Tania B. Huedo-Medina

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.

Efficacy of Exercise Interventions in Modulating Cancer-Related Fatigue among Adult Cancer Survivors: A Meta-Analysis

Background: The purpose of this meta-analysis was to explore the efficacy of exercise as a nonpharmacologic intervention to reduce cancer-related fatigue (CRF) among adult cancer survivors. We also investigated how different components of the exercise prescription (Ex Rx), methodologic considerations, and subject characteristics modulate CRF. Methods: A systematic search for randomized controlled trials was conducted using words related to cancer, exercise, and fatigue. Results: In total, 44 studies with 48 interventions qualified, including 3,254 participants of varying cancer types, stages of diagnosis, treatments, and exercise interventions. Cancer survivors in exercise interventions reduced their CRF levels to a greater extent than usual care controls, d+ = 0.31 (95% CI = 0.22–0.40), an effect that appeared to generalize across several types of cancer. CRF levels improved in direct proportion to the intensity of resistance exercise (β = 0.60, P = 0.01), a pattern that was stronger in higher quality studies (β = 0.23, P < 0.05). CRF levels also reduced to a greater extent when interventions were theoretically driven (β = 0.48, P < 0.001) or cancer survivors were older (β = 0.24, P = 0.04). Conclusions: Exercise reduced CRF especially in programs that involved moderate-intensity, resistance exercise among older cancer survivors and that were guided by theory. Impact: Our results indicate exercise interventions for adult cancer survivors should be multi-dimensional and individualized according to health outcome and cancer type. Cancer Epidemiol Biomarkers Prev; 20(1); 123–33. ©2011 AACR.

Exercise Interventions for Cancer Survivors: A Meta-Analysis of Quality of Life Outcomes

BackgroundExercise improves quality of life (QOL) in cancer survivors, although characteristics of efficacious exercise interventions for this population have not been identified.PurposeThe present meta-analysis examines the efficacy of exercise interventions in improving QOL in cancer survivors, as well as features that may moderate such effects.MethodStudies were identified and coded, and QOL effect sizes were calculated and analyzed for trends.ResultsOverall, exercise interventions increased QOL, but this tendency depended to some extent on exercise and patient features. Although several features were associated with effect sizes, models revealed that interventions were particularly successful if they targeted more intense aerobic exercise and addressed women. These tendencies emerged over longer periods of time and were more prominent in studies with higher methodological quality.ConclusionAppropriately designed exercise interventions enhance QOL for cancer survivors and this pattern is especially evident for women. Limitations are discussed.

Adherence to Highly Active Antiretroviral Therapy (HAART): A Meta-Analysis

This meta-analysis synthesizes eighty-four observational studies, conducted across twenty countries, to determine the mean proportion of people who reported ≥90% adherence to prescribed highly active antiretroviral therapy (HAART) and to identify the factors associated with high levels of adherence. Eight electronic databases were searched to locate all relevant studies available by January 2010, which were then coded for sample characteristics and adherence levels. The average rate of reporting ≥90% adherent HAART adherence is 62%. However, this proportion varies greatly across studies. In particular, a greater proportion of individuals maintaining ≥90% adherence to HAART is more likely in studies with higher proportions of men who have sex with men (MSM) and lower proportions of injection drug users (IDU), with participants in an earlier stage of infection, and in studies conducted in countries characterized by lower Human Development Index (HDI) scores.ResumenEste metaanálisis sintetiza ochenta y cuatro estudios observacionales, realizados en veinte países, para determinar la proporción media de personas que informan de la adherencia a la Terapia Antirretroviral Altamente Activa ≥90% e identificar los factores relacionados con los niveles elevados de adherencia. Para localizar los estudios relevantes disponibles hasta enero de 2010 accedimos a ocho bases de datos electrónicas. Los estudios seleccionados se codificaron según las características de la muestra y los niveles de adherencia. Los resultados obtenidos indican que una media del 62% de las personas que tomaban Terapia Antirretroviral Altamente Activa eran adherentes en un ≥90%. Sin embargo, esta proporción varía enormemente entre los estudios. En particular, una mayor proporción de individuos que muestran una adherencia a la Terapia Antirretroviral Altamente Activa ≥90% es más frecuente en estudios con altas proporciones de hombres que mantienen relaciones sexuales con hombres y con menores proporciones de usuarios de drogas parenterales, con los participantes en un estadio más temprano de la infección y en estudios llevados a cabo en países caracterizados con puntuaciones más bajas en el índice de desarrollo humano.

Interventions to reduce sexual risk for human immunodeficiency virus in adolescents: a meta-analysis of trials, 1985-2008.

OBJECTIVE To provide an updated review of the efficacy of behavioral interventions to reduce sexual risk of human immunodeficiency virus (HIV) among adolescents. DESIGN We searched electronic databases, leading public health journals, and the document depository held by the Synthesis of HIV/AIDS Risk Reduction Project. Studies that fulfilled the selection criteria and were available as of December 31, 2008, were included. SETTING Studies that investigated any behavioral intervention advocating sexual risk reduction for HIV prevention, sampled adolescents (age range, 11-19 years), measured a behavioral outcome relevant to sexual risk, and provided sufficient information to calculate effect sizes. PARTICIPANTS Data from 98 interventions (51,240 participants) were derived from 67 studies, dividing for qualitatively different interventions and gender when reports permitted it. MAIN OUTCOME MEASURES Condom use, sexual frequency, condom use skills, interpersonal communication skills, condom acquisition, and incident sexually transmitted infections (STIs). RESULTS Relative to controls, interventions succeeded at reducing incident STIs, increasing condom use, reducing or delaying penetrative sex, and increasing skills to negotiate safer sex and to acquire prophylactic protection. Initial risk reduction varied depending on sample and intervention characteristics but did not decay over time. CONCLUSIONS Comprehensive behavioral interventions reduce risky sexual behavior and prevent transmission of STIs. Interventions are most successful to the extent that they deliver intensive content.

Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration

Objectives To investigate the effectiveness of non-benzodiazepine hypnotics (Z drugs) and associated placebo responses in adults and to evaluate potential moderators of effectiveness in a dataset used to approve these drugs. Design Systematic review and meta-analysis. Data source US Food and Drug Administration (FDA). Study selection Randomised double blind parallel placebo controlled trials of currently approved Z drugs (eszopiclone, zaleplon, and zolpidem). Data extraction Change score from baseline to post-test for drug and placebo groups; drug efficacy analysed as the difference of both change scores. Weighted raw and standardised mean differences with their confidence intervals under random effects assumptions for polysomnographic and subjective sleep latency, as primary outcomes. Secondary outcomes included waking after sleep onset, number of awakenings, total sleep time, sleep efficiency, and subjective sleep quality. Weighted least square regression analysis was used to explain heterogeneity of drug effects. Data synthesis 13 studies containing 65 separate drug-placebo comparisons by type of outcome, type of drug, and dose were included. Studies included 4378 participants from different countries and varying drug doses, lengths of treatment, and study years. Z drugs showed significant, albeit small, improvements (reductions) in our primary outcomes: polysomnographic sleep latency (weighted standardised mean difference, 95% confidence interval −0.57 to −0.16) and subjective sleep latency (−0.33, −0.62 to −0.04) compared with placebo. Analyses of weighted mean raw differences showed that Z drugs decreased polysomnographic sleep latency by 22 minutes (−33 to −11 minutes) compared with placebo. Although no significant effects were found in secondary outcomes, there were insufficient studies reporting these outcomes to allow firm conclusions. Moderator analyses indicated that sleep latency was more likely to be reduced in studies published earlier, with larger drug doses, with longer duration of treatment, with a greater proportion of younger and/or female patients, and with zolpidem. Conclusion Compared with placebo, Z drugs produce slight improvements in subjective and polysomnographic sleep latency, especially with larger doses and regardless of type of drug. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produced to a reasonably large clinical response.

The Efficacy of Exercise in Reducing Depressive Symptoms among Cancer Survivors: A Meta-Analysis

Introduction The purpose of this meta-analysis was to examine the efficacy of exercise to reduce depressive symptoms among cancer survivors. In addition, we examined the extent to which exercise dose and clinical characteristics of cancer survivors influence the relationship between exercise and reductions in depressive symptoms. Methods We conducted a systematic search identifying randomized controlled trials of exercise interventions among adult cancer survivors, examining depressive symptoms as an outcome. We calculated effect sizes for each study and performed weighted multiple regression moderator analysis. Results We identified 40 exercise interventions including 2,929 cancer survivors. Diverse groups of cancer survivors were examined in seven exercise interventions; breast cancer survivors were examined in 26; prostate cancer, leukemia, and lymphoma were examined in two; and colorectal cancer in one. Cancer survivors who completed an exercise intervention reduced depression more than controls, d + = −0.13 (95% CI: −0.26, −0.01). Increases in weekly volume of aerobic exercise reduced depressive symptoms in dose-response fashion (β = −0.24, p = 0.03), a pattern evident only in higher quality trials. Exercise reduced depressive symptoms most when exercise sessions were supervised (β = −0.26, p = 0.01) and when cancer survivors were between 47–62 yr (β = 0.27, p = 0.01). Conclusion Exercise training provides a small overall reduction in depressive symptoms among cancer survivors but one that increased in dose-response fashion with weekly volume of aerobic exercise in high quality trials. Depressive symptoms were reduced to the greatest degree among breast cancer survivors, among cancer survivors aged between 47–62 yr, or when exercise sessions were supervised.

Efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections: a meta-analysis, 1991 to 2010.

ObjectiveIn the absence of an effective HIV vaccine, safer sexual practices are necessary to avert new infections. Therefore, we examined the efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections (STIs), including HIV. DesignStudies that examined a behavioral intervention focusing on reducing sexual risk, used a randomized controlled trial or a quasi-experimental design with a comparison condition, and provided needed information to calculate effect sizes for condom use and any type of STI, including HIV. MethodsStudies were retrieved from electronic databases (eg, PubMed, PsycINFO) and reference sections of relevant papers. Forty-two studies with 67 separate interventions (N = 40,665; M age = 26 years; 68% women; 59% Black) were included. Independent raters coded participant characteristics, design and methodological features, and intervention content. Weighted mean effect sizes, using both fixed-effects and random-effects models, were calculated. Potential moderators of intervention efficacy were assessed. ResultsCompared with controls, intervention participants increased their condom use [d+ = 0.17, 95% confidence interval (CI) = 0.04, 0.29; k = 67], had fewer incident STIs (d+ = 0.16, 95% CI = 0.04, 0.29; k = 62), including HIV (d+ = 0.46, 95% CI = 0.13, 0.79; k = 13). Sample (eg, ethnicity) and intervention features (eg, skills training) moderated the efficacy of the intervention. ConclusionsBehavioral interventions reduce sexual risk behavior and avert STIs and HIV. Translation and widespread dissemination of effective behavioral interventions are needed.

A role for depression in sexual risk reduction for women? A meta-analysis of HIV prevention trials with depression outcomes

Rates of HIV/AIDS and depression in women are significant public health concerns. The current meta-analysis tested the hypothesis that depression levels moderate change in sexual risk behavior in women participating in HIV prevention interventions. Features of the interventions were also explored as possible factors in decreasing levels of depression and sexual risk behavior. Included were HIV primary prevention interventions that measured sexual risk behavior and depression at baseline and follow-up and reported separate results for women. Ten studies (fourteen intervention groups and ten control groups; N = 4,195 women) met the inclusion criteria. The majority of participants were African American; mean age was 28-years old. Both depression and sexual risk behavior decreased significantly in treatment and control groups from baseline to follow-up. Sexual risk decreased more to the extent that interventions sampled (a) participants with higher baseline levels of depression, (b) older women, (c) Hispanics/Latinas, and/or (d) members of risk groups (e.g., drug users, homeless). Interventions that included (e) condom provision, (f) information about condoms, and/or (g) HIV counseling and testing were also more successful in decreasing sexual risk. Finally (h), interventions were more likely to reduce sexual risk behavior when they decreased depression to a large extent relative to baseline levels. Interventions were more likely to decrease depression when they (a) had samples of only women, (b) targeted risk groups, and/or (c) provided self-management and coping skills. Reducing depression appears to play a role in decreasing sexual risk behavior, suggesting that interventions should actively address depression.

Sex differences in adherence to highly active antiretroviral therapy: A meta-analysis

Abstract Observational studies have found that women tend to have lower adherence to highly active antiretroviral therapy (HAART) than men do, though no meta-analysis has yet investigated this trend. The aims of the current meta-analysis are to determine if and to what degree the percentage of men versus women maintaining ≥90% adherence to prescribed HAART differs, and if the external variables moderating adherence differs by gender. Eight electronic databases were searched to locate all relevant studies available by May 2011. Fifty-six observational studies were eligible for inclusion in the meta-analysis. A random effect model was assumed for the global percentage estimation and to explain the heterogeneity. Across these studies, the difference between men and women in the proportion of individuals with ≥90% adherence to HAART was marginally significant (p<0.1; 67% and 62%, respectively). A greater proportion of men maintaining ≥90% adherence to HAART was more likely in studies with higher proportions of men who have sex with men (MSM), lower proportions of male alcohol users or lower proportions of men in a methadone program. In women, higher rates of adherence were found in studies conducted in Africa, Asia, and South America, when the sample included more widows or when the sample had a lower basal CD4 count. That both the percentage of adherent individuals and the variables associated with such adherence differ between men and women are suggestive of the need for improving gender-tailored interventions for adherence to HAART.