Secondary Antifungal Prophylaxis in Hematological Malignancy Patients with Previous Invasive Fungal Disease: A Retrospective Analysis

Background

Invasive fungal disease (IFD) causes morbidity and mortality in patients with hematological malignancy. Recurrence of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is associated with poor prognosis. The present study aimed to investigate the efficacy of different strategies of secondary antifungal prophylaxis (SAP) for IFD and choose an appropriate SAP regimen.

Methods

Clinical data of patients with previous IFD who underwent chemotherapy or HSCT between Jan 2008 and Jun 2013 were retrospectively reviewed and followed up to 180 days post-chemotherapy or HSCT. The clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IFD. The efficacy of different strategies for SAP and risk factors influencing the failure of SAP were evaluated.

Results

Of the 164 patients enrolled, 121 patients received SAP regimen (73.78%), and IFD recurred in 40 patients: 16.5% (20/121) in SAP group and 46.5% (20/43) in non-SAP group. In SAP group, 58 received SAP agents which were proven effective for their previous IFD, while other 63 patients received other broad-spectrum antifungal agents. There was no significant difference in the recurrence rates between these two subgroups (13.8% (8/58) vs 19.0% (12/63), P = 0.437). The IFD recurrence rates were statistically significant between patients with allogeneic HSCT and chemotherapy or autologous HSCT (25% vs 8.2%, P = 0.013). Multivariate analysis indicated that allogeneic HSCT was the independent risk factor of IFD recurrence after SAP.

Conclusions

Secondary antifungal prophylaxis is necessary to prevent IFD recurrence in patients with hematological malignancy, especially for patients in the setting of allogeneic HSCT.     

Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999–2009

Background

Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa from 1999–2009.

Methods

We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate.

Results

PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6–5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4–91.0). Among individuals aged ≥65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0–14.0).

Conclusion

We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics.     

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

Objective

To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI).

Methods

PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.

Results

A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66).

Conclusions

Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.     

Relevant Obstetric Factors for Cerebral Palsy: From the Nationwide Obstetric Compensation System in Japan

Objective

The aim of this study was to identify the relevant obstetric factors for cerebral palsy (CP) after 33 weeks’ gestation in Japan.

Study design

This retrospective case cohort study (1:100 cases and controls) used a Japanese national CP registry. Obstetric characteristics and clinical course were compared between CP cases in the Japan Obstetric Compensation System for Cerebral Palsy database and controls in the perinatal database of the Japan Society of Obstetrics and Gynecology born as live singleton infants between 2009 and 2011 with a birth weight ≥ 2,000 g and gestation ≥ 33 weeks.

Results

One hundred and seventy-five CP cases and 17,475 controls were assessed. Major relevant single factors for CP were placental abnormalities (31%), umbilical cord abnormalities (15%), maternal complications (10%), and neonatal complications (1%). A multivariate regression model demonstrated that obstetric variables associated with CP were acute delivery due to non-reassuring fetal status (relative risk [RR]: 37.182, 95% confidence interval [CI]: 20.028–69.032), uterine rupture (RR: 24.770, 95% CI: 6.006–102.160), placental abruption (RR: 20.891, 95% CI: 11.817–36.934), and preterm labor (RR: 3.153, 95% CI: 2.024–4.911), whereas protective factors were head presentation (RR: 0.199, 95% CI: 0.088–0.450) and elective cesarean section (RR: 0.236, 95% CI: 0.067–0.828).

Conclusion

CP after 33 weeks’ gestation in the recently reported cases in Japan was strongly associated with acute delivery due to non-reassuring fetal status, uterine rupture, and placental abruption.     

Diagnostic Efficacy of Magnifying Endoscopy with Narrow-Band Imaging for Gastric Neoplasms: A Meta-Analysis

Background

Magnifying endoscopy with narrow-band imaging (ME-NBI) is a novel, image-enhanced endoscopic technique for differentiating gastrointestinal neoplasms and potentially enabling pathological diagnosis.

Objectives

The aim of this analysis was to assess the diagnostic performance of ME-NBI for gastric neoplasms.

Methods

We performed a systematic search of the PubMed, EMbase, Web of Science, and Cochrane Library databases for relevant studies. Meta-DiSc (version 1.4) and STATA (version 11.0) software were used for the data analysis. Random effects models were used to assess diagnostic efficacy. Heterogeneity was tested by the Q statistic and I² statistic. Meta-regression was used to analyze the sources of heterogeneity.

Results

A total of 10 studies, with 2151 lesions, were included. The pooled characteristics of these studies were as follows: sensitivity 0.85 (95% confidence interval [CI]: 0.81–0.89), specificity 0.96 (95% confidence interval [CI]: 0.95–0.97), and area under the curve (AUC) 0.9647. In the subgroup analysis, which compared the diagnostic efficacy of ME-NBI and white light imaging (WLI), the pooled sensitivity and specificity of ME-NBI were 0.87 (95% CI: 0.80–0.92) and 0.93 (95% CI: 0.90–0.95), respectively, and the area under the curve (AUC) was 0.9556. In contrast, the pooled sensitivity and specificity of WLI were 0.61 (95% CI: 0.53–0.69) and 0.65 (95% CI: 0.60–0.69), respectively, and the area under the curve (AUC) was 0.6772.

Conclusions

ME-NBI presents a high diagnostic value for gastric neoplasms and has a high specificity.     

Serum Lipids and Breast Cancer Risk: A Meta-Analysis of Prospective Cohort Studies

Purpose

Epidemiologic studies exploring causal associations between serum lipids and breast cancer risk have reported contradictory results. We conducted a meta-analysis of prospective cohort studies to evaluate these associations.

Methods

Relevant studies were identified by searching PubMed and EMBASE through April 2015. We included prospective cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of specific lipid components (i.e., total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) with breast cancer risk. Either a fixed- or a random-effects model was used to calculate pooled RRs.

Results

Fifteen prospective cohort studies involving 1,189,635 participants and 23,369 breast cancer cases were included in the meta-analysis. The pooled RRs of breast cancer for the highest versus lowest categories were 0.96 (95% CI: 0.86–1.07) for TC, 0.92 (95% CI: 0.73–1.16) for HDL-C, 0.90 (95% CI: 0.77–1.06) for LDL-C, and 0.93 (95% CI: 0.86–1.00) for TG. Notably, for HDL-C, a significant reduction of breast cancer risk was observed among postmenopausal women (RR = 0.77, 95% CI: 0.64–0.93) but not among premenopausal women. Similar trends of the associations were observed in the dose-response analysis.

Conclusions

Our findings suggest that serum levels of TG but not TC and LDL-C may be inversely associated with breast cancer risk. Serum HDL-C may also protect against breast carcinogenesis among postmenopausal women.     

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.     

Dried Blood Spots for Viral Load Monitoring in Malawi: Feasible and Effective

Objectives

To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa.

Methods

We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation).

Results

We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of participants with elevated baseline VL had suppressed (<5,000 copies/ml) on confirmatory testing. Median period between enrollment and specimen testing was 23 days. Adjusting for relevant covariates, participants on ART >4 years were more likely to be failing than participants on therapy 1–4 years (RR 1.7, 95% CI 1.0-2.8); older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98). There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11).

Conclusions

DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy.     

The Effects of Intra-Aortic Balloon Pumps on Mortality in Patients Undergoing High-Risk Coronary Revascularization: A Meta-Analysis of Randomized Controlled Trials of Coronary Artery Bypass Grafting and Stenting Era

Background

Intra-aortic balloon pumps (IABP) have generally been used for patients undergoing high-risk mechanical coronary revascularization. However, there is still insufficient evidence to determine whether they can improve outcomes in reperfusion therapy patients, mainly by percutaneous coronary intervention (PCI) with stenting or coronary artery bypass graft (CABG). This study was designed to determine the difference between high-risk mechanical coronary revascularization with and without IABPs on mortality, by performing a meta-analysis on randomized controlled trials of the current era.

Methods

Pubmed and Embase databases were searched from inception to May 2015. Unpublished data were obtained from the investigators. Randomized clinical trials of IABP and non-IABP in high-risk coronary revascularization procedures (PCI or CABG) were included. In the case of PCI procedures, stents should be used in more than 80% of patients. Numbers of events at the short-term and long-term follow-up were extracted.

Results

A total of 12 randomized trials enrolling 2155 patients were included. IABPs did not significantly decrease short-term mortality (relative risk (RR) 0.66; 95% CI, 0.42–1.01), or long-term mortality (RR 0.79; 95% CI, 0.47–1.35), with low heterogeneity across the studies. The findings remained stable in patients with acute myocardial infarction with or without cardiogenic shock. But in high-risk CABG patients, IABP was associated with reduced mortality (71 events in 846 patients; RR 0.40; 95%CI 0.25–0.67).

Conclusion

In patients undergoing high-risk coronary revascularization, IABP did not significantly decrease mortality. But high-risk CABG patients may be benefit from IABP. Rigorous criteria should be applied to the use of IABPs.     

Rural,Urban and Migrant Differences in Non-Communicable Disease Risk-Factors in Middle Income Countries: A Cross-Sectional Study of WHO-SAGE Data

Background

Understanding how urbanisation and rural-urban migration influence risk-factors for non-communicable disease (NCD) is crucial for developing effective preventative strategies globally. This study compares NCD risk-factor prevalence in urban, rural and migrant populations in China, Ghana, India, Mexico, Russia and South Africa.

Methods

Study participants were 39,436 adults within the WHO Study on global AGEing and adult health (SAGE), surveyed 2007–2010. Risk ratios (RR) for each risk-factor were calculated using logistic regression in country-specific and all country pooled analyses, adjusted for age, sex and survey design. Fully adjusted models included income quintile, marital status and education.

Results

Regular alcohol consumption was lower in migrant and urban groups than in rural groups (pooled RR and 95%CI: 0.47 (0.31–0.68); 0.58, (0.46–0.72), respectively). Occupational physical activity was lower (0.86 (0.72–0.98); 0.76 (0.65–0.85)) while active travel and recreational physical activity were higher (pooled RRs for urban groups; 1.05 (1.00–1.09), 2.36 (1.95–2.83), respectively; for migrant groups: 1.07 (1.0 -1.12), 1.71 (1.11–2.53), respectively). Overweight, raised waist circumference and diagnosed diabetes were higher in urban groups (1.19 (1.04–1.35), 1.24 (1.07–1.42), 1.69 (1.15–2.47), respectively). Exceptions to these trends exist: obesity indicators were higher in rural Russia; active travel was lower in urban groups in Ghana and India; and in South Africa, urban groups had the highest alcohol consumption.

Conclusion

Migrants and urban dwellers had similar NCD risk-factor profiles. These were not consistently worse than those seen in rural dwellers. The variable impact of urbanisation on NCD risk must be considered in the design and evaluation of strategies to reduce the growing burden of NCDs globally.     

Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration: A Meta-Analysis

Importance

The fellow eye of patients with unilateral neovascular age-related degeneration (nAMD) is at increased risk of developing late AMD. Several cohort studies have evaluated the prevalence of pseudodrusen and the association between pseudodrusen and late AMD in the fellow eye of patients with unilateral nAMD. However, these studies have limited sample sizes and their results are inconsistent.

Objective

To evaluate the prevalence rate of pseudodrusen, and the association between pseudodrusen and incidence of late AMD (nAMD and geographic atrophy (GA)) in the fellow eye of patients with unilateral nAMD.

Data Sources

The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to July 2015, as well as other systematic reviews.

Study Selection

All cohort studies for pseudodrusen with late AMD in the fellow eye of patients with unilateral nAMD.

Data Extraction and Synthesis

The numbers of patients with and without pseudodrusen at baseline and the numbers of incident nAMD and GA during follow up among patients with and without pseudodrusen were independently extracted by 2 authors. The results were pooled using random-effects meta-analysis. Heterogeneity was assessed using the I² test.

Main Outcome Measures

Prevalence rate of pseudodrusen, risk ratios (RRs) and their 95% confidence intervals (95% CIs) for associations between pseudodrusen and the incidence of nAMD and GA in the fellow eye.

Results

Five cohort studies (N = 677 patients) from 8 countries across 4 continents were included. The pooled prevalence rate of pseudodrusen in the fellow eye was 48.1% (95% Cl: 36.7–59.5%, I² = 87%). Pseudodrusen were associated with an increased risk of nAMD (RR = 1.54, 95% Cl: 1.10–2.16, I² = 42%), GA (RR = 4.70, 95% Cl: 1.22–18.1, I² = 64%), and late AMD (RR = 2.03, 95% Cl: 1.35–3.06, I² = 60%).

Conclusions

For patients with unilateral nAMD, pseudodrusen were present in about half of the fellow eyes. The presence of pseudodrusen was associated with a 1.5 times higher risk of developing nAMD, a 4.7 times higher risk of developing GA, and a 2 times higher risk of developing late AMD. Pseudodrusen should be considered in evaluating the risk of late AMD development; however, due to considerable heterogeneity across these studies, a larger study is needed to validate these findings.     

Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives

Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods

We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results

Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67–0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74–0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70–0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66–0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76–0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74–0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71–0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77–0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74–0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion

Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.     

Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement

Background

Conventional surgical risk scores lack accuracy in risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR).Elevated levels of midregional proadrenomedullin (MR-proADM) levels are associated with adverse outcome not only in patients with manifest chronic disease states, but also in the general population.

Objectives

We investigated the predictive value of MR-proADM for mortality in an unselected contemporary TAVR population.

Methods

We prospectively included 153 patients suffering from severe aortic stenosis who underwent TAVR from September 2013 to August 2014. This population was compared to an external validation cohort of 205 patients with severe aortic stenosis undergoing TAVR. The primary endpoint was all cause mortality.

Results

During a median follow-up of 258 days, 17 out of 153 patients who underwent TAVR died (11%). Patients with MR-proADM levels above the 75^th percentile (≥ 1.3 nmol/l) had higher mortality (31% vs. 4%, HR 8.9, 95% CI 3.0–26.0, P < 0.01), whereas patients with EuroSCORE II scores above the 75^th percentile (> 6.8) only showed a trend towards higher mortality (18% vs. 9%, HR 2.1, 95% CI 0.8–5.6, P = 0.13). The Harrell’s C-statistic was 0.58 (95% CI 0.45–0.82) for the EuroSCORE II, and consideration of baseline MR-proADM levels significantly improved discrimination (AUC = 0.84, 95% CI 0.71–0.92, P = 0.01). In bivariate analysis adjusted for EuroSCORE II, MR-proADM levels ≥1.3 nmol/l persisted as an independent predictor of mortality (HR 9.9, 95% CI (3.1–31.3), P <0.01) and improved the model’s net reclassification index (0.89, 95% CI (0.28–1.59). These results were confirmed in the independent validation cohort.

Conclusions

Our study identified MR-proADM as a novel predictor of mortality in patients undergoing TAVR. In the future, MR-proADM should be added to the commonly used EuroSCORE II for better risk stratification of patients suffering from severe aortic stenosis.     

Relationship between Television Viewing and Language Delay in Toddlers: Evidence from a Korea National Cross-Sectional Survey

Purpose

This study investigated the relationship between 2-year-old children’s exposure to TV and language delay.

Methods

The subjects of this study were 1,778 toddlers (906 males and 872 females) who participated in the Panel Study on Korean Children conducted in 2010. The linguistic ability of the toddlers was measured with the K-ASQ (Korean-Ages and Stages Questionnaire). The relationship between the amount of young children’s exposure to TV and language delay was analyzed with Poisson regression.

Results

The average daily TV watching time of 2-year-old Korean toddlers in this study was 1.21 hours. After all confounding variables were adjusted, toddlers with over 2 hours and less than 3 hours of TV watching time had 2.7 times more risk (RR = 2.74, 95% CI: 1.13–6.65) of language delay than those with less than 1 hour of TV watching time. Those with more than 3 hours of TV watching time had approximately 3 times (RR = 3.03, 95% CI: 1.12–8.21) more risk (p<0.05). In addition, the risk of language delay increased proportionately with the increase in toddlers’ TV watching time (p = 0.004).

Conclusion

Two-year-old Korean toddlers’ average daily TV watching time of more than 2 hours was related with language delay.     

Documenting Penicillin Allergy: The Impact of Inconsistency

Background

Allergy documentation is frequently inconsistent and incomplete. The impact of this variability on subsequent treatment is not well described.

Objective

To determine how allergy documentation affects subsequent antibiotic choice.

Design

Retrospective, cohort study.

Participants

232,616 adult patients seen by 199 primary care providers (PCPs) between January 1, 2009 and January 1, 2014 at an academic medical system.

Main Measures

Inter-physician variation in beta-lactam allergy documentation; antibiotic treatment following beta-lactam allergy documentation.

Key Results

15.6% of patients had a reported beta-lactam allergy. Of those patients, 39.8% had a specific allergen identified and 22.7% had allergic reaction characteristics documented. Variation between PCPs was greater than would be expected by chance (all p<0.001) in the percentage of their patients with a documented beta-lactam allergy (7.9% to 24.8%), identification of a specific allergen (e.g. amoxicillin as opposed to “penicillins”) (24.0% to 58.2%) and documentation of the reaction characteristics (5.4% to 51.9%). After beta-lactam allergy documentation, patients were less likely to receive penicillins (Relative Risk [RR] 0.16 [95% Confidence Interval: 0.15–0.17]) and cephalosporins (RR 0.28 [95% CI 0.27–0.30]) and more likely to receive fluoroquinolones (RR 1.5 [95% CI 1.5–1.6]), clindamycin (RR 3.8 [95% CI 3.6–4.0]) and vancomycin (RR 5.0 [95% CI 4.3–5.8]). Among patients with beta-lactam allergy, rechallenge was more likely when a specific allergen was identified (RR 1.6 [95% CI 1.5–1.8]) and when reaction characteristics were documented (RR 2.0 [95% CI 1.8–2.2]).

Conclusions

Provider documentation of beta-lactam allergy is highly variable, and details of the allergy are infrequently documented. Classification of a patient as beta-lactam allergic and incomplete documentation regarding the details of the allergy lead to beta-lactam avoidance and use of other antimicrobial agents, behaviors that may adversely impact care quality and cost.     

The Efficacy and Safety of the Probiotic Bacterium Lactobacillus reuteri DSM 17938 for Infantile Colic: A Meta-Analysis of Randomized Controlled Trials

Objective

To evaluate the efficacy and safety of Lactobacillus reuteri DSM 17938 for treating infantile colic.

Methods

A systematic literature retrieval was carried out to obtain randomized controlled trials of L. reuteri DSM 17938 for infantile colic. Trials were performed before May 2015 and retrieved from the PubMed, EMBASE, Cochrane library, CNKI, WanFang, VIP, and CBM databases. Data extraction and quality evaluation of the trials were performed independently by two investigators. A meta-analysis was performed using STATA version 12.0.

Results

Six randomized controlled trials of 423 infants with colic were included. Of these subjects, 213 were in the L. reuteri group, and 210 were in the placebo group. Lactobacillus reuteri increased colic treatment effectiveness at two weeks (RR = 2.84; 95% CI: 1.24–6.50; p = 0.014) and three weeks (relative risk [RR] = 2.33; 95% CI: 1.38–3.93; P = 0.002) but not at four weeks (RR = 1.41; 95% CI: 0.52–3.82; P = 0.498). Lactobacillus reuteri decreased crying time (min/d) at two weeks (weighted mean difference [WMD] = –42.89; 95% CI: –60.50 to –25.29; P = 0.000) and three weeks (WMD = –45.83; 95% CI: –59.45 to –32.21; P = 0.000). In addition, L. reuteri did not influence infants’ weight, length or head circumference and was not associated with serious adverse events.

Conclusions

Lactobacillus reuteri possibly increased the effectiveness of treatment for infantile colic and decreased crying time at two to three weeks without causing adverse events. However, these protective roles are usurped by gradual physiological improvements. The study is limited by the heterogeneity of the trials and should be considered with caution. Higher quality, multicenter randomized controlled trials with larger samples are needed.     

Sites of Peripheral Artery Occlusive Disease as a Predictor for All-Cause and Cardiovascular Mortality in Chronic Hemodialysis

Background

The ankle—brachial blood pressure (BP) index (ABI) not only indicates the presence of peripheral artery occlusive disease (PAOD) but predicts mortality in patients undergoing hemodialysis (HD). However, whether the site of PAOD can provide additional contribution to predicting mortality have not been investigated yet. Our primary objective was to determine the associations between the site of PAOD and all-cause and cardiovascular mortality in chronic HD (CHD) patients.

Methods

A retrospective cohort study was conducted to evaluate 444 Taiwanese CHD patients between December 2006 and June 2013. The site of PAOD together with other explanatory variables such as demographic data, body mass index, a history of cardiovascular diseases, HD vintage, biochemical data, and cardiothoracic ratio (CTR) were assessed by the Cox proportional hazards regression model.

Results

The frequency of PAOD was 14.6% in both legs, 4.9% in the right side only, and 5.1% in the left side only. During the study period, 127 all-cause and 93 cardiovascular deaths occurred. PAOD site was found to have significant predictive power for all-cause mortality with the order of 3.04 (95% CI: 1.56–5.90) hazard ratio on the right side, 2.48 (95% CI: 1.27–4.82) on the left side, and 4.11 (95% CI: 2.76–6.13) on both sides. The corresponding figures for cardiovascular mortality were 3.81 (95% CI: 1.87–7.76) on the right side, 2.76 (95% CI: 1.30–5.82) on the left side, and 3.95 (95% CI: 2.45–6.36) on both sides. After adjustment for other explanatory variables, only right-sided PAOD still remained to have significant predictive power for all-cause and cardiovascular mortality and bilateral PAOD kept the significant association with all-cause mortality.

Conclusions

The site of PAOD revealed various predictive powers for all-cause and cardiovascular mortality in CHD patients and only right-sided PAOD remained an independent predictor for both types of mortality making allowance for relevant confounding factors.     

Prenatal Paracetamol Exposure and Wheezing in Childhood: Causation or Confounding?

Background

Several studies have reported an increased risk of wheezing in the children of mothers who used paracetamol during pregnancy. We evaluated to what extent this association is explained by confounding.

Methods

We investigated the association between maternal paracetamol use in the first and third trimester of pregnancy and ever wheezing or recurrent wheezing/asthma in infants in the NINFEA cohort study. Risks ratios (RR) and 95% confidence intervals (CI) were estimated after adjustment for confounders, including maternal infections and antibiotic use during pregnancy.

Results

The prevalence of maternal paracetamol use was 30.6% during the first and 36.7% during the third trimester of pregnancy. The prevalence of ever wheezing and recurrent wheezing/asthma was 16.9% and 5.6%, respectively. After full adjustment, the RR for ever wheezing decreased from 1.25 [1.07–1.47] to 1.10 [0.94–1.30] in the first, and from 1.26 [1.08–1.47] to 1.10 [0.93–1.29] in the third trimester. A similar pattern was observed for recurrent wheezing/asthma. Duration of maternal paracetamol use was not associated with either outcome. Further analyses on paracetamol use for three non-infectious disorders (sciatica, migraine, and headache) revealed no increased risk of wheezing in children.

Conclusion

The association between maternal paracetamol use during pregnancy and infant wheezing is mainly, if not completely explained by confounding.     

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Methods

2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials.

Results

Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m², follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I² = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00).

Conclusions

In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.