Discover the most talked about and latest scientific content & concepts.

Concept: Odds ratio


Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science,, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.

Concepts: Epidemiology, Upper respiratory tract infection, Adverse event, Odds ratio, Medical statistics, Randomized controlled trial, Clinical trial, Vitamin D


Background Increasing overuse of opioids in the United States may be driven in part by physician prescribing. However, the extent to which individual physicians vary in opioid prescribing and the implications of that variation for long-term opioid use and adverse outcomes in patients are unknown. Methods We performed a retrospective analysis involving Medicare beneficiaries who had an index emergency department visit in the period from 2008 through 2011 and had not received prescriptions for opioids within 6 months before that visit. After identifying the emergency physicians within a hospital who cared for the patients, we categorized the physicians as being high-intensity or low-intensity opioid prescribers according to relative quartiles of prescribing rates within the same hospital. We compared rates of long-term opioid use, defined as 6 months of days supplied, in the 12 months after a visit to the emergency department among patients treated by high-intensity or low-intensity prescribers, with adjustment for patient characteristics. Results Our sample consisted of 215,678 patients who received treatment from low-intensity prescribers and 161,951 patients who received treatment from high-intensity prescribers. Patient characteristics, including diagnoses in the emergency department, were similar in the two treatment groups. Within individual hospitals, rates of opioid prescribing varied widely between low-intensity and high-intensity prescribers (7.3% vs. 24.1%). Long-term opioid use was significantly higher among patients treated by high-intensity prescribers than among patients treated by low-intensity prescribers (adjusted odds ratio, 1.30; 95% confidence interval, 1.23 to 1.37; P<0.001); these findings were consistent across multiple sensitivity analyses. Conclusions Wide variation in rates of opioid prescribing existed among physicians practicing within the same emergency department, and rates of long-term opioid use were increased among patients who had not previously received opioids and received treatment from high-intensity opioid prescribers. (Funded by the National Institutes of Health.).

Concepts: Sensitivity analysis, Retrospective, Odds ratio, Doctor-patient relationship, Patient, Physician, Opioid, Hospital


Background The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. Methods We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. Results A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Conclusions Acute kidney injury is common and is associated with poor outcomes, including increased mortality, among critically ill children and young adults. (Funded by the Pediatric Nephrology Center of Excellence at Cincinnati Children's Hospital Medical Center and others; AWARE number, NCT01987921 .).

Concepts: Ureter, Renal physiology, Renal failure, Odds ratio, Urine, Nephrology, Kidney, Epidemiology


Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.

Concepts: Tobacco smoking, Study design, Medical statistics, Neurodegenerative disorders, Odds ratio, Risk, Cancer, Epidemiology


BACKGROUND: Studies on the association of birth by caesarean section (C/S) and allergies have produced conflicting findings. Furthermore, evidence on whether this association may differ in those at risk of atopy is limited. This study aims to investigate the association of mode of delivery with asthma and atopic sensitization and the extent to which any effect is modified by family history of allergies. METHODS: Asthma outcomes were assessed cross-sectionally in 2216 children at age 8 on the basis of parents' responses to the ISAAC questionnaire whilst skin prick tests to eleven aeroallergens were also performed in a subgroup of 746 children. Adjusted odds ratios of asthma and atopy by mode of delivery were estimated in multivariable logistic models while evidence of effect modification was examined by introducing interaction terms in the models. RESULTS: After adjusting for potential confounders, children born by C/S appeared significantly more likely than those born vaginally to report ever wheezing (OR 1.36, 95% CI 1.07-1.71), asthma diagnosis (OR 1.41, 95% CI 1.09-1.83) and be atopic (OR 1.67, 95% CI 1.08-2.60). There was modest evidence that family history of allergies may modify the effect of C/S delivery on atopy (p for effect modification=0.06) but this was not the case for the asthma outcomes. Specifically, while more than a two-fold increase in the odds of being a topic was observed in children with a family history of allergies if born by C/S (OR 2.62, 95% CI 1.38-5.00), no association was observed in children without a family history of allergies (OR 1.16, 95% CI 0.64-2.11). CONCLUSIONS: Birth by C/S is associated with asthma and atopic sensitization in childhood. The association of C/S and atopy appears more pronounced in children with family history of allergies.

Concepts: Allergen, Caesarean delivery on maternal request, Odds ratio, Hypersensitivity, Allergy, Atopy, Childbirth, Asthma


BACKGROUND: Trachoma is the leading cause of preventable blindness worldwide. It is common in areas where the people are socio-economically deprived. The aim of this study was to assess active trachoma and associated risk factors among children 1–9 years in East Gojjam. METHODS: Community-based cross-sectional study was conducted in Baso Liben District from February to April 2012. A two-stage random cluster-sampling technique was employed and all children 1–9 years old from each household were clinically assessed for trachoma based on simplified WHO 1983 classification. Data were collected by using semi-structured interview, pre-tested questionnaire and observation. The data were entered and analyzed using SPSS version 16 statistical package.Result: From a total of 792 children screened for trachoma (of which 50.6% were girls), the overall prevalence of active trachoma was 24.1% consisting of only 17.2% [95% CI: 14.8, 20.1] TF and 6.8% TI. There were variations among children living in low land (29.3%) and in medium land (21.4%). In multivariate analysis, low monthly income (AOR= adjusted odds ratio) 2.98; 95% CI (confidence interval): 1.85-7.85), illiterate family (AOR =5.18; 95% CI: 2.92-9.17); unclean face (AOR =18.68; 95% CI :1.98-175.55); access to water source (AOR=2.01;95% CI: 1.27-3.15); less than 20 liters of water use (AOR=4.88; 95% CI:1.51-15.78); not using soap for face washing (AOR=5.84; 95%CI :1.98-17.19); not using latrine frequently (AOR=1.75; 95% CI:0.01-0.42); density of flies (AOR=3.77; 95%CI: 2.26-6.29); less knowledgeable family (AOR=3.91; 95%CI :2.40-6.38) and average monthly income (AOR=2.98; 95%CI : 1.85-7.85) were found independently associated with trachoma. CONCLUSION: Active trachoma is a major public problem among 1–9 years children and significantly associated with a number of risky factors. Improvement in awareness of facial hygiene, environmental conditions, mass antibiotic distribution and health education on trachoma transmission and prevention should be strengthened in the District.

Concepts: Multivariate statistics, SPSS, Cross-sectional study, Odds ratio, Medical statistics, Risk, Epidemiology


Background:Tibiotalocalcaneal (TTC) arthrodesis using a nail has been shown to be an effective salvage technique; however, there is a risk of major amputation. A better understanding of the relative risk of amputation after TTC fusion and the factors that influence this could help the preoperative consultation and guide discussion on the economics of limb salvage.Methods:One hundred seventy-nine limbs were treated with TTC fusion with an intramedullary nail. A comprehensive chart and radiographic review was pulled from our intramedullary nail database. Patients were divided into those who went on to eventual amputation and those with successful salvage of their limb. Variables from the database were used to build a statistical model with a biostatistician. Final results were presented, and a formula to determine probability of amputation was created.Results:There were 21 limbs that were eventually treated with major amputation. This represents an overall salvage rate of 88.2% (158/179 patients). Age was a factor in amputation risk, and the highest risk factor for amputation was diabetes with an odds ratio of 7.01 and 95% confidence, P = .0019. The odds of amputation were 6.2 times and 3 times greater for patients undergoing revisions and those with preoperative ulcers, respectively. The probability of amputation could be found preoperatively by using the derived equation: e(x)/(1 + e(x)) where x is a factor of age, diabetes, revision, and ulceration.Conclusion:TTC arthrodesis with a retrograde intramedullary nail has a high rate of limb salvage across a wide range of indications and medical comorbidities. In this patient cohort, diabetes was the most notable risk for amputation, followed by revision surgery, preoperative ulceration, and age. A model has been built to help predict the risk of amputation.Level of Evidence:Level II, prognostic.

Concepts: Biostatistics, Statistics, Surgery, Medical statistics, Odds ratio, Risk, Relative risk, Epidemiology


BACKGROUND: Epidemiologic studies have reported inconsistent results regarding coffee consumption and the risk of liver cancer. We performed a meta-analysis of published case–control and cohort studies to investigate the association between coffee consumption and liver cancer. METHODS: We searched Medline, EMBASE, ISI Web of Science and the Cochrane library for studies published up to May 2012. We performed a meta-analysis of nine case–control studies and seven cohort studies. RESULTS: The summary odds ratio (OR) for high vs no/almost never drinkers was 0.50 (95% confidence interval (CI): 0.42–0.59), with no significant heterogeneity across studies (Q = 16.71; P = 0.337; I2 = 10.2%). The ORs were 0.50 (95% CI: 0.40–0.63) for case–control studies and 0.48 (95% CI: 0.38–0.62) for cohort studies. The OR was 0.38 (95% CI: 0.25–0.56) in males and 0.60 (95% CI: 0.33–1.10) in females. The OR was 0.45 (95% CI: 0.36–0.56) in Asian studies and 0.57 (95% CI: 0.44–0.75) in European studies. The OR was 0.39 (95% CI: 0.28–0.54) with no adjustment for a history of liver disease and 0.54 (95% CI: 0.46–0.66) after adjustment for a history of liver disease. CONCLUSIONS: The results of this meta-analysis suggested an inverse association between coffee consumption and liver cancer. Because of the small number of studies, further prospective studies are needed.

Concepts: Study design, Odds ratio, Infectious disease, Evidence-based medicine, MEDLINE, Cochrane Library, Cancer, Epidemiology


Background Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. Methods A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. Results The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). Conclusions Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 number, NCT01668784 .).

Concepts: Paclitaxel, Cancer, Renal cell carcinoma, Odds ratio, Normal distribution, Clopidogrel, Clinical trial, Bristol-Myers Squibb


Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose.Design Retrospective analysis of claims data, 2001-13.Setting Administrative health claims database.Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid.Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose.Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P<0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P<0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.

Concepts: Pharmacology, Benzodiazepine overdose, Barbiturate, Alprazolam, Morphine, Odds ratio, Benzodiazepine, Opioid