Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study.

OBJECTIVE: To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). METHODS: We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. RESULTS: The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. CONCLUSIONS: CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

Surveillance of SARS-CoV-2 in Sewage Treatment Plants between January 2020 and July 2021 in Taiwan.

An outbreak of a new type of coronavirus pneumonia (COVID-19) began in Wuhan, Hubei Province, China, at the end of 2019, and it later spread to other areas of China and around the world. Taiwan reported the first confirmed case from an individual who returned from Wuhan, China, in January 2020 for Chinese New Year. Monitoring microbes in environmental sewage is an important epidemiological indicator, especially for pathogens that can be shed in feces such as poliovirus. We have conducted additional SARS-CoV-2 sewage testing since January 2020 using a well-established poliovirus environmental sewage surveillance system in Taiwan. Wastewater samples were collected from 11 sewage treatment plants from different parts of Taiwan twice a month for laboratory testing. By the end of July 2021, 397 wastewater specimens had been tested, and two samples were positive for SARS-CoV-2. These two wastewater samples were collected in the northern region of Taiwan from Taipei (site A) and New Taipei City (site C) at the beginning of June 2021. This result is consistent with the significant increase in confirmed COVID-19 cases observed in the same period of time. As the pandemic ebbed after June, the wastewater samples in these areas also tested negative for SARS-CoV-2 in July 2021.

The incidence of stroke among selected patients undergoing elective posterior lumbar fusion: a retrospective cohort study.

BACKGROUND: Although stroke is a rare complication among spinal surgery patients, the recognition of this adverse event is critical given the aging population undergoing surgical procedures. The objective of this study was to estimate the incidence of stroke among selected adults undergoing elective posterior lumbar fusion (PLF) during various post-operative risk windows and among different subgroups. METHODS: A retrospective cohort study using a longitudinal electronic healthcare record (EHR) database was conducted from January 1, 2007 to June 30, 2018. Elective PLF, stroke, and select clinical characteristics were defined based on International Classification of Disease codes. Patients aged 18 to 85 years with ≥183 days of enrollment in the database prior to undergoing elective PLF were followed from the index date until the occurrence of stroke, death, loss to follow-up, or end of study period, whichever occurred first. The incidence of stroke was estimated in the following risk windows: index hospitalization, ≤ 30 days, ≤ 90 days, ≤ 180 days, and ≤ 365 days post-operation. RESULTS: A total of 43,063 patients were eligible for the study. The incidence of stroke following elective PLF was 0.29% (95% confidence interval [CI]: 0.25, 0.35%) during index hospitalization, 0.44% (95% CI: 0.38, 0.50%) ≤ 30 days, 0.59% (95% CI: 0.52, 0.67%) ≤ 90 days, 0.76% (95% CI: 0.68, 0.85%) ≤ 180 days, and 1.12% (95% CI: 1.03, 1.23%) ≤ 365 days post-operation. Stratified analyses revealed that older patients had a higher incidence of stroke. Additionally, black patients had higher stroke incidences. Post-operative stroke incidence was higher among patients with a history of type 2 diabetes than among patients without such history; similarly, stroke incidence was higher among patients with a history of stroke compared to patients without such history. CONCLUSIONS: The incidence of stroke following elective PLF using an EHR database in this study is slightly higher than that reported in the literature. Our results suggest that stroke risk modification prior to PLF may be important for patients who are older, black, type 2 diabetic, and/or have a history of stroke.

Signal Detection for Recently Approved Products: Adapting and Evaluating Self-Controlled Case Series Method Using a US Claims and UK Electronic Medical Records Database.

INTRODUCTION: The Self-Controlled Case Series (SCCS) method has been widely used for hypothesis testing, but there is limited evidence of its performance for safety signal detection. OBJECTIVE: The objective of this study was to evaluate SCCS for signal detection on recently approved products. METHODS: A retrospective study covered the period after three recently marketed drugs were launched through to 31 December 2010 using The Health Improvement Network, a UK primary care database, and Optum, a US claims database. The SCCS method was applied to examine five heterogenous outcomes with desvenlafaxine and escitalopram and six outcomes with adalimumab for Signals of Disproportional Recording (SDRs); a positive finding was determined to be when the lower bound of 95% Confidence Interval of the incidence rate ratio (IRR) estimate was >  1. Multiple design choices were tested and the trend in IRR estimates over calendar time for one drug event pair was examined. RESULTS: All six outcomes with adalimumab, three of five outcomes with desvenlafaxine, and four of five outcomes with escitalopram had SDRs. SCCS highlighted all acute events in the primary analysis but was less successful with slower-onset outcomes. Performance varied by risk period definition. Changes in IRR estimates over quarterly intervals for adalimumab with herpes zoster showed marked higher SDR within 9 months of drug launch. CONCLUSION: SCCS shows promise for signal detection: it may highlight known associations for recent marketed products and has potential for early signal identification. SCCS performance varied by design choice and the nature of both exposure and event pair. Future work is needed to determine how effective the approach is in prospective testing and determining the performance characteristics of the approach.

Assessing performance of sequential analysis methods for active drug safety surveillance using observational data.

The routine use of sequential methods is well established in clinical studies. Recently, there has been increasing interest in applying these methods to prospectively monitor the safety of newly approved drugs through accrual of real-world data. However, the application to marketed drugs using real-world data has been limited and work is needed to determine which sequential approaches are most suited to such data. In this study, the conditional sequential sampling procedure (CSSP), a group sequential method, was compared with a log-linear model with Poisson distribution (LLMP) through a SAS procedure (PROC GENMOD) combined with an alpha-spending function on two large longitudinal US administrative health claims databases. Relative performance in identifying known drug-outcome associations was examined using a set of 50 well-studied drug-outcome pairs. The study finds that neither method correctly identified all pairs but that LLMP often provides better ability and shorter time for identifying the known drug-outcome associations with superior computational performance when compared with CSSP, albeit with more false positives. With the features of flexible confounding control and ease of implementation, LLMP may be a good alternative or complement to CSSP.

Computer-assisted expert case definition in electronic health records.

PURPOSE: To describe how computer-assisted presentation of case data can lead experts to infer machine-implementable rules for case definition in electronic health records. As an illustration the technique has been applied to obtain a definition of acute liver dysfunction (ALD) in persons with inflammatory bowel disease (IBD). METHODS: The technique consists of repeatedly sampling new batches of case candidates from an enriched pool of persons meeting presumed minimal inclusion criteria, classifying the candidates by a machine-implementable candidate rule and by a human expert, and then updating the rule so that it captures new distinctions introduced by the expert. Iteration continues until an update results in an acceptably small number of changes to form a final case definition. RESULTS: The technique was applied to structured data and terms derived by natural language processing from text records in 29,336 adults with IBD. Over three rounds the technique led to rules with increasing predictive value, as the experts identified exceptions, and increasing sensitivity, as the experts identified missing inclusion criteria. In the final rule inclusion and exclusion terms were often keyed to an ALD onset date. When compared against clinical review in an independent test round, the derived final case definition had a sensitivity of 92% and a positive predictive value of 79%. CONCLUSION: An iterative technique of machine-supported expert review can yield a case definition that accommodates available data, incorporates pre-existing medical knowledge, is transparent and is open to continuous improvement. The expert updates to rules may be informative in themselves. In this limited setting, the final case definition for ALD performed better than previous, published attempts using expert definitions.

Evaluating nursing home performance indicators: an illustration exploring the impact of facilities on ADL change.

PURPOSE: Performance measurement systems for nursing homes assume that facility performance contributes heavily to individual outcomes. This research illustrates how that assumption can be assessed using the change in residents' activities of daily living (ADLs). DESIGN AND METHODS: The data used in these analyses were all from residents with both an admission and a quarterly assessment in a sample of all admissions to a randomly chosen 10% of Medicare- or Medicaid-certified nursing homes operating during 2002. RESULTS: Models including both facility and individual variables explained up to 20% of the variation in ADL change after admission. Facility identity in isolation explained between 8% and 14% of the variation in ADL change. IMPLICATIONS: The results suggest that quality indicators based on change in ADLs may be problematic when used in nursing home performance measurement systems. More generally, the results recommend that the level of variation in performance measures attributable to facility identity or performance become a much more central consideration when researchers evaluate quality indicators for use in nursing home performance measurement systems.