Prognostic Implications of Diabetic Ketoacidosis in Adults on Long-term Mortality and Diabetes-related Complications.

OBJECTIVES: Diabetic ketoacidosis (DKA) occurring after diabetes diagnosis is often associated with risk factors for other diabetes-related complications. In this study we aimed to determine the prognostic implications of DKA on all-cause mortality and complications in type 1 diabetes (T1D). METHODS: Previously collected data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study were obtained through the the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository. Using Cox proportional hazards models with time-dependent covariates, we examined age- and sex-adjusted, glycated hemoglobin-adjusted, and fully adjusted associations of DKA with all-cause mortality, cardiovascular disease, microvascular, and acute complications over 34 years. RESULTS: Of the 1,441 study participants, 297 had 488 DKA events. Prior DKA was associated with a higher risk of age- and sex-adjusted all-cause mortality (hazard ratio [HR] 8.28, 95% confidence interval [CI] 3.74 to 18.32, p<0.001), major adverse cardiovascular events (MACEs) (HR 2.05, 95% CI 1.34 to 3.13, p<0.001), and all advanced microvascular and acute complications compared with no prior DKA. Most associations except retinopathy were significant even after adjustment for covariates. In our fully adjusted analysis, prior DKA was associated with a significantly higher risk of subsequent all-cause mortality (HR 9.13, 95% CI 3.87 to 21.50, p<0.001), MACEs (HR 1.66, 95% CI 1.07 to 2.59, p=0.03), advanced kidney disease (HR 2.10, 95% CI 1.00 to 4.22, p=0.049), advanced neuropathy (HR 1.49, 95% CI 1.05 to 2.13, p=0.03), severe hypoglycemia (HR 1.53, 95% CI 1.28 to 1.81, p<0.001), and recurrent DKA (HR 3.24, 95% CI 2.41 to 4.36, p<0.001) compared with person-time without DKA. CONCLUSIONS: DKA is a prognostic marker for diabetes complications, including excess all-cause mortality. Intensified clinical interventions, such as cardiovascular prevention strategies, may be warranted after diagnosis of DKA.

Essential tobacco dependence medicines in 137 countries.

AIMS: To use a database of national essential medicine lists to determine how many include the three tobacco dependence medicines: nicotine replacement therapy, varenicline and bupropion. METHODS: Retrospective observational study using national essential medicine lists for 137 countries. RESULTS: Of the 137 countries, 34 listed at least one of the three tobacco dependence medicines included in this analysis. Bupropion was listed by 23 countries, nicotine replacement therapy by 17 countries and varenicline by eight countries. CONCLUSIONS: Tobacco dependence medicines do not appear on the essential medicines lists of most countries.

Characteristics of SARS-CoV-2 testing for rapid diagnosis of COVID-19 during the initial stages of a global pandemic.

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE = 0.5, p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ct of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct (SE = 0.5, p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.

Health outcomes attributable to carbapenemase-producing Enterobacteriaceae infections: A systematic review and meta-analysis.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant global health threat. OBJECTIVE: To conduct a systematic review of health outcomes and long-term sequelae attributable to CPE infection. METHODS: We followed PRISMA reporting guidelines and published our review protocol on PROSPERO (CRD42018097357). We searched Medline, Embase, CINAHL and the Cochrane Library. We included primary studies with a carbapenem-susceptible control group in high-income countries, published in English. Quality appraisal was completed using Joanna Briggs Institute checklists. We qualitatively summarized frequently reported outcomes and conducted a meta-analysis. RESULTS: Our systematic review identified 8,671 studies; 17 met the eligibility criteria for inclusion. All studies reported health outcomes; none reported health-related quality-of-life. Most studies were from Europe (65%), were conducted in teaching or university-affiliated hospitals (76%), and used case-control designs (53%). Mortality was the most commonly reported consequence of CPE-infections; in-hospital mortality was most often reported (62%). Our meta-analysis (n = 5 studies) estimated an absolute risk difference (ARD) for in-hospital bloodstream infection mortality of 0.25 (95% confidence interval [CI], 0.17-0.32). Duration of antibiotic therapy (range, 4-29.7 vs 1-23.6 days) and length of hospital stay (range, 21-87 vs 15-43 days) were relatively higher for CPE-infected patients than for patients infected with carbapenem-susceptible pathogens. Most studies (82%) met >80% of their respective quality appraisal criteria. CONCLUSIONS: The risk of in-hospital mortality due to CPE bloodstream infection is considerably greater than carbapenem-susceptible bloodstream infection (ARD, 0.25; 95% CI, 0.17-0.32). Health outcome studies associated with CPE infection are focused on short-term (eg, in-hospital) outcomes; long-term sequelae and quality-of-life are not well studied. TRIAL REGISTRATION: PROSPERO (CRD42018097357).

Accuracy of Electrocardiography and Agreement with Echocardiography in the Diagnosis of Pediatric Left Atrial Enlargement.

Left atrial enlargement (LAE) is a marker for diastolic cardiac dysfunction. Echocardiograms are considered the gold-standard for diagnosis, but given their wider access and lower economic cost, electrocardiograms (ECGs) may be useful in identifying patients who would benefit from further investigation. This study investigates the utility of ECG criteria to diagnose LAE in pediatric patients. A retrospective chart review (n = 492) was conducted in patients whose echocardiograms demonstrated LAE by left atrial indexed diameter z-score ≥2.0 and/or increased left atrial to aortic root ratio at various cutoffs (≥1.4, ≥1.6, ≥1.8). ECG criteria studied included: (1) P wave ≥110 msec, (2) P mitrale ≥40 msec, in LII (3) terminal negative P wave deflection in lead V1 > 40 msec, and (4) P/PR segment >1.6 in lead II. Sensitivity, specificity, Cohen's Kappa coefficient (κ), and ROC curves were calculated. A combination of P mitrale ≥40 msec and terminal negative P wave deflection in lead V1 > 40 msec yielded the greatest agreement (κ = 0.221, 95%CI 0.060-0.382), but all ECG criteria used to diagnose LAE had poor diagnostic value (AUC < 0.60). The present ECG criteria should not be used to diagnose LAE in the absence of an echocardiogram and findings should be considered in the context of clinical symptoms.

The crossover design for studies of infertility employing in-vitro fertilization: A methodological survey.

BACKGROUND: Infertility has become increasingly common worldwide. There is a need for the infertility literature to evaluate new interventions with IVF. The crossover design presents many methodological advantages for IVF trials. In addition to providing a within-person comparison of outcomes, it offers participants the opportunity to potentially benefit from more than one available treatment. However, infertility studies present a unique challenge in terms of bias: successful participants do not cross over to the second treatment group. OBJECTIVES: The main objective of our study was to survey the methodological features of crossover trials for infertility with in-vitro fertilization (IVF) based interventions. A secondary focus was reporting key results. STUDY DESIGN & SETTING: We conducted a methodological survey by systematically searching Medline and Embase databases. The capture-recapture technique was used to estimate the number of relevant studies that were not retrieved by our search strategy. We employed the Cochrane risk of bias tool to assess methodological rigour. Crossover-specific methods features were summarized. Treatment effects for pregnancy outcomes across studies are also presented. RESULTS: 15 studies met inclusion criteria. Most studies were deemed to have high or unclear risks of bias, usually because of incomplete reporting of outcome data and assessment procedures. 13 studies did not employ crossover-specific methods to analyze outcome data by period, which may bias treatment effect estimates. Four studies reported pregnancy outcome data with sample sizes from both treatment periods. Of these four studies, three reported that the control intervention was favoured. CONCLUSIONS: The main limitation of our survey was the small sample size of studies. Future reviews should be larger and seek to encompass a broader range of the infertility literature. Despite the issues identified in the included trials, consideration should still be given to using the crossover design in future infertility research. Employing crossover-specific analysis methods, such as accounting for participant non-completion, along with strict adherence to CONSORT reporting guidelines, may significantly reduce the risk of bias in individual studies.