Health-Analytics Data to Evidence Suite (HADES): Open-Source Software for Observational Research.

The Health-Analytics Data to Evidence Suite (HADES) is an open-source software collection developed by Observational Health Data Sciences and Informatics (OHDSI). It executes directly against healthcare data such as electronic health records and administrative claims, that have been converted to the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Using advanced analytics, HADES performs characterization, population-level causal effect estimation, and patient-level prediction, potentially across a federated data network, allowing patient-level data to remain locally while only aggregated statistics are shared. Designed to run across a wide array of technical environments, including different operating systems and database platforms, HADES uses continuous integration with a large set of unit tests to maintain reliability. HADES implements OHDSI best practices, and is used in almost all published OHDSI studies, including some that have directly informed regulatory decisions.

Evaluating the impact of alternative phenotype definitions on incidence rates across a global data network.

Objective: Developing accurate phenotype definitions is critical in obtaining reliable and reproducible background rates in safety research. This study aims to illustrate the differences in background incidence rates by comparing definitions for a given outcome. Materials and Methods: We used 16 data sources to systematically generate and evaluate outcomes for 13 adverse events and their overall background rates. We examined the effect of different modifications (inpatient setting, standardization of code set, and code set changes) to the computable phenotype on background incidence rates. Results: Rate ratios (RRs) of the incidence rates from each computable phenotype definition varied across outcomes, with inpatient restriction showing the highest variation from 1 to 11.93. Standardization of code set RRs ranges from 1 to 1.64, and code set changes range from 1 to 2.52. Discussion: The modification that has the highest impact is requiring inpatient place of service, leading to at least a 2-fold higher incidence rate in the base definition. Standardization showed almost no change when using source code variations. The strength of the effect in the inpatient restriction is highly dependent on the outcome. Changing definitions from broad to narrow showed the most variability by age/gender/database across phenotypes and less than a 2-fold increase in rate compared to the base definition. Conclusion: Characterization of outcomes across a network of databases yields insights into sensitivity and specificity trade-offs when definitions are altered. Outcomes should be thoroughly evaluated prior to use for background rates for their plausibility for use across a global network.

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study.

INTRODUCTION: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. METHODS: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. RESULTS: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. CONCLUSION: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

Infected Radicular Cyst of Deciduous Second Molar Mimicking Dentigerous Cyst of Second Premolar in a Young Child: A Rare Entity.

Radicular cysts are the most common cystic lesions in the oral cavity. Radicular cysts have a rare occurrence in the primary dentition. Radicular cysts arising from deciduous teeth are reported to occur in the age range of 3-19 years with a male predominance. The etiological factor is long-standing dental caries and dental trauma. The present case report describes the inflammatory radicular cyst involving the deciduous mandibular second molar. Surgical management includes enucleation of the cyst along with mandibular second premolar in a 5-year-old female patient. The surgical cavity was closed by an obturator appliance to maintain the patency. Eventful healing was seen after 3 months of follow-up. How to cite this article: Kajjari S, Gowtham A, Meharwade P, et al. Infected Radicular Cyst of Deciduous Second Molar Mimicking Dentigerous Cyst of Second Premolar in a Young Child: A Rare Entity. Int J Clin Pediatr Dent 2021;14(3):434-437.

Comparative evaluation of root ZX Mini® apex locator and radiovisiography in determining the working length of primary molars: An In Vivo study.

INTRODUCTION: Working length determination is a crucial step for success of pulpectomy. Various new modalities have been developed. The newest technology includes EAL. Electronic apex locators require less chair side time, do not produce pain and avoid unnecessary radiation which makes it more superior in paediatric endodontic procedures. AIM: To evaluate and compare Root ZX mini apex locator and Radiovisiography (RVG) for determining working length in primary molars. MATERIALS AND METHODS: A sample of 30 primary molar teeth was subjected to working length determination by Root ZX mini and RVG. The data was collected and then tabulated and subjected to statistical analysis. RESULTS: On comparison among two groups, it was found there was no difference between the efficiency of modalities. A positive correlation was seen among Root ZX mini and RVG (ICC â€‹= â€‹0.99). CONCLUSION: Root ZX mini and radiovisiography are seen to be precise in determination of working length in primary molars. It can be said that Root ZX mini i. e the electronic apex locators can be used as an adjunct to Radiovisiography and conventional radiography.

Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study.

OBJECTIVES: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. METHODS: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. RESULTS: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. CONCLUSION: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. TRIAL REGISTRATION: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

BACKGROUND: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. METHODS: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I 2 value was less than 0·4. FINDINGS: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]). INTERPRETATION: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.

Deep phenotyping of 34,128 patients hospitalised with COVID-19 and a comparison with 81,596 influenza patients in America, Europe and Asia: an international network study.

Background In this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared individuals hospitalised with COVID-19 to those previously hospitalised with influenza. Methods We report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]). These patients were then compared with patients hospitalised with influenza in 2014-19. Results 34,128 (US: 8,362, South Korea: 7,341, Spain: 18,425) individuals hospitalised with COVID-19 were included. Between 4,811 (HM) and 11,643 (CUIMC) unique aggregate characteristics were extracted per patient, with all summarised in an accompanying interactive website (http://evidence.ohdsi.org/Covid19CharacterizationHospitalization/). Patients were majority male in the US (CUIMC: 52%, PHD: 52%, UC HDC: 54%, VA OMOP: 94%,) and Spain (SIDIAP: 54%, HM: 60%), but were predominantly female in South Korea (HIRA: 60%). Age profiles varied across data sources. Prevalence of asthma ranged from 4% to 15%, diabetes from 13% to 43%, and hypertensive disorder from 24% to 70% across data sources. Between 14% and 33% were taking drugs acting on the renin-angiotensin system in the 30 days prior to hospitalisation. Compared to 81,596 individuals hospitalised with influenza in 2014-19, patients admitted with COVID-19 were more typically male, younger, and healthier, with fewer comorbidities and lower medication use. Conclusions We provide a detailed characterisation of patients hospitalised with COVID-19. Protecting groups known to be vulnerable to influenza is a useful starting point to minimize the number of hospital admissions needed for COVID-19. However, such strategies will also likely need to be broadened so as to reflect the particular characteristics of individuals hospitalised with COVID-19.

An international characterisation of patients hospitalised with COVID-19 and a comparison with those previously hospitalised with influenza

BackgroundIn this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared individuals hospitalised with COVID-19 to those previously hospitalised with influenza. MethodsWe report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]). These patients were then compared with patients hospitalised with influenza in 2014-19. Results34,128 (US: 8,362, South Korea: 7,341, Spain: 18,425) individuals hospitalised with COVID-19 were included. Between 4,811 (HM) and 11,643 (CUIMC) unique aggregate characteristics were extracted per patient, with all summarised in an accompanying interactive website (http://evidence.ohdsi.org/Covid19CharacterizationHospitalization/). Patients were majority male in the US (CUIMC: 52%, PHD: 52%, UC HDC: 54%, VA OMOP: 94%,) and Spain (SIDIAP: 54%, HM: 60%), but were predominantly female in South Korea (HIRA: 60%). Age profiles varied across data sources. Prevalence of asthma ranged from 4% to 15%, diabetes from 13% to 43%, and hypertensive disorder from 24% to 70% across data sources. Between 14% and 33% were taking drugs acting on the renin-angiotensin system in the 30 days prior to hospitalisation. Compared to 81,596 individuals hospitalised with influenza in 2014-19, patients admitted with COVID-19 were more typically male, younger, and healthier, with fewer comorbidities and lower medication use. ConclusionsWe provide a detailed characterisation of patients hospitalised with COVID-19. Protecting groups known to be vulnerable to influenza is a useful starting point to minimize the number of hospital admissions needed for COVID-19. However, such strategies will also likely need to be broadened so as to reflect the particular characteristics of individuals hospitalised with COVID-19.

Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study

BackgroundHydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. MethodsNew user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. ResultsOverall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) ConclusionsShort-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19. Trial registration numberRegistered with EU PAS; Reference number EUPAS34497 (http://www.encepp.eu/encepp/viewResource.htm?id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine. Funding sourcesThis research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and Senior Research Fellowship (DPA), US National Institutes of Health, Janssen Research & Development, IQVIA, and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI16C0992]. Personal funding included Versus Arthritis [21605] (JL), MRC-DTP [MR/K501256/1] (JL), MRC and FAME (APU). The European Health Data & Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Unions Horizon 2020 research and innovation programme and EFPIA. No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, NHS or the Department of Health, England.

Development and validation of a prognostic model predicting symptomatic hemorrhagic transformation in acute ischemic stroke at scale in the OHDSI network.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) after cerebral infarction is a complex and multifactorial phenomenon in the acute stage of ischemic stroke, and often results in a poor prognosis. Thus, identifying risk factors and making an early prediction of HT in acute cerebral infarction contributes not only to the selections of therapeutic regimen but also, more importantly, to the improvement of prognosis of acute cerebral infarction. The purpose of this study was to develop and validate a model to predict a patient's risk of HT within 30 days of initial ischemic stroke. METHODS: We utilized a retrospective multicenter observational cohort study design to develop a Lasso Logistic Regression prediction model with a large, US Electronic Health Record dataset which structured to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). To examine clinical transportability, the model was externally validated across 10 additional real-world healthcare datasets include EHR records for patients from America, Europe and Asia. RESULTS: In the database the model was developed, the target population cohort contained 621,178 patients with ischemic stroke, of which 5,624 patients had HT within 30 days following initial ischemic stroke. 612 risk predictors, including the distance a patient travels in an ambulance to get to care for a HT, were identified. An area under the receiver operating characteristic curve (AUC) of 0.75 was achieved in the internal validation of the risk model. External validation was performed across 10 databases totaling 5,515,508 patients with ischemic stroke, of which 86,401 patients had HT within 30 days following initial ischemic stroke. The mean external AUC was 0.71 and ranged between 0.60-0.78. CONCLUSIONS: A HT prognostic predict model was developed with Lasso Logistic Regression based on routinely collected EMR data. This model can identify patients who have a higher risk of HT than the population average with an AUC of 0.78. It shows the OMOP CDM is an appropriate data standard for EMR secondary use in clinical multicenter research for prognostic prediction model development and validation. In the future, combining this model with clinical information systems will assist clinicians to make the right therapy decision for patients with acute ischemic stroke.

Invasive fungal infection in immunocompetent trauma patients - A case series.

Zygomycosis is the third leading cause of invasive fungal infection after candidiasis and aspergillosis. Although zygomycosis mostly affects immunocompromised individuals trauma may potentiate infection in immunocompetent individuals. The mortality rate of Zygomycosis is around 50% due to angioinvasion. Here we report a series of 5 cases of angio invasive fungal infection in immunocompetent individuals who sustained trauma in urban areas, out of which only one patient survived following high above knee amputation.

Prostate Specific Antigen-Growth Curve Model to Predict High-Risk Prostate Cancer.

PURPOSE: To investigate if a prostate specific antigen (PSA)-derived growth curve can predict the occurrence of high-risk prostate cancer (PrCA). METHODS: Data from 38,340 men randomized to the PrCA screening arm in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) were used to develop a PSA growth curve model to estimate PSA rate of change. The model was then used to predict high-risk PrCA in clinical data available from 680,390 veterans seeking routine care. The PSA growth curve was modeled using non-linear mixed regression and the PSA rate was estimated by taking the 1st derivative of the growth curve equation at 1 year prior to diagnosis/exit. RESULTS: In the PLCO, PrCA incidence was 8.1%; ≈19% of whom had high-risk PrCA. Overall, a PSA rate threshold of 0.37 ng/ml/year had the best combination of sensitivity (97.2%) and specificity (97.3%) for detecting high-risk PrCA. In the VA data; 7,347 men were diagnosed with PrCA; of these 4,315 (58.7%) were diagnosed with high-risk PrCA. The PLCO optimal threshold of 0.37 ng/ml/year produced sensitivity = 95.5% and specificity = 85.2%. An optimal threshold of 0.99 ng/ml/year in AA produced sensitivity = 89.1% and specificity = 80.0%. PSA rate was a better predictor than the single last PSA value. CONCLUSIONS: PSA growth curves predicted high-risk PrCA in the PLCO data. Fitting the same algorithm in the VA data produced lower specificity. Although encouraging, this finding underlines the need for further research to prospectively test the algorithm, especially for African-American men, the population group at highest risk of aggressive PrCA. Prostate 77:173-184, 2017. © 2016 Wiley Periodicals, Inc.

The use of multiphase nonlinear mixed models to define and quantify long-term changes in serum prostate-specific antigen: data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

PURPOSE: To test the hypothesis that the pattern of prostate-specific antigen (PSA) change in men diagnosed with high-risk prostate cancer (PrCA) differs from the pattern evident in men diagnosed with low-risk PrCA or those with no evidence of PrCA. METHODS: A retrospective cohort study from which PSA measures were taken before PrCA diagnosis from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Data were fitted using a nonlinear regression model to estimate the adjusted absolute and relative (%) change of PSA. RESULTS: Data on 20,888 men with an average age of 61.61 years were included in the analysis. Of these, the 324 (1.55%) diagnosed with high-risk PrCA had a steeper and earlier transition into an exponential pattern of PSA change than the 1368 men diagnosed with low-risk cancer. At 1 year before diagnosis and/or exit, the average absolute PSA rates were 0.05 ng/mL/year (0.05-0.05), 0.59 (0.52-0.66), and 2.60 (2.11-3.09) for men with no evidence of PrCA, men with low-risk PrCA and those with high-risk PrCA, respectively. CONCLUSIONS: The pattern of PSA change with time was significantly different for men who develop high-risk PrCA from those diagnosed with low-risk PrCA. Further research is required to validate this method and its utilization in PrCA screening.

Cardiac risks associated with antibiotics: azithromycin and levofloxacin.

INTRODUCTION: Azithromycin and levofloxacin have been shown to be efficacious in treating infections. The adverse drug events associated with azithromycin and levofloxacin were considered rare. However, the US FDA released warnings regarding the possible risk of QT prolongation with azithromycin and levofloxacin. AREAS COVERED: Case reports/case series, observational studies and clinical trials assessing cardiovascular risks associated with azithromycin and levofloxacin were critically reviewed, including 15 case reports/series, 5 observational studies and 5 clinical trials that investigated the cardiac risks associated azithromycin and levofloxacin. EXPERT OPINION: Results are discordant. Two retrospective studies utilizing large databases demonstrated an increased risk of cardiovascular death with azithromycin, when azithromycin was compared with amoxicillin. Two other retrospective studies found no difference in cardiovascular death associated with azithromycin and other antibiotics. For levofloxacin, the increased risk of cardiovascular death was only found in one retrospective study. Therefore, the risks and benefits of antibacterial therapies should be considered when making prescription decisions. This study should not preclude clinicians from avoiding azithromycin and levofloxacin. If a patient has an indication to receive an antibiotic and if azithromycin or levofloxacin is needed, it may be used, but the potential risks must be understood.

Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death.

PURPOSE: Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODS: We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. RESULTS: During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82). CONCLUSIONS: Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.

Angiotensin receptor blockers and risk of prostate cancer among United States veterans.

To address concerns regarding increased risk of prostate cancer (PrCA) among angiotensin receptor blocker (ARB) users, we used national retrospective data from the Department of Veterans Affairs (VA) through the Veterans Affairs Informatics and Computing Infrastructure. We identified a total of 543,824 unique Veterans who were classified into either ARB treated or not-treated in 1:15 ratio. The two groups were balanced using inverse probability of treatment weights. A double-robust cox-proportional hazards model was used to estimate the hazard ratio for PrCA incidence. To evaluate for a potential Gleason score stage migration, we conducted weighted Cochrane-Armitage test. Post weighting, the rates of PrCA in treated and not-treated groups were 506 (1.5%) and 8,269 (1.6%), respectively; representing a hazard ratio of (0.91, p-value .049). There was no significant difference in Gleason scores between the two groups. We found a small, but statistically significant, reduction in the incidence of clinically detected PrCA among patients assigned to receive ARB with no countervailing effect on degree of differentiation (as indicated by Gleason score). Findings from this study support Food and Drug Administration's recent conclusion that ARB use does not increase risk of incident PrCA.

Children born to diabetic mothers may be more likely to have intellectual disability.

Intellectual disability (ID) is a major public health condition that usually develops in utero and causes lifelong disability. Despite improvements in pregnancy and delivery care that have resulted in dramatic decreases in infant mortality rates, the incidence of ID has remained constant over the past 20 years. There may still be uncharacterized preventable causes of ID such as Diabetes Mellitus (DM). We used statewide individual level de-identified data for maternal and child pairs obtained by linking Medicaid claims, Department of Education, and Department of Disabilities and Special Needs data from 2000 to 2007 for all mother-child pairs with a minimum follow-up of 3-years post birth or until a diagnosis of ID. To ascertain the adjusted relationship between DM and ID, we fit a logistic regression model taking into account individual level clustering on mothers for multiple pregnancies using the population-averaged Generalized Estimating Equations method. Of the 162,611 eligible maternal and child pairs, 5,667 (3.49 %) of the children were diagnosed with ID between birth and 3-years of age. After adjustment for covariates the independent relationship between DM and ID was significant with odds ratio of 1.10 (1.01-1.12). On sub-analysis, patients with pre-pregnancy DM had the highest effect measure with an estimated odds ratio of 1.32 (0.84, 2.09), although this was not statistically significant. In this large cohort of mothers and children in South Carolina, we found a small but statistically significant increased risk for ID among children born to mothers with DM. Additional information about the association between maternal DM and risk of ID in children may lead to the development of effective preventive interventions on the individual and public health levels.

Statin therapy improves sustained virologic response among diabetic patients with chronic hepatitis C.

BACKGROUND & AIMS: Patients with chronic hepatitis C infection are 2- to 3-fold more likely to develop type 2 diabetes, which reduces their chances of achieving a sustained virologic response (SVR). To identify differences in predictors of SVR in patients with and without diabetes who received combination antiviral therapy, we conducted a retrospective analysis of a national Veterans Affairs administrative database. METHODS: We analyzed data from the Veterans Affairs Medical SAS Datasets and Decision Support System for entire cohort and separately for diabetic patients (n = 1704) and nondiabetic patients (n = 6589). Significant predictors of SVR were identified by logistic regression analysis. RESULTS: Diabetic patients had a lower SVR compared with nondiabetic patients (21% vs 27%, respectively, P < .001). Diabetic patients had higher clustering of previously established negative predictors of SVR. On multivariate analysis of diabetic patients for SVR, the positive predictors were higher low-density lipoprotein (odds ratio [OR], 1.45; P = .0129), use of statin (OR, 1.52; P = .0124), and lower baseline viral load (OR, 2.31; P < .001), whereas insulin therapy (OR, 0.7; P = .0278) was a negative predictor. Diabetic patients on statins had higher pretreatment viral loads (log 6.2 vs 6.4, respectively, P = .006) but better early virologic response. There was a graded inverse relationship between Hemoglobin A1c and SVR rate (P = .0482). This relationship was significant among insulin users (P = .0154) and non-significant among metformin users (P = .5853). CONCLUSIONS: Statin use was associated with an improved SVR among both diabetic patients and nondiabetic patients receiving combination antiviral therapy. Diabetic patients who received insulin achieved lower SVR compared with those not receiving insulin. Poor diabetes control was associated with lower SVR rates.

Predictors of hematological abnormalities in patients with chronic hepatitis C treated with interferon and ribavirin.

Hematological abnormalities including neutropenia, anemia, and thrombocytopenia are commonly seen in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The aim of this study was to identify factors which would help to predict the development of hematological abnormalities in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. During a 4-year period, all patients with chronic hepatitis C started on treatment with pegylated interferon and ribavirin were identified. Patients were defined as having hematological abnormalities if they had the presence of either anemia, neutropenia, thrombocytopenia, or a combination of the above during treatment with pegylated interferon and ribavirin. A total of 136 patients with chronic hepatitis C were included in this study. Fifty-two (38.2%) of the patients developed significant hematological abnormalities during treatment with pegylated interferon and ribavirin with 28 (20.6%), 30 (22.1%), and 11 (8.1%) developed neutropenia, anemia, and thrombocytopenia, respectively. Genotype 1, history of hypertension, low baseline platelet count, low baseline hemoglobin, as well as a raised creatinine were significant factors associated with the development of hematological abnormalities. Significant hematological abnormalities are commonly present in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. This study identifies pretreatment parameters that may help identify high-risk patients who are more likely to develop hematological abnormalities during treatment for chronic hepatitis C.