Establishing and Maintaining Trust: How the U.S. Preventive Services Task Force Uses Strategic Communications to Build Confidence in and Disseminate Its Evidence-Based Recommendations.

In an era of conflicting health guidance and misinformation, the need for evidence-based recommendations-and clear communication about them-is critical. This paper examines the ways in which strategic communications support for the United States Preventive Services Task Force (Task Force) helps to fulfill its mission to improve the health of all people nationwide through evidence-based preventive services recommendations. This paper describes communications challenges specific to the Task Force and how its strategic communications approach helps to address them. To exemplify the Task Force's process for developing recommendations and how it achieves impact, this paper provides two case examples, one that focuses on a topic that garnered a lot of public interest and one that focuses on the perception of "more care is better care." It also presents key principles in building and maintaining trust through focused communications that may assist others in effectively communicating and disseminating health information.

Zrsr2 Is Essential for the Embryonic Development and Splicing of Minor Introns in RNA and Protein Processing Genes in Zebrafish.

ZRSR2 (zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) is an essential splicing factor involved in 3' splice-site recognition as a component of both the major and minor spliceosomes that mediate the splicing of U2-type (major) and U12-type (minor) introns, respectively. Studies of ZRSR2-depleted cell lines and ZRSR2-mutated patient samples revealed its essential role in the U12-dependent minor spliceosome. However, the role of ZRSR2 during embryonic development is not clear, as its function is compensated for by Zrsr1 in mice. Here, we utilized the zebrafish model to investigate the role of zrsr2 during embryonic development. Using CRISPR/Cas9 technology, we generated a zrsr2-knockout zebrafish line, termed zrsr2hg129/hg129 (p.Trp167Argfs*9) and examined embryo development in the homozygous mutant embryos. zrsr2hg129/hg129 embryos displayed multiple developmental defects starting at 4 days post fertilization (dpf) and died after 8 dpf, suggesting that proper Zrsr2 function is required during embryonic development. The global transcriptome analysis of 3 dpf zrsr2hg129/hg129 embryos revealed that the loss of Zrsr2 results in the downregulation of essential metabolic pathways and the aberrant retention of minor introns in about one-third of all minor intron-containing genes in zebrafish. Overall, our study has demonstrated that the role of Zrsr2 as a component of the minor spliceosome is conserved and critical for proper embryonic development in zebrafish.

Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients.

INTRODUCTION: Famotidine has been posited as a potential treatment for coronavirus disease 2019 (COVID-19). We compared the incidence of COVID-19 outcomes (i.e., death and death or intensive services use) among hospitalized famotidine users vs proton pump inhibitors (PPIs) users, hydroxychloroquine users, or famotidine nonusers separately. METHODS: We constructed a retrospective cohort study using data from COVID-19 Premier Hospital electronic health records. The study population was COVID-19 hospitalized patients aged 18 years or older. Famotidine, PPI, and hydroxychloroquine exposure groups were defined as patients dispensed any medication containing 1 of the 3 drugs on the day of admission. The famotidine nonuser group was derived from the same source population with no history of exposure to any drug with famotidine as an active ingredient before or on the day of admission. Time at risk was defined based on the intention-to-treat principle starting 1 day after admission to 30 days after admission. For each study comparison group, we fit a propensity score model through large-scale regularized logistic regression. The outcome was modeled using a survival model. RESULTS: We identified 2,193 users of PPI, 5,950 users of the hydroxychloroquine, 1,816 users of famotidine, and 26,820 nonfamotidine users. After propensity score stratification, the hazard ratios (HRs) for death were as follows: famotidine vs no famotidine HR 1.03 (0.89-1.18), vs PPIs: HR 1.14 (0.94-1.39), and vs hydroxychloroquine: 1.03 (0.85-1.24). Similar results were observed for the risk of death or intensive services use. DISCUSSION: We found no evidence of a reduced risk of COVID-19 outcomes among hospitalized COVID-19 patients who used famotidine compared with those who did not or compared with PPI or hydroxychloroquine users.

Quantifying bias in epidemiologic studies evaluating the association between acetaminophen use and cancer.

Many observational studies explore the association between acetaminophen and cancer, but known limitations such as vulnerability to channeling, protopathic bias, and uncontrolled confounding hamper the interpretability of results. To help understand the potential magnitude of bias, we identify key design choices in these observational studies and specify 10 study design variants that represent different combinations of these design choices. We evaluate these variants by applying them to 37 negative controls - outcome presumed not to be caused by acetaminophen - as well as 4 cancer outcomes in the Clinical Practice Research Datalink (CPRD) database. The estimated odds and hazards ratios for the negative controls show substantial bias in the evaluated design variants, with far fewer of the 95% confidence intervals containing 1 than the nominal 95% expected for negative controls. The effect-size estimates for the cancer outcomes are comparable to those observed for the negative controls. A comparison of exposed and unexposed reveals many differences at baseline for which most studies do not correct. We observe that the design choices made in many of the published observational studies can lead to substantial bias. Thus, caution in the interpretation of published studies of acetaminophen and cancer is recommended.

A systematic assessment of the epidemiologic literature regarding an association between acetaminophen exposure and cancer.

Introduced in the 1950s, acetaminophen is one of the most widely used antipyretics and analgesics worldwide. In 1999, the International Agency for Research on Cancer (IARC) reviewed the epidemiologic studies of acetaminophen and the data were judged to be "inadequate" to conclude that it is carcinogenic. In 2019 the California Office of Environmental Health Hazard Assessment initiated a review process on the carcinogenic hazard potential of acetaminophen. To inform this review process, the authors performed a comprehensive literature search and identified 136 epidemiologic studies, which for most cancer types suggest no alteration in risk associated with acetaminophen use. For 3 cancer types, renal cell, liver, and some forms of lymphohematopoietic, some studies suggest an increased risk; however, multiple factors unique to acetaminophen need to be considered to determine if these results are real and clinically meaningful. The objective of this publication is to analyze the results of these epidemiologic studies using a framework that accounts for the inherent challenge of evaluating acetaminophen, including, broad population-wide use in multiple disease states, challenges with exposure measurement, protopathic bias, channeling bias, and recall bias. When evaluated using this framework, the data do not support a causal association between acetaminophen use and cancer.

Five-year trends in acetaminophen use exceeding the recommended daily maximum dose.

Temporal patterns of acetaminophen use exceeding the recommended daily maximum dosage of 4 g over a 5-year period (4/1/2011-3/31/2016) were evaluated in an online 1-week diary study of 14 434 adult acetaminophen users who also reported acetaminophen use in the previous month. Specific medications taken were identified by list-based prompting; respondents were not required to know their medications contained acetaminophen. Details of use were recorded daily; total daily dosage was determined programmatically. Prevalence of >4 g use over time was modelled and tested for linear changes. The overall prevalence of >4 g use (6.3% of users and 3.7% of usage days) did not change over the 5 years: odds ratio (OR) persons, 1.02 (95% CI, 0.98-1.09); OR days, 0.98 (0.92-1.05). Deviations from label directions were largely unchanged, though concomitant use increased slightly. Thus, over a recent 5-year period, there was no evidence of change in how often acetaminophen use exceeded the labelled maximum daily dose.

Prevalence of exceeding maximum daily dose of paracetamol, and seasonal variations in cold-flu season.

AIMS: To estimate prevalence of excess intake of paracetamol and investigate seasonal variations therein. METHODS: Between 2011 and 2016, 14 481 US adults who used paracetamol in the preceding 30 days were sampled from national online panels and completed a detailed online daily diary of paracetamol medication use for 7 days. Respondents were not told that the study concerned paracetamol. Cold/flu season (CFS), identified using Google Trends data, was contrasted to off-season in symptoms, use of paracetamol medications, and consumption exceeding 4 g (the recommended daily maximum). RESULTS: Overall, 6.3% [95% confidence interval: 5.9-6.7%] of users exceeded 4 g on at least one day; 3.7% [3.5-3.8%] of usage days exceeded 4 g. Cold/flu symptoms were more likely to be experienced and treated with paracetamol in CFS than off-season. Paracetamol users were more likely to exceed 4 g during CFS (6.5% vs. 5.3%; odds ratio = 1.24, 1.04-1.48); days exceeding 4 g also increased (3.9% vs. 2.8%; odds ratio = 1.37, 1.11-1.69). This was not due to differences in characteristics of individuals using paracetamol in CFS, but primarily to increased use of over-the-counter combination medications designed to treat upper respiratory cold/flu symptoms (33.2% of usage days in CFS vs. 24.8% in off-season; odds ratio = 1.58, 1.46-1.72). When such medications were omitted, there was no statistically significant seasonal variation in exceeding 4 g. CONCLUSIONS: Paracetamol use and over-dosing increases in CFS, primarily due to increased use of over-the-counter combinations treating upper respiratory cold/flu symptoms. Pharmacists should warn users to follow labelled dosing directions, especially during CFS.

Exceeding the daily dosing limit of nonsteroidal anti-inflammatory drugs among ibuprofen users.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective and very commonly used, but also have side effects. We determined prevalence of NSAID dosing exceeding the daily limit (EDL) and identified related user characteristics and dosing patterns among current ibuprofen users. METHODS: Online 1-week diary study of 1326 ibuprofen users. NSAIDs were identified by list-based prompting; respondents were not required to know their medications were NSAIDs. Details of hourly use were recorded by respondents daily. Deviations from dosing directions were programmatically determined afterwards. An exit survey obtained information on demographics, medical history, physical and mental health status, attitudes regarding label reading and dosing behavior, and knowledge of product label instructions. RESULTS: Most diary users (90%) took over-the-counter ibuprofen during the week; 37% also took non-ibuprofen NSAIDs. Most did not recognize all products taken as NSAIDs. EDL occurred among 11% of users for ibuprofen, 4% of users for other NSAIDs, and on 9.1% of NSAID usage days. EDL was associated with deviations from detailed dosing directions, particularly exceeding the 1-time dose, which occurred more often with medications with 1-pill doses. Personal characteristics associated with EDL included male sex, ongoing pain, poor physical function, daily smoking, having the attitudes of "choosing my own dose" and not starting with the lowest dose, and poor knowledge of the recommended 1-time and 24-hour doses. CONCLUSIONS: The prevalence of EDL among NSAID users is nontrivial, and it is associated with potentially modifiable factors. Educating consumers about NSAIDs and their dosing directions could reduce excess dosing.

Cost and effectiveness of prescribing emollient therapy for atopic eczema in UK primary care in children and adults: a large retrospective analysis of the Clinical Practice Research Datalink.

BACKGROUND: The Clinical Practice Research Datalink (CPRD) was used to evaluate the overall costs to the National Health Service, including healthcare utilisation, of prescribing emollients in UK primary care for dry skin and atopic eczema (DS&E). METHODS: Primary care patients in the UK were identified using the CPRD and their records were interrogated for the 2 years following first diagnosis of DS&E. Data from patients with (n = 45,218) and without emollient prescriptions (n = 9780) were evaluated. Multivariate regression models were used to compare healthcare utilisation and cost in the two matched groups (age, sex, diagnosis). Two sub-analyses of the Emollient group were performed between matched groups receiving (1) a colloidal oatmeal emollient (Aveeno-First) versus non-colloidal oatmeal emollients (Aveeno-Never) and (2) Aveeno prescribed first-line (Aveeno-First) versus prescribed Aveeno later (Aveeno-Subsequently). Logistic regression models calculated the odds of prescription with either potent / very potent topical corticosteroids (TCS) or skin-related antimicrobials. RESULTS: Costs per patient were £125.80 in Emollient (n = 7846) versus £128.13 in Non-Emollient (n = 7846) matched groups (p = 0.08). The Emollient group had fewer visits/patient (2.44 vs. 2.66; p < 0.0001) and lower mean per-visit costs (£104.15 vs. £113.25; p < 0.0001), compared with the Non-Emollient group. Non-Emollient patients had 18% greater odds of being prescribed TCS and 13% greater odds of being prescribed an antimicrobial than Emollient patients. In the Aveeno-First (n = 1943) versus Aveeno-Never (n = 1943) sub-analysis, costs per patient were lower in the Aveeno-First compared with the Aveeno-Never groups (£133.46 vs. £141.11; p = 0.0069). The Aveeno-Never group had ≥21% greater odds of being prescribed TCS or antimicrobial than the Aveeno-First group. In the Aveeno-First (n = 1357) versus Aveeno-Subsequently (n = 1357) sub-analysis, total costs were lower in the Aveeno-First group (£140.35 vs. £206.43; p < 0.001). Patients in the Aveeno-Subsequently group had 91% greater odds of being prescribed TCS and 75% greater odds of being prescribed an antimicrobial than the Aveeno-First group. CONCLUSIONS: Acknowledging limitations from unknown disease severity in the CRPD, the prescription of emollients to treat DS&E was associated with fewer primary care visits, reduced healthcare utilisation and reduced cost. Prescribing emollients, especially those containing colloidal oatmeal, was associated with fewer TCS and antimicrobial prescriptions. TRIAL REGISTRATION: The study is registered at http://isrctn.com/ISRCTN91126037 .

Exceeding the maximum daily dose of acetaminophen with use of different single-ingredient OTC formulations.

OBJECTIVES: To assess whether there are differences in the likelihood of exceeding the daily limit of 4 grams of acetaminophen when using different formulations (325 mg, 500 mg, 650 mg) of OTC single-ingredient (SI) acetaminophen medications. DESIGN AND SETTING: Multiyear observational study of acetaminophen use via daily online acetaminophen-usage diaries completed for 7 days. PARTICIPANTS: A total of 7579 U.S. adults from online research panels who used acetaminophen in the month preceding enrollment and used an OTC SI acetaminophen medication during the study. OUTCOME MEASURE: Exceeding the daily dose. RESULTS: On days when 325-mg or 500-mg OTC SI formulations were taken, users were not significantly more likely to exceed 4 grams than on days when OTC SI formulations were not used. On days when 650-mg extended-release (ER) formulations were taken, exceeding 4 grams was significantly more likely (8.9% of days vs. 4.4%; P < 0.0001; median on those days was 5.2 g) than on days with 325- or 500-mg OTC SI formulations. Users of 650-mg ER formulations were significantly less likely to know their dosing interval of 8 hours (33% vs. 49%; P < 0.0001) and more likely to redose too soon (26% vs. 10%; P < 0.0001) and to use other acetaminophen medications concomitantly (14% vs. 7%; P < 0.0001). These patterns were strongest among 650-mg ER products that did not include "8-Hour" in the product name. CONCLUSION: Usage of 500-mg OTC SI acetaminophen formulations does not contribute differently to exceeding dosage compared with other OTC SI acetaminophen formulations. Exceeding 4 grams is more likely when 650-mg ER formulations are used. Improved consumer information on the packages and counseling from pharmacists may help to reduce practices that contribute to exceeding the labeled daily limit of these medications.

Knowledge of dosing directions among current users of acetaminophen-containing medications.

OBJECTIVES: Users should know the active ingredients and dosing directions to optimize the safe use of acetaminophen-containing medications. The aim of this work was to examine knowledge of acetaminophen-containing medication directions among current users. DESIGN, SETTING, AND PARTICIPANTS: An Internet panel diary study (2012-2016) of 1-week usage of acetaminophen medications (over-the-counter [OTC] and prescription), recorded daily; 9629 participants. Users were asked about ingredients of medications taken; specific dosing instructions were asked for each OTC medication taken. Subjects were considered to be correct only if an accurate response was provided for all of the medications they used. OUTCOME MEASURES: Analyses examined prevalence of several aspects of knowledge and their relation to the corresponding deviations from directions. Knowledge that acetaminophen was an ingredient was compared between medication types. RESULTS: Two-thirds of 5161 participants who used only 1 acetaminophen medication knew the ingredient; the proportion was almost halved in 4468 users of 2 or more. Ingredient knowledge was highest for single-ingredient medications (74%); for combination medications it ranged from 39% (cough or cold) to 61% (sleep or other non-pain). About one-third knew the prohibition against concomitant use of multiple acetaminophen medications; 85% knew the maximum one-time OTC dose, but only 47% knew the minimum interval between doses. Correct knowledge was inversely associated with violating the relevant label directions; in particular, knowing the one-time dose decreased the odds of taking too much at one time fivefold. Knowing both the ingredient and the concomitant use prohibition decreased the odds of concomitant use by 50%. CONCLUSIONS: Knowledge of directions for safe use of acetaminophen-containing medications is poor, and its deficiency is associated with corresponding deviations from label instructions. This study demonstrates a need for education about safe use of acetaminophen-containing medications, particularly for combination products.

Association of flossing/inter-dental cleaning and periodontitis in adults.

AIM: Assess the association of flossing with periodontitis. MATERIALS AND METHODS: This was a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) years 2011-2014. We used three categories of flossing: 0-1, 2-4 and ≥5 days in the past week and the CDC definition of periodontitis. We calculated odds ratios controlling for age, gender, smoking, drinking, income and dentist visits. RESULTS: A total of 6939 adult subjects were included, 35% flossed ≤1 time a week, and 40% had periodontitis. After adjustment, the odds of periodontitis were 17% lower for subjects who flossed >1 time a week than for subjects who flossed less often (odds ratio=0.83, 95% CI 0.72-0.97). A dose response was not observed. Men were twice as likely as women to have periodontitis. Younger subjects, non-smokers and subjects with the highest incomes had lower odds of having periodontitis. CONCLUSIONS: Flossing was associated with a modestly lower prevalence of periodontitis. Older age, being male, smoking, low income and less frequent dental visits were associated with a higher prevalence of periodontitis. Flossing 2-4 days a week could be as beneficial as flossing more frequently. This is a cross-sectional study so a causal relation between flossing and periodontitis cannot be established.

Primary Intraventricular Hemorrhage: Clinical Characteristics and Outcomes.

BACKGROUND: Primary intraventricular hemorrhage (IVH) in adults is a rare neurologic disorder. The typical course, etiology, complications, and outcomes have not been well established. MATERIALS AND METHODS: Consecutive patient records with a diagnosis of intracerebral hemorrhage admitted between May 2009 and June 2014 at a tertiary care center were retrospectively reviewed. Subjects were included in the study cohort if all neurologists and the radiology report agreed that the subject had an isolated IVH. Patients with intraparenchymal hemorrhage, subarachnoid hemorrhage, malignancy with hemorrhagic components, and hemorrhagic transformation of ischemic stroke were excluded. The electronic medical record, imaging report, and imaging studies were reviewed. FINDINGS: Of 1692 cases reviewed, 33 (1.9%) had primary IVH. The most common presenting symptoms included altered mental status (48.5%), headache, (39.4%), and nausea (24.2%). In 36.3%, hypertension was found to be a contributing factor; 27.2% were attributed solely to hypertension. Vascular abnormalities were the primary etiology in 21.3% of patients. When observing outcomes, 61.8% were discharged home or to rehab, whereas 20.5% died or were placed in hospice care. A higher Graeb score was associated with an increased likelihood of death or hospice (8 versus 5, P = .02) CONCLUSION: This study is one of few to describe the etiology, contributing factors, and outcomes of primary IVH. As in prior studies, hypertension was a contributing factor, and vascular lesions were less common than expected. More research is necessary to further define the course and characteristics of this rare type of intracerebral hemorrhage.

The secretory pathway calcium ATPase PMR-1/SPCA1 has essential roles in cell migration during Caenorhabditis elegans embryonic development.

Maintaining levels of calcium in the cytosol is important for many cellular events, including cell migration, where localized regions of high calcium are required to regulate cytoskeletal dynamics, contractility, and adhesion. Studies show inositol-trisphosphate receptors (IP3R) and ryanodine receptors (RyR), which release calcium into the cytosol, are important regulators of cell migration. Similarly, proteins that return calcium to secretory stores are likely to be important for cell migration. The secretory protein calcium ATPase (SPCA) is a Golgi-localized protein that transports calcium from the cytosol into secretory stores. SPCA has established roles in protein processing, metal homeostasis, and inositol-trisphosphate signaling. Defects in the human SPCA1/ATP2C1 gene cause Hailey-Hailey disease (MIM# 169600), a genodermatosis characterized by cutaneous blisters and fissures as well as keratinocyte cell adhesion defects. We have determined that PMR-1, the Caenorhabditis elegans ortholog of SPCA1, plays an essential role in embryogenesis. Pmr-1 strains isolated from genetic screens show terminal phenotypes, such as ventral and anterior enclosure failures, body morphogenesis defects, and an unattached pharynx, which are caused by earlier defects during gastrulation. In Pmr-1 embryos, migration rates are significantly reduced for cells moving along the embryo surface, such as ventral neuroblasts, C-derived, and anterior-most blastomeres. Gene interaction experiments show changing the activity of itr-1/IP3R and unc-68/RyR modulates levels of embryonic lethality in Pmr-1 strains, indicating pmr-1 acts with these calcium channels to regulate cell migration. This analysis reveals novel genes involved in C. elegans cell migration, as well as a new role in cell migration for the highly conserved SPCA gene family.

Patterns of acetaminophen medication use associated with exceeding the recommended maximum daily dose.

BACKGROUND: Acetaminophen overuse has been linked to liver injury. PURPOSE: To identify patterns of medication use associated with exceeding the recommended daily maximum dose of 4 g acetaminophen. METHODS: Respondents from a national panel completed a detailed daily medication diary online for 7 days (n = 5649), identifying medications taken from a comprehensive list of over-the-counter (OTC) and prescription (Rx) acetaminophen medications. Respondents were not told the study concerned acetaminophen. Total daily intake was calculated from diary data. Generalized estimating equations assessed the association of medication patterns with exceeding 4 g per day among 3618 respondents who used acetaminophen medications (on 13,852 days) during the diary period. RESULTS: Acetaminophen intake exceeded 4 g on 3.1% of usage days; median intake on those days was 5.5 g. As expected, days when intake exceeded 4 g were almost always (92%) marked by deviations from label directions-exceeding the one-time dose, re-dosing too soon, and concomitant use of multiple acetaminophen medications. Re-dosing too soon was the most frequent deviation, and concomitant use was most strongly tied to exceeding the daily limit. Use of both an Rx and an OTC medication on the same day also increased the odds of exceeding 4 g on days when concomitant use occurred. CONCLUSIONS: Excess dosing of acetaminophen is associated with deviations from label directions and by use of both OTC and Rx medications containing acetaminophen within a single concomitant use day.

Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension. OBJECTIVE: The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis. METHODS: Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum's de-identified Clinformatics® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework. RESULTS: In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence. CONCLUSIONS: This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.

Analysis of patient claims data to determine the prevalence of hidradenitis suppurativa in the United States.

BACKGROUND: Recent prevalence estimates for hidradenitis suppurativa (HS), a chronic inflammatory skin condition, are limited by timeliness, population size, and generalizability. OBJECTIVE: We sought to develop prevalence estimates for HS in the United States using large health care claims databases. METHODS: A retrospective analysis used PharMetrics Integrated Database to gather health care claims information for HS among patients with 12 or more months of continuous enrollment in a commercial health care plan throughout 2007. Included patients had: 1 or more diagnoses with International Classification of Diseases, Ninth Revision, Clinical Modification code 705.83 for HS during 2007 without a Current Procedural Terminology code for HS; 1 or more Current Procedural Terminology codes of 11450, 11451, 11462, 11463, 11470, or 11471 during 2007 without International Classification of Diseases, Ninth Revision, Clinical Modification code 705.83; or both. Age- and gender-specific prevalence projections were calculated. RESULTS: Among included patients (n = 7927), mean age (SD) was 38.2 (14.73) years, and 5834 (74%) were women. Most patients (n = 5205; 66%) were aged 30 to 64 years. The overall prevalence estimate was 0.053% (95% confidence interval 0.051-0.054). When adjusted for gender and age, prevalence rates were 0.052% and 0.051%, respectively. The most common procedures for HS were excision of skin and subcutaneous tissue axillary/inguinal simple or intermediate repair. LIMITATIONS: Limitations were a health insured-only population; 12-month enrollment period for 2007; HS-specific procedural codes; and possible HS misclassifications. CONCLUSION: We found a low rate of clinically detected HS (0.053%; approximately 146,000-162,000 patients in the United States in 2007), with affected persons almost 3 times as likely to be female and the highest prevalence in those aged 18 to 44 years.

Prevalence and correlates of exceeding the labeled maximum dose of acetaminophen among adults in a U.S.-based internet survey.

PURPOSE: Acetaminophen is a commonly used analgesic; excessive doses can lead to liver damage. We sought to determine the proportion of acetaminophen users exceeding the recommended maximum daily dose of 4 g and identify correlates of such behavior. METHODS: U.S. adults were recruited from an internet panel in summer 2010, oversampling past 30-day acetaminophen users. Among 47 738 starting the study, 5649 completed all phases; individuals with low education were underrepresented. Subjects completed a 7-day daily diary online, reporting intake of acetaminophen products selected from a comprehensive list; total daily dose was computed from product names. An exit survey elicited: attitudes/knowledge related to product ingredients, label reading, dosing behavior; demographics, medical history, general physical, and mental health status. Unconditional logistic regression identified variables independently associated with use exceeding 4 g. RESULTS: Among 3618 acetaminophen users, 163 took >4 g on ≥1 day (4.5%); the median dose was 5.5 g; 26 took >8 g (0.7%). >4-g users were characterized by chronic pain, poor physical status, and heavy use of medical care. Knowledge of ingredients and recommended OTC doses for all products taken was inversely associated with >4-g use (multivariable odds ratios [ORs] = 0.5-0.6), as was the attitude to start with the lowest dose (OR = 0.6). The attitude that users could choose their own dose was positively associated (OR = 1.3). CONCLUSIONS: The results estimate the proportion of acetaminophen users exceeding 4 g in a group of U.S. adults, identify potentially modifiable attitudes and knowledge associated with such use, and characterize subpopulations at higher risk.

A predictive clinical model for moderate to severe intraventricular hemorrhage in very low birth weight infants.

IMPORTANCE: Intraventricular hemorrhage (IVH) occurs in 15-45% of all very low birth weight (VLBW) preterm infants. Despite improvements in the perinatal care, the incidence of IVH remains high. As more preterm infants survive, there will be a larger burden of neurodevelopmental abnormalities borne by former preterm infants. OBJECTIVE: The objective of this study was to develop a predictive clinical model of IVH risk within the first few hours of life in an effort to augment perinatal counseling and guide the timing of future targeted therapies aimed at preventing or slowing the progression of disease. DESIGN: This is a prospective observational cohort study of VLBW infants born in the NICU at John's Hopkins Children's Center from 2011 to 2019. The presence and severity of IVH was defined on standard head ultrasound screening (HUS) using the modified Papile classification. Clinical variables were identified as significant using absolute risk regression from a general linear model. The model predictors included clinically meaningful variables that were not collinear. SETTING: This study took place at the Johns Hopkins Children's Center Level IV NICU. PARTICIPANTS: The study sample included VLBW infants treated in the neonatal intensive care unit (NICU) at John's Hopkins Children's Center from 2011 to 2019. A total of 683 infants included in the study had no or grade I IVH, and 115 infants had grades II through IV IVH. Exclusion criteria included admission to the JHH NICU after 24 h of age, BW > 1500 g, and failure to consent. MAIN OUTCOME: The main outcome of this study was the presence of grades II-IV IVH on standard head ultrasound screening using the modified Papile classification [1]. RESULTS: A total of 798 VLBW infants were studied in this cohort and 14.4% had moderate to severe IVH. Fifty four percent of the cohort was black, 33% white, and half of the cohort was male. A higher gestational age, 5-min Apgar score, hematocrit, and platelet count were significantly associated with decreased incidence of IVH in a multi-predictor model (ROC 0.826). CONCLUSION AND RELEVANCE: In the face of continued lack of treatments for IVH, prevention is still a primary goal to avoid long-term developmental sequela. This model can be used for perinatal counseling and may provide important information during the narrow therapeutic window for targeted prevention therapies.

The effect of selective serotonin re-uptake inhibitors on the risk of myocardial infarction in a cohort of patients with depression.

AIM: To evaluate whether selective serotonin re-uptake inhibitor (SSRI) exposure influences the risk of myocardial infarction (MI) in patients with depression. METHODS: This study included 693 patients with MI (cases) and 2772 controls. Conditional logistic regression was used to calculate the odds ratio (OR). RESULTS: SSRI exposure may be associated with a reduced MI risk (OR = 0.77, 95% CI 0.57, 1.03). However, reduced risk was only observed with longer term use (OR = 0.73, 95% CI 0.53, 1.00) and not with shorter term use (OR = 1.15, 95% CI: 0.65, 2.05). CONCLUSIONS: Only longer term use of SSRIs was associated with reduced MI risk, suggesting that other mechanisms, besides an acute anti-platelet effect, may reduce MI risk.