Preferred Drug Research Articles

Repeated toluene inhalation in male and female adolescent rats induces persistent drug preference and impairs cognitive and social behavior.

Adolescent inhalant use is an understudied and undertreated disorder, particularly in females. Chronic exposure to inhalants, like toluene, can have long-lasting effects on behavior. However, most animal studies lack the incorporation of both sexes and do not focus on the abstinence period. We assessed the behavioral effects during prolonged abstinence following repeated toluene inhalation in adolescent male and female rats. We repeatedly exposed adolescent male and female Sprague Dawley rats to toluene vapor (1500 or 3000ppm) for 6days using the conditioned place preference (CPP) procedure. We tested drug-associated context preference, locomotion, anxiety-like behavior, object memory, social preference, and cognitive flexibility across 22days of abstinence. In females, 3000ppm toluene increased CPP on days 8 and 22 of abstinence but this effect did not reach significance in males. Instead, males showed a significant increase in locomotion on days 7 and 21. Toluene also impaired social novelty preference and reversal learning during long-term abstinence, but not anxiety-like behavior or object recognition memory. Our rodent findings suggest that female inhalant usersmayshow persistent drug preference during abstinence following chronic use. Furthermore, prolonged cognitive and social deficits should be addressed in treatment programs for adolescents.

Investigating the policy Effect of Medicine Subsidy Plan (Daruyar) on Patients' Out-Of-Pocket Payments :A Case Study of the General Health Insurance Administration of Isfahan Province

Background: The policy of removing the preferred drug currency (Daruyar plan) has been with the approach of increasing the coverage ratio and insurance obligations and paying attention to patients' out of pockets, especially incurable, chronic and low-income patients. Therefore, the purpose of this research is to investigate the effect of this plan on price and consumption ,and ultimately, the out of pocket payments after its implementation. Methods: The research method of this study was descriptive-analytical. Primary sampling included 5 pharmacies selected non-randomly and purposefully. After extracting the drug data of the insured persons related to these pharmacies from the database of the Health Insurance Organization, a sample of 384 people determined from the Morgan table was determined randomly and the number of 1803 items of medicine received by them was checked. Then the data was analyzed using SPSS 17 software and Mann-Whitney test. Results: The survey of 1803 items of medicine in the two periods of November 2021 and 2022 showed that the maximum amount of out-of-pocket payment in November 2021 was equal to 184,000,000 Rials and the average of this variable was 1,357,000 Rials and the median was 177,250 Rials. This number in 2022 was 92,000,000 Rials, 1,805,000 Rials respectively and 181,050 Rials. The results of the analysis of these data showed that after the implementation of Daruyar plan, due to the allocation of compensatory subsidies, there has been no significant change in the total out-of-pocket payment of the patients. Conclusion: This study investigated the effect of Daruyar plan on price changes, consumption and out-of-pocket payments of patients. The comparison of out-of-pocket payment data in the two time frames of November 2021 and 2022 showed that eliminating the preferred drug currency and implementing the drug subsidy plan has not made a significant change regarding patients' out-of-pocket payments.

Evaluation of In Vitro Inhibition of β-Hematin Formation: A Step Towards a Comprehensive Understanding of the Mechanism of Action of New Arylamino Alcohols

Currently, artemisinin-based combination therapy is recommended as first-line treatment of uncomplicated falciparum malaria. Arylamino alcohols (AAAs) such as mefloquine (MQ) are the preferred partner drugs due to their longer half-life, reliable absorption and strong antimalarial activity. However, the mode of action of MQ remains poorly understood and its neurotoxicity limits its use. Furthermore, the emergence of drug-resistant parasites requires development of new antimalarial drugs. The aim of this study was to evaluate the β-hematin inhibition capacity of three pairs of enantiopure AAAs 1–3 (a/S and b/R) derived from MQ or enpiroline (ENP), a pyridine-based MQ analog with strong antimalarial activity. Inhibition of β-hematin—the synthetic counterpart of hemozoin formation—was determined for each compound. Antimalarial activity against W2 and 3D7 Plasmodium falciparum strains as well as percentages of inhibition of β-hematin formation were compared to those of reference molecules, i.e., chloroquine (CQ), MQ and ENP. Furthermore, a cytotoxicity study on the human-derived hepatocarcinoma cell line HepG2 was performed. With high antimalarial activity, stronger ability to inhibit β-hematin formation and low cytotoxicity, AAAs 1a-b and 2a are the most promising. These findings provide a better understanding of their potential mechanisms of action and may pave the way toward developing new lead compounds.

The reality of bronchoscopy care in Germany: a survey by the German Respiratory Society

In September 2022, sites where bronchoscopy was carried out were systematically surveyed regarding structural and process quality features in an anonymized DGP survey with 33 questions. The data collected were analyzed descriptively. Of the 196 participating sites, bronchoscopies were performed regularly at 180 sites. The majority were standard secondary care (n=51) and tertiary care (n=43) hospitals (range of services: diagnostic bronchoscopy, predominantly (80%) including endobronchial ultrasound-guided transbronchial needle aspiration, EBUS-TBNA). Extended treatment options were guaranteed for acute cases at >90% of these locations. University hospitals (n=24) and specialist pulmonary hospitals (n=35) also offered more complex diagnostic procedures and therapeutic-interventional techniques. The performance figures were significantly higher in the specialist pulmonary hospital (specialist pulmonary hospitals: 62%: >2000 bronchoscopies/year; university hospitals: 25%: >2000 bronchoscopies/year; p<0.001). In the practice setting (n=21, partly in co-operation with hospitals) , <500 bronchoscopies/year were performed.Intensive care units were available in 97% of the hospitals; 88% of the hospitals had fluoroscopy facilities in the bronchoscopy room. Propofol (91%) and/or midazolam (62%) were the preferred drugs for sedation. At 21% of the sites, >200 bronchoscopies under ventilation/year were performed. BAL and transbronchial forceps biopsies were mainly performed via the nasal or oral approach, EBUS-TBNA via a bronchoscopy tube or the oral approach, the EBUS mini-probe/navigation, cryotechnique or more complex interventions via the rigid tube or a bronchoscopy tube. ASA >2 led to involvement of a second physician at 46% of clinical sites, at 47% of sites at an ASA classification >3. The majority of bronchoscopic examinations are performed in respiratory departments at secondary care centres as well as maximum care hospitals. For more complex procedures, cooperation with hospitals specialized in bronchoscopy (e.g. university hospital or a specialist lung clinic) is advisable.

Clinical Perspectives of Managing Epilepsy Across Different Patient Populations with a Focus on Brivaracetam: A Cross-sectional Study among Indian Physicians

Objective: To evaluate clinicians' preferences, prescribing patterns, and clinical experiences with brivaracetam compared to other antiepileptic drugs, particularly levetiracetam, in the management of epilepsy across different patient populations. Methodology: This cross-sectional study used a 24-item multi-response questionnaire to gather expert opinion across different Indian settings regarding their perspectives on epilepsy and brivaracetam. Data analysis employed descriptive statistics, with results reported as frequencies and percentages. Results: The survey included 360 participants. Clinicians showed a strong preference for brivaracetam as the first-line antiepileptic drug in patients with newly diagnosed epilepsy, with 72% favoring it for younger patients and 74% for elderly. This preference was particularly notable for managing partial-onset seizures, as cited by 71% of clinicians. Additionally, 65% reported that partial-onset seizures were the primary reason for switching to brivaracetam from other antiepileptics. Behavioral and psychiatric adverse effects were cited by 60% of clinicians as the main reasons for transitioning from levetiracetam to brivaracetam. Moreover, 47% reported that 10-20% of patients experiencing behavioral changes on levetiracetam were switched to brivaracetam, with 49% noting improved efficacy and behavioral outcomes in 20-30% of these cases. The minimal psychiatric and behavioral side effects of brivaracetam were noted as its main advantage by 41% of clinicians in managing partial-onset seizures. Furthermore, 70% of clinicians preferred brivaracetam for treatment-resistant epilepsy, and approximately half of them preferred it for pediatric partial seizures. Conclusion: This study highlighted brivaracetam as a preferred antiepileptic drug in clinical practice, especially for managing partial-onset seizures. It serves as an effective alternative for patients experiencing adverse effects with levetiracetam.

Diagnosis and treatment experience of Chlamydia psittaci pneumonia: A multicenter retrospective study in China

BackgroundIn recent years, clinical cases of Chlamydia psittaci pneumonia have gradually increased. Chlamydia psittaci pneumonia can quickly progress to severe pneumonia, leading to respiratory failure. Chlamydia psittaci cannot be detected by commonly used detection methods, leading to difficulties in clinical diagnosis and treatment, which may eventually develop into severe Chlamydia psittaci pneumonia. Therefore, we should improve our diagnostic and treatment capabilities for this disease.MethodsThis article retrospectively studied 61 cases of pneumonia from 12 different provinces in China, and classified them into severe pneumonia and non-severe pneumonia. Divided into two groups, with 23 cases of severe pneumonia and 38 cases of non-severe pneumonia. We compared the two groups in terms of imaging, laboratory testing, treatment, prognosis, etc., hoping to provide better explanations and help clinical physicians better diagnose the disease.ResultsThere is no difference in age, gender, contact history, smoking history, or basic disease between severe and non-severe Chlamydia psittaci pneumonia. The most prominent symptom is fever, with a median body temperature of 39.7 ℃, and other symptoms similar to common respiratory infections. White blood cells and neutrophils may not show significant elevation, but C-reactive protein (CRP) and procalcitonin (PCT) will both show significant elevation, often accompanied by a decrease in arterial oxygen pressure. Some patients may experience liver and kidney dysfunction, but there is no statistically significant difference between the two groups. Doxycycline remains the preferred drug for severe Chlamydia psittaci pneumonia. The imaging mainly shows consolidation and bronchial inflation sign, and may also present with pleural effusion.ConclusionsThe imaging of Chlamydia psittaci pneumonia usually shows consolidation with bronchial inflation sign, which can also be manifested as ground glass changes or solid masses. Atypical images are prone to misdiagnosis in the early stages. There are some differences in laboratory examination and imaging between severe pneumonia and non-severe pneumonia, which can help identify severe patients in the early stage. Metagenomic next-generation sequencing (mNGS) played an important role in the diagnosis of all cases in this article. Timely treatment has a good prognosis for the disease, and imaging lesions can be completely absorbed.

Mechanism of Astragalus polysaccharides (APS) improving myelosuppression and exerting anti-tumor effects during radiotherapy and chemotherapy

Abstract. Chemoradiotherapy, as a routine method of anti-tumor treatment, is accompanied by severe adverse reactions such as myelosuppression. It not only hinders the treatment process but also reduces the quality of life of patients. Therefore, effective prevention and treatment of myelosuppression during radiotherapy and chemotherapy is an extremely important issue that needs to be addressed in clinical practice. The commonly used method for preventing and treating myelosuppression during radiotherapy and chemotherapy is medication intervention. Human granulocyte colony stimulating factor(Human G-CSF) is the preferred drug, while modern Chinese medicine preparations are used as adjunctive therapy. There are still certain limitations in the clinical use of Human G-CSF, so research on the unique role of modern Chinese medicine in this regard has gradually received attention. By consulting literature, we took Astragalus polysaccharide (APS), a traditional Chinese medicine extract that has been proven to have relevant preventive and curative effects in existing studies, as an entry point to explore the mechanisms involved in the modulation of the signaling pathway by APS to play a role in improving the myelosuppressive and anti-tumour effects. This study aims to explore the mechanism by which APS participates in regulating signaling pathways to improve myelosuppression and anti-tumor effects. Some of its mechanisms are closely related to traditional Chinese medicine theory. This article will briefly discuss them in order to provide some inspiration for expanding drug selection in clinical practice and further conducting related research.

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.

Which antidiabetic drugs do patients of T2DM prefer in India and why? A discrete choice experiment

ABSTRACT Background: Uncontrolled diabetes persists despite guideline-based treatment, partly attributed to inadequate patient involvement. This research addresses shared decision-making by eliciting patient preferences in Type 2 Diabetes Mellitus (T2DM) treatment based on certain key attributes and explores their correlation with socio-demographic-clinical profiles. Methods: A discrete choice experiment (DCE) was conducted among T2DM outpatients in an Indian tertiary care center. A choice card was developed using the contextual choice framework, having six second-line antidiabetic drugs (ADs) from different classes incorporating seven attributes. Face-to-face interviews were conducted with patients, and elicited preferences were analyzed using descriptive statistics, Chi-square analysis, and multinomial logistic regression. Results: Out of the 87 evaluated participant choices, the most preferred drug was Glimepiride (51.7%), followed by Dapagliflozin (22.9%) and Teneligliptin (17.2%). Overall, the most important attributes were the effect on weight (29%), followed by route of administration (24%), and additional benefits offered by the drug (18%). Significant associations were found between participants’ drug preferences and their age (P = 0.002), socioeconomic status (P = 0.04), occupation (P = 0.004), and monthly income (P = 0.03). Age was not a significant predictor of drug choice for any of the drugs. Multinomial logistic regression showed that the overall model was statistically significant (P = 0.025), and it correctly predicted drug choice for 58.6% of the participants. Conclusion: Glimepiride was the most preferred option overall while the effect on weight was the most important attribute for patients in determining their preference. The study highlighted the importance of shared decisions and can guide practitioners in considering patient preferences when prescribing antidiabetic drugs.

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&gt;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&lt;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

BackgroundNon-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...

Cardiac Amyloidosis Screening and Management in Patients With Heart Failure With Preserved Ejection Fraction: An International Survey

Cardiac amyloidosis (CA) is still an underdiagnosed cause of heart failure (HF) and early disease recognition and timely disease-modifying therapy (DMT) administration translate to better outcomes. We aimed to assess CA screening and management approaches for patients with HF preserved ejection fraction (HFpEF) among physicians worldwide. An independent academic web-based survey was distributed worldwide between May 2023 and July 2023. Overall, 1,460 physicians (61% were men, median age was 42 [34 to 49] years) from 95 countries completed the survey. A total of 2/3 of respondents had experience diagnosing CA and reported having 10% of patients with CA in patients with HFpEF. Systematic screening for CA of all patients with HFpEF was performed by 10% of responders, whereas 24% did not consider the screening. Most responders (39%) used left ventricular hypertrophy as a screening criterion. Serum protein electrophoresis with immunofixation of free light chain and urine protein electrophoresis or cardiac magnetic resonance were selected by half of the responders as a first-line diagnostic tool. The combination of serum protein electrophoresis with immunofixation free light chain, urine protein electrophoresis, and bone scintigraphy was considered by 32% of the participants. CA DMT was available for 48% of the physicians. About 82% of responders would administrate HF to patients with HFpEF with CA, with the most preferable drugs being diuretics, sodium-glucose cotransporter-2 inhibitors, and renin-angiotensin-aldosterone system inhibitors. In conclusion, the results reveal the uncertainties among physicians worldwide regarding the need for CA screening of patients with HFpEF. CA remains a disease with very heterogeneous management, particularly, in the screening and diagnostic workup. The HF community should aim to educate on CA and improve access to DMT.

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&amp;lt;0.01) and admissions for HF (24% vs. 5%, p &amp;lt;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 &amp;lt; 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...

Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study

ObjectivesTo identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI). MethodsAn online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups. ResultsRespondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n=126, 38%), lowered for specific antibiotics (n=125, 38%) or lowered for all antibiotics (n=79, 24%). SAT was prescribed for a lifelong duration (n=43, 13%), a fixed duration (range 6 months–3 years) (n=104, 32%) or for an undetermined duration (n=154, 47%). ConclusionsApproach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.

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.