Altitude and regional gradients in chronic kidney disease prevalence in Costa Rica: Data from the Costa Rican Longevity and Healthy Aging Study.

OBJECTIVES: Recent studies in Central America indicate that mortality attributable to chronic kidney disease (CKD) is rising rapidly. We sought to determine the prevalence and regional variation of CKD and the relationship of biologic and socio-economic factors to CKD risk in the older-adult population of Costa Rica. METHODS: We used data from the Costa Rican Longevity and Health Aging Study (CRELES). The cohort was comprised of 2657 adults born before 1946 in Costa Rica, chosen through a sampling algorithm to represent the national population of Costa Ricans >60 years of age. Participants answered questionnaire data and completed laboratory testing. The primary outcome of this study was CKD, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 . RESULTS: The estimated prevalence of CKD for older Costa Ricans was 20% (95% CI 18.5-21.9%). In multivariable logistic regression, older age (adjusted odds ratio [aOR] 1.08 per year, 95% CI 1.07-1.10, P < 0.001) was independently associated with CKD. For every 200 m above sea level of residence, subjects' odds of CKD increased 26% (aOR 1.26 95% CI 1.15-1.38, P < 0.001). There was large regional variation in adjusted CKD prevalence, highest in Limon (40%, 95% CI 30-50%) and Guanacaste (36%, 95% CI 26-46%) provinces. Regional and altitude effects remained robust after adjustment for socio-economic status. CONCLUSIONS: We observed large regional and altitude-related variations in CKD prevalence in Costa Rica, not explained by the distribution of traditional CKD risk factors. More studies are needed to explore the potential association of geographic and environmental exposures with the risk of CKD.

Educational gradients in psychotropic medication use among older adults in Costa Rica and the United States.

OBJECTIVE: The relationship of education, psychiatric diagnoses, and use of psychotropic medication has been explored in the United States, but little is known about this relationship in poorer countries, despite the high burden of mental illness in these countries. This study estimated educational gradients in diagnosis and psychotropic drug use in the United States and Costa Rica, a middle-income country with universal health insurance. METHODS: Analyses were conducted by using data of older adults (≥60) from the 2005 U.S. Medical Expenditure Panel Survey (N=4,788) and the 2005 Costa Rican Longevity and Healthy Aging Study (N=2,827). Logistic regressions examined the effect of education level (low, medium, or high) and urban residence on the rates of self-reported mental health diagnoses, screening diagnosis, and psychotropic medication use with and without an associated psychiatric diagnosis. RESULTS: Rates of self-reported diagnoses were lower in the United States (12%) than in Costa Rica (20%), possibly reflecting differences in survey wording. In both countries, the odds of having depression were significantly lower among persons with high education. In Costa Rica, use of psychotropic medication among persons with self-reported diagnoses increased by education level. CONCLUSIONS: The educational gradients in medication use were different in the United States and Costa Rica, and stigma and access to care in these countries may play an important role in these differences, although type of insurance did not affect educational gradients in the United States. These analyses increase the evidence of the role of education in use of the health care system.

Treatment of hyperprolactinemia: a systematic review and meta-analysis.

BACKGROUND: Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia. METHODS: We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels). RESULTS: After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to -11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists. CONCLUSION: Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.

The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis.

BACKGROUND: Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis. METHODS: We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data. RESULTS: 35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant. CONCLUSIONS: The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.

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.

A systematic review and meta-analysis of the treatments of varicose veins.

OBJECTIVES: Several treatment options exist for varicose veins. In this review we summarize the available evidence derived from comparative studies about the relative safety and efficacy of these treatments. METHODS: We searched MEDLINE, Embase, Current Contents, Cochrane Central Register of Controlled Trials (CENTRAL) expert files, and the reference section of included articles. Eligible studies compared two or more of the available treatments (surgery, liquid or foam sclerotherapy, laser, radiofrequency ablations, or conservative therapy with compression stockings). Two independent reviewers determined study eligibility and extracted descriptive, methodologic, and outcome data. We used random-effects meta-analysis to pool relative risks (RR) and 95% confidence intervals (CI) across studies. RESULTS: We found 39 eligible studies (30 were randomized trials) enrolling 8285 participants. Surgery was associated with a nonsignificant reduction in the risk of varicose vein recurrence compared with liquid sclerotherapy (RR, 0.56; 95% CI, 0.29-1.06) and all endoluminal interventions (RR, 0.63; 95% CI, 0.37-1.07). Studies of laser and radiofrequency ablation and foam sclerotherapy demonstrated short-term effectiveness and safety. The quality of evidence presented in this review was limited by imprecision (small number of events), short-term follow-up, and indirectness (use of surrogate outcomes). CONCLUSION: Low-quality evidence supports long-term safety and efficacy of surgery for the treatment of varicose veins. Short-term studies support the efficacy of less invasive treatments, which are associated with less periprocedural disability and pain.

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

OBJECTIVES: Given the continuous advances in the biomedical sciences, health care professionals need to develop the skills necessary for life-long learning. Self-directed learning (SDL) is suggested as the methodology of choice in this context. The purpose of this systematic review is to determine the effectiveness of SDL in improving learning outcomes in health professionals. METHODS: We searched MEDLINE, EMBASE, ERIC and PsycINFO through to August 2009. Eligible studies were comparative and evaluated the effect of SDL interventions on learning outcomes in the domains of knowledge, skills and attitudes. Two reviewers working independently selected studies and extracted data. Standardised mean difference (SMD) and 95% confidence intervals (95% CIs) were estimated from each study and pooled using random-effects meta-analysis. RESULTS: The final analysis included 59 studies that enrolled 8011 learners. Twenty-five studies (42%) were randomised. The overall methodological quality of the studies was moderate. Compared with traditional teaching methods, SDL was associated with a moderate increase in the knowledge domain (SMD 0.45, 95% CI 0.23-0.67), a trivial and non-statistically significant increase in the skills domain (SMD 0.05, 95% CI-0.05 to 0.22), and a non-significant increase in the attitudes domain (SMD 0.39, 95% CI-0.03 to 0.81). Heterogeneity was significant in all analyses. When learners were involved in choosing learning resources, SDL was more effective. Advanced learners seemed to benefit more from SDL. CONCLUSIONS: Moderate quality evidence suggests that SDL in health professions education is associated with moderate improvement in the knowledge domain compared with traditional teaching methods and may be as effective in the skills and attitudes domains.

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2).

BACKGROUND: Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. METHODS/DESIGN: We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation.Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases. DISCUSSION: A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit.

Clinical review: Drug-induced hypoglycemia: a systematic review.

CONTEXT: Drug-induced hypoglycemia is a significant adverse effect that may cause important morbidity. OBJECTIVE: The aim of the study was to systematically review the literature for drugs reported to cause hypoglycemia and assess the quality of evidence and strength of association supporting this causal link. DATA SOURCES: We searched electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) and the drug information system Micromedex through November 2007 and sought additional references from experts. STUDY SELECTION: Studies were eligible if they reported hypoglycemia as a side effect of a drug not used to treat hyperglycemia, regardless of their design, language, size, or follow-up duration. We excluded hypoglycemia caused by industrial exposures, nonpharmacological chemical exposures, alcohol, herbs, nutritional supplements, and in vitro and animal studies. DATA EXTRACTION: Reviewers extracted study characteristics and methodological quality and, when possible, data to estimate the odds of developing hypoglycemia when exposed to the offending agent. DATA SYNTHESIS: We found 448 eligible studies that described 2696 cases of hypoglycemia associated with 164 different drugs. The quality of evidence supporting associations between drugs and hypoglycemia was mostly very low due to methodological limitations and imprecision. The most commonly reported offending drugs were quinolones, pentamidine, quinine, beta blockers, angiotensin-converting enzyme agents, and IGF. CONCLUSIONS: Very low quality evidence substantiates the association between hypoglycemia and the use of numerous nondiabetic drugs.