Prehypertension Is Not Associated with All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies

Objectives

Quantitative associations between prehypertension or its two separate blood pressure (BP) ranges and cardiovascular disease (CVD) or all-cause mortality have not been reliably documented. In this study, we performed a comprehensive systematic review and meta-analysis to assess these relationships from prospective cohort studies.

Methods

We conducted a comprehensive search of PubMed (1966-June 2012) and the Cochrane Library (1988-June 2012) without language restrictions. This was supplemented by review of the references in the included studies and relevant reviews identified in the search. Prospective studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs) of CVD or all-cause mortality with respect to prehypertension or its two BP ranges (low range: 120–129/80–84 mmHg; high range: 130–139/85–89 mmHg) at baseline. Pooled RRs were estimated using a random-effects model or a fixed-effects model depending on the between-study heterogeneity.

Results

Thirteen studies met our inclusion criteria, with 870,678 participants. Prehypertension was not associated with an increased risk of all-cause mortality either in the whole prehypertension group (RR: 1.03; 95% CI: 0.91 to 1.15, P = 0.667) or in its two separate BP ranges (low-range: RR: 0.91; 95% CI: 0.81 to 1.02, P = 0.107; high range: RR: 1.00; 95% CI: 0.95 to 1.06, P = 0.951). Prehypertension was significantly associated with a greater risk of CVD mortality (RR: 1.32; 95% CI: 1.16 to 1.50, P<0.001). When analyzed separately by two BP ranges, only high range prehypertension was related to an increased risk of CVD mortality (low-range: RR: 1.10; 95% CI: 0.92 to 1.30, P = 0.287; high range: RR: 1.26; 95% CI: 1.13 to 1.41, P<0.001).

Conclusions

From the best available prospective data, prehypertension was not associated with all-cause mortality. More high quality cohort studies stratified by BP range are needed.     

Depression as a Risk Factor for Mortality in Individuals with Diabetes: A Meta-Analysis of Prospective Studies

Objective

To quantify the impact of depression measured by self-reports and depression measured by clinical interview on all-cause mortality in individuals with diabetes and to analyze the strength of both associations, the influence of covariates, and possible differences between studies assessing self-rated depressive symptoms and those using a clinical interview to measure depression as predictors of mortality.

Research Design and Methods

PUBMED and PsycINFO were searched up to July 2013 for prospective studies assessing depression, diabetes and mortality. The pooled hazard ratios were calculated using random-effects models.

Results

Sixteen studies met the inclusion criteria. After adjustment for demographic variables depression measured by self-reports was associated with an increased all-cause mortality risk (pooled HR = 2.56, 95% CI 1.89–3.47), and the mortality risk remained high after additional adjustment for diabetes complications (HR = 1.76, 95% CI 1.45–2.14,). Six studies reporting adjusted HRs for depression measured by clinical interviews supported the results of the other models (HR = 1.49, 95% CI 1.15–1.93).

Conclusions

Both depression measured by self-report and depression measured by clinical interview have an unfavorable impact on mortality in individuals with diabetes. The results, however, are limited by the heterogeneity of the primary studies. It remains unclear whether self-reports or clinical interviews for depression are the more precise predictor.     

Magnesium and the Risk of Cardiovascular Events: A Meta-Analysis of Prospective Cohort Studies

Background

Prospective studies that have examined the association between dietary magnesium intake and serum magnesium concentrations and the risk of cardiovascular disease (CVD) events have reported conflicting findings. We undertook a meta-analysis to evaluate the association between dietary magnesium intake and serum magnesium concentrations and the risk of total CVD events.

Methodology/Principal Findings

We performed systematic searches on MEDLINE, EMBASE, and OVID up to February 1, 2012 without limits. Categorical, linear, and nonlinear, dose-response, heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. The analysis included 532,979 participants from 19 studies (11 studies on dietary magnesium intake, 6 studies on serum magnesium concentrations, and 2 studies on both) with 19,926 CVD events. The pooled relative risks of total CVD events for the highest vs. lowest category of dietary magnesium intake and serum magnesium concentrations were 0.85 (95% confidence interval 0.78 to 0.92) and 0.77 (0.66 to 0.87), respectively. In linear dose-response analysis, only serum magnesium concentrations ranging from 1.44 to 1.8 mEq/L were significantly associated with total CVD events risk (0.91, 0.85 to 0.97) per 0.1 mEq/L (P_nonlinearity = 0.465). However, significant inverse associations emerged in nonlinear models for dietary magnesium intake (P_nonlinearity = 0.024). The greatest risk reduction occurred when intake increased from 150 to 400 mg/d. There was no evidence of publication bias.

Conclusions/Significance

There is a statistically significant nonlinear inverse association between dietary magnesium intake and total CVD events risk. Serum magnesium concentrations are linearly and inversely associated with the risk of total CVD events.     

Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies

Objective

Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence.

Data sources

MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year’s follow-up period were included.

Review methods

Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting.

Results

We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07–1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98–1.24) and 0.98 (0.78–1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results.

Conclusion

Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.     

Mortality Risk After Radioiodine Therapy for Hyperthyroidism: A Systematic Review and Meta-Analysis

ObjectiveRadioiodine has been increasingly used to treat hyperthyroidism for many years. Although widely regarded as an effective therapy, radioiodine treatment for hyperthyroidism has been suspected to be associated with the risk of mortality. This study aimed to quantify the mortality outcomes in patients who were treated for hyperthyroidism with radioiodine.MethodsSystematic search and meta-analysis were performed to determine the risk of mortality in patients treated with radioiodine for hyperthyroidism. Relevant studies were searched through August 2020 and selected in accordance with the inclusion criteria.ResultsA total of 13 studies were identified. The summary odds ratios (ORs) showed an increased risk of all-cause mortality in patients who were treated with radioiodine for hyperthyroidism (OR = 1.20; 95% CI = 1.07-1.35). The risk of death attributed to all forms of circulatory, respiratory, and endocrine and metabolic diseases was significantly increased, with summary ORs of 1.23 (95% CI, 1.12-1.35), 1.43 (95% CI, 1.17-1.75), and 2.38 (95% CI, 1.85-3.06), respectively. The summary ORs revealed no significant association between radioiodine treatment for hyperthyroidism and the risk of cancer mortality (OR = 1.03; 95% CI, 0.98-1.09). Radioiodine treatment for hyperthyroidism was not associated with the risk of mortality from breast, respiratory system, gastrointestinal, and genitourinary cancers.ConclusionRadioiodine treatment for hyperthyroidism is associated with the risk of all-cause mortality but not cancer mortality. Future research needs to address the causes of hyperthyroidism, effects of radioiodine therapy, and potential effects of confounding to identify causality.     

Effect of Ghrelin on Mortality and Cardiovascular Outcomes in Experimental Rat and Mice Models of Heart Failure: A Systematic Review and Meta-Analysis

BackgroundHeart failure (HF) continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF.MethodsData sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014) which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration) on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE’s risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3.ResultsA total of 325 animals (rats and mice) were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47) i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more) as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66) while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48) and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02) were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29) and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6.82, P=0.59).ConclusionsThe existing data provides evidence to suggest that Ghrelin may lower the risk of mortality and improve cardiovascular outcomes. However; the quality of evidence as assessed by GRADEpro is low to very low. Clinical judgments to administer Ghrelin to patients with HF must be made on better designed animal studies.     

Effect of Coffee Consumption on the Risk of Gastric Cancer: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Background and Objectives

Results from observational epidemiologic studies on the relationship between coffee consumption and gastric cancer are inconsistent and inconclusive. To assess the association between coffee consumption and the risk of gastric cancer, we summarized evidence from prospective cohort studies.

Methods

Relevant studies were retrieved through computer searches (PubMed, EmBase and the Cochrane Library) and a review of references up to December 2014. The quality of the included studies was evaluated by Newcastle-Ottawa quality assessment scale. We used a meta-analytic approach to estimate overall hazard ratios (HRs) and 95% confidence intervals (CIs) for regular coffee drinkers versus individuals who seldom drank coffee. Sensitivity analysis and subgroup analysis were performed to assess the reliability of our results. A dose–response analysis was performed to assess the risk of gastric cancer based on the level of coffee consumption.

Results

Nine prospective cohort studies involving 1,250,825 participants and 3027 gastric cancer cases were included in this meta-analysis. The pooled HR of gastric cancer for the study-specific regularly versus seldom coffee drinking categories was 1.05 (95% CI, 0.88 to 1.25) with significant heterogeneity across studies (I² = 74.0%, P = 0.000). After the sensitivity analysis, three studies were deleted; however the association remained insignificant (HR, 0.99; 95% CI, 0.91 to 1.08). Subgroup analysis by anatomic location showed a risk for coffee consumption associated with cardia cancer (HR, 1.23; 95% CI, 1.04 to 1.45; heterogeneity, I² = 36.4, P = 0.207). In the dose–response analysis, there was no significant association between coffee intake (in cups) and the risk of gastric cancer (P for linearity trend and non-linearity > 0.05).

Conclusion

Our meta-analysis demonstrated that coffee consumption was not associated with overall gastric cancer risk; however, coffee consumption may be a risk factor for gastric cardia cancer.     

Inflammatory Markers and the Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Systemic inflammatory factors are inconsistently associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis to summarize the evidence supporting the association between systemic inflammation and the risk of COPD. Pertinent studies were retrieved from PubMed, EmBase, and the Cochrane Library until April 2015. A random-effects model was used to process the data, and the analysis was further stratified by factors affecting these associations. Sensitivity analyses for publication bias were performed. We included 24 observational studies reporting data on 10,677 COPD patients and 28,660 controls. Overall, we noted that COPD was associated with elevated serum CRP (SMD: 1.21; 95%CI: 0.92–1.50; P < 0.001), leukocytes (SMD: 1.07; 95%: 0.25–1.88; P = 0.010), IL-6 (SMD: 0.90; 95%CI: 0.48–1.31; P < 0.001), IL-8 (SMD: 2.34; 95%CI: 0.69–4.00; P = 0.006), and fibrinogen levels (SMD: 0.87; 95%CI: 0.44–1.31; P < 0.001) when compared with control. However, COPD was not significantly associated with TNF-α levels when compared with control (SMD: 0.60; 95%CI: -0.46 to 1.67; P = 0.266). Our findings suggested that COPD was associated with elevated serum CRP, leukocytes, IL-6, IL-8, and fibrinogen, without any significant relationship with TNF-α.     

Depression and Risk of Mortality in People with Diabetes Mellitus: A Systematic Review and Meta-Analysis

Objective

To examine the association between depression and all-cause and cardiovascular mortality in people with diabetes by systematically reviewing the literature and carrying out a meta-analysis of relevant longitudinal studies.

Research Design and Methods

PUBMED and PSYCINFO were searched for articles assessing mortality risk associated with depression in diabetes up until August 16, 2012. The pooled hazard ratios were calculated using random-effects models.

Results

Sixteen studies met the inclusion criteria, which were pooled in an overall all-cause mortality estimate, and five in a cardiovascular mortality estimate. After adjustment for demographic variables and micro- and macrovascular complications, depression was associated with an increased risk of all-cause mortality (HR = 1.46, 95% CI = 1.29–1.66), and cardiovascular mortality (HR = 1.39, 95% CI = 1.11–1.73). Heterogeneity across studies was high for all-cause mortality and relatively low for cardiovascular mortality, with an I-squared of respectively 78.6% and 39.6%. Subgroup analyses showed that the association between depression and mortality not significantly change when excluding three articles presenting odds ratios, yet this decreased heterogeneity substantially (HR = 1.49, 95% CI = 1.39–1.61, I-squared = 15.1%). A comparison between type 1 and type 2 diabetes could not be undertaken, as only one study reported on type 1 diabetes specifically.

Conclusions

Depression is associated with an almost 1.5-fold increased risk of mortality in people with diabetes. Research should focus on both cardiovascular and non-cardiovascular causes of death associated with depression, and determine the underlying behavioral and physiological mechanisms that may explain this association.     

Effects of Intensive Blood Pressure Lowering on Cardiovascular and Renal Outcomes: A Systematic Review and Meta-Analysis

Background

Guidelines recommend intensive blood pressure (BP) lowering in patients at high risk. While placebo-controlled trials have demonstrated 22% reductions in coronary heart disease (CHD) and stroke associated with a 10-mmHg difference in systolic BP, it is unclear if more intensive BP lowering strategies are associated with greater reductions in risk of CHD and stroke. We did a systematic review to assess the effects of intensive BP lowering on vascular, eye, and renal outcomes.

Methods and Findings

We systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and July 2011. We included trials that randomly assigned individuals to different target BP levels.We identified 15 trials including a total of 37,348 participants. On average there was a 7.5/4.5-mmHg BP difference. Intensive BP lowering achieved relative risk (RR) reductions of 11% for major cardiovascular events (95% CI 1%–21%), 13% for myocardial infarction (0%–25%), 24% for stroke (8%–37%), and 11% for end stage kidney disease (3%–18%). Intensive BP lowering regimens also produced a 10% reduction in the risk of albuminuria (4%–16%), and a trend towards benefit for retinopathy (19%, 0%–34%, p = 0.051) in patients with diabetes. There was no clear effect on cardiovascular or noncardiovascular death. Intensive BP lowering was well tolerated; with serious adverse events uncommon and not significantly increased, except for hypotension (RR 4.16, 95% CI 2.25 to 7.70), which occurred infrequently (0.4% per 100 person-years).

Conclusions

Intensive BP lowering regimens provided greater vascular protection than standard regimens that was proportional to the achieved difference in systolic BP, but did not have any clear impact on the risk of death or serious adverse events. Further trials are required to more clearly define the risks and benefits of BP targets below those currently recommended, given the benefits suggested by the currently available data. Please see later in the article for the Editors'' Summary.     

Obesity and Risk of Colorectal Cancer: A Systematic Review of Prospective Studies

Background

Mounting evidence indicates that obesity may be associated with the risk of colorectal cancer (CRC). To conduct a systematic review of prospective studies assessing the association of obesity with the risk of CRC using meta-analysis.

Methodology/Principal Findings

Relevant studies were identified by a search of MEDLINE and EMBASE databases before January 2012, with no restrictions. We also reviewed reference lists from retrieved articles. We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between general obesity [measured using body mass index (BMI)] or central obesity [measured using waist circumference (WC)] and the risk of colorectal, colon, or rectal cancer. Approximately 9, 000, 000 participants from several countries were included in this analysis. 41 studies on general obesity and 13 studies on central obesity were included in the meta-analysis. The pooled RRs of CRC for the obese vs. normal category of BMI were 1.334 (95% CI, 1.253–1.420), and the highest vs. lowest category of WC were 1.455 (95% CI, 1.327–1.596). There was heterogeneity among studies of BMI (P<0.001) but not among studies of WC (P = 0.323).

Conclusions

Both of general and central obesity were positively associated with the risk of CRC in this meta-analysis.     

Organic Solvents as Risk Factor for Autoimmune Diseases: A Systematic Review and Meta-Analysis

Background

Genetic and epigenetic factors interacting with the environment over time are the main causes of complex diseases such as autoimmune diseases (ADs). Among the environmental factors are organic solvents (OSs), which are chemical compounds used routinely in commercial industries. Since controversy exists over whether ADs are caused by OSs, a systematic review and meta-analysis were performed to assess the association between OSs and ADs.

Methods and Findings

The systematic search was done in the PubMed, SCOPUS, SciELO and LILACS databases up to February 2012. Any type of study that used accepted classification criteria for ADs and had information about exposure to OSs was selected. Out of a total of 103 articles retrieved, 33 were finally included in the meta-analysis. The final odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by the random effect model. A sensitivity analysis confirmed results were not sensitive to restrictions on the data included. Publication bias was trivial. Exposure to OSs was associated to systemic sclerosis, primary systemic vasculitis and multiple sclerosis individually and also to all the ADs evaluated and taken together as a single trait (OR: 1.54; 95% CI: 1.25–1.92; p-value<0.001).

Conclusion

Exposure to OSs is a risk factor for developing ADs. As a corollary, individuals with non-modifiable risk factors (i.e., familial autoimmunity or carrying genetic factors) should avoid any exposure to OSs in order to avoid increasing their risk of ADs.     

Nutritional Support for Patients Sustaining Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prospective Studies

Background

In traumatic brain injury (TBI), the appropriate timing and route of feeding, and the efficacy of immune-enhancing formulae have not been well established. We performed this meta-analysis aiming to compare the effects of different nutritional support modalities on clinical outcomes of TBI patients.

Methods

We systematically searched Pubmed, Embase, and the Cochrane Library until October, 2012. All randomized controlled trials (RCTs) and non-randomized prospective studies (NPSs) that compared the effects of different routes, timings, or formulae of feeding on outcomes in TBI patients were selected. The primary outcomes included mortality and poor outcome. The secondary outcomes included the length of hospital stay, the length of ventilation days, and the rate of infectious or feeding-related complications.

Findings

13 RCTs and 3 NPSs were included. The pooled data demonstrated that, compared with delayed feeding, early feeding was associated with a significant reduction in the rate of mortality (relative risk [RR] = 0.35; 95% CI, 0.24–0.50), poor outcome (RR = 0.70; 95% CI, 0.54–0.91), and infectious complications (RR = 0.77; 95% CI, 0.59–0.99). Compared with enteral nutrition, parenteral nutrition showed a slight trend of reduction in the rate of mortality (RR = 0.61; 95% CI, 0.34–1.09), poor outcome (RR = 0.73; 95% CI, 0.51–1.04), and infectious complications (RR = 0.89; 95% CI, 0.66–1.22), whereas without statistical significances. The immune-enhancing formula was associated with a significant reduction in infection rate compared with the standard formula (RR = 0.54; 95% CI, 0.35–0.82). Small-bowel feeding was found to be with a decreasing rate of pneumonia compared with nasogastric feeding (RR = 0.41; 95% CI, 0.22–0.76).

Conclusion

After TBI, early initiation of nutrition is recommended. It appears that parenteral nutrition is superior to enteral nutrition in improving outcomes. Our results lend support to the use of small-bowel feeding and immune-enhancing formulae in reducing infectious complications.     

Risk Factors for Repetition of Self-Harm: A Systematic Review of Prospective Hospital-Based Studies

Background

Self-harm entails high costs to individuals and society in terms of suicide risk, morbidity and healthcare expenditure. Repetition of self-harm confers yet higher risk of suicide and risk assessment of self-harm patients forms a key component of the health care management of self-harm patients. To date, there has been no systematic review published which synthesises the extensive evidence on risk factors for repetition.

Objective

This review is intended to identify risk factors for prospective repetition of self-harm after an index self-harm presentation, irrespective of suicidal intent.

Data sources

PubMed, PsychInfo and Scirus were used to search for relevant publications. We included cohort studies which examining factors associated with prospective repetition among those presenting with self-harm to emergency departments. Journal articles, abstracts, letters and theses in any language published up to June 2012 were considered. Studies were quality-assessed and synthesised in narrative form.

Results

A total of 129 studies, including 329,001 participants, met our inclusion criteria. Some factors were studied extensively and were found to have a consistent association with repetition. These included previous self-harm, personality disorder, hopelessness, history of psychiatric treatment, schizophrenia, alcohol abuse/dependence, drug abuse/dependence, and living alone. However, the sensitivity values of these measures varied greatly across studies. Psychological risk factors and protective factors have been relatively under-researched but show emerging associations with repetition. Composite risk scales tended to have high sensitivity but poor specificity.

Conclusions

Many risk factors for repetition of self-harm match risk factors for initiation of self-harm, but the most consistent evidence for increased risk of repetition comes from long-standing psychosocial vulnerabilities, rather than characteristics of an index episode. The current review will enhance prediction of self-harm and assist in the efficient allocation of intervention resources.     

Treatment Outcomes of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

Background

Treatment outcomes for multidrug-resistant Mycobacterium Tuberculosis (MDRTB) are generally poor compared to drug sensitive disease. We sought to estimate treatment outcomes and identify risk factors associated with poor outcomes in patients with MDRTB.

Methodology/Principal Findings

We performed a systematic search (to December 2008) to identify trials describing outcomes of patients treated for MDRTB. We pooled appropriate data to estimate WHO-defined outcomes at the end of treatment and follow-up. Where appropriate, pooled covariates were analyzed to identify factors associated with worse outcomes. Among articles identified, 36 met our inclusion criteria, representing 31 treatment programmes from 21 countries. In a pooled analysis, 62% [95% CI 57–67] of patients had successful outcomes, while 13% [9]–[17] defaulted, 11% [9]–[13] died, and 2% [1]–[4] were transferred out. Factors associated with worse outcome included male gender 0.61 (OR for successful outcome) [0.46–0.82], alcohol abuse 0.49 [0.39–0.63], low BMI 0.41[0.23–0.72], smear positivity at diagnosis 0.53 [0.31–0.91], fluoroquinolone resistance 0.45 [0.22–0.91] and the presence of an XDR resistance pattern 0.57 [0.41–0.80]. Factors associated with successful outcome were surgical intervention 1.91 [1.44–2.53], no previous treatment 1.42 [1.05–1.94], and fluoroquinolone use 2.20 [1.19–4.09].

Conclusions/Significance

We have identified several factors associated with poor outcomes where interventions may be targeted. In addition, we have identified high rates of default, which likely contributes to the development and spread of MDRTB.     

Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis

Background

Some popular weight loss diets restricting carbohydrates (CHO) claim to be more effective, and have additional health benefits in preventing cardiovascular disease compared to balanced weight loss diets.

Methods and Findings

We compared the effects of low CHO and isoenergetic balanced weight loss diets in overweight and obese adults assessed in randomised controlled trials (minimum follow-up of 12 weeks), and summarised the effects on weight, as well as cardiovascular and diabetes risk. Dietary criteria were derived from existing macronutrient recommendations. We searched Medline, EMBASE and CENTRAL (19 March 2014). Analysis was stratified by outcomes at 3–6 months and 1–2 years, and participants with diabetes were analysed separately. We evaluated dietary adherence and used GRADE to assess the quality of evidence. We calculated mean differences (MD) and performed random-effects meta-analysis. Nineteen trials were included (n = 3209); 3 had adequate allocation concealment. In non-diabetic participants, our analysis showed little or no difference in mean weight loss in the two groups at 3–6 months (MD 0.74 kg, 95%CI −1.49 to 0.01 kg; I² = 53%; n = 1745, 14 trials; moderate quality evidence) and 1–2 years (MD 0.48 kg, 95%CI −1.44 kg to 0.49 kg; I² = 12%; n = 1025; 7 trials, moderate quality evidence). Furthermore, little or no difference was detected at 3–6 months and 1–2 years for blood pressure, LDL, HDL and total cholesterol, triglycerides and fasting blood glucose (>914 participants). In diabetic participants, findings showed a similar pattern.

Conclusions

Trials show weight loss in the short-term irrespective of whether the diet is low CHO or balanced. There is probably little or no difference in weight loss and changes in cardiovascular risk factors up to two years of follow-up when overweight and obese adults, with or without type 2 diabetes, are randomised to low CHO diets and isoenergetic balanced weight loss diets.     

Hyperuricemia and Risk of Incident Hypertension: A Systematic Review and Meta-Analysis of Observational Studies

Background

Observational studies of the relationship between hyperuricemia and the incidence of hypertension are controversial. We conducted a systematic review and meta-analysis to assess the association and consistency between uric acid levels and the risk of hypertension development.

Methods

We searched MEDLINE, EMBASE, CBM (Chinese Biomedicine Database) through September 2013 and reference lists of retrieved studies to identify cohort studies and nested case-control studies with uric acid levels as exposure and incident hypertension as outcome variables. Two reviewers independently extracted data and assessed study quality using Newcastle-Ottawa Scale. Extracted information included study design, population, definition of hyperuricemia and hypertension, number of incident hypertension, effect sizes, and adjusted confounders. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association between hyperuricemia and risk of hypertension were calculated using a random-effects model.

Results

We included 25 studies with 97,824 participants assessing the association between uric acid and incident hypertension in our meta-analysis. The quality of included studies is moderate to high. Random-effects meta-analysis showed that hyperuricemia was associated with a higher risk of incident hypertension, regardless of whether the effect size was adjusted or not, whether the data were categorical or continuous as 1 SD/1 mg/dl increase in uric acid level (unadjusted: RR = 1.73, 95% CI 1.46∼2.06 for categorical data, RR = 1.22, 95% CI 1.03∼1.45 for a 1 SD increase; adjusted: RR = 1.48, 95% CI 1.33∼1.65 for categorical data, RR = 1.15, 95% CI 1.06∼1.26 for a 1 mg/dl increase), and the risk is consistent in subgroup analyses and have a dose-response relationship.

Conclusions

Hyperuricemia may modestly increase the risk of hypertension incidence, consistent with a dose-response relationship.     

Patient-Related Risk Factors for Periprosthetic Joint Infection after Total Joint Arthroplasty: A Systematic Review and Meta-Analysis

Background

Periprosthetic joint infections (PJIs) are dreaded complications of total joint arthroplasties. The risk of developing PJIs is likely to be influenced by several patient factors such as sociodemographic characteristics, body mass index (BMI), and medical and surgical histories. However, the nature and magnitude of the long-term longitudinal associations between these patient-related factors and risk of developing PJIs are uncertain.

Objective

To conduct a systematic review and meta-analysis to assess the associations between several patient-related factors and PJI.

Data Sources

MEDLINE, EMBASE, Web of Science, Cochrane Library, and reference lists of relevant studies from inception to September 2015.

Study Selection

Longitudinal studies with at least one-year of follow-up for PJIs after total joint arthroplasty.

Data Extraction and Synthesis

Two investigators extracted data on study characteristics, methods, and outcomes. A consensus was reached with involvement of a third. The relative risk (RR) with 95% confidence intervals was used as the summary measure of association across studies. Study-specific RRs with 95% confidence intervals were meta-analysed using random effect models and were grouped by study-level characteristics.

Results

Sixty-six observational (23 prospective cohort and 43 retrospective cohort or case-control) studies with data on 512,508 participants were included. Comparing males to females and smokers to non-smokers, the pooled RRs for PJI were 1.36 (1.18–1.57) and 1.83 (1.24–2.70) respectively. There was no evidence of any significant associations of PJI with age and high alcohol intake. Comparing BMI ≥ 30 versus < 30 kg/m²; ≥ 35 versus < 35 kg/m²; and ≥ 40 versus < 40 kg/m²; the pooled RRs were 1.60 (1.29–1.99); 1.53 (1.22–1.92); and 3.68 (2.25–6.01) respectively. Histories of diabetes, rheumatoid arthritis, depression, steroid use, and previous joint surgery were also associated with increased risk of PJI. The results remained similar when grouped by relevant study level characteristics.

Conclusions

Several potentially modifiable patient-related factors are associated with the risk of developing PJIs. Identifying patients with these risk factors who are due to have arthroplasty surgery and modulating these risk factors might be essential in reducing the incidence of PJI. Further research is however warranted to assess the potential clinical utility of these risk factors as risk assessment tools for PJI.

Systematic Review Registration

PROSPERO 2015: CRD42015023485     

Relationship of Self-Rated Health with Fatal and Non-Fatal Outcomes in Cardiovascular Disease: A Systematic Review and Meta-Analysis

Background

People who rate their health as poor experience higher all-cause mortality. Study of disease-specific association with self-rated health might increase understanding of why this association exists.

Objectives

To estimate the strength of association between self-rated health and fatal and non-fatal cardiovascular disease.

Methods

A comprehensive search of PubMed MEDLINE, EMBASE, CINAHL, BIOSIS, PsycINFO, DARE, Cochrane Library, and Web of Science was undertaken during June 2013. Two reviewers independently searched databases and selected studies. Inclusion criteria were prospective cohort studies or cohort analyses of randomised trials with baseline measurement of self-rated health with fatal or non-fatal cardiovascular outcomes. 20 studies were pooled quantitatively in different meta-analyses. Study quality was assessed using Newcastle-Ottawa scales.

Results

‘Poor’ relative to ‘excellent’ self-rated health (defined by most extreme categories in each study, most often’ poor’ or ‘very poor’ and ‘excellent’ or ‘good’) was associated over a follow-up of 2.3–23 years with cardiovascular mortality in studies: where varying degrees of adjustments had been made for cardiovascular disease risk (HR 1.79 (95% CI 1.50 to 2.14); 15 studies, I2 = 71.24%), and in studies reporting outcomes in people with pre-existing cardiovascular disease or ischaemic heart disease symptoms (HR 2.42 (95% CI 1.32 to 4.44); 3 studies; I2 = 71.83%). ‘Poor’ relative to ‘excellent’ self rated health was also associated with the combined outcome of fatal and non-fatal cardiovascular events (HR 1.90 (95% CI 1.26 to 2.87); 5 studies; I² = 68.61%), Self-rated health was not significantly associated with non-fatal cardiovascular disease outcomes (HR 1.66 (95% CI 0.96 to 2.87); 5 studies; I2 = 83.60%).

Conclusions

Poor self rated health is associated with cardiovascular mortality in populations with and without prior cardiovascular disease. Those with current poor self-rated health may warrant additional input from health services to identify and address reasons for their low subjective health.     

Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis

Objective

To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG).

Methods

This is a systematic review and meta-analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively.

Results

Thirteen studies—seven case-control studies and six population-based cohort studies—were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25–1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17–1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06–1.74).

Conclusions

Individuals with DM have an increased risk of developing POAG.