Safety of Ancestral Monovalent BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines in US Children Aged 6 Months to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials.

Objective: To conduct near-real-time monitoring of health outcomes after COVID-19 vaccination in the US pediatric population.

Design, Setting, And Participants: This cohort study evaluated 21 prespecified health outcomes after exposure before early 2023 to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children aged 6 months to 17 years by applying a near-real-time monitoring framework using health care data from 3 commercial claims databases in the US (Optum [through April 2023], Carelon Research [through March 2023], and CVS Health [through February 2023]).

Incidence rates of thrombosis with thrombocytopenia syndrome (TTS) among adults in United States commercial and Medicare claims databases, 2017-2020.

Background: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector-based COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials.

Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years.

Design, Setting, And Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration.

The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths.

Purpose: To evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death.

Methods: We assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time-series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category.

Results: Hydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

Background: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination.

Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years.

Background: Active monitoring of safety outcomes following COVID-19 vaccination is critical to understand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure trials. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals.

Methods: We evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12-64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively.

Evaluating real-world COVID-19 vaccine effectiveness using a test-negative case-control design.

It is important to assess if clinical trial efficacy translates into real-world effectiveness for COVID-19 vaccines. We conducted a modified test-negative design (TND) to evaluate the real-world effectiveness of three COVID-19 vaccines. We defined cases in two ways: self-reported COVID-19-positive tests, and self-reported positive tests with ≥1 moderate/severe COVID-19 symptom.

Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases.

Background: Several passive surveillance systems reported increased risks of myocarditis or pericarditis, or both, after COVID-19 mRNA vaccination, especially in young men. We used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccinations.

Methods: We conducted a retrospective cohort study, examining the primary outcome of myocarditis or pericarditis, or both, identified using the International Classification of Diseases diagnosis codes, occurring 1-7 days post-vaccination, evaluated in COVID-19 mRNA vaccinees aged 18-64 years using health plan claims databases in the USA.

Merging statewide data in a public/university collaboration to address opioid use disorder and overdose.

Objective: Describe methods to compile a unified database from disparate state agency datasets linking person-level data on controlled substance prescribing, overdose, and treatment for opioid use disorder in Connecticut.

Methods: A multidisciplinary team of university, state and federal agency experts planned steps to build the data analytic system: stakeholder engagement, articulation of metrics, funding to establish the system, determination of needed data, accessing data and merging, and matching patient-level data.

Results: Stakeholder meetings occurred over a 6-month period driving selection of metrics and funding was obtained through a grant from the Food and Drug Administration.

Hyperkalemia and Acute Kidney Injury with Spironolactone Use Among Patients with Heart Failure.

Objective: To quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function.

Methods: We identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication.

Discontinuation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease.

Objective: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice.

Patients And Methods: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015.

Elevated Vancomycin Trough Levels in a Tertiary Health System: Frequency, Risk Factors, and Prognosis.

Objective: To investigate the frequency of, risk factors for, and outcomes after elevated levels of vancomycin.

Patients And Methods: We identified hospitalizations among 21,285 individuals in which intravenous vancomycin was given between August 29, 2007, and October 10, 2014. We investigated frequency and risk factors for elevated vancomycin levels (trough levels >30 mg/L) as well as associations with subsequent acute kidney injury (AKI), length of stay, and in-hospital mortality.

Kidney Function, Polypharmacy, and Potentially Inappropriate Medication Use in a Community-Based Cohort of Older Adults.

Background: Chronic kidney disease (CKD) afflicts many older adults and increases the risk for medication-related adverse events.

Objective: The aim of this study was to assess the prevalence and associated morbidity and mortality of polypharmacy (use of several medications concurrently), and potentially inappropriate medication (PIM) use in older adults, looking for differences by CKD status.

Methods: We quantified medication and PIM use (from Beers criteria, the Screening Tool of Older People's Prescriptions, and Micromedex) by level of estimated glomerular filtration rate (eGFR) for participants aged 65 years or older attending a baseline study visit in the Atherosclerosis Risk in Communities study (n =6392).

Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study.

Importance: Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with metformin. This may reflect uncertainty regarding the risk of acidosis in patients with chronic kidney disease.

Objective: To quantify the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR), accounting for change in eGFR stage over time.

Opioid analgesic dose and the risk of misuse, overdose, and death: A narrative review.

Purpose: Despite the rise in serious adverse events paralleling increased prescription opioid analgesic use in the United States over the past 2 decades, the association between opioid analgesic dose and the risk of serious adverse health outcomes is incompletely characterized. We sought to synthesize the medical literature for observational studies examining the association between opioid analgesic dose and the risk of serious adverse health outcomes, with particular attention to the outcomes of misuse, abuse, addiction, overdose, and death.

Methods: Searching MEDLINE using PubMed and bibliography review, we identified 22 observational studies published between 2000 and 2015 that assessed the association between opioid analgesic dose and the risk of serious adverse health outcomes.

Important statistical considerations in the evaluation of post-market studies to assess whether opioids with abuse-deterrent properties result in reduced abuse in the community.

Purpose: Abuse, misuse, addiction, overdose, and death associated with non-medical use of prescription opioids have become a serious public health concern. Reformulation of these products with abuse-deterrent properties is one approach for addressing this problem. FDA has approved several extended-release opioid analgesics with abuse-deterrent labeling, the bases of which come from pre-market studies.

Drug availability adjustments in population-based studies of prescription opioid abuse.

Purpose: Population-based prescription opioid abuse studies in which one drug is compared to another, or drugs are compared across time, often account for the availability of those drugs in the community. The objective of this investigation is to assess consistency in the relative abuse ratios (RARs) across different approaches for adjusting for drug availability.

Methods: For the years 2004 through 2010, RARs for each of four prescription opioids (hydrocodone, oxycodone, hydromorphone, and morphine) were calculated using negative binomial regression.

Measures to quantify the abuse of prescription opioids: a review of data sources and metrics.

Purpose: The abuse and nonmedical use of prescription opioids and its subsequent consequences are an important public health concern. This phenomenon has paralleled the increase in the therapeutic use of opioids for pain management. There is thus a need to measure prescription opioid abuse to understand trends over time and to compare abuse of one product to another.

A comparison of psychosocial and cognitive functioning between depressed and non-depressed patients with cannabis dependence.

Cannabis use and depressive disorders are thought to impair cognitive performance and psychosocial functioning. Both disorders co-occurring may compound the negative effects of these diagnoses. In this study, the authors used the California Computerized Assessment Package as the cognitive performance measure and the Addiction Severity Index as the psychosocial functioning measure to compare individuals who were cannabis dependent and either depressed or not depressed (N= 108: 54 cannabis dependent only, 54 cannabis dependent and depressed or dysthymic).

Atomoxetine Treatment for Cocaine Abuse and Adult Attention-Deficit Hyperactivity Disorder (ADHD): A Preliminary Open Trial.

The purpose of this 12-week open trial was to evaluate the potential utility of atomoxetine for the treatment of attention deficit hyperactivity disorder (ADHD) in cocaine-dependent treatment seekers. The sample consisted of 20 participants with all participants meeting DSM-IV-TR criteria for ADHD and cocaine dependence (CD). Using several measures to assess ADHD, there was a significant reduction in ADHD symptoms.