Preferred Drug Research Articles

Uncovering patients’ preferences for brand among essential classes of coronary heart disease medications using a discrete choice experiment

Patient preferences for medications strongly correlate with adherence; one area of interest is the choice between branded and generic drugs. Despite extensive research about brand-versus-generic drug preferences, few studies have explored severe-illness patients like those with coronary heart disease (CHD). We could not locate studies measuring preference weights of branded drugs in different classes within guideline-recommended regimens using discrete choice experiments (DCE). We aimed to explore the preference for branded medications used for secondary prevention of CHD events among patients receiving treatment at one of the largest Egyptian health insurance clinics. Patients with CHD were interviewed to choose between various therapy regimens containing brand-name and generic versions of aspirin, beta-blockers, statins, and renin–angiotensin–aldosterone system blockers (RAAS blockers). The study employed a DCE technique and followed the recommendations of the International Society of Pharmacoeconomics and Outcomes Research (ISPOR). Seventy-two percent (149) of the 208 patients questioned were dissatisfied with at least one of their generic medications. The majority of unsatisfied patients displayed brand preferences across the four medicine classes, primarily due to the notion that generics may be less effective. Patients preferred the RAAS blocker brand the most (adjusted odds ratio [AOR]: 3.14; 95% confidence interval [CI] 2.83 to 3.48), followed by beta-blockers (AOR: 2.06; 95% CI 1.88 to 2.27) and statins (AOR: 1.5; 95% CI 1.50 to 1.61). The relative importance of each class from the patient’s perspective showed the highest importance with RAAS blockers (22.2%) and beta-blockers (14.1%), while statins and aspirin had minor importance (7.8% and 6.6%, respectively). In the present study, branded drugs for secondary CHD prevention were preferred over generic alternatives. This finding has two implications for clinical practice. Firstly, physicians and pharmacists need to assure patients about the quality of generics to insure patient satisfaction and adherence to medication. Secondly, health insurance providers need to confirm the effectiveness of generics through observational studies. Despite the well-proven protective effects of aspirin and statins, they had minor importance from the patient’s perspective, highlighting the need to enhance patient knowledge. DCE was demonstrated to be a useful tool for eliciting the genuine preferences of patients treated within the setting of health insurance.

Effect of Atomoxetine on Mouse Isolated Vas Deferens Contractility

Objective: Atomoxetine (ATX), a selective noradrenaline re-uptake inhibitor, is a preferred drug with sufficient efficacy and favorable safety profile for the treatment of attention-deficit hyperactivity disorder. Ejaculatory dysfunctions have been reported in the patients receiving ATX as sexual side effect, of which underlying mechanisms are largely unknown. The present study aimed to investigate the effect of ATX on mouse isolated vas deferens (VD) contractility as a potential mechanism of ATX-induced ejaculatory dysfunction. Material and Methods: Isolated organ bath studies were performed on prostatic parts of VD obtained from adult male Balb/c mice. The effect of ATX (10-6, 10-5, 3x10-5 and 10-4 M) on KCl (80 mM), phenylephrine (PhE, 3x10-4 M), adenosine 5’-triphosphate (ATP, 10-2 M) and electrical field stimulation (EFS; 100 V, 64 Hz)-induced contractions of VD strips were evaluated in concentration dependent manner. Results: ATX at 10-6 and 10-5 did not alter the contractile responses (p>0.05), however, higher concentrations of ATX (3x10-5 or 10-4 M) significantly inhibited the KCl, PhE, ATP and EFS-induced contractions of VD strips (p<0.05). Conclusion: The present study demonstrated for the first time that ATX decreased the contractile responses of mouse isolated VD concentration-dependently. Our results suggest that ejaculatory dysfunction might be related to the inhibitory effect on ATX on VD.

Instrumental variable analysis with categorical treatment.

Current instrumental variable methodology focuses mainly on estimating causal effects for a dichotomous or an ordinal treatment variable. Situations with more than two unordered treatments are less explored. The challenge is that assumptions needed to derive point-estimators become increasingly stronger with the number of relevant treatment alternatives. In this article, we aim at deriving causal point-estimators for head-to-head comparisons of the effect of multiple relevant treatments or interventions. We will achieve this with a set of plausible and well-defined rationality assumptions while only considering ordinal instruments. We demonstrate that our methodology provides asymptotically unbiased estimators in the presence of unobserved confounding effects in a simulation study. We then apply the method to compare the effectiveness of five anti-inflammatory drugs in the treatment of rheumatoid arthritis. For this, we use a clinical data set from an observational study in Norway, where price is the primary determinant of the preferred drug and can therefore be considered as an instrument. The developed methodology provides an important addition to the toolbox for causal inference when comparing more than two interventions influenced by an instrumental variable.

Use of immunomodulatory treatment for non-infectious uveitis: an International Ocular Inflammation Society report of real-world practice.

Non-infectious uveitis is a diverse group of inflammatory conditions that collectively account for substantial blindness worldwide. Expert guidelines and results of clinical trials guide treatment, but real-world clinical care is impacted by additional factors. In 2023, an international group of uveitis-specialised ophthalmologists formed the International Study Group for Systemic Immunomodulatory Drug Treatment of Non-Infectious Uveitis to report current practice. 221 study group members from 53 countries completed a 30-item questionnaire on their management of non-infectious uveitis including: indications for and investigations prior to initiating systemic immunomodulatory drugs, use of conventional and biological drugs, and follow-up of treated patients. Major indications to initiate systemic immunomodulatory drugs were: uveitis not controlled with oral prednis(ol)one (n=208, 94.1%), specific uveitis diagnosis (n=197, 89.1%), and patient intolerance of oral prednis(ol)one (n=186, 84.2%). All members (n=221, 100%) performed pretreatment screens including: blood chemistry (n=217, 98.2%), blood examination (n=207, 93.7%), and Quantiferon assay (n=196, 88.7%). Eight conventional and 14 biological drugs were prescribed: methotrexate was the preferred conventional drug overall (n=126, 57.0%) and for 9 of 11 uveitides, and adalimumab was the preferred biological drug overall (n=216, 97.7%) and for 11 of 11 uveitides. When drugs were combined, methotrexate plus adalimumab was most popular (n=158 of 188 members, 84.0%). Patients with inactive uveitis were typically evaluated and screened for drug toxicity every 6-12 weeks (n=161, 72.9%, and 165, 74.7%, respectively). Our report describes practice patterns of a large international group of uveitis specialists treating non-infectious uveitis with systemic immunomodulatory drugs.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Downstream Effects of Market Changes on Inhalers: Impacts on Individuals With Chronic Lung Disease.

COPD and asthma are two of the most common chronic lung diseases, affecting over 545 million people globally and 34 million in the United States. Annual health care costs related to chronic lung disease are estimated at €380 billion in the European Union, and $24-$50 billion in the United States averaging to $4,000 in out-of-pocket costs per person in the U.S. A full-text literature search was conducted for English publications between January 1, 2005-March 18, 2024. It returned over 5,000 publications that were further narrowed using key search words, resulting in 172 peer-reviewed articles. Using their experience and subject expertise, the authors further narrowed the peer-reviewed articles to 55 that were in their opinion relevant. Also, 38 recently published industry reports and news articles specific to downstream effects of inhaler market changes and the future impact were included. The literature suggests that individuals with chronic lung disease face increased challenges with access to inhaled medication due to rising medication costs, discontinuation of branded medications, introduction of generic medications not covered by insurance, exclusionary preferred drug list tactics that force health care providers into non-medical switching of medication or devices, and ongoing medication shortages. Providers experience ongoing hurdles in prescribing appropriate inhaled medications for individuals with chronic lung disease, including increased time and costs spent on administrative tasks due to inhaler denials, a loss of patient trust, and limits on their ability to prescribe appropriate inhaled medication for individuals with chronic lung disease.

Medical Professionals and Pharmacological Intervention for the Treatment of Insomnia: A Cross-Sectional Study

Abstract Objective To explore the preferences of medical practitioners concerning various medications and other remedies to manage insomnia, and to ascertain whether these preferences are associated with their respective medical specialties. Materials and Methods Employing the snowball sampling technique, we administered two versions of a questionnaire to an international group of medical professionals, including trainees and specialists from diverse medical backgrounds. Results Zopiclone, zolpidem, and mirtazapine were evaluated as the most effective treatments for insomnia, while physicians would typically avoid using other tricyclic antidepressants, dual orexin receptor antagonists, and tryptophan for insomnia treatment. Noteworthy statistical correlations between physicians' specialty and preferred drug therapy, were observed in three out of five cases: 1) first-line drug treatment for short-term intervention against insomnia; (2) second-line treatment for long-term intervention; and 3) cases involving the elderly. Discussion Psychiatrists demonstrated a greater preference for antipsychotics and antidepressants for the treatment of insomnia compared with other physicians. Conversely, other medical professionals exhibited a preference for benzodiazepines and Z-drugs (zopiclone and zolpidem). Although Z-drugs were evaluated as the most effective in the treatment of insomnia, in the clinical practice, physicians administer or would administer antidepressant or antipsychotic drugs more often (mirtazapine and quetiapine respectively). Regarding Dual Orexin Receptor Antagonists (DORAs), the high prevalence of “Do not know/No opinion” answers implies that our sample was not familiar with this innovative treatment.

Rationale and design of Dapagliflozin vErsus SacubiTrIl-valsartaN therapY in Heart Failure with reduced ejection fraction (DESTINY-HF): a pragmatic randomised controlled trial protocol

BackgroundHeart failure affects almost 64 million people, with more than half of it constituting heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors...

Medicaid managed care restrictions on medications for the treatment of opioid use disorder.

To examine whether Medicaid managed care plan (MCP) utilization management policies for buprenorphine-naloxone and injectable naltrexone are related to key state Medicaid program policy decisions. We abstracted data on state Medicaid regulatory and policy information from publicly available sources and publicly available insurance benefit documentation from all 241 Medicaid MCPs operating in 2021. In this cross-sectional study, we used bivariate and multivariate analyses to examine whether Medicaid MCP prior authorization and quantity limits on receipt of buprenorphine and injectable naltrexone were associated with key state Medicaid choices to leverage federal funds to expand coverage and eligibility (Medicaid expansion, 1115 waivers) and to regulate Medicaid MCPs (uniform preferred drug lists, medical loss ratio remittance). Models were adjusted for MCP characteristics, including profit status, behavioral health contracting arrangement, National Committee for Quality Assurance accreditation, size, market share, and state opioid overdose death rates. Average marginal effects (AME) were reported. Utilization management was common among MCPs, and restrictions were more commonly applied to buprenorphine than injectable naltrexone, despite its higher cost. States that required MCPs to comply with utilization management policies stipulated in a uniform preferred drug list were more likely to require prior authorization for buprenorphine (AME: 0.29, 95% CI: 0.15-0.42) and injectable naltrexone (AME: 0.25, 95% CI: 0.12-0.38). MCPs in states that required plans to pay back earnings above a certain threshold were less likely to require prior authorization for buprenorphine (AME: -0.30, 95% CI: -0.43 to -0.18). Restrictions on medications for opioid use disorder are widespread among MCPs and vary by medication. State Medicaid regulatory and policy characteristics were strongly linked to MCPs' utilization management approaches. State Medicaid policy and contracting approaches may be levers to eliminate utilization management restrictions on medications for opioid use disorder.

Elucidating disparities in sunscreen coverage among state Medicaid preferred drug lists.

Regular application of over-the-counter (OTC) sunscreen is considered the foundation of skin cancer prevention, yet OTC sunscreen is not eligible for reimbursement in almost all state Medicaid benefit plans. On review of 111 Medicaid preferred drug lists (PDLs) across 50 states and the District of Columbia (DC), only five plans were identified that incorporate coverage of sunscreen. Thus, many recipients of Medicaid, the majority of whom are individuals and families of lower socioeconomic status, may encounter financial difficulty and thus forego utilizing sun protective measures due to financial constraints. Here, we compare current Medicaid coverage of OTC sunscreen and discuss calculated and theoretical annual costs of this skin cancer prevention method.

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis

BackgroundStudies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF.ResultsThe gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups.ConclusionsThis study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

A rare disease with many faces: A multicenter registry of IgG4-related disease in children

Abstract Objectives We aimed to report the characteristics of pediatric IgG4-related disease (IgG4-RD) through a multicentre registry, to assess disease clusters, and to evaluate the performances of the 2019 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria and the 2020 revised comprehensive diagnostic (RCD) criteria in this cohort. Methods Data of IgG4-RD patients in 13 pediatric rheumatology centers were recorded to a web-based registration system. The diagnosis of IgG4-RD was made according to the 2011 comprehensive diagnostic criteria. Results Thirty-five children (19 females and 16 males) with IgG4-RD were enrolled. The median age at diagnosis was 13.3 (25p-75p; 9.9–15.2) years. The most common organ involvement was the eye (n = 21, 60%), followed by lymph nodes (n = 12, 34.3%), musculoskeletal system (n = 12, 34.3%), and neurological system (n = 9, 25.7%). We identified three clusters in our study cohort: those with eye involvement (n = 11, 31.4%), those with eye involvement and neurological findings (n = 15, 42.9%), and those with pancreato-hepatobiliary disease and lymph node involvement (n = 9, 25.7%). Serum IgG4 levels were high in 19 out of 28 patients (67.8%). All patients except one received corticosteroid treatment, and azathioprine was the most preferred drug as a steroid-sparing agent. The sensitivities of the 2019 ACR/EULAR classification criteria and the 2020 RCD criteria were 5.7% and 88.5%, respectively. Conclusion IgG4-RD has a wide variety of clinical manifestations, however in children the most common presentation was orbital involvement. The 2020 RCD criteria had a better performance whereas the 2019 ACR/EULAR classification criteria performed poorly in pediatric patients.

Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges.

The discovery of novel and innovative therapeutic strategies for cancer treatment and management remains a major global challenge. Exosomes are endogenous nanoscale extracellular vesicles that have garnered increasing attention as innovative vehicles for advanced drug delivery and targeted therapy. The attractive physicochemical and biological properties of exosomes, including increased permeability, biocompatibility, extended half-life in circulation, reduced toxicity and immunogenicity, and multiple functionalization strategies, have made them preferred drug delivery vehicles in cancer and other diseases. Small interfering RNAs (siRNAs) are remarkably able to target any known gene: an attribute harnessed to knock down cancer-associated genes as a viable strategy in cancer management. Extensive research on exosome-mediated delivery of siRNAs for targeting diverse types of cancer has yielded promising results for anticancer therapy, with some formulations progressing through clinical trials. This review catalogs recent advances in exosome-mediated siRNA delivery in several types of cancer, including the manifold benefits and minimal drawbacks of such innovative delivery systems. Additionally, we have highlighted the potential of plant-derived exosomes as innovative drug delivery systems for cancer treatment, offering numerous advantages such as biocompatibility, scalability, and reduced toxicity compared to traditional methods. These exosomes, with their unique characteristics and potential for effective siRNA delivery, represent a significant advancement in nanomedicine and cancer therapeutics. Further exploration of their manufacturing processes and biological mechanisms could significantly advance natural medicine and enhance the efficacy of exosome-based therapies.

Correlates of fentanyl preference among people who use drugs in Rhode Island

BackgroundFentanyl is increasingly pervasive in the unregulated drug supply and is a driver of drug overdose deaths in the United States. The aims of this study were to characterize and identify correlates of fentanyl preference among people who use drugs (PWUD) in Rhode Island (RI).MethodsUsing bivariate analysis, we examined associations between fentanyl preference and sociodemographic and psychosocial characteristics at baseline among participants enrolled in the RI Prescription Drug and Illicit Drug Study from August 2020-February 2023. Fentanyl preference was operationalized based on responses to a five-point Likert scale: “I prefer using fentanyl or drugs that have fentanyl in them.” Participants who responded that they “strongly disagree,” “disagree,” or were “neutral” with respect to this statement were classified as not preferring fentanyl, whereas participants who responded that they “agree” or “strongly agree” were classified as preferring fentanyl.ResultsAmong 506 PWUD eligible for inclusion in this analysis, 15% expressed a preference for fentanyl or drugs containing fentanyl as their drug of choice. In bivariate analyses, preference for fentanyl was positively associated with younger age, white race, lifetime history of overdose, history of injection drug use, past month enrollment in a substance use treatment program, past month treatment with medications for opioid use disorder, and preferences for heroin and crystal methamphetamine (all p < 0.05). Descriptive data yielded further insight into reasons for fentanyl preference, the predominant having to do with perceived effects of the drug and desire to avoid withdrawal symptoms.ConclusionsOnly a relatively small subset of study participants preferred drugs containing fentanyl. Given the increased prevalence of fentanyl contamination across substances within the unregulated drug market, the result for PWUD is increasingly less agency with respect to choice of drug; for example, people may be forced to use fentanyl due to restricted supply and the need to mitigate withdrawal symptoms, or may be using fentanyl without intending to do so. Novel and more effective interventions for PWUD, including increased access to age-appropriate harm reduction programs such as fentanyl test strips and overdose prevention centers, are needed to mitigate fentanyl-related harms.

Controlling Prescribing through "Preferred Drug" Targets-The Bavarian Experience.

The rising costs of drugs are putting health care systems under pressure. We report on the Bavarian Drug Agreement, which employs prescribing targets for preferred and generic drugs in ambulatory care. Under this agreement, providers are regularly profiled with individual feedback but also possible sanctions. We investigated the degree to which targets were being met (or not) and why failure occurred. We analysed prescribing data aggregated by practice for the quarter 1/2018. We chose eight specialisation groups and analysed their drug targets with a high prescribing volume, widely missed drug targets (<90%), and drugs preventing drug target achievement. Characterisation of drug targets and preventing drugs was undertaken. Drug targets with a high prescribing volume are mostly achieved, while highly missed drug targets mostly do not affect the main indication area of the specialisation groups considered. Generic drug targets seem to be more easily achieved than recommended drug targets. Paediatrics accounts for the largest number of missed drug targets. The Bavarian tool implemented uses the prescribing volume (DDD) and price components to evaluate the prescription behaviour of physicians. Well-established drugs with demonstrated effectiveness, safety, and lower costs are preferred. Nevertheless, me-too drugs, combination drugs, costly innovations with unclear value, and drugs with application methods of variable convenience challenge the drug prescribers and are reasons for missed drug targets.

The relationship between morningness-eveningness and naturalness bias

ABSTRACT The naturalness bias in which people perceive natural items to be safer, healthier, and better than synthetic alternatives has been found to be associated with numerous individual difference variables (e.g. connectedness to nature and religiosity). However, no research has examined the role of morningness-eveningness in influencing preferences for naturalness. Here, we propose that evening individuals may exhibit a weaker preference for naturalness compared to morning individuals due to their greater exposure to artificial lighting, technology, and stimuli. To systematically test our theoretical perspective, we conducted three complementary and high-powered studies. In an online survey (Study 1), student participants with a stronger evening orientation displayed a diminished preference for natural drugs compared to those with a morning orientation. Using a sample of community adults, Study 2 replicated the findings of Study 1 in a real-world, behavioral context. Study 3 examined the relationship between morningness-eveningness and preference for naturalness within the domain of beverages. The results revealed that individuals with an evening-orientation had decreased odds of selecting natural water without minerals. Taken together, the findings suggest that an individual’s diurnal preference toward eveningness may have implications for their bias toward and perception of naturalness across various domains.

Advances and future directions in ROS1 fusion-positive lung cancer.

ROS1 gene fusions are an established oncogenic driver comprising 1%-2% of non-small cell lung cancer (NSCLC). Successful targeting of ROS1 fusion oncoprotein with oral small-molecule tyrosine kinase inhibitors (TKIs) has revolutionized the treatment landscape of metastatic ROS1 fusion-positive (ROS1+) NSCLC and transformed outcomes for patients. The preferred Food and Drug Administration-approved first-line therapies include crizotinib, entrectinib, and repotrectinib, and currently, selection amongst these options requires consideration of the systemic and CNS efficacy, tolerability, and access to therapy. Of note, resistance to ROS1 TKIs invariably develops, limiting the clinical benefit of these agents and leading to disease relapse. Progress in understanding the molecular mechanisms of resistance has enabled the development of numerous next-generation ROS1 TKIs, which achieve broader coverage of ROS1 resistance mutations and superior CNS penetration than first-generation TKIs, as well as other therapeutic strategies to address TKI resistance. The approach to subsequent therapy depends on the pace and pattern of progressive disease on the initial ROS1 TKI and, if known, the mechanisms of TKI resistance. Herein, we describe a practical approach for the selection of initial and subsequent therapies for metastatic ROS1+ NSCLC based on these clinical considerations. Additionally, we explore the evolving evidence for the optimal treatment of earlier-stage, non-metastatic ROS1+ NSCLC, while, in parallel, highlighting future research directions with the goal of continuing to build on the tremendous progress in the management of ROS1+ NSCLC and ultimately improving the longevity and well-being of people living with this disease.

Diagnosis and Treatment of Eclampsia.

Hypertensive disorders of pregnancy affect approximately 5% to 10% of pregnant women. Eclampsia is a serious hypertensive disorder that is primarily characterized by the onset of grand mal seizure activity in the absence of other causative conditions. While eclampsia is diagnosed clinically, laboratory tests are recommended to assess for complications. Treatment strategies for eclampsia focus on controlling seizures and managing hypertension. Acute care during a seizure is critical because of the need for immediate medical interventions, including the management of the airway, breathing, and circulation, as well as ensuring the safety of the patient during convulsions. Magnesium sulfate is the preferred anticonvulsant drug. Care must be taken during administration to prevent magnesium toxicity. Antihypertensive drugs used in eclampsia include labetalol, hydralazine and nifedipine. The definitive treatment of eclampsia is delivery. Close monitoring of both mother and fetus is important to identify any indications for delivery. The timing and mode of delivery depend on obstetric indications, the severity of eclampsia, the gestational age of the fetus, and the overall clinical status of the patient. Neuraxial anesthesia is the anesthesia of choice for conscious, seizure-free, and with stable vital signs women undergoing cesarean section.

Differences in heart failure with preserved ejection fraction management between care providers: an international survey.

Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by growing incidence and poor outcomes. A large majority of HFpEF patients are cared by non-cardiologists. The availability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as recommended therapy raises the importance of prompt and accurate identification and treatment of HFpEF across diverse healthcare settings. We evaluated HFpEF management across specialties through a survey targeting cardiologists, HF specialists, and non-cardiologists. An independent web-based survey was distributed globally between May and July 2023. We performed a post-hoc analysis, comparing cardiologists, HF specialists, and non-cardiologists. A total of 1460 physicians (61% male, median age 41[34-49]) from 95 countries completed the survey; 20% were HF specialists, 65% cardiologists, and 15% non-cardiologists. Compared with HF specialists, non-cardiologists and cardiologists were less likely to use natriuretic peptides (p = 0.003) and HFpEF scores (p = 0.004) for diagnosis, and were also less likely to have access to or consider specific echocardiographic parameters (p < 0.001) for identifying HFpEF. Diastolic stress tests were used in less than 30% of the cases, regardless of the specialty (p = 1.12). Multidrug treatment strategies were similar across different specialties. While SGLT2i and diuretics were the preferred drugs, angiotensin receptor blockers and angiotensin receptor-neprilysin inhibitors were the least frequently prescribed in all three groups. However, when constrained to choose one drug, the proportion of physicians favoring SGLT2i varied significantly among specialties (66% HF specialists, 52% cardiologists, 51% non-cardiologists). Additionally, 10% of non-cardiologists and 8% of cardiologists considered beta blocker the drug of choice for HFpEF. Significant differences among specialty groups were observed in HFpEF management, particularly in the diagnostic work-up. Our results highlight a substantial risk of underdiagnosis and undertreatment of HFpEF patients, especially among non-HF specialists.

Oral Cannabis Extract for Secondary Prevention of Chemotherapy-Induced Nausea and Vomiting: Final Results of a Randomized, Placebo-Controlled, Phase II/III Trial.

The aim of this randomized, placebo-controlled, two-stage, phase II/III trial was to determine the efficacy of an oral cannabis extract in adults with refractory nausea and/or vomiting during moderately or highly emetogenic, intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Here, we report results of the prespecified combined analysis including the initial phase II and subsequent phase III components. Study treatment consisted of oral capsules containing either tetrahydrocannabinol 2.5 mg plus cannabidiol 2.5 mg capsules (THC:CBD) or matching placebo, taken three times a day from days -1 to 5, in addition to guideline-consistent antiemetics. The primary measure of effect was the difference in the proportions of participants with no vomiting or retching and no use of rescue medications (a complete response) during hours 0-120 after the first cycle of chemotherapy on study (cycle A). We recruited 147 evaluable of a planned 250 participants from 2016 to 2022. Background antiemetic prophylaxis included a corticosteroid and 5-hydroxytryptamine antagonist in 97%, a neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD compared with placebo improved the complete response rate from 8% to 24% (absolute difference 16%, 95% CI, 4 to 28, P = .01), with similar effects for absence of significant nausea, use of rescue medications, daily vomits, and the nausea scale on the Functional Living Index-Emesis quality-of-life questionnaire. More frequent bothersome adverse events of special interest included sedation (18% v 7%), dizziness (10% v 0%), and transient anxiety (4% v 1%). There were no serious adverse events attributed to THC:CBD. THC:CBD is an effective adjunct for chemotherapy-induced nausea and vomiting despite standard antiemetic prophylaxis, but was associated with additional adverse events. Drug availability, cultural attitudes, legal status, and preferences may affect implementation. Future analyses will evaluate the cost-effectiveness of THC:CBD.