Padmini D Ranasinghe

Meditation Programs for Psychological Stress and Well-being: A Systematic Review and Meta-analysis

IMPORTANCE Many people meditate to reduce psychological stress and stress-related health problems. To counsel people appropriately, clinicians need to know what the evidence says about the health benefits of meditation. OBJECTIVE To determine the efficacy of meditation programs in improving stress-related outcomes (anxiety, depression, stress/distress, positive mood, mental health-related quality of life, attention, substance use, eating habits, sleep, pain, and weight) in diverse adult clinical populations. EVIDENCE REVIEW We identified randomized clinical trials with active controls for placebo effects through November 2012 from MEDLINE, PsycINFO, EMBASE, PsycArticles, Scopus, CINAHL, AMED, the Cochrane Library, and hand searches. Two independent reviewers screened citations and extracted data. We graded the strength of evidence using 4 domains (risk of bias, precision, directness, and consistency) and determined the magnitude and direction of effect by calculating the relative difference between groups in change from baseline. When possible, we conducted meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. FINDINGS After reviewing 18 753 citations, we included 47 trials with 3515 participants. Mindfulness meditation programs had moderate evidence of improved anxiety (effect size, 0.38 [95% CI, 0.12-0.64] at 8 weeks and 0.22 [0.02-0.43] at 3-6 months), depression (0.30 [0.00-0.59] at 8 weeks and 0.23 [0.05-0.42] at 3-6 months), and pain (0.33 [0.03- 0.62]) and low evidence of improved stress/distress and mental health-related quality of life. We found low evidence of no effect or insufficient evidence of any effect of meditation programs on positive mood, attention, substance use, eating habits, sleep, and weight. We found no evidence that meditation programs were better than any active treatment (ie, drugs, exercise, and other behavioral therapies). CONCLUSIONS AND RELEVANCE Clinicians should be aware that meditation programs can result in small to moderate reductions of multiple negative dimensions of psychological stress. Thus, clinicians should be prepared to talk with their patients about the role that a meditation program could have in addressing psychological stress. Stronger study designs are needed to determine the effects of meditation programs in improving the positive dimensions of mental health and stress-related behavior.

Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations.

BACKGROUND Given the increase in medications for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. PURPOSE To summarize the benefits and harms of metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists, as monotherapy and in combination, to treat adults with type 2 diabetes. DATA SOURCES MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through April 2010 for English-language observational studies and trials. The MEDLINE search was updated to December 2010 for long-term clinical outcomes. STUDY SELECTION Two reviewers independently screened reports and identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms. DATA EXTRACTION Two reviewers following standardized protocols serially extracted data, assessed applicability, and independently evaluated study quality. DATA SYNTHESIS Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A(1c) level by about 1 percentage point and most 2-drug combinations produced similar reductions. Metformin was more efficacious than the DPP-4 inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about -2.5 kg. Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones. LIMITATIONS Only English-language publications were reviewed. Some studies may have selectively reported outcomes. Many studies were small, were of short duration, and had limited ability to assess clinically important harms and benefits. CONCLUSION Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A(1c) levels, but some increased risk for hypoglycemia and other adverse events. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Comparative Effectiveness and Safety of Methods of Insulin Delivery and Glucose Monitoring for Diabetes Mellitus: A Systematic Review and Meta-analysis

BACKGROUND Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring. PURPOSE To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus. DATA SOURCES MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions. STUDY SELECTION 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4). DATA EXTRACTION 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data. DATA SYNTHESIS In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes. LIMITATION Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus. CONCLUSION Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Systematic Review: Comparative Effectiveness and Safety of Premixed Insulin Analogues in Type 2 Diabetes

Context The relative effects of premixed insulin analogues, other insulin regimens, and noninsulin antidiabetic agents for adults with type 2 diabetes are unclear. Contribution This systematic review of comparative trials in adults with type 2 diabetes found that premixed insulin analogues and premixed human insulin provided similar glycemic control. Premixed analogues provided tighter glycemic control and caused more hypoglycemia than long-acting insulin analogues and noninsulin antidiabetic agents. Caution Evidence for effects on clinical outcomes was scant and inconclusive. Implication We need large, long-term trials that compare premixed insulin analogues with other agents to see whether improvements in glucose control lead to improved clinical outcomes. The Editors According to the National Health Interview Survey, 28% of patients with type 2 diabetes are using insulin, either alone (16%) or in combination with oral antidiabetic agents (12%) (1). In the management of type 2 diabetes, the role of premixed insulin analogues relative to other insulin regimens and noninsulin antidiabetic agents is unclear. Premixed insulin analogues are derived from rapid-acting insulin analogues and consist of a mixture of a rapid-acting insulin analogue and its intermediate-acting protaminated form. Premixed insulin analogues may be a better alternative than premixed human insulin preparations for patients who wish to have a near-physiologic insulin administration regimen but want to avoid multiple daily insulin injections. In addition, they may allow patients flexible meal times, because these preparations can be administered from 15 minutes before meals to immediately after a meal. Given the increasing prevalence of type 2 diabetes (2), the number of patients who use insulin for glycemic control (1), and the importance of glycemic control in decreasing mortality and morbidity (3), it is imperative to establish the weight of evidence for the safety and effectiveness of these relatively newer insulin preparations compared with traditional insulin preparations. Therefore, the Agency for Healthcare Research and Quality commissioned a systematic review of published studies on the comparative effectiveness and safety of all the premixed insulin analogues that are approved by the U.S. Food and Drug Administration and are available in the United States. Methods Data Sources We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and CINAHL from inception to February 2008. The complete search strategy is available at effectivehealthcare.ahrq.gov/. We also reviewed reference lists of included articles, recent issues of 13 medical journals, the U.S. Food and Drug Administration and European Medicines Agency Web sites for the premixed insulin analogues, unpublished data from premixed insulin analogue manufacturers (Eli Lilly and Company, Indianapolis, Indiana; Sanofi-Aventis, Bridgewater, New Jersey; and Novo Nordisk, Bagsvaerd, Denmark), and Web sites of public registries of clinical trials (ClinicalTrials.gov and ClinicalStudyResults.org). Study Selection We included studies that compared a premixed insulin analogue approved by the U.S. Food and Drug Administration as of February 2008 with any other drug for adults with type 2 diabetes and evaluated clinical outcomes (such as mortality), intermediate outcomes (such as hemoglobin A1c level), or adverse events (such as hypoglycemia). We included randomized, controlled trials (RCTs); controlled clinical trials; and observational studies with control groups, regardless of their duration or sample size. However, we used data from crossover studies only for intermediate outcomes and hypoglycemia. We excluded crossover trials from the quantitative evaluation of outcomes that were either progressive (for example, retinopathy) or irreversible (for example, death). For the evaluation of hemoglobin A1c, we included crossover trials with at least 12 weeks of follow-up before and after the crossover phase. We aimed to use within-individual comparisons from crossover trials if trials had reported data in such detail, but no study did so. Because all crossover studies reported results for each intervention and no trial reported a statistically significant carryover effect, we ignored the crossover design and used reported estimates as if they came from a parallel trial. We excluded nonEnglish-language articles, editorials, comments, letters, and abstracts. Data Extraction and Quality Assessment Two investigators independently reviewed the titles, abstracts, and full articles for inclusion and abstracted data by using standardized forms. We developed a study quality assessment tool based on the Jadad criteria (4), the Newcastle-Ottawa Scale (5), and questions from Agency for Healthcare Research and Qualitys guide for conducting comparative effectiveness reviews (6). We adapted the evidence grading scheme recommended by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group (7) to classify the strength of the body of evidence on each comparison as high, moderate, low, or insufficient. Data Synthesis and Analysis We conducted meta-analyses for outcomes when data were sufficient (2 trials). For intermediate outcomes (fasting glucose, postprandial glucose, and hemoglobin A1c levels) and the adverse outcome of weight gain, we recorded the mean difference between groups, along with its measure of dispersion. If this was not reported, we calculated the point estimate by using the mean difference from baseline for each group. If the mean difference from baseline was not reported, we calculated this from the baseline and final values for each group. If no measure of dispersion was reported for the between-group difference, we calculated it by using the sum of the variances for the mean difference from baseline for each group. If there were no measures of dispersion for the mean difference from baseline for each group, we calculated the variance by using the standard deviation of the baseline and final values, assuming a correlation between baseline and final values of 0.5. We pooled the results of the plasma and blood glucose levels from different studies because blood glucose measurements accurately reflect plasma glucose levels (8). For hypoglycemia, we used 2 strategies to synthesize data. If a trial reported the incidence of hypoglycemia, we calculated an odds ratio (OR) by using the incidence of hypoglycemia in each study group. If a trial did not report the incidence of hypoglycemia but reported event rates in episodes per patient per 30 days, we calculated the rate ratio by dividing the event rate in the premixed insulin analogue group by the event rate in the comparator group. If a trial reported the number of episodes in each group or reported an event rate in a form other than episodes per patient per 30 days, we converted this information into episodes per patient per 30 days. We pooled the results of individual studies by using a random-effects model. These analyses were conducted by using Comprehensive Meta-Analysis, version 2.2.046 (Biostat, Englewood, New Jersey). For clinical outcomes, we included all studies that reported any information about clinical events (all-cause mortality and cardiovascular mortality and morbidity). All analyses followed the intention-to-treat principle. We combined results from the premixed insulin analogue group of different trials, assuming that the results were similar enough between premixed insulin analogues. In the study with 3 groups and comparing a premixed insulin analogue with 2 different insulin preparations (9), we chose the most relevant comparison to include in the meta-analyses (premixed insulin analogue vs. long-acting insulin analogue). We calculated pooled ORs and 95% CIs by using a MantelHaenszel fixed-effects model (with a 0.1 continuity correction) in Stata Intercooled, version 9.2 (Stata, College Station, Texas) (10, 11). For analysis of clinical outcomes, we used a fixed-effects model because it is less biased with rare event data (12). For sensitivity analyses, we used 3 meta-analytic methods: the Peto method, the MantelHaenszel fixed-effects model (with 0.5 and 0.01 continuity corrections), and Bayesian analysis (13). Heterogeneity among the trials was tested by using a standard chi-square test, with a significance level of 0.10 or less. We also examined inconsistency among studies by using an I 2 statistic (14); a value greater than 50% represented substantial variability. For all outcomes, we conducted sensitivity analyses by omitting 1 study at a time. We assessed publication bias visually by examining the symmetry of funnel plots and statistically by using the Begg (15) and Egger (16) tests. Role of the Funding Source The Agency for Healthcare Research and Quality suggested the initial questions and provided copyright release for this manuscript but did not participate in the literature search, data analysis, or interpretation of the results. Results Study Characteristics The Appendix Figure shows the results of the literature search. We found 45 studies that reported at least 1 of the intermediate clinical outcomes or adverse events (Appendix Table). All studies except 2 (17, 18) were RCTs. In 1 study (17), patients were enrolled consecutively and followed prospectively, and in the other study (18), data were obtained from the medical record database of a large employer. Among the RCTs, 23 were parallel-group (9, 1940) and 20 were crossovers (4160). The median duration of follow-up in these trials was 16 weeks (range, 1 day to 2 years). Appendix Table. Characteristics of the Included Studies Appendix Figure. Study flow diagram. FDA = U.S. Food and Drug Administration. * The total may exceed the number in the corresponding box because articles could be excluded for more than 1 reason at this level. The trials enrolled a total of 14603 patients (median per trial, 93 patient

Prevalence of and Sex Disparities in Posttraumatic Stress Disorder in an Internally Displaced Sri Lankan Population 6 Months After the 2004 Tsunami

BACKGROUND When the 2004 Indian Ocean tsunami suddenly hit unsuspecting coastal populations in Sri Lanka, it inflicted unprecedented devastation including 35,000 deaths and 500,000 people displaced. Evaluating the psychological impact of this natural disaster provides valuable insights into planning interventions and disaster preparedness. METHODS A cross-sectional survey was conducted among 264 adult males and females > or =16 years old living in temporary shelters housing tsunami survivors at 6 months. Interviewer-administered structured interviews were conducted to measure posttraumatic stress disorder (PTSD) and its risk factors. RESULTS The participation rate was 97%. Of the subjects, 56% met criteria for symptoms of PTSD, with females at 64% and males at 42%. Females had at least twice the risk of experiencing PTSD (odds ratio [OR] 2.27, 95% confidence interval [CI] 1.37-3.76). This sex difference persisted after adjusting for age, marital status, being a parent, loss of family members, amount of social support, education level, and level of depression (OR 2.14, 95% CI 1.21-3.80). Depression was significantly associated with PTSD (OR 7.19, 95% CI 3.83-13.52). CONCLUSIONS In this directly affected population, a majority met criteria for PTSD, indicating a significant long-term public health burden. The findings also confirm that females are at much higher risk for PTSD than males, suggesting that special mental health efforts should be targeted at women exposed to trauma.

The use of blind skin biopsy in the diagnosis of intravascular B-cell lymphoma

Intravascular B-cell lymphoma is a rare type of non-Hodgkins lymphoma that is characterized by a clonal proliferation of lymphoblasts within small blood vessels. Patients present with nonspecific symptoms and are often only given a diagnosis at autopsy. We report a case of intravascular B-cell lymphoma, characterized by pyrexia, anemia, thrombocytopenia, and mental status decline, without obvious cutaneous manifestations, that was diagnosed with blind skin biopsy.

Comparative Effectiveness of Continuous Subcutaneous Insulin Infusion Using Insulin Analogs and Multiple Daily Injections in Pregnant Women with Diabetes Mellitus: A Systematic Review and Meta-Analysis

We systematically reviewed the effectiveness and safety of continuous subcutaneous insulin infusion (CSII) with insulin analogs compared with multiple daily injections (MDI) in pregnant women with diabetes mellitus. We searched Medline®, Embase®, and the Cochrane Central Register of Controlled Trials through May 2013. Studies comparing CSII with MDI in pregnant women with diabetes mellitus were included. Studies using regular insulin CSII were excluded. We conducted meta-analyses where there were two or more comparable studies based on the type of insulin used in the MDI arm. Seven cohort studies of pregnant women with type 1 diabetes reported improvement in hemoglobin A1c (HbA1c) in both groups. Meta-analysis showed no difference in maternal and fetal outcomes for CSII versus MDI. Results were similar when CSII was compared with MDI with insulin analogs or regular insulin. Studies had moderate to high risk bias with incomplete descriptions of study methodology, populations, treatments, follow up, and outcomes. We conclude that observational studies reported similar improvements in HbA1c with CSII and MDI during pregnancy, but evidence was insufficient to rule out possible important differences between CSII and MDI for maternal and fetal outcomes. This highlights the need for future studies to examine the effectiveness and safety of CSII with insulin analogs and MDI in pregnant women with diabetes mellitus.