 12.17 months ( open repair group ) and 13.73 months ( laparoscopic repair group ) . Results Lower abdominal hernias after gynecologic operations constituted the majority of the hernias ( ∼50 % ) in both groups . There was no significant injury to viscera or vessel in either group and no conversions . The defect size was 42.12 cm2 in the open ( group 1 ) and 65.66 cm2 in the laparoscopic group ( group 2 ) , and the prosthesis sizes were , respectively , 152.67 cm2 and 203.83 cm2 . The hospital stay was 3.43 days in open group and 1.47 days in laparoscopic group ( p = 0.007 ) . There was no significant difference in the pain scores between the two groups . More wound-related infectious complications occurred in the open group ( 33 % ) than in the laparoscopic group ( 6 % ) ( p = 0.013 ) . There was one recurrence in the open repair group ( 3 % ) and two recurrences in laparoscopic group ( 6 % ) ( p = 0.55 ) . Conclusions Laparoscopic repair of incisional and ventral hernias is superior to open mesh repair in terms of significantly less blood loss , fewer complications , shorter hospital stay , and excellent cosmetic outcome Background : Although ventral hernia repair is increasingly performed laparoscopically , complication rates with this procedure are not well characterized . For this reason , we performed a prospect i ve study comparing early outcomes after laparoscopic and open ventral hernia repairs . Methods : We identified all the patients undergoing ventral ( including incisional ) hernia repair at a single tertiary care center between September 1 , 1999 and July 1 , 2001 ( overall n = 257 ) . To increase the homogeneity of the sample , we excluded umbilical hernia repairs , parastomal hernia repairs , nonelective procedures , procedures not involving mesh , and repairs performed concurrently with another surgical procedure . Postoperative complications ( in-hospital or within 30-days ) were assessed prospect ively according to st and ardized definitions by trained nurse clinicians . Results : Of the 136 ventral hernia repairs that met the study criteria , 65 ( 48 % ) were laparoscopic repairs ( including 3 conversions to open surgery ) and 71 ( 52 % ) were open repairs . The patients in the laparoscopic group were more likely to have undergone a prior ( failed ) ventral hernia repair ( 40 % vs 27 % ; p = 0.14 ) , but other patient characteristics were similar between the two groups . Overall , fewer complications were experienced by patients undergoing laparoscopic repair ( 8 % vs 21 % ; p = 0.03 ) . The higher complication rate in the open ventral hernia repair group came from wound infections ( 8 % ) and postoperative ileus ( 4 % ) , neither of which was observed in the patients who underwent laparoscopic repair . The laparoscopic group had longer operating room times ( 2.2 vs 1.7 h ; p = 0.001 ) , and there was a nonsignificant trend toward shorter hospital stays with laparoscopic repair ( 1.1 vs 1.5 days ; p = 0.10 ) . Conclusions : The patients undergoing laparoscopic repair had fewer postoperative complications than those receiving open repair . Wound infections and postoperative ileus accounted for the higher complication rates in the open ventral hernia repair group . Otherwise , these groups were very similar . Long-term studies assessing hernia recurrence rates will be required to help determine the optimal approach to ventral hernia repair BACKGROUND Laparoscopic ventral hernia repair is becoming a promising alternative with many potential advantages , but this procedure is still under study . Our objective was to evaluate the efficacy of the laparoscopic approach to ventral hernia repair . METHODS One hundred consecutive laparoscopic ventral hernia repairs between April 2000 and February 2003 were prospect ively entered into a data base and review ed . RESULTS Ninety-seven ventral hernia repairs were completed laparoscopically . The mean time in the operating room was 128 minutes ( range 37 to 255 ) . The average length of stay was 2 days ( range 0 to 9 ) . The mortality rate was 0 % . A total of 23 % of patients experienced postoperative complications . Over a mean follow-up period of 3 months ( range 0 to 26 ) , 6 % ( 6 of 97 ) of patients experienced recurrences . CONCLUSIONS Laparoscopic ventral hernia repair can be safely performed with a low conversion rate and acceptable recurrence rate , operative time , length of stay , and morbidity . Securing the mesh with full-thickness abdominal wall sutures in at least 4 quadrants remains a key factor in preventing early recurrence The importance of study ing health-related quality of life in the general population has increasingly been emphasized . From a public health perspective , this benefits the identification of population inequalities in health status . One of the currently most popular instruments is the EQ-5D . Evaluations of the EQ-5D generally focus on the overall preference-based index . As this index has a built-in value , exploration of the information from the underlying health states is also important . In this study , the ten most commonly reported EQ-5D health states are described using the SF-36 . Data collected in 1999 by question naires mailed to a r and om sample aged 20–74 in south-eastern Sweden were used ( n = 9489 ) . Almost 43 % reported the best possible EQ-5D health state and 78 % were accounted for by three EQ-5D health states . The EQ-5D health state classification was largely reflected by the SF-36 , with the EQ-5D items mobility , usual activities , pain/discomfort and anxiety/depression tapping most clearly on the SF-36 scales physical functioning , role limitations due to physical health problems , bodily pain , and mental health , respectively . However , within the same level of EQ-5D ( i.e. , moderate problems ) there was a rather large variation of SF-36 scale scores , particularly regarding the EQ-5D item pain/discomfort and the SF-36 scale BP Abstract Background : Despite being one of the most exact indications , laparoscopic treatment of eventrations and ventral hernias is barely known among the array of laparoscopic techniques . Methods : A total of 60 patients were assigned at r and om over a 3-year period to two homogeneous groups to be operated on for major ventral hernias with mesh . Half of them were operated upon laparoscopically and the rest with open surgery . Early and longer-term complications were analyzed , as were operative time and postoperative hospital stays . Results : The two groups were homogeneous in terms of demographic and clinical characteristics . The group that was operated on laparoscopically presented a lower rate of postoperative and longer-term complications ; similarly , surgery time was significantly lower ( p < 0.05 ) . Hospitalization time was also significantly lower than in the group undergoing conventional open surgery ( p < 0.05 ) . Conclusions : Laparoscopic treatment of postoperative eventration and primary ventral hernia reduces complications and relapse rates , eliminates reintervention through mesh infection , reduces operative time , and considerably shortens the hospital stay HYPOTHESIS The elective treatment of a spigelian hernia is still under discussion , fundamentally owing to its rarity . The purpose of the study is to analyze the elective surgical treatment of spigelian hernia . DESIGN A prospect i ve , r and omized controlled trial . SETTING University teaching hospital . PATIENTS AND INTERVENTIONS Two surgeons performed 11 conventional and 11 laparoscopic repairs for a spigelian hernia , alternating roles as primary surgeon and assistant . Each time the type of technique was r and omly chosen using a computerized program . MAIN OUTCOME MEASURES Epidemiological , clinical , and surgical factors are analyzed according to treatment , ie , the open or laparoscopic approach . RESULTS The statistical study shows no significant differences for epidemiological or diagnostic factors , but it does show significant advantages for laparoscopy in terms of morbidity ( P<.05 ) and hospital stay ( P<.001 ) . CONCLUSION The approach using extraperitoneal laparoscopy is the technique that offers best results in the elective treatment of spigelian hernia Laparoscopic and open techniques are both recognized treatment options for ventral hernias . We conducted a prospect i ve r and omized trial of both methods , to assess hernia recurrence , postoperative recovery and complications . Fifty‐eight patients with ventral hernias were enrolled into the trial between August 2003 and December 2005 . Of these , 31 underwent laparoscopic repair and 27 underwent open repair . Clinical parameters were documented on all patients during a median follow‐up period of 27.5 months . The demographics of the two groups were similar . There was one recurrence in each of the laparoscopic and open groups . There was an equivalent rate of operative time , length of stay , postoperative pain scores , return to normal activities , wound infection and seroma formation between the two groups . Laparoscopic and open ventral hernia repair are comparable and offer low recurrence rates |
10,991 | 24,344,218 | Exercise training demonstrated benefits in muscular strength , cardiorespiratory fitness , functional task performance , lean body mass , and fatigue , with inconsistent effects observed for adiposity .
Among patients with prostate cancer treated with and rogen-deprivation therapy , appropriately prescribed exercise is safe and may ameliorate a range of treatment-induced adverse effects . | PURPOSE And rogen-deprivation therapy is a commonly used treatment for men with prostate cancer ; however , the adverse effects can be detrimental to patient health and quality of life .
Exercise has been proposed as a strategy for ameliorating a range of these treatment-related adverse effects .
We conducted a systematic review of the literature regarding the effects of exercise on treatment-related adverse effects in men receiving and rogen-deprivation therapy for prostate cancer . | Overweight and obesity affects more than 66 % of the adult population and is associated with a variety of chronic diseases . Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies . Guidelines of the National Heart , Lung , and Blood Institute ( NHLBI ) encourage a 10 % reduction in weight , although considerable literature indicates reduction in health risk with 3 % to 5 % reduction in weight . Physical activity ( PA ) is recommended as a component of weight management for prevention of weight gain , for weight loss , and for prevention of weight regain after weight loss . In 2001 , the American College of Sports Medicine ( ACSM ) published a Position St and that recommended a minimum of 150 min wk(-1 ) of moderate-intensity PA for overweight and obese adults to improve health ; however , 200 - 300 min wk(-1 ) was recommended for long-term weight loss . More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss . To this end , we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain , for weight loss , and prevention of weight regain . Evidence supports moderate-intensity PA between 150 and 250 min wk(-1 ) to be effective to prevent weight gain . Moderate-intensity PA between 150 and 250 min wk(-1 ) will provide only modest weight loss . Greater amounts of PA ( > 250 min wk(-1 ) ) have been associated with clinical ly significant weight loss . Moderate-intensity PA between 150 and 250 min wk(-1 ) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction . Cross-sectional and prospect i ve studies indicate that after weight loss , weight maintenance is improved with PA > 250 min wk(-1 ) . However , no evidence from well- design ed r and omized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss . Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk . Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk . There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain Goals of workProstate cancer patients receiving and rogen deprivation therapy ( ADT ) are vulnerable to a number of potentially debilitating side effects , which can significantly impact quality of life . The role of alternate therapies , such as physical activity ( PA ) , in attenuating these side effects is largely understudied for such a large population . Thus , the purpose of this study was to investigate the effects of PA intervention for men receiving ADT on PA behavior , quality of life , and fitness measures . Patients and methods One hundred participants were r and omized into an intervention ( n = 53 ) or a wait-list control group ( n = 47 ) , with 11 dropping out of the intervention group and 23 dropping out of the wait-list control group prior to post-testing . The intervention consisted of both an individually tailored home-based aerobic and light resistant training program and weekly group sessions . PA , quality of life , fitness , and physiological outcomes were assessed pre and post the 16-week intervention . Results Significant increases in PA , supported by changes in girth measures and blood pressure , support the beneficial impact of the intervention . Positive trends were also evident for depression and fatigue . However , due to the high dropout rate , these results must be interpreted with caution . Conclusions PA effectively attenuates many of the side effects of ADT and should be recommended to prostate survivors as an alternate therapy . Determining the maintenance of this behavior change will be important for underst and ing how the long-term benefits of increased activity levels may alleviate the late effects of ADT Advice to rest and take things easy if patients become fatigued during radiotherapy may be detrimental . Aerobic walking improves physical functioning and has been an intervention for chemotherapy‐related fatigue . A prospect i ve , r and omized , controlled trial was performed to determine whether aerobic exercise would reduce the incidence of fatigue and prevent deterioration in physical functioning during radiotherapy for localized prostate carcinoma And rogen-deprivation therapy ( ADT ) is a widely used treatment for prostate cancer . Recently , several studies have reported an association between ADT and an increased risk of cardiovascular events , including myocardial infa rct ion and cardiovascular mortality.1 - 5 These reports have led to increased interest and discussion regarding the metabolic effects of ADT and its possible association with increased cardiovascular risk . In addition , likely as a result of these reports , internists , endocrinologists , and cardiologists are now being consulted regarding the evaluation and management of patients in whom ADT is being initiated . Most of these physicians are not aware of the possible effects of ADT on cardiovascular risk factors or the issues regarding ADT and cardiovascular disease . Therefore , this multidisciplinary writing group has been commissioned to review and summarize the metabolic effects of ADT , to evaluate the data regarding a possible relation between ADT and cardiovascular events in patients with prostate cancer , and to generate suggestions regarding the evaluation and management of patients , both with and without known cardiac disease , in whom ADT is being initiated ( Table 1 ) . TABLE 1 Prospect i ve Studies of the Effects of ADT on Cardiac Risk Factors ADT was first used in prostate cancer for patients with overt metastatic disease,7 and it remains the mainstay of therapy for this group . ADT combined with external-beam radiation therapy is a st and ard of care in the treatment of men with high-risk prostate cancer , on the basis of evidence that shows a survival benefit in multiple r and omized controlled trials.8 - 13 However , ADT is also often used for other prostate cancer states ( eg , for prostate volume reduction in men planning to undergo definitive local therapy with brachytherapy , or in the case of rising prostate-specific antigen after definitive local treatment),14,15 and in these cases , its role in prolonging survival is less certain Background : Healthy lifestyle behaviors could have a role in ameliorating some of the adverse effects of and rogen suppression therapy ( AST ) in men with prostate cancer . The primary aim of this study was to assess the feasibility of a tapered supervised exercise program in combination with dietary advice in men with advanced prostate cancer receiving AST . Methods : Advanced prostate cancer patients receiving AST for a minimum of 6 months were r and omized to a 12-week lifestyle program comprising aerobic and resistance exercise , plus dietary advice ( n = 25 ) , or st and ard care ( n = 25 ) . Exercise behavior , dietary macronutrient intake , quality of life , fatigue , functional fitness , and biomarkers associated with disease progression were assessed at baseline , after the intervention , and at 6 months . Results : The lifestyle group showed improvements in exercise behavior ( P < 0.001 ) , dietary fat intake ( P = 0.001 ) , total energy intake ( P = 0.005 ) , fatigue ( P = 0.002 ) , aerobic exercise tolerance ( P < 0.001 ) , and muscle strength ( P = 0.033 ) compared with st and ard care controls . Although a high rate of attrition ( 44 % ) was observed at 6 months , the improvements in key health outcomes were sustained . No effects on clinical prostate cancer disease markers were observed . Conclusions : This preliminary evidence suggests that pragmatic lifestyle interventions have potential to evoke improvements in exercise and dietary behavior , in addition to other important health outcomes in men with advanced prostate cancer receiving AST . Impact : This study shows for the first time that pragmatic lifestyle interventions are feasible and could have a positive impact on health behaviors and other key outcomes in men with advanced prostate cancer receiving AST . Cancer Epidemiol Biomarkers Prev ; 20(4 ) ; 647–57 . © 2011 AACR PURPOSE To examine the effect of progressive resistance training on muscle function , functional performance , balance , body composition , and muscle thickness in men receiving and rogen deprivation for prostate cancer . METHODS Ten men aged 59 - 82 yr on and rogen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum ( RM ) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic . Outcome measures included muscle strength and muscle endurance for the upper and lower body , functional performance ( repeated chair rise , usual and fast 6-m walk , 6-m backwards walk , stair climb , and 400-m walk time ) , and balance by sensory organization test . Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound . Blood sample s were assessed for prostate specific antigen ( PSA ) , testosterone , growth hormone ( GH ) , cortisol , and hemoglobin . RESULTS Muscle strength ( chest press , 40.5 % ; seated row , 41.9 % ; leg press , 96.3 % ; P < 0.001 ) and muscle endurance ( chest press , 114.9 % ; leg press , 167.1 % ; P < 0.001 ) increased significantly after training . Significant improvement ( P < 0.05 ) occurred in the 6-m usual walk ( 14.1 % ) , 6-m backwards walk ( 22.3 % ) , chair rise ( 26.8 % ) , stair climbing ( 10.4 % ) , 400-m walk ( 7.4 % ) , and balance ( 7.8 % ) . Muscle thickness increased ( P < 0.05 ) by 15.7 % at the quadriceps site . Whole-body lean mass was preserved with no change in fat mass . There were no significant changes in PSA , testosterone , GH , cortisol , or hemoglobin . CONCLUSIONS Progressive resistance exercise has beneficial effects on muscle strength , functional performance and balance in older men receiving and rogen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects OBJECTIVE To show fatigue prevention and quality of life ( QOL ) improvement from cardiovascular exercise during radiotherapy . DESIGN Prospect i ve enrollment ( n=21 ) , r and omized to exercise ( n=11 ) and control groups ( n=10 ) , with pre- and post-radiotherapy between- and within-group comparisons . SETTING Academic medical center . PARTICIPANTS Localized prostate cancer patients undergoing radiotherapy . INTERVENTIONS The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise . MAIN OUTCOME MEASURES Pre- and post-radiotherapy differences in cardiac fitness , fatigue , depression , functional status , physical , social , and functional well-being , leg strength , and flexibility were examined within and between 2 groups . RESULTS No significant differences existed between 2 groups at pre-radiotherapy assessment . At post-radiotherapy assessment , the exercise group showed significant within group improvements in : cardiac fitness ( P<.001 ) , fatigue ( P=.02 ) , Functional Assessment of Cancer Therapy-Prostate ( FACT-P ) ( P=.04 ) , physical well-being ( P=.002 ) , social well-being ( P=.02 ) , flexibility ( P=.006 ) , and leg strength ( P=.000 ) . Within the control group , there was a significant increase in fatigue score ( P=.004 ) and a decline in social well-being ( P<.05 ) at post-radiotherapy assessment . Between-group differences at post-radiotherapy assessment were significant in cardiac fitness ( P=.006 ) , strength ( P=.000 ) , flexibility ( P<.01 ) , fatigue ( P<.001 ) , FACT-P ( P=.006 ) , physical well-being ( P<.001 ) , social well-being ( P=.002 ) , and functional well-being ( P=.04 ) . CONCLUSIONS An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness , flexibility , muscle strength , and overall QOL and prevented fatigue 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 Insulin resistance and changes in body composition are side effects of and rogen deprivation therapy ( ADT ) given to prostate cancer patients . The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients . Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training . Primary endpoints were insulin sensitivity ( euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion ) and body composition ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) . The secondary endpoint was systemic inflammation . Statistical analysis was carried out using two-way ANOVA . Endurance training increased VO2max ( ml(O2)/min per kg ) by 11 and 13 % in the patients and controls respectively ( P<0.0001 ) . The patients and controls demonstrated an increase in peripheral tissue insulin sensitivity of 14 and 11 % respectively ( P<0.05 ) , with no effect on hepatic insulin sensitivity ( P=0.32 ) . Muscle protein content of GLUT4 ( SLC2A4 ) and total AKT ( AKT1 ) was also increased in response to the training ( P<0.05 and P<0.01 respectively ) . Body weight ( P<0.0001 ) and whole-body fat mass ( FM ) ( P<0.01 ) were reduced , while lean body mass ( P=0.99 ) was unchanged . Additionally , reductions were observed in abdominal ( P<0.01 ) , subcutaneous ( P<0.05 ) , and visceral ( P<0.01 ) FM amounts . The concentrations of plasma markers of systemic inflammation were unchanged in response to the training . No group × time interactions were observed , except for thigh intermuscular adipose tissue ( IMAT ) ( P=0.01 ) , reflecting a significant reduction in the amount of IMAT in the controls ( P<0.05 ) not observed in the patients ( P=0.64 ) . In response to endurance training , ADT-treated prostate cancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men Background : Previous research has shown exercise to be an effective method to mitigate many adverse treatment-related effects of and rogen suppression therapy ( AST ) but the potential impact of exercise on sexual activity remains unknown . The purpose of this investigation was to report the effect of a 12-week exercise program on sexual activity in prostate cancer patients undergoing AST . Methods : Fifty-seven prostate cancer patients undergoing AST were r and omly assigned to an exercise program ( resistance and aerobic modes ; n=29 ) or usual care control ( n=28 ) . Sexual activity was assessed by the European Organization for Research and Treatment of Cancer prostate cancer-specific quality of life question naire ( QLQ-PR25 ) . Results : QLQ-PR25 data were log transformed and analysis of covariance was used to compare sexual activity between groups following the intervention adjusted for baseline activity . No differences in sexual activity were observed between the exercise and control groups before the intervention . There was a significant ( P=0.045 ) adjusted group difference in sexual activity following the 12-week intervention . Patients undergoing usual care decreased sexual activity while patients in the exercise program maintained their level of sexual activity . At baseline , 20.6 and 22.2 % of participants in the exercise and control groups reported a major interest in sex ( that is , high libido ) . Following the intervention , the exercise group had a significantly higher percentage of participants reporting a major interest in sex ( exercise=17.2 % vs control=0 % ; P=0.024 ) . Conclusions : Participation in a short-term exercise program result ed in the maintenance of sexual activity in prostate cancer patients undergoing AST CONTEXT Although and rogen deprivation therapy ( ADT ) for prostate cancer is associated with bone loss , little is known about when this bone loss occurs . OBJECTIVE We postulated that men on ADT would experience the greatest bone loss acutely after initiation of ADT . DESIGN AND SETTING We conducted a 12-month prospect i ve study at an academic medical center . PATIENTS OR OTHER PARTICIPANTS We studied 152 men with prostate cancer ( 30 with acute ADT , < 6 months ; 50 with chronic ADT , > or = 6 months ; and 72 with no ADT ) and 43 healthy age-matched controls . MAIN OUTCOME MEASURES We assessed bone mineral density ( BMD ) of the hip , wrist , total body , and spine ; body composition ; and markers of bone turnover . RESULTS After 12 months , men receiving acute ADT had a significant reduction in BMD of 2.5 + /- 0.6 % at the total hip , 2.4 + /- 1.0 % at the trochanter , 2.6 + /- 0.5 % at the total radius , 3.3 + /- 0.5 % at the total body , and 4.0 + /- 1.5 % at the posteroanterior spine ( all P < 0.05 ) . Men with chronic ADT had a 2.0 + /- 0.6 % reduction in BMD at the total radius ( P < 0.05 ) . Healthy controls and men with prostate cancer not receiving ADT had no significant reduction in BMD . Both use and duration of ADT were associated with change in bone mass at the hip ( P < 0.05 ) . Men receiving acute ADT had a 10.4 + /- 1.7 % increase in total body fat and a 3.5 + /- 0.5 % reduction in total body lean mass at 12 months , whereas body composition did not change in men with prostate cancer on chronic ADT or in healthy controls ( P < 0.05 ) . Markers of bone formation and resorption were elevated in men receiving acute ADT after 6 and 12 months compared with the other men with prostate cancer and controls ( P < 0.05 ) . Men in the highest tertile of bone turnover markers at 6 months had the greatest loss of bone density at 12 months . CONCLUSIONS Men with prostate cancer who are initiating ADT have a 5- to 10-fold increased loss of bone density at multiple skeletal sites compared with either healthy controls or men with prostate cancer who are not on ADT , placing them at increased risk of fracture . Bone loss is maximal in the first year after initiation of ADT , suggesting initiation of early preventive therapy PURPOSE And rogen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue , functional decline , increased body fatness , and loss of lean body tissue . These physical changes can negatively affect health-related quality of life . Resistance exercise may help to counter some of these side effects by reducing fatigue , elevating mood , building muscle mass , and reducing body fat . METHODS In a two-site study , 155 men with prostate cancer who were scheduled to receive and rogen deprivation therapy for at least 3 months after recruitment were r and omly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks ( 82 men ) or to a waiting list control group ( 73 men ) . The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported question naires after 12 weeks . Secondary outcomes were muscular fitness and body composition . RESULTS Men assigned to resistance exercise had less interference from fatigue on activities of daily living ( P = .002 ) and higher quality of life ( P = .001 ) than men in the control group . Men in the intervention group demonstrated higher levels of upper body ( P = .009 ) and lower body ( P < .001 ) muscular fitness than men in the control group . The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight , body mass index , waist circumference , or subcutaneous skinfolds . CONCLUSION Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving and rogen deprivation therapy . This form of exercise can be an important component of supportive care for these patients Purpose The purpose of this study is to examine the effects of age ( ≤65 years or > 65 years ) and and rogen-deprivation therapy ( ADT , presence or absence ) as factors that may predict changes in body composition and fitness following a 24-week exercise program in prostate cancer patients . Methods One hundred twenty-one men were r and omly allocated to either : ( 1 ) aerobic exercise ( AE ) , ( 2 ) resistance exercise ( RE ) , or ( 3 ) usual care ( UC ) . Body composition was assessed by DXA . Aerobic fitness was assessed through a maximal treadmill test . Muscular strength was assessed by leg extension and bench press using the eight-repetition maximum test . Responses were compared between younger ( ≤65 years ) and older ( > 65 years ) patients with or without ADT . Results There did not appear to be an interaction between age and ADT on body composition or fitness , nor were there any significant changes in body composition for participants ≤65 years . In participants aged > 65 years , lean mass decreased in AE ( p = 0.013 ) and UC ( p = 0.006 ) , but was preserved in RE . In participants receiving ADT , there was a decrease in lean mass in AE ( p = 0.003 ) and UC ( p < 0.001 ) but not in RE . The non-ADT group did not show any changes in body composition but did show improvements in muscular fitness following resistance training ( p < 0.001 ) . Conclusion Changes in body composition and physical fitness following a 24-week exercise program in men with prostate cancer are not influenced by age and /or ADT . Resistance training appears to attenuate the age-related decrease in lean mass and increase in body fat in older patients with prostate cancer and those receiving ADT OBJECTIVES To assess the effects of and rogen deprivation therapy on body composition in men with nonmetastatic prostate cancer . METHODS In a multicenter study , men with Stage M0 prostate cancer were prospect ively evaluated during initial and rogen deprivation therapy ( gonadotropin-releasing hormone agonist or bilateral orchiectomy ) . The main outcomes were changes in weight , percentage fat mass , and percentage lean mass from baseline to 12 months . RESULTS Seventy-nine subjects were assessed . Serum testosterone concentrations decreased by 79.7 % + /- 3.0 % ( P < 0.001 ) . Weight increased by 1.8 % + /- 0.5 % ( P < 0.001 ) . The percentage fat mass increased by 11.0 % + /- 1.7 % , and the percentage lean mass decreased by 3.8 % + /- 0.6 % ( P < 0.001 for each comparison ) . CONCLUSIONS And rogen deprivation therapy increased weight and fat mass and decreased lean mass in men with nonmetastatic prostate cancer And rogen-deprivation therapy ( ADT ) for prostate cancer ( PCa ) has side effects that significantly impair health-related quality of life ( HRQOL ) . Exercise ameliorates many side effects of ADT , but different modalities , particularly in the home-based setting , have not been well studied . In this study the authors r and omly assigned 66 PCa survivors receiving ADT to 6 mo of home-based aerobic or resistance training . Psychosocial well-being and physical fitness were measured at baseline , 3 and 6 mo , and then 6 mo postintervention . Intention-to-treat analyses showed that fatigue and HRQOL were not significantly different between groups ; however , in a per- protocol analysis the resistance-exercise training group demonstrated clinical ly significant improvements in HRQOL . Differential within-group effects on physical fitness were also observed at various time points . At all time points , the aerobic-training group engaged in significantly more physical activity than the resistance-training group , a finding that should be further examined given evidence -based guidelines for activity volume in cancer survivors OBJECTIVES To determine the feasibility of an eccentric resistance exercise training protocol in men with prostate cancer and to assess whether men with prostate cancer who are receiving and rogen deprivation therapy ( ADT ) have a blunted effect from the training as compared with prostate cancer survivors not receiving ADT . DESIGN Prospect i ve pilot study . SETTING Academic medical center . PARTICIPANTS Sixteen men with prostate cancer ( Gleason scores 3 + 3 to 4 + 4 ) were initially enrolled . Ten men ( mean age 66 , range 48 - 86 ) completed the study , 5 were currently receiving ADT . Analysis was performed on these 10 men . INTERVENTIONS Subjects were evaluated at baseline . All men underwent a 12-week resistance exercise training protocol using a recumbent , high-force eccentric , leg cycle ergometer 3 times per week at a " somewhat hard " perceived exertion for 12 to 15 minutes . Preexercise and postexercise training changes were examined within and between groups . MAIN OUTCOME MEASURES Quadriceps muscle volume ( magnetic resonance imaging ) , isometric knee extension strength , functional mobility ( Timed Up and Go Test [ TUG ] and 6-minute walk [ 6MW ] ) , health-related quality of life ( FACT-P ) , and fatigue ( FACIT-fatigue scale ) . RESULTS The ADT group demonstrated significant within-group improvements in the 6MW ( P = .01 ) and isometric knee extension strength ( P = .03 ) . This group also demonstrated a clinical ly relevant change in the FACT-P ; however , this did not meet statistical significance . The non-ADT group demonstrated significant within-group improvements in the physical subscale of the FACT-P ( P = .03 ) and an increase in muscle volume ( P = .04 ) . Their improvements in the TUG approached significance ( P = .08 ) . No between-group differences existed . CONCLUSIONS Eccentric resistance exercise was well tolerated , and both groups derived some benefits in strength and functional mobility . Men receiving ADT did not appear to have a blunted response to the exercise as compared with prostate cancer survivors not receiving ADT The aim of this study was to determine the effects of initial treatment with a GnRH agonist on body composition in asymptomatic men with nonmetastatic prostate cancer . Forty men with locally advanced , node-positive or biochemically recurrent prostate cancer , no radiographic evidence of metastases , and no prior and rogen deprivation therapy were treated with leuprolide 3-month depot 22.5 mg i m every 12 wk for 48 wk . The main outcome measures were percentage changes in weight , percentage fat body mass , percentage lean body mass , fat distribution , and muscle size after 48 wk . Thirty-two subjects were evaluable . Serum T concentrations decreased by 96.3 % plus or minus 0.4 % ( P < 0.001 ) . Weight increased by 2.4 % plus or minus 0.8 % ( P = 0.005 ) . Percentage fat body mass increased by 9.4 % plus or minus 1.7 % ( P < 0.001 ) , and percentage lean body mass decreased by 2.7 % plus or minus 0.5 % ( P < 0.001 ) . Cross-sectional areas of the abdomen and abdominal sc fat increased by 3.9 % plus or minus 1.2 % ( P = 0.003 ) and 11.1 % plus or minus 3.4 % ( P = 0.003 ) , respectively . In contrast , the cross-sectional area of intraabdominal fat did not change significantly ( P = 0.94 ) . Cross-sectional paraspinal muscle area decreased by 3.2 % plus or minus 1.3 % ( P = 0.02 ) . GnRH agonists increase weight and percentage fat body mass and decrease percentage lean body mass and muscle size in men with nonmetastatic prostate cancer . Increased fatness result ed primarily from accumulation of sc rather than intraabdominal adipose tissue Objective To examine prospect ively the association between muscular strength and mortality from all causes , cardiovascular disease , and cancer in men . Design Prospect i ve cohort study . Setting Aerobics centre longitudinal study . Participants 8762 men aged 20 - 80 . Main outcome measures All cause mortality up to 31 December 2003 ; muscular strength , quantified by combining one repetition maximal measures for leg and bench presses and further categorised as age specific thirds of the combined strength variable ; and cardiorespiratory fitness assessed by a maximal exercise test on a treadmill . Results During an average follow-up of 18.9 years , 503 deaths occurred ( 145 cardiovascular disease , 199 cancer ) . Age adjusted death rates per 10 000 person years across incremental thirds of muscular strength were 38.9 , 25.9 , and 26.6 for all causes ; 12.1 , 7.6 , and 6.6 for cardiovascular disease ; and 6.1 , 4.9 , and 4.2 for cancer ( all P<0.01 for linear trend ) . After adjusting for age , physical activity , smoking , alcohol intake , body mass index , baseline medical conditions , and family history of cardiovascular disease , hazard ratios across incremental thirds of muscular strength for all cause mortality were 1.0 ( referent ) , 0.72 ( 95 % confidence interval 0.58 to 0.90 ) , and 0.77 ( 0.62 to 0.96 ) ; for death from cardiovascular disease were 1.0 ( referent ) , 0.74 ( 0.50 to 1.10 ) , and 0.71 ( 0.47 to 1.07 ) ; and for death from cancer were 1.0 ( referent ) , 0.72 ( 0.51 to 1.00 ) , and 0.68 ( 0.48 to 0.97 ) . The pattern of the association between muscular strength and death from all causes and cancer persisted after further adjustment for cardiorespiratory fitness ; however , the association between muscular strength and death from cardiovascular disease was attenuated after further adjustment for cardiorespiratory fitness . Conclusion Muscular strength is inversely and independently associated with death from all causes and cancer in men , even after adjusting for cardiorespiratory fitness and other potential confounders Objective : To evaluate tolerability and compliance to a walking exercise program and its effect on fatigue during and after radical external beam radiation therapy ( EBRT ) for prostate cancer . Methods : A total of 50 subjects with prostate cancer undergoing EBRT over 6 to 8 weeks were prospect ively accrued to an exercise intervention group , matched for age and clinical characteristics to 30 subjects in a historical control group who underwent EBRT with no specific exercise intervention . Starting 1 week before EBRT , exercise participants performed moderate-intensity walking targeting 60 % to 70 % age-predicted maximum heart rate , at least 20 min/d , 3 d/wk over 12 weeks . The Brief Fatigue Inventory was administered at baseline , mid-EBRT ( week 3–4 ) , end-EBRT ( week 6–8 ) , and 6 months post-EBRT . Results : Of 50 , 42 ( 84 % ) of exercise participants completed the walking program . There were no cardiovascular complications , musculoskeletal injuries , or other adverse events . A total of 89 % subjects reported “ Good-Excellent ” satisfaction during and up to 6 months post-EBRT . Fatigue in control subjects escalated from baseline to end-EBRT , remaining high at 6 months post-EBRT ( P[r ] = 0.03 ) . In contrast , mean total fatigue scores in exercise subjects were stable from baseline up to 6 months post-EBRT ( P = 0.52 ) . Trends for higher fatigue interference with quality of life were observed in the control group as compared with the exercise group . Conclusions : Moderate-intensity walking exercise during radical EBRT is safe and feasible . The high convenience and satisfaction ratings , in conjunction with the observed fatigue trends , indicate that this activity has the potential to attenuate fatigue and improve quality of life for patients with localized prostate cancer undergoing curative therapy PURPOSE Radiotherapy for prostate cancer ( PCa ) may cause unfavorable changes in fatigue , quality of life ( QOL ) , and physical fitness . We report results from the Prostate Cancer Radiotherapy and Exercise Versus Normal Treatment study examining the effects of 24 weeks of resistance or aerobic training versus usual care on fatigue , QOL , physical fitness , body composition , prostate-specific antigen , testosterone , hemoglobin , and lipid levels in men with PCa receiving radiotherapy . PATIENTS AND METHODS Between 2003 and 2006 , we conducted a r and omized controlled trial in Ottawa , Canada , where 121 PCa patients initiating radiotherapy with or without and rogen deprivation therapy were r and omly assigned to usual care ( n = 41 ) , resistance ( n = 40 ) , or aerobic exercise ( n = 40 ) for 24 weeks . Our primary end point was fatigue assessed by the Functional Assessment of Cancer Therapy-Fatigue scale . RESULTS The follow-up assessment rate for our primary end point of fatigue was 92.6 % . Median adherence to prescribed exercise was 85.5 % . Mixed-model repeated measures analyses indicated both resistance ( P = .010 ) and aerobic exercise ( P = .004 ) mitigated fatigue over the short term . Resistance exercise also produced longer-term improvements ( P = .002 ) . Compared with usual care , resistance training improved QOL ( P = .015 ) , aerobic fitness ( P = .041 ) , upper- ( P < .001 ) and lower-body ( P < .001 ) strength , and triglycerides ( P = .036 ) , while preventing an increase in body fat ( P = .049 ) . Aerobic training also improved fitness ( P = .052 ) . One serious adverse event occurred in the group that performed aerobic exercise . CONCLUSION In the short term , both resistance and aerobic exercise mitigated fatigue in men with PCa receiving radiotherapy . Resistance exercise generated longer-term improvements and additional benefits for QOL , strength , triglycerides , and body fat |
10,992 | 29,256,626 | Conclusion : Significant effects of Tai Chi have been found in improving aerobic endurance and psychosocial well-being among coronary heart disease patients .
Tai Chi could be a cost-effective and safe exercise option in cardiac rehabilitation . | Introduction : Tai Chi is an attractive exercise to improve cardiovascular health .
This review aim ed to synthesize articles written both in Chinese and in English to evaluate the effects of Tai Chi-based cardiac rehabilitation on aerobic endurance , psychosocial well-being and cardiovascular diseases risk reduction for coronary heart diseases patients .
However , the effect of Tai Chi on cardiovascular disease risk reduction has not been amply investigated among coronary heart disease patients . | The Flexibility , Toning , and Balance ( FlexToBa ) Trial is a two-armed r and omized controlled trial which will contrast the effects of a DVD-delivered , home-based , physical activity intervention and a Healthy Aging attention control condition on physical activity , functional performance , functional limitations , and quality of life in low active , older adults . This innovative trial will recruit 300 participants across central Illinois who will be r and omized into the intervention arm or control arm of the study . The intervention will last 6 months with a 6 month follow-up . Assessment s at baseline , post intervention and follow-up will include physical activity ( self-report and accelerometry ) , a battery of functional performance measures , functional limitations , quality of life , and an array of psychological health measures . In addition , measures of external validity will be included to determine public health significance of a successful outcome . Participants will engage in a progressive series of activities focusing on flexibility , strengthening , and balance exercises which are demonstrated by a trained exercise leader and age-appropriate models on a series of DVDs . Delivery of the intervention has its basis in social cognitive theory . The specific aims of the trial are ( a ) to determine the effects of the DVD-delivered FlexToBa program on physical activity , functional performance , functional limitations , and quality of life , ( b ) to examine the mediators of the relationships between physical activity and functional limitations and quality of life , ( c ) to assess external validity indicators relative to the intervention , and ( d ) to determine differential effects of the intervention on psychosocial health measures How should health care professionals choose among the many therapies cl aim ed to be efficacious for treating specific disorders ? The practice of evidence -based medicine provides an answer . Advocates of this approach urge health care professionals to base treatment choices on the best evidence from systematic research on both the efficacy and adverse effects of various therapeutic alternatives . Ideally , health care professionals would compare different treatments by referring to r and omized , double-blind , head-to-head trials that compared the treatment options . Although individual medications are typically well research ed when these placebo-controlled studies are performed , studies that directly compare treatments are rare . In the absence of direct head-to-head trials , other evidence comes from indirect comparisons of two or more therapies by examining individual studies involving each treatment . This article provides an introductory review of methods of such indirect comparisons of therapies across studies , provides examples of how these methods can be used to make treatment decisions , and presents a general overview of relevant issues and statistics for readers interested in underst and ing these methods more thoroughly Obesity , metabolic syndrome , dyslipidemia , and poor quality of life are common conditions associated with hypertension , and incidence of hypertension is age dependent . However , an effective program to prevent hypertension and to improve biomedical factors and quality of life has not been adequately examined or evaluated in Chinese older adults . This study aims to examine the effectiveness of a Tai Chi program to improve health status in participants with hypertension and its related risk factors such as dyslipidemia , hyperglycemia , and quality of life in older adults in China . A r and omized study design was used . At the conclusion of the intervention , 266 patients remained in the study . Blood pressure and biomedical factors were measured according to the World Diabetes Association st and ard 2002 . A st and ardized quality -of-life measure was used to measure health-related quality of life . It was found that a Tai Chi program to improve hypertension in older adults is effective in reducing blood pressure and body mass index , maintaining normal renal function , and improving physical health of health-related quality of life . It did not improve existing metabolic syndrome levels , lipid level ( dyslipidemia ) or fasting glucose level ( hyperglycemia ) , to prevent further deterioration of the biomedical risk factors . In conclusion , Tai Chi is effective in managing a number of risk factors associated with hypertension in Chinese older adults . Future research should examine a combination of Tai Chi and nutritional intervention to further reduce the level of biomedical risks In this study , 126 patients ( 90 males , average age 56 years , range 39 - 80 ) were r and omised to Wu Chian-Ch'uan style Tai Chi ( 38 ) , aerobic exercise ( 41 ) or a non-exercise support group ( 47 ) following acute myocardial infa rct ion . Patients attended twice weekly for three weeks then weekly for a further five weeks . Heart rate and blood pressure were recorded before and after each session . Over the 11 sessions of exercise there was a negative trend in diastolic blood pressure only in the Tai Chi group ( Rs = 0.79 , p < 0.01 ) . Significant trends in systolic blood pressure occurred in both exercise groups ( Rs = 0.64 and 0.63 , both p < 0.05 ) . Only four ( 8 % ) patients completed the support group eight-week programme which was less than the number completing Tai Chi ( 82 % ; p < 0.001 ) and aerobic exercise groups ( 73 % ; p < 0.001 ) PURPOSE This study prospect ively evaluated the training effect of a 1-yr Tai Chi Chuan ( TCC ) program for low-risk patients with coronary artery bypass surgery ( CABS ) after a postoperative outpatient ( phase II ) cardiac rehabilitation program . METHODS Twenty patients with mean age of 56.5+/-7.4 yr completed this study . The TCC group included nine men who practice d classical Yang TCC with an exercise intensity of 48 - 57 % heart rate range ( HRR ) . The control group included 11 men whom were recommended to do a home-based self-adjusted exercise program with similar intensity of phase II cardiac rehabilitation . Grade d exercise tests were performed before and after 1 yr of training for all subjects . RESULTS Mean attendance of the TCC group was 3.8+/-1.5 times weekly in contrast to 1.7+/-1.1 times for the control group . During the follow-up examination , the TCC group increased 10.3 % in VO2peak ( from 26.2+/-4.4 to 28.9+/-5.0 mL x kg(-1 ) min(-1 ) , P<0.01 ) and increased 11.9 % in peak work rate ( from 135+/-26 W to 151+/-28 W , P<0.01 ) . However , the control group showed slight decrease in VO2peak from 26.0+/-3.9 to 25.6+/-4.6 mL x kg(-1 ) x min(-1 ) and in peak work rate from 131+/-23 W to 128+/-32 W. At the ventilatory threshold , the TCC group also showed significant increase in VO2 and work rate ( P<0.05 ) . The control group did not significantly change in these variables . CONCLUSIONS The study demonstrated that a 1-yr TCC program for low-risk patients with CABS could favorably enhance cardiorespiratory function BACKGROUND Patients with chronic heart failure ( HF ) and with elevated depression symptoms are at greater risk of morbidity and mortality . Somatic symptoms of depression are particularly prevalent in HF and are related to worse disease prognosis . T'ai chi practice is related to increased emotional well-being in various clinical population s ; however , relatively little is known about t'ai chi 's effects on somatic versus cognitive symptom dimensions of depression in HF . PURPOSE The objective of the study was to measure whether a t'ai chi intervention effectively reduces somatic and /or cognitive symptoms of depression in patients with HF . METHODS Patients with HF were assigned to either t'ai chi training ( n=16 ) or a usual-care group ( n=12 ) . At baseline and after the 12-week intervention period , participants were evaluated for changes in depressive symptoms using Beck Depression Inventory ( BDI ) total scores ( BDI-t ) and subcategorized scores of BDI-somatic ( BDI-s ) and BDI-cognitive ( BDI-c ) , and for symptoms of fatigue using the Multidimensional Fatigue Symptom Inventory-Short Form . RESULTS Patients with HF in the t'ai chi group compared to the usual-care group had reduced BDI-s ( p≤0.017 ) , but not BDI-c ( p=0.50 ) scores from pre- to postintervention . Although t'ai chi did not significantly reduce fatigue , changes in physical fatigue ( p≤0.05 ) were independently associated with changes in BDI-t scores . CONCLUSIONS T'ai chi practice reduced somatic symptoms of depression , which have been linked to worse prognosis in HF . Reductions in fatigue appear to explain some but not all of the reductions in somatic symptoms of depression OBJECTIVES To evaluate the effects on blood pressure , lipid profile , and anxiety status on subjects received a 12-week Tai Chi Chuan exercise program . DESIGN R and omized controlled study of a Tai Chi Chuan group and a group of sedentary life controls . SETTING Taipei Medical University Hospitals and University campus in the Taipei , Taiwan , area . SUBJECTS Two ( 2 ) selected groups of 76 healthy subjects with blood pressure at high-normal or stage I hypertension . INTERVENTION A 12-week Tai Chi Chuan exercise training program was practice d regularly with a frequency of 3 times per week . Each session included 10-minute warm-up , 30-minute Tai Chi exercise , 10-minute cool-down . Exercise intensity was estimated to be approximately 64 % of maximal heart rate . OUTCOME MEASURES Blood pressure , lipid profile and anxiety status ( State-Trait Anxiety Inventory ; STAI ) were evaluated . RESULTS After 12-weeks of Tai Chi training , the treatment group showed significant decrease in systolic blood pressure of 15.6 mm Hg and diastolic blood pressure 8.8 mm Hg . The serum total cholesterol level decreased 15.2 mg/dL and high-density lipoprotein cholesterol increased 4.7 mg/dL. By using STAI evaluation , both trait anxiety and state anxiety were decreased . CONCLUSIONS This study shows that under well- design ed conditions , Tai Chi exercise training could decrease blood pressure and results in favorable lipid profile changes and improve subjects ' anxiety status . Therefore , Tai Chi could be used as an alternative modality in treating patients with mild hypertension , with a promising economic effect Although exercise is an important component of heart failure management , optimal regimens , particularly in heart failure with preserved ejection fraction ( HFPEF ) , are uncertain . Tai chi ( TC ) is a mind-body exercise that may have potential benefits but has not been studied in this population . The authors r and omized 16 patients with HFPEF to either 12 weeks TC or aerobic exercise . Assessment s included peak oxygen uptake , 6-minute walk , quality of life , echocardiography , mood , and self-efficacy at baseline and at 12 weeks . Cardiorespiratory measures during exercise were obtained to characterize training intensities . Baseline characteristics were as follows : age 66±12 years , E/A ratio 1.3±0.7 , and E/e ' ratio 15.9±4.8 . Overall , adherence was excellent ( 89 % attendance ) . Change in peak oxygen uptake was similar between groups after 12 weeks , but 6-minute walk distance increased more after TC ( 69±46 m vs 10±31 m , P=.02 ) . While both groups had improved Minnesota Living With Heart Failure scores and self-efficacy , Profile of Mood States (POMS)-Depression scores improved more with TC ( -1.7±2.8 vs 1.6±3 , P=.05 ) . Cardiorespiratory assessment during TC showed lower oxygen uptake ( 4.3 mL/kg/min vs 9.4 mL/kg/min , P<.01 ) , respiratory rate , and heart rate . TC is feasible and safe in HFPEF . Therepeutic endpoints appear similar with TC relative to aerobic exercise despite a lower aerobic training workload BACKGROUND Patients with a recent myocardial infa rct ion ( MI ) present a reduction in functional capacity expressed as a decrease in peak oxygen consumption ( Vo2 peak ) . The impact of a Tai Chi Chuan ( TCC ) cardiac rehabilitation program for patients recovering from recent MI has yet to be assessed . Our goal is to evaluate functional capacity after a TCC-based cardiac rehabilitation program in patients with recent MI . METHODS A single-blind r and omized clinical trial was conducted . The research ers who performed the tests were blinded to group allocation . Between the 14th and 21st days after hospital discharge , all patients performed a cardiopulmonary exercise testing and a laboratory blood workup . Mean age was similar ( 56±9 years in the TCC group and 60±9 years in the control group ) . Patients allocated to the intervention group performed 3 weekly sessions of TCC Beijin style for 12 weeks ( n=31 ) . The control group participated in 3 weekly sessions of full-body stretching exercises ( n=30 ) . RESULTS After the 12-week study period , participants in the TCC group experienced a significant 14 % increase in Vo2 peak from baseline ( 21.6 ± 5.2 to 24.6 ± 5.2 mL/kg per minute ) , whereas control participants had a nonsignificant 5 % decline in Vo2 peak ( 20.4 ± 5.1 to 19.4 ± 4.4 mL/kg per minute ) . There was a significant difference between the 2 groups ( P<.0001 ) . CONCLUSIONS Tai Chi Chuan practice was associated with an increase in Vo2 peak in patients with a recent MI and may constitute an effective form of cardiac rehabilitation in this patient population Background : Cardiac rehabilitation improves physical , cognitive and psychosocial functioning , yet services are greatly underutilized with increasing patterns of attrition over time . Tai Chi has been suggested as a possible adjunct to cardiac rehabilitation exercise training . Aim : To describe differences in physical , cognitive and psychosocial functioning among adults ≥ 45 years old attending phase III cardiac rehabilitation , who have or have not self-selected Tai Chi exercise as an adjunct physical activity . Methods : A cross-sectional design compared subjects attending group-based Wu style Tai Chi classes plus cardiac rehabilitation , with cardiac rehabilitation only . Subjects had a battery of physical and cognitive functioning tests administered to examine aerobic endurance , balance , strength , and flexibility , verbal retrieval/recall , attention , concentration and tracking . Subjects completed a health survey to ascertain cardiac event information , medical history , and psychosocial functioning ( i.e. health-related quality of life , stress , depressive symptoms , social support , and Tai Chi self-efficacy ) . Results : A total of 51 subjects ( 75 % married , 84 % college-educated , 96 % White/European-American ) participated . Subjects were on average 70 ( ± 8) years old and had attended cardiac rehabilitation for 45 ( ± 37 ) months . Approximately 45 % ( n = 23 ) attended Tai Chi classes plus cardiac rehabilitation , while 55 % ( n = 28 ) attended cardiac rehabilitation only . Subjects attending Tai Chi plus cardiac rehabilitation had better balance , perceived physical health , and Tai Chi self-efficacy compared to those attending cardiac rehabilitation only ( p ≤ 0.03 ) . Conclusion : Tai Chi can be easily implemented in any community/cardiac rehabilitation facility , and may offer adults additional options after a cardiac event BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application BACKGROUND Exercise training has been demonstrated to enhance physical function and to have a protective effect against functional limitations and disability in older adults . PURPOSE The objective of this study was to determine whether the effects of a home-based , DVD-delivered exercise intervention on functional performance and limitations were maintained 6-month postintervention termination . METHODS Follow-up assessment s of functional performance and limitations were conducted in a sample of community-dwelling older adults ( N = 237 ) who participated in a 6-month r and omized controlled exercise trial . Participants were initially r and omized to a DVD-delivered exercise intervention or an attentional control condition . The Short Physical Performance Battery , measures of flexibility and strength , and functional limitations were assessed immediately before and after the intervention and then again 6 months later . Analyses of covariance were conducted to examine changes in physical function between the two conditions at the end of the intervention to 6-month follow-up . RESULTS There were statistically significant adjusted group differences in the Short Physical Performance Battery ( η(2 ) = 0.03 , p = .01 ) , upper-body strength ( η(2 ) = 0.03 , p = .005 ) , and lower-body flexibility ( η(2 ) = 0.02 , p = .05 ) , indicating that gains brought about by the intervention were maintained 6 months later . CONCLUSIONS A DVD-delivered exercise program specifically design ed to target elements of functional fitness in older adults can produce clinical ly meaningful gains in physical function that are maintained beyond intervention cessation BACKGROUND Over one-third of cardiac patients practice Mind-Body Therapy ( MBT ) , particularly women . Considering women are less likely to engage in conventional physical activity , few studies have examined why MBT is well-accepted by women . OBJECTIVES To qualitatively explore gender differences in the motivations for , and perceived effects of MBT , and the inter-relationships among alternative and conventional physical activities and secondary prevention programs . METHODS A r and om sub sample of 16 participants ( 8 female ) who reported practicing MBT in a larger study of 661 cardiac patients was interviewed until theme saturation was achieved . Audiotapes were transcribed and coded based on interpretive-descriptive technique within Nvivo-7 software . An audit trail and second coder were utilized to ensure the transparency and validity of results . After main themes emerged , the data were split by gender to identify differences for each theme . RESULTS Five themes emerged : ( 1 ) promotes positive well-being , ( 2 ) physical health benefits , ( 3 ) intrinsic and extrinsic motivations , ( 4 ) proactive health orientation , and ( 5 ) MBT as a preferred complementary and /or alternative physical activity . Men more often expressed preference for MBT for increased positive mood and cardiac-specific benefits , whereas women emphasized stress reduction , increasing self-efficacy , and physical activity , and were eager to see MBT offered in cardiac rehabilitation ( CR ) . CONCLUSIONS Both male and female users perceived substantial psychosocial and physical benefits of MBT practice . MBT addresses some of women 's common barriers to CR OBJECTIVE The objective of this study was to evaluate the effect of t'ai chi ( TC ) on heart rate variability ( HRV ) from baseline to 9 months in patients with coronary artery disease ( CAD ) . DESIGN A comparative trial was undertaken comparing the acute and long-term effect of TC on HRV in patients with CAD . PARTICIPANTS Sixty-one ( 61 ) subjects with CAD undergoing percutaneous intervention or coronary bypass grafting for a period of more than 1 month were recruited from the clinics of cardiology and cardiovascular surgery at Chia-Yi Christian Hospital , Taiwan . INTERVENTIONS The experimental group ( n = 22 ) practice d weekly 90-minute Yang 's style TC for 9 months and the control group ( n = 39 ) continued their normal daily physical activity . MAIN OUTCOME MEASURES HRV was recorded at baseline , 3 months , 6 months , and 9 months in the control group . Resting HRV was recorded before TC exercise and recovery HRV was recorded 30 minutes post TC at the same four time points in the experimental group . RESULTS The change in the normalized low-frequency power , normalized high-frequency power , and the low-/high-frequency power ratio between resting and post-TC was significantly different at 9 months when compared with those at baseline , 3 , and 6 months . The mean difference in normalized low-frequency power and the low/high-frequency power ratio changed from positive values at baseline , 3 , and 6 months to negative values at 9 months . However , there were no significant differences in resting HRV between the patients in TC and control groups in either time domain or frequency domain HRV indices . CONCLUSIONS The change in heart rate and HRV between resting and post-TC suggested that TC exercise could enhance vagal modulation . The potential beneficial effect of long-term regular TC exercise in patients with CAD merits further investigation |
10,993 | 26,212,600 | The article ends by explaining how Simonton 's chance configuration theory and Campbell 's evolutionary epistemology can illuminate why meta- analysis occurred with these scholars when it did and not in medical sciences | This article looks at the impact of meta- analysis and then explores why meta- analysis was developed at the time and by the scholars it did in the social sciences in the 1970s .
For the first problem , impact , it examines the impact of meta- analysis using citation network analysis .
The impact is seen in the sciences , arts and humanities , and on such contemporaneous developments as multilevel modeling , medical statistics , qualitative methods , program evaluation , and single-case design .
Then , the article examines why meta- analysis came to be in the 1970s in the social sciences through the work of Gene Glass , Robert Rosenthal , and Frank Schmidt , each of whom developed similar theories of meta- analysis at about the same time . | A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor This study aims to compare h and search ing to a basic MEDLINE search for the identification of reports of r and omized trials in specialized health care journals . Twenty-two specialized health care journals , published in the U.K. , were h and search ed for all reports of controlled trials ( as defined by the Cochrane Collaboration ) . The reports of trials , which were judged to be definitely r and omized , were identified from a r and om sample of three years per journal and form one element of this study . A MEDLINE search using the publication type terms ' r and omized controlled trial ' and ' controlled clinical trial ' was also performed for the same journal years . The reports of trials retrieved by h and search ing were then compared against those retrieved from the MEDLINE search , to identify differences in retrieval between the two techniques . Reports of r and omized trials identified by the MEDLINE search but not found by h and search ing were individually assessed to see if they met the Cochrane eligibility criteria for a report of a r and omized trial . A total of 714 reports of r and omized trials were found by using a combination of both h and search ing and MEDLINE search ing . Of these , 369 ( 52 per cent ) were identified only by h and search ing and 32 ( 4 per cent ) were identified only by MEDLINE search ing . Of the reports identified only by h and search ing , 252 had no MEDLINE record , of which 232 ( 92 per cent ) were meeting abstract s or published in supplements ; 117 ( 25 per cent ) of the 462 reports of r and omized trials which had a MEDLINE record were missed by the electronic search because they did not have either of the publication type terms ' r and omized controlled trial ' or ' controlled clinical trial ' . This proportion varied depending on when the reports of r and omized trials were published ( that is , before or after the introduction of the MEDLINE publication type terms above ) . The highest additional yield from h and search ing compared to MEDLINE search ing was for reports of r and omized trials published prior to 1991 and from h and search ing the non- MEDLINE indexed parts of a journal . The results of this study suggest that a combination of MEDLINE and h and search ing is required to identify adequately reports of r and omized trials In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies Dr. Joseph Lau is a world-leading expert in meta- analysis and systematic review s. Currently a professor in the Department of Health Services , Policy and Practice and co-director of the Center for Evidence -based Medicine at Brown University , Professor Lau has applied evidence -based methods to a variety of clinical , biomedical and healthcare topics ; has developed reliable and efficient methods and tools to conduct systematic review s and meta-analyses ; and has advanced an underst and ing on the impact of factors that may contribute to differences of results in scientific studies . His past research includes cumulative meta- analysis of r and omized controlled trials , comparison of results from large trials and meta-analyses of small trials , effect of baseline risk in the interpretation of clinical trial results , and empirical evaluation of existing methods of combining data . His current focus is on a Web-based repository of systematic review data , review s of diagnostic tests , nutrition , clinical practice guidelines , and dissemination of evidence -based methods to varied health-care disciplines . This report is a conversation from an adapted version of an interview , more or less chronologically arranged , between Joseph C. Cappelleri as interviewer and Joseph Lau as interviewee , with Meghan Ingerick recording and transcribing the interview Abstract An increased mortality in early breast cancer can be correlated to the routine use of local postoperative irradiation . The decreased survival is statistically significant . Of controlled clinical trials so far published , all six , including more than 3400 patients , demonstrate decreased survival of between 1 and 10 % in irradiated patients when compared with those treated by mastectomy alone |
10,994 | 26,423,913 | As there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism , anticoagulation may be advisable in certain newly diagnosed adult GBM patients who display a history of thromboembolism and /or more serious risk factors for thromboembolic events | Previous evidence suggests that the humanized anti-VEGF antibody bevacizumab increases thrombosis risk in glioma patients .
Here , we comprehensively assessed the risk of adverse vascular events in adult glioma patients receiving bevacizumab therapy . | BACKGROUND Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme . This study combined bevacizumab , a vascular endothelial growth factor inhibitor , and erlotinib , an epidermal growth factor receptor inhibitor , with st and ard radiation and temozolomide ( TMZ ) , with the goal of improving overall survival ( OS ) . METHODS Treatment consisted of fractionated radiotherapy to 60 Gy , with daily TMZ at 75 mg/m²/d and erlotinib 150 - 200 mg/d ( or 500 - 600 mg/d for patients on enzyme-inducing antiepileptic drugs ) . Bevacizumab was given at 10 mg/kg every 2 weeks , starting ≥4 weeks after surgery . After radiotherapy , adjuvant TMZ was given at 200 mg/m²/d × 5d per 28-day cycle , with unchanged erlotinib and bevacizumab doses . Treatment continued until progression or for 12 months . Efficacy was compared against an institutional historical control . A sample of 55 patients was calculated to provide 85 % power to detect a hazard ratio of 0.67 for OS . RESULTS Fifty-nine patients were enrolled for efficacy analysis after a 15-patient safety lead-in . For the efficacy group , median age was 54 years ; median KPS was 90 . Gross total and subtotal resections were achieved in 33 % and 53 % , respectively . The most frequent related grade 3/4 adverse effects were lymphopenia , thrombocytopenia , neutropenia , diarrhea , weight loss , and fatigue . One patient died of disseminated aspergillosis . Median OS was 19.8 months ( vs 18 mo for HC , P = .33 ) and median progression-free survival was 13.5 months ( vs 8.6 mo for HC , P = .03 ) . CONCLUSIONS The combination of bevacizumab , erlotinib , TMZ , and radiotherapy appears to be well tolerated and improved progression-free survival but did not reach the primary endpoint of improved OS BACKGROUND Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the st and ard of care for patients with newly diagnosed glioblastoma . Bevacizumab , a humanized monoclonal antibody against vascular endothelial growth factor A , is currently approved for recurrent glioblastoma . Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known . METHODS In this r and omized , double-blind , placebo-controlled trial , we treated adults who had central ly confirmed glioblastoma with radiotherapy ( 60 Gy ) and daily temozolomide . Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy . At disease progression , the assigned treatment was revealed , and bevacizumab therapy could be initiated or continued . The trial was design ed to detect a 25 % reduction in the risk of death and a 30 % reduction in the risk of progression or death , the two co primary end points , with the addition of bevacizumab . RESULTS A total of 978 patients were registered , and 637 underwent r and omization . There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group ( median , 15.7 and 16.1 months , respectively ; hazard ratio for death in the bevacizumab group , 1.13 ) . Progression-free survival was longer in the bevacizumab group ( 10.7 months vs. 7.3 months ; hazard ratio for progression or death , 0.79 ) . There were modest increases in rates of hypertension , thromboembolic events , intestinal perforation , and neutropenia in the bevacizumab group . Over time , an increased symptom burden , a worse quality of life , and a decline in neurocognitive function were more frequent in the bevacizumab group . CONCLUSIONS First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma . Progression-free survival was prolonged but did not reach the prespecified improvement target . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00884741 . ) BACKGROUND Prognosis of unresectable glioblastoma ( GB ) remains poor , despite temozolomide (TMZ)-based chemoradiation . Activity of bevacizumab ( BEV ) and irinotecan ( IRI ) has been reported in recurrent disease . We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB . PATIENTS AND METHODS Patients with unresectable GB , age 18 - 70 , IK ≥50 were eligible . The experimental arm ( BEV/IRI ) consisted of neo-adjuvant intravenous BEV , 10 mg/kg , and IRI , 125 mg/m(2 ) , every 2 weeks for four cycles before radiotherapy ( RT ) ( 60 Gy ) , concomitant oral TMZ , 75 mg/m(2)/day , and BEV , 10 mg/kg every 2 weeks . Adjuvant BEV and IRI were given every 2 weeks for 6 months . The control arm consisted of concomitant oral TMZ , 75 mg/m(2)/day during RT , and 150 - 200 mg/m(2 ) for 5 days every 28 days for 6 months . The use of BEV was allowed at progression in the control arm . RESULTS Patients ( 120 ) were included from April 2009 to January 2011 . The working hypothesis was that treatment would increase the progression-free survival at 6 month ( PFS-6 ) from 50 % to 66 % . The primary objective was not achieved , and only 30 out of 60 patients were alive without progression at 6 months ( 50.0 % [ IC95 % ( 36.8 ; 63.1 ) ] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules . PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm . The median overall survival was not different between the two arms ( 11.1 months ) . Main toxicities were three fatal intracranial bleedings , three bile duct or digestive perforations/infections ( 1 fatal ) , and six thrombotic episodes in the BEV/IRI arm , whereas there was one intracranial bleeding , two bile duct or digestive perforations/infections ( 1 fatal ) , and one thrombotic episode in the control arm . CONCLUSIONS Neo-adjuvant and adjuvant BEV/IRI , combined with TMZ-radiation , is not recommended for further evaluation in the first-line treatment of unresectable GB . CLINICAL TRIAL REGISTRATION Clinical trial registered under EUDRACT number 2008 - 002775 - 28 ( NCT01022918 ) BACKGROUND High- grade gliomas ( HGGs ) are among the most prothrombotic of malignancies . METHODS We performed a prospect i ve study to investigate 11 potential biomarkers for prediction of venous thromboembolism ( VTE ) in newly diagnosed HGG patients who had undergone a neurosurgical intervention . In addition , we tested 2 VTE risk assessment models ( RAMs ) . The strongest predictors of VTE , which were identified by statistical forward selection , were used for the first RAM . The parameters used for the second RAM were both predictive of VTE and available in routine clinical practice . RESULTS One hundred forty-one HGG patients were included in this study , and 24 ( 17 % ) of them developed VTE during follow-up . An association with the risk of future VTE was found for the following parameters : leukocyte count , platelet count , sP-selectin , prothrombin-fragment 1 + 2 , FVIII activity , and D-dimer . The first RAM included low platelet count ( < 25th percentile of the study population ) and elevated sP-selectin ( ≥75th percentile ) . The cumulative VTE probability after 12 months was 9.7 % for score 0 ( n = 76 ) , 18.9 % for score 1 ( n = 59 ) , and 83.3 % for score 2 ( n = 6 ) . The second RAM included low platelet count ( < 25th percentile ) , elevated leukocyte count , and elevated D-dimer ( ≥75th percentile ) . The probability of VTE was 3.3 % for score 0 ( n = 63 ) , 23.0 % for score 1 ( n = 53 ) , and 37.7 % for score 2 ( n = 22 ) or score 3 ( n = 3 ) . CONCLUSIONS We identified biomarkers suitable for assessing the VTE risk in newly diagnosed HGG patients . The application of 2 RAMs allowed identification of patients at high risk of developing VTE . We could also define patients at low risk of VTE , who would most probably not benefit from extended primary thromboprophylaxis PURPOSE To determine the safety of the addition of bevacizumab to st and ard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme ( GBM ) . METHODS AND MATERIAL S A total of 125 patients with newly diagnosed GBM were enrolled in the study , and received st and ard radiation therapy and daily temozolomide . All patients underwent a craniotomy and were at least 2 weeks postoperative . Radiation therapy was administered in 1.8-Gy fractions , with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy , followed by a boost of 9 to 14.4 Gy , to a total dose of 59.4 Gy . Patients received temozolomide at 75 mg/m(2 ) daily throughout the course of radiation therapy . Bevacizumab was given at 10 mg/kg intravenously every 14 days , beginning a minimum of 4 weeks postoperatively . RESULTS Of the 125 patients , 120 ( 96 % ) completed the protocol -specified radiation therapy . Five patients had to stop the protocol therapy , 2 patients with pulmonary emboli , and 1 patient each with a Grade 2 central nervous system hemorrhage , Grade 4 pancytopenia , and wound dehiscence requiring surgical intervention . All 5 patients ultimately finished the radiation therapy . After radiation therapy , 3 patients had progressive disease , 2 had severe fatigue and decreased performance status , 1 patient had a colonic perforation , and 1 had a rectal fissure ; these 7 patients therefore did not proceed with the protocol -specified adjuvant temozolomide , bevacizumab , and irinotecan . However , 113 patients ( 90 % ) were able to continue on study . CONCLUSIONS The addition of bevacizumab to st and ard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM PURPOSE Venous thromboembolism ( VTE ) is a well-recognized complication of cancer . Laboratory parameters might be useful to assess the VTE risk in patients with cancer . The aim of this study was to investigate D-dimer and prothrombin fragment 1 + 2 ( F 1 + 2 ) , which reflect activation of blood coagulation and fibrinolysis , for prediction of cancer-associated VTE . PATIENTS AND METHODS In a prospect i ve , observational , cohort study of 821 patients with newly diagnosed cancer or progression of disease who did not recently receive chemotherapy , radiotherapy , or surgery were enrolled and followed for a median of 501 days ( interquartile range , 255 to 731 days ) . The malignancies in these patients were as follows : breast ( n = 132 ) , lung ( n = 119 ) , stomach ( n = 35 ) , lower gastrointestinal tract ( n = 106 ) , pancreas ( n = 46 ) , kidney ( n = 22 ) , and prostate ( n = 101 ) cancers ; high- grade glioma ( n = 102 ) ; malignant lymphoma ( n = 94 ) ; multiple myeloma ( n = 17 ) ; and other tumor types ( n = 47 ) . The study end point was occurrence of objective ly confirmed symptomatic or fatal VTE . RESULTS VTE occurred in 62 patients ( 7.6 % ) . The cutoff level for elevated D-dimer and elevated F 1 + 2 was set at the 75th percentile of the total study population . In multivariable analysis that included elevated D-dimer , elevated F 1 + 2 , age , sex , surgery , chemotherapy , and radiotherapy , the hazard ratios ( HRs ) of VTE in patients with elevated D-dimer ( HR , 1.8 ; 95 % CI , 1.0 to 3.2 ; P = .048 ) and elevated F 1 + 2 ( HR , 2.0 ; 95 % CI , 1.2 to 3.6 ; P = .015 ) were statistically significantly increased . The cumulative probability of developing VTE after 6 months was highest in patients with both elevated D-dimer and elevated F 1 + 2 ( 15.2 % ) compared with patients with nonelevated D-dimer and nonelevated F 1 + 2 ( 5.0 % ; P < .001 ) . CONCLUSION High D-dimer and F 1 + 2 levels independently predict occurrence of VTE in patients with cancer BACKGROUND St and ard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide . In this phase 3 study , we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma . METHODS We r and omly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab ( 10 mg per kilogram of body weight every 2 weeks ) or placebo , plus radiotherapy ( 2 Gy 5 days a week ; maximum , 60 Gy ) and oral temozolomide ( 75 mg per square meter of body-surface area per day ) for 6 weeks . After a 28-day treatment break , maintenance bevacizumab ( 10 mg per kilogram intravenously every 2 weeks ) or placebo , plus temozolomide ( 150 to 200 mg per square meter per day for 5 days ) , was continued for six 4-week cycles , followed by bevacizumab monotherapy ( 15 mg per kilogram intravenously every 3 weeks ) or placebo until the disease progressed or unacceptable toxic effects developed . The co primary end points were investigator-assessed progression-free survival and overall survival . RESULTS A total of 458 patients were assigned to the bevacizumab group , and 463 patients to the placebo group . The median progression-free survival was longer in the bevacizumab group than in the placebo group ( 10.6 months vs. 6.2 months ; stratified hazard ratio for progression or death , 0.64 ; 95 % confidence interval [ CI ] , 0.55 to 0.74 ; P<0.001 ) . The benefit with respect to progression-free survival was observed across subgroups . Overall survival did not differ significantly between groups ( stratified hazard ratio for death , 0.88 ; 95 % CI , 0.76 to 1.02 ; P=0.10 ) . The respective overall survival rates with bevacizumab and placebo were 72.4 % and 66.3 % at 1 year ( P=0.049 ) and 33.9 % and 30.1 % at 2 years ( P=0.24 ) . Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group , and the glucocorticoid requirement was lower . More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events ( 66.8 % vs. 51.3 % ) and grade 3 or higher adverse events often associated with bevacizumab ( 32.5 % vs. 15.8 % ) . CONCLUSIONS The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma . Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab ; however , the rate of adverse events was higher with bevacizumab than with placebo . ( Funded by F. Hoffmann-La Roche ; Clinical Trials.gov number , NCT00943826 . ) |
10,995 | 25,924,187 | RESULTS The analysis demonstrated it is feasible to build and run a complex clinical decision aid using DES .
The model results support current guidelines for most vignettes but suggest that earlier repair may be effective in younger , fitter patients and ongoing surveillance may be effective in elderly patients with comorbidities .
The model adds information to support decisions for patients with aneurysms outside current indications .
The economic evaluation suggests that using the ARDA compared with current guidelines could be cost-effective but there is a high level of uncertainty .
LIMITATIONS Lack of high- quality long-term data to populate all sections of the model meant that there is high uncertainty about the long-term clinical and economic consequences of repair .
The ARDA provides detailed information on the potential consequences of AAA repair or a decision not to repair that may be helpful to vascular surgeons and their patients in reaching informed decisions . | BACKGROUND Abdominal aortic aneurysm ( AAA ) repair aims to prevent premature death from AAA rupture .
Elective repair is currently recommended when AAA diameter reaches 5.5 cm ( men ) and 5.0 cm ( women ) .
Applying population -based indications may not be appropriate for individual patient decisions , as the optimal indication is likely to differ between patients based on age and comorbidities .
OBJECTIVE To develop an Aneurysm Repair Decision Aid ( ARDA ) to indicate when elective AAA repair optimises survival for individual patients and to assess the cost-effectiveness and associated uncertainty of elective repair at the aneurysm diameter recommended by the ARDA compared with current practice . | OBJECTIVE To assess the efficacy of endovascular aneurysm repair ( EVAR ) against st and ard alternative management in patients with large abdominal aortic aneurysm ( AAA ) . DESIGN Two national , multicentre r and omised trials - EVAR trials 1 and 2 . SETTING Patients were recruited from 38 out of 41 eligible UK hospitals . PARTICIPANTS Men and women aged at least 60 years , with an AAA measuring at least 5.5 cm on a computerised tomography scan that was regarded as anatomically suitable for EVAR , were assessed for fitness for open repair . Patients considered fit were r and omised to EVAR or open repair in EVAR trial 1 and patients considered unfit were r and omised to EVAR or no intervention in EVAR trial 2 . INTERVENTIONS EVAR , open repair or no intervention . MAIN OUTCOME MEASURES The primary outcome was mortality ( operative , all-cause and AAA related ) . Patients were flagged at the UK Office for National Statistics with central ly coded death certificates assessed by an Endpoints Committee . Power calculations based upon mortality indicated that 900 and 280 patients were required for EVAR trials 1 and 2 , respectively . Secondary outcomes were graft-related complications and re interventions , adverse events , renal function , health-related quality of life and costs . Cost-effectiveness analyses were performed for both trials . RESULTS Recruitment occurred between 1 September 1999 and 31 August 2004 , with targets exceeded in both trials : 1252 r and omised into EVAR trial 1 ( 626 to EVAR ) and 404 r and omised into EVAR trial 2 ( 197 to EVAR ) . Follow-up closed in December 2009 with very little loss to follow-up ( 1 % ) . In EVAR trial 1 , 30-day operative mortalities were 1.8 % and 4.3 % in the EVAR and open-repair groups , respectively : adjusted odds ratio 0.39 [ 95 % confidence interval ( CI ) 0.18 to 0.87 ] , p = 0.02 . During a total of 6904 person-years of follow-up , 524 deaths occurred ( 76 AAA related ) . Overall , there was no significant difference between the groups in terms of all-cause mortality : adjusted hazard ratio ( HR ) 1.03 ( 95 % CI 0.86 to 1.23 ) , p = 0.72 . The EVAR group did demonstrate an early advantage in terms of AAA-related mortality , which was sustained for the first few years , but lost by the end of the study , primarily due to fatal endograft ruptures : adjusted HR 0.92 ( 95 % CI 0.57 to 1.49 ) , p = 0.73 . The EVAR procedure was more expensive than open repair ( mean difference £ 1177 ) and not found to be cost-effective , but the model was sensitive to alternative assumptions . In EVAR trial 2 , during a total of 1413 person-years of follow-up , a total of 305 deaths occurred ( 78 AAA related ) . The 30-day operative mortality was 7.3 % in the EVAR group . However , this group later demonstrated a significant advantage in terms of AAA-related mortality , but this became apparent only after 4 years : overall adjusted HR 0.53 ( 95 % CI 0.32 to 0.89 ) , p = 0.02 . Sadly , this advantage did not result in any benefit in terms of all-cause mortality : adjusted HR 0.99 ( 95 % CI 0.78 to 1.27 ) , p = 0.97 . Overall , EVAR was more expensive than no intervention ( mean difference £ 10,222 ) and not found to be cost-effective . CONCLUSIONS EVAR offers a clear operative mortality benefit over open repair in patients fit for both procedures , but this early benefit is not translated into a long-term survival advantage . Among patients unfit for open repair , EVAR is associated with a significant long-term reduction in AAA-related mortality but this does not appear to influence all-cause mortality . TRIAL REGISTRATION Current Controlled Trials IS RCT N 55703451 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 16 , No. 9 . See the HTA programme website for further project information BACKGROUND The Positive Impact of EndoVascular Options for Treating Aneurysms Early ( PIVOTAL ) trial enrolled individuals with small ( 4.0- to 5.0-cm diameter ) abdominal aortic aneurysms ( AAA ) and reported no difference in rupture or aneurysm-related death for patients who received early endovascular repair ( EVAR ) vs surveillance with serial imaging studies . We evaluated re source use , medical cost , and quality of life outcomes associated with the PIVOTAL treatment strategies . METHODS This prospect i ve economic and quality of life study was conducted within a r and omized trial , with PIVOTAL sites participating in the quality of life ( n = 67 ) and economic ( n = 63 ) studies . The PIVOTAL trial r and omized 728 patients ( 366 early EVAR and 362 surveillance ) . We used information from 701 quality of life ( 351 early EVAR and 350 surveillance ) and 614 economic ( 314 early EVAR and 300 surveillance ) study participants enrolled in the PIVOTAL trial . The main outcome measures were total medical costs and the aneurysm repair rate at 48 months . RESULTS After 6 months , the rate of aneurysm repair was 96 vs 10 per 100 patients in the early EVAR and surveillance groups , respectively ( difference , 86 ; 95 % confidence interval [ CI ] , 82 - 90 ; P < .0001 ) , and total medical costs were greater in the early EVAR group ( $ 33,471 vs $ 5520 ; difference , $ 27,951 ; 95 % CI , $ 25,156-$30,746 ; P < .0001 ) . In months 7 through 48 , however , the rate of aneurysm repair was 54 per 100 patients in the surveillance group , and total medical costs were higher for patients in the surveillance vs the early EVAR group ( $ 40,592 vs $ 15,197 ; difference , $ 25,394 ; 95 % CI , $ 15,184-$35,605 ; P < .0001 ) . At 48 months ' follow-up , early EVAR patients had greater cumulative use of AAA repair ( 97 vs 64 per 100 patients ; difference , 34 ; 95 % CI , 21 - 46 ; P < .0001 ) , but there was no difference in total medical costs ( $ 48,669 vs $ 46,112 ; difference , $ 2557 ; 95 % CI , -$8043 to $ 13,156 ; P = .64 ) . After discounting at 3 % per annum , total medical costs for early EVAR and surveillance patients remained similar ( $ 47,765 vs $ 43,532 ; difference , 4232 ; 95 % CI , -$5561 to $ 14,025 ; P = .40 ) . There were no treatment-related differences in quality of life at 24 months . CONCLUSIONS A treatment strategy involving early repair of smaller AAA with EVAR is associated with no difference in total medical costs at 48 months vs surveillance with serial imaging studies . Longer follow-up is required to determine whether the late medical cost increases observed for surveillance will persist beyond 48 months OBJECTIVE This study was conducted to determine the costs and comparative cost-effectiveness of two methods of abdominal aortic aneurysm ( AAA ) repair in the Open Versus Endovascular Repair ( OVER ) Veterans Affairs ( VA ) Cooperative Study , a multicenter r and omized trial of 881 patients . METHODS The primary outcomes of this analysis were mean total health care cost per life-year and per quality -adjusted life-year ( QALY ) from r and omization to 2 years after . QALYs were calculated from EuroQol (EQ)-5D question naires collected at baseline and annually . Health care utilization data were obtained directly from patients and from national VA and Medicare data sources . VA costs were obtained from national VA sources using methods previously developed by the VA Health Economics Re source Center . Costs for non-VA care were determined from Medicare cl aims data or billing data from the patient 's health care providers . RESULTS After 2 years of follow-up , mean life-years were 1.78 in the endovascular repair group and 1.74 in the open repair group ( difference , 0.04 ; 95 % confidence interval [ CI ] , -0.03 to 0.09 ; P = .29 ) . Mean QALYs were 1.462 in the endovascular group and 1.461 in the open group ( difference adjusting for baseline EQ-5D score , 0.006 ; 95 % CI , -0.038 to 0.052 ; P = .78 ) . Mean graft costs were higher in the endovascular group ( $ 14,052 vs $ 1363 ; P < .001 ) , but length of stay was shorter ( 5.0 vs 10.5 days ; P < .001 ) , result ing in a lower mean cost of the hospital admission for the AAA procedure in the endovascular repair group of $ 37,068 vs $ 42,970 ( difference , -$5901 ; 95 % CI , -$12,135 to -$821 ; P = .04 ) . After 2 years , total health care costs remained lower in the endovascular group , but the difference was no longer significant ( -$5019 ; 95 % CI , -$16,720 to $ 4928 ; P = .35 ) . The probability of endovascular repair being less costly and more effective was 70.9 % for life-years and 51.4 % for QALYs . CONCLUSIONS In this multicenter r and omized trial , endovascular AAA repair result ed in lower cost and better survival than open repair after the initial hospitalization for repair ; but after 2 years , survival , quality of life , and costs were not significantly different between the two treatments Objective To assess the cost effectiveness of screening men aged 65 for abdominal aortic aneurysm . Design Cost effectiveness analysis based on a probabilistic , enhanced economic decision analytical model from screening to death . Population and setting Hypothetical population of men aged 65 invited ( or not invited ) for ultrasound screening in the Danish healthcare system . Data sources Published results from r and omised trials and observational epidemiological studies retrieved from electronic bibliographic data bases , and supplementary data obtained from the Danish Vascular Registry . Data synthesis A hybrid decision tree and Markov model was developed to simulate the short term and long term effects of screening for abdominal aortic aneurysm compared with no systematic screening on clinical and cost effectiveness outcomes . Probabilistic sensitivity analyses using Monte Carlo simulation were carried out . Results were presented in a cost effectiveness acceptability curve , an expected value of perfect information curve , and a curve showing the expected ( net ) number of avoided deaths from abdominal aortic aneurysm over time after the introduction of screening . The model was vali date d by calibrating base case health outcomes and expected activity levels against evidence from the recent Cochrane review of screening for abdominal aortic aneurysm . Results The estimated costs per quality adjusted life year ( QALY ) gained discounted at 3 % per year over a lifetime for costs and QALYs was £ 43 485 ( € 54 852 ; $ 71 160 ) . At a willingness to pay threshold of £ 30 000 the probability of screening for abdominal aortic aneurysm being cost effective was less than 30 % . One way sensitivity analyses showed the incremental cost effectiveness ratio varying from £ 32 640 to £ 66 001 per QALY . Conclusion Screening for abdominal aortic aneurysm does not seem to be cost effective . Further research is needed on long term quality of life outcomes and costs The Glasgow Aneurysm Score ( GAS ) , developed and published by the same authors , is a clinical prognostic scoring system that predicts mortality when operating on either intact or ruptured abdominal aortic aneurysms ( AAA ) taking into account these clinical criteria : patient 's age , shock at presentation , myocardial disease , cerebrovascular disease and renal disease . The GAS was prospect ively evaluated by study ing 320 consecutive patients with AAA who were operated on at Glasgow , Aberdeen and Inverness , Scotl and , in the period between January 1990 and May 1993 . Logistic regression analysis showed very similar results to the original analysis used in developing the score . Age , shock , myocardial disease and renal disease were highly significant . Although it was not significant , cerebrovascular disease weight was not significantly different to its value in the original analysis . The mortality correlated well with the values of the score and ranged from 0 % for scores below ' 70 GAS ' to 80 % for scores over ' 95 GAS ' . The GAS appears , therefore , to be a reliable clinical predicative tool in foretelling the outcome of operating on AAA in terms of operative in-hospital mortality CONTEXT Among patients with abdominal aortic aneurysm ( AAA ) who have high operative risk , repair is usually deferred until the AAA reaches a diameter at which rupture risk is thought to outweigh operative risk , but few data exist on rupture risk of large AAA . OBJECTIVE To determine the incidence of rupture in patients with large AAA . DESIGN AND SETTING Prospect i ve cohort study in 47 Veterans Affairs medical centers . PATIENTS Veterans ( n = 198 ) with AAA of at least 5.5 cm for whom elective AAA repair was not planned because of medical contraindication or patient refusal . Patients were enrolled between April 1995 and April 2000 and followed up through July 2000 ( mean , 1.52 years ) . MAIN OUTCOME MEASURE Incidence of AAA rupture by strata of initial and attained diameter . RESULTS Outcome ascertainment was complete for all patients . There were 112 deaths ( 57 % ) and the autopsy rate was 46 % . Forty-five patients had probable AAA rupture . The 1-year incidence of probable rupture by initial AAA diameter was 9.4 % for AAA of 5.5 to 5.9 cm , 10.2 % for AAA of 6.0 to 6.9 cm ( 19.1 % for the subgroup of 6.5 - 6.9 cm ) , and 32.5 % for AAA of 7.0 cm or more . Much of the increased risk of rupture associated with initial AAA diameters of 6.5 - 7.9 cm was related to the likelihood that the AAA diameter would reach 8.0 cm during follow-up , after which 25.7 % ruptured within 6 months . CONCLUSION The rupture rate is substantial in high-operative-risk patients with AAA of at least 5.5 cm in diameter and increases with larger diameter A representation and interpretation of the area under a receiver operating characteristic ( ROC ) curve obtained by the " rating " method , or by mathematical predictions based on patient characteristics , is presented . It is shown that in such a setting the area represents the probability that a r and omly chosen diseased subject is ( correctly ) rated or ranked with greater suspicion than a r and omly chosen non-diseased subject . Moreover , this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic . These two relationships are exploited to ( a ) provide rapid closed-form expressions for the approximate magnitude of the sampling variability , i.e. , st and ard error that one uses to accompany the area under a smoothed ROC curve , ( b ) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area , and ( c ) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques After the introduction of endovascular repair of abdominal aortic aneurysms ( AAA ) , both benefits and drawbacks of this new technique have been reported . To assess whether the new technique is an adequate substitute of conventional AAA repair , a r and omised study is due . The Dutch R and omised Endovascular Aneurysm Management ( DREAM ) trial is a r and omised multicenter trial enrolling patients eligible for elective treatment of infrarenal AAAs . In this study , the cost-effectiveness of endovascular aneurysm repair ( EAR ) is compared with that of conventional transabdominal surgery , in patients that are considered suitable for both types of treatment . The primary endpoint is combined operative mortality and morbidity . Secondary endpoints and additional assessment s include event free survival , quality of life , length of hospital stay and costs . It is expected that the DREAM-trial will lead to a safe and controlled introduction of a new technology . Also , the medical community will obtain valid scientific evidence of the merits of endovascular AAA repair . Finally , policy makers will be provided with accurate cost-effectiveness data for the Dutch healthcare system . The aim of the present paper is to describe the background , methods and design of the DREAM-trial OBJECTIVES To develop and vali date an " in house " risk model for predicting perioperative mortality following elective AAA repair and to compare this with other models . DESIGN Multivariate logistics regression analysis was used to identify risk factors for perioperative-day mortality from one tertiary institution 's prospect ively maintained data base . MATERIAL S AND METHODS Consecutive elective open ( 564 ) and endovascular ( 589 ) AAA repairs ( 2000 - 2010 ) were split r and omly into development ( 810 ) and validation ( 343 ) data sets . The result ant model was compared to Glasgow Aneurysm Score ( GAS ) , Modified Customised Probability Index ( m-CPI ) , CPI , the Vascular Governance North West ( VGNW ) model and the Medicare model . RESULTS Variables associated with perioperative mortality included : increasing age ( P = 0.034 ) , myocardial infa rct within last 10 years ( P = 0.0008 ) , raised serum creatinine ( P = 0.005 ) and open surgery ( P = 0.0001 ) . The areas under the receiver operating characteristic curve ( AUC ) for predicted probability of 30-day mortality in development and validation data sets were 0.79 and 0.82 respectively . AUCs for GAS , m-CPI and CPI were poor ( 0.63 , 0.58 and 0.58 respectively ) , whilst VGNW and Medicare model were fair ( 0.73 and 0.79 respectively ) . CONCLUSIONS In this study , an " in-house " developed and vali date d risk model has the most accurate discriminative value in predicting perioperative mortality after elective AAA repair . For purpose s of comparative audit with case mix adjustments , national models such as the VGNW or Medicare models should be used OBJECTIVE To study the growth rate and factors influencing progression of small infrarenal abdominal aortic aneurysms ( AAA ) . DESIGN Observational , longitudinal , prospect i ve study . PATIENTS AND METHODS We followed patients with AAA < 5 cm in diameter in two groups . Group I ( AAA 3 - 3.9 cm , n = 246 ) underwent annual ultrasound scans . Group II ( AAA 4 - 4.9 cm , n = 106 ) underwent 6-monthly CT scans . RESULTS We included 352 patients ( 333 men and 19 women ) followed for a mean of 55.2+/-37.4 months ( 6.3 - 199.8 ) . The mean growth rate was significantly greater in group II ( 4.72+/-5.93 vs. 2.07+/-3.23 mm/year ; p<0.0001 ) . Group II had a greater percentage of patients with rapid aneurysm expansion ( > 4 mm/year ) ( 36.8 vs. 13.8 % ; p<0.0001 ) . The classical cardiovascular risk factors did not influence the AAA growth rate in group I. Chronic limb ischemia was associated with slower expansion ( < or = 4 mm/year ) ( OR 0.47 ; CI 95 % 0.22 - 0.99 ; p = 0.045 ) . Diabetic patients in group II had a significantly smaller mean AAA growth rate than non-diabetics ( 1.69+/-3.51 vs. 5.22+/-6.11 mm/year ; p = 0.032 ) . CONCLUSIONS The expansion rate of small AAA increases with the AAA size . AAA with a diameter of 3 - 3.9 cm exp and slowly , and they are very unlikely to require surgical repair in 5 years . Many 4 - 4.9 cm AAA can be expected to reach a surgical size in the first 2 years of follow-up . Chronic limb ischemia and diabetes are associated with reduced aneurysm growth rates Economic evaluation is often seen as a branch of health economics divorced from mainstream econometric techniques . Instead , it is perceived as relying on statistical methods for clinical trials . Furthermore , the statistic of interest in cost-effectiveness analysis , the incremental cost-effectiveness ratio is not amenable to regression-based methods , hence the traditional reliance on comparing aggregate measures across the arms of a clinical trial . In this paper , we explore the potential for health economists undertaking cost-effectiveness analysis to exploit the plethora of established econometric techniques through the use of the net-benefit framework - a recently suggested reformulation of the cost-effectiveness problem that avoids the reliance on cost-effectiveness ratios and their associated statistical problems . This allows the formulation of the cost-effectiveness problem within a st and ard regression type framework . We provide an example with empirical data to illustrate how a regression type framework can enhance the net-benefit method . We go on to suggest that practical advantages of the net-benefit regression approach include being able to use established econometric techniques , adjust for imperfect r and omisation , and identify important subgroups in order to estimate the marginal cost-effectiveness of an intervention Screening for abdominal aortic aneurysm ( AAA ) is commonly restricted to men . Recent studies have indicated a possible increase in deaths due to ruptured AAA in women , and a higher rate of rupture in women than in men . The present report details results from a r and omized controlled trial that assessed the effects of screening women for AAA BACKGROUND Although the initial results of endovascular repair of abdominal aortic aneurysms were promising , current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair . METHODS We conducted a multicenter , r and omized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable c and i date s for both techniques . The outcome events analyzed were operative ( 30-day ) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications . RESULTS The operative mortality rate was 4.6 percent in the open-repair group ( 8 of 174 patients ; 95 percent confidence interval , 2.0 to 8.9 percent ) and 1.2 percent in the endovascular-repair group ( 2 of 171 patients ; 95 percent confidence interval , 0.1 to 4.2 percent ) , result ing in a risk ratio of 3.9 ( 95 percent confidence interval , 0.9 to 32.9 ) . The combined rate of operative mortality and severe complications was 9.8 percent in the open-repair group ( 17 of 174 patients ; 95 percent confidence interval , 5.8 to 15.2 percent ) and 4.7 percent in the endovascular-repair group ( 8 of 171 patients ; 95 percent confidence interval , 2.0 to 9.0 percent ) , result ing in a risk ratio of 2.1 ( 95 percent confidence interval , 0.9 to 5.4 ) . CONCLUSIONS On the basis of the overall results of this trial , endovascular repair is preferable to open repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diameter . Long-term follow-up is needed to determine whether this advantage is sustained BACKGROUND Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms . The Multicentre Aneurysm Screening Study was design ed to assess whether or not such screening is beneficial . METHODS A population -based sample of men ( n=67800 ) aged 65 - 74 years was enrolled , and each individual r and omly allocated to either receive an invitation for an abdominal ultrasound scan ( invited group , n=33839 ) or not ( control group , n=33961 ) . Men in whom abdominal aortic aneurysms ( > or =3 cm in diameter ) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years . Surgery was considered on specific criteria ( diameter > or = 5.5 cm , expansion > or = 1 cm per year , symptoms ) . Mortality data were obtained from the Office of National Statistics , and an intention-to-treat analysis was based on cause of death . Quality of life was assessed with four st and ardised scales . The primary outcome measure was mortality related to abdominal aortic aneurysm . FINDINGS 27147 of 33839 ( 80 % ) men in the invited group accepted the invitation to screening , and 1333 aneurysms were detected . There were 65 aneurysm-related deaths ( absolute risk 0.19 % ) in the invited group , and 113 ( 0.33 % ) in the control group ( risk reduction 42 % , 95 % CI 22 - 58 ; p=0.0002 ) , with a 53 % reduction ( 95 % CI 30 - 64 ) in those who attended screening . 30-day mortality was 6 % ( 24 of 414 ) after elective surgery for an aneurysm , and 37 % ( 30 of 81 ) after emergency surgery . INTERPRETATION Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors prevent the expansion and rupture of aortic aneurysms in animals . We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms . METHODS We did a population -based case-control study of linked administrative data bases in Ontario , Canada . The sample included consecutive patients older than 65 ( n=15,326 ) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1 , 1992 , and April 1 , 2002 . FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm ( odds ratio [ OR ] 0.82 , 95 % CI 0.74 - 0.90 ) than those who did not receive ACE inhibitors . Adjustment for demographic characteristics , risk factors for rupture , comorbidities , contraindications to ACE inhibitors , measures of health-care use , and aneurysm screening yielded similar results ( 0.83 , 0.73 - 0.95 ) . Consistent findings were noted in subgroups at high risk of rupture , including patients older than 75 years and those with a history of hypertension . Conversely , such protective associations were not observed for beta blockers ( 1.02 , 0.89 - 1.17 ) , calcium channel blockers ( 1.01 , 0.89 - 1.14 ) , alpha blockers ( 1.15 , 0.86 - 1.54 ) , angiotensin receptor blockers ( 1.24 , 0.71 - 2.18 ) , or thiazide diuretics ( 0.91 , 0.78 - 1.07 ) . INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm , unlike other antihypertensive agents . R and omised trials of ACE inhibitors for prevention of aortic rupture might be warranted CONTEXT Limited data are available to assess whether endovascular repair of abdominal aortic aneurysm ( AAA ) improves short-term outcomes compared with traditional open repair . OBJECTIVE To compare postoperative outcomes up to 2 years after endovascular or open repair of AAA in a planned interim report of a 9-year trial . DESIGN , SETTING , AND PATIENTS A r and omized , multicenter clinical trial of 881 veterans ( aged > or = 49 years ) from 42 Veterans Affairs Medical Centers with eligible AAA who were c and i date s for both elective endovascular repair and open repair of AAA . The trial is ongoing and this report describes the period between October 15 , 2002 , and October 15 , 2008 . INTERVENTION Elective endovascular ( n = 444 ) or open ( n = 437 ) repair of AAA . MAIN OUTCOME MEASURES Procedure failure , secondary therapeutic procedures , length of stay , quality of life , erectile dysfunction , major morbidity , and mortality . RESULTS Mean follow-up was 1.8 years . Perioperative mortality ( 30 days or inpatient ) was lower for endovascular repair ( 0.5 % vs 3.0 % ; P = .004 ) , but there was no significant difference in mortality at 2 years ( 7.0 % vs 9.8 % , P = .13 ) . Patients in the endovascular repair group had reduced median procedure time ( 2.9 vs 3.7 hours ) , blood loss ( 200 vs 1000 mL ) , transfusion requirement ( 0 vs 1.0 units ) , duration of mechanical ventilation ( 3.6 vs 5.0 hours ) , hospital stay ( 3 vs 7 days ) , and intensive care unit stay ( 1 vs 4 days ) , but required substantial exposure to fluoroscopy and contrast . There were no differences between the 2 groups in major morbidity , procedure failure , secondary therapeutic procedures , aneurysm-related hospitalizations , health-related quality of life , or erectile function . CONCLUSIONS In this report of short-term outcomes after elective AAA repair , perioperative mortality was low for both procedures and lower for endovascular than open repair . The early advantage of endovascular repair was not offset by increased morbidity or mortality in the first 2 years after repair . Longer-term outcome data are needed to fully assess the relative merits of the 2 procedures . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00094575 OBJECTIVES This study evaluated the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity ( POSSUM ) , Portsmouth ( P ) POSSUM and Vascular ( V ) POSSUM . The primary aim was to assess the validity of these scoring systems in a population of patients undergoing elective and emergency open AAA repair . The secondary intention was in the event that these equations did not fit all patients with an aneurysm ; a new model would be developed and tested using logistic regression from the local data ( Cambridge POSSUM ) . METHODS POSSUM data items were collected prospect ively in a group of 452 patients undergoing elective and emergency open AAA repair over an eight-year period . The operative mortality rates were compared with those predicted by POSSUM , P-POSSUM , V-POSSUM and Cambridge POSSUM . RESULTS All models except V-POSSUM ( physiology only ) showed significant lack of fit when predicting mortality after open AAA surgery . It was found that the locally generated single unified model ( Cambridge POSSUM ) could successfully describe both elective and ruptured AAA mortality with good discrimination ( chi(2)=9.24 , 7 d.f . , p=0.236 , c-index=0.880 ) . CONCLUSIONS POSSUM , V-POSSUM and P-POSSUM may not be robust tools for comparing mortality between population s undergoing elective and emergency open AAA repair as once thought . The development and successful validation of Cambridge POSSUM provides a unified model to describe both elective and emergency AAAs together and should be vali date d in other geographical setting The prevalence of abdominal aortic aneurysm ( AAA ) in a community‐based sample of men and women aged 65–79 years was correlated with known risk factors . In addition , the effect of high blood pressure and the use of antihypertensive medication on growth of AAAs were studied Aortic aneurysm is the 10th leading cause of death in older men [ 1 ] , but fundamental issues about the cause and epidemiology of this condition remain unresolved . A fourfold variation in the prevalence of abdominal aortic aneurysm ( AAA ) has been seen among participants in screening programs [ 2 ] , and the traditional view that AAA is a manifestation of atherosclerosis has been challenged by recent studies that suggest a role for specific genetic factors [ 3 ] . Most information on the epidemiology of AAA has come from screening studies [ 4 - 10 ] . However , the studies that have reported on potential risk factors have screened fewer than 5500 patients each , result ing in too few cases for multivariable analysis . Two nested casecontrol studies have reported multiple risk factor analyses for aortic aneurysms [ 11 , 12 ] , but these studies were also relatively small ( one contained 41 and one contained 165 aneurysms ) , did not attempt to identify all cases of AAA in their study population s , did not consider such important factors as family history of AAA , and disagreed about the significance of such factors as height and serum cholesterol levels . To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups , we collected and analyzed self-reported information from a large cohort of veterans who participated in a multicenter ultrasonographic screening program . Methods Participants The Aneurysm Detection and Management ( ADAM ) study is an ongoing r and omized clinical trial comparing two strategies for the management of AAA ( immediate surgery and surgery reserved for aneurysms that enlarge to 5.5 cm , enlarge rapidly , or cause symptoms ) in patients 50 to 79 years of age with asymptomatic AAAs 4.0 to 5.4 cm in diameter [ 13 ] . Ultrasonography screening clinics were established at the 15 participating Department of Veterans Affairs medical centers to support recruitment into the trial . Active patients at these centers ( that is , patients treated during the current or previous fiscal year and those who had future appointments ) who met the age criteria for the study were invited by mail to attend the clinic . Throughout the screening period , the letters were mailed in batches according to patient social security number using the continuously up date d administrative patient data at each participating center . A second mailing that was done at some centers excluded persons who had previously been seen in the screening clinic . Active patients at the participating centers were also accepted for screening on a walk-in basis ; patients 50 to 79 years of age were included in the analysis because they were members of the target population and eventually would have been invited to participate . Inadvertent repeated screenings were identified by patient social security number , and results of second screenings were excluded . Patients who reported previously having been told that they had an AAA were also excluded . We include data from patients who were screened from the beginning of the program in October 1992 through March 1995 . The study was approved by the human rights committee at the Veterans Affairs Cooperative Studies Program coordinating center and by the institutional review boards at the 15 participating centers . Assessment of Associated Factors Before ultrasonographic examination , all patients completed a brief question naire that asked about demographic information and possible risk factors for AAA . Patients were asked whether they had ever been told by a physician that they had the condition in question ( for example , high blood pressure ) . The question naire was developed for the study , tested at the participating centers , and revised accordingly before the study began . The reliability of the data from the self-reported question naire was assessed by comparing this data with data collected in the subset of screened patients who had an AAA and who were later included in the clinical trial . These data were recorded by a study nurse after discussion with the patient and review of the patient 's medical records . Ascertainment of Abdominal Aortic Aneurysm The abdominal aorta was measured above and below the renal arteries using a 3.5-MHz real-time sector scanner . The ultrasonographers were instructed to 1 ) scan the aorta in the anteroposterior and lateral planes and 2 ) report the maximum external diameter at the widest point of any dilatation for the suprarenal and infrarenal segments . The ultrasonographers met twice during the study period to review techniques and compare measurement distributions . Patients found to have an AAA or another suspected abnormality were referred for evaluation , and discrepancies between the results of subsequent testing and the results of the initial screening were reported back to the study ultrasonographer . Screening appointments for patients whose examinations were inadequate because of insufficient fasting were rescheduled . An infrarenal aortic diameter of 4.0 cm or larger is generally agreed to constitute AAA , but no method for defining a smaller AAA has gained wide acceptance [ 14 ] . Most investigators have used unadjusted aortic diameter ( with such cutoff points as 3.0 cm , which is known to be associated with risk for rupture [ 15 ] ) but this practice may exaggerate the prevalence of AAA in larger people . To avoid this problem , use of a ratio of infrarenal aortic diameter to suprarenal aortic diameter of 1.5 or greater has been proposed [ 14 ] . However , this method labels some small aortas as having an AAA and fails to account for aneurysmal dilatation of the suprarenal aorta . The latter problem has , in turn , been addressed by a proposal to define AAA as an aortic diameter more than 1.5 times the diameter that would be expected on the basis of age , sex , body size , and other factors . However , values for the expected diameter have not been well defined [ 14 ] . Therefore , we considered several definitions of AAA , including an infrarenal aortic diameter of at least 3.0 cm , a diameter of at least 4.0 cm , and a ratio of infrarenal to suprarenal aortic diameter of 1.5 or greater . Statistical Analysis Analyses to determine the association between the items on the question naire and the presence of AAA were done using univariable and multivariable logistic regression . Because the purpose of the analysis was descriptive , the multivariable models included all variables that were considered in the question naire . Composite variables were formed from several questions that were used to identify coronary artery disease ; hypertension ; hypercholesterolemia ; and , in a separate analysis , any atherosclerosis . Responses of do n't know were treated as responses of no for specific diseases under the assumption that if a person had a disease , he or she would be aware of it . This assumption was not made for hypercholesterolemia or hypertension , which are often asymptomatic ; responses of do n't know for these conditions were considered to be missing . Because of the result ing large number of missing responses for hypercholesterolemia , an indicator variable was included for this item to prevent deletion of these patients from the logistic models ( as was otherwise done for missing responses ) [ 16 ] . Extreme values for height ( < 152 cm and > 198 cm ) , weight ( < 45 kg and > 182 kg ) , waist circumference ( < 56 cm and > 152 cm ) , and cholesterol levels ( < 2.59 mmol/L and > 12.93 mmol/L ) and smoking history incompatible with age were also excluded . To compare the many cases of smaller , borderline AAA with cases of larger , definite AAA , separate regression models were developed 1 ) for comparing patients who had AAAs of 3.0 to 3.9 cm with those who had infrarenal aortic diameters less than 3.0 cm and 2 ) for comparing those who had AAAs of 4.0 cm or larger with those who had infrarenal aortic diameters less than 3.0 cm . A third model was developed for comparing patients whose ratio of infrarenal to suprarenal aortic diameter was 1.5 or greater with those whose ratio was less than 1.5 . Comparison of question naire data with data collected for the clinical trial was made for categorical variables by using percent-pair agreement and the statistic and for continuous variables by using the mean difference ( question naire value minus clinical trial value ) and limits of agreement ( the range within which 95 % of the differences would be expected to occur , calculated as the mean difference 1.96 times the SD of the differences [ 17 ] ) . Results During the study period , 320 000 letters were mailed ; 5.3 % of these were returned because of an invalid address or death . Of the remaining letters , 30 % ( 91 000 letters ) were returned by persons willing to be screened . A total of 73 943 persons who were 50 to 79 years of age and did not have a history of AAA were screened ; 492 were excluded because the aorta could not be visualized . The remaining 73 451 patients constitute the study group , of whom 3.5 % were walk-ins . As Table 1 shows , the study group consisted primarily of men who had a history of smoking ( 97.2 % were male ; 75.5 % had a history of smoking ) . This closely reflects the population of U.S. veterans ( 96 % are male ; 74 % have a history of smoking [ 18 ] ) ; however , the study group also included 2078 women and 17 981 persons who had never smoked . Table 1 . Characteristics of 73 451 U.S. Veterans 50 to 79 Years of Age Screened for Abdominal Aortic Aneurysm * Abdominal aortic aneurysm , defined as an infrarenal aortic diameter of 3.0 cm or more , was detected in 3366 patients ( 4.6 % ) ; the infrarenal aortic diameter was at least 4.0 cm in 1031 patients ( 1.4 % ) . The frequencies of larger AAAs were as follows : Three hundred sixty-eight ( 0.50 % ) patients had an AAA of 5.0 cm or larger , 224 ( 0.30 % ) patients had an AAA of 5.5 cm or larger , 137 ( 0.19 % ) patients had an AAA of 6.0 cm or larger , 48 ( 0.07 % ) patients had an AAA of 7.0 cm or larger , and 22 ( 0.03 % ) patients had an AAA of 8.0 cm or larger . It can BACKGROUND Early elective surgery may prevent rupture of abdominal aortic aneurysms , but mortality is 5 - 6 % . The risk of rupture seems to be low for aneurysms smaller than 5 cm . We investigated whether prophylactic open surgery decreased long-term mortality risks for small aneurysms . METHODS We r and omly assigned 1090 patients aged 60 - 76 years , with symptomless abdominal aortic aneurysms 4.0 - 5.5 cm in diameter to undergo early elective open surgery ( n=563 ) or ultrasonographic surveillance ( n=527 ) . Patients were followed up for a mean of 4.6 years . If the diameter of aneurysms in the surveillance group exceeded 5.5 cm , surgical repair was recommended . The primary endpoint was death . Mortality analyses were done by intention to treat . FINDINGS The two groups had similar cardiovascular risk factors at baseline . 93 % of patients adhered to the assigned treatment . 309 patients died during follow-up . The overall hazard ratio for all-cause mortality in the early-surgery group compared with the surveillance group was 0.94 ( 95 % CI 0.75 - 1.17 , p=0.56 ) . The 30-day operative mortality in the early-surgery group was 5.8 % , which led to a survival disadvantage for these patients early in the trial . Mortality did not differ significantly between groups at 2 years , 4 years , or 6 years . Age , sex , or initial aneurysm size did not modify the overall hazard ratio . INTERPRETATION Ultrasonographic surveillance for small abdominal aortic aneurysms is safe , and early surgery does not provide a long-term survival advantage . Our results do not support a policy of open surgical repair for abdominal aortic aneurysms of 4.0 - 5.5 cm in diameter OBJECTIVES To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm ( AAA ) in men . DESIGN A trial of ultrasound screening for AAA in a population -based r and om sample of men aged 65 - 83 years , and a cross-sectional case-control comparison of men in the same sample . PARTICIPANTS 12,203 men who had an ultrasound examination of their abdominal aorta , and completed a question naire covering demographic , behavioural and medical factors . MAIN OUTCOME MEASURES Prevalence of AAA , and independent associations of AAA with demographic , medical and lifestyle factors . RESULTS Invitations to screening produced a corrected response of 70.5 % . The prevalence of AAAs ( > 30 mm ) rose from 4.8 % in men aged 65 - 69 years to 10.8 % in those aged 80 - 83 years . The overall prevalence of large ( > 50 mm ) aneurysms was 0.69 % . In a multivariate logistic model Mediterranean-born men had a 40 % lower risk of AAA ( > 30 mm ) compared with men born in Australia ( odds ratio [ OR ] , 0.6 ; 95 % CI , 0.4 - 0.8 ) , while ex-smokers had a significantly increased risk of AAA ( OR , 2.3 ; 95 % CI , 1.9 - 2.8 ) , and current smokers had even higher risks . AAA was significantly associated with established coronary and peripheral arterial disease and a waist : hip ratio greater than 0.9 ; men who regularly undertook vigorous exercise had a lower risk ( OR , 0.8 ; 95 % CI , 0.7 - 1.0 ) . CONCLUSION Ultrasound screening for AAA is acceptable to men in the likely target population . AAA shares some but not all of the risk factors for occlusive vascular disease , but the scope for primary prevention of AAA in later life is limited BACKGROUND Endovascular aneurysm repair ( EVAR ) is a new technology to treat patients with abdominal aortic aneurysm ( AAA ) when the anatomy is suitable . Uncertainty exists about how endovascular repair compares with conventional open surgery . EVAR trial 1 was instigated to compare these treatments in patients judged fit for open AAA repair . METHODS Between 1999 and 2003 , 1082 elective ( non-emergency ) patients were r and omised to receive either EVAR ( n=543 ) or open AAA repair ( n=539 ) . Patients aged at least 60 years with aneurysms of diameter 5.5 cm or more , who were fit enough for open surgical repair ( anaesthetically and medically well enough for the procedure ) , were recruited for the study at 41 British hospitals proficient in the EVAR technique . The primary outcome measure is all-cause mortality and these results will be released in 2005 . The primary analysis presented here is operative mortality by intention to treat and a secondary analysis was done in per- protocol patients . FINDINGS Patients ( 983 men , 99 women ) had a mean age of 74 years ( SD 6 ) and mean AAA diameter of 6.5 cm ( SD 1 ) . 1047 ( 97 % ) patients underwent AAA repair and 1008 ( 93 % ) received their allocated treatment . 30-day mortality in the EVAR group was 1.7 % ( 9/531 ) versus 4.7 % ( 24/516 ) in the open repair group ( odds ratio 0.35 [ 95 % CI 0.16 - 0.77 ] , p=0.009 ) . By per- protocol analysis , 30-day mortality for EVAR was 1.6 % ( 8/512 ) versus 4.6 % ( 23/496 ) for open repair ( 0.33 [ 0.15 - 0.74 ] , p=0.007 ) . Secondary interventions were more common in patients allocated EVAR ( 9.8 % vs 5.8 % , p=0.02 ) . INTERPRETATION In patients with large AAAs , treatment by EVAR reduced the 30-day operative mortality by two-thirds compared with open repair . Any change in clinical practice should await durability and longer term results OBJECTIVE The aim was to model vascular surgical outcome in a national study using POSSUM scoring . METHODS One hundred and twenty-one British and Irish surgeons completed data question naires on patients undergoing arterial surgery under their care ( mean 12 patients , range 1 - 49 ) in May/June 1998 . A total of 1480 completed data records were available for logistic regression analysis using P-POSSUM methodology . Information collected included all POSSUM data items plus other factors thought to have a significant bearing on patient outcome : " extra items " . The main outcome measures were death and major postoperative complications . The data were checked and inconsistent records were excluded . The remaining 1313 were divided into two sets for analysis . The first " training " set was used to obtain logistic regression models that were applied prospect ively to the second " test " data set . RESULTS using POSSUM data items alone , it was possible to predict both mortality and morbidity after vascular reconstruction using P-POSSUM analysis . The addition of the " extra items " found significant in regression analysis did not significantly improve the accuracy of prediction . It was possible to predict both mortality and morbidity derived from the preoperative physiology components of the POSSUM data items alone . CONCLUSION this study has shown that P-POSSUM methodology can be used to predict outcome after arterial surgery across a range of surgeons in different hospitals and could form the basis of a national outcome audit . It was also possible to obtain accurate models for both mortality and major morbidity from the POSSUM physiology scores alone OBJECTIVE Recently generated r and omized screening trial data have provided good evidence in favour of routine screening for abdominal aortic aneurysm ( AAA ) to reduce AAA-related deaths in men aged 65 years and older . We developed an economic model that assessed the incremental cost-utility of AAA screening to help decision makers judge the relevance of a national screening program in Canada . METHODS We constructed a 14 health state Markov model comparing 2 cohorts of 65-year-old men , where the first cohort was invited to attend screening for AAA using ultrasonography ( US ) and the second cohort followed the current practice of opportunistic detection . Lifetime outcomes included the life-years gained , AAA rupture avoided , AAA-related mortality , quality -adjusted life years ( QALYs ) and costs . Transition probabilities were derived from a systematic review of the literature , and a probabilistic sensitivity analysis was carried out to examine the effect of joint uncertainty in the variables of our analysis . The perspective adopted was that of the health care provider . RESULTS Invitations to attend screening produced an undiscounted gain in life expectancy of 0.049 years and a gain in discounted QALY of 0.019 for an estimated incremental lifetime cost of CAN$118 . The estimated incremental cost-utility ratio was CAN$6194 per QALY gained ( 95 % confidence interval [ CI ] 1892 - 10 837 ) . The numbers needed to invite to attend screening , and the numbers needed to screen to prevent 1 AAA-related death were 187 ( 95 % CI 130 - 292 ) and 137 ( 95 % CI 85 - 213 ) , respectively . The acceptability curve showed a greater than 95 % probability of the program 's being cost-effective , and the model was robust to changes in the values of key parameters within plausible ranges . CONCLUSION Our results support the economic viability of a national screening program for men reaching 65 years of age in Canada . More clinical studies are needed to define the role of screening in subgroups at high risk , especially in the female population P= mean arterial pressure ( MAP ) , R= radius of the vessel , and W= wall thickness of the vessel . The wall tension was approximated with the more readily accessible patient parameters of AAA diameter , MAP , height , and weight . This approximation was termed the body mass index ( BMI ) –pressure approximation for tension ( BPAT ) , which is AAA diameter/ BMI × MAP . Data were analyzed using one-sided t-tests , chi-squared tests , and a regression analysis for the relationship between aortic wall tension and the BPAT . AAA wall tension is a significant predictor of pending rupture . BPAT used to approximate the actual tension in the AAA wall is a more sensitive predictor of rupture than aneurysm diameter alone . A prospect i ve study has been initiated to vali date these conclusions BACKGROUND Two r and omized trials have shown similar mid-term outcomes for survival and quality of life after endovascular and conventional open repair of abdominal aortic aneurysms ( AAA ) . With reduced hospital and intensive care stay , endovascular repair has been hypothesized to be more efficient than open repair . The Dutch R and omized Endovascular Aneurysm Management ( DREAM ) trial was undertaken to assess the balance of costs and effects of endovascular vs open aneurysm repair . METHODS We conducted a multicenter , r and omized trial comparing endovascular repair with open repair in 351 patients with an AAA and studied costs , cost-effectiveness , and clinical outcome 1 year after surgery . In addition to clinical outcome , costs and quality of life were recorded up to 1 year in 170 patients in the endovascular repair group and in 170 in the open repair group . Incremental cost-effectiveness ratios were estimated for cost per life-year , event-free life-year , and quality adjusted life-year ( QALY ) gained . Uncertainty regarding these outcomes was assessed using bootstrapping . RESULTS Patients in the endovascular repair group experienced 0.72 QALY vs 0.73 in the open repair group ( absolute difference , 0.01 ; 95 % confidence interval [ CI ] , -0.038 to 0.058 ) . Endovascular repair was associated with additional euro 4293 direct costs ( euro 18,179 vs euro 13.886 ; 95 % CI , euro 2,770 to euro 5,830 ) . Most of the bootstrap estimates indicated that endovascular repair result ed in slightly longer overall and event-free survival associated with respective incremental cost-effectiveness ratios of euro76,100 and euro 171,500 per year gained . Open repair appeared the dominant strategy in costs per QALY . CONCLUSION Presently , routine use of endovascular repair in patients also eligible for open repair does not result in a QALY gain at 1 year postoperatively , provides only a marginal overall survival benefit , and is associated with a substantial , if not prohibitive , increase in costs BACKGROUND We previously reported the prevalence and associations of abdominal aortic aneurysm ( AAA ) in 73451 veterans aged 50 to 79 years who underwent ultrasound screening . OBJECTIVE To underst and the prevalence of and principal positive and negative risk factors for AAA , and to assess reproducibility of our previous findings . METHODS In the new cohort of veterans undergoing screening , 52 745 subjects aged 50 to 79 without history of AAA underwent successful ultrasound screening for AAA , after completing a question naire on demographics and potential risk factors . RESULTS We detected AAA of 4.0 cm or larger in 613 participants ( 1.2 % ; compared with 1.4 % in the earlier cohort ) . The direction and magnitude of the important associations reported in the first cohort were confirmed . Respective odds ratios for the major associations with AAA for the second and for the combined cohorts were as follows : 1.81 and 1.71 for age ( per 7 years ) , 0.12 and 0 . 18 for female sex , 0.59 and 0.53 for black race , 1.94 and 1.94 for family history of AAA , 4.45 and 5.07 for smoking , 0.50 and 0.52 for diabetes , and 1.60 and 1.66 for atherosclerotic diseases . The excess prevalence associated with smoking accounted for 75 % of all AAAs of 4.0 cm or larger in the total population of 126 196 . Associations for AAA of 3.0 to 3.9 cm were similar but tended to be somewhat weaker . CONCLUSIONS Our findings confirm our previous cohort findings . Age , smoking , family history of AAA , and atherosclerotic diseases remained the principal positive associations with AAA , and female sex , diabetes , and black race remained the principal negative associations Background : The EQ-5D is a widely used generic health-related quality of life instrument that has been used to describe population health and health outcomes in clinical trials and health economic evaluations . Aims : To generate Danish population norms for the EQ-5D index score , stratified by age and gender . Methods : The EQ-5D data from three population health surveys were pooled , thus providing EQ-5D profile data for 15,700 individuals aged 20 - 79 years . The Danish TTO scoring algorithm was used to weight each respondent 's profile data to derive a single index score . Mean values were computed by gender and 10-year age groups , and educational groups . Results : In a r and om sample from the general Danish population , the mean EQ-5D index score ranged between 0.93 for 20—29 year-olds and 0.83 for 70—79 year-olds . Men had a significantly higher score than women in all age groups . Longer education was associated with higher EQ-5D index score in most age groups . Conclusions : The calculated mean values for the EQ-5D index score may be used as reference values for comparative purpose s in future Danish population health and evaluative studies BACKGROUND Cardiopulmonary exercise ( CPX ) testing measures how efficiently subjects meet increased metabolic dem and . This study aim ed to determine whether preoperative CPX testing predicted postoperative survival following elective abdominal aortic aneurysm ( AAA ) repair . METHODS Some 130 patients had CPX testing before elective open AAA repair . Additional preoperative , operative and postoperative variables were recorded prospect ively . Median follow-up was 35 months . The correlation of variables with survival was assessed by single and multiple regression analyses . RESULTS CPX testing identified 30 of 130 patients who had been unfit before surgery . Two years after surgery the Kaplan-Meier survival estimate was 55 per cent for the 30 unfit patients , compared with 97 per cent for the 100 fit patients . The absolute difference in survival between these two groups at 2 years was 42 ( 95 per cent confidence interval 18 to 65 ) per cent ( P < 0.001 ) . CONCLUSION Preoperative CPX testing , combined with simple co-morbidity scoring , identified patients unlikely to survive in the mid-term , even after successful AAA repair OBJECTIVE Open infrarenal abdominal aortic aneurysm ( oAAA ) repair is associated with significant morbidity and mortality . Although there has been a shift toward endovascular repair , many patients continue to undergo an open repair due to anatomic considerations . Tools currently existing for estimation of periprocedural risk in patients undergoing open aortic surgery have certain limitations . The objective of this study was to develop a risk index to estimate the risk of 30-day perioperative mortality after elective oAAA repair . METHODS Patients who underwent elective oAAA repair ( n = 2845 ) were identified from the American College of Surgeons ' 2007 to 2009 National Surgical Quality Improvement Program ( NSQIP ) , a prospect i ve data base maintained at > 250 centers . Univariable and multivariable analyses were performed to evaluate risk factors associated with 30-day mortality after oAAA repair and a risk index was developed . RESULTS The 30-day mortality after oAAA repair was 3.3 % . Multivariable analysis identified six preoperative predictors of mortality , and a risk index was created by assigning weighted points to each predictor using the β-coefficients from the regression analysis . The predictors included dyspnea ( at rest : 8 points ; on moderate exertion : 2 points ; none : 0 points ) , history of peripheral arterial disease requiring revascularization or amputation ( 3 points ) , age > 65 years ( 3 points ) , preoperative creatinine > 1.5 mg/dL ( 2 points ) , female gender ( 2 points ) , and platelets < 150,000/mm(3 ) or > 350,000/mm(3 ) ( 2 points ) . Patients were classified as low ( < 7 % ) , intermediate ( 7%-15 % ) , and high ( > 15 % ) risk for 30-day mortality based on a total point score of < 8 , 8 to 11 , and > 11 , respectively . There were 2508 patients ( 88.2 % ) patients in the low-risk category , 278 ( 9.8 % ) in the intermediate-risk category , and 59 ( 2.1 % ) in the high-risk category . CONCLUSIONS This risk index has excellent predictive ability for mortality after oAAA repair and awaits validation in subsequent studies . It is anticipated to aid patients and surgeons in informed patient consent , preoperative risk assessment , and optimization BACKGROUND & OBJECTIVES The aim of this study was to apply three simple risk - scoring systems to prospect ively collected data on all elective open Abdominal Aortic Aneurysm ( AAA ) operations in the Cambridge Academic Vascular Unit over a 6 - year period ( January 1998 to January 2004 ) , to compare their predictive values and to evaluate their validity with respect to prediction of mortality and post-operative complications . METHODS 204 patients underwent elective open infra-renal AAA repair . Data were prospect ively collected and risk assessment scores were calculated for mortality and morbidity according to the Glasgow Aneurysm Score ( GAS ) , VBHOM ( Vascular Biochemistry and Haematology Outcome Models ) and Estimation of Physiologic Ability and Surgical Stress ( E-PASS ) . RESULTS The mortality rate was 6.3 % ( 13/204 ) and 59 % ( 121/204 ) experienced a post-operative complication ( 30-day outcome ) . For GAS , VBHOM and E-PASS the receiver operating characteristics ( ROC ) curve analysis for prediction of in-hospital mortality showed area under the curve ( AUC ) of 0.84 ( 95 % confidence interval [ CI ] , 0.76 to 0.92 ; p<0.0001 ) , 0.82 ( 95 % CI , 0.68 to 0.95 ; p=0.0001 ) and 0.92 ( 95 % CI , 0.87 to 0.97 ; p<0.0001 ) respectively . There were also significant correlations between post-operative complications and length of hospital stay and each of the three scores , but the correlation was substantially higher in the case of E-PASS . CONCLUSIONS All three scoring systems accurately predicted the risk of mortality and morbidity in patients undergoing elective open AAA repair . Among these , E-PASS seemed to be the most accurate predictor in this patient population OBJECTIVE The aim of this study was to determine if a single preoperative B-type natriuretic peptide ( BNP ) level correlated with perioperative cardiac events , cardiac death , and all-cause mortality in elective open abdominal aortic aneurysm ( AAA ) repair in the short term , intermediate term , and long term . METHODS A prospect i ve , 2-year multicenter observational cohort study in the three vascular units in Glasgow was performed . All patients who were admitted for elective open AAA repair were recruited . Preoperative BNP levels were performed and batch analyzed at the end of the study . Postoperative screening for cardiac events ( nonfatal myocardial infa rct ion and cardiac death ) was performed at 2 , 5 , and 30 days . Follow-up for all-cause mortality was sustained to a minimum of 3 years , where possible . RESULTS A total of 106 of 111 patients were recruited . Median BNP concentrations were higher in the 16 patients ( 15 % ) with immediate postoperative cardiac events ( P = .001 ) and the five with cardiac death ( P = .043 ) . Area under the receiver-operating characteristic ( AUC ) curve analysis indicated BNP concentrations of 99.5 pg/mL best predicted cardiac events ( AUC , 0.927 ) , and 448 pg/mL predicted cardiac death ( AUC , 0.963 ) . BNP also predicted all-cause mortality in the short-term ( P = .028 ) , intermediate-term ( P < .001 ) , and long-term ( P < .001 ) postoperative periods . CONCLUSIONS Preoperative serum BNP concentration predicted postoperative cardiac events , cardiac death , and all-cause mortality in patients undergoing elective open AAA repair on short-term , intermediate-term , and long-term follow-up on an individual basis with greater accuracy than currently available risk prediction tools OBJECTIVE The risks of myocardial infa rct ion ( MI ) and stroke after abdominal aortic aneurysm ( AAA ) resection are not known . Prophylaxis with aspirin and statins is not generally recommended , although patients with AAAs have an increased prevalence of cardiovascular atherosclerosis . We report the incidences of MI , stroke , and death in an unselected national cohort of patients operated on for AAAs , with the general population as the control group . METHODS In a matched cohort study , 11,094 Danish patients who underwent acute or elective open AAA repair from January 1986 through June 2009 were compared with four r and omly chosen age- and sex-matched individuals ( controls ) from the general population ( n = 44,364 ) . Data were collected retrospectively from the Danish Vascular Registry ( Karbase ) , the National Population Registry , and the National Inpatient Registry . The groups were analyzed for the incidences of MI , stroke , and death , with up to 20 years of follow-up . RESULTS AAA patients had an annual MI incidence of 2.5 % ( hazard ratio , 2.1 ; 95 % confidence interval [ CI ] , 1.9 - 2.2 ) compared with the general population . The annual incidence of stroke was 2.9 % ( hazard ratio , 1.8 ; 95 % CI , 1.6 - 1.9 ) , and there was a 2.4-fold ( 95 % CI , 2.3 - 2.4 ) increase in the hazard of all-cause mortality compared with the general population . CONCLUSION AAA patients of both sexes have a high risk of atherosclerotic events ( MI , stroke ) and death , so lifelong prophylaxis must be considered from our epidemiologic data . R and omized trials investigating the potential benefit of aspirin and statin therapy in AAA patients are needed A group of 88 patients with abdominal aortic dilatation found in four ulrasonographic screening studies was followed prospect ively by repeated ultrasonography . The initial aortic diameter ranged between 18 and 70 mm . In 19 patients ( 22 per cent ) the aortic diameter exceeded 39 mm . The mean(s.e.m . ) annual expansion rate of dilatations < 40 mm in diameter was 0.8(1.2 ) mm ; among those ⩽ 40 mm it was 3.3(1.2 ) mm . The expansion rate increased with increasing initial diameter . Thirty‐eight patients died ; the overall mortality rate in the group was high in comparison with an age‐ and sex‐matched population . One patient died after elective aneurysm surgery but none died from a ruptured aneurysm . In conclusion , in about 80 per cent of dilatations found in screening studies the aortic diameter was < 40 mm , with a low risk of rupture . One annual rescanning of an aneurysm < 35 mm in diameter is sufficient ; a high overall mortality rate must be expected From family medical practice s 15775 men and women aged 65‐80 years were identified and r and omized into two groups : one group was invited for ultrasonographic screening for abdominal aortic aneurysm ( AAA ) , and the other acted as age‐ and sex‐matched controls . Of the 7887 invited for screening 5394 ( 68·4 per cent ) accepted . AAA was detected in 218 ( 4·0 per cent overall and 7·6 per cent of men ) . Aortic surgery was offered to the screened group if certain criteria were met and no patient died from rupture who was fit for operation and accepted elective treatment . The incidence of rupture was reduced by 55 per cent in men in the group invited for screening , compared with controls . The incidence of rupture in women was low in both groups BACKGROUND Excessive cytokine production has been implicated in the development of organ failure . Polymorphic sites in cytokine genes have been shown to affect levels of production in vitro and may influence cytokine production in vivo . The aims of this study were to determine if cytokines or their genetic polymorphisms were related to outcome after abdominal aortic aneurysm ( AAA ) repair . METHODS A prospect i ve study of 135 patients undergoing open AAA repair . Plasma levels of TNF-alpha , IL-1beta , IL-6 and IL-10 were measured 24 h post-operatively and genotypes for the TNF-alpha -308 , IL-1beta+3953 , IL-6 -174 , IL-10 -1082 and IL-10 -592 polymorphisms were determined for each patient . RESULTS After elective AAA high levels of IL-10 were associated with both prolonged critical care ( P<0.001 ) and hospital stay ( P=0.001 ) . The presence of a G allele at the IL-6 -174 locus was associated with a higher incidence of organ failure ( P=0.04 ) and an A allele at TNF-alpha -308 with prolonged critical care stay ( P=0.03 ) . After ruptured AAA the development of multi-organ failure was associated with high levels of IL-6 ( P=0.01 ) and TNF-alpha ( P=0.04 ) . High TNF-alpha levels were also associated with mortality ( P=0.01 ) . CONCLUSION Post-operative cytokine levels are related to outcome after AAA repair . Cytokine gene polymorphisms may provide a method for determining which patients are at high risk of complications BACKGROUND Several studies , including three r and omized controlled trials ( RCTs ) , have shown that endovascular repair ( EVAR ) of abdominal aortic aneurysms ( AAA ) offered better early results than open surgical repair ( OSR ) but a similar medium-term to long-term mortality and a higher incidence of re interventions . Thus , the role of EVAR , most notably in low-risk patients , remains debated . METHODS The ACE ( Anevrysme de l'aorte abdominale : Chirurgie versus Endoprothese ) trial compared mortality and major adverse events after EVAR and OSR in patients with AAA anatomically suitable for EVAR and at low-risk or intermediate-risk for open surgery . A total of 316 patients with > 5 cm aneurysms were r and omized in institutions with proven expertise for both treatments : 299 patients were available for analysis , and 149 were assigned to OSR and 150 to EVAR . Patients were monitored for 5 years after treatment . Statistical analysis was by intention to treat . RESULTS With a median follow-up of 3 years ( range , 0 - 4.8 years ) , there was no difference in the cumulative survival free of death or major events rates between OSR and EVAR : 95.9 % ± 1.6 % vs 93.2 % ± 2.1 % at 1 year and 85.1 % ± 4.5 % vs 82.4 % ± 3.7 % at 3 years , respectively ( P = .09 ) . In-hospital mortality ( 0.6 % vs 1.3 % ; P = 1.0 ) , survival , and the percentage of minor complications were not statistically different . In the EVAR group , however , the crude percentage of reintervention was higher ( 2.4 % vs 16 % , P < .0001 ) , with a trend toward a higher aneurysm-related mortality ( 0.7 % vs 4 % ; P = .12 ) . CONCLUSIONS In patients with low to intermediate risk factors , open repair of AAA is as safe as EVAR and remains a more durable option |
10,996 | 19,691,713 | CONCLUSIONS New school-based programs are needed to address current issues in tobacco control . | BACKGROUND Cigarette use remains the leading preventable cause of death in the United States .
Although school is an ideal setting for antismoking interventions , school-based programs have not been successful in the long term .
The purpose of this study was to explore characteristics of programs deemed to be successful short-term Research -Tested Intervention Programs ( RTIPs ) by the National Cancer Institute ( NCI ) . | BACKGROUND No long-term impact has yet been observed with the use of the social-influences approach to school-based smoking prevention for youth . However , whether this lack of impact is due to method ologic problems with the studies or to the failure of the interventions is unclear . The Hutchinson Smoking Prevention Project ( HSPP ) , conducted from September 1984 through August 1999 , aim ed to attain the most rigorous r and omized trial possible to determine the long-term impact of a theory-based , social-influences , grade 3 - 12 intervention on smoking prevalence among youth . METHODS Forty Washington school districts were r and omly assigned to the intervention or to the control condition . Study participants were children enrolled in two consecutive 3rd grade s in the 40 districts ( n = 8388 ) ; they were followed to 2 years after high school . The trial achieved high implementation fidelity and 94 % follow-up . Data were analyzed with the use of group-permutation methods , and all statistical tests were two-sided . RESULTS No significant difference in prevalence of daily smoking was found between students in the control and experimental districts , either at grade 12 ( difference [ Delta ] = 0.2 % , 95 % confidence interval [ CI ] = -4.6 % to 4.4 % , and P = .91 for girls ; Delta = 0.3 % , 95 % CI = -5.0 % to 5.5 % , and P = .89 for boys ) or at 2 years after high school ( Delta = -1.4 % , 95 % CI = -5.0 % to 1.6 % , and P = .38 for girls ; Delta = 2.6 % , 95 % CI = -2.5 % to 7.7 % , and P = .30 for boys ) . Moreover , no intervention impact was observed for other smoking outcomes , such as extent of current smoking or cumulative amount smoked , or in subgroups that differ in a priori specified variables , such as family risk for smoking . CONCLUSION The rigor of the HSPP trial suggests high credence for the intervention impact results . Consistent with previous trials , there is no evidence from this trial that a school-based social-influences approach is effective in the long-term deterrence of smoking among youth BACKGROUND Interventions design ed to prevent tobacco and alcohol use targeting high-risk adolescents are limited . In addition , few studies have attempted to improve parent-child communication skills as a way of improving and maintaining healthy youth decision-making . METHODS A total of 660 Hispanic migrant families participated in a r and omized pre-post control group study that was utilized to determine the impact of the intervention on parent-child communication . Both treatment and attention-control groups of youth were exposed to an eight-session culturally sensitive program presented by bilingual/bicultural college students . Parents jointly attended three of the eight sessions and participated in helping their child complete homework assignments supporting the content of each session . The content of the treatment intervention included ( 1 ) information about tobacco and alcohol effects , ( 2 ) social skills training ( i.e. , refusal skills ) , and ( 3 ) the specific development of parent-child communication skills to support healthy youth decisions . RESULTS Significant intervention by household size interactions for both parent and youth perceptions of communication were found indicating that the treatment was effective in increasing communication in families with fewer children . Based on the effect size and the previously established relationship between communication and susceptibility to tobacco and alcohol use , it was determined that the intervention effect could be translated into a future 5 to 10 % decrease in susceptibility for these smaller families . CONCLUSIONS A culturally sensitive family-based intervention for migrant Hispanic youth was found to be effective in increasing perceived parent-child communication in families with fewer children . It is expected that increases in this important protective factor will lead to later observed decreases in tobacco and alcohol use Background Although waterpipe tobacco smoking seems to be increasing on U.S. university campuses , these data have come from convenience sample s. Purpose We aim ed to determine the prevalence of and associations with waterpipe tobacco smoking among a r and om sample of students . Methods We surveyed a r and om sample of graduate and undergraduate students at a large , urban university . We used multivariate modeling to determine independent associations between belief-related predictors and waterpipe tobacco smoking . Results Of the 647 respondents , waterpipe smoking was reported in 40.5 % , over the past year in 30.6 % , and over the past 30 days in 9.5 % . Over half of the sample ( 52.1 % ) perceived that tobacco smoking from a waterpipe was less addictive than cigarette smoking . In fully adjusted multivariate models , 1-year waterpipe smoking was associated with low perceived harm ( OR = 2.54 , 95 % CI = 1.68 , 3.83 ) , low perceived addictiveness ( OR = 4.64 , 95 % CI = 3.03 , 7.10 ) , perception of high social acceptability ( OR = 20.00 , 95 % CI = 6.03 , 66.30 ) , and high perception of popularity ( OR = 4.72 , 95 % CI = 2.85 , 7.82 ) . Conclusions In this sample , lifetime waterpipe use was as common as lifetime cigarette use . Perception of harm , perception of addictiveness , social acceptability , and popularity were all strongly related to waterpipe smoking Sc and inavian moist snuff ( snus ) is cl aim ed to be a safer alternative to smoking . We aim ed to quantify cancer incidence among male snus users and to shed light on the net health outcome by study ing their overall mortality . A cohort , comprised of 9,976 men who participated in a population -based survey , was compiled in 1973 - 74 . Follow-up until January 31 , 2002 , was accomplished through record-linkages with nation-wide and essentially complete registers of demographics , cancer and causes of deaths . Adjusted relative risks among exposed relative to unexposed men were estimated using Cox proportional hazards regression . The cohort members contributed more than 220,000 person-years at risk for cancer . A statistically significant increase in the incidence of the combined category of oral and pharyngeal cancer among daily users of snus ( incidence rate ratio 3.1 , 95 % confidence interval 1.5 - 6.6 ) was found . Overall mortality was also slightly increased ( hazard ratio 1.10 , 95 % confidence interval 1.01 - 1.21 ) . Although the combined previous literature on snus and oral cancer weigh toward no association , this population -based prospect i ve study provided suggestive evidence of snus-related risks that can not be lightly ignored OBJECTIVES This study investigated the efficacy of a social-influences tobacco prevention program conducted with adolescents living in a high tobacco production area . METHODS Students in 10 experimental schools completed the tobacco prevention program and a booster intervention . Control students received health education as usual . RESULTS After 2 years of treatment , smoking rates in the treatment group ( vs the control group ) were lower for 30-day , 7-day , and 24-hour smoking . The intervention had more of an impact on those who were involved in raising tobacco than it did on those not involved in raising tobacco . CONCLUSIONS Although modest , effects were achieved with minimal intervention time in a high-risk group , indicating that social-influences prevention programs may be effective in such groups BACKGROUND This article discusses the development , implementation , and preliminary testing of an intervention to reduce cancer risks through tobacco use prevention and dietary modification among Native American youth in the Northeastern United States . METHODS The intervention outcome study includes a research design and outcome measurement instruments . In collaboration with Native American communities , reservations , and organizations in the Northeastern United States , implementation of the design quantifies the separate and combined effects of a tobacco use prevention and a dietary modification intervention . RESULTS Native American youths in the tobacco prevention intervention and in the combined tobacco and dietary intervention increased their knowledge of tobacco facts and their awareness of the motives of tobacco advertising , and showed higher ratings for an ability to resist peer pressure and to refuse offers of tobacco use between pretest and posttest . Youths in the combined intervention were significantly less apt to report smoking of any kind . Youths in the tobacco use prevention-only condition reported significantly less smoking than their counterparts in the dietary modification-only condition and control condition on 4 of 8 measurement items . As for dietary variables , pretest to posttest measurement scores showed that , after receiving the curriculum , youths in the dietary modification intervention and in the combined intervention improved their knowledge of the health implication s of consuming dietary fat , fiber , fruits , and vegetables . Youths in the dietary modification and combined intervention also improved their scores of knowledge related to cancer risk-reducing nutritional practice s , cultural dietary habits , and healthy food choices available for Native American cultures . Youths in the dietary modification-only condition report significantly increasing their consumption of complex carbohydrates and significantly decreasing their fat intake between pretest and posttest occasions . CONCLUSIONS Data from this longitudinal study suggest the value of the FACETS curriculum for helping Native American youth reduce their risks for cancer associated with tobacco use and dietary preference and consumption patterns . In particular , results indicate the enhanced effects of the combined tobacco use prevention and dietary modification intervention for preventing tobacco use and for improving youths ' knowledge and attitudes with regard to tobacco use and diet . Further , the study demonstrates the value of collaborating with Native American organizations to design a cancer risk-reducing curriculum and to implement tests of that curriculum OBJECTIVES Previous research has suggested that early smoking initiation predicts longer duration of smoking , heavier daily consumption , and increased chances of nicotine dependence . This report set out to estimate the relationship between smoking cessation and age of initiation , as well as nicotine dependence , sex , race , and education . METHODS A sample of 1007 young adults was r and omly selected from a large health maintenance organization in southeast Michigan . Hazard ratios of quitting associated with age at smoking initiation were estimated among 414 persons who smoked daily for 1 month or more . RESULTS With potential confounders controlled for , the likelihood of cessation was significantly higher in smokers who initiated smoking after age 13 . The hazard ratio for quitting associated with smoking initiation at ages 14 to 16 was 1.6 and with initiation at or after age 17 was 2.0 , compared with initiation at or before 13 years of age . Factors that decreased the likelihood of cessation were nicotine dependence and low education . CONCLUSIONS Public policy to discourage early smoking , if it succeeds in delaying the initiation of smoking , might contribute to the reduction of smoking-related mortality and morbidity by increasing the potential for quitting BACKGROUND This paper examines whether the Massachusetts Tobacco Control Program is affecting the rates of smoking and smokeless tobacco use among Massachusetts ' youth . METHODS School survey data from the Massachusetts Prevalence Study were analyzed to estimate differences between 1993 and 1996 rates of youth cigarette and smokeless tobacco use , attitudes toward smoking , and awareness of cigarette ads and promotions of antismoking messages . RESULTS Lifetime and Current Smoking rates declined significantly among middle school males , contrasting with stable national trends . Among girls in this age group , Lifetime and Current Smoking did not change significantly . Hispanic middle school students exhibited a significant decline in Lifetime Use . There were no significant changes in Lifetime or Current Smoking rates among high school students . Lifetime use of smokeless tobacco declined among middle school students while Current Use declined among both middle and high school students . Students reported declines in awareness of cigarette ads or promotions and increases in awareness of antismoking messages . CONCLUSIONS These results provide evidence for cautious optimism regarding the impact of tobacco control , but indicate that these efforts should begin earlier and that additional research is needed to underst and and address the problems of tobacco use by girls This paper describes the curricula contents , and presents data to evaluate the implementation , process and immediate post-test knowledge of Project Towards No Tobacco Use ( Project TNT ) . Four different school-based tobacco use prevention curricula were developed to counteract the effects of three types of tobacco use acquisition variables typically addressed within a comprehensive social influences program : ( 1 ) peer approval for using tobacco ( normative social influence ) , ( 2 ) incorrect social informational provided about tobacco use ( information social influence ) and ( 3 ) lack of knowledge or misperceptions about physical consequences result ing from tobacco use . Three curricula were design ed to counteract the effects of single acquisition variables , whereas a fourth curriculum was design ed to counteract the effects of combined social and physical consequences-related influences . These curricula were delivered to seventh grade students by trained project health educators to maximize implementation . ' Program ' schools , those schools that received one of these curricula , were compared to ' control ' schools that provided a systematic health education delivered by school personnel . A total of five conditions were contrasted through use of a r and omized experiment involving 48 southern California junior high schools . This paper documents high levels of implementation in all program conditions . Also , favorable process ratings were obtained across the four program conditions , using multiple measures and sources of ratings ( students , health educators and classroom teachers who observed curricula delivery ) . Finally , knowledge item sets completed by the students demonstrated discriminant validity across all five conditions . Because the program conditions were discriminable , yet were quite similar in implementation and process ratings , planned future study of behavioral outcomes can be interpreted as relatively uncontaminated by delivery or credibility confounds |
10,997 | 27,378,557 | Neither the renal ultrasound nor the DMSA scan is accurate enough to detect VUR ( of all grade s ) .
Although a child with a negative DMSA test has an < 1 % probability of having high- grade VUR , performing a screening DMSA will result in a large number of children falsely labelled as being at risk for high- grade VUR . | BACKGROUND There is considerable interest in detecting vesicoureteral reflux ( VUR ) because its presence , especially when severe , has been linked to an increased risk of urinary tract infections and renal scarring .
Voiding cystourethrography ( VCUG ) , also known as micturating cystourethrography , is the gold st and ard for the diagnosis of VUR , and the grading of its severity .
Because VCUG requires bladder catheterisation and exposes children to radiation , there has been a growing interest in other screening strategies that could identify at-risk children without the risks and discomfort associated with VCUG .
OBJECTIVES The objective of this review is to evaluate the accuracy of two alternative imaging tests - the dimercaptosuccinic acid renal scan ( DMSA ) and renal-bladder ultrasound ( RBUS ) - in diagnosing VUR and high- grade VUR ( Grade III-V VUR ) . | OBJECTIVE : To evaluate the yield , economic , and radiation costs of 5 diagnostic algorithms compared with a protocol where all tests are performed ( ultrasonography scan , cystography , and late technetium99dimercaptosuccinic acid scan ) in children after the first febrile urinary tract infections . METHODS : A total of 304 children , 2 to 36 months of age , who completed the diagnostic follow-up ( ultrasonography , cystourethrography , and acute and late technetium99dimercaptosuccinic acid scans ) of a r and omized controlled trial ( Italian Renal Infection Study 1 ) were eligible . The guidelines applied to this cohort in a retrospective simulation were : Melbourne Royal Children ’s Hospital , National Institute of Clinical Excellence ( NICE ) , top down approach , American Academy of Pediatrics ( AAP ) , and Italian Society of Pediatric Nephrology . Primary outcomes were the yield of abnormal tests for each diagnostic protocol ; secondary outcomes were the economic and radiation costs . RESULTS : Vesicoureteral reflux ( VUR ) was identified in 66 ( 22 % ) children and a parenchymal scarring was identified in 45 ( 15 % ) . For detection of VUR ( 47/66 ) and scarring ( 45/45 ) , the top down approach showed the highest sensitivity ( 76 % and 100 % , respectively ) but also the highest economic and radiation costs ( € 52 268 . 624 mSv ) . NICE ( 19/66 ) and AAP ( 18/66 ) had the highest specificities for VUR ( 90 % ) and the Italian Society of Pediatric Nephrology had the highest specificity ( 20/45 ) for scars ( 86 % ) . NICE would have been the least costly ( € 26 838 ) and AAP would have result ed in the least radiation exposure ( 42 mSv ) . CONCLUSIONS : There is no ideal diagnostic protocol following a first febrile urinary tract infection . An aggressive protocol has a high sensitivity for detecting VUR and scarring but carries high financial and radiation costs with question able benefit Abstract . We attempted to verify in a group of 101 children with first urinary tract infection whether it was possible to identify groups of patients with different risks of developing renal scarring by taking into account both the extent of kidney involvement documented in the acute phase of infection using a dimercaptosuccinic acid ( DMSA ) scan , and the presence or absence of vesicoureteral reflux ( VUR ) . The frequency of persistent lesions in kidneys with mild-moderate lesions ( less than 50 % of kidney involvement ) in the presence of VUR or in non-refluxing kidneys was similar ( P=0.1447 ) , while the frequency of persistent lesions in kidneys with severe lesions in the presence of VUR was significantly higher than the frequency of persistent lesions in non-refluxing kidneys ( P=0.0089 ) . The extent of kidney involvement and the presence of VUR make possible the identification of different categories of risk of scarring : in the ” low risk group ” ( normal kidney with/without VUR ) the risk of scarring is 0 % ; in the ” intermediate risk group ” ( mild lesions with/without VUR ; extensive lesions without VUR ) the risk of scarring is between 14 % and 38 % , while in the ” high risk group ” ( extensive lesions with VUR ) the risk of scarring is 88 % . Quantifying the risk of scarring could help in planning the treatment or in modifying the later strategy BACKGROUND Guidelines from the American Academy of Pediatrics recommend obtaining a voiding cystourethrogram and a renal ultrasonogram for young children after a first urinary tract infection ; renal scanning with technetium-99m-labeled dimercaptosuccinic acid has also been endorsed by other authorities . We investigated whether imaging studies altered management or improved outcomes in young children with a first febrile urinary tract infection . METHODS In a prospect i ve trial involving 309 children ( 1 to 24 months old ) , an ultrasonogram and an initial renal scan were obtained within 72 hours after diagnosis , contrast voiding cystourethrography was performed one month later , and renal scanning was repeated six months later . RESULTS The ultrasonographic results were normal in 88 percent of the children ( 272 of 309 ) ; the identified abnormalities did not modify management . Acute pyelonephritis was diagnosed in 61 percent of the children ( 190 of 309 ) . Thirty-nine percent of the children who underwent cystourethrography ( 117 of 302 ) had vesicoureteral reflux ; 96 percent of these children ( 112 of 117 ) had grade I , II , or III vesicoureteral reflux . Repeated scans were obtained for 89 percent of the children ( 275 of 309 ) ; renal scarring was noted in 9.5 percent of these children ( 26 of 275 ) . CONCLUSIONS An ultrasonogram performed at the time of acute illness is of limited value . A voiding cystourethrogram for the identification of reflux is useful only if antimicrobial prophylaxis is effective in reducing reinfections and renal scarring . Renal scans obtained at presentation identify children with acute pyelonephritis , and scans obtained six months later identify those with renal scarring . The routine performance of urinalysis , urine culture , or both during subsequent febrile illnesses in all children with a previous febrile urinary tract infection will probably obviate the need to obtain either early or late scans BACKGROUND Antibiotics are widely administered to children with the intention of preventing urinary tract infection , but adequately powered , placebo-controlled trials regarding efficacy are lacking . This study from four Australian centers examined whether low-dose , continuous oral antibiotic therapy prevents urinary tract infection in predisposed children . METHODS We r and omly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension ( as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight ) or placebo for 12 months . The primary outcome was microbiologically confirmed symptomatic urinary tract infection . Intention-to-treat analyses were performed with the use of time-to-event data . RESULTS From December 1998 to March 2007 , a total of 576 children ( of 780 planned ) underwent r and omization . The median age at entry was 14 months ; 64 % of the patients were girls , 42 % had known vesicoureteral reflux ( at least grade III in 53 % of these patients ) , and 71 % were enrolled after the first diagnosis of urinary tract infection . During the study , urinary tract infection developed in 36 of 288 patients ( 13 % ) in the group receiving trimethoprim-sulfamethoxazole ( antibiotic group ) and in 55 of 288 patients ( 19 % ) in the placebo group ( hazard ratio in the antibiotic group , 0.61 ; 95 % confidence interval , 0.40 to 0.93 ; P = 0.02 by the log-rank test ) . In the antibiotic group , the reduction in the absolute risk of urinary tract infection ( 6 percentage points ) appeared to be consistent across all subgroups of patients ( P > or = 0.20 for all interactions ) . CONCLUSIONS Long-term , low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children . The treatment effect appeared to be consistent but modest across subgroups . ( Australian New Zeal and Clinical Trials Registry number , ACTRN12608000470392 . A prospect i ve blind study comparing the findings of ultrasonography , intravenous pyelography , and voiding cystourethrography was conducted on 81 patients to examine the place of ultrasonography in the initial radiologic evaluation of children with urinary tract infection . The patients ' mean age was 4.8 years ; 15 were male . Forty-eight were in patients ( mean age , 3.2 years ) and 33 were out patients ( mean age 7.2 years ) . In 29 patients ( 35.8 % ) abnormality of the urinary system was detected by one or more of the three imaging procedures ; 21 were in patients and eight were out patients . The most frequent finding was vesicoureteral reflux , occurring in 62.1 % of the pathologic cases . The findings at ultrasonography correlated well with those of intravenous pyelography in 73 of the 81 studies ( 90.1 % ) , but they failed to demonstrate double collecting systems and several of the minor changes . However , ultrasonography in combination with cystourethrography identified all patients who had abnormal urinary systems , except for two children with negligible findings . Moreover , ultrasonography and cystourethrography together identified all 11 patients , nine of them in patients , in whom surgical treatment was indicated . It is concluded that ultrasonography can successfully replace intravenous pyelography as a screening imaging procedure for the urinary system , but because of the superiority of intravenous pyelography in the detection of some types of lesions , intravenous pyelography will be required whenever ultrasonography or cystourethrography results are abnormal . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To track the clinical evolution of febrile urinary tract infection ( UTI ) diagnosed in 0- to 3-month-old infants and characterize uropathogen frequencies , antimicrobial resistance rates , renal abnormalities , and differences in the sexes in this age group . STUDY DESIGN We observed prospect ively 46 infants identified in a cohort of 209 children with first UTI diagnosed between July 2006 and July 2008 at the age of 0 to 3 months . Renal ultrasound scanning and voiding cystourethrography examinations were performed in all infants . RESULTS Infants < 3 months old represented 21 % of all children with first UTI . Of these children , 26 % were female and 74 % were male . Escherichia coli was isolated in 88 % of cases and had a high rate of resistance to ampicillin ( 71 % ) and to trimethoprim/sulfamethoxazole ( 47 % ) ; 21 % of children had vesicoureteral reflux , which was of low- grade in 67 % of cases , with spontaneous resolution before 2 years in all cases . In infants with normal ultrasound scanning results , a low- grade vesicoureteral reflux was subsequently found in 10 % of cases . CONCLUSION Infants aged 0 to 3 months represent 21 % of children treated for febrile UTI . Boys represent 74 % of these cases . E coli is responsible for 88 % of UTIs , with a high rate of resistance to antibiotics . When ultrasound scanning examination results are normal , the risk of missing a significant renal abnormality is expected to be extremely low This prospect i ve study was done to assess the frequency of acute pyelonephritis ( APN ) in febrile children with positive urine culture as documented by Tc99 m DMSA scintigraphy ( DMSA ) and the frequency of vesicoureteric reflux ( VUR ) in these children . Secondly , to determine the frequency of APN , in febrile children with supportive evidence for UTI but with negative urine culture , as documented by DMSA and frequency of VUR in them . Thirdly to stress the utility of DMSA to diagnose APN in urine culture negative febrile children and to suggest DMSA as a clinical tool in evaluation of fever of unknown origin ( FUO ) . This study included 42 children with positive urine culture and 26 children with negative urine culture who had supportive evidence of UTI as determined by the predetermined criteria and diagnosed to have APN by DMSA . All of them had ultrasonogram ( USG ) , DMSA and voiding cystourethrogram ( VCU ) . They were followed up for a minimum period of 6 months . Out of the 42 children with positive urine culture 92.9 % had features of APN in the DMSA of whom 82.1 % had vesicoureteric relux ( VUR ) . The DMSA was abnormal in 26 children with negative urine culture , of whom 65.4 % had VUR . Ultrasound suggestive of parenchymal change was observed in 47.6 % in the culture positive group and 65.4 % in the culture negative group . In conclusion , it is suggested , that DMSA is a useful investigation for the diagnosis of APN in febrile UTI . DMSA is indicated in febrile children with negative urine culture but with supportive evidence of UTI and in FUO . An abnormal DMSA is a strong indication for work up for VUR We assessed the role of therapeutic delay time ( TDT ) in acute renal cortical scintigraphic lesion ( ASL ) and ultimate scar formation ( USF ) in children with first febrile UTI and whether it is affected by the presence of vesico-ureteral reflux ( VUR ) . 230 children , 90 girls and 140 boys with first febrile UTI were included . Radiologic ( USG , DMSA , and VCUG ) , clinical ( age , gender , peak fever , therapeutic delay time ) and laboratory ( CBC with differential count , ANC ( absolute neutrophil count ) , BUN , Creatinine , urine analysis , gram stain , culture , CRP and ESR ) variables were analysed . DMSA was performed within 5 days and after six months . VCUG was performed after acute phase of UTI . The differences in TDT according to the presence of ASL , USF and VUR were assessed . And the correlation between ASL or USF with the duration of TDT was assessed . Of 230 patients enrolled , 142 patients had refluxing UTI and 88 patients had non-refluxing UTI . TDT was the risk factor associated with ASL and USF along with presence of VUR . TDT was longer in ASL positive group compared with the ASL negative group . Also USF group showed longer TDT compared with those without USF in both refluxing UTI and non refluxing UTI . The TDT was significantly shorter in USF group with the presence of VUR . Positive linear association was noted between prevalence of ASL and USF and duration of TDT . In conclusion , the impact of UTI on formation of USF may be enhanced by the presence of VUR with shorter duration of TDT It is generally believed that infants are more susceptible to development of renal scarring after pyelonephritis than children over 5 years old . This view has led to differences in investigations and treatment according to age . The aim of this prospect i ve study was to assess the occurrence of renal parenchymal lesion in children over 5 years admitted with a first-time symptomatic urinary tract infection ( UTI ) . Between October 2000 and April 2002 , 52 children aged over 5 years who were admitted to our department with probable acute pyelonephritis ( APN ) and a positive urine culture were included in this study . All children received antibiotics for 14 days . During the acute phase of infection , scintigraphy with technetium-99 m -labeled dimercaptosuccinic acid ( DMSA ) and ultrasonography ( US ) were done . Voiding cystourethrography ( VCUG ) was performed in all children early in the course of the illness , generally within 5–7 days of hospitalization . When scintigraphy showed renal parenchymal changes , repeat scintigraphy was done after at least 3 months to assess the progression of renal abnormalities . Of the 52 children with a first-time documented pyelonephritis , cortical scintigraphy showed renal lesion in 41 children ( 78.8 % ) . US was normal in all children with normal renal scintigraphy , while it detected renal abnormalities in 16 of the 41 ( 39 % ) with abnormal scintigraphy ( p < 0.0001 ) . Topographic analysis of the 165 focal lesions showed that 42.4 % were localized to the upper poles , 17.5 % to the middle third , and 40 % to the lower poles of the kidneys . Repeat scintigraphy showed persistent lesions corresponding to those on the initial scan in nine ( 28.2 % ) of the 32 children . Renal lesions had partly regressed in 23 ( 71.8 % ) of the patients who underwent repeat scintigraphy . Vesicoureteral reflux was observed in 13.4 % of kidneys and renal parenchymal abnormalities were identified in 71.4 % and 72.2 % of renal units , respectively , with and without reflux ( p > 0.05 ) . In conclusion , our data did not confirm the conventional opinion that the risk of renal scarring after pyelonephritis is low in children over the age of 5 years . Our findings suggest that renal scintigraphy may be a more appropriate method of investigation than VCUG for evaluation of the children over 5 years with acute pyelonephritis . Additionally , the frequency of scintigraphic changes is high , and a strategy based exclusively on ultrasound findings would miss about 61 % of the abnormal renal units . We recommend that all children , irrespective of age , will benefit from further investigations that might prevent or limit the development of scarring process and renal complications OBJECTIVE : To revise the American Academy of Pediatrics practice parameter regarding the diagnosis and management of initial urinary tract infections ( UTIs ) in febrile infants and young children . METHODS : Analysis of the medical literature published since the last version of the guideline was supplemented by analysis of data provided by authors of recent publications . The strength of evidence supporting each recommendation and the strength of the recommendation were assessed and grade d. RESULTS : Diagnosis is made on the basis of the presence of both pyuria and at least 50 000 colonies per mL of a single uropathogenic organism in an appropriately collected specimen of urine . After 7 to 14 days of antimicrobial treatment , close clinical follow-up monitoring should be maintained to permit prompt diagnosis and treatment of recurrent infections . Ultrasonography of the kidneys and bladder should be performed to detect anatomic abnormalities . Data from the most recent 6 studies do not support the use of antimicrobial prophylaxis to prevent febrile recurrent UTI in infants without vesicoureteral reflux ( VUR ) or with grade I to IV VUR . Therefore , a voiding cystourethrography ( VCUG ) is not recommended routinely after the first UTI ; VCUG is indicated if renal and bladder ultrasonography reveals hydronephrosis , scarring , or other findings that would suggest either high- grade VUR or obstructive uropathy and in other atypical or complex clinical circumstances . VCUG should also be performed if there is a recurrence of a febrile UTI . The recommendations in this guideline do not indicate an exclusive course of treatment or serve as a st and ard of care ; variations may be appropriate . Recommendations about antimicrobial prophylaxis and implication s for performance of VCUG are based on currently available evidence . As with all American Academy of Pediatrics clinical guidelines , the recommendations will be review ed routinely and incorporate new evidence , such as data from the R and omized Intervention for Children With Vesicoureteral Reflux ( RIVUR ) study . CONCLUSIONS : Changes in this revision include criteria for the diagnosis of UTI and recommendations for imaging Objective The role of dimercaptosuccinic acid ( DMSA ) renal scintigraphy in the first episode of urinary tract infection ( UTI ) has been the subject of debate for many years . The aim of this study was to evaluate the relationship of voiding cystourethrography ( VCUG ) , renal ultrasonography and DMSA renal scintigraphy and to detect renal parenchymal changes by performing DMSA renal scintigraphy at 6 months after the first episode of UTI . Methods A prospect i ve study was conducted in 67 hospitalized children ( 46 boys , 21 girls ) . Mean age of the patients was 0.97 ± 1.57 years ( 0.02–7.26 years ) . All children received VCUG , renal ultrasonography and DMSA renal scintigraphy . DMSA renal scintigraphy was performed at 1 and 6 months after UTI . Results Of 67 children , 17 ( 25.4 % ) , 23 ( 34.3 % ) and 20 ( 29.9 % ) had vesicoureteral reflux ( VUR ) , abnormal renal ultrasonography and abnormal DMSA renal scintigraphy , respectively . Unilateral hydronephrosis had a significant correlation with VUR at p value 0.024 . In renal units , abnormal renal ultrasonography and hydronephrosis had significant correlations with VUR at p values 0.039 and 0.021 , respectively . In patients and renal units , hydronephrosis had no significant correlation with abnormal DMSA renal scintigraphy at 1 month after UTI . However , abnormal renal ultrasonography and VUR had significant correlations with abnormal DMSA renal scintigraphy at p values 0.022 and < 0.001 in patients and at p values 0.024 and < 0.001 in renal units , respectively . Both in patients and renal units , VUR ( Grade I – III ) had no significant correlation with abnormal DMSA renal scintigraphy . However , severe VUR ( Grade IV – V ) had significant correlations with abnormal DMSA renal scintigraphy at p values < 0.001 and < 0.001 , respectively . Seventeen patients underwent DMSA renal scintigraphy at 6 months after UTI . In addition , 15 ( 88.2 % ) developed persistent renal scarring . Conclusion Abnormal renal ultrasonography and severe VUR identify renal parenchymal changes . DMSA renal scintigraphy in the first episode of UTI should be carried out in those patients . Abnormal DMSA renal scintigraphy at 1 month after UTI has a tendency to persist OBJECTIVE To test the hypothesis that infants with dilating vesicoureteral reflux ( VUR ) have abnormal acute dimercaptosuccinic acid ( DMSA ) scintigraphy results , as was suggested by an earlier retrospective study . STUDY DESIGN We conducted a prospect i ve study of infants < 1 year old with first diagnosed symptomatic urinary tract infection at the Children 's Hospital of Göteborg , Sweden . Two hundred ninety consecutive children ( 161 boys and 129 girls ) with complete records were examined . Renal ultrasound scanning and DMSA scintigraphy were performed within a few days from diagnosis , and VCU was performed within 2 months . RESULTS VUR was found in 52 children , of which 27 had dilating VUR ( grade III-V ) . DMSA scintigraphy results were abnormal in 149 infants ( 51 % ) , 105 of 238 ( 44 % ) without VUR , 18 of 25 ( 72 % ) with VUR grade I to II , and 26 of 27 ( 96 % ) with VUR grade III to V ( P < .001 ) . CONCLUSION DMSA scintigraphy results were abnormal in all 27 infants with dilating VUR except 1 . This single false-negative finding should be compared with 140 unnecessary VCU investigations . This supports our hypothesis that DMSA scintigraphy results are abnormal when there is dilating VUR . Thus , a normal DMSA scan makes VCU unnecessary in the primary examination of infants with UTI Technetium-99 m dimercaptosuccinic acid ( DMSA ) study has been advocated as a method for the assessment of renal sequelae after acute febrile urinary tract infection ( UTI ) . However , it is not known whether DMSA scintigraphy performed during acute UTI has any prognostic value for outcome assessment . The objective of this study was to evaluate the usefulness of DMSA scintigraphy performed during UTI as a predictor of patient outcome , to identify children at risk of events [ vesico-ureteral reflux ( VUR ) or recurrent UTI ] that may lead to the development of progressive renal damage . One hundred and fifty-two children ( including 78 girls ) with a mean age of 20 months ( range 1 month to 12 years ) with first febrile UTI were evaluated by DMSA scintigraphy during acute UTI . After acute UTI , children were explored by voiding cysto-urethrography . Children who presented an abnormal DMSA study , or a normal DMSA study but VUR or recurrent UTI , underwent a DMSA control study 6 months after UTI . Children with VUR were followed up by direct radionuclide cystography . DMSA scintigraphy performed during acute UTI was normal in 112 children ( 74 % ) . In 95 of these children , follow-up DMSA scintigraphy was not performed owing to a good clinical outcome . In the remaining 17 children , follow-up scintigraphy was normal . Forty children ( 26 % ) presented abnormal DMSA study during acute UTI . Twenty-five of them presented a normal follow-up DMSA , and 15 presented cortical lesions . Children with abnormal DMSA had a higher frequency of VUR than children with normal DMSA ( 48 % vs 12 % ) . It is concluded that children with normal DMSA during acute UTI have a low risk of renal damage . Children with normal follow-up DMSA and low- grade VUR have more frequent spontaneous resolution of VUR PURPOSE We evaluated the role of ultrasound in diagnosing and treating infants with a first urinary tract infection with a focus on important structural abnormalities . MATERIAL S AND METHODS In a setting of limited prenatal ultrasound screening this population based , prospect i ve , 3-year study included 161 male and 129 female infants . Ultrasound and dimercapto-succinic acid scintigraphy were performed as initial investigations and voiding cystourethrography was conducted within 2 months . RESULTS Ultrasound revealed dilatation in 15 % of patients and increased kidney length in 28 % . Sensitivity for detecting scintigraphic abnormality was 48 % . Renal length was significantly correlated to inflammatory parameters , including scintigraphic abnormalities . Important structural abnormalities were detected in 40 cases , with 30 on ultrasound , while 10 of 27 cases of dilating reflux ( mostly grade III ) were missed . Outside the study there were 28 additional cases of structural abnormality , of which 15 were detected prenatally . CONCLUSIONS Ultrasound detected most structural abnormalities except grade III reflux . Since it is noninvasive , ultrasound has a place in the evaluation of infants with urinary tract infection , especially in the absence of prenatal ultrasound during late pregnancy . Kidney length in infants with acute infection correlated with inflammatory parameters , and the clinical importance of this finding needs to be studied further Abstract A prospect i ve study was performed on 185 children with symptomatic urinary tract infection ( UTI ) , 130F and 55 M , having a median age of 0.9 y ( range 0.1–9.8 ) at the time of UTI . The aim of the study was to find out how the 99mTechnetium‐dimercaptosuccinic acid ( DMS A ) scan should be used to investigate UTI , and to follow the development of renal changes during pyelonephritis into subsequent permanent renal damage . All children were investigated with a DMSA scan within 5 days after admission and after 3.9–53.3 ( median 9.2 ) weeks , and 159 were studied again after approximately 2 y ( range 1.5‐3.9 y ) . They all underwent micturition cystourethrography at the time of the second study . At the time of infection , the DMSA scan was abnormal in 85 % of the children , in 58 % at the first follow‐up and in 36 % at the second follow‐up . An abnormal DMSA scan performed within 20 weeks from infection became normal in 38 % of cases on the third study , while only 1/10 abnormal DMSA scans performed more than 20 weeks after infection became normal after 1.5‐3.9 y. Persistent renal changes were more common in children > 4 y of age than in children 1 y of age . Two months after the presenting infection , it was unusual to see a normal DMSA scan in a child with a VUR gr . ≥ 3 . The study suggests that DMSA changes after an index UTI may be transient for a longer period of time than has been previously considered . Therefore , in order to detect persistent changes , a DMSA scan should be performed more than 5 months after UTI The aim of this study was to determine the prevalence of renal scarring in a group of Kuwaiti Arab children with their first documented acute pyelonephritis ( APN ) . Eighty-two Kuwaiti Arab children ( 10 males and 72 females ) who had abnormal 99mTc DMSA renal scan findings of acute pyelonephritis were prospect ively studied with the same imaging modality 6 months after treatment to identify those who developed renal scarring . A micturition cystourethrogram ( MCUG ) was performed for all of the children 1 month after diagnosis . Children were divided into 3 age groups ( < 2 years , 2–5 years and above 5 years ) . The follow-up DMSA renal scans 6 months after diagnosis revealed normalization of renal changes in 56 % ( 46 patients ) , much improvement with residual renal abnormality in 6 % ( 5 patients ) , and persistent parenchymal defects in 38 % ( 31 patients ) . Vesicoureteric reflux ( VUR ) was found in 32 % of children ( 26/82 ) and the majority were between grade I and III . Thirteen of those with VUR ( 50 % ) developed renal scars on follow-up . Fifty-three percent of the scarred kidneys ( 19/36 ) were drained by non-refluxing ureters . In this study , children older than 2 years had less VUR yet were more susceptible to APN and to the development of renal scars . Girls were more prone to developing APN and renal scarring than boys . This work shows that APN is a serious cause for renal scarring in our patients , particularly if associated with other risk factors such as recurrent infections and the female sex BACKGROUND Acute pyelonephritis often leaves children with permanent renal scarring . AIMS To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days . METHODS In a prospect i ve two centre trial , 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy , were r and omly assigned to receive intravenous ceftriaxone ( 50 mg/kg once daily ) for 10 or three days , followed by oral cefixime ( 4 mg/kg twice daily ) to complete a 15 day course . After three months , scintigraphy was repeated in order to diagnose renal scars . RESULTS Renal scarring developed in 33 % of the 110 children in the 10 day intravenous group and 36 % of the 110 children in the three day group . Children older than 1 year had more renal scarring than infants ( 42 % ( 54/129 ) and 24 % ( 22/91 ) , respectively ) . After adjustment for age , sex , duration of fever before treatment , degree of inflammation , presence of vesicoureteric reflux , and the patients ' recruitment centres , there was no significant difference between the two treatments on renal scarring . During follow up , 15 children had recurrence of urinary infection with no significant difference between the two treatment groups . CONCLUSION In children with acute pyelonephritis , initial intravenous treatment for 10 days , compared with three days , does not significantly reduce the development of renal scarring Ninety-four children with febrile urinary tract infection were studied prospect ively to determine the relationship between vesicoureteral reflux , P-fimbriated Escherichia coli , and acute pyelonephritis , and to evaluate the diagnostic reliability of commonly used clinical and laboratory observations . By using renal scan with dimercaptosuccinic acid labeled with technetium 99 m as the st and ard of reference , we documented acute pyelonephritis in 62 ( 66 % ) of 94 patients . Vesicoureteral reflux was demonstrated in 29 ( 31 % ) of the total group and in only 23 ( 37 % ) of 62 patients with pyelonephritis . Of the 70 E. coli urinary isolates , 48 ( 69 % ) were P-fimbriated , including 30 ( 64 % ) of 47 isolates from patients with pyelonephritis and 18 ( 78 % ) of 23 isolates from patients with normal renal scans . The prevalence of P-fimbriated E. coli in patients with pyelonephritis and vesicoureteral reflux was 46 % , compared with 71 % in those with pyelonephritis who had no concurrent vesicoureteral reflux ( p = 0.222 ) . Multiple clinical and laboratory variables commonly used in the diagnosis of acute pyelonephritis did not adequately predict the presence or absence of parenchymal involvement . These data show the following : ( 1 ) Acute pyelonephritis in the absence of demonstrable vesicoureteral reflux is common . ( 2 ) Febrile urinary tract infections in children are commonly associated with P-fimbriated E. coli , both in the presence and absence of vesicoureteral reflux . ( 3 ) The presence of P fimbriae alone does not fully explain the pathophysiology of renal parenchymal invasion by bacteria in the absence of vesicoureteral reflux . ( 4 ) The diagnosis of acute pyelonephritis in children with febrile urinary tract infections on the basis of clinical and laboratory observations is unreliable Vesicoureteric reflux ( VUR ) is found in 1 % of all children and in 30%-50 % of those with urinary tract infection . Furthermore , VUR in childhood is the main reason for pyelonephritis , hypertension and chronic kidney disease . Recently , a variety of procedures with low radiation have been recommended for diagnosis of VUR . Therefore , in this study , voiding urosonography ( VUS ) or cystosonography was performed for evaluation of VUR and for comparing it with radio nucleotide cystography ( RNC ) . We studied 25 children admitted with initial diagnosis of VUR in our center in the year 2007 . Simultaneously , RNC and VUS were performed for all the patients . VUR was detected in eight patients with the VUS procedure and in nine children with RNC . Another patient was diagnosed only by RNC , and two other patients by only VUS . The two methods were concordant in detection and exclusion of urinary reflux in 87 % ( P : 0.000 , r : 0.728 ) . Furthermore , the diagnosis of various grade s of reflux by these two schemes were comparable ( P : 0.0000 , r : 0.724 ) . Sensitivity and specifity of VUS was determined as 87 % and 88 % , respectively , with a 94 % positive predictive value and a 77 % negative predictive value . We conclude that VUS is a highly accurate , safe and inexpensive tool for the screening , diagnosis and follow-up of VUR For the comparison of long-term outcome of the management of medical or surgical treatment of children with severe vesicoureteral reflux ( VUR ) , children aged < 11 years with non-obstructive grade III/IV reflux , previous urinary tract infection ( UTI ) and glomerular filtration rate ( GFR ) ≥70 ml/min per 1.73 m2 body surface area were recruited , and 306 were r and omly allocated to receive antimicrobial prophylaxis or ureteral reimplantation . Primary endpoints were new renal scars and renal growth . Follow up , originally planned for 5 years , was extended to 10 years for 252 children , 223 of whom had follow-up imaging . Up to 5 years , 40 new urographic scars ( medical 19 , surgical 21 ) were seen . Between 5 years and 10 years , only two further scars were observed . Renal growth and UTI recurrence rate were similar , except that medically treated patients had more febrile infections . There was no difference in somatic growth , radionuclide imaging or renal function . A GFR < 70 ml/min per 1.73 m2 was found in only one patient . Three patients developed hypertension requiring treatment . We conclude that , with close supervision and prompt treatment of recurrences , children entering the study with GFR ≥70 ml/min per 1.73 m2 progressed remarkably well under either medical or surgical management , emphasizing the importance of continued supervision and the entry level of renal function BACKGROUND Children with febrile urinary tract infection commonly have vesicoureteral reflux . Because trial results have been limited and inconsistent , the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial . METHODS In this 2-year , multisite , r and omized , placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection , we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences ( primary outcome ) . Secondary outcomes were renal scarring , treatment failure ( a composite of recurrences and scarring ) , and antimicrobial resistance . RESULTS Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo ( relative risk , 0.55 ; 95 % confidence interval [ CI ] , 0.38 to 0.78 ) . Prophylaxis reduced the risk of recurrences by 50 % ( hazard ratio , 0.50 ; 95 % CI , 0.34 to 0.74 ) and was particularly effective in children whose index infection was febrile ( hazard ratio , 0.41 ; 95 % CI , 0.26 to 0.64 ) and in those with baseline bladder and bowel dysfunction ( hazard ratio , 0.21 ; 95 % CI , 0.08 to 0.58 ) . The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups ( 11.9 % and 10.2 % , respectively ) . Among 87 children with a first recurrence caused by Escherichia coli , the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63 % in the prophylaxis group and 19 % in the placebo group . CONCLUSIONS Among children with vesicoureteral reflux after urinary tract infection , antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring . ( Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others ; RIVUR Clinical Trials.gov number , NCT00405704 . ) We design ed a prospect i ve study to evaluate the ability of dimercaptosuccinic acid cortical scintigraphy and ultrasonography to detect renal parenchymal lesions in children with pyelonephritis . One hundred eleven patients 1 week to 16 years of age ( median 5.5 months ) with a urine culture positive for pathogens were included in the study ; cortical scintigraphy and ultrasonography were repeated in 25 children after a mean follow-up of 10.5 months . Cortical scintigraphy showed renal changes in 74 children ( 67 % ) , and ultrasonography showed renal changes in 39 ( 35 % ) ( p < 0.001 ) ; results of the two examinations were discordant in 49 patients ( kappa = 0.19 ) . Children more than 1 year of age had a higher incidence of renal lesions than did younger children ( 85 % vs 66 % ; p = 0.04 ) . The presence of inflammatory signs ( erythrocyte sedimentation rate or C-reactive protein ) had an 89 % sensitivity and a 25 % specificity in identifying renal lesions . Among children with renal changes , vesicoureteric reflux was present in 39 % . At follow-up examination , 16 children ( 64 % ) had scars . Thus we found a high incidence of renal involvement in children with pyelonephritis . We found that cortical scintigraphy is more sensitive than ultrasonography in detecting renal changes , and we believe that it should be added to the initial examination of children with suspected pyelonephritis OBJECTIVE : To evaluate prospect ively whether normal scintigraphic results during urinary tract infections ( UTIs ) in neonates were predictive of the absence of dilating vesicoureteral reflux ( VUR ) ( grade ≥III ) and permanent renal damage ( PRD ) . METHODS : Term neonates with a first symptomatic , community-acquired UTI participated in the study . Urinary tract ultrasonography and technetium-99m-labeled dimercaptosuccinic acid ( 99mTc-DMSA ) scintigraphy were performed within 72 hours after diagnosis and voiding cystourethrography within 1 to 2 months . DMSA scintigraphy , to determine the development of PRD , was repeated 6 months after UTI . RESULTS : Seventy-two neonates ( 144 renal units ) were enrolled . Acute pyelonephritis was diagnosed through early DMSA scintigraphy in 19 % of renal units , VUR in 22 % , and grade ≥III VUR in 13 % . The majority ( 71 % ) of renal units with grade ≥III VUR had normal early DMSA scintigraphic results . The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade ≥III VUR were 29 % ( 95 % confidence interval : 11%–55 % ) and 82 % ( 95 % confidence interval : 74%–88 % ) , respectively . PRD was found in 7 % of renal units , all of which had abnormal early DMSA scintigraphic results . PRD was significantly more frequent among renal units with grade ≥III VUR than among nonrefluxing renal units ( P < .05 ) . CONCLUSIONS : Normal early DMSA scintigraphic results for neonates with symptomatic UTIs were helpful in ruling out later development of PRD but were not predictive of the absence of dilating VUR . To rule out dilating VUR , voiding cystourethrography may be required Background The lack of good evidence for improved outcomes in children and young infants with febrile urinary tract infection ( UTI ) after aggressive treatment for vesicoureteral reflux ( VUR ) has raised doubts regarding the need for routine voiding cystourethrography ( VCUG ) , and the appropriate imaging evaluation in these children remains controversial . Objectives This prospect i ve study aim ed to determine whether abnormalities found on acute dimercaptosuccinic acid ( DMSA ) scan and ultrasound ( US ) can help indicate the necessity of voiding cystourethrography ( VCUG ) in young infants . Methods For 3.5 years , all infants younger than 3 months presenting with first febrile UTI were prospect ively studied . All infants were hospitalized and investigated using US ( <3 days after admission ) , DMSA scan ( < 5 days after admission ) , and VCUG ( 7–10 days after antibiotic treatment ) after diagnosis . The association among findings of US , DMSA scan , and VCUG were evaluated . Results From 220 infants , there were abnormal results in 136 ( 61.8 % ) US and in 111 ( 50.5 % ) DMSA scans . By US , ten infants ( 4.5 % ) with abscess or structural abnormalities other than VUR were diagnosed . High- grade ( III – V ) VUR was present in 39 patients ( 17.7 % ) . The sensitivities for high- grade VUR of renal US alone ( 76.9 % ) or DMSA scan alone ( 82.1 % ) were not as good as that of the “ OR rule ” strategy , which had 92.3 % sensitivity and 94.3 % negative predictive value . Conclusions To screen high- grade VUR in young infants with febrile UTI , US and acute DMSA scan could be performed first . VCUG is only indicated when abnormalities are apparent on either US or DMSA scan or both PURPOSE Evaluation in children after febrile urinary tract infection involves voiding cystourethrogram , which emphasizes urinary reflux rather than renal risk . We believe that early dimercapto-succinic acid renal scan after febrile urinary tract infection predicts clinical ly significant reflux and which children should undergo voiding cystourethrogram . The criticism of this approach is that some reflux and preventable renal damage would be missed . This study vali date s the use of initial dimercapto-succinic scan and presents 5-year renal outcomes . MATERIAL S AND METHODS We prospect ively studied children with febrile urinary tract infection using initial dimercapto-succinic acid renal scan , voiding cystourethrogram and renal/bladder ultrasound . Children with anatomical or neurological genitourinary abnormality and protocol failures were excluded from analysis . Dimercapto-succinic acid scan was repeated at 6 months if initially abnormal . Followup was done every 6 months in all children for at least 5 years . RESULTS A total of 121 children fit study inclusion criteria and completed the 5-year study . Overall 88 initial dimercapto-succinic acid scans ( 73 % ) were abnormal and 78 children ( 64 % ) had urinary reflux . The OR of having clinical ly significant reflux predicted by abnormal initial scan was 35.4 . Abnormal followup scan did not predict clinical ly significant reflux . Overall subsequent urinary tract infection developed in 32 patients ( 26.5 % ) and 27 ( 85 % ) had an abnormal initial scan . No child with a normal initial scan had clinical ly significant reflux . CONCLUSIONS Dimercapto-succinic acid scan can predict clinical ly significant reflux and children at greatest renal risk . Initial dimercapto-succinic acid scan should be done in all children after febrile urinary tract infection while voiding cystourethrogram should be reserved for those with an abnormal initial dimercapto-succinic acid scan Several less harmful methods than voiding cysto-urethrography for detecting significant ureteric reflux have been proposed . The present prospect i ve study investigated whether ultrasonography was effective in identifying ureteric reflux in infants with their first febrile urinary infection . The subjects were 27 infants ( 24 boys and 3 girls ) aged from 0 to 8 months . The urinary tract was scanned when the bladder was full , and before and during induced voiding . Infants with abnormal ultrasound findings underwent voiding cysto-urethrography . The other infants were followed and those who had a recurrence of urinary infection underwent voiding cystography . Ten children underwent cysto-urethrography , with eight refluxing ureters identified in six boys . Ultrasound revealed transient dilatation of the renal pelvis on voiding in five kidneys , transient dilatation of distal ureters in 12 and hydro-ureteronephrosis in two . Each of the five kidneys with pelvic dilatation on voiding was associated with ureteric reflux grade s III or IV . Of the 17 children who did not undergo cysto-urethrography , only one had recurrence of urinary infection and was diagnosed with ureteric reflux . This girl was one of the three babies who were not scanned during voiding . More than half of the infants with febrile urinary infection were excluded from invasive examination without having recurrence of urinary infection . Thus , ultrasound scanning during voiding was effective for screening infants with their first urinary infection to detect significant ureteric reflux OBJECTIVE To compare the findings of renal ultrasonography ( RUS ) , 99mTc glucoheptonate renal scan ( GHS ) , and voiding cystourethrography ( VCUG ) in children with urinary tract infection . DESIGN Prospect i ve , masked , clinical study . SETTING Single center , multidisciplinary , in patients . PATIENTS Consecutive cases ( N = 50 ) of children aged 2 months to 15 years ( 8 boys , 42 girls ) with pyelonephritis in whom uroradiologic investigation was indicated . MEASUREMENTS AND MAIN RESULTS All patients underwent GHS , 48 had RUS , and 2 had intravenous pyelography . All but one of the patients had a VCUG . Fifteen children were found to have vesicoureteral reflux ( 6 unilaterally , 9 bilaterally ) . Of 96 kidneys evaluated by both GHS and RUS , 53 were abnormal by GHS versus 28 by RUS ( p < 0.001 ) . Findings of both GHS and US were normal in 36 kidneys and abnormal in 21 kidneys . In 32 kidneys only GHS showed abnormalities . In 7 kidneys only RUS showed abnormalities ; 5 of them had mild to moderate pelvic dilation caused by reflux , which was confirmed in all 5 by VCUG . The VCUG demonstrated reflux in another four units with normal GHS and RUS findings . All combined , GHS and VCUG detected 62 of 64 abnormal renal units ( 96.9 % ) . In the other two cases , RUS showed only focal hyperechogenicity of question able importance . CONCLUSION In the event that one elects to use GHS for the uroradiologic evaluation of children with urinary tract infection , it can be supplemented by VCUG alone , and RUS can be saved for special cases PURPOSE To directly compare various renal ultrasonography ( US ) criteria for vesicoureteral reflux ( VUR ) with voiding cystography , the reference method , for diagnostic accuracy in helping to determine an intermediate strategy of screening children who require cystography . MATERIAL S AND METHODS Institutional review board approval and parental consent were obtained for this prospect i ve hospital-based cohort study involving children with urinary tract infections ( UTIs ) . Renal length , ureteral dilatation , pelvic dilatation , and corticomedullary differentiation were analyzed and compared . One hundred seventeen patients ( median age , 0.8 year ; age range , 0.0 - 13.9 years ) were included : 46 ( 39 % ) boys ( median age , 0.3 year ; age range , 0.5 - 13.9 years ) and 71 girls ( median age , 1.2 years ; age range , 0.0 - 11.5 years ) . A two-level logistic regression model was used to analyze data , and diagnostic accuracy calculations were performed . RESULTS Thirty-two ( 27 % ) children had all- grade VUR , and eight ( 7 % ) had VUR of grade 3 or higher . Only ureteral dilatation was significantly related to all- grade VUR ( odds ratio [ OR ] , 7.5 ; 95 % confidence interval [ CI ] : 1.0 , 58.2 ; P = .05 ) , with 25 % sensitivity ( 95 % CI : 15 % , 39 % ) and 88 % specificity ( 95 % CI : 83 % , 92 % ) . Ureteral , pelvic , and urinary tract dilatations were significantly associated with VUR of grade 3 or higher , with ORs of 20.2 ( 95 % CI : 3.5 , 118.2 ; P = .001 ) , 13.7 ( 95 % CI : 4.1 , 46.0 ; P < .001 ) , and 20.0 ( 95 % CI : 4.4 , 90.1 ; P < .001 ) , respectively . The best compromise between sensitivity and specificity was achieved by using the ureteral dilatation criterion , which had 73 % sensitivity ( 95 % CI : 43 % , 90 % ) and 88 % specificity ( 95 % CI : 84 % , 92 % ) for high- grade VUR . CONCLUSION Ureteral dilatation may yield the best accuracy for the US-based diagnosis of both all- grade and high- grade VUR . This US criterion , perhaps in combination with other predictors , might find a place in an evidence -based selective strategy for limiting cystography in children with UTIs OBJECTIVE Current imaging recommendations for investigating any infantile febrile urinary tract infection ( UTI ) are ultrasound scan ( US ) , micturating cystourethrogram ( MCUG ) and dimercaptosuccinic acid ( DMSA ) scan . The aim of this retrospective cohort study was to determine the need and indications for MCUG in the investigation of a first febrile infantile UTI , as doubts have been raised over its benefit . PATIENTS AND METHODS Information on 427 infants who had undergone US , MCUG and DMSA following a first febrile UTI was prospect ively recorded . The infants were divided into two groups : A ( 354 ) with normal renal US and B ( 73 ) with abnormal US . DMSA findings were correlated with findings on MCUG . Main outcome measures were incidence of recurrent UTIs , change in management or intervention as a result of MCUG , and outcome at discharge . RESULTS Only 21/354 ( 6 % ) infants in Group A had both scarring on DMSA and vesicoureteric reflux ( VUR ) , predominantly low- grade on MCUG . In Group B ( abnormal US ) , 23/73 ( 32 % ) had scarring on DMSA and vesicoureteric reflux , predominantly high grade on MCUG . Of the infants with non-scarred kidneys , 73 % had dilating reflux . Successful conservative treatment was performed in 423 infants , and 4 infants in Group B required surgery . CONCLUSION We recommend US and DMSA in all infantile febrile UTI cases . Where US is normal , MCUG should be reserved for those cases with abnormal DMSA . Where US is abnormal , MCUG should be performed irrespective of findings on DMSA scan . A r and omized prospect i ve study is necessary to evaluate this further Background : Our objective is to provide the clinical characteristics , uropathogen frequencies , and antimicrobial resistance rates of first urinary tract infection ( UTI ) diagnosed in febrile Belgian children . The ability of noninvasive ultrasound to detect renal abnormalities and vesicoureteral reflux ( VUR ) in these patients was also assessed . Methods : We prospect ively followed ( median , 20 months ) 209 children treated for first febrile UTI . Renal ultrasound ( US ) and voiding cystourethrography examinations were performed in all patients . Results : Among these children , 63 % were females and 37 % were males , and 75 % of them had their first UTI before the age of 2 years . The most common causative agent was Escherichia coli ( 91 % of cases ) with high rate resistance to ampicillin ( 58 % ) and trimethoprim/sulfamethoxazole ( 38 % ) . Of these children , 25 % had evidence of VUR ( 15 boys and 38 girls ) . VUR was of low grade in 85 % of cases . The overall performance of renal US as a diagnostic test to detect significant uropathies excluding low- grade VUR was excellent ; the sensitivity attained 97 % and the specificity 94 % . Conclusion : Girls represent 63 % of cases with first UTI . For 91 % of UTIs , Escherichia coli is held responsible with a high rate of resistance to ampicillin and trimethoprim/sulfamethoxazole . US is an excellent screening tool that allows avoidance of unjustified voiding cystourethrography studies This study was undertaken to determine the predisposing factors for renal scarring in children with urinary tract infection . In this prospect i ve cohort study , 176 children with documented urinary tract infection were categorized into four groups : ≤1 year old , 1 - 2 years old , 2 - 7 years and 7 - 14 years old . Ultrasonography and Technetium-99 m-DMSA scan were used to detect the possible abnormalities . Infants under 12 months old presented as the most common group for renal scarring ( 27 cases , 52.9 % ) , and vesicoureteral reflux ( VUR ) was diagnosed in 29 cases ( 56.8 % ) . Fifteen ( 41.67 % ) children between the ages of one and two years had renal scar , and VUR was detected in half of the patients . In the third group , 36.3 % , and in fourth group , 41.6 % of the patients had renal scar . Also , 38.6 % in group three and 50 % in the final group had VUR . A co-incidental finding that was observed in this study was the high incidence of pseudohypoaldesteronism ( PHA ) in our patients : in 39.2 % of the children in group one , 22.2 % in group two and 4 % in group three . In group four however , none of the patients had PHA . Risk of scar formation with urinary tract infection ( UTI ) was higher in the younger age group and in those with recurrent UTIs The aim of this study was to determine the incidence of abnormal dimercaptosuccinic acid-Tc-99 m ( (99m)Tc-DMSA ) renal scintigraphy findings in children with culture proved urinary tract infection ( UTI ) with or without vesicoureteral reflux ( VUR ) . (99m)Tc-DMSA renal scintigraphy was performed in 343 children with culture documented UTI ( 247 girls and 96 boys ) aged from three months to 14 years ( middle age of 4.82 years ) . The children studied were all those su bmi tted for renal scintiscan to the Institute of Nuclear Medicine , Military Medical Academy , Bel grade during a five-year period ( 2000 - 2004 ) . Micturating cystoureterography ( MCU ) performed in all patients before (99m)Tc-DMSA scan , revealed VUR in 213 children , while in 130 children VUR was not detected by MCU . In 15 of the 213 children the grade of VUR was I , in 88 was II , in 57 was III , in 33 was IV and 20 children had grade V of VUR . Findings of (99m)Tc-DMSA renal scintigraphy were classified as : normal , equivocal and abnormal . Statistical analysis was performed using c(2)test . In all patients abnormal findings were detected in 38 % ( 131/343 ) , normal in 51 % ( 174/343 ) and equivocal findings in 11 % ( 38/343 ) . In children with UTI and VUR the incidence of abnormal findings was 53 % ( 112/213 ) , of normal 37 % ( 80/213 ) and of equivocal findings 10 % ( 21/213 ) . In children with UTI without VUR the incidence of abnormal findings was 15 % ( 19/130 ) , of normal findings 72 % ( 94/130 ) , and of equivocal findings 13 % ( 17/130 ) . The incidence of abnormal findings was significantly higher in children with UTI and VUR than in those with UTI without VUR ( P<0.001 ) . In children with VUR grade s I , II , III , IV and V abnormal findings were 33 % , 32 % , 60 % , 79 % and 95 % respectively . The incidence of abnormal findings was higher in children with VUR grade s IV and V , than in grade I and II ( P<0.001 ) . Our results suggest that (99m)Tc-DMSA renal scintigraphy in children can discriminate between grade I-II and IV-V of VUR and also that in children with UTI and VUR abnormal findings in the scintiscan were more than three times higher than in children with UTI alone A prospect i ve study examining the incidence of dimercaptosuccinic acid ( DMSA ) abnormalities in children at the time of acute urinary tract infection , the progression of these abnormalities following treatment and their correlation with the presence of vesicoureteral reflux is reported . DMSA scans performed within 72 hours of presentation in 65 previously healthy children with acute urinary tract infection were abnormal in 34 ( 52 % ) . The scan appearances of 30 of 36 ( 83 % ) initially abnormal kidneys improved or became normal on the repeat DMSA study performed at 3 to 6 months after the acute urinary tract infection . A cystogram demonstrated significant vesicoureteral reflux in 11 of 45 cases ( 24 % ) . Of these 11 cases 10 had abnormal DMSA studies and 1 had dilated upper tracts on ultrasound . Several conclusions may be drawn from our study . The incidence of DMSA abnormalities at the time of acute urinary tract infection is high but these abnormalities tend to resolve with time . An abnormal DMSA study at the time of urinary tract infection identifies most children with significant vesicoureteral reflux , and in our series a combination of ultrasound and DMSA identified all cases . This study may have major implication s for the clinical investigation of children with urinary tract infection PURPOSE We analyzed clinical data for prediction of permanent renal damage in infants with first time urinary tract infection . MATERIAL S AND METHODS This population based , prospect i ve , 3-year study included 161 male and 129 female consecutive infants with first time urinary tract infection . Ultrasonography and dimercapto-succinic acid scintigraphy were performed as acute investigations and voiding cystourethrography within 2 months . Late scintigraphy was performed after 1 year in infants with abnormality on the first dimercapto-succinic acid scan or recurrent febrile urinary tract infections . End point was renal damage on the late scan . RESULTS A total of 270 patients had end point data available , of whom 70 had renal damage and 200 did not . Final kidney status was associated with C-reactive protein , serum creatinine , temperature , leukocyturia , non-Escherichia coli bacteria , anteroposterior diameter on ultrasound and recurrent febrile urinary tract infections . In stepwise multiple regression analysis C-reactive protein , creatinine , leukocyturia , anteroposterior diameter and non-E.coli bacteria were independent predictors of permanent renal damage . C-reactive protein 70 mg/l or greater combined with anteroposterior diameter 10 mm or greater had sensitivity of 87 % and specificity of 59 % for renal damage . An algorithm for imaging of infants with first time urinary tract infection based on these results would have eliminated 126 acute dimercapto-succinic acid scans compared to our study protocol , while missing 9 patients with permanent renal damage . CONCLUSIONS C-reactive protein can be used as a predictor of permanent renal damage in infants with urinary tract infection and together with anteroposterior diameter serves as a basis for an imaging algorithm Aim : To establish the variables that correlate with uptake defects in dimercaptosuccinic acid ( DMSA ) scintigraphy performed in the acute phase of a first episode of urinary tract infection ( UTI ) . Methods : A prospect i ve observational study was conducted in a cohort of 158 consecutive children with a first episode of symptomatic UTI . The therapeutic delay time ( TDT ) was recorded . DMSA scintigraphy was performed in all children and voiding cystourethrography in 150 of them . Results : 85 % of the patients were younger than 2 y. Mean TDT was 33.5 h. The aetiological agent was Escherichia coli in 140 children . DMSA scintigraphy was normal in 81 . Vesicoureteric reflux was detected in 33 . After a multivariate logistic regression analysis the following variables were retained in the final model : TDT ≥48 h , growth of bacteria other than E. coli , percentage of polymorphonuclear cells ≥60 % and C‐reactive protein ≥30 mg−1 Objective Accurate diagnosis of pyelonephritis using clinical and laboratory parameters is often difficult , especially in children . The main aims of this prospect i ve study were to compare the value of different imaging techniques [ renal sonography , cortical scintigraphy with technetium-99 m dimercaptosuccinic acid ( 99mTc DMSA ) and computed tomography ( CT ) ] in detecting renal involvement in acute urinary tract infections and to determine the sensitivity of DMSA scans for permanent renal scars 6 months later . Material s and methods Between February 1992 and January 1993 , 55 children admitted to our pediatric unit with febrile symptomatic urinary tract infections were eligible for analysis . Ultrasonography ( US ) , DMSA scanning and micturating cystourethrography were performed in every case . Only 18 children underwent CT . A second DMSA scan was performed in 48 children a mean of 7.5 months after the first . Results US abnormalities were found in 25 children ( 45 % ) . The first DMSA scan showed a parenchymal aspect suggestive of pyelonephritis in 51 patients ( 93 % ) . Among the 18 patients studied by CT , 14 had abnormalities . Normal US findings did not rule out renal parenchymal involvement . Scintigraphy appeared to be more sensitive than CT for renal involvement . The frequency and degree of initial renal parenchymal damage seemed to correlate with vesicoureteral reflux , but the most severe initial parenchymal defects were not associated with marked clinical or laboratory manifestations . Repeat DMSA scans , performed on 45 kidneys with abnormalities at the first examination , showed resolution in 19 , improvement in 16 , persistence in 8 and deterioration in 2 . The prevalence of vesicoureteral reflux was not higher in patients with renal scarring on the second DMSA scan than in patients whose scans showed an improvement . Conclusion DMSA scans should be considered as a reference in the detection and follow-up of renal scarring associated with acute urinary tract infection as this technique is more sensitive than US and CT , the latter being unsuitable because it entails radiation exposure and sedation of patients A series of 208 patients was prospect ively assessed for reflux nephropathy by intravenous urography ( IVU ) and 99mTc-dimercaptosuccinate ( DMSA ) scintigraphy . All patients were studied at least 3 months after their most recent urinary tract infection and micturating cystourethrography ( MCU ) was performed prior to the scintigraphic studies . DMSA scintigraphy detected significantly more cortical abnormalities than did IVU . There was also a correlation between cortical abnormalities in the DMSA studies and the degree of reflux on MCU . The validity of DMSA as a cortical imaging agent is evaluated and the histological evidence for its efficacy derived from the animal model is review ed , lending weight to its establishment as the " gold st and ard " for renal cortical scarring The purpose of our prospect i ve study was to find out whether ureteric jet Doppler waveform ( UJDW ) could be a reliable predictor of vesicoureteral reflux ( VUR ) in children , compared with echo-enhanced voiding ultrasonography ( VUS ) . Echo-enhanced VUS was performed in 75 children , 57 girls and 18 boys , aged 3 years to 12 years , following the accepted indications for this procedure . During the same procedure the measurement of UJDW was also performed and was considered to be successful ( in 70 children ) when at least ten UJDWs were recorded per ureteric unit . Depending on the shape of the UJDWs , the sequences were classified into three groups : monophasic , suggestive of VUR ; complex , not suggestive of VUR ; and mixed sequence , suggestive of VUR when a certain ratio between monophasic and complex UJDWs was achieved . When all three sequences were taken into account , the overall sensitivity and specificity of this method in detecting VUR were 88.5 % and 82.3 % , respectively . These values seem high enough for this method to be considered as a good alternative to invasive micturating cystographies in screening children for VUR OBJECTIVE Defects seen on early cortical scintigrams of the renal cortex in children with urinary tract infection may represent acute inflammatory change or established scar . The purpose of this study was to determine the relationship between these defects and age , sex , the presence and grade of vesicoureteral reflux , and infective organism in a cohort of children examined after their first proved urinary tract infection . SUBJECTS AND METHODS We prospect ively examined 193 consecutive patients less than 5 years old who were seen at the ambulatory pediatric department during a 3-year period and had a first proved urinary tract infection . Children with obstructed or solitary kidneys were excluded . All patients were imaged with scintigraphy of the renal cortex and radiographic voiding cystourethrography within 15 days of diagnosis . The association of age , sex , the presence and grade of vesicoureteral reflux , and infective organism with a defect ( acute pyelonephritis or a renal scar ) seen on a cortical renal scan was studied . RESULTS The prevalence of cortical defects was greater in the kidneys of patients less than 2 years old ( 96/290 , 33 % ) than in older children ( 16/96 , 17 % ) and greater in those with vesicoureteral reflux ( 41/92 , 45 % ) than in those without it ( 71/294 , 24 % ) . Vesicoureteral reflux was absent in 63 % ( 71/112 ) of kidneys with a cortical defect . No association with sex or infective organism was established . As well as having a greater prevalence of cortical defects , 145 ( 75 % ) of the 193 urinary tract infections included in the study were in children less than 2 years old . The kidneys of these younger patients also had a greater severity and prevalence of vesicoureteral reflux ( 74/290 , 26 % ) than did those of older children ( 18/96 , 19 % ) . CONCLUSION Early cortical defects are associated with an age less than 2 years and vesicoureteral reflux . However , the association of early defects with the presence and grade of vesicoureteral reflux is confounded by the declining prevalence and severity of reflux with age . A significant proportion of cortical defects occur in the absence of vesicoureteral reflux , and the contribution of reflux to scar formation might be less than previously considered Objective : The aim of this article was to assess the usefulness of procalcitonin ( PCT ) as a marker for predicting dilating ( grade s III – V ) vesicoureteral reflux ( VUR ) in young children with a first febrile urinary tract infection . Methods : Children ⩽2 years of age with a first febrile urinary tract infection were prospect ively evaluated . Serum sample s were tested for PCT at the time of admission to a tertiary hospital . All children underwent renal ultrasonography ( US ) , 99mTc-dimercaptosuccinic acid renal scan , and voiding cystourethrography . The diagnostic characteristics of PCT test for acute pyelonephritis and dilating VUR were calculated . Results : Of 272 children analyzed ( 168 boys and 104 girls ; median age , 5 months ) , 169 ( 62.1 % ) had acute pyelonephritis . There was VUR demonstrated in 97 ( 35.7 % ) , including 70 ( 25.7 % ) with dilating VUR . The median PCT value was significantly higher in children with VUR than in those without ( P < 0.001 ) . Using a PCT cutoff value of ≥1.0 ng/mL , the sensitivity and negative predictive value for predicting dilating VUR were 94.3 % and 95.4 % , respectively , for PCT , and 97.1 % and 97.8 % , respectively , for the combined PCT and US studies , whereas the positive and negative likelihood ratios were 2.03 and 0.107 , respectively , for PCT , and 1.72 and 0.067 , respectively , for the combined studies . By multivariate analysis , high PCT values and abnormalities on US were independent predictors of dilating VUR . Conclusions : PCT is useful for diagnosing acute pyelonephritis and predicting dilating VUR in young children with a first febrile urinary tract infection . A voiding cystourethrography is indicated only in children with high PCT values ( ≥1.0 ng/mL ) and /or abnormalities found on a US BACKGROUND The general belief about the relation between risk of renal sequelae after pyelonephritis and age is that infants are at highest risk and children older than 5 years at lower risk . This assumption has led to differences in treatment based on age . The aim of this prospect i ve study was to investigate the occurrence of renal lesions in children aged 0 - 16 years . METHODS Between May , 1994 , and January , 1996 , all children aged 0 - 16 years who were admitted to our department with a diagnosis of probable pyelonephritis and a positive urine culture were included in this prospect i ve study . All patients received antibiotics for 7 - 21 days . During the acute phase of urinary-tract infection , scintigraphy with technetium-99m-dimercaptosuccinic acid ( DMSA ) and ultrasonography were done . Voiding cystourethrography was undertaken at least 6 weeks after the end of antibiotic treatment . When scintigraphy showed renal parenchymal lesions , repeat scintigraphy was done after at least 2 months to assess the progression of renal lesions . For the analysis , children were grouped by age according to presumed risk of renal sequelae after pyelonephritis : high risk ( < 1 year ) , moderate risk ( 1 - 5 years ) , low risk ( > 5 years ) . FINDINGS 201 patients were enrolled in the study ( 119 < 1 year , 47 aged 1 - 5 years , 35 > 5 years ) . During the acute phase of urinary-tract infection , renal lesions were found in 66 ( 55 % ) infants under 1 year , in 37 ( 79 % ) children aged 1 - 5 years , and in 24 ( 69 % ) children older than 5 years . Of these 127 children , 108 underwent repeat scintigraphy after an average of 3 months ( 50 < 1 year , 36 aged 1 - 5 years , 22 > 5 years ) . Overall , renal scars were found on repeat scintigraphy in 20 ( 40 % ) infants under 1 year , in 31 ( 86 % ) children aged 1 - 5 years , and in 14 ( 64 % ) children older than 5 years . 38 ( 36 % ) of these 65 patients had vesicoureteric reflux . Among 88 children who had a first documented urinary-tract infection and underwent repeat scintigraphy , renal scars were found in 20 ( 43 % ) under 1 year , in 26 ( 84 % ) aged 1 - 5 years , and in eight ( 80 % ) older than 5 years . INTERPRETATION This study did not confirm the conventional view that the risk of renal scars after pyelonephritis diminishes with age . We believe that all children , irrespective of age , will benefit from any measure that prevents the development of renal sequelae PURPOSE We prospect ively determined the risk factors for renal scar formation after the first episode of acute pyelonephritis as confirmed on dimercapto-succinic acid scintigraphy in children younger than 1 year . MATERIAL S AND METHODS A total of 213 infants with acute pyelonephritis were enrolled in the study . Infants with urological abnormalities other than vesicoureteral reflux were excluded from analysis . Followup scanning was performed 6 months after acute pyelonephritis and voiding cystourethrography was performed after the acute phase of infection . Possible risk factors were evaluated including gender , peak fever , duration of fever before and after treatment with antibiotics , white blood cell count , C-reactive protein concentration , presence of vesicoureteral reflux and reflux grade . RESULTS Six months after acute pyelonephritis 37 of 213 ( 17.4 % ) infants and 41 of 248 ( 16.5 % ) renal units with acute photon defects on initial dimercapto-succinic acid scintigraphy had renal scars . The rates of scar formation were significantly higher in infants with vesicoureteral reflux than in those without ( 39.4 % vs 7.5 % , p < 0.001 , OR 9.433 ) and in renal units with vesicoureteral reflux than in those without ( 39.4 % vs 8.2 % , p < 0.001 , OR 7.237 ) . Renal scar formation was related to reflux grade ( none-8.2 % , grade I-20 % , grade II-22.7 % , grade III-40 % , grade IV-70 % , grade V-55.6 % , p < 0.001 ) but not to any other clinical or laboratory variables . CONCLUSIONS The presence of vesicoureteral reflux was the only independent risk factor for renal scar formation after acute pyelonephritis in infants . The prevalence of renal scarring was significantly correlated with reflux grade . Voiding cystourethrography is necessary in infants after the first acute pyelonephritis episode is confirmed on dimercapto-succinic acid renal scintigraphy OBJECTIVES . Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications . Antimicrobial prophylaxis has been used to reduce the risk for recurrence . We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection . METHODS . The study was a controlled , r and omized , open-label , 2-armed , noninferiority trial comparing no prophylaxis with prophylaxis ( co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day ) for 12 months . A total of 338 children who were aged 2 months to < 7 years and had a first episode of febrile urinary tract infection were enrolled : 309 with a confirmed pyelonephritis on a technetium 99 m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux . The primary end point was recurrence rate of febrile urinary tract infections during 12 months . Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99 m dimercaptosuccinic acid scan after 12 months . RESULTS . Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis : 12 ( 9.45 % ) of 127 vs 15 ( 7.11 % ) of 211 . In the subgroup of children with reflux , the recurrence of febrile urinary tract infections was 9 ( 19.6 % ) of 46 on no prophylaxis and 10 ( 12.1 % ) of 82 on prophylaxis . No significant difference was found in the secondary outcome : 2 ( 1.9 % ) of 108 on no prophylaxis versus 2 ( 1.1 % ) of 187 on prophylaxis . Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections . Whereas increasing age was protective , use of no prophylaxis was not a risk factor . CONCLUSIONS . For children with or without primary nonsevere reflux , prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode |
10,998 | 27,820,466 | In the end , eight controlled trials were included The main results were : • Cognitive-behavioural and sensorial stimulation programs reduce perceived chronic pain .
• Interventions based on psycho-education and music therapy programs reduce osteoarticular pain .
• Magnetic therapy and guided imagery are interventions that may relieve chronic headache .
• An intervention including a physical exercise program in incontinent elderly increases mobility but does not relieve pain , and may even worsen it .
Other outcome measures showed an improvement in the quality of life ( sensorial stimulation and guided imagery ) , in depression , disability and empowerment ( music therapy ) and physical functioning ( program of psycho-education ) . | Objectives To determine the best available evidence regarding the effectiveness of nursing interventions for adult patients experiencing chronic pain . | Objectives : To assess the effectiveness of multidisciplinary rehabilitation in the treatment of fibromyalgia in comparison to st and ard medical care . Methods : Seventy-nine men and women were r and omly assigned to one of two groups . The intervention group consisted of a rheumatologist and physical therapist intake and discharge , 18 group supervised exercise therapy sessions , 2 group pain and stress management lectures , 1 group education lecture , 1 group dietary lecture , and 2 massage therapy sessions . The control group consisted of st and ard medical care with the patients ' family physician . Outcome measures included self-perceived health status , pain-related disability , average pain intensity , depressed mood , days in pain , hours in pain , prescription and nonprescription medication usage , and work status . Outcomes were measured at the end of the 6-week intervention and at 15-month follow-up . Results : Thirty-five out of 43 patients from the intervention group and 36 out of 36 patients from the control group completed the study . There were no statistically significant differences between the 2 groups prior to intervention . Intention-to-treat analysis revealed that the intervention group , in comparison to the control group , experienced statistically significant changes at intervention completion in self-perceived health status , average pain intensity , pain related disability , depressed mood , days in pain , and hours in pain , but no significant differences in nonprescription drug use , prescription drug use , or work status . At 15 months , all health outcomes retained their significance except health status . Nonprescription and prescription drug use demonstrated significant reductions at 15 months . Binary logistic regression indicated that long-term changes in Pain Disability Index were influenced by long-term exercise adherence and income status . Conclusions : Positive health-related outcomes in this mostly unresponsive condition can be obtained with a low-cost , group multidisciplinary intervention in a community-based , non clinical setting Background Massage is increasingly used to manage chronic pain but its benefit has not been clearly established . The aim of the study is to determine the effectiveness of a single session of nurse-administered massage for the short term relief of chronic non-malignant pain and anxiety . Methods A r and omised controlled trial design was used , in which the patients were assigned to a massage or control group . The massage group received a 15 minute manual massage and the control group a 15 minute visit to talk about their pain . Adult patients attending a pain relief unit with a diagnosis of chronic pain whose pain was described as moderate or severe were eligible for the study . An observer blind to the patients ' treatment group carried out assessment s immediately before ( baseline ) , after treatment and 1 , 2 , 3 and 4 hours later . Pain was assessed using 100 mm visual analogue scale and the McGill Pain Question naire . Pain Relief was assessed using a five point verbal rating scale . Anxiety was assessed with the Spielberger short form State-Trait Anxiety Inventory . Results 101 patients were r and omised and evaluated , 50 in the massage and 51 in the control group . There were no statistically significant differences between the groups at baseline interview . Patients in the massage but not the control group had significantly less pain compared to baseline immediately after and one hour post treatment . 95 % confidence interval for the difference in mean pain reduction at one hour post treatment between the massage and control groups is 5.47 mm to 24.70 mm . Patients in the massage but not the control group had a statistically significant reduction in anxiety compared to baseline immediately after and at 1 hour post treatment . Conclusion Massage is effective in the short term for chronic pain of moderate to severe intensity . Trial Registration [ IS RCT N98406653 To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia ( PCA ) , we conducted a prospect i ve , blinded , r and omized controlled trial . Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music . They were then premedicated with morphine and ketorolac and r and omly allocated into two groups . Group 1 ( n = 97 ) had music started 10 min before the procedure and maintained until 10 min after its conclusion . Group 2 ( n = 96 ) had music begun at the conclusion of lithotripsy and continued for 10 min . Pain intensity , alfentanil requirement , side effects , quality of analgesia , patient satisfaction , and acceptance of the technique were evaluated . Demographics , alfentanil requirement , pain levels , side effects , quality of analgesia , and patient satisfaction were similar in both groups . The addition of music did not provide any benefit . This result raises the possibility that some nonpharmacologic therapies have minimal impact in setting s where the painful stimulus is moderate to severe and adequate pharmacotherapy is available OBJECTIVE Studies have suggested that the Arthritis Self-Management Program ( ASMP ) course is effective at reducing arthritis pain and health care costs in volunteer participants . There have been no reports of trials of the ASMP in the context of primary care physicians ' practice s , where the potential for spreading the program may be greatest . We conducted a r and omized controlled trial of the ASMP course in a large primary care physician network . METHODS Patients with osteoarthritis , rheumatoid arthritis , or fibromyalgia were recruited for the study . Subjects in the intervention practice s received the 6 week course and those in the control practice s received only the ASMP book , without course . Disability , pain , self-efficacy , mental health , and satisfaction were measured using vali date d instruments at baseline and at 4 months . RESULTS One hundred thirteen patients were recruited for the ASMP course ( intervention ) and completed baseline and 4 month followup question naires . Eighty-four percent completed at least 4 of 6 classes . Seventy-four patients received the ASMP manual ( controls ) and completed both question naires . Patients in the intervention and control groups had similar baseline pain ( p = 0.94 ) , self-efficacy to control pain ( p = 0.90 ) , mental health ( p = 0.10 ) , and vitality scores ( p = 0.21 ) , but those in the intervention arm had slightly less disability ( p = 0.04 ) . At 4 months , there was no significant improvement from baseline in any endpoint and no difference between patients in the intervention and control groups ( all p > 0.2 ) . Patient satisfaction with arthritis care and outcomes was no different for intervention and control patients ( all p > 0.3 ) . All types of health care re source use were similar at baseline and followup for both intervention and control groups ( all p > 0.2 ) . CONCLUSION While the ASMP course has been found to be effective in other patient groups , there were no significant clinical benefits noted at 4 months in patients recruited from primary care practice Objective To determine the effectiveness of lessons in the Alex and er technique , massage therapy , and advice from a doctor to take exercise ( exercise prescription ) along with nurse delivered behavioural counselling for patients with chronic or recurrent back pain . Design Factorial r and omised trial . Setting 64 general practice s in Engl and . Participants 579 patients with chronic or recurrent low back pain ; 144 were r and omised to normal care , 147 to massage , 144 to six Alex and er technique lessons , and 144 to 24 Alex and er technique lessons ; half of each of these groups were r and omised to exercise prescription . Interventions Normal care ( control ) , six sessions of massage , six or 24 lessons on the Alex and er technique , and prescription for exercise from a doctor with nurse delivered behavioural counselling . Main outcome measures Rol and Morris disability score ( number of activities impaired by pain ) and number of days in pain . Results Exercise and lessons in the Alex and er technique , but not massage , remained effective at one year ( compared with control Rol and disability score 8.1 : massage −0.58 , 95 % confidence interval −1.94 to 0.77 , six lessons −1.40 , −2.77 to −0.03 , 24 lessons −3.4 , −4.76 to −2.03 , and exercise −1.29 , −2.25 to −0.34 ) . Exercise after six lessons achieved 72 % of the effect of 24 lessons alone ( Rol and disability score −2.98 and −4.14 , respectively ) . Number of days with back pain in the past four weeks was lower after lessons ( compared with control median 21 days : 24 lessons −18 , six lessons −10 , massage −7 ) and quality of life improved significantly . No significant harms were reported . Conclusions One to one lessons in the Alex and er technique from registered teachers have long term benefits for patients with chronic back pain . Six lessons followed by exercise prescription were nearly as effective as 24 lessons . Trial registration National Research Register N0028108728 . How does the Alex and er Technique work ? What are the authors findings about the clinical and cost effectiveness of the treatment ? Watch this video to find out ( 12 mins ) . A cognitive-behavioral pain management program for elderly nursing home residents with chronic pain was compared with an attention/support control treatment in a r and omized pre-/post-comparison group design with follow-up . Thirteen women and nine men , ranging in age from 61 to 98 ( M = 77.2 ) , from two large nursing homes participated in the treatment programs through 10 weekly group sessions . Results revealed that the subjects who received the cognitive-behavioral training reported less pain and pain-related disability , although the two programs were perceived as equally credible both before and after treatment . No significant treatment effects were found for depression and physician medication ratings . Treatment effects were maintained at 4-month follow-up , despite an overall increase in reported pain . Findings indicate that elderly nursing home residents with chronic pain and without serious cognitive impairment can benefit substantially from training in cognitive and behavioral pain management strategies that are known to be effective with younger age groups and the community-resident elderly population OBJECTIVE To determine if the chronic pain frequently presented by postpolio patients can be relieved by application of magnetic fields applied directly over an identified pain trigger point . DESIGN Double-blind r and omized clinical trial . SETTING The postpolio clinic of a large rehabilitation hospital . PATIENTS Fifty patients with diagnosed postpolio syndrome who reported muscular or arthritic-like pain . INTERVENTION Application of active or placebo 300 to 500 Gauss magnetic devices to the affected area for 45 minutes . MAIN OUTCOME MEASURE Score on the McGill Pain Question naire . RESULTS Patients who received the active device experienced an average pain score decrease of 4.4 + /- 3.1 ( p < .0001 ) on a 10-point scale . Those with the placebo devices experienced a decrease of 1.1 + /- 1.6 points ( p < .005 ) . The proportion of patients in the active-device group who reported a pain score decrease greater than the average placebo effect was 76 % , compared with 19 % in the placebo-device group ( p < .0001 ) . CONCLUSIONS The application of a device delivering static magnetic fields of 300 to 500 Gauss over a pain trigger point results in significant and prompt relief of pain in postpolio subjects BACKGROUND Chronic pain is recognised as an important problem in the community but our underst and ing of the epidemiology of chronic pain remains limited . We undertook a study design ed to quantify and describe the prevalence and distribution of chronic pain in the community . METHODS A r and om sample of 5036 patients , aged 25 and over , was drawn from 29 general practice s in the Grampian region of the UK and surveyed by a postal self-completion question naire . The question naire included case-screening questions , a question on the cause of the pain , the chronic pain grade question naire , the level of expressed needs question naire , and sociodemographic questions . FINDINGS 3605 question naires were returned completed . 1817 ( 50.4 % ) of patients self reported chronic pain , equivalent to 46.5 % of the general population . 576 reported back pain and 570 reported arthritis ; these were the most common complaints and accounted for a third of all complaints . Backward stepwise logistic-regression modelling identified age , sex , housing tenure , and employment status as significant predictors of the presence of chronic pain in the community . 703 ( 48.7 % ) individuals with chronic pain had the least severe grade of pain , and 228 ( 15.8 % ) the most severe grade . Of those who reported chronic pain , 312 ( 17.2 % ) reported no expressed need , and 509 ( 28.0 % ) reported the highest expressed need . INTERPRETATION Chronic pain is a major problem in the community and certain groups within the population are more likely to have chronic pain . A detailed underst and ing of the epidemiology of chronic pain is essential for efficient management of chronic pain in primary care Objective : To evaluate the efficacy of a treatment programme for patients with fibromyalgia ( FM ) based on self management , using pool exercises and education . Methods : R and omised controlled trial with a 6 month follow up to evaluate an outpatient multidisciplinary programme ; 164 patients with FM were allocated to an immediate 6 week programme ( n = 84 ) or to a waiting list control group ( n = 80 ) . The main outcomes were changes in quality of life , functional consequences , patient satisfaction and pain , using a combination of patient question naires and clinical examinations . The question naires included the Fibromyalgia Impact Question naire ( FIQ ) , Psychological General Well-Being ( PGWB ) index , regional pain score diagrams , and patient satisfaction measures . Results : 61 participants in the treatment group and 68 controls completed the programme and 6 month follow up examinations . Six months after programme completion , significant improvements in quality of life and functional consequences of FM were seen in the treatment group as compared with the controls and as measured by scores on both the FIQ ( total score p = 0.025 ; fatigue p = 0.003 ; depression p = 0.031 ) and PGWB ( total score p = 0.032 ; anxiety p = 0.011 ; vitality p = 0.013 , ) . All four major areas of patient satisfaction showed greater improvement in the treatment than the control groups ; between-group differences were statistically significant for “ control of symptoms ” , “ psychosocial factors ” , and “ physical therapy ” No change in pain was seen . Conclusion : A 6 week self management based programme of pool exercises and education can improve the quality of life of patients with FM and their satisfaction with treatment . These improvements are sustained for at least 6 months after programme completion Abstract Objectives : To compare the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain . Design : Prospect i ve , r and omised , placebo controlled trial . Setting : Three outpatient departments in Germany . Participants : 177 patients aged 18–85 years with chronic neck pain . Interventions : Patients were r and omly allocated to five treatments over three weeks with acupuncture ( 56 ) , massage ( 60 ) , or “ sham ” laser acupuncture ( 61 ) . Main outcome measures : Primary outcome measure : maximum pain related to motion ( visual analogue scale ) irrespective of direction of movement one week after treatment . Secondary outcome measures : range of motion ( 3D ultrasound real time motion analyser ) , pain related to movement in six directions ( visual analogue scale ) , pressure pain threshold ( pressure algometer ) , changes of spontaneous pain , motion related pain , global complaints ( seven point scale ) , and quality of life ( SF-36 ) . Assessment s were performed before , during , and one week and three months after treatment . Patients ' beliefs in treatment were assessed . Results : One week after five treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage ( difference 24.22 ( 95 % confidence interval 16.5 to 31.9 ) , P=0.0052 ) but not compared with sham laser ( 17.28 ( 10.0 to 24.6 ) , P=0.327 ) . Differences between acupuncture and massage or sham laser were greater in the subgroup who had had pain for longer than five years ( n=75 ) and in patients with myofascial pain syndrome ( n=129 ) . The acupuncture group had the best results in most secondary outcome measures . There were no differences in patients ' beliefs in treatment . Conclusions : Acupuncture is an effective short term treatment for patients with chronic neck pain , but there is only limited evidence for long term effects after five treatments . What is already known on this topic Acupuncture is a widespread complementary treatment Evidence from trials have given conflicting results on its use in the treatment of neck pain because of method ological shortcomings and because effects were compared either with alternative treatments or with different sham procedures imitating acupuncture , but not both What this study adds Compared with sham laser acupuncture and massage , needle acupuncture has beneficial effects on mobility and pain related to motion in patients with chronic neck pain Acupuncture was clearly more effective than massage , but differences were not always significant compared with sham laser acupuncture Acupuncture was the best treatment for patients with the myofascial syndrome and those who had had pain for longer than five Abstract Objective To determine the effectiveness of dynamic muscle training and relaxation training for chronic neck pain . Design R and omised controlled trial . Setting Five occupational healthcare centres , Tampere , Finl and . Participants 393 female office workers ( mean age 45 years ) with chronic non-specific neck pain r and omly assigned to 12 weeks of dynamic muscle training ( n = 135 ) or relaxation training ( n = 128 ) , plus one week of reinforcement training six months after baseline ; or ordinary activity ( control group ; n = 130 ) . Main outcome measure Change in intensity of neck pain at three , six , and 12 months . Results No significant difference was found in neck pain between the groups at follow up . However , the range of motion for cervical rotation and lateral flexion increased more in the training groups than in the control group . Conclusions Dynamic muscle training and relaxation training do not lead to better improvements in neck pain compared with ordinary activity OBJECTIVES The aim was to assess the effect of wool use in patients with fibromyalgia . BACKGROUND Various studies concerning the treatment of patients with fibromyalgia using nonpharmacological methods have been carried out . There are , however , no reports on the use of wool clothing and bedding in treating these patients . DESIGN AND METHODS The study employed two-group , experimental design . A total of 50 patients with fibromyalgia , based on the criteria of the American College of Rheumatology , were selected for the study . They were distributed equally into two groups : a control group and a treatment group . The 25 patients in each group were r and omly selected and the compositions of the two groups were statistically identical . The patients in the treatment group wore woolen underwear ( which covered the body from the shoulders to the thighs ) and used woolen bedding such as woolen bed liner , woolen quilt and pillow during the experimental period of 6 weeks . All patients were assessed at the beginning the trial ( pre-test ) and the end of 6th ( post-test ) week . Data were collected using the visual analogue scale ( 0 - 10 ) , tender points count , and Fibromyalgia Impact Question naire . RESULTS Patients in the treatment group reported significant improvements in their conditions including a reduction in pain levels , tender point counts , and all scores of the Fibromyalgia Impact Question naire ( p < or= 0.001 ) . CONCLUSIONS The use of woolen underwear and woolen bedding were effective in reducing the symptoms of patients suffering from fibromyalgia . The use of wool is recommended as a means of treatment for alleviating the pain of fibromyalgia . RELEVANCE TO CLINICAL PRACTICE Nurses provide professional support to patients with fibromyalgia . They select suitable clothes and sleeping material s for their patients with this object in mind : to keep their patients warm and to protect them from the cold OBJECTIVE To investigate to what extent a single 60-minute session of transcutaneous electrical nerve stimulation ( TENS ) would modify chronic clinical pain , acute experimental pain , and the flexion reflex evoked in chronic low back pain patients . STUDY DESIGN Thirty young subjects with chronic low back pain were r and omly allocated to two groups , receiving either TENS or placebo stimulation to the lumbosacral region for 60 minutes . The flexion reflex was elicited by an electrical stimulation applied to the subject 's right sole and recorded electromyographically from the biceps femoris and the tibialis anterior muscles . MAIN OUTCOME MEASURES Subjective sensation of low back pain and the electrically induced pain were measured by two separate visual analog scales , termed VAS(LBP ) and VAS(FR ) , respectively . Data obtained before , during , and 60 minutes after TENS and placebo stimulations were analyzed using repeated measures ANOVA . RESULTS The VAS(LBP ) score was significantly reduced to 63.1 % of the prestimulation value after TENS ( p<.001 ) , but the reduction was negligible after placebo stimulation ( to 96.7 % , p = .786 ) . In contrast , no significant change was found in the VASFR score ( p = .666 ) and the flexion reflex area ( p = .062 ) during and after stimulation within each group and between the two groups ( p = .133 for VASFR and p = .215 for flexion reflex area ) . CONCLUSIONS The same TENS protocol had different degrees of antinociceptive influence on chronic and acute pain in chronic low back pain patients CONTEXT Chronic low back pain is one of the most prevalent and costly medical conditions in the United States . Permanent magnets have become a popular treatment for various musculoskeletal conditions , including low back pain , despite little scientific support for therapeutic benefit . OBJECTIVE To compare the effectiveness of 1 type of therapeutic magnet , a bipolar permanent magnet , with a matching placebo device for patients with chronic low back pain . DESIGN R and omized , double-blind , placebo-controlled , crossover pilot study conducted from February 1998 to May 1999 . SETTING An ambulatory care physical medicine and rehabilitation clinic at a Veterans Affairs hospital . PATIENTS Nineteen men and 1 woman with stable low back pain of a mean of 19 years ' duration , with no past use of magnet therapy for low back pain . Twenty patients were determined to provide 80 % power in the study at P<.05 to detect a difference of 2 points ( the difference believed to be clinical ly significant ) on a visual analog scale ( VAS ) . INTERVENTIONS For each patient , real and sham bipolar permanent magnets were applied , on alternate weeks , for 6 hours per day , 3 days per week for 1 week , with a 1-week washout period between the 2 treatment weeks . MAIN OUTCOME MEASURES Pretreatment and posttreatment pain intensity on a VAS ; sensory and affective components of pain on the Pain Rating Index ( PRI ) of the McGill Pain Question naire ; and range of motion ( ROM ) measurements of the lumbosacral spine , compared by real vs sham treatment . RESULTS Mean VAS scores declined by 0.49 ( SD , 0.96 ) points for real magnet treatment and by 0.44 ( SD , 1.4 ) points for sham treatment ( P = .90 ) . No statistically significant differences were noted in the effect between real and sham magnets with any of the other outcome measures ( ROM , P = .66 ; PRI , P = .55 ) . CONCLUSIONS Application of 1 variety of permanent magnet had no effect on our small group of subjects with chronic low back pain Study Design . A r and omized controlled trial with single-blind outcome assessment s. Objective . To evaluate the efficacy of a neck exercise program in patients with chronic neck pain . Summary of Background Data . The effect of exercise for patients with chronic neck pain has been investigated in a number of studies . The efficacy is , however , question able . Methods . A total of 145 patients were r and omly allocated into an exercise ( n = 67 ) and a nonexercise ( control ) group ( n = 78 ) . Patients in the control group were given infrared irradiation and neck care advice . In addition to infrared irradiation and advice , patients in the exercise group had undergone an exercise program with activation of the deep neck muscles and dynamic strengthening of the neck muscles for 6 weeks . Subjective pain and disability and isometric neck muscle strength were measured at baseline , 6 weeks , and 6 months . Analysis was by intention-to-treat . Results . At week 6 , the exercise group had a significantly better improvement in disability score ( P = 0.03 ) , subjective report of pain ( P = 0.01 ) , and in isometric neck muscle strength ( P = 0.57–0.00 ) in most of the directions than the control group . However , significant differences between the two groups were found only in the subjective report of pain and patient satisfaction at the 6-month follow-up . Conclusions . At week 6 , patients with chronic neck pain can benefit from the neck exercise program with significant improvement in disability , pain , and isometric neck muscle strength in different directions . However , the effect of exercise was less favorable at 6 months Background About half of all newly presented episodes of shoulder complaints ( SC ) in general practice are reported to last for at least six months . Early interventions aim ed at the psychological and social determinants of SC are not common in general practice , although such interventions might prevent the development of chronic SC.The Education and Activation Programme ( EAP ) consists of an educational part and a time-contingent activation part . The aim of the EAP is to provide patients with the proper cognitions by means of education , and to stimulate adequate behaviour through advice on activities of daily living . Design The article describes the design of a r and omised clinical trial ( RCT ) to evaluate the effectiveness and cost-effectiveness of an EAP in addition to usual care , compared to usual care only , in the prevention of chronic SC after six months . It also describes the analysis of the cost and effect balance . Patients suffering from SC for less than three months are recruited in general practice and through open recruitment . A trained general practitioner or a trained therapist administers the EAP . Primary outcome measures are patient-perceived recovery , measured by self- assessment on a seven-point scale , and functional limitations in activities of daily living . Question naires are used to study baseline measures , prognostic measures , process measures and outcome measures . Discussion The inclusion of patients in the study lasted until December 31st 2003 . Data collection is to end in June 2004 AIM This paper reports a study testing the effect of music on power , pain , depression and disability , and comparing the effects of research er-provided music ( st and ard music ) with subject-preferred music ( patterning music ) . BACKGROUND Chronic non-malignant pain is characterized by pain that persists in spite of traditional interventions . Previous studies have found music to be effective in decreasing pain and anxiety related to postoperative , procedural and cancer pain . However , the effect of music on power , pain , depression , and disability in working age adults with chronic non-malignant pain has not been investigated . METHOD A r and omized controlled clinical trial was carried out with a convenience sample of 60 African American and Caucasian people aged 21 - 65 years with chronic non-malignant pain . They were r and omly assigned to a st and ard music group ( n = 22 ) , patterning music group ( n = 18 ) or control group ( n = 20 ) . Pain was measured with the McGill Pain Question naire short form ; depression was measured with the Center for Epidemiology Studies Depression scale ; disability was measured with the Pain Disability Index ; and power was measured with the Power as Knowing Participation in Change Tool ( version II ) . RESULTS The music groups had more power and less pain , depression and disability than the control group , but there were no statistically significant differences between the two music interventions . The model predicting both a direct and indirect effect for music was supported . CONCLUSION Nurses can teach patients how to use music to enhance the effects of analgesics , decrease pain , depression and disability , and promote feelings of power Abstract Objectives : To evaluate cardiovascular fitness exercise in people with fibromyalgia Design : R and omised controlled trial Setting : Hospital rheumatology out patients . Group based classes took place at a “ healthy living centre . ” Participants : 132 patients with fibromyalgia . Interventions : Prescribed grade d aerobic exercise ( active treatment ) and relaxation and flexibility ( control treatment ) . Main outcome measures : Participants ' self assessment of improvement , tender point count , impact of condition measured by fibromyalgia impact question naire , and short form McGill pain question naire . Results : Compared with relaxation exercise led to significantly more participants rating themselves as much or very much better at three months : 24/69 ( 35 % ) v 12/67 ( 18 % ) , P=0.03 . Benefits were maintained or improved at one year follow up when fewer participants in the exercise group fulfilled the criteria for fibromyalgia ( 31/69 v 44/67 , P=0.01 ) . Peoplein the exercise group also had greater reductions in tender point counts ( 4.2 v 2.0 , P=0.02 ) and in scores on the fibromyalgia impact question naire ( 4.0 v 0.6 , P=0.07 ) . Conclusions : Prescribed grade d aerobic exercise is a simple , cheap , effective , and potentially widely available treatment for fibromyalgia OBJECTIVE To evaluate the effects of 6 months of pool exercise combined with a 6 session education program for patients with fibromyalgia syndrome ( FM ) . METHODS The study population comprised 58 patients , r and omized to a treatment or a control group . Patients were instructed to match the pool exercises to their threshold of pain and fatigue . The education focused on strategies for coping with symptoms and encouragement of physical activity . The primary outcome measurements were the total score of the Fibromyalgia Impact Question naire ( FIQ ) and the 6 min walk test , recorded at study start and after 6 mo . Several other tests and instruments assessing functional limitations , severity of symptoms , disabilities , and quality of life were also applied . RESULTS Significant differences between the treatment group and the control group were found for the FIQ total score ( p = 0.017 ) and the 6 min walk test ( p < 0.0001 ) . Significant differences were also found for physical function , grip strength , pain severity , social functioning , psychological distress , and quality of life . CONCLUSION The results suggest that a 6 month program of exercises in a temperate pool combined with education will improve the consequences of FM Background Fibromyalgia ( FM ) , one of the most common musculoskeletal disorders , is associated with high levels of impaired health and inadequate or limited symptom relief . The cause of this complex syndrome is unknown , and there is no known cure . Numerous research results indicate that a combination of physical exercise and mind-body therapy is effective in symptom management . T’ai Chi , an ancient Chinese exercise , combines physical exercise with mind-body therapy . Purpose To investigate the effects of T’ai Chi exercise on FM symptoms and health-related quality of life . Design Pilot study , one group pre-to-post posttest design . Methods Participants with FM ( n = 39 ) formed a single group for 6 weeks of 1-hour , twice weekly T’ai Chi exercise classes . FM symptoms and health-related quality of life were measured before and after exercise . Findings Twenty-one participants completed at least 10 of the 12 exercise sessions . Although the dropout rate was higher than expected , measurements on both the Fibromyalgia Impact Question naire ( FIQ ) ( Buckhardt , Clark , & Bennett , 1991 ) and the Short Form-36 ( SF-36 ) ( Ware & Sherbourne , 1992 ) revealed statistically significant improvement in symptom management and health-related quality of life . Implication s for Nursing Research Knowledge of interventions to enhance health for the patient with musculoskeletal problems is a National Association of Orthopaedic Nurses priority . T’ai Chi is potentially beneficial to patients with FM . Further research is needed to support evidence -based practice BACKGROUND Osteoarthritis is the most common degenerative disease in humans . It usually begins in middle age and is progressive . Chronic pain in older people presents a significant obstacle in maintaining function and independence . Previous studies have shown that music can improve motivation , elevate mood , and increase feelings of control in older people . PURPOSE The purpose of this r and omized clinical trial was to examine the influence of music as a nursing intervention on osteoarthritis pain in elders . METHOD Data were collected using the short form of the McGill Pain Question naire with 66 elders suffering from chronic osteoarthritis pain . Differences in perceptions of pain were measured over 14 days in an experimental group who listened to music for 20 minutes daily and a control group who sat quietly for 20 minutes daily . All participants completed the Short Form McGill Pain Question naire ( SF-MPQ ) on day 1 , 7 , and 14 of the study . RESULTS Results of t-tests indicated that those who listened to music had less pain on both the Pain Rating Index on day 1 ( P = 0.001 ) , day 7 ( P = 0.001 ) and day 14 ( P = 0.001 ) and on the Visual Analogue Scale on day 1 ( P = 0.001 ) , day 7 ( P = 0.001 ) and day 14 ( P = 0.001 ) , when compared with those who sat quietly and did not listen to music . A repeated measure analysis of variance controlling for pretest measures demonstrated a significant decrease in pain among experimental group participants when compared with the control group on the pain descriptor section of the SF-MPQ ( P = 0.001 ) and the visual analogue portion of the SF-MPQ ( P = 0.001 ) . CONCLUSION Listening to music was an effective nursing intervention for the reduction of chronic osteoarthritis pain in the community-dwelling elders in this study OBJECTIVE To evaluate the efficacy of a 6-week exercise and educational program for patients with fibromyalgia . METHODS Forty-one subjects were r and omly assigned to the program or served as waiting list controls . Program outcome was assessed with a 6-minute walk test , the Fibromyalgia Impact Question naire , a Self-Efficacy Scale , and a " knowledge " question naire ( based on information provided during the educational sessions ) . Waiting list control subjects subsequently completed the program . Program outcome was reassessed 3 or 6 months post-program . RESULTS The program produced significant improvements in 6-minute walk distance , well-being , fatigue , self-efficacy ( for controlling pain and other symptoms ) , and knowledge . At followup , immediate gains in walk distance , well-being , and self-efficacy were maintained , but gains in fatigue and knowledge were lost . CONCLUSION Short-term exercise and educational programs can produce immediate and sustained benefits for patients with fibromyalgia . The benefits of our program may be due to exercise or education since both interventions were given AIM To investigate the effectiveness of a new community nursing model of care for clients with chronic leg ulcers in terms of levels of pain and ulcer healing . METHOD A r and omised controlled trial comparing the new model of care with st and ard community nursing care was conducted with a sample of 56 clients with chronic venous leg ulcers , 28 clients in the intervention group and 28 in the control group . Data were collected on admission to the study and at 12 weeks from admission . RESULTS Significant improvements in levels of pain and ulcer healing were found in the intervention group receiving the new model of care . CONCLUSION Results from this study have implication s for health professionals providing care for clients with chronic leg ulcers Purpose : Loving-kindness meditation has been used for centuries in the Buddhist tradition to develop love and transform anger into compassion . This pilot study tested an 8-week loving-kindness program for chronic low back pain patients . Method : Patients ( N = 43 ) were r and omly assigned to the intervention or st and ard care . St and ardized measures assessed patients ’ pain , anger , and psychological distress . Findings : Post and follow-up analyses showed significant improvements in pain and psychological distress in the loving-kindness group , but no changes in the usual care group . Multilevel analyses of daily data showed that more loving-kindness practice on a given day was related to lower pain that day and lower anger the next day . Conclusions : Preliminary results suggest that the loving-kindness program can be beneficial in reducing pain , anger , and psychological distress in patients with persistent low back pain . Implication s : Clinicians may find loving-kindness meditation helpful in the treatment of patients with persistent pain & NA ; To evaluate immediate effects of two different modes of acupuncture on motion‐related pain and cervical spine mobility in chronic neck pain patients compared to a sham procedure . Thirty‐six patients with chronic neck pain and limited cervical spine mobility participated in a prospect i ve , r and omized , double‐blind , sham‐controlled crossover trial . Every patient was treated once with needle acupuncture at distant points , dry needling ( DN ) of local myofascial trigger points and sham laser acupuncture ( Sham ) . Outcome measures were motion‐related pain intensity ( visual analogue scale , 0–100 mm ) and range of motion ( ROM ) . In addition , patients scored changes of general complaints using an 11‐point verbal rating scale . Patients were assessed immediately before and after each treatment by an independent ( blinded ) investigator . Multivariate analysis was used to assess the effects of true acupuncture and needle site independently . For motion‐related pain , use of acupuncture at non‐local points reduced pain scores by about a third ( 11.2 mm ; 95 % CI 5.7 , 16.7 ; P=0.00006 ) compared to DN and sham . DN led to an estimated reduction in pain of 1.0 mm ( 95 % CI −4.5 , 6.5 ; P=0.7 ) . Use of DN slightly improved ROM by 1.7 ° ( 95 % CI 0.2 , 3.2 ; P=0.032 ) with use of non‐local points improving ROM by an additional 1.9 ° ( 95 % CI 0.3 , 3.4 ; P=0.016 ) . For patient assessment of change , non‐local acupuncture was significantly superior both to Sham ( 1.7 points ; 95 % CI 1.0 , 2.5 ; P=0.0001 ) and DN ( 1.5 points ; 95 % CI 0.4 , 2.6 ; P=0.008 ) but there was no difference between DN and Sham ( 0.1 point ; 95 % CI −1.0 , 1.2 ; P=0.8 ) . Acupuncture is superior to Sham in improving motion‐related pain and ROM following a single session of treatment in chronic neck pain patients . Acupuncture at distant points improves ROM more than DN ; DN was ineffective for motion‐related pain Objectives To report preliminary data relevant to the effects of an exercise and toileting intervention on pain among incontinent nursing home ( NH ) residents . Design A r and omized controlled intervention trial . Setting and Participants Fifty-one incontinent residents in one skilled NH . InterventionThe intervention was implemented by research staff for a total of 4 times a day ( every 2 hours ) , 5 days a week , for 32 weeks . Residents were provided with incontinence care and assistance to either walk or , if nonambulatory , wheel their chairs , and to repeat sit-to-st and movements . Measurements Pain was measured in two ways at baseline and again at 32 weeks : ( 1 ) a count of the number of verbal expressions and pain behaviors during a st and ardized physical performance assessment ; and ( 2 ) a modified Geriatric Pain Measure administered in a one-on-one interview format . Results There were significant differences between intervention and control groups on all physical performance measures over time , with the intervention group remaining stable and the control group showing a significant decline in sit-to-st and , walking , and wheelchair propulsion endurance . Both groups showed mild to moderate pain at baseline according to each of the two pain measures , while there were no significant changes in pain reports between groups over time based on either measure . There was , however , a trend for pain to increase in the intervention group . Conclusions No significant changes in pain reports were attributable to exercise despite significant improvements in physical performance . In fact , there was a tendency for pain reports to increase with exercise . These preliminary findings suggest that exercise alone may be ineffective for pain management among incontinent NH residents . Care providers should consider that exercise to improve physical function may increase pain symptoms , requiring preemptive analgesia , other pain control strategies , or modified exercise techniques for this frail segment of the NH population OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P<.001 ) , a 12 % lower score on the knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P<.001 ) , mean ( + /-SE ) time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P<.001 ) , and mean ( + /-SE ) time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P<.001 ) than the health education group . The resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis & NA ; The study was carried out to examine whether acupuncture treatment can reduce chronic pain in the neck and shoulders and related headache , and also to examine whether possible effects are long‐lasting . Therefore , 24 female office workers ( 47±9 years old , mean±SD ) who had had neck and shoulder pain for 12±9 years were r and omly assigned to a test group ( TG ) or a control group ( CG ) . Acupuncture was applied 10 times during 3–4 weeks either at presumed anti‐pain acupoints ( TG ) or at placebo‐points ( CG ) . A physician measured the pain threshold ( PPT ) in the neck and shoulder regions with algometry before the first treatment , and after the last one and six months after the treatments . Question naires on muscle pain and headache were answered at the same occasions and again 3 years after the last treatment . The intensity and frequency of pain fell more for TG than for CG ( Pb≤0.04 ) during the treatment period . Three years after the treatments TG still reported less pain than before the treatments ( Pw<0.001 ) , contrary to what CG did ( Pb<0.04 ) . The degree of headache fell during the treatment period for both groups , but more for TG than for CG ( Pb=0.02 ) . Three years after the treatments the effect still lasted for TG ( Pw<0.001 ) while the degree of headache for CG was back to the pre‐treatment level ( Pb<0.001 ) . PPT of some muscles rose during the treatments for TG and remained higher 6 months after the treatments ( Pw<0.05 ) , which contrasts the situation for CG . Adequate acupuncture treatment may reduce chronic pain in the neck and shoulders and related headache . The effect lasted for 3 years OBJECTIVES We determined -- in women with fibromyalgia (FM)--effects of essential oils used with a 12-week exercise program on exercise volume , pain , physical performance , and physical function . DESIGN This was a r and omized clinical trial comparing 024 essential oil with sham oil combined with exercise . SETTING S SETTING S included community sites in southern California . SUBJECTS The study included 20 women r and omized to 024 oil , 23 to sham oil . INTERVENTIONS Women were trained in oil application before exercise , at bedtime on exercise days ; the 12-week program included weekly group sessions with trained leaders guided by a prerecorded regimen ( allowing choice of program level ) plus 2 days of home exercise with the recorded regimen . OUTCOME MEASURES Primary : Exercise volume ( number of days exercised multiplied by exercise level -- intensity and duration ) . Secondary : Pain ( Brief Pain Inventory ) , measures of physical performance ( 30-second chair st and s , 6-minute walk , multidimensional balance ) , and self-reported physical function ( Composite Physical Function scale ) . RESULTS The average participant was 54 years old , had some college education , was married , Caucasian , and minimally/mildly depressed . There was no significant difference in exercise volume between women using 024 as compared with those using sham oil after 12 weeks ( depression as covariate ) . There were no significant group nor pre- to postexercise changes in pain intensity or interference . There were greater positive changes in 30-second chair st and s , 6-minute walk distance , and multidimensional balance scores in the 024 group than in the sham group , but these were not significant . The counterirritant 024 oil was not different from the sham oil in its effect on exercise volume ( frequency , exercise level -- intensity and duration ) for women with FM . It is unknown whether 024 actually decreases local pain when used with exercise . CONCLUSIONS Increases in physical function found , while not significant , may be attributable to the exercise regimen or to the interaction of the oils and exercise regimen OBJECTIVE To determine the efficacy of training in fibromyalgia ( FM ) , we compared the effects of high intensity fitness training ( HIF ) and low intensity fitness training ( LIF ) . METHODS Thirty-seven female patients with FM were r and omly allocated to either a HIF group ( n = 19 ) or a LIF group ( n = 18 ) . Four patients ( 1 HIF group , 3 LIF group ) refused to participate after r and omization but before the start of the intervention . They were excluded from the analysis . Assessment s were performed at baseline and after 20 weeks of HIF or LIF . The primary outcome was patient 's global assessment [ on 100 mm visual analog scale ( VAS ) ] . Secondary endpoints were pain , number of tender points , total myalgic score , physical fitness , health status , and psychological distress . RESULTS One patient in the HIF group ( n = 18 ) and 2 in the LIF group ( n = 15 ) stopped training sessions during the course of the study . Nine of 18 patients in the HIF group compared to 8 of 15 patients in the LIF group achieved a participation rate of 67 % or more . Most important reasons for nonadherence were postexercise pain and fatigue , time consumption , and stress . The VAS for global well being improved slightly from 64 to 56 mm in the HIF group , and did not change in the LIF group ( 58 to 61 mm ) ( p = 0.07 ) . The Wmax ( physical fitness ) changed modestly from 110 to 123 watt in the HIF group , and from 97 to 103 watt in the LIF group ( p = 0.3 ) . VAS for pain increased from 53 to 64 mm in the HIF group and from 52 to 54 mm in the LIF group . The large st and ard deviations around mean change in global assessment s , number of tender points , total myalgic score , and psychological distress ( by SCL-90 ) severely influenced the power to detect within- and between-group differences . Analysis limited to those patients who accomplished a high attendance rate ( > 67 % ) showed similar results . CONCLUSION High intensity physical fitness training compared to low intensity physical fitness training leads to only modest improvements in physical fitness and general well being in patients with FM , and does not positively affect psychological status and general health This is the second of two papers which describes a research project which was design ed to evaluate the use of Snoezelen for the management of chronic pain . Part I explored the concepts underpinning both chronic pain and the Snoezelen itself which subsequently result ed in the development of an appropriate study design . The purpose of the study was to compare the use of Snoezelen for the management of chronic pain as a potential relaxation and distraction strategy , compared to the traditional relaxation approach used within the clinic . This paper will present the results that were obtained with the research project and in the light of these findings the author will discuss implication s for future investigation and practice OBJECTIVES To investigate the contribution of two principal features that underlie traditional Chinese acupuncture : site specificity and application of needle manipulation . DESIGN Thirteen volunteers completed a r and omised , dual blind ( subject and assessor ) repeated measures study involving five interventions . Pressure pain threshold ( PPT ) was measured with an algometer , before and after intervention at 10 sites ( acupoints and nonacupoints ) across the body . INTERVENTIONS Deep needling , with or without manual needle rotation , applied to the acupoint Large Intestine 4 ( LI4 ) or to a nonacupoint located on the medial side of the second metacarpal . Inactive laser to LI4 was used as a control . All interventions were administered for 21 min . MAIN OUTCOME MEASURES Percentage change in PPT from preintervention baseline at the 10 sites during the 18 min immediately following intervention . RESULTS Statistically significant increases from preintervention PPT means were obtained at all 10 sites following needling of LI4 with manipulation compared with one site after needling LI4 without manipulation . Needling the nonacupoint led to statistically significant increases at six sites when manipulation was present compared with none in the absence of manipulation . No significant changes in mean PPT followed inactive laser . Needling LI4 with manipulation produced mean increases that were statistically significantly greater than those for the other interventions with one exception : needling the nonacupoint with manipulation was as effective as needling LI4 with manipulation at one measurement site only . CONCLUSIONS Both manipulation and site of needling contributed significantly to the elevation of PPT following acupuncture . Distribution of effects on PPT did not support either neural segmental or Traditional Chinese Medicine channel theories . Psychological and physiological nonspecific effects appeared to play a minimal role in changes to PPT Objective The aim of this study was to compare pool-based exercise and balneotherapy in fibromyalgia syndrome ( FMS ) patients . Methods Fifty female patients diagnosed with FMS according to the American College of Rheumatism ( ACR ) criteria were r and omly assigned to two groups : group 1 ( n=25 ) with pool-based exercise , and in group 2 ( n=25 ) balneotherapy was applied in the same pool without any exercise for 35 min three times a week for 12 weeks . In both groups , pre- ( week 0 ) and post-treatment ( weeks 12 and 24 ) evaluation was performed by one of the authors , who was blind to the patient group . Evaluation parameters included pain , morning stiffness , sleep , tender points , global evaluation by the patient and the physician , fibromyalgia impact question naire , chair test , and Beck depression inventory . Statistical analysis was done on data collected from three evaluation stages . Results Twenty-four exercise and 22 balneotherapy patients completed the study . Pretreatment ( week 0 ) measurements did not show any difference between the groups . In group 1 , statistically significant improvement was observed in all parameters ( P<0.01 ) except for the chair test at both weeks 12 and 24 . In group 2 , week 12 measurements showed significant improvement in all parameters ( P<0.01 ) except for the chair test and Beck depression inventory . Week 24 evaluation results in group 2 showed significant improvements in pain and fatigue according to visual analogue scale ( VAS ) , 5-point scale , number of tender points , algometric and myalgic scores , and patient and physician global evaluation ( P<0.01 and P<0.05 , respectively ) , while improvements were nonsignificant in morning stiffness , sleep , fibromyalgia impact question naire ( FIQ ) , chair test , and Beck depression inventory parameters in this group . Comparison of the two groups based on the post-treatment ( weeks 12 and 24 ) percent changes and difference scores relative to pretreatment ( week 0 ) values failed to show a significant difference between the groups for any parameter except Beck depression inventory ( P<0.01 ) . Conclusion The results of our study showed that pool-based exercise had a longer-lasting effect on some of the FMS symptoms , but statistical analysis failed to show a significant superiority of pool-based exercise over balneotherapy without exercise . While we believe that exercise is a gold st and ard in FMS treatment , we also suggest in light of our results that balneotherapy is among the valid treatment options in FMS , and further research regarding the type and duration of the exercise programs is necessary BACKGROUND The purpose of this study was to determine if therapeutic touch , an alternative medicine modality , is effective in the treatment of osteoarthritis of the knee . METHODS A single-blinded r and omized control trial was conducted in a family practice center of a community hospital family practice residency program in Pennsylvania . The patients were between the ages of 40 and 80 , had been given a diagnosis of osteoarthritis of at least one knee , had not had knee replacement , and had no other connective tissue disease . The patients were r and omized to therapeutic touch , mock therapeutic touch , or st and ard care . The main outcome measures were pain and its impact , general well-being , and health status measured by st and ardized , vali date d instruments , as well as the qualitative measurement of a Depth interview . RESULTS Twenty-five patients completed the study . The treatment group had significantly decreased pain and improved function as compared with the placebo and control groups . The qualitative Depth interview confirmed this result . CONCLUSION Despite the small numbers , significant differences were found in improvement in function and pain for patients receiving therapeutic touch . A larger study is needed to confirm these results . Alternative therapies can neither be accepted nor rejected without being subjected to the scientific method Objectives To assess the efficacy of a self-management group intervention in improving physical functioning , mood , and pain among elderly persons with chronic pain , and to identify factors that may be associated with improvement . Material s and Methods Forty-five residents of three retirement communities ( 86 % women ; mean age , 82.0 years ) were assigned r and omly to a 7-week pain self-management group or an educational booklet control condition . Participants completed self-report measures of pain , functioning , depression , and pain-related beliefs at baseline , 9 weeks later ( after treatment ) , and 3 months after the post-treatment assessment . Results The self-management group showed significantly greater pre- to post-treatment improvement in physical role function ( P = 0.04 ) and characteristic pain intensity ( P = 0.02 ) . No significant differences were found between groups on measures of pain-related activity interference , depression , and pain-related beliefs . Improvement in characteristic pain and physical role function was not associated with baseline depression scores , pretreatment expectations , or changes in pain-related beliefs . Discussion This study provides preliminary support for the efficacy of a self-management group intervention for older adults with chronic pain and has implication s for future studies of such approaches for this and similar population It is well established that the treatment of pain is improved by the incorporation of psychological , social and behavioural components in that treatment ( Rosenthiel and Keefe ) , 1983 ) . However , until very recently , the management of sickle cell disease ( SCD ) in British hospitals has focused exclusively on the physical dimension of pain ( Thomas et al , 1998 ) . Although pain is wrong ( vaso-occlusive crisis ) , every individual reacts in a different way . This reaction is influenced in part by immediate role models , usually within the family , and by a person 's cognition ( thought patterns , beliefs and expectations ) in relation to the pain . This paper presents research that has shown that cognitive behavioural therapy ( CBT ) in SCD is an effective aid in the treatment of chronic pain , reducing psychological distress and boosting confidence STUDY DESIGN A r and omized controlled trial , prestest-posttest design , with a 3- , 6- , and 12-month follow-up . OBJECTIVES To investigate the efficacy of a therapeutic exercise approach in a population with chronic low back pain ( LBP ) . BACKGROUND Therapeutic approaches developed from the Pilates method are becoming increasingly popular ; however , there have been no reports on their efficacy . METHODS AND MEASURES Thirty-nine physically active subjects between 20 and 55 years old with chronic LBP were r and omly assigned to 1 of 2 groups . The specific-exercise-training group participated in a 4-week program consisting of training on specialized ( Pilates ) exercise equipment , while the control group received the usual care , defined as consultation with a physician and other specialists and healthcare professionals , as necessary . Treatment sessions were design ed to train the activation of specific muscles thought to stabilize the lumbar-pelvic region . Functional disability outcomes were measured with The Rol and Morris Disability Question naire ( RMQ/RMDQ-HK ) and average pain intensity using a 101-point numerical rating scale . RESULTS There was a significantly lower level of functional disability ( P = .023 ) and average pain intensity ( P = .002 ) in the specific-exercise-training group than in the control group following the treatment intervention period . The posttest adjusted mean in functional disability level in the specific-exercise-training group was 2.0 ( 95 % CI , 1.3 to 2.7 ) RMQ/RMDQ-HK points compared to a posttest adjusted mean in the control group of 3.2 ( 95 % CI , 2.5 to 4.0 ) RMQ/RMDQ-HK points . The posttest adjusted mean in pain intensity in the specific-exercise-training group was 18.3 ( 95 % CI , 11.8 to 24.8 ) , as compared to 33.9 ( 95 % CI , 26.9 to 41.0 ) in the control group . Improved disability scores in the specific-exercise-training group were maintained for up to 12 months following treatment intervention . CONCLUSIONS The individuals in the specific-exercise-training group reported a significant decrease in LBP and disability , which was maintained over a 12-month follow-up period . Treatment with a modified Pilates-based approach was more efficacious than usual care in a population with chronic , unresolved LBP OBJECTIVE To evaluate the effectiveness of a disease management model for primary headache by : ( 1 ) assessing improvement in patients ' quality of life , ( 2 ) decreasing headache-related visits to primary care and emergency departments , and ( 3 ) maintaining high levels of patient and physician satisfaction . BACKGROUND Patients with headache regularly seek health care but , in general , are dissatisfied with the care they receive . Patients with primary headaches utilize re sources and cost health plans more than patients with other chronic diseases . Primary care visits are time restricted , prohibiting adequate headache evaluation and management . Practice guidelines are inconsistently followed , and access to headache specialists is limited . This headache management program implemented an alternative means of delivering care to manage large volumes of patients with headache . A multidisciplinary team approach coordinated by a neurologist , utilizing education and a nurse practitioner as the main provider of care , was the central process of the program . METHODS This was a pilot study involving a prospect i ve cohort with defined outcome measures . Inclusion criteria were adult patients with primary headaches . Patients initially attended an educational session instructed by a neurologist and a nurse practitioner . The patient was subsequently evaluated by the nurse practitioner who developed and coordinated a comprehensive individual treatment plan . The Migraine-Specific Quality of Life and the Medical Outcomes Study 36-Item Short Form Question naires were completed at baseline , at follow-up visits , and 6 months after completion of the program . Subjective patient assessment of improvement in their headaches , chart review for tabulation of headache-related visits , and primary care physician satisfaction surveys were measured . RESULTS Both the Migraine-Specific question naire and the Short Form-36 measurements demonstrated a statistically significant improvement at 8 weeks , and this was maintained for 6 months after completing the program . At completion of the program , 92 % of patients reported subjective improvement . Patient visits for headaches to primary care and emergency departments showed a significant decrease . High levels of satisfaction for primary care physicians were achieved . CONCLUSIONS A disease management model using a multidisciplinary team improved individualized patient care . This model increased patient/provider rapport and communication through an educational class . It empowered the patient to take control of their health care by utilizing shared decision making . Patient satisfaction improved and overall health care utilization was reduced OBJECTIVE To test the effectiveness of a multidisciplinary management program for migraine treatment in a group , low cost , non clinical setting . DESIGN A prospect i ve , r and omized , clinical trial . BACKGROUND Although numerous studies document the efficacy of pharmacological migraine management , it is unclear whether an effective long-term management approach exists . METHODS Eighty men and women were r and omly assigned to 1 of 2 groups . The intervention group consisted of a neurologist and physical therapist intake and discharge , 18 group-supervised exercise therapy sessions , 2 group stress management and relaxation therapy lectures , 1 group dietary lecture , and 2 massage therapy sessions . The control group consisted of st and ard care with the patient 's family physician . Outcome measures included self-perceived pain intensity , frequency , and duration ; functional status ; quality of life ; health status ; depression ; prescription and nonprescription medication use ; and work status . Outcomes were measured at the end of the 6-week intervention and at a 3-month follow-up . Results .-Forty-one of 44 patients from the intervention group and all 36 patients from the control group completed the study . There were no statistically significant differences between the 2 groups before intervention . Intention to treat analysis revealed that the intervention group experienced statistically significant changes in self-perceived pain frequency ( P = .000 ) , pain intensity ( P = .001 ) , pain duration ( P = .000 ) , functional status ( P = .000 ) , quality of life ( P = .000 ) , health status ( P = .000 ) , pain related disability ( P = .000 ) , and depression ( P = .000 ) ; these differences retained their significance at the 3-month follow-up . There were no statistically significant changes in medication use or work status . CONCLUSIONS Positive health related outcomes in migraine can be obtained with a low cost , group , multidisciplinary intervention in a community based non clinical setting Abstract This r and omised controlled study investigated the effect of outpatient multidisciplinary pain centre treatment ( MPT ) compared with treatment by a general practitioner after initial supervision by a pain specialist ( GP‐group ) and with a group of patients waiting for 6 months before treatment was initiated ( WL‐group ) . One‐hundred‐ and ‐eighty‐nine chronic non‐malignant pain patients were studied . At referral , and after 3 and 6 months patients filled in question naires evaluating pain intensity , health related quality of life ( HRQL ) and use of analgesics . HRQL was evaluated using the Medical Outcome Study ‐Short Form ( SF‐36 ) , the Hospital Anxiety and Depression scale ( HAD ) and the Psychological General Well‐being Scale ( PGWB ) . After 6 months patients allocated to MPT ( n=63 ) reported statistically significant reduction in pain intensity ( VAS‐score , P<0.001 ) , improvement in psychological well‐being ( PGWB , P<0.001 ) , quality of sleep ( P<0.05 ) and physical functioning ( SF‐36‐Phycical Functioning , P<0.05 ) . No improvements were seen in the GP‐group ( n=63 ) . In the WL‐group ( n=63 ) a statistically significant deterioration was observed in PGWB‐scores , HAD‐scores and in 6 of 8 SF‐36‐subscores ( P ≤ 0.05 ) . A reduction in use of opioids administered on dem and was obtained in the group receiving MPT ( P<0.001 ) . In the MPT‐ and GP‐groups a decrease in the use of short acting opioids was observed ( P<0.01 ) . No change in use of analgesics was seen in the WL‐group . The study showed that ( i ) in the MPT‐group there was a significant reduction in pain intensity and improvement of HRQL compared to the WL‐group , and ( ii ) the mere establishment of a pain diagnosis and a pain management plan by a pain specialist was not sufficient to enable the referring GP to manage severely chronic pain patients Study Design : A r and omized between-groups design evaluated massage therapy versus relaxation for chronic low back pain . Objectives : Treatment effects were evaluated for reducing pain , depression , anxiety and stress hormones , and sleeplessness and for improving trunk range of motion associated with chronic low back pain . Summary of Background Data : Twenty-four adults ( M age = 39.6 years ) with low back pain of nociceptive origin with a duration of at least 6 months participated in the study . The groups did not differ on age , socioeconomic status , ethnicity or gender . Methods : Twenty-four adults ( 12 women ) with lower back pain were r and omly assigned to a massage therapy or a progressive muscle relaxation group . Sessions were 30 minutes long twice a week for five weeks . on the first and last day of the 5-week study participants completed question naires , provided a urine sample and were assessed for range of motion . Results : By the end of the study , the massage therapy group , as compared to the relaxation group , reported experiencing less pain , depression , anxiety and improved sleep . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher . Conclusions : Massage therapy is effective in reducing pain , stress hormones and symptoms associated with chronic low back pain . Precis : Adults ( M age = 39.6 years ) with low back pain with a duration of at least 6 months received two 30-min massage or relaxation therapy sessions per week for 5 weeks . Participants receiving massage therapy reported experiencing less pain , depression , anxiety and their sleep had improved . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher Abstract Objective To determine the effectiveness of commercially available magnetic bracelets for pain control in osteoarthritis of the hip and knee . Design R and omised , placebo controlled trial with three parallel groups . Setting Five rural general practice s. Participants 194 men and women aged 45 - 80 years with osteoarthritis of the hip or knee . Intervention Wearing a st and ard strength static bipolar magnetic bracelet , a weak magnetic bracelet , or a non-magnetic ( dummy ) bracelet for 12 weeks . Main outcome measures Change in the Western Ontario and McMaster Universities osteoarthritis lower limb pain scale ( WOMAC A ) after 12 weeks , with the primary comparison between the st and ard and dummy groups . Secondary outcomes included changes in WOMAC B and C scales and a visual analogue scale for pain . Results Mean pain scores were reduced more in the st and ard magnet group than in the dummy group ( mean difference 1.3 points , 95 % confidence interval 0.05 to 2.55 ) . Self reported blinding status did not affect the results . The scores for secondary outcome measures were consistent with the WOMAC A scores . Conclusion Pain from osteoarthritis of the hip and knee decreases when wearing magnetic bracelets . It is uncertain whether this response is due to specific or non-specific ( placebo ) effects Purpose : The sensory environment ( Snoezelen ) has been advocated by those working in the field of learning disabilities and mental health as a strategy to induce relaxation . The purpose of the current study was to explore this potential within the field of pain management where the use of relaxation techniques is often employed as a strategy for the management of chronic pain . Thus the current study was design ed in order to determine the use of the sensory environment compared against a traditional relaxation programme used within a District General hospital pain clinic . Method : Seventy three patients were r and omly allocated into either a control or experimental group . Data collection involved the administration of question naires , which were selected in order to reflect the multidimensional nature of the chronic pain experience . Hence measures included : pain intensity , pain quality , anxiety , depression , self-efficacy , coping and sickness impact . Analysis was performed using SPSS and included Friedman two-way analysis and repeated measures analysis of variance . Results : The results indicated that the experimental group experienced a significant increase in pain ( p = 0.03 ) , but they improved significantly in disability associated with sleep ( p = 0.01 ) , psychosocial ( p = 0.03 ) and sickness impact total ( p = 0.004 ) . The experimental group experienced a significant decrease in pain ( sensory - p = 0.002 ) , ( number of words chosen - p = 0 . 008 ) , ( pain rating index - p = 0.002 ) . Furthermore a reduction in disability associated with physical ( p = 0.009 ) , psychosocial ( p = 0.009 ) , sleep ( p = 0.001 ) , recreation ( p = 0.001 ) and SIP total ( p = 0.001 ) . Repeated measures analysis of variance revealed a significant improvement with the experimental group in terms of pain ( p = 0.04 ) and self-efficacy ( p = 0.02 ) . Conclusions : The patients who attended the sensory environment did slightly better that those who attended the traditional relaxation programme in terms of self-efficacy . Thus the current study indicates the potential for future research into chronic pain management OBJECTIVE To determine whether the addition of patient education to routine medical management improves the clinical status of migraine patients and reduces their utilization of healthcare re sources . BACKGROUND Optimal migraine management typically requires effective patient education . Such education often is difficult to accomplish in the busy clinic setting . METHODS One hundred consecutive patients with migraine presenting to an university-based headache clinic were r and omized to receive or not receive a st and ardized course of didactic instruction regarding migraine biogenesis and management . The course consisted of 3 classes taught by lay migraineurs who themselves previously had undergone intensive training . All patients were evaluated initially and at 1 , 3 , and 6 months by a neurologist blinded as to the results of r and omization . Clinical variables examined included headache frequency/severity , migraine disability assessment ( MIDAS ) scores , patient compliance , presence versus absence of analgesic use/overuse , and headache-related unscheduled visits or phone calls . Comparisons were made between baseline findings and findings at the 6-month follow-up visit , with the change in mean MIDAS score serving as the primary outcome variable . RESULTS At 6 months the group r and omized to receive intensive education exhibited a significantly greater reduction in mean MIDAS score than the group r and omized to routine medical management only ( 24 vs. 14 points ; P < .05 ) . Those patients also experienced a reduction in mean headache days per month and a greater reduction in functionally incapacitating headache days per month , exhibited less analgesic overuse and need for abortive therapy , were more compliant with prophylactic therapy prescribed , and made fewer headache-related calls to the clinic or unscheduled visits . CONCLUSION Intensive education of migraine patients by trained lay instructors may convey significant benefit to those patients and reduce their utilization of healthcare re sources Study Design . Cluster r and omized controlled trial . Objective . To improve quality of care for patients with low back pain ( LBP ) a multifaceted general practitioner education alone and in combination with motivational counseling by practice nurses has been implemented in German general practice s. We studied effects on functional capacity ( main outcome ) , days in pain , physical activity , quality of life , or days of sick leave ( secondary outcomes ) compared with no intervention . Summary of Background Data . International research has lead to the development of the German LBP guideline for general practitioners . However , there is still doubt about the most effective implementation strategy . Although effects on process of care have been observed frequently , changes in patient outcomes are rarely seen . Methods . We recruited 1378 patients with LBP in 118 general practice s , which were r and omized to 1 of 3 study arms : a multifaceted guideline implementation ( GI ) , GI plus training of practice nurses in motivational counseling ( MC ) , and the postal dissemination of the guideline ( controls , C ) . Data were collected ( question naires and patient interviews ) at baseline and after 6 and 12 months . Multilevel mixed effects modeling was used to adjust for clustering of data and potential confounders . Results . After 6 months , functional capacity was higher in the intervention groups with a cluster adjusted mean difference of 3.650 between the MC group and controls ( 95 % CI = 0.320–6.979 , P = 0.032 ) and 2.652 between the GI group and controls ( 95 % CI = −0.704 to 6.007 , P = 0.120 ) . Intervention effects were more pronounced regarding days in pain per year with an average reduction of 16 ( GI ) to 17 days ( MC ) after 6 months ( 12 and 9 days after 12 months ) compared with controls . Conclusion . Active implementation of the German LBP guideline results in slightly better outcomes during 6 months follow-up than its postal dissemination . Results are more distinct when practice nurses are trained in motivational counseling OBJECTIVES ( 1 ) To investigate the effects of a 6-week intervention of guided imagery on pain level , functional status , and self-efficacy in persons with fibromyalgia ( FM ) ; and ( 2 ) to explore the dose-response effect of imagery use on outcomes . DESIGN Longitudinal , prospect i ve , two-group , r and omized , controlled clinical trial . SETTING AND SUBJECTS The sample included 48 persons with FM recruited from physicians ' offices and clinics in the mid-Atlantic region . INTERVENTION Participants r and omized to Guided Imagery ( GI ) plus Usual Care intervention group received a set of three audiotaped guided imagery scripts and were instructed to use at least one tape daily for 6 weeks and report weekly frequency of use ( dosage ) . Participants assigned to the Usual Care alone group su bmi tted weekly report forms on usual care . MEASURES All participants completed the Short-Form McGill Pain Question naire ( SF-MPQ ) , Arthritis Self- Efficacy Scale ( ASES ) , and Fibromyalgia Impact Question naire ( FIQ ) , at baseline , 6 , and 10 weeks , and su bmi tted frequency of use report forms . RESULTS FIQ scores decreased over time in the GI group compared to the Usual Care group ( p = 0.03 ) . Ratings of self-efficacy for managing pain ( p = 0.03 ) and other symptoms of FM also increased significantly over time ( p = < 0.01 ) in the GI group compared to the Usual Care group . Pain as measured by the SF-MPQ did not change over time or by group . Imagery dosage was not significant . CONCLUSIONS This study demonstrated the effectiveness of guided imagery in improving functional status and sense of self-efficacy for managing pain and other symptoms of FM . However , participants ' reports of pain did not change . Further studies investigating the effects of mind-body interventions as adjunctive self-care modalities are warranted in the fibromyalgia patient population This pilot study assessed the role of Healing Touch ( HT ) , an energy-based therapy , in modulating chronic neuropathic pain and the associated psychological distress from post spinal cord injury . Twelve veterans were assigned to either HT or guided progressive relaxation for six weekly home visits . The instruments selected showed sensitivity , although there was a large variation among the groups . There was a significant difference in the composite of interference on the Brief Pain Inventory ( t = -2.71 , p = .035 ) . The mean score of the fatigue subscale of the Profile of Moods decreased ( ns ) in the HT group and in the subscale of confusion yet remained stable in the control group . The Diener Satisfaction With Life Scale showed increased well-being in the HT group and no change in the control group . Participants reported various experiences with HT sessions indicating that it may have benefit in the complex response to chronic pain & NA ; Although chronic pain is a frequent cause of suffering and disability and is costly to society , there continues to be limited access to specialty pain clinic services . Hence , there is a need for cost‐effective , accessible interventions that will help people find ways to better manage this difficult problem . This r and omized controlled trial examined the effect of a low‐cost , community‐based , nurse‐delivered , group psychoeducation program entitled the Chronic Pain Self‐Management Program ( CPSMP ) . It has a st and ard protocol that was modified from the successful Arthritis Self‐Management Program ( ASMP ) . One hundred and ten individuals with mixed idiopathic chronic pain conditions were enrolled in the study ( 75 % female ; mean age 40 years ; mean chronicity 6 years ) and were r and omly assigned to one of two conditions : the 12‐h ( CPSMP ) intervention group , or the 3‐month wait‐list control group . Self‐report measures of pain‐related and other quality of life variables as well as two hypothesized mediating variables were collected pre‐treatment and 3 months later by assessors blind to group allocation . One hundred and two subjects completed the study . Results of intention‐to‐treat analysis indicated that the treatment group made significant short‐term improvements in pain , dependency , vitality , aspects of role functioning , life satisfaction and in self‐efficacy and re source fulness as compared to the wait‐list control group . Because it has a st and ard protocol , this intervention has the potential to be reliably delivered at low cost in varied urban and rural community setting s and hence be more widely accessible to a greater number of people suffering from chronic pain than is currently the case with more specialized pain clinic services . Based on the results of this study , further research evaluating the long‐term impact and potential cost savings to the individual and to the health care system is warranted Qi therapy ( or external Qi ) is an oriental complementary therapy preventing , curing disease and strengthens health and improving the human potentiality through regulation of body . It is increasingly being used to improve the quality of life , but there is little direct evidence of its efficacy . This study assessed the effects of Qi therapy ( QT ) on reducing pain and enhancing mood states in elderly subjects with chronic pain . We studied 40 elderly participants with chronic pain , who were r and omly allocated to receive QT ( n=20 ) or st and ard care ( n=20 ) . The experimental group receives Qi therapy twice a week for 2 weeks ( total 4 times ) , and control group received general care at the same time and the same amount of duration . We measured pain level and Profile of Mood State ( POMS ) to explore participants ' response to Qi therapy . There was a significant reduction in pain ( p<0.0001 ) after QT and an improved positive mood state ( p<0.0001 ) . These findings suggest that Qi therapy may have a role in helping the elderly to cope with their pain and mood disturbances & NA ; Back pain is a significant health care problem that has been managed unsatisfactorily in primary care setting s. Providers typically address medical issues but do not adequately address patient concerns or functional limitations related to back pain . We evaluated a brief intervention for primary care back pain patients design ed to provide accurate information about back pain , instill attitudes favorable towards self care , reduce fears and worries , assist patients in developing personalized action plans to manage their back pain , and improve functional outcomes . Patients enrolled in a large health maintenance organization were invited to participate in an educational program to improve back pain self care skills 6–8 weeks after a primary care back pain visit . Patients ( n=226 ) were r and omly assigned to a Self Care intervention or to Usual Care , and were assessed at baseline , 3‐ , 6‐ , and 12‐months . The intervention involved a two‐session Self Care group and an individual meeting and telephone conversation with the group leader , a psychologist experienced in chronic pain management . The intervention was supplemented by educational material s ( book and videos ) supporting active management of back pain . The control group received usual care supplemented by a book on back pain care . Participants assigned to the Self Care intervention showed significantly greater reductions in back‐related worry and fear‐avoidance beliefs than the control group . Modest , but statistically significant , effects on pain ratings and interference with activities were also observed Chronic pain can be devastating , it impinges upon the life of the sufferer , causing psychological , physical , social and financial problems , leaving the individual search ing for an explanation and a cure . Although there are no major epidemiological studies to date , it has been suggested that the impact of chronic pain , not only to the patient , but also to society and the NHS is phenomenal , with loss of production and costs of treatments ( Fordyce 1995 ) . Specialists within the field of chronic pain have advocated the use of the multidisciplinary approach to deal with the problems and thus suggest the use of the pain management programme , which is design ed to teach the patient coping strategies . Recently , however , there has been a call within the literature to identify the effectiveness of singular strategies , which may be equally as effective and less expensive ( Keefe et al 1992 ) . The purpose of these papers is to introduce one such strategy , which has been evaluated over the past four years in order to investigate the use of the sensory environment ( Snoezelen ) for the management of chronic pain . In part II of this paper , an evaluation of Snoezelen and chronic pain will be presented , along with the findings of an investigation into its use This experimental study investigated the use of Snoezelen - a sensory environment purported to produce relaxation - against traditional relaxation within the pain clinic setting . The variables measured included pain , anxiety , depression , coping , self-efficacy and disability . Assessment s were carried out at three time intervals on a range of symptoms design ed to reflect the multidimensional nature of the chronic pain experience , including pain intensity and quality , anxiety , depression , coping , confidence and quality of life . The experimental group experienced significant reductions in pain ( sensory score P=0.002 ) , and an improvement in self-efficacy ( P=0.02 ) and sickness impact for the following scales : physical ( P=0.009 ) , psychosocial ( P=0.009 ) , recreation ( P=0.001 ) , sleep ( P=0.001 ) and sickness impact total ( P=0.001 ) . The control group experienced significant improvements in sickness impact scales of psychosocial ( P=0.05 ) , sleep ( P=0.01 ) and sickness impact total ( P=0.004 ) . The findings suggest that Snoezelen environments are as effective as , if not slightly better than , teaching relaxation within the traditional pain clinic environment for this group of patients Background To determine whether music influences intraoperative sedative and analgesic requirements , two r and omized controlled trials were performed . Methods In phase 1 , 35 adults undergoing urologic procedures with spinal anesthesia and patient‐controlled intravenous propofol sedation were r and omly assigned to hear favorable intraoperative music via headset or to have no music . In phase 2 , 43 adults undergoing lithotripsy treatment of renal or ureteral calculi and receiving patient‐controlled intravenous opioid analgesia were r and omly assigned to either a music or no‐music group . The effect of music on sedatives and analgesics requirements , recovery room duration , and adverse outcomes was assessed . Results In phase 1 , patients in the music group required significantly less propofol for sedation than patients in the control group ( 0 [ 0–150 ] mg vs. 90 [ 0–240 ] mg , median[range ] ; P < 0.001 ) . These findings persisted after adjusting for duration of surgery ( 0.3 + /‐ 0.1 mg/min vs. 1.6 + /‐ 0.4 mg/min ; P < 0.001 ) . Similarly , in phase 2 , patients who listened to music had a significant reduction in alfentanil requirements ( 1,600 [ 0–4,250 ] [ micro sign]g vs. 3,900 [ 0–7,200 ] [ micro sign]g ; P = 0.005 ) . This persisted after adjusting for duration of surgery ( 52 + /‐ 9 [ micro sign]g/min vs. 119 + /‐ 16 [ micro sign]g/min , mean + /‐ SD , P < 0.001 ) . Duration of stay in the postanesthesia care unit and the rate of adverse events was similar in both groups ( P = NS ) . Conclusions Use of intraoperative music in awake patients decreases patient‐controlled sedative and analgesic requirements . It should be noted , however , that patients in the no‐music group did not use a headset during operation . Thus , the decrease in sedative and analgesic requirements could be caused by elimination of ambient operating room noise and not by the effects of music This pilot study tested the effectiveness of 6 therapeutic touch treatments on the experience of pain and quality of life for persons with fibromyalgia syndrome . Its findings support that subjects who received therapeutic touch had a statistically significant decrease in pain for each pretherapeutic to posttherapeutic touch treatment , as well as significant improvement in quality of life from pre-first to pre-sixth treatment . Therapeutic touch may be an effective treatment for relieving pain and improving quality of life in this specific population of persons with fibromyalgia syndrome OBJECTIVE To determine the effect of adjuvant guided imagery on patients with chronic tension-type headache . BACKGROUND Management of chronic tension-type headache often requires a combination of pharmacological and nonpharmacological therapies . Guided imagery is a relaxation technique based on visualizing pleasant images and body awareness . METHODS One hundred twenty-nine patients with chronic tension-type headache completed the Headache Disability Inventory and the Medical Outcomes Study Short Form ( SF-36 ) at their initial visit to a specialty headache center and again 1 month after the visit . In addition to individualized headache therapy , patients listened to a guided imagery audiocassette tape daily for the month . One hundred thirty-one control subjects received individualized therapy without guided imagery . RESULTS Controls and the patients who listened to the guided imagery tape improved in headache frequency , headache severity , patient global assessment , quality of life , and disability caused by headache . More guided imagery patients ( 21.7 % ) than controls ( 7.6 % ) reported that their headaches were much better ( P = .004 ) . The guided imagery patients had significantly more improvement than the controls in three of the SF-36 domains : bodily pain ( 95 % CI ; guided imagery patients 11.0 , controls 0.2 ) , vitality ( 95 % CI ; guided imagery patients 10.9 , controls 1.7 ) , and mental health ( 95 % CI ; guided imagery patients 7.8 , controls 0.4 ) . CONCLUSIONS Guided imagery is an effective adjunct therapy for the management of chronic tension-type headache This study explored whether there is a significant difference in perceived low back pain relief between patients receiving massage versus traditional therapy , using a 2-variable by 3-variable fully crossed , factorial , comparative research design . Statistical results showed slightly more efficacy for traditional therapy ; however , the additional benefits of massage add to its value for holistic nursing practice OBJECTIVE To determine the feasibility of developing a headache management program and to assess the outcomes of patients referred to the program for treatment of chronic headache . BACKGROUND Effective headache treatment requires that the patient receives the correct headache diagnosis ; that appropriate acute and , if indicated , preventive medications be prescribed ; and that the patient receives adequate education , including headache self-management skills . DESIGN / METHODS A headache management program was established at a northern California staff-model health maintenance organization . Fifty-four patients were enrolled in the program and followed for 6 months . Patients participated in a structured program of group and individual sessions with the program manager . Data collection at baseline and 6 months included the Migraine Disability Assessment ( MIDAS ) , the Short Form-36 Health Survey ( SF-36 ) , a patient satisfaction survey , and 2 additional short surveys -- one that assessed patient worries about their headaches and another that queried patients on their problems with headache management . RESULTS All enrolled patients participated in the initial group visit ; 74 % had at least one additional visit . All but one patient suffered from more than one headache type . Sixty-one percent of patients suffered from migraine headache and 98 % from tension-type headache . At baseline , patients were severely disabled , with a mean MIDAS score of 41 . At 6 months , MIDAS scores decreased an average of 21.2 points ( P < .005 ) . Patients reported 14.5 fewer days with headache over the preceding 3 months ( P < .0001 ) and experienced clinical ly significant improvements in 6 of the SF-36 subscales . Patients were significantly more satisfied with their headache care ( P < .0001 ) , reported less problems with their headache management ( P < .0001 ) , and were less worried about their headaches ( P < .01 ) . During the intervention , emergency department visits for headache decreased ( P < .02 ) . CONCLUSIONS A headache management program was successfully established . Patients referred to the program experienced significant improvement in headache-related disability and functional health status and reported greater satisfaction with care . Even so , these results were obtained at one site and in a small sample that was not r and omized . We currently are conducting a r and omized controlled trial to better evaluate the clinical and financial impact of a headache management program for patients with chronic headache Study Design . Pragmatic , r and omized , assessor blinded , clinical trial with economic analysis . Objective . To compare the effectiveness and cost-effectiveness of three kinds of physiotherapy commonly used to reduce disability in chronic low back pain . Summary of Background Data . Physiotherapy reduces disability in chronic back pain , but there are several forms of physiotherapy and it is unclear which is most effective or cost effective . Methods . A total of 212 patients referred to physiotherapy with chronic low back pain were r and omized to receive usual outpatient physiotherapy , spinal stabilization classes , or physiotherapist-led pain management classes . Primary outcome was Rol and Disability Question naire score 18 months from baseline ; secondary measures were pain , health-related quality of life , and time off work . Healthcare costs associated with low back pain and quality -adjusted life years ( QALYs ) were also measured . Results . A total of 71 participants were assigned to usual outpatient physiotherapy , 72 to spinal stabilization , and 69 to physiotherapist-led pain management . A total of 160 ( 75 % ) provided follow-up data at 18 months , showing similar improvements with all interventions : mean ( 95 % confidence intervals ) Rol and Disability Question naire score improved from 11.1 ( 9.6–12.6 ) to 6.9 ( 5.3–8.4 ) with usual outpatient physiotherapy , 12.8 ( 11.4−14.2 ) to 6.8 ( 4.9–8.6 ) with spinal stabilization , and 11.5 ( 9.8–13.1 ) to 6.5 ( 4.5–8.6 ) following pain management classes . Pain , quality of life , and time off work also improved within all groups with no between-group differences . Mean ( SD ) healthcare costs and QALY gain were £ 474 ( 840 ) and 0.99 ( 0.27 ) for individual physiotherapy , £ 379 ( 1040 ) and 0.90 ( 0.37 ) for spinal stabilization , and £ 165 ( 202 ) and 1.00 ( 0.28 ) for pain management . Conclusions . For chronic low back pain , all three physiotherapy regimens improved disability and other relevant health outcomes , regardless of their content . Physiotherapist-led pain management classes offer a cost-effective alternative to usual outpatient physiotherapy and are associated with less healthcare use . A more widespread adoption of physiotherapist-led pain management could result in considerable cost savings for healthcare providers Nurses routinely use a variety of nonpharmacologic and patient education interventions design ed to reduce pain and promote independence . Research on group programs that combine these nursing strategies in a systematic approach provides evidence that chronic pain patients can realize an enhanced confidence in their ability to manage pain ( improved self-efficacy ) in addition to reductions in pain , emotional distress , and disability . The purpose of this study was to investigate the effect of participating in a nurse-led cognitive-behavioral treatment ( CBT ) pain management program on self-efficacy , pain intensity , pain-related disability , and depressive symptoms among patients with chronic pain . Pre- and postprogram data from 154 participants were examined to identify changes in pain intensity , self-efficacy , disability , and depressive symptoms . Mean differences , effect sizes , and 95 % confidence intervals were computed for the study variables and paired t-tests were done to determine if changes were significant . Z-scores were then calculated . Pearson product moment correlations were examined to test the association between changes in self-efficacy and changes in the other variables of interest . Patients in this study reported significant improvements in all scores postprogram . Self-efficacy , pain-intensity , pain-related disability , and symptoms of depression can be changed through participation in a nurse-led outpatient CBT program . In concert with results from other research on CBT pain programs this study provides further evidence that reduction in suffering and improved sense of well-being is possible even for people who have experienced pain for many years & NA ; Recent developments in chronic pain research suggest that effectiveness of cognitive‐behavioral therapy ( CBT ) may be optimized when applying early , customized treatments to patients at risk . For this purpose , a r and omized , controlled trial with tailor‐made treatment modules was conducted among patients with relatively early rheumatoid arthritis ( RA disease duration of < 8 years ) , who had been screened for psychosocial risk profiles . All participants received st and ard medical care from a rheumatologist and rheumatology nurse consultant . Patients in the CBT condition additionally received an individual CBT treatment with two out of four possible treatment modules . Choice of treatment modules was determined on the basis of patient priorities , which result ed in most frequent application of the fatigue module , followed by the negative mood , social relationships and pain and functional disability modules . Analyses of completers and of intention‐to‐treat revealed beneficial effects of CBT on physical , psychological and social functioning . Specifically , fatigue and depression were significantly reduced at post‐treatment and at the 6‐month follow‐up in the CBT condition in comparison to the control condition , while perceived support increased at follow‐up assessment . In addition , helplessness decreased at post‐treatment and follow‐up assessment , active coping with stress increased at post‐treatment , and compliance with medication increased at follow‐up assessment in the CBT condition in comparison to the control condition . Results indicate the effectiveness of tailor‐made CBT for patients at risk in relatively early RA , and supply preliminary support for the idea that customizing treatments to patient characteristics may be a way to optimize CBT effectiveness in RA patients Study Design . R and omized clinical trial . Objectives . To compare the effects of spinal manipulation combined with low-tech rehabilitative exercise , MedX rehabilitative exercise , or spinal manipulation alone in patient self-reported outcomes over a two-year follow-up period . Summary of Background Data . There have been few r and omized clinical trials of spinal manipulation and rehabilitative exercise for patients with neck pain , and most have only reported short-term outcomes . Methods . One hundred ninety-one patients with chronic neck pain were r and omized to 11 weeks of one of the three treatments . Patient self-report question naires measuring pain , disability , general health status , improvement , satisfaction , and OTC medication use were collected after 5 and 11 weeks of treatment and 3 , 6 , 12 , and 24 months after treatment . Data were analyzed taking into account all time points using repeated measures analyses . Results . Ninety-three percent ( 178 ) of r and omized patients completed the 11-week intervention phase , and 76 % ( 145 ) provided data at all evaluation time points over the two-year follow-up period . A difference in patient-rated pain with no group-time interaction was observed in favor of the two exercise groups [ F(2141 ) = 3.2;P = 0.04 ] . There was also a group difference in satisfaction with care [ F(2143 ) = 7.7;P = 0.001 ] , with spinal manipulation combined with low-tech rehabilitative exercise superior to MedX rehabilitative exercise ( P = 0.02 ) and spinal manipulation alone ( P < 0.001 ) . No significant group differences were found for neck disability , general health status , improvement , and OTC medication use , although the trend over time was in favor of the two exercise groups . Conclusion . The results of this study demonstrate an advantage of spinal manipulation combined with low-tech rehabilitative exercise and MedX rehabilitative exercise versus spinal manipulation alone over two years and are similar in magnitude to those observed after one-year follow-up . These results suggest that treatments including supervised rehabilitative exercise should be considered for chronic neck pain sufferers . Further studies are needed to examine the cost effectiveness of these therapies and how spinal manipulation compares to no treatment or minimal intervention |
10,999 | 30,049,703 | Conclusions In patients aged < 60 years , PFO closure probably confers an important reduction in ischaemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation .
PFO closure incurs a risk of persistent atrial fibrillation and device-related adverse events .
Compared with alternatives , anticoagulation probably increases major bleeding . | Objective To examine the relative impact of three management options in patients aged < 60 years with cryptogenic stroke and a patent foramen ovale ( PFO ) : PFO closure plus antiplatelet therapy , antiplatelet therapy alone and anticoagulation alone . | BACKGROUND Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown . We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age . METHODS In this prospect i ve , multicenter , r and omized , event-driven trial , we r and omly assigned patients , in a 1:1 ratio , to medical therapy alone or closure of the patent foramen ovale . The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . The medical-therapy group received one or more antiplatelet medications ( 74.8 % ) or warfarin ( 25.2 % ) . Treatment exposure between the two groups was unequal ( 1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group , P=0.009 ) owing to a higher dropout rate in the medical-therapy group . In the intention-to-treat cohort , 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke ( hazard ratio with closure , 0.49 ; 95 % confidence interval [ CI ] , 0.22 to 1.11 ; P=0.08 ) . The between-group difference in the rate of recurrent stroke was significant in the prespecified per- protocol cohort ( 6 events in the closure group vs. 14 events in the medical-therapy group ; hazard ratio , 0.37 ; 95 % CI , 0.14 to 0.96 ; P=0.03 ) and in the as-treated cohort ( 5 events vs. 16 events ; hazard ratio , 0.27 ; 95 % CI , 0.10 to 0.75 ; P=0.007 ) . Serious adverse events occurred in 23.0 % of the patients in the closure group and in 21.6 % in the medical-therapy group ( P=0.65 ) . Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group ( 4.2 % ) , but the rate of atrial fibrillation or device thrombus was not increased . CONCLUSIONS In the primary intention-to-treat analysis , there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke . However , closure was superior to medical therapy alone in the prespecified per- protocol and as-treated analyses , with a low rate of associated risks . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . ) 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 BACKGROUND Trials of patent foramen ovale ( PFO ) closure to prevent recurrent stroke have been inconclusive . We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation , as compared with antiplatelet therapy . METHODS In a multicenter , r and omized , open‐label trial , we assigned , in a 1:1:1 ratio , patients 16 to 60 years of age who had had a recent stroke attributed to PFO , with an associated atrial septal aneurysm or large interatrial shunt , to transcatheter PFO closure plus long‐term antiplatelet therapy ( PFO closure group ) , antiplatelet therapy alone ( antiplatelet‐only group ) , or oral anticoagulation ( anticoagulation group ) ( r and omization group 1 ) . Patients with contraindications to anticoagulants or to PFO closure were r and omly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy ( r and omization groups 2 and 3 ) . The primary outcome was occurrence of stroke . The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from r and omization groups 1 and 2 , and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from r and omization groups 1 and 3 . RESULTS A total of 663 patients underwent r and omization and were followed for a mean ( ±SD ) of 5.3±2.0 years . In the analysis of r and omization groups 1 and 2 , no stroke occurred among the 238 patients in the PFO closure group , whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group ( hazard ratio , 0.03 ; 95 % confidence interval , 0 to 0.26 ; P<0.001 ) . Procedural complications from PFO closure occurred in 14 patients ( 5.9 % ) . The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group ( 4.6 % vs. 0.9 % , P=0.02 ) . The number of serious adverse events did not differ significantly between the treatment groups ( P=0.56 ) . In the analysis of r and omization groups 1 and 3 , stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone . CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt , the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone . PFO closure was associated with an increased risk of atrial fibrillation . ( Funded by the French Ministry of Health ; CLOSE Clinical Trials.gov number , NCT00562289 . BACKGROUND Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown . METHODS In a multicenter , r and omized , open‐label trial , with blinded adjudication of end‐point events , we r and omly assigned patients 18 to 60 years of age who had a patent foramen ovale ( PFO ) and had had a cryptogenic ischemic stroke to undergo closure of the PFO ( PFO closure group ) or to receive medical therapy alone ( aspirin , warfarin , clopidogrel , or aspirin combined with extended‐release dipyridamole ; medical‐therapy group ) . The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke , fatal ischemic stroke , or early death after r and omization . The results of the analysis of the primary outcome from the original trial period have been reported previously ; the current analysis of data from the extended follow‐up period was considered to be exploratory . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . Patients were followed for a median of 5.9 years . Treatment exposure in the two groups was unequal ( 3141 patient‐years in the PFO closure group vs. 2669 patient‐years in the medical‐therapy group ) , owing to a higher dropout rate in the medical‐therapy group . In the intention‐to‐treat population , recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical‐therapy group , result ing in rates of 0.58 events per 100 patient‐years and 1.07 events per 100 patient‐years , respectively ( hazard ratio with PFO closure vs. medical therapy , 0.55 ; 95 % confidence interval [ CI ] , 0.31 to 0.999 ; P=0.046 by the log‐rank test ) . Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical‐therapy group ( hazard ratio , 0.38 ; 95 % CI , 0.18 to 0.79 ; P=0.007 ) . Venous thromboembolism ( which comprised events of pulmonary embolism and deep‐vein thrombosis ) was more common in the PFO closure group than in the medical‐therapy group . CONCLUSIONS Among adults who had had a cryptogenic ischemic stroke , closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow‐up . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . BACKGROUND The efficacy of closure of a patent foramen ovale ( PFO ) in the prevention of recurrent stroke after cryptogenic stroke is uncertain . We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infa rct ions . METHODS In this multinational trial involving patients with a PFO who had had a cryptogenic stroke , we r and omly assigned patients , in a 2:1 ratio , to undergo PFO closure plus antiplatelet therapy ( PFO closure group ) or to receive antiplatelet therapy alone ( antiplatelet‐only group ) . Imaging of the brain was performed at the baseline screening and at 24 months . The co primary end points were freedom from clinical evidence of ischemic stroke ( reported here as the percentage of patients who had a recurrence of stroke ) through at least 24 months after r and omization and the 24‐month incidence of new brain infa rct ion , which was a composite of clinical ischemic stroke or silent brain infa rct ion detected on imaging . RESULTS We enrolled 664 patients ( mean age , 45.2 years ) , of whom 81 % had moderate or large interatrial shunts . During a median follow‐up of 3.2 years , clinical ischemic stroke occurred in 6 of 441 patients ( 1.4 % ) in the PFO closure group and in 12 of 223 patients ( 5.4 % ) in the antiplatelet‐only group ( hazard ratio , 0.23 ; 95 % confidence interval [ CI ] , 0.09 to 0.62 ; P=0.002 ) . The incidence of new brain infa rct ions was significantly lower in the PFO closure group than in the antiplatelet‐only group ( 22 patients [ 5.7 % ] vs. 20 patients [ 11.3 % ] ; relative risk , 0.51 ; 95 % CI , 0.29 to 0.91 ; P=0.04 ) , but the incidence of silent brain infa rct ion did not differ significantly between the study groups ( P=0.97 ) . Serious adverse events occurred in 23.1 % of the patients in the PFO closure group and in 27.8 % of the patients in the antiplatelet‐only group ( P=0.22 ) . Serious device‐related adverse events occurred in 6 patients ( 1.4 % ) in the PFO closure group , and atrial fibrillation occurred in 29 patients ( 6.6 % ) after PFO closure . CONCLUSIONS Among patients with a PFO who had had a cryptogenic stroke , the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone ; however , PFO closure was associated with higher rates of device complications and atrial fibrillation . ( Funded by W.L. Gore and Associates ; Gore REDUCE Clinical Trials.gov number , NCT00738894 . BACKGROUND Recent reports showing the favorable role of patent foramen ovale ( PFO ) closure in patients with cryptogenic stroke have raised the issue of selecting optimal c and i date s. OBJECTIVES This study , DEFENSE-PFO ( Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale ) , evaluated whether the benefits of PFO closure can be determined on the basis of the morphologic characteristics of the PFO , as evaluated by transesophageal echocardiography . METHODS Patients with cryptogenic stroke and high-risk PFO were divided between a transcatheter PFO closure and a medication-only group . High-risk PFO included PFO with atrial septal aneurysm , hypermobility ( phasic septal excursion into either atrium ≥10 mm ) , or PFO size ( maximum separation of the septum primum from the secundum ) ≥2 mm . The primary endpoint was a composite of stroke , vascular death , or Thrombolysis In Myocardial Infa rct ion-defined major bleeding during 2 years of follow-up . RESULTS From September 2011 until October 2017 , 120 patients ( mean age : 51.8 years ) underwent r and omization . PFO size , frequency of septal aneurysm ( 13.3 % vs. 8.3 % ; p = 0.56 ) , and hypermobility ( 45.0 % vs. 46.7 % ; p > 0.99 ) were similar between the groups . All PFO closures were successful . The primary endpoint occurred exclusively in the medication-only group ( 6 of 60 patients ; 2-year event rate : 12.9 % [ log-rank p = 0.013 ] ; 2-year rate of ischemic stroke : 10.5 % [ p = 0.023 ] ) . The events in the medication-only group included ischemic stroke ( n = 5 ) , cerebral hemorrhage ( n = 1 ) , Thrombolysis In Myocardial Infa rct ion-defined major bleeding ( n = 2 ) , and transient ischemic attack ( n = 1 ) . Nonfatal procedural complications included development of atrial fibrillation ( n = 2 ) , pericardial effusion ( n = 1 ) , and pseudoaneurysm ( n = 1 ) . CONCLUSIONS PFO closure in patients with high-risk PFO characteristics result ed in a lower rate of the primary endpoint as well as stroke recurrence . ( Device Closure Versus Medical Therapy for Cryptogenic Stroke Patients With High-Risk Patent Foramen Ovale [ DEFENSE-PFO ] ; NCT01550588 ) OBJECTIVE To test the reliability and validity of specific instructions to classify blinding , when unclearly reported in r and omized trials , as " probably done " or " probably not done . " STUDY DESIGN AND SETTING We assessed blinding of patients , health care providers , data collectors , outcome adjudicators , and data analysts in 233 r and omized trials in duplicate and independently using detailed instructions . The response options were " definitely yes , " " probably yes , " " probably no , " and " definitely no. " We contacted authors for data verification ( 46 % response ) . For each of the five questions , we assessed reliability by calculating the agreement between the two review ers and validity by calculating the agreement between review ers ' consensus and verified data . RESULTS The percentage with unclear blinding status varied between 48.5 % ( patients ) and 84.1 % ( data analysts ) . Reliability was moderate for blinding of outcome adjudicators ( κ=0.52 ) and data analysts ( κ=0.42 ) and substantial for blinding of patients ( κ=0.71 ) , providers ( κ=0.68 ) , and data collectors ( κ=0.65 ) . The raw agreement between the consensus record and the author-verified record varied from 84.1 % ( blinding of data analysts ) to 100 % ( blinding of health care providers ) . CONCLUSION With the possible exception of blinding of data analysts , use of " probably yes " and " probably no " instead of " unclear " may enhance the assessment of blinding in trials 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 —Patent foramen ovale ( PFO ) is associated with stroke , but there are no r and omized studies to evaluate the efficacy of antithrombotic therapies . Methods and Results —The PFO in Cryptogenic Stroke Study was a 42-center study that evaluated transesophageal echocardiographic findings in patients r and omly assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study . In this study , 630 stroke patients were enrolled , of whom 312 ( 49.5 % ) were r and omized to warfarin and 318 ( 50.5 % ) to aspirin . Of these , 265 patients experienced cryptogenic stroke and 365 experienced known stroke subtypes . End points were recurrent ischemic stroke or death . PFO was present in 203 patients ( 33.8 % ) . There was no significant difference in the time to primary end points between those with and those without PFO in the overall population ( P = 0.84 ; hazard ratio 0.96 ; 95 % CI 0.62 to 1.48 ; 2-year event rates 14.8 % versus 15.4 % ) or in the cryptogenic subset ( P = 0.65 ; hazard ratio 1.17 ; 95 % CI 0.60 to 2.37 ; 2-year event rates 14.3 % versus 12.7 % ) . There was no significant difference among those with no , small , or large PFO ( P = 0.41 for small PFO and P = 0.16 for large PFO ; 2-year event rates for no , small , and large PFO , 15.4 % , 18.5 % , and 9.5 % , respectively ) . There was no significant difference between patients with isolated PFO and those with PFO in association with atrial septal aneurysm ( P = 0.84 ; 2-year event rates 14.5 % versus 15.9 % ) . In patients with PFO , there was no significant difference in the time to primary end points between those treated with warfarin and those treated with aspirin ( P = 0.49 ; hazard ratio 1.29 ; 95 % CI 0.63 to 2.64 ; 2-year event rates 16.5 % versus 13.2 % ) . Conclusions —On medical therapy , the presence of PFO in stroke patients did not increase the chance of adverse events regardless of PFO size or the presence of atrial septal aneurysm BACKGROUND The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale . We investigated whether closure is superior to medical therapy . METHODS We performed a multicenter , superiority trial in 29 centers in Europe , Canada , Brazil , and Australia in which the assessors of end points were unaware of the study -group assignments . Patients with a patent foramen ovale and ischemic stroke , transient ischemic attack ( TIA ) , or a peripheral thromboembolic event were r and omly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy . The primary end point was a composite of death , nonfatal stroke , TIA , or peripheral embolism . Analysis was performed on data for the intention-to-treat population . RESULTS The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group . The primary end point occurred in 7 of the 204 patients ( 3.4 % ) in the closure group and in 11 of the 210 patients ( 5.2 % ) in the medical-therapy group ( hazard ratio for closure vs. medical therapy , 0.63 ; 95 % confidence interval [ CI ] , 0.24 to 1.62 ; P=0.34 ) . Nonfatal stroke occurred in 1 patient ( 0.5 % ) in the closure group and 5 patients ( 2.4 % ) in the medical-therapy group ( hazard ratio , 0.20 ; 95 % CI , 0.02 to 1.72 ; P=0.14 ) , and TIA occurred in 5 patients ( 2.5 % ) and 7 patients ( 3.3 % ) , respectively ( hazard ratio , 0.71 ; 95 % CI , 0.23 to 2.24 ; P=0.56 ) . CONCLUSIONS Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy . ( Funded by St. Jude Medical ; Clinical Trials.gov number , NCT00166257 . ) Background : This r and omized clinical trial compared rates of stroke or transient ischemic attack recurrence or death in patients with cryptogenic stroke and patent foramen ovale ( PFO ) who received medical treatment with aspirin or warfarin . Material s and Methods : Forty-four Iranian patients with cryptogenic stroke and patent foramen ovale participated in this r and omized , single-blind trial between July 2007 and June 2010 . All patients underwent transesophageal echocardiography and contrast-transcranial Doppler sonography to confirm the presence of patent foramen ovale . The patients were r and omly assigned to receive aspirin or warfarin and were followed for 18 months for the recurrence of ischemic events or death . The principal investigator was blind to the group assignment . This trial is registered under number I RCT 138805192323N1 . Results : Five ( 11.4 % ) patients had a stroke , 2 ( 4.5 % ) had a transient ischemic attack and 2 ( 4.5 % ) died . There was no difference in the rate of ischemic events or death between the aspirin- and warfarin-treated groups ( hazard ratio : 0.45 ; 95 % CI : 0.1 - 1.8 ; P = 0.259 ) . Conclusion : There was no difference in ischemic event recurrence , death rates or side-effects between patients with cryptogenic stroke and patent foramen ovale who were treated with aspirin vs. warfarin BACKGROUND AND PURPOSE Patent foramen ovale ( PFO ) has been identified as a potential risk factor for stroke , but the mechanisms of PFO-associated stroke remain unsettled . The aim of our study was to evaluate possible differences in stroke risk factors and stroke patterns between patients with and without PFO that may give clues to the mechanism of PFO-associated stroke . METHODS This prospect i ve , multicentric study involved 581 young cryptogenic stroke patients . The presence of PFO and atrial septal aneurysm was assessed by transesophageal echocardiography and review ed independently by 2 experienced sonographers . Clinical , brain , and vascular imaging findings were review ed by 2 neurologists and 2 neuroradiologists . RESULTS Of the 581 stroke patients , 267 ( 45.9 % ) had PFO . Patients with PFO were younger ( OR , 0.95 ; 95 % CI , 0.93 to 0.97 ) and less likely to have traditional risk factors such as hypertension ( OR , 0.49 ; 95 % CI , 0.28 to 0.85 ) , hypercholesterolemia ( OR , 0.56 ; 95 % CI , 0.34 to 0.93 ) , or current smoking ( OR , 0.67 ; 95 % CI , 0.47 to 0.97 ) . Features suggestive of paradoxical embolism , such as Valsalva-provoking activities or deep vein thrombosis , were not more frequent in patients with PFO . Migraine was more common in patients with PFO ( 27.3 % ) than in those without PFO ( 14.0 % ) . PFO ( OR , 1.75 ; 95 % CI , 1.08 to 2.82 ) , particularly when associated with atrial septal aneurysm ( OR , 2.71 ; 95 % CI , 1.36 to 5.41 ) , was significantly associated with migraine after adjustment for age and sex . CONCLUSIONS Differences in stroke risk factors and stroke patterns suggest that different stroke mechanisms occur in patients with and without PFO . PFO is significantly and independently associated with migraine , and this association is even stronger in patients with PFO and atrial septal aneurysm BACKGROUND The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population . Closure with a percutaneous device is often recommended in such patients , but it is not known whether this intervention reduces the risk of recurrent stroke . METHODS We conducted a multicenter , r and omized , open-label trial of closure with a percutaneous device , as compared with medical therapy alone , in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack ( TIA ) and had a patent foramen ovale . The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up , death from any cause during the first 30 days , or death from neurologic causes between 31 days and 2 years . RESULTS A total of 909 patients were enrolled in the trial . The cumulative incidence ( Kaplan-Meier estimate ) of the primary end point was 5.5 % in the closure group ( 447 patients ) as compared with 6.8 % in the medical-therapy group ( 462 patients ) ( adjusted hazard ratio , 0.78 ; 95 % confidence interval , 0.45 to 1.35 ; P=0.37 ) . The respective rates were 2.9 % and 3.1 % for stroke ( P=0.79 ) and 3.1 % and 4.1 % for TIA ( P=0.44 ) . No deaths occurred by 30 days in either group , and there were no deaths from neurologic causes during the 2-year follow-up period . A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events . CONCLUSIONS In patients with cryptogenic stroke or TIA who had a patent foramen ovale , closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA . ( Funded by NMT Medical ; Clinical Trials.gov number , NCT00201461 . ) |
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