Life Course Tobacco Smoking and Risk of HPV-Negative Squamous Cell Carcinomas of Oral Cavity in Two Countries.

Background: Tobacco smoking remains one of the major risk factors for oral cavity cancers (OCC), a subgroup of head and neck cancer (HNC) less attributed to human papillomavirus (HPV) infection. Although a strong dose-dependent association between tobacco smoking and OCC exists, several important questions on the age-dependent effects of this habit remain unanswered. We investigated which life course hypothesis best describes the association between tobacco smoking and HPV-negative (HPV-ve ) OCC in Canada and India. Methods: We used data from the HeNCe Life study, a hospital-based case-control study conducted in Canada and India, using similar protocols. Cases were newly diagnosed subjects with primary squamous cell carcinomas of the head and neck region. Control subjects were patients with non-cancer selected from various outpatient clinics in a hospital located in the same catchment area as the cases and frequency-matched to cases according to age and sex. We collected information on an array of life course exposures using a structured questionnaire with the help of a life grid. Tobacco exposure (pack-years) during three life periods (≤ 30, 31-50, and >50 years of age) was calculated from the entire life course history of smoking. We used CDx brushes to collect oral exfoliated cells. Alpha HPV DNA detection and genotyping were performed for 36 HPV genotypes using the linear array. Participants who tested positive for HPV were excluded from the analysis. We used the Bayesian relevant life course exposure model (BRLM) to identify the life course hypothesis that best described the relationship between tobacco smoking and HPV-ve OCC. Results: We show evidence for a late-life sensitive period (>50 years of age) for tobacco smoking in relation to the risk of HPV-ve OCC in both Canada and India. An increase of 1 pack-year of tobacco smoking increased the risk of OCC by ~3% in both countries. Conclusion: Our findings from the Canadian and Indian data suggest that smoking tobacco after 50 years of age may carry a higher risk of developing oral cancer than earlier in life. Further studies are warranted to confirm the results.

Latency of tobacco smoking for head and neck cancer among HPV-positive and HPV-negative individuals.

Human papillomavirus (HPV) infection and tobacco smoking are well-known risk factors for head and neck cancers (HNC). Although an effect modification between oral HPV infection and tobacco smoking may exist, evidence is lacking on how they interact temporally. We investigated the latency and life course effects of tobacco smoking on risk of HNC among HPV-positive (HPV+ve ) and negative (HPV-ve ) individuals. We used data from 631 ever-smoker participants of a hospital-based case-control study conducted in four major hospitals in Montréal, Canada. Cases (n = 320), incident, histologically confirmed, primary squamous cell carcinomas, were frequency-matched to controls (n = 311) by age and sex. Sociodemographic and behavioral factors (e.g., tobacco and alcohol use and sexual history) were collected using a structured interview applying a life grid technique. Oral exfoliated cells were used for HPV DNA detection and genotyping. Latency effects were estimated flexibly using a Bayesian relevant exposure model and further extended with a life course approach. Retrospective smoking trajectories for HPV+ve cases and controls had similar shapes. Exposure to tobacco smoking even 40 years before diagnosis was associated with an increased HNC risk among both HPV+ve and HPV-ve participants. The effect of smoking before the start of sexual activity compared to afterwards was higher among HPV+ve individuals. This pattern of association was less profound among HPV-ve participants. Temporal interactions may exists between oral HPV infection and life course smoking trajectories in relation to HNC risk.

Expostats: A Bayesian Toolkit to Aid the Interpretation of Occupational Exposure Measurements.

INTRODUCTION: Interpretation of exposure measurements has evolved into a framework based on the lognormal distribution. Most available practical tools are based on traditional frequentist statistical procedures that do not satisfactorily account for censored data and are not amenable to simple probabilistic risk statements. Bayesian methods offer promising solutions to these challenges. Such methods have been proposed in the literature but are not widely and freely available to practitioners. METHODS: A set of computer applications were developed aimed at answering typical inferential questions that are important to occupational health practitioners: Is a group of workers compliant with an occupational exposure limit? Are some individuals within this group likely to experience substantially higher exposure than its average member? How does an intervention influence the distribution of exposures? These questions were addressed using Bayesian models, simultaneously accounting for left, right, and interval-censored data with multiple censoring points. The models are estimated using the JAGS Gibbs sampler called through the R statistical package. RESULTS: The Expostats toolkit is freely available from www.expostats.ca as four tools accessible through a Web application, an offline standalone application or algorithms. The tools include a variety of calculations and graphical outputs useful according to current practices in analysis and interpretation of exposure measurements collected by occupational hygienists. Tool1 and its simplified version Tool1 Express focus on inferences from data from a similarly exposed group. Tool2 evaluates within- and between-worker components of variability, as well as the probability that an individual worker might be overexposed. Tool3 compares exposure data across groups, e.g. evaluates the effect of an intervention. Uncertainty management includes the calculation of credible intervals and produces probabilistic statements about the exposure metrics (e.g. probability that over 5% of exposures are above a limit). DISCUSSION: Expostats is the first freely available toolkit that leverages the flexibility of Bayesian analysis to perform an extensive list of calculations recommended in several international guidelines on the practice of occupational hygiene.

An Unsupervised Smart App-Optimized HIV Self-Testing Program in Montreal, Canada: Cross-Sectional Study.

BACKGROUND: Although HIV self-testing strategies have been recommended by the World Health Organization, HIV self-tests are not yet approved in Canada. Currently approved HIV self-tests offer toll-free lines that are insufficient for initiating expedited linkages to counseling and care, accurate interpretation, and support during HIV self-testing. We developed an innovative, multilingual software app called HIVSmart! to plug these gaps. OBJECTIVE: This study aimed to test our app-optimized oral HIV self-testing strategy for feasibility in men who have sex with men (MSM) who presented to test at a large sexual health clinic (Clinique Médicale L'Actuel) in Montreal. METHODS: Between July 2016 and February 2017, we offered a strategy consisting of the OraQuick In-Home HIV Test (an investigational device) and a tablet installed with the HIVSmart! app to study participants, who presented at a private office in the clinic, mimicking an unsupervised home environment. We evaluated the strategy for its feasibility, acceptability, and preference. Using the HIVSmart! app, participants were guided through the self-testing process. We determined feasibility with a metric defined as the completion rate, which consisted of the following 3 steps: (1) self-test conduct; (2) self-test interpretation; and (3) linkages to care. Participants independently performed, interpreted, recorded their self-test and result, engaged in pre- and posttest counseling, and sought linkages to care. Laboratory tests (p24, Western Blot, and RNA), as per country algorithms, were expedited, and linkages based on the rapid test status were arranged. RESULTS: Mean age of the 451 participants enrolled was 34 (range, 18-73) years. Of all participants, 97.1% (438/451) completed and submitted the survey through the HIVSmart! app. In total, 84.7% (371/438) of the participants were well educated (beyond high school) and 52.5% (230/438) had been tested within the past 6 months. Of the 451, 11.5% (52/451) were on pre-exposure prophylaxis. Feasibility (completion rate), an average proportion of the 3 steps, was computed to be 96.6% (419/451). The acceptability of the strategy was high at 98.5% (451/458). A majority of the participants (448/451, 99.3%) were found to be self-tested and lab-confirmed negative and were counseled after self- and rapid tests. In total, 0.7% (3/451) of the participants who self-tested positive and were lab-confirmed positive were linked to a physician within the same day. Furthermore, 98.8% (417/422) of the participants found the app to be useful and 94.0% (424/451) were willing to recommend it to a friend or partner. CONCLUSIONS: The HIVSmart! app-optimized strategy was feasible, accepted, and preferred by an educated, urban MSM population of Montreal. With the app, participants were able to perform, interpret, store results, and get rapidly linked to care. The HIVSmart!-optimized, self-testing strategy could be adapted and contextualized to many at-risk populations within Canada and worldwide, thereby maximizing its public health impact.

A Bayesian approach to investigate life course hypotheses involving continuous exposures.

Background: Different hypotheses have been proposed in life course epidemiology on how a time-varying exposure can affect health or disease later in life. Researchers are often interested in investigating the probability of these hypotheses based on observed life course data. However, current techniques based on model/variable selection do not provide a direct estimate of this probability. We propose an alternative technique for a continuous exposure, using a Bayesian approach that has specific advantages, to investigate which life course hypotheses are supported by the observed data. Methods: We demonstrate the technique, the relevant life course exposure model (RLM), using simulations. We also analyse data from a case-control study on risk factors of oral cancer, with repeated measurements of betel quid chewing across life. We investigate the relative importance of chewing one quid of betel per day, at three life periods: ≤20 years, 21-40 years and above 40 years of age, on the risk of developing oral cancer. Results: RLM was able to correctly identify the life course hypothesis under which the data were simulated. Results from the case-control study showed that there was 74.3% probability that betel quid exposure earlier in life, compared with later, results in higher odds of developing oral cancer later in life. Conclusions: RLM is a useful option to identify the life course hypothesis supported by the observed data prior to the estimation of a causal effect.

Defining the "Critical Elements" for the Most Common Procedures in Spine Surgery: A Consensus of Orthopedic and Neurosurgical Surgeons.

STUDY DESIGN: Survey. OBJECTIVE: To define the critical elements of common spine surgeries. SUMMARY OF BACKGROUND DATA: Despite significant relevance to the field of spine surgery, the term "critical element" of surgery has not been clearly defined. Every surgical procedure involves numerous steps, each with its own potential for complications and harm to the patient. Despite its crucial role in surgical training, billing, and the ethicality of concurrent surgery, the term "critical element" of surgery has not been defined. METHODS: A survey was administered to surgeons associated with AO Spine North America and the Society for Minimally Invasive Spine Surgery to determine the critical elements for four common spine procedures: open lumbar laminectomy and fusion, microdiscectomy, anterior cervical discectomy and fusion (ACDF), and posterior cervical laminectomy and fusion. Respondents were asked which steps necessitated their direct supervision. Surgical subspecialty, level of experience, and practice demographics were also recorded. RESULTS: For all applicable procedures, decompression, instrumentation, and fusion were designated as critical elements. Patient positioning and fascial closure were not. Radiographic localization was considered critical for all procedures, except posterior cervical laminectomy and fusion. Exposure was not considered critical for any procedures, except ACDF. Certain substeps of decompression in ACDF and open lumbar laminectomy and fusion were not considered critical. Orthopaedic surgeons considered exposure and fusion in ACDF procedures to be critical whereas neurosurgeons did not. Surgeons operating in private practice considered every step of these common procedures to be critical elements. CONCLUSION: Decompression, instrumentation, and fusion were considered critical elements of common spine surgeries. There were significant differences in responses according to surgical specialty and practice setting. Future research is necessary to determine the implications of these findings and guide the definition of the "critical portions" of surgery. LEVEL OF EVIDENCE: 1.

A two-stage model in a Bayesian framework to estimate a survival endpoint in the presence of confounding by indication.

Background Biomarker series can indicate disease progression and predict clinical endpoints. When a treatment is prescribed depending on the biomarker, confounding by indication might be introduced if the treatment modifies the marker profile and risk of failure. Objective Our aim was to highlight the flexibility of a two-stage model fitted within a Bayesian Markov Chain Monte Carlo framework. For this purpose, we monitored the prostate-specific antigens in prostate cancer patients treated with external beam radiation therapy. In the presence of rising prostate-specific antigens after external beam radiation therapy, salvage hormone therapy can be prescribed to reduce both the prostate-specific antigens concentration and the risk of clinical failure, an illustration of confounding by indication. We focused on the assessment of the prognostic value of hormone therapy and prostate-specific antigens trajectory on the risk of failure. Methods We used a two-stage model within a Bayesian framework to assess the role of the prostate-specific antigens profile on clinical failure while accounting for a secondary treatment prescribed by indication. We modeled prostate-specific antigens using a hierarchical piecewise linear trajectory with a random changepoint. Residual prostate-specific antigens variability was expressed as a function of prostate-specific antigens concentration. Covariates in the survival model included hormone therapy, baseline characteristics, and individual predictions of the prostate-specific antigens nadir and timing and prostate-specific antigens slopes before and after the nadir as provided by the longitudinal process. Results We showed positive associations between an increased prostate-specific antigens nadir, an earlier changepoint and a steeper post-nadir slope with an increased risk of failure. Importantly, we highlighted a significant benefit of hormone therapy, an effect that was not observed when the prostate-specific antigens trajectory was not accounted for in the survival model. Conclusion Our modeling strategy was particularly flexible and accounted for multiple complex features of longitudinal and survival data, including the presence of a random changepoint and a time-dependent covariate.

Evolution of gender representation among Canadian OTL-HNS residents: a 27-year analysis.

BACKGROUND: The proportion of females enrolling into medical schools has been growing steadily. However, the representation of female residents among individual specialties has shown considerable variation. The purpose of this study was to compare the trends of gender representation in Otolaryngology - Head and Neck Surgery (OTL-HNS) residency programs with other specialty training programs in Canada. In order to contextualize these findings, a second phase of analysis examined the success rate of applicants of different genders to OTL-HNS residency programs. METHOD: Anonymized data were obtained from the Canadian Residency Matching Service (CaRMS) and from the Canadian Post-M.D. Education Registry (CAPER) from 1988 to 2014. The differences in gender growth rates were compared to other subspecialty programs of varying size. Descriptive analysis was used to examine gender representation among OTL-HNS residents across years, and to compare these trends with other specialties. Bayesian hierarchical models were fit to analyze the growth in program rates in OTL-HNS based on gender. RESULTS: CaRMS and CAPER data over a 27 year period demonstrated that OTL-HNS has doubled its female representation from 20% to 40% between 1990 and 1994 and 2010-2014. The difference in annual growth rate of female representation versus male representation in OTL-HNS over this time period was 2.7%, which was similar to other large specialty programs and surgical subspecialties. There was parity in success rates of female and male candidates ranking OTL-HNS as their first choice specialty for most years. CONCLUSIONS: Female representation in Canadian OTL-HNS residency programs is steadily increasing over the last 27 years. Large variation in female applicant acceptance rates was observed across Canadian universities, possibly attributable to differences in student body or applicant demographics. Factors influencing female medical student career selection to OTL-HNS require further study to mitigate disparities in gender representation and identify barriers to prospective female OTL-HNS applicants.

Adverse events following live-attenuated intranasal influenza vaccination of children with cystic fibrosis: Results from two influenza seasons.

BACKGROUND: Despite the approved use of live-attenuated intranasal influenza vaccine (LAIV) for seasonal immunization of patients with cystic fibrosis (CF), many questions remain unanswered regarding the timing, duration, and types of adverse events that occur following administration of this vaccine. METHODS: In 2012 and 2013, 264 LAIV doses were administered to 198 patients aged 2-19 with CF. Vaccinees were followed prospectively for 55 days after vaccination (day 0) and information on adverse events was collected. Bayesian change-point analysis was used to identify the risk period following LAIV during which participants had a higher risk of reporting adverse events. Multivariable zero-inflated Poisson regression models were then used to estimate the adjusted incidence rate ratio (aIRR) and 95% credible interval (CrI) of reporting each adverse event in the risk period versus the control period. RESULTS: There was a higher risk of reporting serious adverse events (SAEs) (aIRR 1.45, 95% CrI (0.29, 5.17)) and solicited symptoms during days 0-6 of follow-up compared to control period days 7-55. However, most SAEs were not causally related to LAIV and the solicited symptom episodes were brief, usually lasting 1-2 days. There was no increased risk of antibiotic prescriptions for respiratory conditions in the risk vs. control periods (aIRR 0.48, 95% CrI (0.23, 0.91)). CONCLUSIONS: Adverse events were most common 0-6 days after LAIV administration but were generally benign and self-limiting. Pulmonary exacerbations did not increase in frequency.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

OBJECTIVE: To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. METHODS: Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. RESULTS: A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. CONCLUSION: Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Clinically Apparent Arterial Thrombosis in Persons with Systemic Vasculitis.

OBJECTIVE: To estimate the incidence rate of clinically apparent arterial thrombotic events and associated comorbidities in patients with primary systemic vasculitis. METHODS: Using large cohort administrative data from Quebec, Canada, we identified patients with vasculitis, including polyarteritis nodosa (PAN) and granulomatosis with polyangiitis (GPA). Incident acute myocardial infarctions (AMIs) and cerebrovascular accidents (CVAs) after the diagnosis of vasculitis were ascertained in the PAN and GPA group via billing and hospitalization data. These were compared to rates of a general population comparator group. The incidences of comorbidities (type 2 diabetes mellitus, dyslipidemia, and hypertension) were also collected. RESULTS: Among the 626 patients identified with vasculitis, 19.7% had PAN, 2.9% had Kawasaki disease, 23.8% had GPA, 52.4% had GCA, and 1.3% had Takayasu arteritis. The AMI rate was substantially higher in males aged 18-44 with PAN, with rates up to 268.1 events per 10,000 patient years [95% CI 67.1-1070.2], approximately 30 times that in the age- and sex-matched control group. The CVA rate was also substantially higher, particularly in adults aged 45-65. Patients with vasculitis had elevated incidences of diabetes, dyslipidemia, and hypertension versus the general population. CONCLUSION: Atherothrombotic rates were elevated in patients identified as having primary systemic vasculitis. While incident rates of cardiovascular comorbidities were also increased, the substantial elevation in AMIs seen in young adults suggests a disease-specific component which requires further investigation.

Industrial air emissions, and proximity to major industrial emitters, are associated with anti-citrullinated protein antibodies.

OBJECTIVE: To determine the association of anti-citrullinated antibodies (ACPA) with the ambient air pollutants fine particulate matter (PM2.5) and sulfur dioxide (SO2). METHODS: The CARTaGENE first-wave cohort includes 20,000 general population subjects from Quebec (Canada). On a sample of unselected 1586 subjects, we determined serum, ACPA and performed multivariable logistic regression, for the outcome of positive ACPA, assessing for independent effects of our air pollution variables, adjusting for age, sex, smoking, and French Canadian origin. Two models assessed distance to main industrial emitters of PM2.5, and of SO2, and two models assessed tons of SO2 and of PM2.5 annual emissions. We also assessed associations with PM2.5 regional ambient concentrations estimated with satellite imagery. RESULTS: Adjusted analyses suggested a positive association between annual industrial PM2.5 and SO2 emissions and the presence of ACPA antibodies (OR: 1.02, 95%CI 1.00-1.04 per 10t of PM2.5 and 100t of SO2). The data were also consistent with a negative association between the presence of ACPA, and distance to a major industrial emitter of both PM2.5 and SO2. We found no association with PM2.5 estimates of ambient levels. CONCLUSIONS: These analyses suggest that exposure to industrial emissions of air pollutants is related to ACPA positivity.

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis.

BACKGROUND: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA. METHODS: Before the 2013-2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated. RESULTS: Influenza RNA was detected in 16% fewer participants (95% CrI: -7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: -16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: -2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: -0.37, 1.26). CONCLUSION: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and -negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.

Efficacy and Safety of Smoking Cessation Interventions in Patients With Cardiovascular Disease: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although the efficacy and safety of smoking cessation interventions are well established, their efficacy and safety in patients with cardiovascular disease (CVD) remain unclear. The objective of this study was to evaluate the efficacy and safety of pharmacological and behavioral smoking cessation interventions in CVD patients via a meta-analysis of randomized controlled trials. METHODS AND RESULTS: EMBASE, PsycINFO, MEDLINE, PubMed, and the Cochrane Tobacco Addiction Specialized Register were searched for randomized controlled trials evaluating the efficacy of smoking cessation pharmacotherapies and behavioral therapies in CVD patients. Outcomes of interest were smoking abstinence at 6 and 12 months, defined using the most rigorous criteria reported. Data were pooled across studies for direct comparisons using random-effects models. Network meta-analysis using a graph-theoretical approach was used to generate the indirect comparisons. Seven pharmacotherapy randomized controlled trials (n=2809) and 17 behavioral intervention randomized controlled trials (n=4666) met our inclusion criteria. Our network meta-analysis revealed that varenicline (relative risk [RR]: 2.64; 95% confidence interval [CI], 1.34-5.21) and bupropion (RR: 1.42; 95% CI, 1.01-2.01) were associated with greater abstinence than placebo. The evidence about nicotine replacement therapies was inconclusive (RR: 1.22; 95% CI, 0.72-2.06). Telephone therapy (RR: 1.47; 95% CI: 1.15-1.88) and individual counseling (RR: 1.64, 95% CI: 1.17-2.28) were both more efficacious than usual care, whereas in-hospital behavioral interventions were not (RR: 1.05; 95% CI, 0.78-1.43). CONCLUSIONS: Our meta-analysis suggests varenicline and bupropion, as well as individual and telephone counseling, are efficacious for smoking cessation in CVD patients.

Influenza Virus Detection Following Administration of Live-Attenuated Intranasal Influenza Vaccine in Children With Cystic Fibrosis and Their Healthy Siblings.

Background. We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2-19 years with and without cystic fibrosis (CF). Methods. Before the 2013-2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (nCF: 57; nhealthy: 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results. Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73-2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70-0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02-29.9). Conclusion. Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups.

Diagnostic Test Accuracy in Childhood Pulmonary Tuberculosis: A Bayesian Latent Class Analysis.

Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography. We estimated the prevalence of CPTB to be 27% (95% credible interval (CrI): 21, 35). The sensitivities of culture, Xpert, and smear microscopy were estimated to be 60% (95% CrI: 46, 76), 49% (95% CrI: 38, 62), and 22% (95% CrI: 16, 30), respectively; specificities of these tests were estimated in accordance with prior information and were close to 100%. Chest radiography was estimated to have a sensitivity of 64% (95% CrI: 55, 73) and a specificity of 78% (95% CrI: 73, 83). Sensitivity of the TST was estimated to be 75% (95% CrI: 61, 84), and it decreased substantially among children who were malnourished and infected with human immunodeficiency virus (56%). The specificity of the TST was 69% (95% CrI: 63%, 76%). Furthermore, it was estimated that 46% (95% CrI: 42, 49) of CPTB-negative cases and 93% (95% CrI: 82; 98) of CPTB-positive cases received antituberculosis treatment, which indicates substantial overtreatment and limited undertreatment.

Combination Therapies for Smoking Cessation: A Hierarchical Bayesian Meta-Analysis.

CONTEXT: Treatment guidelines recommend the use of combination therapies for smoking cessation, particularly behavioral therapy (BT) as an adjunct to pharmacotherapy. However, these guidelines rely on previous reviews with important limitations. This study's objective was to evaluate the efficacy of combination therapies compared with monotherapies, using the most rigorous data available. EVIDENCE ACQUISITION: A systematic review and meta-analysis of RCTs of pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase, PsycINFO, and PubMed databases were systematically searched from inception to July 2015. Inclusion was restricted to RCTs reporting biochemically validated abstinence at 12 months. Direct and indirect comparisons were made in 2015 between therapies using hierarchical Bayesian models. EVIDENCE SYNTHESIS: The search identified 123 RCTs meeting inclusion criteria (60,774 participants), and data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT increased abstinence more than other combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy compared with pharmacotherapy alone was inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement therapy appears safe and increases abstinence versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other pharmacotherapy combinations and their safety and tolerability. CONCLUSIONS: Evidence suggests that combination therapy benefits may be less than previously thought. Combined with BT, varenicline increases abstinence more than other pharmacotherapy with BT combinations.

Cessation treatment adherence and smoking abstinence in patients after acute myocardial infarction.

BACKGROUND: Previous trials examining the use of bupropion for smoking cessation therapy after myocardial infarction (MI) have been inconclusive. To understand better the observed lack of effectiveness of bupropion in this population, we examined abstinence rates by level of adherence across treatment groups. METHODS: We used data from a randomized, double-blind, placebo-controlled trial of bupropion in smokers (n = 388) hospitalized with MI to study the association of interest. Patients were classified as being fully adherent if they reported taking 2 pills/d; partially adherent if they reported 0, 1, and/or 2 pills/d; and nonadherent if they reported 0 and/or 1 pill/d throughout the 9-week treatment period. Abstinence was assessed by 7-day biochemically validated self-report at 4 and 9 weeks and 6 and 12 months. RESULTS: A total of 156 patients were fully adherent to the study medication (66 bupropion and 90 placebo), 149 were partially adherent (76 and 73, respectively), and 83 were nonadherent (46 and 37, respectively). Regardless of treatment group, patients who were fully or partially adherent reported greater abstinence than did nonadherent patients. Among partially adherent patients, bupropion conferred an important benefit at 12 months (% difference 13.3, 95% CI 1.3-25.3). At 12 months, patients who were fully adherent were more likely to be abstinent compared with those who were nonadherent (adjusted odds ratio 7.6, 95% CI 3.2-17.6). CONCLUSIONS: Adherence to study medication, regardless of assigned treatment, is associated with a substantial increase in abstinence. Patients who are motivated to quit smoking should be targeted for smoking cessation treatment after MI.

Adenoma detection rates decline with increasing procedural hours in an endoscopist's workload.

BACKGROUND: Operator fatigue may negatively influence adenoma detection (AD) during screening colonoscopy. OBJECTIVE: To better characterize factors affecting AD, including the number of hours worked, and the number and type of procedures performed before an index screening colonoscopy. METHODS: A retrospective cohort study was conducted involving individuals undergoing a screening colonoscopy at a major tertiary care hospital in Montreal, Quebec. Individuals were identified using an endoscopic reporting database; AD was identified by an electronic chart review. A hierarchical logistic regression analysis was performed to determine the association between patient- and endoscopist-related variables and AD. RESULTS: A total of 430 consecutive colonoscopies performed by 10 gastroenterologists and two surgeons were included. Patient mean (± SD) age was 63.4±10.9 years, 56.3% were males, 27.7% had undergone a previous colonoscopy and the cecal intubation rate was 95.7%. The overall AD rate was 25.7%. Age was associated with AD (OR 1.06 [95% CI 1.03 to 1.08]), while female sex (OR 0.44 [95% CI 0.25 to 0.75]), an indication for average-risk screening (OR 0.47 [95% CI 0.27 to 0.80]) and an increase in the number of hours during which endoscopies were performed before the index colonoscopy (OR 0.87 [95% CI 0.76 to 0.99]) were associated with lower AD rates. On exploratory univariable analysis, a threshold of 3 h of endoscopy time performed before the index colonoscopy was associated with decreased AD. CONCLUSION: The number of hours devoted to endoscopies before the index colonoscopy was inversely associated with AD rate, with decreased performance possibly as early as within 3 h. This metric should be confirmed in future studies and considered when optimizing scheduling practices.

Transcatheter reduction of paravalvular leaks: a systematic review and meta-analysis.

BACKGROUND: Significant paravalvular leak (PVL) after surgical valve replacement can result in intractable congestive heart failure and hemolytic anemia. Because repeat surgery is performed in only few patients, transcatheter reduction of PVL is emerging as an alternative option, but its safety and efficacy remain uncertain. In this study we sought to assess whether a successful transcatheter PVL reduction is associated with an improvement in clinical outcomes. METHODS: We identified 12 clinical studies that compared successful and failed transcatheter PVL reductions in a total of 362 patients. A Bayesian hierarchical meta-analysis was performed using cardiac mortality as a primary end point. The combined occurrence of improvement in New York Heart Association functional class or hemolytic anemia and the need for repeat surgery, were used as secondary end points. RESULTS: A successful transcatheter PVL reduction was associated with a lower cardiac mortality rate (odds ratio [OR], 0.08; 95% credible interval [CrI], 0.01-0.90) and with a superior improvement in functional class or hemolytic anemia, compared with a failed intervention (OR, 9.95; 95% CrI, 2.10-66.73). Fewer repeat surgeries were also observed after successful procedures (OR, 0.08; 95% CrI, 0.01-0.40). CONCLUSIONS: A successful transcatheter PVL reduction is associated with reduced all-cause mortality and improved functional class in patients deemed unsuitable for surgical correction.