Adherence, clinical benefits, and adverse effects of endocrine therapies among women with nonmetastatic breast cancer in developing countries: A systematic review and meta-analysis.

BACKGROUND: Despite significant advances in breast cancer control and survival with endocrine therapies (ETs), treatment utilization and outcomes in developing countries have not been adequately explored. This review evaluated ET adherence, potential benefits, and harms in populations across developing countries. METHODS: A literature search was conducted through August 2023 in five databases: PubMed, Cochrane Library, Web of Science, Global Health, and WHO Global Index Medicus. Retrieved records were screened to identify observational research presenting at least one outcome in women with nonmetastatic breast cancer in developing countries who received ET (tamoxifen or aromatase inhibitors). A random effects model was used to compute the rates of adherence, discontinuation, adverse events (AEs), disease progression, and death. RESULTS: A total of 104 studies met the inclusion criteria. Risk of bias was low in most studies, and a large portion of the patients involved Asians. The overall heterogeneity between studies was partially attributed to variations in study design or outcome measurement method. Results showed a pooled adherence rate of 75% (95% confidence interval [CI], 67%-81%) and a discontinuation rate of 16% (95% CI, 10%-25%). Treatment side effects and young age consistently emerged as significant predictors of nonadherence. A wide range of AEs was identified in our analysis. The estimated average rates of cancer recurrence and mortality at 5-years were 16% and 8%, respectively. CONCLUSIONS: The findings of this study underscore suboptimal ET use in developing countries and provide comprehensive insights into treatment experiences in the real-world setting. Targeted strategies are warranted to enhance adherence and subsequently optimize treatment benefits.

Bruton tyrosine kinase inhibitor monotherapy in B-cell lymphoma and risk of infection: A systematic review and meta-analysis of randomized controlled trials.

Bruton's tyrosine kinase (BTK) inhibitors are important therapeutic advances with promising efficacy outcomes in the treatment of patients with chronic lymphocytic leukemia and other B-cell lymphoma subtypes. However, the utility of BTK inhibitors can be limited by adverse events such as infections. In this systematic review and meta-analysis, we aim to determine the risk of various infections associated with BTK inhibitor monotherapy in B-cell lymphoma patients. A comprehensive search was conducted in MEDLINE/PubMed, Embase, and Web of Science databases from their inception until October 2023. ClinicalTrials.gov, bibliographies, and relevant conference abstracts were also searched for additional records. Randomized controlled trials that included any B-cell lymphoma patients treated with BTK inhibitor monotherapy and reported infection were included. Meta-analysis was performed to calculate risk ratio (RR) using a random-effects model in R Statistical Software, version 4.3.2. Of 3292 studies retrieved, we included 12 studies in this systematic review and meta-analysis. The median age of patients across the study arms ranged between 64 and 73 years. The overall pooled RR for any grade upper respiratory tract infections (URTI) associated with BTK inhibitor treatment was 1.55 (95% Confidence Interval (CI) 1.22-1.97). The RR of grade ≥3 URTI was reported in 14 out of 1046 patients, yielding an RR of 1.46 (95% CI 0.61-3.54), which was not statistically significant. The pooled RR of any grade pneumonia was 1.20 (95% CI 0.68-2.10) and grade ≥3 pneumonia was 1.12 (95% CI 0.67-1.85), both of which were not statistically significant. Patients with B-cell lymphoma who are undergoing BTK inhibitor monotherapy face an elevated risk of developing URTI. Clinicians prescribing BTK inhibitors should be aware of the potential infectious events that may occur. Close monitoring and the implementation of effective prophylactic measures are essential for managing these patients.

Exploring Safety in Gender-Affirming Hormonal Treatments: An Observational Study on Adverse Drug Events Using the Food and Drug Administration Adverse Event Reporting System Database.

BACKGROUND: People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking. OBJECTIVE: To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity. RESULTS: For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%). CONCLUSIONS AND RELEVANCE: The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution.

Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS).

BACKGROUND: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). OBJECTIVE: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). METHODS: We conducted a disproportionality analysis using FAERS data from January 2004 through June 2020. The reporting odds ratio (ROR) and observed-to-expected ratio (O/E) with shrinkage for adverse events related to colchicine's toxicity (ie, rhabdomyolysis/myopathy, agranulocytosis, hemorrhage, acute renal failure, hepatic failure, arrhythmias, torsade de pointes/QT prolongation, and cardiac failure) were compared between FAERS reports. RESULTS: A total of 787 reports included the combined mention of colchicine, an inhibitor of both CYP3A4 and P-gp drug, and an adverse event of interest. Among reports that indicated the severity, 61% mentioned hospitalization and 24% death. A total of 37 ROR and 34 O/E safety signals involving colchicine and a CYP3A4/P-gp inhibitor were identified. The strongest ROR signal was for colchicine + atazanavir and rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6), and the strongest O/E signal was for colchicine + atazanavir and agranulocytosis (O/E = 3.79, 95% credibility interval: 3.44-4.03). CONCLUSION AND RELEVANCE: This study identifies numerous safety signals for colchicine and CYP3A4/P-gp inhibitor drugs. Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended.

Cost-effectiveness analysis of five anti-obesity medications from a US payer's perspective.

BACKGROUND AND AIMS: To determine the cost-effectiveness of anti-obesity medications (AOM): tirzepatide, semaglutide, liraglutide, phentermine plus topiramate (PpT), and naltrexone plus bupropion (NpB). METHODS AND RESULTS: From a U.S. perspective we developed a Markov model to simulate weight change over a 40-year time horizon using results from clinical studies. According to the body mass index (BMI), cardiovascular diseases, diabetes and mortality risk were the health states considered in the model, being mutually exclusive. Costs of AOM, adverse events, cardiovascular events, and diabetes were included. We applied a 3% per-year discount rate and calculated the incremental cost-effectiveness ratios (ICERs) of cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analyses incorporated uncertainty in input parameters. A deterministic analysis was conducted to determine the robustness of the model. The model included a cohort of 78.2% females with a mean age of 45 years and BMI of 37.1 (SD 4.9) for females and 36.8 (SD 4.9) for males. NpB and PpT were the least costly medications and, all medications differed no more than 0.5 QALYs. Tirzepatide ICER was $355,616 per QALY. Liraglutide and semaglutide options were dominated by PpT. CONCLUSION: Compared to other AOM, PpT was lowest cost treatment with nearly identical QALYs with other agents.

Colchicine and macrolides: a cohort study of the risk of adverse outcomes associated with concomitant exposure.

Colchicine is increasingly used as the number of potential indications expands. However, it also has a narrow therapeutic index that is associated with bothersome to severe side effects. When concomitantly use with medications inhibiting its metabolism, higher plasma levels will result and increase likelihood of colchicine toxicity. We conducted a cohort study using electronic health records comparing encounters with colchicine plus a macrolide and colchicine with an antibiotic non-macrolide. We assessed the relationship between the two groups using adjusted multivariate logistic regression models and the risk of rhabdomyolysis, pancytopenia, muscular weakness, heart failure, acute hepatic failure and death. 12670 patients on colchicine plus an antibiotic non-macrolide were compared to 2199 patients exposed to colchicine plus a macrolide. Patients exposed to colchicine and a macrolide were majority men (n = 1329, 60.4%) and white (n = 1485, 67.5%) in their late sixties (mean age in years 68.4, SD 15.6). Heart failure was more frequent in the colchicine plus a macrolide cohort (n = 402, 18.3%) vs the colchicine non-macrolide one (n = 1153, 9.1%) (p < 0.0001) and also had a higher mortality rate [(85 (3.87%) vs 289 (2.28%), p < 0.0001 macrolides vs non-macrolides cohorts, respectively]. When the sample was limited to individuals exposed to either clarithromycin or erythromycin and colchicine, the adjusted OR for acute hepatic failure was 2.47 (95% CI 1.04-5.91) and 2.06 for death (95% CI 1.07-3.97). There is a significant increase in the risk of hepatic failure and mortality when colchicine is concomitantly administered with a macrolide. Colchicine should not be used concomitantly with these antibiotics or should be temporarily discontinued to avoid toxic levels of colchicine.

Complications Associated with Foodborne Listeriosis: A Scoping Review.

Listeria monocytogenes is a relatively rare but highly pathogenic bacterium that can cause foodborne infections. In the United States there are ∼1600 cases per year, 94% of which result in hospitalizations and 20% in deaths. Per-case burden is high because the disease also causes serious complications, including sepsis, encephalitis, meningitis, miscarriage, and stillbirth. The disease burden of L. monocytogenes is underestimated because some of these acute complications can also result in long-term outcomes. In this article, we conducted a scoping review of L. monocytogenes complications and longer term outcomes from articles published between 2000 and 2018. Search terms were developed for four major databases (PubMed, Scopus, Web of Science, and Embase) as well as gray literature and hand searches of review articles. We follow standard scoping review methodology and assessment. Out of 10,618 unique articles originally identified, 115 articles were included, representing 49 unique outcomes. The majority of studies were cohort designs (n = 67) and conducted in the United States or Europe (n = 98). Four major outcome groupings were death, neurological disorders, sepsis, and congenital infection. This study identifies substantial research on the common acute complications of L. monocytogenes and few long-term consequences of L. monocytogenes. We identify the need for additional studies to determine the longer term impacts of these acute complications.

Scoping Review of Toxoplasma Postinfectious Sequelae.

Previous economic estimates of infection with Toxoplasma gondii and chronic sequelae following infection lack sufficient data to establish the true burden of disease and its chronic sequelae. This scoping review aims to fill this gap by updating existing literature regarding the development of postinfectious sequelae following T. gondii infection. Literature published between January 1, 2000, and November 6, 2018, in PubMed, EMBASE, and Scopus was searched for a wide range of postinfectious sequelae and economic estimate terms. This scoping review includes summaries from the 108 articles covering 5 main groupings of outcomes (categories are not exclusive) including vision disorders (n = 58), psychological and mental health disorders (n = 27), neurological disorders (n = 17), fetal death and infection (n = 15), and hearing loss (n = 6), as well as a description of other outcomes reported. While the majority of the included studies assessed the incidence of these outcomes postinfection, very few followed participants long-term. These prospective studies are needed to understand the true burden of postinfectious sequelae over the life course, particularly because congenital infection with Toxoplasma can lead to severe outcomes for newborns. This scoping review can be used as an important resource for other researchers wishing to conduct future systematic reviews and meta-analyses, as well as for policy makers interested in developing guidance for public and health care partners.

Expanding pharmacists' roles: Pharmacists' perspectives on barriers and facilitators to collaborative practice.

OBJECTIVE: The pharmacy profession is shifting from transactional dispensing of medication to a more comprehensive, patient-centered model of care. Collaborative practice agreements (CPAs) extend the role of a pharmacist to initiate, monitor, modify, and discontinue drug therapies and provide other clinical services. Although collaborative practice has been shown to improve health system efficiency and patient outcomes, little is known about how pharmacists perceive CPAs. To explore pharmacists' perspectives of CPAs, including barriers and facilitators to CPA implementation. METHODS: Semistructured key informant interviews were used to elicit information from licensed pharmacists practicing in a variety of settings in Arizona. Thematic analysis was used to identify key qualitative themes. RESULTS: Seventeen interviews of pharmacists with (n = 11, 64.7%) and without (n = 6, 35.3%) CPAs were conducted in April-May 2019. The pharmacists saw their role in CPAs as supportive, filling a care gap for overburdened providers. A heightened sense of job satisfaction was reported owing to increased pharmacist autonomy, application of advanced knowledge and clinical skills, and ability to have a positive impact on patients' health. Challenges to the implementation of CPAs included liability and billing issues, logistic concerns, some experiences with provider hesitancy, and lack of information and resources to establish and maintain a CPA. The barriers could be overcome with conscious team-building efforts to establish trust and prove the worth of pharmacists in health care teams; strategic engagement of stakeholders in the development of CPAs, including billing and legal departments; and mentorship in the CPA creation process. CONCLUSIONS: The pharmacists in this study enjoyed practicing collaboratively and had overall positive perceptions of CPAs. As health worker shortages become more dire and pharmacy practice evolves to expand the role of pharmacists in providing direct patient care, CPAs will be an important tool for restructuring care tasks within health systems.

Benefit of Incorporating Clinical Pharmacists in an Adult Intensive Care Unit: A Cost-saving Study.

WHAT IS KNOWN AND OBJECTIVE: A framework to evaluate the impact of clinical pharmacists in intensive care units (ICUs) in Chile has not yet been established. This study evaluates the cost avoidance and cost-benefit ratios of clinical pharmacist interventions in terms of treatment optimization in an adult ICU in southern Chile. METHODS: Clinical pharmacist interventions in a multidisciplinary adult ICU were assessed between January and December 2019. Only interventions suggested by pharmacists and accepted by the healthcare team were included in the analysis. Interventions were classified into six categories, and cost avoidance (in US dollars) was calculated for each category using a systematic validated approach. A cost-benefit ratio for clinical pharmacy services in the adult ICU was also calculated. RESULTS AND DISCUSSION: Over the 12-month period, 505 interventions were performed in 169 patients, of whom 62% were male. Interventions were classified into the following six categories: adverse drug event prevention (18%), which led to $87 882 in savings; resource utilization (ie change in medication route) (10%), which led to $50 525 in savings; individualization of patient care (ie dose adjustment) (36%), which led to $57 089 in savings; prophylaxis (ie initiation of stress ulcer prophylaxis) (<1%), which led to $167 in savings; hands-on care (ie bedside monitoring) (23%), which led to $57 846 in savings; and administrative and supportive tasks (ie patient own medication evaluation) (13%), which led to $9988 in savings. The total cost savings over the year-long period were $263 500, resulting in a cost-benefit ratio of 1:24.2. WHAT IS NEW AND CONCLUSION: The participation of a clinical pharmacist in a multidisciplinary ICU team reduces healthcare expenditures through treatment optimization translated into cost avoidance. This study has corroborated prior evidence that clinical pharmacist involvement in ICUs provides economic value and quality assurance in healthcare settings.

Chronic Gastrointestinal and Joint-Related Sequelae Associated with Common Foodborne Illnesses: A Scoping Review.

To strengthen the burden estimates for chronic sequelae of foodborne illness, we conducted a scoping review of the current literature for common foodborne pathogens and their associated sequelae. We aim to describe the current literature and gaps in knowledge of chronic sequelae associated with common foodborne illnesses. A comprehensive search was conducted in PubMed, EMBASE, and Web of Science for peer-reviewed articles published January 1, 2000 to April 1, 2018. Articles available in English, of any epidemiological study design, for 10 common foodborne pathogens (Campylobacter, Salmonella, Escherichia coli, Listeria, Shigella, Cryptosporidium, Cyclospora, Giardia, Yersinia, and norovirus) and their associated gastrointestinal (GI)- and joint-related sequelae were included. Of the 6348 titles screened for inclusion, 380 articles underwent full-text review; of those 380, 129 were included for data extraction. Of the bacterial pathogens included in the search terms, the most commonly reported were Salmonella (n = 104) and Campylobacter (n = 99); E. coli (n = 55), Shigella (n = 49), Yersinia (n = 49), and Listeria (n = 15) all had fewer results. Norovirus was the only virus included in our search, with 28 article that reported mostly GI-related sequelae and reactive arthritis (ReA) reported once. For parasitic diseases, Giardia (n = 26) and Cryptosporidium (n = 18) had the most articles, and no results were found for Cyclospora. The most commonly reported GI outcomes were irritable bowel syndrome (IBS; n = 119) and inflammatory bowel disease (n = 29), and ReA (n = 122) or "joint pain" (n = 19) for joint-related sequelae. Salmonella and Campylobacter were most often associated with a variety of outcomes, with ReA (n = 34 and n = 27) and IBS (n = 17 and n = 20) reported most often. This scoping review shows there are still a relatively small number of studies being conducted to understand specific pathogen/outcome relationships. It also shows where important gaps in the impact of chronic sequelae from common foodborne illnesses still exist and where more focused research would best be implemented.

Pharmacists' perceptions of the pharmacists' patient care process and performance in a simulated patient interaction.

OBJECTIVES: To (1) evaluate the use of the pharmacists' patient care process (PPCP) by licensed pharmacists through a simulated patient activity and (2) describe pharmacists' awareness and perceptions of the PPCP in the state of Arizona. DESIGN: Interviews were conducted to elicit pharmacists' perceptions and awareness of the PPCP. A simulated patient activity involved a role-play pharmacist-patient interaction in a community pharmacy setting. The PPCP was employed as the evaluative framework to assess pharmacist behavior. SETTING AND PARTICIPANTS: Pharmacists licensed in the state of Arizona practicing in various pharmacy settings were recruited through e-mail list serves and snowball recruitment. Data were collected in person, by telephone, and via video chat. OUTCOME MEASURES: Emergent qualitative themes from interviews were used to describe pharmacists' awareness and perceptions of the PPCP. The presence or absence of PPCP elements were assessed during the simulations. RESULTS: A total of 17 pharmacists were interviewed; 16 participated in the simulated activity. Of these, 7 (41.2%) participants recalled specific details regarding the PPCP process. Participants felt that the PPCP accurately reflected their daily workflow. Accordingly, a mean of 15.8 of the 19 PPCP elements was observed in simulated pharmacist-patient interactions, still allowing room for improvement in pharmacist-led care planning. Participants indicated perceived value in a shared patient care process that facilitates collaboration with myriad health professionals and as an aid to leverage pharmacists' role on health care teams. CONCLUSION: In this study, pharmacists practicing in Arizona in various settings expressed an awareness of the PPCP, felt it accurately reflected the work they do, and expressed that the tool potentially added value to their work.

[Pharmacokinetics/pharmacodinamic (PK/PD) evaluation of a short course of oral administration of metronidazole for the management of infections caused by Bacteroides fragilis]. / Evaluación farmacocinética/farmacodinámica (PK/PD) de un esquema de administración oral de metronidazol en intervalo ampliado para el manejo de infecciones producidas por Bacteroides fragilis.

INTRODUCTION: Metronidazole is the antibiotic of choice for the management of infections caused by anaerobes. Its administration requires multiple daily doses causing increased medication errors. Due to its high post-antibiotic effect and rapid concentration-dependent bactericidal activity, administration of this antibiotic in an extended dosing interval would achieve PK/PD parameters effectively. OBJECTIVE: To assess the probability of achieving effective PK/PD relationship with the administration of 1,000 mg every 24 hours of metronidazole for Bacteroides fragilis infections. METHODS: A clinical trial was conducted in a group of volunteers who received a single oral dose of 500 or 1,000 mg of metronidazole. Determinations of values of Cmax, t max, and AUCC0-24 h. determined using the trapezoidal method, were obtained for a Markov simulation that would allow for determining the likelihood of achieving a AUC0-24 h/MIC ratio above 70 for infections caused by susceptible B. fragilis. RESULTS: Cmax (24,03 ± 6,89 mg/L) and t max (1,20 ± 0.80 hrs) and the value of AUC0-24 h (241.91 ± 48.14 mg * h/L) were determined. The probability of obtaining a AUC0-24 h/MIC ratio greater than 70 was greater than 99%. CONCLUSION: From a pharmacokinetic perspective, with the administration of a daily dose of 1,000 mg of metronidazole, it is possible to achieve a therapeutic goal of AUC0-24 h/MIC ratio above 70 for the treatment of anaerobic infections.

Innovation, affordability, access: Alzheimer disease drugs and the Inflation Reduction Act.

OBJECTIVES: This analysis examines the implications of new Alzheimer disease drugs in the era of the Inflation Reduction Act (IRA). It focuses on balancing innovation in Alzheimer disease treatment with affordability and access, assessing the impact on Medicare's budget, patient cost, and health care system readiness. STUDY DESIGN: A comprehensive review was conducted, synthesizing information from recent FDA drug approvals, drug pricing models, Medicare coverage policies, and the updated regulations under the IRA. This analysis reflects on the broader clinical and economic consequences of introducing new Alzheimer disease treatments. METHODS: The study employs a qualitative review of existing literature, policy documents, and economic data. It explores the implications of Alzheimer disease drugs on health care policy, analyzing the economic and clinical impacts within the current health care landscape in the US. RESULTS: The study highlights the economic challenges posed by the high costs of new Alzheimer disease drugs, contrasting with their moderate clinical benefits and potential risks. It discusses the limitations of the IRA in regulating drug prices and the resulting implications for Medicare's budget. Additionally, it examines disparities in health care access and system preparedness for these new treatments. CONCLUSIONS: The study findings underscore the need for a comprehensive approach to ensure fair pricing and equitable access to Alzheimer disease treatments. It suggests the application of frameworks such as the ISPOR Value Flower, focusing on diversity, equity, and comprehensive economic evaluations, to navigate the evolving landscape of Alzheimer disease treatment in the context of the IRA.

Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis.

Importance: Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety. Objective: To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety. Data Sources: MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023. Study Selection: Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened. Data Extraction and Synthesis: Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results. Main Outcomes and Measures: The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety. Results: Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder. Conclusions and Relevance: In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

Chimeric antigen receptor T-cell immunotherapies adverse events reported to FAERS database: focus on cytopenias.

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04-53.00), leukopenia (4.04, 95%CI 3.52-4.64), and thrombocytopenia (4.01, 95%CI 3.19-5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia.

Cost-effectiveness analysis of nivolumab-chemotherapy as first-line therapy for locally advanced/metastatic gastric cancer: a United States payer perspective.

OBJECTIVES: Nivolumab, an immune checkpoint inhibitor, was approved by the United States (US) Food and Drug administration as a first-line systemic therapy for locally advanced/metastatic gastric cancer patients. The current study aimed to investigate the cost-effectiveness of nivolumab-chemotherapy combination versus chemotherapy alone as a first-line therapy from a US payer perspective. METHODS: An economic evaluation was conducted using a partitioned survival model in Microsoft Excel® using data from the CheckMate 649 trial. Three discrete mutually exclusive health states (progression-free, post-progression, and death) were included in the model. The health state occupancy was calculated using the overall survival and progression-free survival curves derived from the CheckMate 649 trial. Cost, resource use, and health utility estimates were estimated from a US payer perspective. Deterministic and probabilistic sensitivity analyses assessed the uncertainty of the model parameters. RESULTS: Nivolumab-chemotherapy provided additional 0.25 life years compared to chemotherapy alone and the quality-adjusted life years (QALYs) were 0.701 and 0.561, respectively, producing a gain of 0.140 QALYs and an incremental cost-effectiveness ratio of $574,072/QALY. CONCLUSION: From the US payer perspective, at a willingness to pay threshold of $US150,000/QALY, nivolumab-chemotherapy was not found to be cost-effective as a first-line therapy for locally advanced/metastatic gastric cancer.

Barriers to Adoption of Tailored Drug-Drug Interaction Clinical Decision Support.

OBJECTIVE: Despite the benefits of the tailored drug-drug interaction (DDI) alerts and the broad dissemination strategy, the uptake of our tailored DDI alert algorithms that are enhanced with patient-specific and context-specific factors has been limited. The goal of the study was to examine barriers and health care system dynamics related to implementing tailored DDI alerts and identify the factors that would drive optimization and improvement of DDI alerts. METHODS: We employed a qualitative research approach, conducting interviews with a participant interview guide framed based on Proctor's taxonomy of implementation outcomes and informed by the Theoretical Domains Framework. Participants included pharmacists with informatics roles within hospitals, chief medical informatics officers, and associate medical informatics directors/officers. Our data analysis was informed by the technique used in grounded theory analysis, and the reporting of open coding results was based on a modified version of the Safety-Related Electronic Health Record Research Reporting Framework. RESULTS: Our analysis generated 15 barriers, and we mapped the interconnections of these barriers, which clustered around three entities (i.e., users, organizations, and technical stakeholders). Our findings revealed that misaligned interests regarding DDI alert performance and misaligned expectations regarding DDI alert optimizations among these entities within health care organizations could result in system inertia in implementing tailored DDI alerts. CONCLUSION: Health care organizations primarily determine the implementation and optimization of DDI alerts, and it is essential to identify and demonstrate value metrics that health care organizations prioritize to enable tailored DDI alert implementation. This could be achieved via a multifaceted approach, such as partnering with health care organizations that have the capacity to adopt tailored DDI alerts and identifying specialists who know users' needs, liaise with organizations and vendors, and facilitate technical stakeholders' work. In the future, researchers can adopt the systematic approach to study tailored DDI implementation problems from other system perspectives (e.g., the vendors' system).