Development and evaluation of an algorithm to link mothers and infants in two US commercial healthcare claims databases for pharmacoepidemiology research.

BACKGROUND: Administrative healthcare claims databases are used in drug safety research but are limited for investigating the impacts of prenatal exposures on neonatal and pediatric outcomes without mother-infant pair identification. Further, existing algorithms are not transportable across data sources. We developed a transportable mother-infant linkage algorithm and evaluated it in two, large US commercially insured populations. METHODS: We used two US commercial health insurance claims databases during the years 2000 to 2021. Mother-infant links were constructed where persons of female sex 12-55 years of age with a pregnancy episode ending in live birth were associated with a person who was 0 years of age at database entry, who shared a common insurance plan ID, had overlapping insurance coverage time, and whose date of birth was within ± 60-days of the mother's pregnancy episode live birth date. We compared the characteristics of linked vs. non-linked mothers and infants to assess similarity. RESULTS: The algorithm linked 3,477,960 mothers to 4,160,284 infants in the two databases. Linked mothers and linked infants comprised 73.6% of all mothers and 49.1% of all infants, respectively. 94.9% of linked infants' dates of birth were within ± 30-days of the associated mother's pregnancy episode end dates. Characteristics were largely similar in linked vs. non-linked mothers and infants. Differences included that linked mothers were older, had longer pregnancy episodes, and had greater post-pregnancy observation time than mothers with live births who were not linked. Linked infants had less observation time and greater healthcare utilization than non-linked infants. CONCLUSIONS: We developed a mother-infant linkage algorithm and applied it to two US commercial healthcare claims databases that achieved a high linkage proportion and demonstrated that linked and non-linked mother and infant cohorts were similar. Transparent, reusable algorithms applied to large databases enable large-scale research on exposures during pregnancy and pediatric outcomes with relevance to drug safety. These features suggest studies using this algorithm can produce valid and generalizable evidence to inform clinical, policy, and regulatory decisions.

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.

Evaluating the impact of covariate lookback times on performance of patient-level prediction models.

BACKGROUND: The goal of our study is to examine the impact of the lookback length when engineering features to use in developing predictive models using observational healthcare data. Using a longer lookback for feature engineering gives more insight about patients but increases the issue of left-censoring. METHODS: We used five US observational databases to develop patient-level prediction models. A target cohort of subjects with hypertensive drug exposures and outcome cohorts of subjects with acute (stroke and gastrointestinal bleeding) and chronic outcomes (diabetes and chronic kidney disease) were developed. Candidate predictors that exist on or prior to the target index date were derived within the following lookback periods: 14, 30, 90, 180, 365, 730, and all days prior to index were evaluated. We predicted the risk of outcomes occurring 1 day until 365 days after index. Ten lasso logistic models for each lookback period were generated to create a distribution of area under the curve (AUC) metrics to evaluate the discriminative performance of the models. Calibration intercept and slope were also calculated. Impact on external validation performance was investigated across five databases. RESULTS: The maximum differences in AUCs for the models developed using different lookback periods within a database was < 0.04 for diabetes (in MDCR AUC of 0.593 with 14-day lookback vs. AUC of 0.631 with all-time lookback) and 0.012 for renal impairment (in MDCR AUC of 0.675 with 30-day lookback vs. AUC of 0.687 with 365-day lookback ). For the acute outcomes, the max difference in AUC across lookbacks within a database was 0.015 (in MDCD AUC of 0.767 with 14-day lookback vs. AUC 0.782 with 365-day lookback) for stroke and < 0.03 for gastrointestinal bleeding (in CCAE AUC of 0.631 with 14-day lookback vs. AUC of 0.660 with 730-day lookback). CONCLUSIONS: In general the choice of covariate lookback had only a small impact on discrimination and calibration, with a short lookback (< 180 days) occasionally decreasing discrimination. Based on the results, if training a logistic regression model for prediction then using covariates with a 365 day lookback appear to be a good tradeoff between performance and interpretation.

Understanding patient journey in ulcerative colitis prior to biologic initiation: a 5-year exploration.

BACKGROUND: There has been a more pronounced shift toward earlier, more aggressive therapies in Crohn's disease than in ulcerative colitis (UC). The aim of this study was to describe the pre-biologic treatment and health care experience, including co-morbidities and overall health care utilization, for UC patients who initiated biologic therapies, in the 5 years prior to the initiation of the first biologic agent. METHODS: UC patients who initiated a biologic agent approved for UC between 9/15/2005 and 1/30/2018 were identified from the IBM® MarketScan® Commercial Database, a large US database. The date of the first recorded UC biologic exposure was defined as the index date, and ≥ 5 years of pre-index records were required to evaluate patients' treatment, disease progression and overall health care utilization prior to initiating biologic agents. RESULTS: Among the 1891 eligible patients, treatment with oral corticosteroids, 5-aminosalicylates, and other non-biologic immunomodulators, all increased progressively across the 5 years prior to the index. From within year-five to within year-one prior to the index, the median duration of oral corticosteroid treatment increased from 34 to 88 days per year and the proportion of patients who experienced more extensive/pancolitis disease increased from 16 to 59%. Overall, the frequency of all-cause health care visits also increased. CONCLUSIONS: Patients with UC experienced increasing morbidity and treatment burden in the 5 years prior to initiating biologic therapy. To achieve reduced corticosteroids in UC management, better risk stratification is needed to help identify patients for more timely biologic treatment.

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.

Using a data-driven approach for the development and evaluation of phenotype algorithms for systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin. The objective of this research was to develop phenotype algorithms for SLE suitable for use in epidemiological studies using empirical evidence from observational databases. METHODS: We used a process for empirically determining and evaluating phenotype algorithms for health conditions to be analyzed in observational research. The process started with a literature search to discover prior algorithms used for SLE. We then used a set of Observational Health Data Sciences and Informatics (OHDSI) open-source tools to refine and validate the algorithms. These included tools to discover codes for SLE that may have been missed in prior studies and to determine possible low specificity and index date misclassification in algorithms for correction. RESULTS: We developed four algorithms using our process: two algorithms for prevalent SLE and two for incident SLE. The algorithms for both incident and prevalent cases are comprised of a more specific version and a more sensitive version. Each of the algorithms corrects for possible index date misclassification. After validation, we found the highest positive predictive value estimate for the prevalent, specific algorithm (89%). The highest sensitivity estimate was found for the sensitive, prevalent algorithm (77%). CONCLUSION: We developed phenotype algorithms for SLE using a data-driven approach. The four final algorithms may be used directly in observational studies. The validation of these algorithms provides researchers an added measure of confidence that the algorithms are selecting subjects correctly and allows for the application of quantitative bias analysis.

Characteristics and treatment pathways in pediatric and adult hidradenitis suppurativa: An examination using real world data.

Background: Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory disease. Contemporaneous real-world data can be used to elucidate the clinical treatment of pediatric patients and how treatment strategies compare with adult hidradenitis suppurativa patients. Objective: The objective of this study is to evaluate clinical and treatment characteristics of pediatric and adult HS patients. Methods: HS adult and pediatric patients were identified in 3 the United States administrative claims databases during the study period between 2016 to 2021. Patients were required to have 2 diagnostic codes for HS and have at least 365 days of prior observation time to the first HS diagnosis. Results: Pediatric and adult HS treatments were similar. The proportions of subjects treated with topical and oral antibiotic or oral antibiotic alone or topical medication alone or surgery alone covered 90% of the treated pediatric subjects and 91% of treated adult subjects. The remaining proportion of subjects received other treatment combinations. Limitations: The databases represent subjects with commercial or government insurance coverage and thus do not necessarily represent the broader US population. The databases do not capture information about medications obtained without insurance. Conclusions: Although subtle differences exist, this study confirms that topical and systemic therapeutic treatment of HS in adults and adolescents is very similar.

Large-scale characterization of gender differences in diagnosis prevalence and time to diagnosis.

We carry out an analysis of gender differences in patterns of disease diagnosis across four large observational health datasets and find that women are routinely older when first assigned most diagnoses. Among 112 acute and chronic diseases, women experience longer lengths of time between symptom onset and disease diagnosis than men for most diseases regardless of metric used, even when only symptoms common to both genders are considered. These findings are consistent for patients with private as well as government insurance. Our analysis highlights systematic gender differences in patterns of disease diagnosis and suggests that symptoms of disease are measured or weighed differently for women and men. Data and code leverage the open-source common data model and analytic code and results are publicly available.

The Epidemiology of Palmoplantar Pustulosis: An Analysis of Multiple Health Insurance Claims and Electronic Health Records Databases.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory condition characterized by sterile pustules on the palms and soles. This study evaluated the epidemiology of PPP using claims and electronic health record (EHR) databases. METHODS: Patients coded for PPP in the United States (US) and Japan from 2016 to 2020 were identified. Several PPP definitions were evaluated; the specific definition (≥ 2 visits coded for PPP, the second 31-730 days after diagnosis) was chosen for characterizing PPP epidemiology. Baseline characteristics and pre- and post-diagnosis treatments were summarized. Prevalence and incidence rates were analyzed by calendar year, sex, age, and database. RESULTS: Prevalence and incidence of PPP were higher in Japan than the US. PPP prevalence increased over time. PPP occurred predominantly in adulthood and was more common among women. Features of metabolic syndromes, anxiety, and depression were more common among US PPP patients. Consistently high baseline use of anti-bacterial, anti-inflammatory/anti-rheumatic, and obstructive airway disease treatments was observed among PPP patients. Potential miscoding or misclassification of PPP limited this analysis. Prevalence estimates from databases may differ from field- and population-based approaches. CONCLUSIONS: The burden of PPP was greater in Japan than in the US. Additional studies are needed to further elucidate PPP epidemiology worldwide.

Phenotype Algorithms to Identify Hidradenitis Suppurativa Using Real-World Data: Development and Validation Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a potentially debilitating, chronic, recurring inflammatory disease. Observational databases provide opportunities to study the epidemiology of HS. OBJECTIVE: This study's objective was to develop phenotype algorithms for HS suitable for epidemiological studies based on a network of observational databases. METHODS: A data-driven approach was used to develop 4 HS algorithms. A literature search identified prior HS algorithms. Standardized databases from the Observational Medical Outcomes Partnership (n=9) were used to develop 2 incident and 2 prevalent HS phenotype algorithms. Two open-source diagnostic tools, CohortDiagnostics and PheValuator, were used to evaluate and generate phenotype performance metric estimates, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value. RESULTS: We developed 2 prevalent and 2 incident HS algorithms. Validation showed that PPV estimates were highest (mean 86%) for the prevalent HS algorithm requiring at least two HS diagnosis codes. Sensitivity estimates were highest (mean 58%) for the prevalent HS algorithm requiring at least one HS code. CONCLUSIONS: This study illustrates the evaluation process and provides performance metrics for 2 incident and 2 prevalent HS algorithms across 9 observational databases. The use of a rigorous data-driven approach applied to a large number of databases provides confidence that the HS algorithms can correctly identify HS subjects.

Impact of consumption of vegetable, fruit, grain, and high glycemic index foods on aggressive prostate cancer risk.

Prostate cancer is a common but complex disease, and distinguishing modifiable risk factors such as diet for more aggressive disease is extremely important. Previous work has detected intriguing associations between vegetable, fruit, and grains and more aggressive prostate cancer, although these remain somewhat unclear. Here we further investigate such potential relationships with a case-control study of 982 men (470 more aggressive prostate cancer cases and 512 control subjects). Comparing the highest to lowest quartiles of intake, we found that increasing intakes of leafy vegetables were inversely associated with risk of aggressive prostate cancer [adjusted odds ratio (OR) = 0.66, 95% CI: 0.46, 0.96; P trend = 0.02], as was higher consumption of high carotenoid vegetables (OR = 0.71, 95% CI: 0.48, 1.04; P trend = 0.04). Conversely, increased consumption of high glycemic index foods were positively associated with risk of aggressive disease (OR = 1.64, 95% CI: 1.05, 2.57; P trend = 0.02). These results were driven by a number of specific foods within the food groups. Our findings support the hypothesis that diets high in vegetables and low in high glycemic index foods decrease risk of aggressive prostate cancer.

Medications for attention-deficit/hyperactivity disorder in Japan: A retrospective cohort study of label compliance.

AIM: To assess label compliance in prescription of medications approved for treatment of attention-deficit/hyperactivity disorder (ADHD) in Japan at the time of this study: methylphenidate (MPH), atomoxetine, and guanfacine. METHODS: Retrospective descriptive study was conducted in prevalent-user cohorts from the Japan Medical Data Center database. Patients who were prescribed a study drug between January 1, 2013 and September 30, 2018 and were in the database for ≥30 days were included. A prescription was considered compliant if all 4 criteria were satisfied: appropriate age, daily dose not exceeding the approved maximum, no contraindicated concurrent medications, and no contraindicated conditions. RESULTS: Among 17 418 patients who were prescribed a study drug during 2013-2018, 73% were male and 53% were children (aged <18 years). Fewer than 2% of prescriptions were for patients outside the approved age, 10%-13% of patients in the atomoxetine and MPH cohorts received ≥1 prescription exceeding maximum approved dose, no patients were co-prescribed a contraindicated medication, and 16%-18% of patients in the MPH cohorts had ≥1 contraindicated condition. During their first 500 days of use, for approximately 73%-86% of patients, all prescriptions were compliant with all label requirements. CONCLUSIONS: Among patients exposed to ADHD medications in Japan during 2013-2018, nearly all prescriptions for these medications were label-compliant for age. For >85% of patients, all prescriptions were label-compliant for dose, and for approximately 80%, all prescriptions were label-compliant for contraindicated conditions. We did not find evidence of widespread abuse or noncompliant use of prescribed ADHD medications.

Real-World Anticoagulant Use and Incidence of Venous Thromboembolism and Major Bleeding in Children.

PURPOSE: Children generally have a lower risk of venous thromboembolism (VTE) than adults, but those with acute and chronic conditions requiring hospitalization and surgical procedures are at increased risk. Anticoagulant use in children has not been systematically studied, and limited data exist. This study aimed to provide data on the conditions associated with use of anticoagulants, the type of anticoagulant used in children, and the incidence of thromboembolism and major bleeding events reported in this population. METHODS: To increase understanding of the use of anticoagulant therapies in children with at-risk conditions, 3 health claims databases in the United States were analyzed to describe the characteristics of use of heparins, warfarin, and direct oral anticoagulants (DOACs). Cumulative drug exposure was determined for continuous exposure, defined as >30 days. Unadjusted event rates of VTE and major bleeding after exposure to these therapies were reported. The data were presented descriptively and are not intended for comparison or to imply any causation. FINDINGS: Anticoagulants were infrequently used in the pediatric population, including at any time point after Fontan surgery for congenital heart disease. Heparins were used most frequently in the population overall and especially for patients aged <12 years. DOACs were used least often and primarily for patients ages 12 to <18 years. Among pediatric patients exposed to anticoagulants, unadjusted incidence rates of VTE per 1000 person-years of exposure ranged from 30.8 to 34.0 for all DOACs, 21.6 to 46.2 for warfarin, and 6.0 to 7.3 for heparins. Rates per 1000 person-years for major bleeding ranged from 0 to 4.9 for all DOACs, 4.3 to 6.7 for warfarin, and 3.7 to 4.6 for heparins. IMPLICATIONS: With results from clinical trials evaluating DOACs in the pediatric population expected in the next 2 years, these descriptive real-world data may provide a baseline understanding of current prescribing patterns and outcomes associated with the use of DOACs and other anticoagulants in routine pediatric clinical practice. This information represents the use of real-world evidence and may function as the benchmark for evaluating changes in prescription practices and potential outcomes in the future.

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 adult patients hospitalised with COVID-19 in an international network study.

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

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.

Whole genome microarray analysis, from neonatal blood cards.

BACKGROUND: Neonatal blood, obtained from a heel stick and stored dry on paper cards, has been the standard for birth defects screening for 50 years. Such dried blood samples are used, primarily, for analysis of small-molecule analytes. More recently, the DNA complement of such dried blood cards has been used for targeted genetic testing, such as for single nucleotide polymorphism in cystic fibrosis. Expansion of such testing to include polygenic traits, and perhaps whole genome scanning, has been discussed as a formal possibility. However, until now the amount of DNA that might be obtained from such dried blood cards has been limiting, due to inefficient DNA recovery technology. RESULTS: A new technology is employed for efficient DNA release from a standard neonatal blood card. Using standard Guthrie cards, stored an average of ten years post-collection, about 1/40th of the air-dried neonatal blood specimen (two 3 mm punches) was processed to obtain DNA that was sufficient in mass and quality for direct use in microarray-based whole genome scanning. Using that same DNA release technology, it is also shown that approximately 1/250th of the original purified DNA (about 1 ng) could be subjected to whole genome amplification, thus yielding an additional microgram of amplified DNA product. That amplified DNA product was then used in microarray analysis and yielded statistical concordance of 99% or greater to the primary, unamplified DNA sample. CONCLUSION: Together, these data suggest that DNA obtained from less than 10% of a standard neonatal blood specimen, stored dry for several years on a Guthrie card, can support a program of genome-wide neonatal genetic testing.

Simple and inexpensive point-of-care tests improve diagnosis of vaginal infections in resource constrained settings.

OBJECTIVE: Bacterial vaginosis (BV) and Trichomonas vaginalis infection (TV) have been associated with adverse birth outcomes and increased risk for HIV. We compare the performance of simple inexpensive point-of-care (POC) tests to laboratory diagnosis and syndromic management of BV and TV in poor settings. METHODS: Between November 2005 and March 2006, 898 sexually active women attending two reproductive health clinics in Mysore, India were recruited into a cohort study investigating the relationship between vaginal flora and HSV-2 infection. Participants were interviewed and screened for reproductive tract infections. Laboratory tests included serology for HSV-2; cultures for TV, Candida sp., and Neisseria gonorrhoeae; Gram stains; and two POC tests: vaginal pH; and Whiff test. RESULTS: Of the 898 participants, 411 [45.7%, 95% confidence interval (95% CI): 42.4-49.0%] had any laboratory diagnosed vaginal infection. BV was detected in 165 women (19.1%, 95%CI: 16.5-21.9%) using Nugent score. TV was detected in 76 women (8.5%, 95%CI: 6.7-10.4%) using culture. Among the entire study population, POC correctly detected 82% of laboratory diagnosed BV cases, and 83% of laboratory diagnosed TV infections. Among women with complaints of vulval itching, burning, abnormal vaginal discharge, and/or sores (445/898), POC correctly detected 83% (60 of 72 cases) of laboratory diagnosed BV cases vs. 40% (29 of 72 cases) correctly managed using the syndromic approach (P < 0.001). Similarly, POC would have detected 82% (37 of 45 cases) of TV cases vs. 51% (23 of 45 cases) correctly managed using the syndromic approach (P = 0.001). CONCLUSIONS: In the absence of laboratory diagnostics, POC is not only inexpensive and practical, but also significantly more sensitive than the syndromic management approach, resulting in less overtreatment. .

The estimated probability of dizygotic twins: a comparison of two methods.

This study presents a general model of two binary variables and applies it to twin sex pairing data from 21 twin data sources to estimate the frequency of dizygotic twins. The purpose of this study is to clarify the relationship between maximum likelihood and Weinberg's differential rule zygosity estimation methods. We explore the accuracy of these zygosity estimation measures in relation to twin ascertainment methods and the probability of a male. Twin sex pairing data from 21 twin data sources representing 15 countries was collected for use in this study. Maximum likelihood estimation of the probability of dizygotic twins is applied to describe the variation in the frequency of dizygotic twin births. The differences between maximum likelihood and Weinberg's differential rule zygosity estimation methods are presented as a function of twin data ascertainment method and the probability of a male. Maximum likelihood estimation of the probability of dizygotic twins ranges from 0.083 (95% approximate CI: 0.082, 0.085) to 0.750 (95% approximate CI: 0.749, 0.752) for voluntary ascertainment data sources and from 0.374 (95% approximate CI: 0.373, 0.375) to 0.987 (95% approximate CI: 0.959, 1.016) for active ascertainment data sources. In 17 of the 21 twin data sources differences of 0.01 or less occur between maximum likelihood and Weinberg zygosity estimation methods. The Weinberg and maximum likelihood estimates are negligibly different in most applications. Using the above general maximum likelihood estimate, the probability of a dizygotic twin is subject to substantial variation that is largely a function of twin data ascertainment method.

Trends in the probability of twins and males in California, 1983-2003.

This study examines the probability of twins by birth year, maternal race-ethnicity, age, and parity and the influences of these demographic factors on the probability of male in twins and singletons in a large, racially diverse population. Recent publications note steep increases in twin births while the probability of male births has been reported to vary by parental race-ethnicity and age and birth order. Probability of male stratified by plurality has not been investigated in California prior to this study. Cubic spline estimates and Poisson regression techniques were employed to describe trends in twins and males using California vital statistics birth and fetal death records over the period from 1983-2003. This study includes 127,787 twin pair and 11,025,106 singleton births. The probability of twins varied by birth year, maternal race-ethnicity, age, and parity. The probability of twins increased by 10.1% from 1983-1992 and increased by 20.1% from 1993-2003, nearly doubling the previous increase. All maternal race-ethnicity groups showed increases in probability of twins with increasing maternal age. Parous women compared to nulliparous women had larger increases in the probability of twins. The probability of males in twins decreased from 1983-1992 and increased from 1993-2003; while in singletons the probability appeared unchanged. These findings show increases in the probability of twins in California from 1983-2003 and identify maternal age, race-ethnicity, and parity groups most likely to conceive twins. The cause of the increase in twins is unknown but coincides with trends towards delayed childbearing and increased use of subfertility treatments.