Impact of statins and ACE inhibitors on mortality after COPD exacerbations

Background

The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.

Methods

We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.

Results

We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.

Conclusion

Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.     

Meta-Analysis of Combined Therapy with Angiotensin Receptor Antagonists versus ACE Inhibitors Alone in Patients with Heart Failure

Background

There is insufficient evidence whether the benefit of adding angiotensin II receptor blockers (ARBs) to angiotensin-converting enzyme (ACE) inhibitors outweighs the increased risk of adverse effects in patients with heart failure.

Methodology/Principal Findings

Two independent reviewers searched and abstracted randomized controlled trials of ARBs and ACE inhibitors compared to ACE inhibitor therapy alone in patients with heart failure reporting mortality and hospitalizations having a follow-up of at least 6 months identified by a systematic literature search. Eight trials including a total of 18,061 patients fulfilled our inclusion criteria. There was no difference between patients treated with combination therapy and ACE inhibitor therapy alone for overall mortality, hospitalization for any reason, fatal or nonfatal MI. Combination therapy was, however, associated with fewer hospital admissions for heart failure (RR 0.81, 95%CI 0.72–0.91), although there was significant heterogeneity across trials (p-value for heterogeneity = 0.04; I² = 57% [95%CI 0–83%]). Patients treated with combination therapy had a higher risk of worsening renal function and symptomatic hypotension, and their trial medications were more often permanently discontinued. Lack of individual patient data precluded the analysis of time-to-event data and identification of subgroups which potentially benefit more from combination therapy such as younger patients with preserved renal function and thus at lower risk to experience worsening renal function or hyperkalemia.

Conclusions/Significance

Combination therapy with ARBs and ACE inhibitors reduces admissions for heart failure in patients with congestive heart failure when compared to ACE inhibitor therapy alone, but does not reduce overall mortality or all-cause hospitalization and is associated with more adverse events. Thus, based on current evidence, combination therapy with ARBs and ACE inhibitors may be reserved for patients who remain symptomatic on therapy with ACE inhibitors under strict monitoring for any signs of worsening renal function and/or symptomatic hypotension.     

Cardiovascular and Renal Outcomes of Renin–Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses

Background

Medications aimed at inhibiting the renin–angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.

Methods and Findings

Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke—singly and as a composite endpoint, major cardiovascular outcome—and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality—singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90–1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79–1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96–1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73–1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90–1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72–1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65–1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78–1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints.

Conclusions

In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment.

Review registration

PROSPERO CRD42014014404     

Factors Associated with Appointment Non-Adherence among African-Americans with Severe,Poorly Controlled Hypertension

Background

Missed appointments are associated with an increased risk of hospitalization and mortality. Despite its widespread prevalence, little data exists regarding factors related to appointment non-adherence among hypertensive African-Americans.

Objective

To investigate factors associated with appointment non-adherence among African-Americans with severe, poorly controlled hypertension.

Design and Participants

A cross-sectional survey of 185 African-Americans admitted to an urban medical center in Maryland, with severe, poorly controlled hypertension from 1999–2004. Categorical and continuous variables were compared using chi-square and t-tests. Adjusted multivariable logistic regression was used to assess correlates of appointment non-adherence.

Main Outcome Measures

Appointment non-adherence was the primary outcome and was defined as patient-report of missing greater than 3 appointments out of 10 during their lifetime.

Results

Twenty percent of participants (n = 37) reported missing more than 30% of their appointments. Patient characteristics independently associated with a higher odds of appointment non-adherence included not finishing high school (Odds ratio [OR] = 3.23 95% confidence interval [CI] (1.33–7.69), hypertension knowledge ([OR] = 1.20 95% CI: 1.01–1.42), lack of insurance ([OR] = 6.02 95% CI: 1.83–19.88), insurance with no medication coverage ([OR] = 5.08 95% CI: 1.05–24.63), cost of discharge medications ([OR] = 1.20 95% CI: 1.01–1.42), belief that anti-hypertensive medications do not work ([OR] = 3.67 95% CI: 1.16–11.7), experience of side effects ([OR] = 3.63 95% CI: 1.24–10.62), medication non-adherence ([OR] = 11.31 95% CI: 3.87–33.10). Substance abuse was not associated with appointment non-adherence ([OR] = 1.05 95% CI: 0.43–2.57).

Conclusions

Appointment non-adherence among African-Americans with poorly controlled hypertension was associated with many markers of inadequate access to healthcare, knowledge, attitudes and beliefs.     

Association of Body Mass Index with Cause Specific Deaths in Chinese Elderly Hypertensive Patients: Minhang Community Study

Background

Most studies have suggested that elevated body mass index (BMI) was associated with the risk of death from all cause and from specific causes. However, there was little evidence illustrating the effect of BMI on the mortality in elderly hypertensive patients in Chinese population.

Methods

The information of 10,957 hypertensive patients at baseline not less than 60 years were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from the Electronic Health Record (EHR) system. All study participants were divided into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28 and 30 kg/m²). Relative hazard ratio of death from all cause, cardiovascular and non-cardiovascular cause by baseline BMI groups were calculated, standardized for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment.

Results

During follow up (median: 3.7 years), 561 deaths occurred. Underweight (BMI<18 kg/m²) was associated with significantly increased mortality from all cause mortality (OR: 2.00; 95% CI: 1.43–2.79) and non cardiovascular mortality (OR: 2.76; 95% CI: 1.87–4.07), but not with cardiovascular mortality. For the cause specific analysis, the underweight was associated significantly with neoplasms (OR: 2.15; 95% CI: 1.16–4.00) and respiratory disorders (OR: 3.41; 95% CI: 1.64–7.06). The results for total mortality and specific cause mortality were not influenced by sex, age and smoking status.

Conclusion

Our study revealed an association between underweight and increased mortality from non-cardiovascular disorders in elderly hypertensive patients in Chinese community. Overweight and obesity were not associated with all cause or cause specific death.     

Factors associated with the use of evidence-based therapies after discharge among elderly patients with myocardial infarction

Background

In an accompanying article, we report moderate between-hospital variation in the postdischarge use of β-blockers, angiotensin-modifying drugs and statins by elderly patients who had been admitted to hospital with acute myocardial infarction. Our objective was to identify the characteristics of patients, physicians, hospitals and communities associated with differences in the use of these medications after discharge.

Methods

For this retrospective, population-based cohort study, we used linked administrative databases. We examined data for all patients aged 65 years or older who were discharged from hospital in 2005/06 with a diagnosis of myocardial infarction. We determined the effect of patient, physician, hospital and community characteristics on the rate of postdischarge medication use.

Results

Increasing patient age was associated with lower postdischarge use of medications. The odds ratios (ORs) for a 1-year increase in age were 0.98 (95% confidence interval [CI] 0.97–0.99) for β-blockers, 0.97 (95% CI 0.97–0.98) for angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers and 0.94 (95% CI 0.93–0.95) for statins. Having a general or family practitioner, a general internist or a physician of another specialty as the attending physician, relative to having a cardiologist, was associated with lower postdischarge use of β-blockers, angiotensin-modifying agents and statins (ORs ranging from 0.46 to 0.82). Having an attending physician with 29 or more years experience, relative to having a physician who had graduated within the past 15 years, was associated with lower use of β-blockers (OR 0.71, 95% CI 0.60–0.84) and statins (OR 0.81, 95% CI 0.67–0.97).

Interpretation

Patients who received care from noncardiologists and physicians with at least 29 years of experience had substantially lower use of evidence-based drug therapies after discharge. Dissemination strategies should be devised to improve the prescribing of evidence-based medications by these physicians.The use of medications such as acetylsalicylic acid (ASA), β-blockers, angiotensin-modifying drugs (angiotensin-converting-enzyme [ACE] inhibitors and angiotensin-receptor blockers) and statins is a mainstay of secondary prevention of myocardial infarction. In a companion study published in this issue of CMAJ, we report substantial increases in the use of evidence-based drug therapies after discharge among elderly patients with myocardial infarction over a 14-year period.¹ However, despite temporal improvements, the prescribing of evidence-based drug therapies differed among hospitals in 2005.Studies from the late 1980s to the mid-1990s showed that the prescribing of evidence-based drug therapies was influenced by patient characteristics.^2–6 However, the extent to which postdischarge prescribing is influenced by patient, physician, hospital and community characteristics has not been extensively explored.Our objective was to identify patient, physician, hospital and community characteristics associated with the use of of evidence-based drug therapies after discharge among patients with myocardial infarction.     

Large Daily Stock Variation Is Associated with Cardiovascular Mortality in Two Cities of Guangdong,China

Objective

The current study aimed to examine the effects of daily change of the Shenzhen Stock Exchange Index on cardiovascular mortality in Guangzhou and Taishan, China.

Methods

Daily mortality and stock performance data during 2006–2010 were collected to construct the time series for the two cities. A distributed lag non-linear model was utilized to examine the effect of daily stock index changes on cardiovascular mortality after controlling for potential confounding factors.

Results

We observed a delayed non-linear effect of the stock index change on cardiovascular mortality: both rising and declining of the stock index were associated with increased cardiovascular deaths. In Guangzhou, the 15–25 lag days cumulative relative risk of an 800 index drop was 2.08 (95% CI: 1.38–3.14), and 2.38 (95% CI: 1.31–4.31) for an 800 stock index increase on the cardiovascular mortality, respectively. In Taishan, the cumulative relative risk over 15–25 days lag was 1.65 (95% CI: 1.13–2.42) for an 800 index drop and 2.08 (95% CI: 1.26–3.42) for an 800 index rising, respectively.

Conclusions

Large ups and downs in daily stock index might be important predictor of cardiovascular mortality.     

Differential Impact of Statin on New-Onset Diabetes in Different Age Groups: A Population-Based Case-Control Study in Women from an Asian Country

Background

Statins reduce cardiovascular risks but increase the risk of new-onset diabetes (NOD). The aim of this study is to determine what effect, if any, statins have on the risk of NOD events in a population-based case-control study. An evaluation of the relationship between age and statin-exposure on NOD risks was further examined in a female Asian population.

Method

In a nationwide case-controlled study, the authors assessed 1065 female NOD patients and 10650 controls with matching ages, genders and physician visit dates. The impact of statin-exposure on NOD was examined through multiple logistic regression models. Subgroup analysis for exploring the risk of NOD and statin-exposure in different age groups was performed.

Results

Statin-exposure was statistically significantly associated with increased new-onset diabetes risks using multivariate analysis. Interaction effect between age and statin-exposure on NOD risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57–24.90). For rosuvastatin, the risk of cDDDs>60 was highest among the 40–54 year-olds (adjusted OR, 14.8; 95% CI, 2.27–96.15). For simvastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted OR, 15.8; 95% CI, 5.77–43.26). For pravastatin, the risk of cDDDs>60 was highest among the 55–64 year-olds (adjusted OR, 14.0; 95% CI, 1.56–125.18).

Conclusions

This population-based study found that statin use is associated with an increased risk of NOD in women. The risk of statin-related NOD was more evident for women aged 40–64 years compared to women aged 65 or more, and was cumulative-dose dependent. The use of statins should always be determined by weighing the clinical benefits and potential risks for NOD, and the patients should be continuously monitored for adverse effects.     

Statin use and the presence of microalbuminuria. Results from the ERICABEL trial: a non-interventional epidemiological cohort study

Background

Microalbuminuria (MAU) is considered as a predictor or marker of cardiovascular and renal events. Statins are widely prescribed to reduce cardiovascular risk and to slow down progression of kidney disease. But statins may also generate tubular MAU. The current observational study evaluated the impact of statin use on the interpretation of MAU as a predictor or marker of cardiovascular or renal disease.

Methodology/Principal Findings

We used cross-sectional data of ERICABEL, a cohort with 1,076 hypertensive patients. MAU was defined as albuminuria ≥20 mg/l. A propensity score was created to correct for “bias by indication” to receive a statin. As expected, subjects using statins vs. no statins had more cardiovascular risk factors, pointing to bias by indication. Statin users were more likely to have MAU (OR: 2.01, 95%CI: 1.34–3.01). The association between statin use and MAU remained significant after adjusting for the propensity to receive a statin based on cardiovascular risk factors (OR: 1.82, 95%CI: 1.14–2.91). Next to statin use, only diabetes (OR: 1.92, 95%CI: 1.00–3.66) and smoking (OR: 1.49, 95%CI: 0.99–2.26) were associated with MAU.

Conclusions

Use of statins is independently associated with MAU, even after adjusting for bias by indication to receive a statin. In the hypothesis that this MAU is of tubular origin, statin use can result in incorrect labeling of subjects as having a predictor or marker of cardiovascular or renal risk. In addition, statin use affected the association of established cardiovascular risk factors with MAU, blurring the interpretation of multivariable analyses.     

Influenza Morbidity and Mortality in Elderly Patients Receiving Statins: A Cohort Study

Background

Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks.

Methodology/Principal Findings

We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. We identified all adults older than 65 years who had received an influenza vaccination prior to the start of influenza season and distinguished those also prescribed statins (23%) from those not also prescribed statins (77%). Propensity-based matching, which accounted for each individual''s likelihood of receiving a statin, yielded a final cohort of 2,240,638 patients, exactly half of whom received statins. Statins were associated with small protective effects against pneumonia hospitalization (odds ratio [OR] 0.92; 95% CI 0.89–0.95), 30-day pneumonia mortality (0.84; 95% CI 0.77–0.91), and all-cause mortality (0.87; 95% CI 0.84–0.89). These protective effects attenuated substantially after multivariate adjustment and when we excluded multiple observations for each individual, declined over time, differed across propensity score quintiles and risk groups, and were unchanged during post-influenza season periods. The main limitations of this study were the observational study design, the non-specific outcomes, and the lack of information on medications while hospitalized.

Conclusions/Significance

Statin use is associated with a statistically significant but minimal protective effect against influenza morbidity that can easily be attributed to residual confounding. Public health officials and clinicians should focus on other measures to reduce morbidity and mortality from the next influenza pandemic.     

Polymorphisms of C242T and A640G in CYBA Gene and the Risk of Coronary Artery Disease: A Meta-Analysis

Background

Coronary artery disease (CAD) is a leading cause of mortality in many countries. Considerable studies have been carried out to investigate the relationship between the C242T and A640G polymorphisms of CYBA gene and CAD, but the results were still inconsistent. Hence we conducted a meta-analysis to clarify the association.

Methods and Results

A total of 21 eligible literatures were included in the meta-analysis. We observed a significant decreased risk of CAD for C242T polymorphism in Asian population under an allelic model (OR 0.75; 95% CI 0.67–0.84) and a dominant model (OR 0.69; 95% CI 0.61–0.79), however, in overall population and other population no significant association was revealed. We also found A640G polymorphism may contribute to reducing CAD risk under an allelic model (OR 0.84; 95% CI 0.75–0.93), dominant model (OR0.77; 95% CI 0.64–0.92) and recessive model (OR0.82; 95% CI 0.69–0.97). No publication bias was found.

Conclusion

Our meta-analysis confirmed a protective effect of C242Tpolymorphism on CAD in Asian population and indicated that A640G polymorphism was significantly associated with decreased risk of CAD.     

Efficacy of Standard and Intensive Statin Treatment for the Secondary Prevention of Cardiovascular and Cerebrovascular Events in Diabetes Patients: A Meta-Analysis

Aims

To estimate the efficacy of standard and intensive statin treatment in the secondary prevention of major cardiovascular and cerebrovascular events in diabetes patients.

Methods

A systematic search was conducted in Medline over the years 1990 to September 2013. Randomized, double-blind, clinical trials comparing a standard-dose statin with placebo or a standard-dose statin with an intensive-dose statin for the secondary prevention of cardiovascular and cerebrovascular events in diabetes patients were selected. Trial and patient characteristics were extracted independently by two researchers. The combined effect on the composite primary endpoint was measured with a fixed-effect model. Potential publication bias was examined with a funnel plot.

Results

Five trials were included in the analysis comparing standard-dose statins with placebo with a total of 4 351 participants. Four trials were included for comparing standard-dose with intensive-dose statins, including 4 805 participants. Compared with placebo, standard-dose statin treatment resulted in a significant relative risk (RR) reduction of 15% in the occurrence of any major cardiovascular or cerebrovascular event (RR 0.85, 95% CI 0.79–0.91). Compared with standard-dose statin treatment, intensive-dose statin treatment resulted in an additional 9% relative risk reduction (RR 0.91, 95% CI 0.84–0.98).

Conclusion

Treatment with standard-dose statins to prevent cardiovascular or cerebrovascular events in diabetes patients with manifest cardiovascular disease results in an estimated 15% relative risk reduction and intensive-dose statin treatment adds 9%. If proven cost-effective, more intensive statin treatment should be recommended for diabetes patients at high cardiovascular risk.     

Inappropriate Drugs in Elderly Patients with Severe Cognitive Impairment: Results from the Shelter Study

Background

It has been estimated that Nursing Home (NH) residents with impaired cognitive status receive an average of seven to eight drugs daily. The aim of this study was to determine prevalence and factors associated with use of inappropriate drugs in elderly patients with severe cognitive impairment living in NH in Europe.

Methods

Cross-sectional data from a sample of 1449 NH residents with severe cognitive impairment, participating in the Services and Health for Elderly in Long TERm care (SHELTER) study were analysed. Inappropriate drug use was defined as the use of drugs classified as rarely or never appropriate in patients with severe cognitive impairment based on the Holmes criteria published in 2008.

Results

Mean age of participating residents was 84.2±8.9 years, 1087 (75.0%) were women. Inappropriate drug use was observed in 643 (44.9%) residents. Most commonly used inappropriate drugs were lipid-lowering agents (9.9%), antiplatelet agents (excluding Acetylsalicylic Acid – ASA –) (9.9%), acetylcholinesterase, inhibitors (7.2%) and antispasmodics (6.9%). Inappropriate drug use was directly associated with specific diseases including diabetes (OR 1.64; 95% CI 1.21–2.24), heart failure (OR 1.48; 95% CI 1.04–2.09), stroke (OR 1.43; 95% CI 1.06–1.93), and recent hospitalization (OR 1.69; 95% CI 1.20–2.39). An inverse relation was shown between inappropriate drug use and presence of a geriatrician in the facility (OR 0.55; 95% CI 0.39–0.77).

Conclusion

Use of inappropriate drugs is common among older EU NH residents. Determinants of inappropriate drug use include comorbidities and recent hospitalization. Presence of a geriatrician in the facility staff is associated with a reduced rate of use of these medications.     

Negative Events in Childhood Predict Trajectories of Internalizing Symptoms Up to Young Adulthood: An 18-Year Longitudinal Study

Background

Common negative events can precipitate the onset of internalizing symptoms. We studied whether their occurrence in childhood is associated with mental health trajectories over the course of development.

Methods

Using data from the TEMPO study, a French community-based cohort study of youths, we studied the association between negative events in 1991 (when participants were aged 4–16 years) and internalizing symptoms, assessed by the ASEBA family of instruments in 1991, 1999, and 2009 (n = 1503). Participants'' trajectories of internalizing symptoms were estimated with semi-parametric regression methods (PROC TRAJ). Data were analyzed using multinomial regression models controlled for participants'' sex, age, parental family status, socio-economic position, and parental history of depression.

Results

Negative childhood events were associated with an increased likelihood of concurrent internalizing symptoms which sometimes persisted into adulthood (multivariate ORs associated with > = 3 negative events respectively: high and decreasing internalizing symptoms: 5.54, 95% CI: 3.20–9.58; persistently high internalizing symptoms: 8.94, 95% CI: 2.82–28.31). Specific negative events most strongly associated with youths'' persistent internalizing symptoms included: school difficulties (multivariate OR: 5.31, 95% CI: 2.24–12.59), parental stress (multivariate OR: 4.69, 95% CI: 2.02–10.87), serious illness/health problems (multivariate OR: 4.13, 95% CI: 1.76–9.70), and social isolation (multivariate OR: 2.24, 95% CI: 1.00–5.08).

Conclusions

Common negative events can contribute to the onset of children''s lasting psychological difficulties.     

The Role of Statins in Prevention and Treatment of Community Acquired Pneumonia: A Systematic Review and Meta-Analysis

Background

Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications.

Purpose

Performed a systematic review to address the role of statins in the prevention or treatment of CAP.

Data Source

Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies.

Study Selection

Two authors independently reviewed studies that examined the role of statins in CAP.

Data Extraction

Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted.

Data Synthesis

Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74–0.95), I² = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59–0.78), I² = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77–0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder.

Conclusions

Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias.     

Risk Factors Associated with Death in In-Hospital Pediatric Convulsive Status Epilepticus

Objective

To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort.

Patients and Methods

We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant.

Results

We identified 12,365 (5,541 female) patients with convulsive SE aged 0–20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years) among 14,965,571 pediatric inpatients (0.08%). Of these, 117 died while in the hospital (0.9%). The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure.Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4–426.8), hemorrhagic shock (OR 17.83; CI 6.5–49.1), sepsis (OR 10.14; CI 4.0–25.6), massive aspiration (OR 9.1; CI 1.8–47), mechanical ventilation >96 hours (OR9; 5.6–14.6), transfusion (OR 8.25; CI 4.3–15.8), structural brain lesion (OR7.0; CI 3.1–16), hypoglycemia (OR5.8; CI 1.75–19.2), sepsis with liver failure (OR 14.4; CI 5–41.9), and admission in December (OR3.4; CI 1.6–4.1). African American ethnicity (OR 0.4; CI 0.2–0.8) was associated with a decreased risk of death in SE.

Conclusion

Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management.     

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes High Risk for Chronic Kidney Disease in Asian Male with Hypertension–A Meta-Regression Analysis of 98 Observational Studies

Background

Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial.

Objectives

This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk.

Data sources

PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013.

Study eligibility criteria, participants, and interventions

Cross-sectional surveys and case–control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity.

Study appraisal and synthesis methods

The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models.

Results

Ethnicity [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.08–1.42] and hypertension (OR: 1.55; 95% CI: 1.04–2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84–7.65) for CKD in hypertensive Asian males.

Conclusions and implications of key findings

The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.