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OBJECTIVE: To determine patient characteristics and dose titration patterns of real-world semaglutide (Wegovy) users. RESEARCH DESIGN AND METHODS: We used a population-based cohort study including Danish adults who filled semaglutide prescriptions from 12 December 2022 to 31 December 2023. Outcomes were patient characteristics, prescriber type, and dose titration patterns. RESULTS: We identified 110,748 individuals (median age 49 years; 70% female) filling 773,708 prescriptions for semaglutide. General practitioners initiated treatment in 86%. Common comorbidities included hypertension (30%), dyslipidemia (17%), and arthrosis (17%). Only 13% reached the maximum dose of 2.4 mg by their fifth prescription, while 5.7% stopped after the first prescription. Few users (10%) followed recommended dose increases every 4 weeks. Overall, 25% filled at least one prescription of 2.4 mg, while 33–48% continued with the 1.0-mg dosage from the fourth prescription onward. CONCLUSIONS: Real-world semaglutide users generally resembled trial participants, but few follow the dose titration schemes tested in premarket clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To describe utilization patterns, characteristics of users and prescribers of the new oral antiviral medication, molnupiravir, indicated for mild‐to‐moderate COVID‐19. Methods: Using nationwide registries, we identified all Danish adults who filled a prescription for molnupiravir from December 16th, 2021, to August 31st, 2022. We described weekly incidence rates and patient characteristics over time, prescriber characteristics as well as time between molnupiravir initiation and a positive SARs‐CoV‐2 test. Patient characteristics were compared to matched, untreated SARS‐CoV‐2 positive reference groups. Results: By August 31st, 2022, 5847 individuals had filled a prescription for molnupiravir. The incidence rate gradually increased to 16 weekly prescriptions per 1000 RT‐PCR SARS‐CoV‐2 positives. Users of molnupiravir were most often men (55% vs. 45% women). The majority (81%) had a positive RT‐PCR SARS‐CoV‐2 test and few (2.9%) redeemed molnupiravir outside the recommended window of 5 days from the positive test result. Compared to matched, untreated SARS‐CoV‐2 positive reference groups, users of molnupiravir had a median age of 74 years versus 49 years, a higher proportion resided in a nursing home (12% vs. 1.5%) and had a higher number of comorbidities (median of 3 vs. 0); most commonly hypertension (38%), chronic lung disease (35%), diabetes (20%) and mood disorders (20%). General practitioners were the primary prescribers of molnupiravir (91%). Conclusions: Molnupiravir was mainly prescribed by general practitioners to RT‐PCR SARS‐CoV‐2 positive individuals who had a potentially increased risk of severe COVID‐19. Though some off‐label prescribing occurred, our study indicates a high level of adherence to contemporary guidelines. [ABSTRACT FROM AUTHOR]

Background and aims: Bariatric surgery remains a mainstay for treatment of morbid obesity. However, long-term adverse outcomes include chronic abdominal pain and persistent opioid use. The aim of this review was to assess the existing data on prevalence, possible mechanisms, risk factors, and outcomes regarding chronic abdominal pain and persistent opioid use after bariatric surgery. Methods: PubMed was screened for relevant literature focusing on chronic abdominal pain, persistent opioid use and pharmacokinetic alterations of opioids after bariatric surgery. Relevant papers were cross-referenced to identify publications possibly not located during the ordinary screening. Results: Evidence regarding general chronic pain status after bariatric surgery is sparse. However, our literature review revealed that abdominal pain was the most prevalent complication to bariatric surgery, presented in 3–61% of subjects with health care contacts or readmissions 1–5 years after surgery. This could be explained by behavioral, anatomical, and/or functional disorders. Persistent opioid use and doses increased after bariatric surgery, and 4–14% initiated a persistent opioid use 1–7 years after the surgery. Persistent opioid use was associated with severe pain symptoms and was most prevalent among subjects with a lower socioeconomic status. Alteration of absorption and distribution after bariatric surgery may impact opioid effects and increase the risk of adverse events and development of addiction. Changes in absorption have been briefly investigated, but the identified alterations could not be separated from alterations caused solely by excessive weight loss, and medication formulation could influence the findings. Subjects with persistent opioid use after bariatric surgery achieved lower weight loss and less metabolic benefits from the surgery. Thus, remission from comorbidities and cost effectiveness following bariatric surgery may be limited in these subjects. Conclusions: Pain, especially chronic abdominal, and persistent opioid use were found to be prevalent after bariatric surgery. Physiological, anatomical, and pharmacokinetic changes are likely to play a role. However, the risk factors for occurrence of chronic abdominal pain and persistent opioid use have only been scarcely examined as have the possible impact of pain and persistent opioid use on clinical outcomes, and health-care costs. This makes it difficult to design targeted preventive interventions, which can identify subjects at risk and prevent persistent opioid use after bariatric surgery. Future studies could imply pharmacokinetic-, pharmacodynamics-, and physiological-based modelling of pain treatment. More attention to social, physiologic, and psychological factors may be warranted in order to identify specific risk profiles of subjects considered for bariatric surgery in order to tailor and optimize current treatment recommendations for this population. [ABSTRACT FROM AUTHOR]

Oral controlled‐release formulations are playing an ever‐increasing role in opioid therapy; however, little is known about their influence on the relationship between pharmacokinetics and pharmacodynamics. The study aim was to characterize the pharmacokinetic‐pharmacodynamics of two controlled‐release tablet formulations and a liquid formulation of oxycodone in healthy, opioid‐naïve volunteers, which can serve as a reference for future patient studies. A semi‐double‐blinded, three‐way crossover study was conducted, with fifteen healthy volunteers receiving two differently designed 20 mg monophasic controlled‐release oxycodone tablets and 10 mg oral solution oxycodone in a randomized order. Venous plasma concentrations and pupil diameter were determined pre‐dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.33, 2.66, 3, 3.33, 3.66, 4, 5, 6, 8, 12 and 24 hour post‐dose. Oxycodone pharmacokinetics was best described by a two‐compartment model with first‐order absorption. The controlled‐release formulations had an absorption lag of 0.23 hour and a slower absorption rate constant (kaCR = 0.19 hour‐1) compared to the oral solution (kaSOL = 0.94 hour‐1). Effects on pupil diameter were delayed relative to plasma (14 minutes half‐life) for all formulations and were best described by a proportional Emax model. The plasma concentration of oxycodone at half‐maximum effect was lower in males (31.1 μg/L) compared to females (52.8 μg/L; P <.001). The absorption profile of controlled‐release oxycodone formulations provided a prolonged onset and offset of action compared to oral solution oxycodone. The controlled‐release formulations showed no differences in pharmacokinetic and pharmacodynamic parameters suggesting that both may be used interchangeably in human beings with normal gastrointestinal function. [ABSTRACT FROM AUTHOR]

Ongoing monitoring and targeted treatment are important to ensure the best blood-pressure control and thus prevent cardiovascular risks. In this review, we evaluate the findings of four clinical studies investigating the effects of morning versus bedtime dosing of antihypertensives. In three out of four studies, overwhelming results were found favouring bedtime dosing. The same studies have been criticized for mechanistic implausible results and multiple study biases. No harmful effects were reported in relation to bedtime dosing. Thus, antihypertensives can be taken as it is most convenient for the patient., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)