Larry J. Prokop

Sexual Abuse and Lifetime Diagnosis of Psychiatric Disorders: Systematic Review and Meta-analysis

OBJECTIVE To systematically assess the evidence for an association between sexual abuse and a lifetime diagnosis of psychiatric disorders. PATIENTS AND METHODS We performed a comprehensive search (from January 1980-December 2008, all age groups, any language, any population) of 9 databases: MEDLINE, EMBASE, CINAHL, Current Contents, PsycINFO, ACP Journal Club, CCTR, CDSR, and DARE. Controlled vocabulary supplemented with keywords was used to define the concept areas of sexual abuse and psychiatric disorders and was limited to epidemiological studies. Six independent reviewers extracted descriptive, quality, and outcome data from eligible longitudinal studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled across studies by using the random-effects model. The I(2) statistic was used to assess heterogeneity. RESULTS The search yielded 37 eligible studies, 17 case-control and 20 cohort, with 3,162,318 participants. There was a statistically significant association between sexual abuse and a lifetime diagnosis of anxiety disorder (OR, 3.09; 95% CI, 2.43-3.94), depression (OR, 2.66; 95% CI, 2.14-3.30), eating disorders (OR, 2.72; 95% CI, 2.04-3.63), posttraumatic stress disorder (OR, 2.34; 95% CI, 1.59-3.43), sleep disorders (OR, 16.17; 95% CI, 2.06-126.76), and suicide attempts (OR, 4.14; 95% CI, 2.98-5.76). Associations persisted regardless of the victims sex or the age at which abuse occurred. There was no statistically significant association between sexual abuse and a diagnosis of schizophrenia or somatoform disorders. No longitudinal studies that assessed bipolar disorder or obsessive-compulsive disorder were found. Associations between sexual abuse and depression, eating disorders, and posttraumatic stress disorder were strengthened by a history of rape. CONCLUSION A history of sexual abuse is associated with an increased risk of a lifetime diagnosis of multiple psychiatric disorders.

Fibrosis Progression in Nonalcoholic Fatty Liver vs Nonalcoholic Steatohepatitis: A Systematic Review and Meta-analysis of Paired-Biopsy Studies

BACKGROUND & AIMS Little is known about differences in rates of fibrosis progression between patients with nonalcoholic fatty liver (NAFL) vs nonalcoholic steatohepatitis (NASH). We conducted a systematic review and meta-analysis of all studies that assessed paired liver biopsy specimens to estimate the rates of fibrosis progression in patients with nonalcoholic fatty liver disease (NAFLD) including NAFL and NASH. METHODS Through a systematic search of multiple databases and author contact, up to June 2013, we identified studies of adults with NAFLD that collected paired liver biopsy specimens at least 1 year apart. From these, we calculated a pooled-weighted annual fibrosis progression rate (number of stages changed between the 2 biopsy samples) with 95% confidence intervals (CIs), and identified clinical risk factors associated with progression. RESULTS We identified 11 cohort studies including 411 patients with biopsy-proven NAFLD (150 with NAFL and 261 with NASH). At baseline, the distribution of fibrosis for stages 0, 1, 2, 3, and 4 was 35.8%, 32.5%, 16.7%, 9.3%, and 5.7%, respectively. Over 2145.5 person-years of follow-up evaluation, 33.6% had fibrosis progression, 43.1% had stable fibrosis, and 22.3% had an improvement in fibrosis stage. The annual fibrosis progression rate in patients with NAFL who had stage 0 fibrosis at baseline was 0.07 stages (95% CI, 0.02-0.11 stages), compared with 0.14 stages in patients with NASH (95% CI, 0.07-0.21 stages). These findings correspond to 1 stage of progression over 14.3 years for patients with NAFL (95% CI, 9.1-50.0 y) and 7.1 years for patients with NASH (95% CI, 4.8-14.3 y). CONCLUSIONS Based on a meta-analysis of studies of paired liver biopsy studies, liver fibrosis progresses in patients with NAFL and NASH.

Sexual Abuse and Lifetime Diagnosis of Somatic Disorders: A Systematic Review and Meta-analysis

CONTEXT Many patients presenting for general medical care have a history of sexual abuse. The literature suggests an association between a history of sexual abuse and somatic sequelae. OBJECTIVE To systematically assess the association between sexual abuse and a lifetime diagnosis of somatic disorders. Data Sources and Extraction A systematic literature search of electronic databases from January 1980 to December 2008. Pairs of reviewers extracted descriptive, quality, and outcome data from included studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled across studies by using the random-effects model. The I(2) statistic was used to assess heterogeneity. STUDY SELECTION Eligible studies were longitudinal (case-control and cohort) and reported somatic outcomes in persons with and without history of sexual abuse. RESULTS The search identified 23 eligible studies describing 4640 subjects. There was a significant association between a history of sexual abuse and lifetime diagnosis of functional gastrointestinal disorders (OR, 2.43; 95% CI, 1.36-4.31; I(2) = 82%; 5 studies), nonspecific chronic pain (OR, 2.20; 95% CI, 1.54-3.15; 1 study), psychogenic seizures (OR, 2.96; 95% CI, 1.12-4.69, I(2) = 0%; 3 studies), and chronic pelvic pain (OR, 2.73; 95% CI, 1.73-4.30, I(2) = 40%; 10 studies). There was no statistically significant association between sexual abuse and a lifetime diagnosis of fibromyalgia (OR, 1.61; 95% CI, 0.85-3.07, I(2) = 0%; 4 studies), obesity (OR, 1.47; 95% CI, 0.88-2.46; I(2) = 71%; 2 studies), or headache (OR, 1.49; 95% CI, 0.96-2.31; 1 study). We found no studies that assessed syncope. When analysis was restricted to studies in which sexual abuse was defined as rape, significant associations were observed between rape and a lifetime diagnosis of fibromyalgia (OR, 3.35; 95% CI, 1.51-7.46), chronic pelvic pain (OR, 3.27; 95% CI, 1.02-10.53), and functional gastrointestinal disorders (OR, 4.01; 95% CI, 1.88-8.57). CONCLUSION Evidence suggests a history of sexual abuse is associated with lifetime diagnosis of multiple somatic disorders.

Efficacy of Complementary and Alternative Medicine Therapies in Relieving Cancer Pain: A Systematic Review

PURPOSE Despite widespread popular use of complementary and alternative medicine (CAM) therapies, a rigorous evidence base about their efficacy for cancer-related pain is lacking. This is a systematic review of randomized controlled trials (RCTs) evaluating CAM therapies for cancer-related pain. METHODS RCTs using CAM interventions for cancer-related pain were abstracted using Medline, EMBASE, CINAHL, AMED, and Cochrane database. RESULTS Eighteen trials were identified (eight poor, three intermediate, and seven high quality based on Jadad score), with a total of 1,499 patients. Median sample size was 53 patients, and median intervention duration was 45 days. All studies were from single institutions, four had sample size justification, and none reported any adverse effects. Seven trials reported significant benefit for the following CAM therapies: acupuncture (n = 1), support groups (n = 2), hypnosis (n = 1), relaxation/imagery (n = 2), and herbal supplement/HESA-A (n = 1, but study was of low quality without control data). Seven studies reported immediate postintervention or short-term benefit of the following CAM interventions: acupuncture (n = 2), music (n = 1), herbal supplement/Ai-Tong-Ping (n = 1), massage (n = 1), and healing touch (n = 2). Four studies reported no benefit of CAM interventions (music, n = 2; massage, n = 2) in reducing cancer pain compared with a control arm. CONCLUSION There is paucity of multi-institutional RCTs evaluating CAM interventions for cancer pain with adequate power, duration, and sham control. Hypnosis, imagery, support groups, acupuncture, and healing touch seem promising, particularly in the short term, but none can be recommended because of a paucity of rigorous trials. Future research should focus on methodologically strong RCTs to determine potential efficacy of these CAM interventions.

The effectiveness of self‐directed learning in health professions education: a systematic review

Medical Education 2010: 44: 1057–1068

Mortality Associated With Atrial Fibrillation in Patients With Myocardial Infarction A Systematic Review and Meta-Analysis

Background— Atrial fibrillation (AF) is a common finding in patients with myocardial infarction (MI). Atrial fibrillation is not generally perceived by clinicians as a critical event during the acute phase of MI; however, its prognostic influence in MI remains controversial. Furthermore, contradictory data exist concerning the risk of death according to AF timing. This article, a systematic review and first meta-analysis, aims to quantify the mortality risk associated with AF in MI patients and its timing. Methods and Results— A comprehensive search of several electronic databases (1970 to 2010; adults, any language) identified MI studies that evaluated mortality related to AF. Evidence was reviewed by 2 blinded reviewers with a formal assessment of the methodological quality of the studies. Adjusted odds ratios were pooled across studies using the random-effects model. The I2 statistic was used to assess heterogeneity. In the 43 included studies (278 854 subjects), the mortality odds ratio associated with AF was 1.46 (95% confidence interval, 1.35 to 1.58; I2=76%; 23 studies). This worse prognosis persisted regardless of the timing of AF; the odds ratio of mortality for new AF with no prior history of AF was 1.37 (95% confidence interval, 1.26 to 1.49), I2=28%, 9 studies), and for prior AF was 1.28 (95% confidence interval, 1.16 to 1.40; I2=24%; 4 studies). The sensitivity analysis of new AF studies adjusting for confounding factors did not show a decrease in risk of death. Conclusions— Atrial fibrillation is associated with increased risk of mortality in MI patients. New AF with no history of AF before MI remained associated with an increased risk of mortality even after adjustment for several important AF risk factors. These subsequent increases in mortality suggest that AF can no longer be considered a nonsevere event during MI.

Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis

IMPORTANCE Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.

Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta‐analysis

Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence‐based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate‐quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate‐quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low‐quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen‐positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen‐negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low‐level viremia. Conclusion: Most of the current literature focuses on the immune active phases of chronic HBV infection; decision‐making in other commonly encountered and challenging clinical settings depends on indirect evidence. (Hepatology 2016;63:284–306)

Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis

Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage–specific risk of all‐cause and liver‐related mortality in NAFLD. Through a systematic review and meta‐analysis, we identified five adult NAFLD cohort studies reporting fibrosis stage–specific mortality (0‐4). Using fibrosis stage 0 as a reference population, fibrosis stage–specific mortality rate ratios (MRRs) with 95% confidence intervals (CIs) for all‐cause and liver‐related mortality were estimated. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Included were 1,495 NAFLD patients with 17,452 patient years of follow‐up. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all‐cause mortality, and this risk increased with increases in the stage of fibrosis: stage 1, MRR = 1.58 (95% CI 1.19‐2.11); stage 2, MRR = 2.52 (95% CI 1.85‐3.42); stage 3, MRR = 3.48 (95% CI 2.51‐4.83); and stage 4, MRR = 6.40 (95% CI 4.11‐9.95). The results were more pronounced as the risk of liver‐related mortality increased exponentially with each increase in the stage of fibrosis: stage 1, MRR = 1.41 (95% CI 0.17‐11.95); stage 2, MRR = 9.57 (95% CI 1.67‐54.93); stage 3, MRR = 16.69 (95% CI 2.92‐95.36); and stage 4, MRR = 42.30 (95% CI 3.51‐510.34). Limitations of the study include an inability to adjust for comorbid conditions or demographics known to impact fibrosis progression in NAFLD and the inclusion of patients with simple steatosis and nonalcoholic steatohepatitis without fibrosis in the reference comparison group. Conclusion: The risk of liver‐related mortality increases exponentially with increase in fibrosis stage; these data have important implications in assessing the utility of each stage and benefits of regression of fibrosis from one stage to another. (Hepatology 2017;65:1557‐1565).

Glycemic Control in Non-Critically Ill Hospitalized Patients: A Systematic Review and Meta-Analysis

BACKGROUND The effect of intensive therapy to achieve tight glycemic control in patients hospitalized in non-critical care settings is unclear. METHODS We conducted a systematic review and meta-analysis to determine the effect of intensive glycemic control strategies on the outcomes of death, stroke, myocardial infarction, incidence of infection, and hypoglycemia. We included randomized and observational studies. Bibliographic databases were searched through February 2010. Random effects model was used to pool results across studies. RESULTS Nineteen studies (nine randomized and 10 observational studies) were included. The risk of bias across studies was moderate. Meta-analysis demonstrates that intensive glycemic control was not associated with significant effect on the risk of death, myocardial infarction, or stroke. There was a trend for increased risk of hypoglycemia (relative risk, 1.58; 95% confidence interval, 0.97-2.57), particularly in surgical studies and when the planned glycemic target was achieved. Intensive glycemic control was associated with decreased risk of infection (relative risk, 0.41; 95% confidence interval, 0.21-0.77) that was mainly derived from studies in surgical settings. CONCLUSION Intensive control of hyperglycemia in patients hospitalized in non-critical care settings may reduce the risk of infection. The quality of evidence is low and mainly driven by studies in surgical settings.