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Matthew W Reynolds,1 Yiqiong Xie,1 Kendall B Knuth,1 Christina D Mack,1 Emma Brinkley,1 Stephen Toovey,2 Nancy A Dreyer1 1Real World Solutions, IQVIA, Cambridge, MA, USA; 2Virology, Pegasus Research, London, UKCorrespondence: Matthew W Reynolds, Real-World Solutions, IQVIA, 201 Broadway, Cambridge, MA, 02139, USA, Email Matthew.Reynolds@IQVIA.comPurpose: Coronavirus disease 2019 (COVID-19) has highlighted the need for new methods of pharmacovigilance. Here, we use adult community volunteers to obtain systematic information on vaccine effectiveness and the nature and severity of breakthrough infections.Methods: Between December 15, 2020 and September 16, 2021, 11,826 unpaid community-based volunteers reported the following information to an on-line registry: COVID-19 test results, vaccination (Pfizer, Moderna, or Johnson & Johnson) and COVID-19 symptoms. COVID-19 infections were described based on vaccination status at the time of infection: 1) fully vaccinated, 2) partially vaccinated (received first of two-dose vaccines or were < 14 days post-final dose), or 3) unvaccinated.Results: Among 8554 participants who received any COVID-19 vaccine, COVID-19 infections were reported by 74 (1.0%) of those who were fully vaccinated and 198 (2.3%) of those who were partially vaccinated at the time of infection. Among the 74 participants who reported a breakthrough infection after full vaccination, the median time from vaccination to reported positive test result was 104.5 days (interquartile range: 77– 135 days), with no difference among vaccine manufacturers. One quarter (25.7%) of breakthrough infections in the fully vaccinated cases were asymptomatic and most (> 97%) fully vaccinated participants reported no symptoms or only mild symptoms compared to 89.3% of the unvaccinated cases. Only 1.4% of fully vaccinated participants reported experiencing at least 3 moderate-to-severe symptoms compared to 7.8% in the unvaccinated.Conclusion: Person-generated health data, also referred to as patient-reported outcomes, is a useful approach for quantifying breakthrough infections and their severity and for comparing vaccines.Trial Registration: Clinicaltrials.gov NCT04368065, EU PAS Register EUPAS36240.Keywords: COVID-19, vaccines, breakthrough infections, SARS-CoV-2, symptoms, patient-reported outcomes

Nancy Dreyer,1 Natalia Petruski-Ivleva,1 Lisa Albert,1 Damir Mohamed,2 Emma Brinkley,1 Matthew Reynolds,1 Stephen Toovey3 1Real World Solutions, IQVIA Cambridge, Cambridge, MA, USA; 2Real World Solutions, IQVIA Courbevoie, Courbevoie, France; 3Pegasus Research, Bottmingen, SwitzerlandCorrespondence: Nancy DreyerReal World Solutions, IQVIA Cambridge, 201 Broadway, 5th Floor, Cambridge, MA, 02139, USATel +1 617 733 9478Email Nancy.Dreyer@IQVIA.comPurpose: Evidence is emerging that a significant percentage of COVID-19 cases experience symptom persistence beyond 30 days and go on to develop post-acute sequelae. Our objective was to compare the risk for COVID-19 symptom persistence by self-reported use of medications for autoimmune disease among participants of an on-line COVID-19 registry.Patients and Methods: A community-based online survey collected weekly data on COVID-19 symptom presentation. Participants who completed informed consent online, reported a positive COVID-19 test result within 14 days prior to enrollment and also reported demographics, underlying illnesses, and medication use were included. Symptom presence and severity were evaluated weekly after enrollment and compared between participants reporting use of medications for autoimmune conditions and all others. Logistic regression was used to evaluate the odds of more severe acute illness and symptom persistence approximately 30 days after enrollment.Results: A total of 1,518 COVID-19-positive participants were included. Participants reporting use of medications for autoimmune disease (n=70) were more likely to have experienced symptoms at all time points over a 30-day time period and were more likely to report more severe presentation of COVID-19 during acute illness (adjusted OR (95% CI)=1.32 (0.76– 2.29)) compared to those reporting not taking medications for autoimmune disease. At about 30 days after enrollment, users of medications for autoimmune disease were more than twice as likely to report three or more symptoms (adjusted OR (95% CI)=2.53 (1.21– 5.29)). In particular, their risk of persistent shortness of breath and fatigue was elevated (adjusted OR (95% CI)=2.66 (1.15– 6.18) and 4.73 (2.17– 10.34), respectively).Conclusion: Individuals with underlying autoimmune conditions appear to be particularly vulnerable to post-acute sequelae from COVID-19; early intervention might be considered.Keywords: COVID-19, PASC, autoimmune, direct-to-patient, fatigue, shortness of breath

Mary P Panaccio,1 Gordon Cummins,2 Charles Wentworth,3 Stephan Lanes,4 Shannon L Reynolds,5 Matthew W Reynolds,3 Raymond Miao,1 Andrew Koren1 1US Medical Affairs, Sanofi, Bridgewater, NJ, USA; 2Health Engagement and Communications, Quintiles, Durham, NC, USA; 3Evidera, Lexington, MA, USA; 4HealthCore Inc., Andover, MA, USA; 5Comprehensive Health Insights, Louisville, KY, USA Purpose: Atrial fibrillation/flutter (AF) is frequently associated with cardiovascular comorbidities. Observational health care databases are commonly used for research purposes in studies of quality of care, health economics, outcomes research, drug safety, and epidemiology. This retrospective cohort study applied a common data model to administrative claims data (Truven Health Analytics MarketScan® claims databases [MS-Claims]) and electronic medical records data (Geisinger Health System's MedMining electronic medical record database [MG-EMR]) to examine the risk of cardiovascular hospitalization and all-cause mortality in relation to clinical risk factors in recent-onset AF and to assess the consistency of analyses for each data source. Methods: Cohorts of patients with newly diagnosed AF (n=105,262 [MS-Claims] and n=3,919 [MG-EMR]) and demographically similar patients without AF (n=105,262 [MS-Claims] and n=3,872 [MG-EMR]) were followed from the qualifying AF diagnosis until cardiovascular hospitalization, death, database disenrollment, or study completion. A common data model standardized the data in structure, format, content, and nomenclature to allow for systematic assessment and comparison of outcomes from two disparate data sets. Results: In both databases, AF patients had greater overall baseline comorbidity and higher incidence rates of cardiovascular hospitalization (threefold higher) and all-cause mortality (46% higher) than non-AF patients. For AF patients, incidence rates of cardiovascular hospitalization and all-cause mortality were increased by the concomitant presence of coronary disease, chronic obstructive pulmonary disease, and stroke at baseline. Overall, the pattern of cardiovascular hospitalization in the MS-Claims database was similar to that in the MG-EMR database. Compared with the MS-Claims database, the use of cardiovascular medications and the capture of certain comorbidities among AF patients appeared to be higher in the MG-EMR data set. Conclusion: Similar standardized analyses across EMR and Claims databases were consistent in the association of AF with acute morbidity and an increased risk of all-cause mortality. Areas of inconsistency were due to differences in underlying population demographics and cardiovascular risks and completeness of certain data fields. Keywords: atrial fibrillation, cardiovascular hospitalization, common data models, epidemiology, observational databases

Abstract Aims: The safety and efficacy of exenatide BID (exenatide) and insulin glargine (glargine) have been studied in clinical trials with few elderly patients. This study examined the clinical effectiveness of exenatide compared to glargine in patients 65 years and older with type 2 diabetes mellitus (T2DM). Methods: A retrospective analysis was conducted using the General Electric electronic medical record database. Patients aged 65 years and older with T2DM who initiated exenatide or glargine were identified between November 1, 2006 and April 30, 2009 with 12 months of pre- and post-index continuous eligibility. Propensity-score matching (1:1) was used to balance baseline differences between the cohorts. The effectiveness endpoints were changes in A1C (primary endpoint), weight, body mass index (BMI), and blood pressure (BP). Matched cohorts were compared using paired t tests and nonparametric tests as appropriate. Results: The matched exenatide and glargine patients (n = 804 each) were comparable in their baseline characteristics, including age (70 vs. 71 years), and male sex (44.9% vs. 45.2%). In the 12-month follow-up, exenatide patients experienced significantly greater mean reductions in A1C (-0.5 vs. -0.2%), weight (-2.8 vs. -0.2 kg), BMI (-1.0 vs. -0.1 kg/m(2)), and systolic BP (-2.2 vs. 1.0 mmHg) (all: P < 0.05). More exenatide-treated patients reached the A1C goal of <7% (53.9% vs. 43.0%, P < 0.01). Diastolic BP was similar between the cohorts. Limitations: Unmeasured confounding bias may still exist and thus findings should be interpreted as associations instead of causations. Due to incomplete data, adverse events and medication use were not examined. Conclusion: Exenatide was associated with significant improvement in A1C, weight, BMI and BP compared to glargine for management of T2DM in an elderly patient population treated in ambulatory care settings. [ABSTRACT FROM AUTHOR]

Abstract Background: Exposure to over-the-counter (OTC) ibuprofen and other OTC non-steroidal anti-inflammatory drugs (NSAIDs) is substantial. Although the literature on gastrointestinal (GI) safety of NSAID therapy is extensive, the risk profiles of OTC and prescription dosing are seldom separated, and few studies provide risks specific to OTC ibuprofen. Objective: To conduct a literature review to evaluate the risk of GI bleeding events related to OTC ibuprofen use. Methods: Published clinical trials, observational studies, and meta-analyses of OTC ibuprofen use, defined as up to 1200 mg/day or stated as 'over the counter,' reporting endpoints of incidence rates and proportions of GI bleeding events (e.g., GI bleeding-related hospitalizations and deaths) were identified via MEDLINE through 2010. Data from these studies were summarized. Results: Twenty studies (nine observational, ten clinical trials, one meta-analysis) reporting incidence rates and proportions of a GI bleeding-related event associated with OTC or OTC-specific doses of ibuprofen were included. The frequency of a GI-related hospitalization was <0.2% for patients on OTC-comparable doses. Incidence rates among those using OTC-comparable doses ranged from 0 to 3.19 per 1000 patient-years. The incidence of a GI bleeding-related event increased with age and the use of concomitant medications, and there was a general, though not always statistically significant, ibuprofen dose-response relationship. The relative risk of any GI bleeding-related event ranged from 1.1 to 2.4 for users of OTC-specific doses of ibuprofen compared to non-users. Conclusions: Studies reported low incidence of GI bleeding events with use of OTC ibuprofen. Few published studies that specifically investigated OTC ibuprofen use were identified. Varying methodologies and definitions of exposure and outcomes prevented direct comparison of many results. Only studies that used the methods herein described were identified. Further research evaluating the risk of GI bleeding events in patients taking OTC-specific ibuprofen use may be useful. [ABSTRACT FROM AUTHOR]

Background: Surgical site infection (SSI) is an important cause of morbidity and occasionally death after coronary artery bypass graft (CABG) surgery. These infections also are associated with higher costs and poorer surgical outcomes. We used a retrospective observational database to examine and quantify the effects of the topical skin adhesive 2-octyl cyanoacrylate, used as the final layer of site closure in patients undergoing CABG surgery, on the incidence of post-operative SSI.Methods: All patients in the Premier Perspective™ Comparative Database of inpatient hospitalizations who underwent CABG surgery in 2005 and 2006 were identified. Qualifying patients were classified into four groups according to the method of surgical site closure on the basis of detailed hospital billing charges: Sutures only; sutures and 2-octyl cyanoacrylate; sutures and staples; and sutures, 2-octyl cyanoacrylate, and staples. Site infections were identified by a combination of International Classification of Diseases (ICD-9-CM) diagnosis codes, patterns of post-operative use of antibiotics, and All Patient Refined Diagnostic Related Group (APR-DRG) and Diagnostic Related Group (DRG) codes indicating post-operative infections at hospital re-admission.Results: A total of 59,006 patients qualified for the study: 38,799 who had sutures only; 10,262 having sutures and 2-octyl cyanoacrylate; 8,180 having sutures and staples; and 1,765 having sutures, 2-octyl cyanoacrylate, and staples. The lowest unadjusted rate of post-CABG SSI was found in the sutures and 2-octyl cyanoacrylate group (4.3%; 95% confidence interval [CI] 3.9-4.7), followed by sutures only (5.3%; 95% CI 5.1-5.5); sutures and staples (6.2%; 95% CI 5.7-6.8); and sutures, staples, and 2-octyl cyanoacrylate (7.1%; 95% CI 6.0%-8.4%). A logistic regression model that controlled for selected baseline patient, hospital, and surgical characteristics showed significantly lower rates of post-CABG SSI (odds ratio 0.76; 95% CI 0.68-0.85) in patients closed with sutures and 2-octyl cyanoacrylate relative to patients who had only sutures.Conclusions: The observed rates of post-CABG SSI were consistent with the rates observed in the literature. The SSI rate for patients who had sutures and 2-octyl cyanoacrylate used as the final layer of site closure was significantly lower than the rates for patients having other types of closure. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. METHODS: A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. RESULTS: Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. CONCLUSION: Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting. [ABSTRACT FROM AUTHOR]

School mental health programs have become a more prevalent setting for providing mental health services to adolescents. Evaluation of outcomes for these programs is lacking. The purpose of this research was to examine the relations among treatment goals, time in therapy, and change in behavioral and emotional functioning for adolescents receiving school-based mental health services, using student and clinician reports. Results indicated that both clinicians and students reported improved functioning for youth. Analyses indicated that students identified as having fewer treatment goals showed more progress than those with higher numbers of treatment goals. Girls reported more impairment in functioning than did boys. Father presence in the home and number of treatment goals were related to attrition. [ABSTRACT FROM AUTHOR]

This current review of the literature attempts to identify all published empirical evidence regarding art therapy effectiveness. The authors attempt to identify any outcome trends associated with study design (single group with no control group, controlled clinical trial, and randomized controlled clinical trial) and to review the overall literature base concerning art therapy effectiveness. The literature search identifies 17 published studies which met the authors' inclusion criteria. Results show that these three types of study designs produce very similar results regarding the positive effects of art therapy, but their conclusions may appear very different. The clarification of study design differences may lend some insight into the perceived effectiveness of art therapy. [ABSTRACT FROM AUTHOR]

Background: The world's first clinical 0.5 T inline rotating biplanar Linac-MR system is commissioned for clinical use. For reference dosimetry, unique features to device, including an SAD = 120 cm, bore clearance of 60 cm × 110 cm, as well as 0.5 T inline magnetic field, provide some challenges to applying a standard dosimetry protocol (i.e., TG-51)., Purpose: In this work, we propose a simple and practical clinical reference dosimetry protocol for the 0.5T biplanar Linac-MR and validated its results., Methods: Our dosimetry protocol for this system is as follows: tissue phantom ratios at 20 and 10 cm are first measured and converted into %dd10x beam quality specifier using equations provided and Kalach and Rogers. The converted %dd10x is used to determine the ion chamber correction factor, using the equations in the TG-51 addendum for the Exradin A12 farmer chamber used, which is cross-calibrated with one calibrated at a standards laboratory. For a 0.5 T parallel field, magnetic field effect on chamber response is assumed to have no effect and is not explicitly corrected for. Once the ion chamber correction factor for a non-standard SAD (k Q,msr ) is determined, TG-51 is performed to obtain dose at a depth of 10 cm at SAD = 120 cm. The dosimetry protocol is repeated with the magnetic field ramped down. To validate our dosimetry protocol, Monte Carlo (EGSnrc) simulations are performed to confirm the determined k Q,msr values. MC Simulations and magnetic Field On versus Field Off measurements are performed to confirm that the magnetic field has no effect. To validate our overall dosimetry protocol, external dose audits, based on optical simulated luminescent dosimeters, thermal luminescent dosimeters, and alanine dosimeters are performed on the 0.5 T Linac-MR system., Results: Our EGSnrc results confirm our protocol-determined k Q,msr values, as well as our assumptions about magnetic field effects (k B  = 1) within statistical uncertainty for the A-12 chamber. Our external dosimetry procedures also validated our overall dosimetry protocol for the 0.5 T biplanar Linac-MR hybrid. Ramping down the magnetic field has resulted in a dosimetric difference of 0.1%, well within experimental uncertainty., Conclusion: With the 0.5 T parallel magnetic field having minimal effect on the ion chamber response, a TPR 20,10 approach to determine beam quality provides an accurate method to perform clinical dosimetry for the 0.5 T biplanar Linac-MR., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Brain somatic gene recombination (SGR) and the endogenous reverse transcriptases (RTs) that produce it have been implicated in the etiology of Alzheimer's disease (AD), suggesting RT inhibitors as novel prophylactics or therapeutics. This retrospective, proof-of-concept study evaluated the incidence of AD in people with human immunodeficiency virus (HIV) with or without exposure to nucleoside RT inhibitors (NRTIs) using de-identified medical claims data. Eligible participants were aged ≥60 years, without pre-existing AD diagnoses, and pursued medical services in the United States from October 2015 to September 2016. Cohorts 1 (N = 46,218) and 2 (N = 32,923) had HIV. Cohort 1 had prescription claims for at least one NRTI within the exposure period; Cohort 2 did not. Cohort 3 (N = 150,819) had medical claims for the common cold without evidence of HIV or antiretroviral therapy. The cumulative incidence of new AD cases over the ensuing 2.75-year observation period was lowest in patients with NRTI exposure and highest in controls. Age- and sex-adjusted hazard ratios showed a significantly decreased risk for AD in Cohort 1 compared with Cohorts 2 (HR 0.88, p < 0.05) and 3 (HR 0.84, p < 0.05). Sub-grouping identified a decreased AD risk in patients with NRTI exposure but without protease inhibitor (PI) exposure. Prospective clinical trials and the development of next-generation agents targeting brain RTs are warranted.

Background: This exploratory study compares self-reported COVID-19 vaccine side effects and breakthrough infections in people who described themselves as having diabetes with those who did not identify as having diabetes., Objective: The study uses person-reported data to evaluate differences in the perception of COVID-19 vaccine side effects between adults with diabetes and those who did not report having diabetes., Methods: This is a retrospective cohort study conducted using data provided online by adults aged 18 years and older residing in the United States. The participants who voluntarily self-enrolled between March 19, 2021, and July 16, 2022, in the IQVIA COVID-19 Active Research Experience project reported clinical and demographic information, COVID-19 vaccination, whether they had experienced any side effects, test-confirmed infections, and consented to linkage with prescription claims. No distinction was made for this study to differentiate prediabetes or type 1 and type 2 diabetes nor to verify reports of positive COVID-19 tests. Person-reported medication use was validated using pharmacy claims and a subset of the linked data was used for a sensitivity analysis of medication effects. Multivariate logistic regression was used to estimate the adjusted odds ratios of vaccine side effects or breakthrough infections by diabetic status, adjusting for age, gender, education, race, ethnicity (Hispanic or Latino), BMI, smoker, receipt of an influenza vaccine, vaccine manufacturer, and all medical conditions. Evaluations of diabetes medication-specific vaccine side effects are illustrated graphically to support the examination of the magnitude of side effect differences for various medications and combinations of medications used to manage diabetes., Results: People with diabetes (n=724) reported experiencing fewer side effects within 2 weeks of vaccination for COVID-19 than those without diabetes (n=6417; mean 2.7, SD 2.0 vs mean 3.1, SD 2.0). The adjusted risk of having a specific side effect or any side effect was lower among those with diabetes, with significant reductions in fatigue and headache but no differences in breakthrough infections over participants' maximum follow-up time. Diabetes medication use did not consistently affect the risk of specific side effects, either using self-reported medication use or using only diabetes medications that were confirmed by pharmacy health insurance claims for people who also reported having diabetes., Conclusions: People with diabetes reported fewer vaccine side effects than participants not reporting having diabetes, with a similar risk of breakthrough infection., Trial Registration: ClinicalTrials.gov NCT04368065; https://clinicaltrials.gov/study/NCT04368065., (©Nancy A Dreyer, Kendall B Knuth, Yiqiong Xie, Matthew W Reynolds, Christina D Mack. Originally published in JMIR Diabetes (https://diabetes.jmir.org), 27.02.2024.)

In January 2021, 999 COVID-19 positive adults in the US enrolled in an online, direct-to-patient registry to describe daily symptom severity and progression over 28 days. The most commonly reported and persistent symptoms were fatigue, headache, decreased sense of taste, decreased sense of smell, and cough. Fast resolving symptoms included gastrointestinal symptoms (nausea, vomiting, diarrhea) and those related to fever and chills. While more than half (56%) of patients reported overall symptom improvement during the 28-day study period, 60% of patients were still reporting at least 1 COVID-19 symptom at the end of 28 days. Risk factors for experiencing symptoms for longer duration included at least one of the following: older age (> 60 years), higher BMI, lung disease, and receiving medication for hypertension. The study demonstrates the value of patient-reported data to provide important and timely insights to COVID-19 disease and symptom progression and the potential of using real-world data to inform clinical trial design and endpoints., (© 2023. The Author(s).)

Objective: To describe cognitive symptoms in people not hospitalised at study enrolment for SARS-CoV-2 infection and associated demographics, medical history, other neuropsychiatric symptoms and SARS-CoV-2 vaccination., Design: Longitudinal observational study., Setting: Direct-to-participant registry with community-based recruitment via email and social media including Google, Facebook and Reddit, targeting adult US residents. Demographics, medical history, COVID-19-like symptoms, tests and vaccinations were collected through enrolment and follow-up surveys., Participants: Participants who reported positive COVID-19 test results between 15 December 2020 and 13 December 2021. Those with cognitive symptoms were compared with those not reporting such symptoms., Main Outcome Measure: Self-reported cognitive symptoms (defined as 'feeling disoriented or having trouble thinking' from listed options or related written-in symptoms) RESULTS: Of 3908 participants with a positive COVID-19 test result, 1014 (25.9%) reported cognitive symptoms at any time point during enrolment or follow-up, with approximately half reporting moderate/severe symptoms. Cognitive symptoms were associated with other neuropsychiatric symptoms, including dysgeusia, anosmia, trouble waking up, insomnia, headache, anxiety and depression. In multivariate analyses, female sex (OR, 95% CI): 1.7 (1.3 to 2.2), age (40-49 years (OR: 1.5 (1.2-1.9) compared with 18-29 years), history of autoimmune disease (OR: 1.5 (1.2-2.1)), lung disease (OR: 1.7 (1.3-2.2)) and depression (OR: 1.4 (1.1-1.7)) were associated with cognitive symptoms. Conversely, black race (OR: 0.6 (0.5-0.9)) and COVID-19 vaccination before infection (OR: 0.6 (0.4-0.7)) were associated with reduced occurrence of cognitive symptoms., Conclusions: In this study, cognitive symptoms among COVID-19-positive participants were associated with female gender, age, autoimmune disorders, lung disease and depression. Vaccination and black race were associated with lower occurrence of cognitive symptoms. A constellation of neuropsychiatric and psychological symptoms occurred with cognitive symptoms. Our findings suggest COVID-19's full health and economic burden may be underestimated., Trial Registration Number: NCT04368065., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The objective of this study was to describe the acute side effects experienced by pregnant women who received a coronavirus disease 2019 (COVID-19) vaccine in the United States and to compare their experience to nonpregnant women of similar age., Study Design: Adults who received a COVID-19 vaccine in the United States were invited via social media to enroll in an online, longitudinal, community-based registry ( www.helpstopCOVID19.com ). Participants self-reported pregnancy status, vaccination dates, manufacturer, acute side effects, impact on work and self-care, medical consultation, and hospitalization. This analysis was restricted to women aged 20 to 39 at the time of vaccination. Side effects reported by pregnant women were compared to those reported by nonpregnant women., Results: This analysis included 946 pregnant women, with 572 (60%) receiving at least one dose of Pfizer, 321 (34%) Moderna, and 53 (6%) J&J, and 1,178 nonpregnant women. Demographic and medical history were similar across manufacturers for both cohorts.Overall, pregnant women reported similar side effects as nonpregnant women, with the most common being injection site reactions (83 vs. 87%), fatigue (72 vs.78%), and headache (45 vs. 59%). Pregnant women reported fewer side effects (median: 3 vs. 4, respectively). In both cohorts, very few reported seeking medical care (<5%) or being hospitalized (<0.3%) after vaccination. Fewer pregnant women reported working less after vaccination than nonpregnant women (32 vs. 40%) or trouble with self-care (32 vs. 46%), respectively., Conclusion: Pregnant women reported similar COVID-19 vaccine side effects as nonpregnant women, although fewer total side effects; pregnant women judged these side effects to have less impact on work and self-care. While these results do not address pregnancy outcomes or long-term effects, findings about acute side effects and impact offer reassurance for all three vaccines in terms of tolerability., Key Points: · COVID vaccines were well tolerated by pregnant women.. · Pregnant women reported fewer total side effects.. · Pregnant women reported less impact on work and self-care.., Competing Interests: None declared., (Thieme. All rights reserved.)

Aim: It is important to assess if clinical trial efficacy translates into real-world effectiveness for COVID-19 vaccines. Materials & methods: 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. Results: Any vaccination was associated with a 95% reduction in subsequently reporting a positive COVID-19 test, and a 71% reduction in reporting a positive test and ≥1 moderate/severe symptom. Conclusion: We observed high effectiveness across all three marketed vaccines, both for self-reported positive COVID-19 tests and moderate/severe COVID-19 symptoms. This innovative TND approach can be implemented in future COVID-19 vaccine and treatment real-world effectiveness studies. Clinicaltrials.gov identifier: NCT04368065.

Introduction: Our objective was to describe and compare self-reported side effects ofCOVID-19 vaccinesin theUSA., Methods: Aweb-basedregistry enrolled volunteers who received a COVID-19 vaccine between March 19-July 15, 2021. We collected self-reported short-term side effects, medical consultation, hospitalization, and quality of life impact following completed vaccination regimens (Pfizer, Moderna, J&J)., Results: We recruited 6,966 volunteers who completed their full course of vaccination (median age 48 years, IQR 35.0-62.0; 83.6% female): Pfizer 3,486; Moderna 2,857; J&J 623. Few (3.1%) sought medical care for post-vaccination side effects. Hospitalization (n = 17; 0.3%) and severe allergic reactions (n = 39; 0.6%) also were rare. Those with autoimmune disease or lung disease were approximately twice as likely to seek medical care (adjusted odds ratio (aOR) 2.01, 95% CI:1.39; 2.92 and aOR 1.70, 95% CI: 1.12; .58 respectively). 92.4% of participantsreported ≥ 1side effect (median 3), with injection site reactions (78.9%), fatigue (70.3%), headache (49.0%) reported most frequently. More side effects were reported after the second dose of two-dose vaccines (medians: 1 vs. 2 for Pfizer and 1 vs. 3 for Moderna for first and second doses respectively) versus 3 for J&J's single-dose vaccine. For the employed, the median number of workdays missed was one. Diabetics and those vaccinated against influenza were substantially less likely to report 3 or more symptoms (aOR 0.68, 95% CI: 0.56;0.82] and aOR 0.82, 95% CI: 0.73;0.93, respectively)., Discussion: The total side effect burden was, not unexpectedly, greater with two-dose regimens but all three vaccines appear relatively safe. Very few subjects reported side effects serious enough to warrant medical care or reported post-vaccination hospitalization. While these findings do not address possible long-term effects, they do inform on their short-term safety and tolerability and will hopefully provide some reassurance and positively inform the benefit-risk and pharmacoeconomic assessment for all three vaccines. See Clinicaltrials.gov NCT04368065., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IQVIA reports financial support was provided by US Food and Drug Administration., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To evaluate whether automated methods are sufficient for deriving ICD-10-CM algorithms by comparing ICD-9-CM to ICD-10-CM crosswalks from general equivalence mappings (GEMs) with physician/clinical coder-derived crosswalks., Patients and Methods: Forward mapping was used to derive ICD-10-CM crosswalks for 10 conditions. As a sensitivity analysis, forward-backward mapping (FBM) was also conducted for three clinical conditions. The physician/coder independently developed crosswalks for the same conditions. Differences between the crosswalks were summarized using the Jaccard similarity coefficient (JSC)., Results: Physician/coder crosswalks were typically far more inclusive than GEMs crosswalks. Crosswalks for peripheral artery disease were most dissimilar (JSC: 0.06), while crosswalks for mild cognitive impairment (JSC: 1) and congestive heart failure (0.85) were most similar. FBM added ICD-10-CM codes for all three conditions but did not consistently increase similarity between crosswalks., Conclusion: The GEMs and physician/coder algorithms rarely aligned fully; human review is still required for ICD-9-CM to ICD-10-CM crosswalk development., (Copyright © 2021 by the American Health Information Management Association.)

Purpose: To provide guidance on data linkage appropriateness and feasibility to plan purposeful and sustainable new linkages that advance pharmacoepidemiology and healthcare research. Planning a new data linkage requires careful evaluation to weigh the resources required with the potential overall benefits., Methods: In response to an International Society for Pharmacoepidemiology (ISPE) call for manuscripts, a working group comprised of members from academic, industry, and government determined priority content areas; appropriateness and feasibility of data linkage was selected. Within this topic, scientific and operational considerations were determined, reviewed, and formulated into key areas, and translated into 12 consensus recommendations., Results: Guidance for feasibility assessment was categorized into five key areas: (1) research objectives and justification; (2) data quality and completeness; (3) the linkage process; (4) data ownership and governance; and (5) overall value added by linkage. Within these key areas, recommendations to consider prior to initiation were developed to evaluate suitability of the linkage to meet research objectives, assess source data completeness and population coverage, and ensure well-defined data governance standards and protections. When creating novel linked datasets, researchers must assess the feasibility of both scientific (data quality and linkage methods) and operational (access, data use and transfer, governance, and cost) aspects., Conclusions: The data linkage feasibility assessment considerations outlined can be used as a guide when designing sustainable linked data resources to generate actionable evidence in healthcare research. These recommendations were constructed for wide applicability and can be adapted depending on the geographic, structural, and data components of the linkage., (© 2020 John Wiley & Sons, Ltd.)

Bovine trichomoniasis is a notifiable, reproductive disease of cattle caused by the parasite Tritrichomonas foetus. Culturing with modified Diamond's medium (MDM) is required to increase the low number of organisms received from a preputial sample, but is limited in application to remote areas as it requires continuous cold chain storage. This study utilized lyophilization to sustain the viability of MDM during transport in lieu of a continuous cold chain. All lyophilized MDM was able to sustain T. foetus after storage for 42 days at 24 °C, and the results demonstrated that lyophilized MDM was equally as viable as refrigerated liquid MDM. Storage of lyophilized MDM at room temperature for 1 and 7 days did not impact T. foetus yield, both with and without exposure to light. A limitation of the lyophilized MDM was demonstrated with a significant decrease in T. foetus yield when the media was stored at 37 and 58 °C. The lyophilization of MDM provides a robust method of transporting and storing medium prior to reconstitution and inoculation, for use in T. foetus diagnosis and surveillance in remote areas.

Dabigatran is approved for stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data from diverse clinical practice settings will help establish whether the risk:benefit ratio seen in clinical trials is comparable with routine clinical care. This study aimed to compare the safety and effectiveness of dabigatran and warfarin in clinical practice. We undertook a propensity score-matched (PSM) cohort study (N=12,793 per group; mean age 74) comparing treatment with dabigatran or warfarin in the US Department of Defense claims database, October 2009 to July 2013. Treatment-naïve patients with first prescription claim for dabigatran (either FDA-approved dose) or warfarin between October 2010 and July 2012 (index) and a diagnosis of NVAF during the 12 months before index date were included. Primary outcomes were stroke and major bleeding. Secondary outcomes included ischaemic and haemorrhagic stroke, major gastrointestinal (GI), urogenital or other bleeding, myocardial infarction (MI) and death. Time-to-event was investigated using Kaplan-Meier survival analyses. Outcomes comparisons were made utilising Cox-proportional hazards models of PSM groups. Dabigatran users experienced fewer strokes (adjusted hazard ratio [95 % confidence intervals] 0.73 [0.55-0.97]), major intracranial (0.49 [0.30-0.79]), urogenital (0.36 [0.18-0.74]) and other (0.38 [0.22-0.66]) bleeding, MI (0.65 [0.45-0.95]) and deaths (0.64 [0.55-0.74]) than the warfarin group. Major bleeding (0.87 [0.74-1.03]) and major GI bleeding (1.13 [0.94-1.37]) was similar between groups and major lower GI bleeding events were more frequent (1.30 [1.04-1.62]) with dabigatran. In conclusion, compared with warfarin, dabigatran treatment was associated with a lower risk of stroke and most outcomes measured, but increased incidence of major lower GI bleeding.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disease. Little is known about how patient clinical features and healthcare utilization varies by human immunodeficiency virus (HIV) status and disease subtype. Data of MCD patients identified between 2000 and 2009 were collected from medical records at two United States treatment centres. Clinical, demographic, and biochemical characteristics, drug therapies and medical utilization were descriptively reported by HIV status and cell histology, and statistically compared with the Fisher's Exact and Kruskal-Wallis tests. Patients (n = 59) had a pathologically and clinically confirmed MCD diagnosis: plasmacytic (42%), hyaline vascular (29%) and mixed (15%); 10% had HIV infection. In the first year after diagnosis, MCD patients on average saw a healthcare provider more than six times, were hospitalized at least once and underwent frequent radiological and laboratory testing. Rituximab was the most commonly used drug therapy, followed by corticosteroids and conventional chemotherapy. One- and 2-year survival was excellent in HIV-negative patients (100% and 97%, respectively) but inferior for HIV-positive cases (67% and 67%, respectively). Heterogeneous treatment decisions were observed in this MCD study; HIV status was the only distinguishing clinical criteria associated with pharmacotherapies. Additional research is necessary to guide treatment of this rare lymphoproliferative disorder., (© 2014 John Wiley & Sons Ltd.)

Pseudobulbar affect (PBA), a neurological syndrome characterized primarily by involuntary episodes of laughing and crying, can develop secondary to neurological conditions including traumatic brain injury (TBI). Veterans of the wars in Afghanistan and Iraq have an unprecedented risk for TBI, primarily from blast-related munitions. In this cross-sectional study with linkage to Department of Veterans Affairs (VA) clinical data, Veterans screening positive for TBI on the VA TBI screen (N = 4,282) were mailed packets containing two PBA symptom assessments: a single PBA symptom screen question and the Center for Neurologic Study-Lability Scale (CNS-LS) questionnaire. Seventy percent (n = 513) of the 728 Veteran respondents screened positive for PBA symptoms with a CNS-LS score of 13 or greater. There was strong concordance between PBA symptom prevalence measured with the single screening question and CNS-LS, with high sensitivity (0.87) and positive predictive value (0.93), and moderate specificity (0.79). Posttraumatic stress disorder (54% vs 32%), major depression (35% vs 22%), and anxiety disorder (20% vs 13%) were more common for Veterans with PBA symptoms than for those without. PBA symptoms were common in this Veteran cohort, were detected using simple screening tools, and often co-occurred with other psychiatric disorders common in Veterans.

Objective: To examine the clinical effectiveness of concomitant therapy of exenatide twice daily and basal insulin in patients with type 2 diabetes mellitus in the United States., Methods: Data from adults with type 2 diabetes were selected from an electronic medical record database. Concomitant therapy was defined as a basal insulin prescription within 6 months before or after an exenatide prescription between May 2005 and April 2009. Upon initiation, patients were treated with both medications. Clinical effectiveness was measured as mean changes in hemoglobin A1c (primary outcome), body weight, body mass index, blood pressure, and lipid values from a 6-month baseline to mean-adjusted values in a 12-month follow-up period. These changes were assessed by a bootstrapping test., Results: There were 1752 patients (mean age, 57 years) who initiated concomitant therapy (75% added exenatide to basal insulin, 25% added basal insulin to exenatide). Patients achieved significant mean reductions in hemoglobin A1c (0.5%), body weight (1.8 kg), body mass index (0.6 kg/m2), diastolic blood pressure (0.5 mm Hg), and various lipid measures (all P<.05). Hemoglobin A1c reduction was consistent irrespective of the treatment order. However, body weight, body mass index, and blood pressure reductions were observed in only patients who added exenatide to basal insulin., Conclusions: Overall, exenatide and basal insulin concomitant therapy was associated with significant reductions in hemoglobin A1c, body weight, body mass index, diastolic blood pressure, and lipids in a large, diverse patient population treated in ambulatory care settings in the United States. In the subgroup analysis, body weight, body mass index, and diastolic blood pressure reductions were observed in only patients who added exenatide to basal insulin.

Background and Objective: Febrile neutropenia (FN) is a potentially life-threatening condition that may develop in cancer patients treated with myelosuppressive chemotherapy and result in considerable costs. This study was designed to estimate US healthcare utilization and costs in those experiencing FN by location of care, tumour type and mortality., Methods: Cancer patients who received chemotherapy between 2001 and 2006 were identified from the HealthCore Integrated Research Database®, a longitudinal claims database with enrolment, medical, prescription and mortality information covering 12 health plans and more than 20 million US patients. Patients who experienced FN were prospectively matched using propensity score methods within each tumour type of interest (non-Hodgkin's lymphoma, breast, lung, colorectal and ovarian cancer) to those not experiencing FN. Health resource utilization was compared per patient per month for unique prescriptions and visits (inpatient and outpatient) over the length of follow-up. Healthcare total paid costs adjusted to 2009 US dollars per patient per month were examined by FN group (FN vs non-FN, FN died vs FN survived), by source of care (physician office visit, outpatient services, hospitalization and prescriptions) and by tumour type. The number of unique FN-related encounters (inpatient and outpatient) and the number of patients experiencing at least one FN-related encounter were examined. The costs per encounter were tabulated. FN encounters differ from FN episodes in that a single FN episode may include multiple FN encounters (i.e. a patient is seen multiple times [encounters] for treatment of a single FN event [episode])., Results: A total of 5990 patients each were successfully matched between the FN and non-FN (control) groups. Health resource utilization was generally higher in those with FN than in controls. FN patients incurred greater costs (mean ± SD: $US9628 ± 12 517 per patient-month) than non-FN patients ($US8478 ± 12 978). Chemotherapy comprised the majority of costs for both FN (33.5%) and non-FN (40.6%) patients. The largest cost difference by categorical source of care was for hospitalization (p < 0.001). FN patients who died had the highest mean total costs compared with FN surviving patients ($US21 214 ± 25 596 per patient-month vs $US8227 ± 8850, respectively). Follow-up time for those surviving was, on average, 6.6 months longer. Hospitalization accounted for 53.1% of costs in those experiencing mortality with FN, while chemotherapy accounted for the majority of costs (37.1%) in surviving FN patients. A total of 6574 patients with at least one FN encounter experienced a total of 55 726 unique FN-related encounters, 90% of which were outpatient in nature. The majority of FN-related encounters (79%) occurred during the first chemotherapy course. The average costs for FN encounters were highest for inpatient encounters, $US22 086 ± 43 407, compared with $US985 ± 1677 for outpatient encounters., Conclusions: The occurrence of FN in cancer patients receiving chemotherapy results in greater healthcare resource utilization and costs, with FN patients who die accounting for the greatest healthcare costs. Most FN patients experience at least one outpatient FN encounter, and the total cost of treatment for FN continues to be high.

Aim: This observational study evaluated the clinical effectiveness of exenatide BID (exenatide) vs. insulin glargine (glargine) in patients with type 2 diabetes mellitus in ambulatory clinical practice., Methods: Retrospective analyses were conducted using an electronic medical record (EMR) database among adult patients with type 2 diabetes mellitus initiating exenatide or glargine between 1 November 2006 and 30 April 2009. The cohorts were propensity-score matched to control baseline demographics, clinical measures, health status and medication use. The changes from baseline to a 12-month follow-up period for A1C (primary outcome), weight, body mass index (BMI), blood pressure and lipid levels were compared between the matched cohorts using paired tests., Results: Propensity-score matching between the exenatide (n = 4494) and glargine (n = 5424) cohorts led to 2683 matched pairs with comparable characteristics, including age, gender and baseline clinical values. The exenatide cohort achieved a greater mean reduction in A1C (-0.6% vs. -0.4%, p < 0.01), weight (-2.6 kg vs. -0.2 kg, p < 0.01), BMI (-0.8 kg/m(2) vs. -0.04 kg/m(2) , p < 0.01) and systolic blood pressure (SBP) (-1.8 mmHg vs. -0.1 mmHg, p < 0.01) in the follow-up period. The changes in diastolic blood pressure and lipid levels were not significantly different between cohorts., Conclusions: Compared to glargine, exenatide-treated patients experienced significant reductions in A1C, weight, BMI and SBP. Acknowledging the limitations of observational research, exenatide showed greater clinical effectiveness than glargine from a large EMR database in the ambulatory care setting., (© 2012 Blackwell Publishing Ltd.)

Purpose: Published evidence on quality-of-life (QOL) outcomes and health care costs in patients with postthrombotic syndrome (PTS), a common and difficult-to-diagnose complication of venous thromboembolism (VTE), is reviewed., Summary: Occurring in as many as 70% of patients with VTE, PTS remains a challenging and costly disorder, partly due to the lack of a standard diagnostic definition and varying classification systems. Searches of Medline and EMBASE identified 12 articles on humanistic and economic outcomes associated with PTS. The results of U.S. and international studies indicate that PTS is a key determinant of long-term QOL among patients with VTE. In one large study, 37% of patients with VTE developed PTS within two years of a diagnosis of deep venous thrombosis (DVT), and 4% developed severe PTS, with the occurrence of PTS linked to clinically relevant declines in measures of physical and mental health. Research indicates that the economic burden of PTS in the United States may be as high as $200 million annually. Recent progress in efforts to develop standard PTS terminology may facilitate the dissemination of clear consensus guidelines to assist in timely PTS detection and optimal care., Conclusion: Appropriate measures to decrease PTS-related burdens may include the prevention of DVT, clear diagnostic criteria for PTS, and an education campaign aimed at increased standardization in the management of DVT. Gaps in the current understanding of the risk factors, diagnostic criteria, preventive strategies, and even treatment modalities for PTS hamper the ability of clinicians to employ measures that could reduce the occurrence of this disorder and the associated morbidity.

Purpose: The Food and Drug Administration's Mini-Sentinel pilot program initially aimed to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of pulmonary fibrosis and interstitial lung disease., Methods: PubMed and Iowa Drug Information Service Web searches were conducted to identify citations applicable to the pulmonary fibrosis/interstitial lung disease HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify pulmonary fibrosis and interstitial lung disease, including validation estimates of the coding algorithms., Results: Our search revealed a deficiency of literature focusing on pulmonary fibrosis and interstitial lung disease algorithms and validation estimates. Only five studies provided codes; none provided validation estimates. Because interstitial lung disease includes a broad spectrum of diseases, including pulmonary fibrosis, the scope of these studies varied, as did the corresponding diagnostic codes used., Conclusions: Research needs to be conducted on designing validation studies to test pulmonary fibrosis and interstitial lung disease algorithms and estimating their predictive power, sensitivity, and specificity., (Copyright © 2012 John Wiley & Sons, Ltd.)

Purpose: The Food and Drug Administration's Mini-Sentinel pilot program initially aims to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest from administrative and claims data. This article summarizes the process and findings of the algorithm review of anaphylaxis., Methods: PubMed and Iowa Drug Information Service searches were conducted to identify citations applicable to the anaphylaxis health outcome of interest. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify anaphylaxis and including validation estimates of the coding algorithms., Results: Our search revealed limited literature focusing on anaphylaxis that provided administrative and claims data-based algorithms and validation estimates. Only four studies identified via literature searches provided validated algorithms; however, two additional studies were identified by Mini-Sentinel collaborators and were incorporated. The International Classification of Diseases, Ninth Revision, codes varied, as did the positive predictive value, depending on the cohort characteristics and the specific codes used to identify anaphylaxis., Conclusions: Research needs to be conducted on designing validation studies to test anaphylaxis algorithms and estimating their predictive power, sensitivity, and specificity., (Copyright © 2012 John Wiley & Sons, Ltd.)