Gabriela Prutsky

Patient engagement in research: a systematic review

BackgroundA compelling ethical rationale supports patient engagement in healthcare research. It is also assumed that patient engagement will lead to research findings that are more pertinent to patients’ concerns and dilemmas. However; it is unclear how to best conduct this process. In this systematic review we aimed to answer 4 key questions: what are the best ways to identify patient representatives? How to engage them in designing and conducting research? What are the observed benefits of patient engagement? What are the harms and barriers of patient engagement?MethodsWe searched MEDLINE, EMBASE, PsycInfo, Cochrane, EBSCO, CINAHL, SCOPUS, Web of Science, Business Search Premier, Academic Search Premier and Google Scholar. Included studies were published in English, of any size or design that described engaging patients or their surrogates in research design. We conducted an environmental scan of the grey literature and consulted with experts and patients. Data were analyzed using a non-quantitative, meta-narrative approach.ResultsWe included 142 studies that described a spectrum of engagement. In general, engagement was feasible in most settings and most commonly done in the beginning of research (agenda setting and protocol development) and less commonly during the execution and translation of research. We found no comparative analytic studies to recommend a particular method. Patient engagement increased study enrollment rates and aided researchers in securing funding, designing study protocols and choosing relevant outcomes. The most commonly cited challenges were related to logistics (extra time and funding needed for engagement) and to an overarching worry of a tokenistic engagement.ConclusionsPatient engagement in healthcare research is likely feasible in many settings. However, this engagement comes at a cost and can become tokenistic. Research dedicated to identifying the best methods to achieve engagement is lacking and clearly needed.

Drugs Commonly Associated With Weight Change: A Systematic Review and Meta-analysis

CONTEXT Various drugs affect body weight as a side effect. OBJECTIVE We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. DATA SOURCES MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. STUDY SELECTION We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change. DATA EXTRACTION We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. RESULTS We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. CONCLUSIONS Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.

Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.

CONTEXT Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. OBJECTIVE The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. DATA SOURCES Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). STUDY SELECTION We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. DATA EXTRACTION Two authors performed the data extraction independently. DATA SYNTHESIS We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, -2.3 mg/dL; 95% confidence interval, -4.5 to -0.1, I² = 72%, P = .04) and fasting blood insulin (weighted mean difference, -2.1 μU/mL, 95% confidence interval, -3.3 to -1.0, I² = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. CONCLUSIONS The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis.

OBJECTIVE To summarise the evidence about the efficacy and safety of using GH in adults with GH deficiency focusing on quality of life and body composition. DATA SOURCES We searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through April 2011. We also reviewed reference lists and contacted experts to identify candidate studies. STUDY SELECTION Reviewers, working independently and in duplicate, selected randomised controlled trials (RCTs) that compared GH to placebo. DATA SYNTHESIS We pooled the relative risk (RR) and weighted mean difference (WMD) by the random effects model and assessed heterogeneity using the I(2) statistic. RESULTS Fifty-four RCTs were included enrolling over 3400 patients. The quality of the included trials was fair. GH use was associated with statistically significant reduction in weight (WMD, 95% confidence interval (95% CI): -2.31 kg, -2.66 and -1.96) and body fat content (WMD, 95% CI: -2.56 kg, -2.97 and -2.16); increase in lean body mass (WMD, 95% CI: 1.38, 1.10 and 1.65), the risk of oedema (RR, 95% CI: 6.07, 4.34 and 8.48) and joint stiffness (RR, 95% CI: 4.17, 1.4 and 12.38); without significant changes in body mass index, bone mineral density or other adverse effects. Quality of life measures improved in 11 of the 16 trials although meta-analysis was not feasible. RESULTS GH therapy in adults with confirmed GH deficiency reduces weight and body fat, increases lean body mass and increases oedema and joint stiffness. Most trials demonstrated improvement in quality of life measures.

Out of context: clinical practice guidelines and patients with multiple chronic conditions: a systematic review.

Background:Poor fidelity to practice guidelines in the care of people with multiple chronic conditions (MCC) may result from patients and clinicians struggling to apply recommendations that do not consider the interplay of MCC, socio-personal context, and patient preferences. Objective:The objective of the study was to assess the quality of guideline development and the extent to which guidelines take into account 3 important factors: the impact of MCC, patients’ socio-personal contexts, and patients’ personal values and preferences. Research Design:We conducted a systematic search of clinical practice guidelines for patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two reviewers working independently selected studies, extracted data, and evaluated the quality of the guidelines. Results:We found 28 eligible guidelines, which, on average, had major methodological limitations (AGREE II mean score 3.8 of 7, SD=1.6). Patients or methodologists were not included in the guideline development process in 20 (71%) and 24 (86%) guidelines, respectively. There was a complete absence of incorporating the impact of MCC, socio-personal context, and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines, respectively. When mentioned, MCC were considered biologically, but not as contributors of complexity or patient work or as motivation to focus on patient-centered outcomes. Conclusions:Extant clinical practice guidelines for one chronic disease sometimes consider the context of the patient with that disease, but only do so narrowly. Guideline panels must remove their contextual blinders if they want to practically guide the care of patients with MCC.

Treatment outcomes of human bartonellosis: a systematic review and meta-analysis.

BACKGROUND Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis are responsible for the majority of cases of bartonellosis in humans. These species have various unique epidemiologic characteristics, clinical manifestations, and treatment approaches. The objective of this study was to summarize the evidence on the treatment for the three most common species of Bartonella in humans. METHODS We searched electronic databases through August 2011 for randomized controlled trials and observational studies designed to evaluate the efficacy and safety of the regimens used to treat diseases produced by B. henselae, B. quintana, and B. bacilliformis. Study selection and appraisal were done in duplicate. RESULTS We found two randomized and seven non-randomized studies at high risk of bias. For cat scratch disease, antibiotics did not significantly affect the cure rate or time to achieve cure. In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate. The recommended treatment was not better than other regimens for infectious endocarditis and bacillary angiomatosis. CONCLUSIONS Current clinical practice for the treatment of bartonellosis relies mostly on expert opinion and antimicrobial susceptibility data. Randomized controlled trials are needed in the field to compare different treatment options.

Adverse Effects of the Common Treatments for Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

CONTEXT Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. OBJECTIVE We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. DATA SOURCE Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. STUDY SELECTION We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. DATA EXTRACTION Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. DATA SYNTHESIS We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. CONCLUSIONS Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

Glucose Targets in Pregnant Women With Diabetes: A Systematic Review and Meta-Analysis

BACKGROUND Glucose-lowering treatments are used during pregnancy to reduce the risk for complications in the mother and offspring, yet treatment targets have not been established. OBJECTIVE Our objective was to appraise and summarize the available evidence regarding the association between different blood glucose targets during pregnancy and fetal and maternal outcomes. METHODS We searched Medline, EMBASE, Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011 for randomized trials and observational studies that enrolled women with diabetes during pregnancy and reported planned or achieved glucose targets. We used random-effects meta-regression models to estimate the odds ratio for the association of outcomes of interest and glucose targets. When possible, we adjusted for diabetes type, trimester, and diabetes treatment. RESULTS We included 34 studies enrolling 9433 women. The studies had moderate to high risk of bias due to evidence of reporting bias and insufficient adjustment for important covariates, particularly maternal body mass index. A fasting glucose target of <90 mg/dL was the most commonly reported and the one most strongly associated with reduced risk of macrosomia (odds ratio = 0.53, 95% confidence interval = 0.31-0.90, P = .02) for women with gestational diabetes during the third trimester. For type 1 and type 2 diabetes, and for pre- and postprandial targets, data were sparse and inconclusive. CONCLUSIONS Evidence warranting very low confidence in the estimates suggests that a fasting glucose target of <90 mg/dL is associated with a lower risk of macrosomia and other outcomes of different importance in women with gestational diabetes. Whether this target can be extrapolated to women with pregestational diabetes or whether targets above or below this threshold offer a better benefit/risk balance remains unclear.

A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome

OBJECTIVE The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less intensive glycemic control in preventing diabetic foot syndrome. METHODS We used the umbrella design (systematic review of systematic reviews) to identify eligible RCTs. Two reviewers determined RCT eligibility and extracted descriptive, methodologic, and diabetic foot outcome data. Random-effects meta-analysis was used to pool outcome data across studies, and the I(2) statistic was used to quantify heterogeneity. RESULTS Nine RCTs enrolling 10,897 patients with type 2 diabetes were included and deemed to be at moderate risk of bias. Compared with less intensive glycemic control, intensive control (hemoglobin A1c, 6%-7.5%) was associated with a significant decrease in risk of amputation (relative risk [RR], 0.65; 95% confidence interval [CI], 0.45-0.94; I(2) = 0%). Intensive control was significantly associated with slower decline in sensory vibration threshold (mean difference, -8.27; 95% CI, -9.75 to -6.79). There was no effect on other neuropathic changes (RR, 0.89; 95% CI, 0.75-1.05; I(2) = 32%) or ischemic changes (RR, 0.92; 95% CI, 0.67-1.26; I(2) = 0%). The quality of evidence is likely moderate. CONCLUSIONS Compared with less intensive glycemic control therapy, intensive control may decrease the risk of amputation in patients with diabetic foot syndrome. The reported risk reduction is likely overestimated because the trials were open and the decision to proceed with amputation could be influenced by glycemic control.

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers

BACKGROUND Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting. METHODS We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest were complete wound healing and amputation. RESULTS We identified 18 interventional studies; of which 9 were randomized, enrolling 1526 patients. The risk of bias in the included studies was moderate. In multiple randomized trials, the addition of HBOT to conventional therapy (wound care and offloading) was associated with increased healing rate (Peto odds ratio, 14.25; 95% confidence interval, 7.08-28.68) and reduced major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10-0.89), compared with conventional therapy alone. In one small trial, arterial pump devices had a favorable effect on complete healing compared with HBOT and in another small trial compared with placebo devices. Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy. No comparative studies were identified for cilostazol in diabetic foot ulcers. CONCLUSIONS There is low- to moderate-quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation. However, there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions.