Tyler Williamson

Transobturator tape compared with tension-free vaginal tape for stress incontinence: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of transobturator tape with tension-free vaginal tape (TVT) in terms of objective cure of stress urinary incontinence (SUI) at 12 months postoperatively. METHOD: Women with SUI were randomly allocated to either transobturator tape or TVT procedures and reviewed at 12 months after surgery. The primary outcome was objective evidence of “cure,” evaluated by standardized pad test (cure defined as less than 1 g urine leaked). Other outcomes included complications, subjective cure, incontinence-related quality of life, return to usual sexual activity, and satisfaction with surgery. Primary analysis compared the proportion of patients in each group who were cured at 12-month follow-up. RESULTS: A total of 199 women participated (94 in the transobturator tape group, 105 in the TVT group). Sixty-eight women (81%) in the transobturator tape group were cured, compared with 67 (77%) in the TVT group (relative risk 1.05, 95% confidence interval 0.90–1.23, P=.577). On vaginal examination, the tape was palpable for 68 women (80%) in the transobturator tape group and for 24 (27%) in the TVT group (relative risk 0.22, 95% confidence interval 0.13–0.37, P<.001). More women in the transobturator tape group experienced groin pain during vaginal palpation (13 [15%] in the transobturator tape group and five [6%] in the TVT group, P=.044). Quality of life improved significantly from baseline in both groups (30-point improvement in IIQ-7 score for both groups). CONCLUSION: At 12 months, the majority of women had minimal leakage and their quality of life had improved significantly, but differences were not observed between groups. The presence of palpable tape, particularly among the transobturator tape group, is concerning; longer follow-up is needed to determine whether this outcome leads to extrusion or resolves over time. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00234754. LEVEL OF EVIDENCE: I

Validating the 8 CPCSSN Case Definitions for Chronic Disease Surveillance in a Primary Care Database of Electronic Health Records

PURPOSE The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is Canada’s first national chronic disease surveillance system based on electronic health record (EHR) data. The purpose of this study was to develop and validate case definitions and case-finding algorithms used to identify 8 common chronic conditions in primary care: chronic obstructive pulmonary disease (COPD), dementia, depression, diabetes, hypertension, osteoarthritis, parkinsonism, and epilepsy. METHODS Using a cross-sectional data validation study design, regional and local CPCSSN networks from British Columbia, Alberta (2), Ontario, Nova Scotia, and Newfoundland participated in validating EHR case-finding algorithms. A random sample of EHR charts were reviewed, oversampling for patients older than 60 years and for those with epilepsy or parkinsonism. Charts were reviewed by trained research assistants and residents who were blinded to the algorithmic diagnosis. Sensitivity, specificity, and positive and negative predictive values (PPVs, NPVs) were calculated. RESULTS We obtained data from 1,920 charts from 4 different EHR systems (Wolf, Med Access, Nightingale, and PS Suite). For the total sample, sensitivity ranged from 78% (osteoarthritis) to more than 95% (diabetes, epilepsy, and parkinsonism); specificity was greater than 94% for all diseases; PPV ranged from 72% (dementia) to 93% (hypertension); NPV ranged from 86% (hypertension) to greater than 99% (diabetes, dementia, epilepsy, and parkinsonism). CONCLUSIONS The CPCSSN diagnostic algorithms showed excellent sensitivity and specificity for hypertension, diabetes, epilepsy, and parkinsonism and acceptable values for the other conditions. CPCSSN data are appropriate for use in public health surveillance, primary care, and health services research, as well as to inform policy for these diseases.

The Safety of Yellow Fever Vaccine 17D or 17DD in Children, Pregnant Women, HIV+ Individuals, and Older Persons: Systematic Review

Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups.

Emergency Medical Services Response Time and Mortality in an Urban Setting

Abstract Background. A common tenet in emergency medical services (EMS) is that faster response equates to better patient outcome, translated by some EMS operations into a goal of a response time of 8 minutes or less for advanced life support (ALS) units responding to life-threatening events. Objective. To explore whether an 8-minute EMS response time was associated with mortality. Methods. This was a one-year retrospective cohort study of adults with a life-threatening event as assessed at the time of the 9-1-1 call (Medical Priority Dispatch System Echo- or Delta-level event). The study setting was an urban all-ALS EMS system serving a population of approximately 1 million. Response time was defined as 9-1-1 call receipt to ALS unit arrival on scene, and outcome was defined as all-cause mortality at hospital discharge. Potential covariates included patient acuity, age, gender, and combined scene and transport interval time. Stratified analysis and logistic regression were used to assess the response time–mortality association. Results. There were 7,760 unit responses that met the inclusion criteria; 1,865 (24%) were ≥8 minutes. The average patient age was 56.7 years (standard deviation = 21.5). For patients with a response time ≥8 minutes, 7.1% died, compared with 6.4% for patients with a response time ≤7 minutes 59 seconds (risk difference 0.7%; 95% confidence interval [CI]: –0.5%, 2.0%). The adjusted odds ratio of mortality for ≥8 minutes was 1.19 (95% CI: 0.97, 1.47). An exploratory analysis suggested there may be a small beneficial effect of response ≤7 minutes 59 seconds for those who survived to become an inpatient (adjusted odds ratio = 1.30; 95% CI: 1.00, 1.69). Conclusions. These results call into question the clinical effectiveness of a dichotomous 8-minute ALS response time on decreasing mortality for the majority of adult patients identified as having a life-threatening event at the time of the 9-1-1 call. However, this study does not suggest that rapid EMS response is undesirable or unimportant for certain patients. This analysis highlights the need for further research on who may benefit from rapid EMS response, whether these individuals can be identified at the time of the 9-1-1 call, and what the optimum response time is.

Drip and Ship Versus Direct to Comprehensive Stroke Center: Conditional Probability Modeling

The outcome of ischemic stroke is related to the volume of brain that is infarcted, and the volume of infarction is directly related to the time to reperfusion.1 In an anterior circulation, large-vessel ischemic stroke 1.9 million neurons are lost every minute.2 Treatment efficacy is dependent on time to treatment initiation. Acute ischemic stroke is treated medically with the administration of intravenous alteplase. Recent results of several randomized trials established the efficacy of endovascular treatment in ischemic stroke.3–8 The facilities and expertise needed for endovascular procedures are only available at endovascular capable centers (ECCs), which are typically tertiary care hospitals. Medical treatment with alteplase is more widely available. This creates 2 options for prehospital destination decision-making for suspected stroke: (1) transport the patient directly to the nearest ECC to receive alteplase and, if appropriate, immediate endovascular therapy even though this might mean bypassing a closer non-ECC (nECC; mothership model); or (2) transport the patient to the nearest nECC to receive alteplase and then transfer the patient to the nearest ECC for endovascular therapy (drip and ship model). There are advantages and disadvantages to each of these options, and it is currently unknown which of these options will lead to the highest probability of good outcome for the patient. The RACECAT trial in Barcelona, Spain, is planned to directly address this question (NCT02795962). Herein, we propose a methodology for addressing this problem using statistical probability modeling and suggest a candidate model for evaluation. ### Assumptions We make several assumptions in the development of the prediction models (Table I in the online-only Data Supplement). First, these models apply when there is uncertainty on which transport and treatment decision to choose. Second, the nECC is the closest treatment center to the location of stroke occurrence. If an ECC is the …

High rabbit-antihuman thymocyte globulin levels are associated with low likelihood of graft-vs-host disease and high likelihood of posttransplant lymphoproliferative disorder.

Rabbit-antithymocyte globulin (ATG) given with conditioning has the potential to decrease the likelihood of graft-versus-host disease (GVHD) or graft failure and to increase the likelihood of relapse or infections. After a given ATG dose, serum ATG levels are variable. Here we determined ATG levels on days 7 and 28 in 153 patients whose conditioning included 4.5 mg/kg ATG (thymoglobulin). Median follow-up was 547 days (range: 14-1519, minimum for patients who have not died, relapsed, developed second malignancy, or had graft failure, 365). Both high day 7 levels and high day 28 levels were associated with low likelihoods of grade II-IV acute GVHD and chronic GVHD needing systemic immunosuppressive therapy, and a high likelihood of posttransplant lymphoproliferative disorder (PTLD). Patients with day 7 ATG levels above 0.803 mg/L had 0.52-fold risk of developing chronic GVHD needing systemic therapy (P = 0.012) and patients with day 7 ATG levels above 1.436 mg/L had 5.84-fold risk of developing PTLD (P = 0.001) compared to patients with lower ATG levels. There was no association of ATG levels with relapse, death, or non-PTLD infections. Association with graft failure could not be evaluated due to only 4 graft failures in the cohort. In conclusion, patients with slow clearance of ATG have a low risk of GVHD, but a high risk of PTLD. The clearance of this relatively low dose of ATG does not impact the likelihood of relapse, death, or non-PTLD infections.

Effect of an emergency department sepsis protocol on time to antibiotics in severe sepsis.

OBJECTIVE We sought to evaluate the time to antibiotics for emergency department (ED) patients meeting criteria for severe sepsis before and after the implementation of an ED sepsis protocol. Compliance with published guidelines for time to antibiotics and initial empiric therapy in sepsis was also assessed. METHODS A retrospective chart review was conducted. Emergency department patient encounters with International Classification of Diseases codes related to severe infections were screened during a 3-month period before and after the implementation of a sepsis protocol. Encounters meeting criteria for severe sepsis were further assessed. The time to initiation of antibiotics was determined as well as the initial choice of antimicrobial therapy based on the presumed source of infection. RESULTS We reviewed 213 unique ED patient encounters meeting criteria for severe sepsis. Analysis of the period before implementation showed a median time from the time criteria for severe sepsis were met to delivery of antibiotics of 163 minutes (95% confidence interval [CI] 124 to 210 min). Analysis of the period after implementation of the protocol revealed a median time of 79 minutes (95% CI 64 to 94 min), representing an overall reduction of 84 minutes (95% CI 42 to 126 min). Before the implementation of the protocol, 47% of patients received correct antibiotic coverage for the presumed source of infection in compliance with locally published guidelines. After the initiation of the protocol, 73% received appropriate initial antibiotics, for an overall improvement of 26%. CONCLUSION A guideline-based ED sepsis protocol for the evaluation and treatment of the septic patient appears to improve the time to administration of antibiotics as well as the appropriateness of initial antibiotic therapy in patients with severe sepsis.

Log-binomial models: exploring failed convergence

BackgroundRelative risk is a summary metric that is commonly used in epidemiological investigations. Increasingly, epidemiologists are using log-binomial models to study the impact of a set of predictor variables on a single binary outcome, as they naturally offer relative risks. However, standard statistical software may report failed convergence when attempting to fit log-binomial models in certain settings. The methods that have been proposed in the literature for dealing with failed convergence use approximate solutions to avoid the issue. This research looks directly at the log-likelihood function for the simplest log-binomial model where failed convergence has been observed, a model with a single linear predictor with three levels. The possible causes of failed convergence are explored and potential solutions are presented for some cases.ResultsAmong the principal causes is a failure of the fitting algorithm to converge despite the log-likelihood function having a single finite maximum. Despite these limitations, log-binomial models are a viable option for epidemiologists wishing to describe the relationship between a set of predictors and a binary outcome where relative risk is the desired summary measure.ConclusionsEpidemiologists are encouraged to continue to use log-binomial models and advocate for improvements to the fitting algorithms to promote the widespread use of log-binomial models.

Donor Serostatus Has an Impact on Cytomegalovirus-Specific Immunity, Cytomegaloviral Disease Incidence, and Survival in Seropositive Hematopoietic Cell Transplant Recipients

More cytomegalovirus (CMV)-specific T cells are transferred with grafts from CMV seropositive than seronegative donors. We hypothesized that seropositive recipients of grafts from seropositive donors (D+R+) have higher counts of CMV-specific T cells than seropositive recipients of grafts from seronegative donors (D-R+), and that this is clinically relevant in the setting of in vivo T cell depletion using rabbit-antihuman thymocyte globulin (ATG). We reviewed charts of 298 ATG-conditioned, seropositive recipients for CMV reactivation (pp65 antigenemia or CMV DNAemia above institutional threshold for preemptive therapy), recurrent CMV reactivation, CMV disease, and death. In 77 of these patients, we enumerated CMV-specific T cells. Median follow-up was 564 days. CMV-specific CD4+ and, to a lesser degree, CD8+ T cell counts were higher in D+R+ than D-R+ patients. D+R+ patients had lower cumulative incidence of CMV reactivation (21% versus 48%, P < .001), recurrent reactivation (4% versus 15%, P = .003), CMV disease (3% versus 13%, P = .005) and mortality (42% versus 56%, P = .006). We conclude that in the setting of in vivo T cell depletion using ATG, seropositive donors should be used for seropositive recipients. For scenarios where only seronegative donors are available, strategies to improve CMV-specific immunity (e.g., donor vaccination) should be explored.

Prevalence and Epidemiology of Diabetes in Canadian Primary Care Practices: A Report from the Canadian Primary Care Sentinel Surveillance Network

OBJECTIVE The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is a large, validated national primary care Electronic Medical Records (EMR)-based database. Our objective was to describe the epidemiology of diabetes in this Canadian sample. METHODS We analyzed the records of 272 469 patients10 years of age and older, with at least 1 primary care clinical encounter between January 1, 2011, and December 31, 2012. We calculated the age-gender standardized prevalence of diabetes. We compared health care utilization and comorbidities for 7 selected chronic conditions in patients with and without diabetes. We also examined patterns of medication usage. RESULTS The estimated population prevalence of diabetes was 7.6%. Specifically, we studied 25 425 people with diabetes who had at least 1 primary care encounter in 2 years. On average, patients with diabetes had 1.42 times as many practice encounters as patients without diabetes (95% CI 1.42 to 1.43, p<0.0001). Patients with diabetes had 1.29 times as many other comorbid conditions as those without diabetes (95% CI 1.27 to 1.31, p<0.0001). We found that 85.2% of patients taking hypoglycemic medications were taking metformin, and 51.8% were taking 2 or more classes of medications. CONCLUSIONS This study is the first national Canadian report describing the epidemiology of diabetes using primary care EMR-based data. We found significantly higher rates of primary care use, and greater numbers of comorbidities in patients with diabetes. Most patients were on first-line hypoglycemic medications. Data routinely recorded in EMRs can be used for surveillance of chronic diseases such as diabetes in Canada. These results can enable comparisons with other national EMR-based datasets.