Search

Background: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system.Methods: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed.Results: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper.Conclusions: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration.Trial Registration: NCT Clinicaltrials.gov identifier: NCT02158637. [ABSTRACT FROM AUTHOR]

Purpose: With the rapid development of immunotherapy, cancer treatment has entered a new phase. Medical imaging, as a primary diagnostic method, is closely related to cancer immunotherapy. However, until now, there has been no systematic bibliometric analysis of the state of this field. Therefore, the main purpose of this article is to clarify the past research trajectory, summarize current research hotspots, reveal dynamic scientific developments, and explore future research directions. Patients and Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to immunotherapy specifically for the medical imaging of carcinoma. The search spanned the period from the year 2003 to 2023. Several analytical tools were employed. These included CiteSpace (6.2.4), and the Microsoft Office Excel (2016). Results: By searching the database, a total of 704 English articles published between 2003 and 2023 were obtained. We have observed a rapid increase in the number of publications since 2018. The two most active countries are the United States (n=265) and China (n=170). Pittock, Sean J and Abu-sbeih, Hamzah are very concerned about the relationship between cancer immunotherapy and medical images and have published more academic papers (n = 5; n = 4). Among the top 10 co-cited authors, Topalian Sl (n=43) cited ranked first, followed by Graus F (n=40) cited. According to clustering, timeline, and burst word analysis, the results show that the current research focus is on "MRI", "deep learning", "tumor microenvironment" and so on. Conclusion: Medical imaging and cancer immunotherapy are hot topics. The United States is the country with the most publications and the greatest influence in this field, followed by China. "MRI", "PET/PET-CT", "deep learning", "immune-related adverse events" and "tumor microenvironment" are currently hot research topics and potential targets. [ABSTRACT FROM AUTHOR]

Objective: Pharmacotherapeutic Follow-up is the Professional Pharmaceutical Care Service aimed at detecting Drug-Related Problems for the prevention and resolution of negative medicine outcomes. The Dader Method is considered a clear and simple tool to develop Pharmacotherapeutic Follow-up. This research aims to analyze the evolution of the international scientific production related to Pharmacotherapeutic Follow-up and the Dader Method to show the current situation of this Professional Pharmacy Assistance Service. In addition, from the data obtained, we give a critical perspective on the implementation of the Dader Method in Community Pharmacy, considering its advantages and disadvantages based on the published scientific literature. Methods: Using bibliometrics tools, indicators were obtained to analyze the international production of scientific articles on Pharmacotherapeutic Follow-up and the Dader Method during the period (1999-2022) through the Scopus database. Results: The results showed a growth in the international scientific production of publications on Pharmacotherapeutic Follow-up, obtaining 30,287 papers, placing the United States, the United Kingdom, Australia, Canada and Spain as the five most productive countries. The publication of 83 papers on the Dader Method places Spain with the highest number of publications, followed by other Spanish or Portuguese speaking countries, among which Brazil and Colombia have the most prominent number of published papers in Latin America. The most frequent international journal covering the topic of Pharmacotherapeutic Follow-up was the American Journal of Health-Pharmacy (12.4%), while on the Dader Method, the journal Pharmaceutical Care Spain (21.7%) is in the first position, followed by Farmacia Hospitalaria (8.4%). Conclusion: The publications on the Dader method highlighs the greater productivity of the University of Granada and the author María José Faus Dáder. The inclusion of patients in the PTF service using the Dader Method, is more frequent in the hospital context, and is based on the presence of defined chronic pathologies (mainly diabetes), polymedication or specialized care follow-up, with elderly population being the most represented in all cases. [ABSTRACT FROM AUTHOR]

Drug overdose claimed more than 100,000 lives in the United States in 2021. Drug‐induced homicide (DIH) laws create specific criminal liability for individuals who provide drugs that cause or contribute to the death of another person. DIH prosecutions in the United States have increased substantially over the past decade despite the absence of meaningful evidence of their individual‐ or community‐level impacts. Recently, Lee et al. analyzed the impact of DIH laws on county‐level opioid overdose mortality across 92 counties in 10 states and concluded that DIH laws are associated with significant reductions in rates of opioid overdose death. In this commentary, we present evidence demonstrating that the Lee et al. study is fundamentally flawed. Specifically, the legal data used by Lee et al. to define their treatment condition (the presence or absence of a state‐level DIH law) is incorrect in almost every aspect. We also describe significant methodological weaknesses, including flawed sampling strategies that resulted in a biased sample of county overdose rates as well as flawed modeling strategies that cannot effectively evaluate the hypothesis that DIH laws negatively impact opioid overdose mortality. More research on the individual‐ and community‐level impacts of DIH laws is needed. In the meantime, we advise policymakers to strengthen state 911 Good Samaritan laws, as DIH laws appear to erode the efficacy of this proven overdose‐prevention strategy. Key points: Drug‐induced homicide laws create specific criminal liability for individuals who provide drugs that cause or contribute to the death of another person and are increasingly used in the United States despite little evidence of their impact on overdose and other harms.This paper critically evaluates a recent paper that analyzed the impact of these laws on county‐level opioid overdose mortality across 92 counties in 10 US states, concluding that these laws are associated with reduced opioid overdose deaths.We present evidence demonstrating that the previous paper is fundamentally flawed, detailing serious errors in the underlying legal research as well as significant methodological weaknesses that render the results of the paper unreliable.Reliable research on the impact of these laws is urgently needed. In the meantime, policymakers are urged to implement policies with robust evidence demonstrating their overdose‐prevention impacts: medications for opioid use disorder, naloxone access, and syringe services programs. [ABSTRACT FROM AUTHOR]

This paper discusses methodological issues that emerged during the design and implementation of a large-scale survey of licensed social workers in the USA. Benefits and challenges of survey research are identified. The paper provides recommendations for future workforce studies and surveys that assess behavioral health problems. [ABSTRACT FROM AUTHOR]

This paper reviews the main tools for communicating benefit-risk medicines information to patients that are used, or could be used, by pharmaceutical regulators. One highly successful tool from the food safety sector (front-of-package traffic-light labelling) and the mental models approach (which provides a framework for developing new tools) are also reviewed as they show great promise for being usefully adapted to the pharmaceutical context. The evolution of benefit-risk medicines communication is first contextualised within the broader risk communication literature. Three distinct goals are then made explicit before critically examining the evidence for and against tools developed in the US (e.g. at the Food and Drug Administration [FDA]) and Europe (e.g. at the European Medicines Agency [EMA]). These goals are (i) sharing information (e.g. publishing clinical trial and adverse event data online); (ii) changing patients' beliefs by conveying factual knowledge (e.g. patient information leaflets and the drugs facts box); and (iii) changing behaviour (e.g. patient alert cards and warning labels). The mental models approach and traffic-light labelling, developed outside the pharmaceutical context, are then examined. Ultimately, the paper provides a helicopter view of the variety of benefit-risk communication tools that are used, or could be used, by pharmaceutical regulators in the US and Europe. [ABSTRACT FROM AUTHOR]

The 2010 US Food and Drug Administration and European Medicines Agency regulatory approaches to establish bioequivalence in highly variable drugs are both based on linearly scaling the bioequivalence limits, both take a 'scaled average bioequivalence' approach. The present paper corroborates previous work suggesting that none of them adequately controls type I error or consumer's risk, so they result in invalid test procedures in the neighbourhood of a within-subject coefficient of variation osf 30% for the reference (R) formulation. The problem is particularly serious in the US Food and Drug Administration regulation, but it is also appreciable in the European Medicines Agency one. For the partially replicated TRR/RTR/RRT and the replicated TRTR/RTRT crossover designs, we quantify these type I error problems by means of a simulation study, discuss their possible causes and propose straightforward improvements on both regulatory procedures that improve their type I error control while maintaining an adequate power. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Drug-drug interactions (DDIs) are a common cause of adverse drug events (ADEs). The electronic medical record (EMR) database and the FDA's adverse event reporting system (FAERS) database are the major data sources for mining and testing the ADE associated DDI signals. Most DDI data mining methods focus on pair-wise drug interactions, and methods to detect high-dimensional DDIs in medical databases are lacking. In this paper, we propose 2 novel mixture drug-count response models for detecting high-dimensional drug combinations that induce myopathy. The "count" indicates the number of drugs in a combination. One model is called fixed probability mixture drug-count response model with a maximum risk threshold (FMDRM-MRT). The other model is called count-dependent probability mixture drug-count response model with a maximum risk threshold (CMDRM-MRT), in which the mixture probability is count dependent. Compared with the previous mixture drug-count response model (MDRM) developed by our group, these 2 new models show a better likelihood in detecting high-dimensional drug combinatory effects on myopathy. CMDRM-MRT identified and validated (54; 374; 637; 442; 131) 2-way to 6-way drug interactions, respectively, which induce myopathy in both EMR and FAERS databases. We further demonstrate FAERS data capture much higher maximum myopathy risk than EMR data do. The consistency of 2 mixture models' parameters and local false discovery rate estimates are evaluated through statistical simulation studies. [ABSTRACT FROM AUTHOR]

This paper argues that mandatory, government-enforced vaccination can be justified even within a libertarian political framework. If so, this implies that the case for mandatory vaccination is very strong indeed as it can be justified even within a framework that, at first glance, loads the philosophical dice against that conclusion. I argue that people who refuse vaccinations violate the 'clean hands principle', a (in this case, enforceable) moral principle that prohibits people from participating in the collective imposition of unjust harm or risk of harm. In a libertarian framework, individuals may be forced to accept certain vaccines not because they have an enforceable duty to serve the common, and not because cost-benefit analysis recommends it, but because anti-vaxxers are wrongfully imposing undue harm upon others. [ABSTRACT FROM AUTHOR]

Background: Capecitabine has been reported to be associated with severe gastrointestinal (GI) adverse drug reactions (gastrointestinal ulceration, haemorrhage, and obstruction). However, statistical correlations have not been demonstrated, and specific GI adverse drug reactions, such as GI obstruction, are not listed on its label. Aim: We aimed to determine the associations between capecitabine and GI ulceration, haemorrhage, or obstruction among patients with breast cancer by examining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We performed disproportionality analysis of GI ulceration, haemorrhage, and obstruction by evaluating the reporting odds ratio (ROR) and the information component (IC) with their 95% confidence intervals (CIs). Results: We identified 279 patients with capecitabine-associated GI ulceration, haemorrhage, or obstruction reported between 1 January 2004 and 31 December 2020. One-fourth of the cases of GI ulceration, haemorrhage, or obstruction resulted in death. Capecitabine as a drug class had disproportionately high reporting rates for GI ulceration [ROR 1.94 (1.71-2.21); IC 0.80 (0.60-0.99)], haemorrhage [ROR 2.27 (1.86-2.76); IC 0.99 (0.69-1.28)], and obstruction [ROR 2.19 (1.63-2.95); IC 0.96 (0.51-1.40)]. Conclusion: Pharmacovigilance research on the FAERS has revealed a slight increase in reports of GI ulceration, haemorrhage, and obstruction in capecitabine users, which may cause serious or deadly consequences. In addition to the adverse reactions described in the package insert, close attention should be paid to GI obstruction to avoid discontinuation or lifethreatening outcomes. [ABSTRACT FROM AUTHOR]

During the past decade, patient safety issues during care transitions have gained greater attention at both the local and national level. Readmission rates to U.S. hospitals are high, often because of poor care transitions. Serious adverse drug events ( ADEs) caused by an incomplete understanding of changes in complex drug regimens can be an important factor contributing to readmission rates. This paper describes the roles and responsibilities of pharmacists in ensuring optimal outcomes from drug therapy during care transitions. Barriers to effective care transitions, including inadequate communication, poor care coordination, and the lack of one clinician ultimately responsible for these transitions, are discussed. This paper also identifies specific patient populations at high risk of ADEs during care transitions. Several national initiatives and newer care transition models are discussed, including multi- and interdisciplinary programs with pharmacists as key members. Among their potential roles, pharmacists should participate on medical rounds where available, perform medication reconciliation and admission drug histories, apply their knowledge of drug therapy to anticipate and resolve problems during transitions, communicate changes in drug regimens between providers and care settings, assess the appropriateness and patient understanding of drug regimens, promote adherence, and assess health literacy. In addition, this paper identifies barriers and ongoing challenges limiting greater involvement of pharmacists from different practice settings during care transitions. Professional degree programs and residency training programs should increase their emphasis on pharmacists' roles, especially as part of interdisciplinary teams, in improving patient safety during care transitions in diverse practice settings. This paper also recommends that Accreditation Council for Pharmacy Education ( ACPE) standards include specific language regarding the exposure of students to issues regarding care transitions and that students have several opportunities to practice the skills needed for effective care transitions. Moreover, reimbursement mechanisms that permit greater pharmacist involvement in providing medication assistance to patients going through care transitions should be explored. Although health information technology offers the potential for safer care transitions, pharmacists' use of information technology must be integrated into the national initiatives for pharmacists to be effectively involved in care transitions. This paper concludes with a discussion about the importance of recognizing and addressing health literacy issues to promote patient empowerment during and after care transitions. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this paper was to describe primary care prescribers' perspectives on electronic prescribing drug alerts at the point of prescribing.Design: We used a mixed-method study which included clinician surveys (web-based and paper) and focus groups with prescribers and staff.Participants: Prescribers (n = 157) working in one of 64 practices using 1 of 6 e-prescribing technologies in 6 US states completed the quantitative survey and 276 prescribers and staff participated in focus groups.Measurements: The study measures self-reported frequency of overriding of drug alerts; open-ended responses to: "What do you think of the drug alerts your software generates for you?"Results: More than 40% of prescribers indicated they override drug-drug interactions most of the time or always (range by e-prescribing system, 25% to 50%). Participants indicated that the software and the interaction alerts were beneficial to patient safety and valued seeing drug-drug interactions for medications prescribed by others. However, they noted that alerts are too sensitive and often unnecessary. Participant suggestions included: (1) run drug alerts on an active medication list and (2) allow prescribers to set the threshold for severity of alerts.Conclusions: Primary care prescribers recognize the patient safety value of drug prescribing alerts embedded within electronic prescribing software. Improvements to increase specificity and reduce alert overload are needed. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to review whether the $50m spent by the US National Institute of Mental Health in doing the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trials found any useful evidence to change the clinical management of schizophrenia by psychiatrists. Conclusion: The CATIE trials were conducted in the US on 1460 enrolled patients in an effort to track how the drugs used to treat schizophrenia actually work in clinical practice (rather than in 6-week clinical trials). In a complex 3- phase design, patients were randomized to various types of (mostly) atypical antipsychotic drugs. Some 69-74% of patients switched antipsychotics for one reason or another during the 18 months of treatment. Some of the results were expensive confirmations of known prior results; of the commonly prescribed drugs, clozapine was the most effective, and olanzapine and ziprasidone caused the most and fewest metabolic side effects, respectively. The most stunning finding was that psychiatrists tend to ignore life-threatening, treatable medical conditions in patients presenting for treatment with schizophrenia. Of patients entering the study, 45% had untreated diabetes, 89% had untreated hyperlipidemias and 62% had untreated hypertension. This study failed to reveal anything of significant importance in the psychopharmacological treatment of schizophrenia, but did expose a woeful standard in the medical management of schizophrenia offered by psychiatrists. Psychiatrists should learn to properly treat diabetes, hyperlipidemia and hypertension when detected. [ABSTRACT FROM AUTHOR]

Introduction: An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions.Methods: We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action.Results: A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing boxed warning.Conclusion: Although drugs approved with a boxed warning or priority review are more likely to experience serious post-marketing safety events, other information provided during the FDA drug review that is easy to quantify is generally not associated with post-marketing safety events. It appears that these post-marketing events are not discernible during a pre-marketing review and therefore might not be avoidable using current review data. [ABSTRACT FROM AUTHOR]

In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells. [ABSTRACT FROM AUTHOR]

Depo-Provera is an anti-androgen medication that has been approved by the FDA for use as an injectable contraceptive for women. It has also been used in the treatment of sex offenders. Exactly how this anti-androgen works is not completely known. This paper presents three clinical case studies in which Depo-Provera was an adjunct to the treatment of adult males with sexual behavior problems. A survey of 17 patients currently using DepoProvera in their treatment is outlined. A psychopharmacological explanation of the action of anti-androgens is followed by a study of some of the possible side effects on 61 patients using DepoProvera over a nine-month period. This paper suggests that side effects can be monitored and controlled during treatment, allowing a patient to gain from the benefits of an anti-androgen medication a "sexual vacation" from obsessions and dangerous behaviors during which significant cognitive-behavioral gains can be made. [ABSTRACT FROM AUTHOR]

Background: Migraine imposes a substantial global burden, impacting patients and society. Pharmacotherapy, as a primary treatment, entails specific adverse reactions. Emphasizing these reactions is pivotal for improving treatment strategies and enhancing patients' well-being. Thus, we conducted a comprehensive bibliometric and visual analysis of relevant literature. Methodology: We conducted a comprehensive search on the Science Citation Index Expanded within the Web of Science, restricting the literature for analysis based on criteria such as document type, publication date, and language. Subsequently, we utilized various analytical tools, including VOSviewer, Scimago Graphica, the R package 'bibliometrix', CiteSpace, and Excel programs, for a meticulous examination and systematic organization of data concerning journals, authors, countries/regions, institutions, keywords, and references. Results: By August 31, 2023, the literature was distributed across 379 journals worldwide, authored by 4,235 individuals from 1726 institutions. It featured 2,363 keywords and 38,412 references. 'HEADACHE' led in publication count, with 'SILBERSTEIN S' as the most prolific author. The United States ranked highest in publication volume, with 'UNIV COPENHAGEN' leading among institutions. Conclusion: Our research findings indicate that researchers in the field continue to maintain a focus on the calcitonin gene-related peptide (CGRP) system and explore diverse mechanisms for drug development through the application of novel biotechnological approaches. Furthermore, it is imperative to enhance the assessment of clinical trial outcomes, consistently monitor the efficacy and safety of prominent drugs such as Erenumab and Fremanezumab. There is a need for further evaluation of acute and preventive treatments tailored to different populations and varying types of migraine. [ABSTRACT FROM AUTHOR]

Purpose: This paper investigates consumer attitudes and behavioural intentions related to direct-to-consumer advertising (DTCA) as influenced by the health locus of control and selfefficacy of the consumer. This study examines how consumers' health locus of control and selfefficacy influence their attitude toward a pharmaceutical advertisement and their subsequent intention to obtain a medical prescription. Design/methodology/approach: Using ordinary least squares and Chronbach's alpha, this study measures the attitude towards advertisement and side effects of drugs in advertising. 128 responses of individuals who are in good health comprised the sample size. Findings: The results indicate that attitude toward the advertisement for both benefits and side effects of the DTCA for a specific prescription drug was a determinant in the intentions to seek medical advice. Results also show a strong correlation between HLOC and attitude toward the ad in both benefits and side effects; however, self-efficacy was not significantly correlated to attitude toward the advertisement. Practical/social implications: Pharmaceutical advertisers can adjust and alter ads based on attitudes towards drug side effects. Further research can be done via focus groups and surveys to find what words or alterations may have a positive effect on these attitudes. Originality: This research is unique in that there are no prior studies that examine consumer attitudes toward drug side effects using the General Self Efficacy Scale. [ABSTRACT FROM AUTHOR]

The article discusses the healthcare industry. Topics discussed include paper on ignoring adverse effects (AEs) by Golder and colleagues, statement of the U.S. Food and Drug Administration (FDA) and the pharmaceutical giants on problems emerged after prescriptions are dispensed and issues over execution of clinical trials.

An increase in new drugs first launched in the U.S. and shorter lags between first global drug launch and U.S. approval indicate that the U.S. drug lag has declined. This paper examines the impact of these changes on drug safety using adverse drug reaction data for FDA-approved drugs in 1990 to 2004. Results show two different effects. First, drugs having longer U.S. launch lags (more foreign market experience) have fewer post approval drug risks compared to drugs with shorter launch lags. This result implies that foreign market experience prior to U.S. entry provides information to help alleviate drug-related risks for U.S. patients. Second, drugs that are first launched in the U.S. have fewer serious drug reactions compared to those that were first launched abroad. This result is surprising, and may suggest that first U.S. drug launch signals information about unobserved application quality, which translates into lower post approval drug risks. [ABSTRACT FROM AUTHOR]

This paper outlines aspects of the interface between law and science in the domain of treatment induced injury, using examples drawn from litigation on SSRIs. In the face of claims that randomized controlled trials provide uniquely appropriate evidence and that there should be a statistically significant doubling of the risks on treatment, the examples used demonstrate that the methods of assessing the possibility of causal links between treatment and injuries must necessarily be tailored to both the injury and the treatment. [ABSTRACT FROM AUTHOR]

Atypical antipsychotic use is prevalent in ID, and can result in serious side effects, particularly long-term. The purpose of this paper was to examine side effects over time and adjustments in atypicals in ID, tardive dyskinesia (TD), and akathisia. Side effects of 84 ID adults were assessed across four administrations of the Matson Evaluation of Drug Side-Effects (MEDS). Persons with TD or akathisia who experienced changes in atypicals were more likely to evince side effects. These trends were evident across total MEDS scores and subscales for cardiovascular and hematology, CNS for parkinsonism/dyskinesia and behavioral/akathisia. Atypical antipsychotic use poses a risk for side effects in individuals with ID, particularly in relation to medication adjustments over time and the presence of neuroleptic-induced movement disorders. [ABSTRACT FROM AUTHOR]

Methadone is a synthetic opioid increasingly used for pain management, yet it can be challenging to use safely. The most serious and potentially fatal side effects of methadone are respiratory depression and cardiac arrhythmias. Preventing these side effects is of paramount importance to ensuring the safe use of methadone for pain management. The safe use of methadone is being guided by the US Food and Drug Administration (FDA), the Drug Enforcement Administration (DEA), the manufacturer of methadone (Roxane Laboratories, Inc., Columbus, OH, USA), the Institute for Safe Medication Practices (ISMP), and experts in the field of pain management. The purpose of this paper is to discuss actions taken by the FDA, DEA and the drug manufacturer and to review recommendations made by the ISMP and other experts for initiating, prescribing, dispensing, administering, and monitoring methadone in adults. The main emphasis is on translating practice recommendations into actions that healthcare practitioners should take to safeguard the use of methadone for pain management. [ABSTRACT FROM AUTHOR]

Background: Multi-item adverse drug event (ADE) associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS) with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work. Results: Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total) of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4%) of associations were characterized and validated as known drug-drug interactions. Conclusions: Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA's adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data. [ABSTRACT FROM AUTHOR]

Background: Endocrine disruptors (EDs) and their broad range of potential adverse effects in humans and other animals have been a concern for nearly two decades. Many putative EDs are widely used in commercial products regulated by the Food and Drug Administration (FDA) such as food packaging materials, ingredients of cosmetics, medical and dental devices, and drugs. The Endocrine Disruptor Knowledge Base (EDKB) project was initiated in the mid 1990's by the FDA as a resource for the study of EDs. The EDKB database, a component of the project, contains data across multiple assay types for chemicals across a broad structural diversity. This paper demonstrates the utility of EDKB database, an integral part of the EDKB project, for understanding and prioritizing EDs for testing. Results: The EDKB database currently contains 3,257 records of over 1,800 EDs from different assays including estrogen receptor binding, androgen receptor binding, uterotropic activity, cell proliferation, and reporter gene assays. Information for each compound such as chemical structure, assay type, potency, etc. is organized to enable efficient searching. A user-friendly interface provides rapid navigation, Boolean searches on EDs, and both spreadsheet and graphical displays for viewing results. The search engine implemented in the EDKB database enables searching by one or more of the following fields: chemical structure (including exact search and similarity search), name, molecular formula, CAS registration number, experiment source, molecular weight, etc. The data can be cross-linked to other publicly available and related databases including TOXNET, Cactus, ChemlDplus, ChemACX, Chem Finder, and NCI DTP. Conclusion: The EDKB database enables scientists and regulatory reviewers to quickly access ED data from multiple assays for specific or similar compounds. The data have been used to categorize chemicals according to potential risks for endocrine activity, thus providing a basis for prioritizing chemicals for more definitive but expensive testing. The EDKB database is publicly available and can be found online at http://edkb.fda.gov/webstart/edkb/index.html. Disclaimer: The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Objectives: The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) was designed to evaluate the conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for primary prevention of Alzheimer's dementia (AD). On 17 December 2004, after the Adenoma Prevention with Celecoxib (APC) trial reported increased cardiovascular risks with celecoxib, the ADAPT Steering Committee suspended treatment and enrollment. This paper reports on cardiovascular and cerebrovascular events in ADAPT. Design: ADAPT is a randomized, placebo-controlled, parallel chemoprevention trial with 1-46 mo of follow-up. Setting: The trial was conducted at six field sites in the United States: Baltimore, Maryland; Boston, Massachusetts; Rochester, New York; Seattle, Washington; Sun City, Arizona; and Tampa, Florida. Participants: The 2,528 participants were aged 70 y and older with a family history of AD. Interventions: Study treatments were celecoxib (200 mg b.i.d.), naproxen sodium (220 mg b.i.d.), and placebo. Outcome measures: Outcome measures were deaths, along with nonfatal myocardial infarction (MI), stroke, congestive heart failure (CHF), transient ischemic attack (TIA), and antihypertensive treatment recorded from structured interviews at scheduled intervals. Cox proportional hazards regression was used to analyze these events individually and in several composites. Results: Counts (with 3-y incidence) of participants who experienced cardiovascular or cerebrovascular death, MI, stroke, CHF, or TIA in the celecoxib-, naproxen-, and placebo-treated groups were 28/717 (5.54%), 40/713 (8.25%), and 37/1070 (5.68%), respectively. This yielded a hazard ratio (95% confidence interval [CI]) for celecoxib of 1.10 (0.67-1.79) and for naproxen of 1.63 (1.04-2.55). Antihypertensive treatment was initiated in 160/440 (47.43%), 147/427 (45.00%), and 164/644 (34.08%). This yielded hazard ratios (CIs) of 1.56 for celecoxib (1.26-1.94) and 1.40 for naproxen (1.12-1.75). Conclusions: For celecoxib, ADAPT data do not show the same level of risk as those of the APC trial. The data for naproxen, although not definitive, are suggestive of increased cardiovascular and cerebrovascular risk. [ABSTRACT FROM AUTHOR]

Pharmacovigilance science has traditionally been a discipline focussed on the postmarketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre- and peri-approval stages of drug development, leading to a maturing of drug safety risk management. Further advances in biology, pharmacology and improvements in computational applications to medicine have led to the development of more complex medicines previously unobtainable and have also permitted a more thorough assessment of risks and potential benefits even earlier in the development process. Elevated public concern with the safety of more sophisticated medicines, combined with new science, have led pharmaceutical innovators, regulators and healthcare professionals to collaborate to develop guidelines, which drive enhanced pharmacovigilance and safety risk management earlier in drug development.In this paper, we review international guidelines on pharmacovigilance planning applicable to the pre-approval phases of medicines development and provide author opinion on these guidelines’ potential drug safety implications. We discuss the possible evolution of a pharmaceutical industry model to respond to these guidelines; a view on multidisciplinary safety management teams is provided to encourage refinement of safety-signal identification and risk assessment early in drug development and to communicate important safety concerns to internal research efforts, patients, investigators and regulators. We further describe these functions in the context of the complexities of vulnerable populations, including the example of medicines research for paediatric populations. We also discuss the special role of epidemiology in pre-approval drug development and the impact on epidemiological science of changes to the pharmacovigilance paradigm. [ABSTRACT FROM AUTHOR]

The fairly recent discovery and growing use of costly, revolutionary biotechnology drugs (e.g., GM-CSFs) in hospitals represent a major technical innovation in clinical pharmacy intervention. This paper models the translog production cost impacts of ten distinct clinical pharmacy tasks including pharmacokinetics, consultations with MDs, monitoring drug interactions, . . . , and presents results on decomposed technical change, economies of scope, scale economies, total factor productivity, and the alternatively defined pairwise factor substitution possibilities. The model was fitted to 1981-1990 time-series/cross-sectional data of US hospital pharmacies (source: Eli-Lilly Co.®), Zellner's ISURE (Iterative Seemingly Unrelated Regression Equations) system estimates reveal a non-homothetic underlying technology with biased and pure technical change effects dominating scale-augmentation. Certain clinical tasks increase costs but are cost-saving if jointly produced with selective others. One of the largest and statistically significant economies of scope estimates is between 'monitoring drug interactions' and 'consultations with MDs', Cost implications of findings are given in light of the recent trends in hospital pharmacy clinical activities, related professional health manpower, and piecemeal health policy reforms. [ABSTRACT FROM AUTHOR]

The cardiovascular and cerebrovascular safety of ranibizumab, bevacizumab, and aflibercept for ocular diseases is unclear. This study aimed to evaluate and compare the cardiovascular and cerebrovascular safety in patients receiving ranibizumab, bevacizumab, and aflibercept for ocular disease. A cross‐sectional study was conducted from 2017 (Q1) to 2021 (Q4) in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The outcomes of interest were central nervous system vascular disorders, ischemic heart disease, hypertension, pulmonary hypertension, torsade de pointes/QT prolongation, embolic and thrombotic events, cardiac arrhythmias, cardiac failure, and cardiomyopathy. Data mining was performed by a disproportional method with a compression, using compressed reporting odds ratios (sRORs) with 95% confidence intervals (CIs) to measure signals. The results showed 1462 cardiovascular and cerebrovascular events associated with aflibercept, 834 with ranibizumab, and 150 with bevacizumab. Ranibizumab, bevacizumab, and aflibercept were linked to central nervous system vascular disorders (sROR, 5.57[95%CI, 4.95‐6.26] vs sROR, 2.23 [95%CI, 1.75‐2.85] vs sROR, 2.73[95%CI, 2.43–3.06]), ischemic heart disease (sROR, 3.31[95%CI, 2.65–4.13] vs sROR, 1.98 [95%CI, 1.24‐3.16] vs sROR, 3.00 [95%CI, 2.46‐3.65]), embolic and thrombotic (sROR, 3.36 [95%CI, 3.04‐3.72] vs sROR, 2.16 [95%CI, 1.70‐2.74] vs sROR, 5.25 [95%CI, 4.82‐5.72]). Both ranibizumab and bevacizumab produced hypertension (sROR, 1.73 [95%CI, 1.41‐2.12] vs sROR, 1.46 [95%CI, 1.03‐2.06]) and arrhythmias (sROR, 2.82 [95%CI, 1.99‐3.99] vs sROR, 2.13 [95%CI, 1.08‐4.22]) signals. The signals of heart failure were detected in ranibizumab (sROR, 5.64 [95%CI, 4.08‐7.79]) and aflibercept (sROR, 2.80 [95%CI, 2.03‐3.86]). Ranibizumab, bevacizumab, and aflibercept for ocular disease have different safety profiles in cardiovascular and cerebrovascular. The overall cardiovascular and cerebrovascular risk of the patient should be thoroughly assessed in order to select the safest drug for treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Drug‐induced acute pancreatitis (DIAP) linked to several medications is a diagnosis of exclusion and is associated with significant morbidity and mortality, contributing to the US healthcare cost burden. Existing studies on DIAP focus on the drug classes that can cause acute pancreatitis. Hence, our retrospective study aims to determine the rates and predictors for 30‐day readmissions (30‐DR) in patients with index hospitalization for DIAP. Methods: From the Nationwide Readmissions Database, we followed adults admitted for DIAP who were discharged alive for 30 days. During 30‐DR, we evaluated the rates, predictors, and outcomes of DIAP. Results: Of the 4457 DIAP patients surviving at discharge, 12.5% were readmitted at 30 days. During readmissions, the predictors of 30‐DR for DIAP were young age, the Charlson–Deyo Comorbidity Index of 2 and 3, protein‐energy malnutrition, and dyslipidemia. During 30‐DR, DIAP had a higher mortality rate (2.4% vs. 0.7%; P < 0.020), extended hospital stays (5.6 days vs. 4 days, 0.000), and higher hospital charges ($12 983.6 vs. $8 255.6; P 0.000). Conclusions: DIAP has high 30‐DR rates and poorer outcomes. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the safety of direct-acting antivirals (DAA), even though they are widely used. This study aims to evaluate the adverse events of DAA using post-market data. Methods: FDA Adverse Events Reporting System (FAERS) data from January 2019 through December 2019 were analyzed. FERAS reports in which the suspected drug contained the DAA drugs were extracted and included in the analysis. Univariable and bivariable analyses were performed in this study. Results: Most of the reported side effects were non-serious (62%). The number of times the drug was reported as ineffective was significantly higher while using Harvoni vs. Mavyret (32.14% vs. 1.05%) (p-value < 0.0001). On the other hand, hospitalization was significantly more reported while using Mavyret compared to Harvoni (52.02% vs. 22.45%) (p-value < 0.0001). Liver cancer was significantly more reported while using Harvoni vs. Mavyret (7.65% vs. 1.20%) (p-value < 0.0001). No significant difference in death cases was reported while using both drugs. Conclusion: Depending on the FDA Adverse Events Reporting System (FAERS) database, most of the non-serious adverse effects were headache and fatigue. There was no significant difference in cases of death reported while using both drugs. Liver cancer was more reported while using Harvoni. Hospitalization was more reported while using Mavyret. [ABSTRACT FROM AUTHOR]

The number of drugs with boxed warnings and the detail in the box are much greater in the USA than Australia. US warnings are up to ten times longer and often include a great deal of detail and qualified advice. Australian warnings are usually just a few sentences long and the expected response unequivocal. Other details are relegated to the relevant section within the product information. The restriction of warnings such that they are succinct and used sparingly are explicitly highlighted in the guidelines for boxed warnings in Australia. In addition, the range of other risk management strategies used may be broader. Widespread prescription drug subsidies and mechanisms set up to implement the ''Quality Use of Medicines'' policy provide a complementary range of options. Withdrawal of registration, removal of subsidies for all or selected indications, changed product information and labels, consumer-targeted information, prescriber mail outs, education programmes, restriction to authorised prescribers, and changed pack size and packaging have all been applied at some time in response to safety concerns. The diversity of approaches around the world provides an opportunity for a systematic approach to look at the effects of boxed warnings on prescribing practices so that we might discover what works best. While there are many studies on the effect of warnings from the USA, there are few comparable studies done where different approaches are used. Further, it is not possible to easily examine the total number and purpose of boxed warnings via any government websites. If there were always explicit and potentially verifiable changes in practice as the stated goal for each boxed warning in each jurisdiction and a requirement that the effectiveness of the intervention was measured against these goals, then we might have the evidence base for better policy around boxed warnings. [ABSTRACT FROM AUTHOR]

Abstract: This paper poses three questions: (1) Does mortality from natural causes spike around Christmas and New Year? (2) If so, does this spike exist for all major disease groups or only specialized groups? (3) If twin holiday spikes exist, need this imply that Christmas and New Year are risk factors for death? To answer these questions, we used all official U.S. death certificates, 1979–2004 (n = 57,451,944) in various hospital settings to examine daily mortality levels around Christmas and New Year. We measured the Christmas increase by comparing observed deaths with expected deaths in the week starting on Christmas. The New Year increase was measured similarly. The expected number of deaths was determined by locally weighted regression, given the null hypothesis that mortality is affected by seasons and trend but not by holidays. On Christmas and New Year, mortality from natural causes spikes in dead-on-arrival (DOA) and emergency department (ED) settings. There are more DOA/ED deaths on 12/25, 12/26, and 1/1 than on any other day. In contrast, deaths in non-DOA/ED settings display no holiday spikes. For DOA/ED settings, there are holiday spikes for each of the top five disease groups (circulatory diseases; neoplasms; respiratory diseases; endocrine/nutritional/metabolic diseases; digestive diseases). For all settings combined, there are holiday spikes for most major disease groups and for all demographic groups, except children. In the two weeks starting with Christmas, there is an excess of 42,325 deaths from natural causes above and beyond the normal winter increase. Christmas and New Year appear to be risk factors for deaths from many diseases. We tested nine possible explanations for these risk factors, but further research is needed. [ABSTRACT FROM AUTHOR]

When Samuel Hahnemann devised homoeopathy he constructed multiple arguments that both vehemently supported his new system and criticized the conventional medical practice of his day. At the end of the 19th century when homeopathy had grown within Britain and America, homeopaths failed to make use of some of Hahnemann?s most successful arguments. Instead, homeopaths found themselves lose significant cognitive ground to their long time conventional rivals with the dawn of the 20th century, a ground they have not yet recovered. This paper uses the theoretical framework of Berger and Luckmann to analyse the dynamics of the arguments used against homeopathy and suggests that homeopaths failed to adopt a universalizing medical explanation that was available to them: the reverse action of drugs. Had they used this argument homoeopaths could have explained conventional medicine successes within their own universe of meaning and thus neutralized the impact of conventional on their practice. The implications of these conclusions for the future survival and success of homoeopathy are considered. [ABSTRACT FROM AUTHOR]

Abstract: Background: This paper reports on qualitative research on smoking in contexts associated with drinking among college students. Although a plethora of survey research has shown a positive association between smoking and alcohol use, little attention has been given to the utility functions of these co-occurring behaviors. Methods: Data are drawn from semi-structured interviews with college freshmen at a large Mid-western university in the U.S. (n =35). In addition, eleven focus groups with fraternity and sorority members were conducted (n =70). Interviews and focus groups focused on a range of issues including current smoking behavior, reasons for smoking, and smoking and drinking. Results: A review of qualitative responses reveals that smoking served multiple utility functions for this population including (1) facilitating social interaction across gender, (2) allowing one to structure time and space at a party, (3) enabling “party” smokers to smoke with fewer negative side effects, and (4) helping to calm one down when drunk. Conclusions: Whereas smoking was stigmatized during the context of one''s everyday life as a student, at parties while consuming alcohol, smoking was viewed as normative and socially acceptable. Preventive interventions are needed on college campus that target co-substance use and address widespread misperceptions about the harm of tobacco use and addiction. [Copyright &y& Elsevier]

Background: First-line agents approved in the United States for treatment of relapsing multiple sclerosis (MS) include intramuscular interferon beta (IFNβ)-1a, subcutaneous (SC) IFNβ-1a, SC IFNβ-1b, and SC glatiramer acetate. Intravenous mitoxantrone is the only agent approved for secondary progressive MS, progressive relapsing MS, and worsening relapsing MS. Intravenous natalizumab is approved for relapsing forms of MS generally in patients who have an inadequate response to, or are unable to tolerate, first-line therapies. Corticosteroids are commonly used to treat relapses. This paper reviews the incidence and management of common adverse events (AEs) associated with these treatments.Methods: MEDLINE and EMBASE were searched for clinical trials and other publications between 1985 and 2007 reporting AEs associated with MS therapies, using these search terms: multiple sclerosis, interferon, Avonex, Betaseron, Rebif, glatiramer, copolymer 1, Copaxone, mitoxantrone, natalizumab, adverse events.Results: A class-specific flu-like syndrome associated with IFNβ can be managed through initial dose escalation and administration of analgesics and antipyretics, prophylactically or symptomatically. Injection-site reactions can occur in patients receiving injectable therapies, particularly SC IFNβ or glatiramer acetate. The greatest risk to patients receiving mitoxantrone is cardiotoxicity; thus, the cumulative dose is limited. Allergic reactions occur rarely with natalizumab, and there is a potential risk of progressive multifocal leukoencephalopathy. AEs associated with short-term pulse corticosteroid therapy are usually transient and largely resolve after treatment is completed.Conclusions: To improve adherence to therapy, it is important to educate patients regarding AEs and to manage AEs proactively. [ABSTRACT FROM AUTHOR]

The article presents a study on the management of hepatitis C (HCV) disease among patients with schizophrenia and substance use disorders in the U.S. This study found that the subjects had a significantly higher risk of HCV infection than patients who did not have these diagnoses. However, this paper recommends future studies on the factors that influence testing rates and treatment outcomes in high-risk groups.

Over the past decade and a half, psychedelic drug-induced experiences have been returning to psychiatry as promising new healing modalities. The case of psychedelic-assisted psychotherapy can inform how we think about the context of drug use because psychedelics are commonly considered to be sensitive to the '[mind] set and setting' of their use. As such, epistemic and therapeutic concerns among psychedelic researchers and therapists over the importance of set and setting are interwoven. My ethnography of psychedelic therapeutics both inside and outside of the clinical trials on the east coast of the United States from 2015 to 2019 suggests that there are added political and economic imperatives to contain psychedelic use. Working with this insight, I suggest psychedelic researchers and therapists are producing immense experiences that tend to overflow the attempts at their containment. I also identify two qualities central to the set and setting of the emerging modality of psychedelic-assisted psychotherapy. The first is a labor of protecting spaces which reveals an attentiveness to disconnection that can be read as in tension with the more commonly evoked emphasis on connection found within psychedelic discourses. The second is how psychedelic experiences (as 'mind-manifesting') are understood to reflect the self, and in so doing re-present epistemic disagreements about the nature of the self thus reflected. Taken together, I propose that these two qualities of psychedelic containment offer an analytics for reading the contemporary cultural politics of psychedelic use. [ABSTRACT FROM AUTHOR]

Objective: Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). Methods: We conducted an active comparator safety study of HCQ in a propensity score–matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease‐modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. Results: Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia‐related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68–1.95]). All‐cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non‐HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84–1.34]). During the first 30 days of follow‐up, there were no long QT syndrome events, 2 arrhythmia‐related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). Conclusion: Our findings indicate that the incidence of long QT syndrome and arrhythmia‐related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between adverse events (AEs) suspected to be immune‐related and health care resource utilization, costs, and mortality among patients receiving programmed cell death 1/programmed cell death ligand 1 immune checkpoint inhibitor (ICI) monotherapy for urothelial carcinoma, renal cell carcinoma, non‐small cell lung cancer, or Merkel cell carcinoma. Patients and Methods: We conducted a retrospective cohort study using medical and pharmacy claims and enrollment information from U.S. commercial and Medicare Advantage with Part D enrollees in the Optum Research Database from March 1, 2014, through April 30, 2019. Claims were linked with mortality data from the Social Security Death Index and the National Death Index. Eligible patients had at least one ICI claim between September 1, 2014, and April 30, 2019. Results: After adjusting for potential confounding variables, we found patients with AEs had more than double the risk of an inpatient stay (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.9–2.5) and an 80% higher risk of an emergency visit (HR, 1.8; 95% CI, 1.6–2.1) than patients without AEs. Adjusted 6‐month total costs were $24,301 higher among patients with an AE versus those without ($99,037 vs. $74,736; 95% CI, $18,828–29,774; p <.001). Mean ± SD AE‐related medical costs averaged $2,359 ± $7,496 per patient per month, driven by inpatient visits, which accounted for 89.9% of AE‐related costs. Adjusted risk of mortality was similar in patients with and without AEs. Conclusion: Patients with AEs had higher risks of hospitalizations, emergency room visits, and higher health care costs, driven by inpatient stays, than patients without AEs. The adjusted risk of mortality was similar between the two cohorts. Implications for Practice: Patients taking immune checkpoint inhibitors (ICIs) who had adverse events (AEs) had significantly higher health care costs and utilization, driven by inpatient stays, compared with patients who did not. Given this high cost associated with AEs and the differences in the side effect profile of ICIs versus traditional chemotherapy, it is important for physicians to be cognizant of these differences when treating patients with ICIs. Ongoing evaluation, earlier recognition, and more effective, multidisciplinary management of AEs may improve patient outcomes and reduce the need for costly inpatient stays. This article reports on the association between immune‐related adverse events and health care resource utilization, costs, and mortality among patients receiving PD‐1/PD‐L1 immune checkpoint inhibitor monotherapy for urothelial carcinoma, renal cell carcinoma, non‐small cell lung cancer, or Merkel cell carcinoma. [ABSTRACT FROM AUTHOR]

Background and Aims: Naloxone access laws (NALs) have been suggested to be an important strategy to reduce opioid‐related harm. We describe the evolution of NALs across states and over time and review existing evidence of their overall association with naloxone distribution and opioid overdose as well as the potential effects of specific NAL components. Methods: Descriptive analysis of temporal variation in US regional adoption of NAL components, accompanied by a systematic search of 13 databases for studies (published between 2005 and 20 December 2019) assessing the effects of NALs on naloxone distribution or opioid‐related health outcomes. Eleven studies, all published since 2018, met inclusion criteria. Study time‐frames spanned 1999–2017. Opioid‐related overdose mortality, emergency department episodes and naloxone distribution were correlated with the presence of a NAL and, where data were available, NAL components. Results: Existing evidence suggests mixed, but generally beneficial, effects for NALs. Nearly all studies show that NALs, particularly those that permit naloxone distribution without patient‐specific prescriptions, are associated with increased naloxone access [incidence rate ratios (IRR) range from 1.40, 95% confidence interval (CI) = 1.15–1.66 to 7.75, 95% CI = 1.22–49.35] and increased opioid‐related emergency department visits (IRR range from 1.14, 95% CI = 1.07–1.20 to 1.15, 95% CI = 1.02–1.29). Most studies show NALs are associated with reduced overdose mortality, although findings vary depending on the specific NAL components and time‐period analyzed (IRR range from 0.66, 95% CI = 0.42–0.90 to 1.27, 95% CI = 1.27–1.27). Few studies account for the variation in opioid environments (i.e. illicit versus prescription) or other policy dimensions that may be correlated with outcomes. Conclusions: The existing literature on naloxone access laws in the United States supports beneficial effects for increased naloxone distribution, but provides inconclusive evidence for reduced fatal opioid overdose. Mixed findings may reflect variation in the laws' design and implementation, confounding effects of concurrent policy adoption, or differential effectiveness in light of changing opioid environments. [ABSTRACT FROM AUTHOR]

Introduction: Colchicine is currently approved for the treatment of gout and familial Mediterranean fever, among other conditions. Clarithromycin, a strong inhibitor of CYP3A4 and P-glycoprotein, dramatically increases colchicine's half-life, augmenting the risk of a life-threatening adverse reaction when used inadvertently with colchicine.Objectives: The aim of this study was to examine the evidence and clinical implications of concomitant use of colchicine and clarithromycin.Methods: Case reports of colchicine-clarithromycin co-administration were searched using the FDA's Adverse Event Reporting System (FAERS) database. PubMed, EMBASE, and Web of Science electronic databases were also searched from January 2005 through November 2019 for articles reporting colchicine-clarithromycin concomitant use. Individual reports were reviewed to identify consequences of coadministration, dose, days to onset of interaction, symptoms, evidence of renal disease, time to resolution of symptoms, and Drug Interaction Probability Scale (DIPS) rating.Results: The FAERS search identified 58 reported cases, nearly 53% of which were from patients aged between 65 and 85 years. Of 30 reported deaths, 11 occurred in males, and 19 in females. Other frequent complications reported in FAERS included diarrhea (31%), pancytopenia (22%), bone marrow failure (14%), and vomiting (14%). From published literature, we identified 20 case reports of concomitant exposure, 19 of which were rated 'probable' and one 'possible' according to DIPS rating. Of these cases, four 'probable' patients expired. The documented onset of colchicine toxicity occurred within 5 days of starting clarithromycin, and death within 2 weeks of concomitant exposure.Conclusion: Clinical manifestations of colchicine-clarithromycin interaction may resemble other systemic diseases and may be life threatening. Understanding this clinically meaningful interaction can help clinicians avoid unsafe medication combinations. [ABSTRACT FROM AUTHOR]