Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

Background and Aims

Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.

Methods

Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.

Results

In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H₂ blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.

Conclusions

Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.     

Adjunctive Corticotherapy for Community Acquired Pneumonia: A Systematic Review and Meta-Analysis

Background

Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP.

Methods

We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications.

Results

14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96).

Conclusion

Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain.     

Lack of an Association between Angiotensin Receptor Blocker Based Therapy and Increased Risk of Cancer: Evidence from Large Observational Studies

Background

A previous meta-analysis of randomized controlled studies that were not designed to investigate cancer as a primary outcome suggested that ARB-based therapy is associated with increased risk of cancer; however, results of recent observational studies considering the association have been contradictory. This study sought to evaluate the association between angiotensin receptor blocker (ARB)-based therapy and risk of cancer by conducting a meta-analysis of observational studies.

Methods

Relevant articles published before February 2014 were identified by searching PubMed and the Cochrane Library. Pooled relative risks (RRs) were determined using a random effects model and were used to assess the strength of association between use of ARB-based therapy and risk of cancer.

Results

Six retrospective cohort studies involving a total of 3,827,109 participants and four case-control studies involving a total of 193,029 cases were included. The present study found that ARB-based therapy was not significantly associated with an increased risk of cancer (RR = 0.87, 95%CI: [0.75, 1.01]). However, an analysis including only cohort studies suggested a significantly decreased risk of cancer among individuals with any history of ARB use as compared to those with no history of ARB use (RR = 0.80, 95%CI: [0.55, 0.95]); no significant association was found between ARB use and risk of cancer when the case-control studies were separately considered (RR = 1.03, 95%CI: [0.93, 1.13]). Subgroup analyses showed that use of ARB-based therapy was associated with decreased risk of lung cancer (RR = 0.81, 95%CI: [0.69, 0.94]); however, no significant associations were found with the other cancer sites investigated. Furthermore, no association was observed upon adjustment by type of ARB drug. No publication bias was detected.

Conclusion

Overall, ARB-based therapy was not associated with increased risk of cancer. However, its use may be related to decreased incidence of lung cancer; this finding should be considered carefully and confirmed with further studies.     

Quantifying the Evidence for the Risk of Metabolic Syndrome and Its Components following Androgen Deprivation Therapy for Prostate Cancer: A Meta-Analysis

Background

No meta-analysis is yet available for the risk of metabolic syndrome (MetS) following androgen deprivation therapy (ADT) for men with prostate cancer. To summarize the evidence for the link between ADT and MetS or its components quantitatively with a meta-analysis including all studies published to date.

Methods

PubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on the association between metabolic syndrome, hyperglycemia, diabetes, hypertension, dyslipidemia or obesity and androgen deprivation therapy in patients with prostate cancer. Random effects methods were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CI).

Results

A total of nine studies was included. There was a positive association between ADT and risk of MetS (RR: 1.75 (95% CI: 1.27–2.41)). Diabetes was the only MetS component present in more than 3 studies, and also showed an increased risk following ADT (RR: 1.36 (95% CI: 1.17–1.58)).

Conclusion

This is the first quantitative summary addressing the potential risk of MetS following ADT in men with PCa. The positive RRs indicate that there is a need to further elucidate how type and duration of ADT affect these increased risks of MetS and diabetes as the number of men with PCa treated with ADT is increasing.     

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

Background

Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD).

Method

Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses.

Main results

The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08–2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other.

Conclusions

Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients.     

Association between Proton Pump Inhibitor Therapy and Clostridium difficile Infection: A Contemporary Systematic Review and Meta-Analysis

Introduction

Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI).

Methods

Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings.

Results

We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I² = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year.

Conclusions

In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship.     

Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis

Context

Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results.

Objective

To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations.

Data Source and Study Selection

MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality.

Data Extraction

Performed independently by two investigators, using a standardized data extraction sheet.

Data Synthesis

In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45).

Conclusions

Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease.     

Association between Alcohol Consumption and Pancreatic Cancer Risk: A Case-Control Study

Purpose

Evidence is inconsistent regarding alcohol and pancreatic cancer risk, although heavy drinking may increase risk.

Methods

A population-based case-control study was conducted using 345 pancreas cancer cases diagnosed 2011–2012 and 1,285 frequency-matched controls from Ontario, Canada. Logistic regression was used to evaluate alcohol consumption and pancreatic cancer risk; data was also stratified by sex and smoking status to assess interaction.

Results

Alcohol consumption was not associated with pancreatic cancer risk (age-adjusted odds ratio=0.78, 95% CI: 0.58, 1.05 for 1 - 3 drinks/week; age-adjusted odds ratio=0.86, 95% CI: 0.63, 1.17 for 4 - 20 drinks/week), however there was a non-significant increased risk for heavy drinkers consuming ≥21 drinks/week (age-adjusted odds ratio=1.35, 95% CI: 0.81, 2.27). Cigarette smoking modified the alcohol-cancer relationship; among current smokers, heavy alcohol consumption was associated with a significantly increased pancreatic cancer risk (age-adjusted odds ratio=4.04, 95% CI: 1.58, 10.37), whereas this significant association with heavy drinking was not observed among non-smokers (age-adjusted odds ratio=2.01, 95% CI: 0.50, 8.18). Furthermore, light – moderate alcohol intake was associated with increased pancreas cancer risk among current smokers.

Conclusions

While alcohol was not significantly associated with pancreatic cancer risk, smoking status modified this relationship such that among current smokers, alcohol intake was associated with a greater than two-fold increased risk of pancreatic cancer. The results should be interpreted with caution due to small sample sizes within subgroups and correction for multiple comparisons should be considered. These findings should be replicated in larger studies where more precise estimates of risk can be obtained.     

Statin Use and the Risk of Parkinson's Disease: An Updated Meta-Analysis

Introduction

In response to the ongoing debate over the relationship between the use of statins and the risk of Parkinson''s disease (PD), we performed a systematic review and meta-analysis of observational studies to examine their association.

Methods

We conducted a review of the literature using electronic databases supplemented by a manual search to identify potentially relevant case-control or cohort studies. Summary relative risk (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity and subgroup analyses were also conducted.

Results

Eleven studies (five case-control and six cohort) with a total of 3,513,209 participants and 21,011 PD cases were included. Statin use was associated with a lower risk of PD, with a summary RR of 0.81 (95% CI 0.71–0.92). Sensitivity analysis demonstrated the robustness of results. Subgroup analyses showed that neither study design nor study region significantly influenced the effect estimates. However, subgroup studies adjusted for age or sex had a greater inverse association than did unadjusted analyses (age-adjusted RR 0.75, 95% CI 0.60–0.95; age-unadjusted RR 0.86, 95% CI 0.75–0.99 and sex-adjusted RR 0.76, 95% CI 0.59–0.98; sex-unadjusted RR 0.85, 95% CI 0.79–0.92).

Conclusions

Results of this systematic review suggest that statin use is associated with a reduced PD risk. However, randomized controlled trials and more observational studies should be performed before strong conclusions are drawn.     

Severity of Depression,Anxious Distress and the Risk of Cardiovascular Disease in a Swedish Population-Based Cohort

Background

Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association.

Methods

We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases.

Findings

Overall increased odds ratios of 1.5 to 2.6 were seen for the different severity levels of depression, with the highest adjusted OR for moderate depression (OR 2.1 (95% CI 1.3, 3.5). Similar odds ratios were seen for sub-groups of CVD: ischemic/hypertensive heart disease and stroke, 2.4 (95% CI 1.4, 3.9) and OR 2.1 (95%CI 1.2, 3.8) respectively. Depression with anxious distress as a specifier of severity showed OR of 2.1 (95% CI 1.5, 2.9) for CVD.

Conclusion

This study found that severity level of depression seems to be of significance for increased risk of CVD among depressed persons, although not in a dose-response manner which might be obscured due to treatment of depression. Further, we found a higher risk of CVD among depressed individuals with symptoms of anxious distress.     

Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis

Objective

To evaluate the association between hypoxaemia and mortality from acute lower respiratory infections (ALRI) in children in low- and middle-income countries (LMIC).

Design

Systematic review and meta-analysis.

Study Selection

Observational studies reporting on the association between hypoxaemia and death from ALRI in children below five years in LMIC.

Data Sources

Medline, Embase, Global Health Library, Lilacs, and Web of Science to February 2015.

Risk of Bias Assessment

Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger’s test to evaluate publication bias.

Results

Out of 11,627 papers retrieved, 18 studies from 13 countries on 20,224 children met the inclusion criteria. Twelve (66.6%) studies had either low or moderate risk of bias. Hypoxaemia defined as oxygen saturation rate (SpO2) <90% associated with significantly increased odds of death from ALRI (OR 5.47, 95% CI 3.93 to 7.63) in 12 studies on 13,936 children. An Sp02 <92% associated with a similar increased risk of mortality (OR 3.66, 95% CI 1.42 to 9.47) in 3 studies on 673 children. Sensitivity analyses (excluding studies with high risk of bias and using adjusted OR) and subgroup analyses (by: altitude, definition of ALRI, country income, HIV prevalence) did not affect results. Only one study was performed on children living at high altitude.

Conclusions

The results of this review support the routine evaluation of SpO2 for identifying children with ALRI at increased risk of death. Both a Sp02 value of 92% and 90% equally identify children at increased risk of mortality. More research is needed on children living at high altitude. Policy makers in LMIC should aim at improving the regular use of pulse oximetry and the availability of oxygen in order to decrease mortality from ALRI.     

Antenatal Depressive Symptoms and the Risk of Preeclampsia or Operative Deliveries: A Meta-Analysis

Background

The purpose of the study was to investigate the association between depression and/or depressive symptoms during pregnancy and the risk of an operative delivery or preeclampsia, and to quantify the strength of the association.

Methods

A search of the PubMed, SCI/SSCI, Proquest PsycARTICLES and CINAHL databases was supplemented by manual searches of bibliographies of key retrieved articles and review articles. We aimed to include case control or cohort studies that reported data on antenatal depression and /or depressive symptoms and the risk of an operative delivery and/or preeclampsia.

Results

Twelve studies with self-reported screening instruments were eligible for inclusion with a total of 8400 participants. Seven articles that contained 4421 total participants reported the risk for an operative delivery, and five articles that contained 3979 total participants reported the risk for preeclampsia. The pooled analyses showed that both operative delivery and preeclampsia had a statistically significant association with antenatal depressive symptoms (RR = 1.24; 95% CI, 1.14 to 1.35, and OR = 1.63, 95% CI, 1.32 to 2.02, respectively). When the pre-pregnancy body mass indices were controlled in their initial design, the risk for preeclampsia still existed (OR = 1.48, 95% CI, 1.04 to 2.01), while the risk for an operative delivery became uncertain (RR = 1.01, 95% CI, 0.85 to 1.22).

Conclusions

Antenatal depressive symptoms are associated with a moderately increased risk of an operative delivery and preeclampsia. An abnormal pre-pregnancy body mass index may modify this association.     

Antiphospholipid Antibody and Risk of Retinal Vein Occlusion: A Systematic Review and Meta-Analysis

Background

Retinal vein occlusion (RVO) is a common retinal vascular disease and it is one of the most frequently reported causes of visual damage and blindness in the elderly. The current study investigated the potential association between antiphospholipid antibodies (APLA) and RVO risk by conducting a meta-analysis of case–control studies.

Methods

A systematic literature search of Pubmed and Embase databases was conducted in August 1^st, 2014. Odds ratios (ORs) were used to evaluate the associations between APLA and the incidence of RVO. A random-effects model was obtained for the quantitative synthesis.

Results

A total of 11 studies were included in this meta-analysis. A meta-analysis of all studies assessing the risk of RVO revealed that APLA was associated with a statistically increased risk of RVO incidence (OR = 5.18, 95% CI = [3.37, 7.95]). The association between anticardiolipin antibodies (ACA) and the risk of RVO was significant (n =8, OR = 4.59, 95% CI = [2.75, 7.66]). However, the association between lupus anticoagulants (LA) and risk of RVO was non-significant (n = 5, OR = 3.90, 95% CI = [0.99, 15.37]). No significant publication bias was found in the 11 selected studies.

Conclusion

APLA was significantly associated with the risk of RVO. Advanced analyses showed that ACA rather than LA affected the risk of RVO. Additional well-designed and well-conducted epidemiological studies are required to further our understanding of the relationship between APLA and RVO risk.     

Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia

Background

Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP).

Objective

To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.

Results

We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07–1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50–2.04) and renal disease (OR, 1.57; 95% CI, 1.21–2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52–0.73). Bacteremia (OR, 1.37; 95% CI, 1.05–1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31–1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10–2.49) were associated with severe sepsis CAP.

Conclusions

CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.     

Type,Number or Both? A Population-Based Matched Case-Control Study on the Risk of Fall Injuries among Older People and Number of Medications beyond Fall-Inducing Drugs

Objectives

Drug use is a modifiable risk factor for fall-related injuries in older people. Whereas the injurious effect of polypharmacy is established, that of low numbers of medications has not been fully ascertained. Neither do we know whether it is the number per se or the type of medications that actually matters. We assessed this question for fall injuries leading to hospitalization.

Design

National register-based, population-based, matched case-control study.

Setting

Community dwellers aged 65+ years living in Sweden between March 2006 and December 2009.

Methods

Cases (n = 64,399) were identified in the national inpatient register and four controls per case were randomly matched by gender, date of birth and residential area. The association between number of prescribed medications, assessed through linkage with the Swedish prescribed drug register, and the risk of injurious falls was estimated with odds ratios with 95% confidence intervals using conditional logistic regression, adjusted for demographic and health status.

Results

The number of medications was associated with an increased risk of fall injury in a dose-response fashion, even after adjustment for marital status, comorbidity and number of fall-risk-inducing drugs (FRIDs). Using ten or more medications was associated with an almost two-fold higher risk (adjusted OR: 1.76, 95% CI: 1.66 to 1.88). When stratified by use (or not) of at least one FRID, the association weakened slightly among both non-users (adjusted OR: 1.50, 95% CI: 1.34 to 1.67) and users (adjusted OR: 1.67, 95% CI: 1.58 to 1.77).

Conclusion

In older people, not only large but also small numbers of medications may affect the risk for them to sustain injurious falls. Although the mechanisms lying behind this are complex, the finding challenges the prevention strategies targeting either specific types of medications (FRIDs) or high numbers of them.     

Tobacco Use and Suicide Attempt: Longitudinal Analysis with Retrospective Reports

Background

Suicide has been associated with smoking/tobacco use but its association of and change in smoking/tobacco use status with suicide attempt (SA) is not well established.

Methods

We investigated whether persistent, former tobacco use, initiation, quitting tobacco use, relapse to tobacco use, and DSM-IV nicotine dependence predict independently SA using Wave 1 and 2 data of the National Epidemiologic Survey of Alcohol and Related Conditions. Data from 34,653 US adults interviewed at Wave 1 (2001-02) and Wave 2 (2004-05) were analyzed. The main outcome measure was SA between Wave 1 and Wave 2 as reported at Wave 2.

Results

Among the 1,673 respondents reporting lifetime SA at Wave 2, 328 individuals reported SA between Wave 1 and Wave 2. Current and former tobacco use at Wave 1 predicted Wave 2 SA independently of socio-demographic characteristics, psychiatric history, and prior SA (Adjusted Odds Ratio (AOR): 1.49; 95% CI: 1.13-1.95, AOR: 1.31; 95% CI:1.01-1.69, respectively versus never tobacco users). The strongest association with SA was observed among former tobacco users who relapsed after Wave 1 (AOR: 4.66; 95% CI: 3.49-6.24) and among tobacco use initiators after Wave 1 (AOR: 3.16; 95% CI: 2.23-4.49). Persistent tobacco use (current tobacco use at both Wave 1 and Wave 2) also had an increased risk of SA (AOR: 1.89; 95% CI: 1.47-2.42). However, former tobacco users in both Waves 1 and 2 did not show a significantly elevated risk for SA in Wave 2 (AOR:1.09, 95% CI: 0.78-1.52) suggesting that the risk resided mainly in Wave 1 former tobacco users who relapsed to tobacco use by Wave 2. DSM-IV nicotine dependence did not predict SA at Wave 2.

Conclusion

In a representative sample of US adults, relapse, tobacco use initiation, and persistent tobacco use, which are amenable to intervention, were associated with risk of SA.     

Fish Intake and Risk of Liver Cancer: A Meta-Analysis

Background

Increasing laboratory findings indicate that n-3 fatty acids, mainly derived from fish, inhibit cancer development and progression, but results from epidemiologic studies have been inconsistent and inconclusive.

Objective

To evaluate the association of fish intake with risk of liver cancer by conducting a meta-analysis.

Methods

Published case-control/cohort studies that evaluated the relationship between total fish intake and risk of liver cancer were found on PubMed and EMBASE. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were obtained with the random-effects model.

Results

Five retrospective case-control studies and 5 prospective cohort studies were included in the final analysis, involving a total of 3 624 liver cancer cases. Comparing the highest with the lowest category of total fish intake, the pooled RRs of liver cancer were 0.79 (95% CI, 0.59-1.06) for case-control studies, 0.82 (95% CI, 0.70-0.96) for cohort studies and 0.82 (95% CI, 0.71-0.94) for all studies combined. The protective effects of total fish intake against liver cancer were confirmed by stratified and sensitivity analyses. In addition, an increase in fish intake of 1 serving/week was estimated to be significantly associated with 6% lower risk of liver cancer (RR = 0.94, 95% CI, 0.91-0.98).

Conclusions

Findings from this meta-analysis suggest that a higher fish intake is associated with reduced risk of liver cancer.     

Opioids Contribute to Fracture Risk: A Meta-Analysis of 8 Cohort Studies

Objective

To evaluate the association between chronic opioid use for non-cancer pain and fracture risk by conducting a meta-analysis of cohort studies.

Methods

Cohort studies were identified by searching PubMed and EMBASE from their inception to July 2014. A fracture was considered an endpoint. The information was extracted by two authors independently. When the heterogeneity was significant, a random-effects model was used to calculate the overall pooled risk estimates.

Results

Eight cohort studies were included in the final meta-analysis. On the basis of the Newcastle-Ottawa Scale (NOS), six studies were considered to be of high quality. The overall combined relative risk for the use of opioids and fractures was 1.88 (95% confidence interval [CI] 1.51-2.34). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed.

Conclusions

This meta-analysis of cohort studies demonstrates that opioids significantly increase the risk of fractures.     

Serum Levels of Monocyte Chemoattractant Protein-1 and All-Cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.     

Antipyretic Therapy in Critically Ill Patients with Sepsis: An Interaction with Body Temperature

Background and Objective

The effect of antipyretic therapy on mortality in patients with sepsis remains undetermined. The present study aimed to investigate the role of antipyretic therapy in ICU patients with sepsis by using a large clinical database.

Methods

The multiparameter intelligent monitoring in intensive care II (MIMIC- II) database was employed for the study. Adult patients with sepsis were included for analysis. Antipyretic therapy included antipyretic medication and external cooling. Multivariable model with interaction terms were employed to explore the association of antipyretic therapy and mortality risk.

Main Results

A total of 15,268 patients fulfilled inclusion criteria and were included in the study. In multivariable model by treating temperature as a continuous variable, there was significant interaction between antipyretic therapy and the maximum temperature (T_max). While antipyretic therapy had no significant effect on mortality in low temperature quintiles, antipyretic therapy was associated with increased risk of death in the quintile with body temperature >39°C (OR: 1.29, 95% CI: 1.04–1.61).

Conclusion

Our study shows that there is no beneficial effect on reducing mortality risk with the use of antipyretic therapy in ICU patients with sepsis. External cooling may even be harmful in patients with sepsis.