Olaparib, a poly ADP-ribose polymerase inhibitor, was approved by the European Commission in December 2022 and for which the Health for technology Assessment (HtA body) issued a favorable opinion for reimbursement in France on 5 April, 2023, following the results of the PROpel phase III clinical trial, for the first-line treatment of metastatic castration-resistant prostate cancer in combination with abiraterone and prednisone or prednisolone in adult men for whom chemotherapy is not clinically indicated. This publication aimed to report the first real-world data of patients with metastatic castration-resistant prostate cancer who received a combination of first-line olaparib with abiraterone, plus prednisone or prednisolone in the funded Early Access (fEA) for olaparib in France, from 30 March, 2023, to 25 September, 2024. Eligible patients were adult men with first-line metastatic castration-resistant prostate cancer. Olaparib 300-mg twice-daily tablets was given in combination with abiraterone plus prednisone or prednisolone regardless of the homologous recombination repair gene mutation status. Characteristics of the population, treatment duration, reasons for discontinuation, and safety data were collected during the fEA period. Patients could continue to receive olaparib after the end of the fEA. A total of 84 physicians spread over 72 hospitals in metropolitan France requested a fEA for 176 patients, 154 (87.5%) of whom were eligible to be included in the early access program. In total, 118 (76.6%) patients had an unknown homologous recombination repair status. Half of the patients (76, 49.7%) had very aggressive cancer with a Gleason score of 8 while 11 (7.2%) of them had a low-grade cancer with a Gleason score of 6 at the diagnosis. The most common metastatic sites were bone (107 patients, 69.5%) and distant (60, 39.0%) or regional (42, 27.3%) lymph nodes. Among the 154 patients, 84 (54.5%) had medical history, 47 (56.0%) of whom had arterial hypertension. All included patients had received at least one prior treatment prior to the metastatic castration resistance stage. Most patients (145, 94.2%) had received androgen suppression and 70 (45.5%) had been treated with androgen receptor pathway inhibitors. Of the 154 patients, 153 (99.4%) had at least one concomitant treatment with abiraterone and prednisone or prednisolone. Data confirming administration of olaparib treatment were provided for 149 patients (exposed patients), of whom 140 (94.0%) received olaparib at initiation at the dose of 300 mg twice daily. Fifty-seven patients experienced a total of 60 adverse events (36 serious adverse events and 24 non-serious adverse events). Over this period, three fatal and five life-threatening events were reported. The three fatal adverse events were one death assessed as a suspected adverse reaction (pancytopenia) and two deaths assessed as unrelated to olaparib: one attributed to disease progression and one to suicide. Because of adverse events, dose reductions were made in five patients, treatment was temporarily interrupted in one patient and discontinued in 20 patients. These are the first results describing the real-world use of olaparib in France in prostate cancer. Most patients included in the fEA had generally similar characteristics as the patients randomized in the PROpel clinical trial (NCT03732820) and initiated at the standard dose of 300 mg twice daily. No new safety signals were reported in this real-world patient population. The analyzed data did not modify the benefit-risk balance of olaparib.

The opioid epidemic, once a major concern in the United States, has escalated worldwide through three waves driven by prescription and synthetic opioids like oxycodone and fentanyl. Regional patterns of misuse and dependence remain unclear due to data heterogeneity. To address this, we compared adverse events reporting for these opioids using VigiBase. We analyzed "drug abuse and dependence" adverse events using VigiBase, a global pharmacovigilance database containing more than 40 million Individual Case Safety Reports (ICSRs). A regional comparison of opioid-related adverse event reporting was performed, with oxycodone and fentanyl as the primary drugs and morphine and tramadol as comparators. Adverse events were defined by Standardized MedDRA Query (SMQ) criteria and cases were stratified by three periods (1990-2009, 2010-2012, 2013-2024) and regions (Americas, Western Pacific, Europe). Opioid-related death was additionally assessed as a secondary outcome. Disproportionality analysis was conducted to identify safety signals, using the reporting odds ratio (ROR). Signals were considered significant if ROR > 2, χ2 > 4, and more than three reports were observed. Oxycodone-related reports peaked in 2005 (n=8395), 2011 (n=10,444), and 2021 (n=45,025), while fentanyl peaked in 2011 (n=11,451) and 2017 (n=32,704). The safety signals for oxycodone were found across all predefined periods in the Americas (1990-2009: ROR 4.40, n=9102; 2010-2012: ROR 2.13, n=2299; 2013-2024: ROR 5.20, n=108,068), and in two periods in the Western Pacific (2010-2012: ROR 6.53, n=81; 2013-2024: ROR 5.94, n=1066). No signals were detected for oxycodone in Europe, and fentanyl did not meet signal criteria in any region or period in the primary analyses. Oxycodone showed consistent safety signals in the Americas and Western Pacific. The absence of signals for fentanyl and in Europe may reflect under-reporting, highlighting the need for improved surveillance of illicit opioid use.

Hand‒foot syndrome (HFS) is a common cutaneous toxicity of capecitabine that can impair treatment continuity and quality of life. This study aimed to assess the prevalence, clinical characteristics, and factors associated with capecitabine-induced HFS. A cross-sectional analytical study was conducted at Khartoum Oncology Hospital, Sudan (June-October 2022), among adult patients with cancer receiving capecitabine monotherapy. Hand‒foot syndrome was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events and a modified Black Patient Scale. Multivariable logistic regression was used to identify factors associated with HFS, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) reported. Data analysis was performed using SPSS version 27. A total of 135 patients were included in the analysis, 90 (66.7%) of whom were female and 52 (38.5%) were aged 56-70 years. The most common cancer type was breast cancer (n = 56) [41.5%]. The overall prevalence of HFS was 74 (54.8%), with 37 (50.0%) involving the hands only and 28 (37.8%) involving both the hands and feet. Onset occurred within 7-21 days in 47 (63.5%) patients. Pain was reported by 41 (30.4%), predominantly moderate by 20 (48.8). Grade I was the most frequent by National Cancer Institute criteria (n = 33) [44.5%] and the Black Patient Scale (n = 33) [44.5%]. Hand‒foot syndrome was more prevalent in female patients (n = 58) [64.4%, p = 0.001], patients with breast cancer (n = 35) [62.5%] (p = 0.049), and those receiving >6 cycles (n = 6) [75%] (p = 0.006). After adjustment, female sex (aOR = 0.224, 95% CI 0.074-0.681; p = 0.008), patients without concomitant diseases (aOR = 2.389, 95% CI 1.011-5.646; p = 0.047), and patients receiving 4-6 cycles compared with those receiving 1-3 cycles (aOR = 0.359, 95% CI 0.155-0.828; p = 0.016) were independent predictors. Capecitabine-induced HFS affects more than half of patients and generally occurs early in onset. After adjustment, female patients and those who received 4-6 chemotherapy cycles were less likely to experience HFS, whereas the absence of concomitant diseases was associated with a greater likelihood of developing HFS. Early monitoring and proactive supportive care remain essential to optimize treatment continuity.

Patients with transfusion-dependent thalassemia (TDT) require lifelong blood transfusions; data on the psychosocial and economic impact on patients and their caregivers remain limited. The study aims to address this gap by describing the burden of TDT on pediatric, young, and adult patients, as well as their caregivers, within real-world settings in Italy. This is a cross-sectional, descriptive study conducted between May and December 2021. TDT patients and their caregivers from Italian sites were invited to complete an online survey with the Ratip and Modell questionnaire (1996) and another bespoke questionnaire. All subjects signed an online informed consent before responding to the questionnaires. Seventy-nine subjects completed the survey: 59 patients (43 adults and 16 children) and 20 caregivers (the majority of adult patients were aged 41-50 years). The age at diagnosis differed between adults and pediatric patients, being earlier in the latter (0-2 months in 43.8%). Nearly half of patients received more than one transfusion/month. More than half of the patients experienced blood shortages, particularly during the summer. School absenteeism was reported as a major issue. TDT continues to impose a significant burden, negatively impacting daily life, work, education, and social interactions. The availability of blood resources remains a critical issue, particularly in high-prevalence regions. The study highlights the need for ongoing research, innovative approaches, and enhanced support to ensure improved well-being for TDT patients and their caregivers.

Opioid use is common in rheumatoid arthritis (RA) for pain management; however, evidence of opioid-associated adverse events is increasing. While biological (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) improve functional outcomes such as pain, little is known about their impact on opioid utilization patterns. This study investigated opioid utilization before and after b/tsDMARD initiation and assessed effect modification by sex. Using 5% Medicare claims data from 2012 to 2020, this cohort study included older adults (≥ 65 years) with RA who initiated b/tsDMARDs (first prescription = index date), and had continuous Medicare Parts A, B, and D, but not Part C enrollment, during 12 months before and after initiation. The outcomes of interest were any opioid use and long-term opioid therapy (LTOT). McNemar's test was performed to compare outcomes before and after b/tsDMARD initiation. Sex-based differences in changes in opioid use after b/tsDMARD initiation were also evaluated. The study cohort included 3585 individuals with RA initiating b/tsDMARDs; most were female (75.87%) with a mean (SD) age of 73.15 (5.99) years. Following b/tsDMARD initiation, any opioid use decreased significantly from 2094 (58.41%) to 2017 (56.26%) (p = 0.015). However, LTOT use increased significantly from 733 (20.45%) to 900 (25.10%) (p < 0.001), following b/tsDMARD initiation. No evidence of sex differences in the association between b/tsDMARD initiation and opioid utilization was identified. Initiating b/tsDMARDs was associated with a modest reduction in any opioid use. However, LTOT use in RA remained persistently high. The impact of different b/tsDMARD initiation on opioid utilization patterns needs further investigation.

BackgroundChronic obstructive pulmonary disease (COPD) is a significant public health concern, and inhalation therapy is a critical component of its management. However, using an inhaler is challenging, especially for patients with COPD, who are often elderly and experience reduced dexterity, visual and cognitive impairment, and difficulty synchronizing inhalation with dose actuation. Synchrobreathe® is an easy-to-use, breath-actuated inhaler that releases medication during inhalation, addressing these challenges. Although its use in asthma is well documented, evidence in COPD is limited.MethodsThis prospective, multicenter, observational study carried out during August 2021 and August 2022 evaluated the clinical outcomes of the budesonide/formoterol combination (BUD/FORM) delivered through Synchrobreathe® in patients with COPD in India. The primary endpoint was disease control, that is, change from baseline in COPD Assessment Test (CAT) score at 12 weeks. Secondary endpoints included changes in CAT and modified Borg Dyspnea Scale (mBDS) scores and device usability. Adverse events were monitored over 12 weeks.ResultsIn the study population (N = 250), significant reductions from baseline were observed in mean CAT (−6.56 ± 0.33; p < 0.001) and mBDS (−1.60 ± 0.09; p < 0.0001) scores at 12 weeks. Almost all (98%) patients were satisfied with Synchrobreathe® and preferred it over their previous inhalers. No significant adverse events were reported.ConclusionBUD/FORM delivered through Synchrobreathe® significantly improved CAT and mBDS scores, with no reported serious adverse events in patients with COPD. Its simple usage makes it an effective option for this patient population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-025-00522-w.

Background and ObjectiveNontuberculous mycobacteria (NTM) are opportunistic pathogens that can cause lung disease (NTMLD) in susceptible individuals, but NTMLD management is challenging. This study aims to describe real-world NTMLD treatment patterns in Belgium.MethodsThis retrospective study used data from the IQVIA longitudinal pharmacy database. Patients with presumed NTMLD (i.e., who initiated prespecified NTM treatments from October 2015 through September 2019) were included. Variables of interest were initiated prescribed regimens, medication possession rate (MPR), and treatment persistence, switches, and restarts.ResultsOverall, 199 presumed NTMLD patients initiated 72 triple- and 130 dual-drug regimens. The average triple-drug therapy MPR was 88%, and median treatment duration was 225 days. Sixty percent and 30% of patients remained on initial therapy at 6 and 12 months, respectively. Therapy switches were common, with up to five switches per patient. Seventeen percent of initiated therapies were stopped for more than 60 days but restarted within 1 year.ConclusionDespite inherent methodological limitations, results indicate therapy switches, premature treatment interruption, and restarting multidrug oral NTM treatment are common. These findings underscore the need for improved management of NTMLD through enhanced monitoring as well as more tolerable and effective treatment options.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-025-00507-9.

Background and ObjectiveAnticholinergic medications are known to affect the prognosis of older nursing home residents. Various anticholinergic scales were developed to measure the cumulative anticholinergic burden; among them, the CRIDECO Anticholinergic Load Scale (CALS) has recently emerged as a new tool to identify patients with cognitive impairment due to anticholinergic burden. This study aimed to externally validate the CALS and to evaluate the association of CALS and the anticholinergic cognitive burden (ACB) scales with baseline cognitive and functional impairment, as well as with 3-year mortality rates.MethodsA prospective cohort of 600 nursing home residents (mean age 80.4 ± 8.0 years; 69.8% women) underwent a comprehensive geriatric assessment. Anticholinergic burden was assessed at baseline using both CALS and ACB scales. Cognitive impairment (Mini-Mental State Examination < 24) and physical disability (one or more impaired activities of daily living) were evaluated cross-sectionally using a logistic regression model. Cox proportional hazards models were used to estimate the association between anticholinergic burden and 3-year mortality, adjusting for age, sex, multimorbidity, nutritional status, and cognitive and functional status.ResultsAmong 600 nursing home residents included in the study, 72.0% had cognitive impairment and 56.3% had at least one activity of daily living limitation. The CALS and ACB scores were significantly correlated (rho = 0.76), but CALS identified a higher number of residents with moderate-to-high anticholinergic burden. Multivariate logistic regression showed that CALS ≥ 2 was independently associated with cognitive impairment (odds ratio 1.84, 95% confidence interval 1.02–3.34), whereas ACB ≥ 2 was not. Both scales were associated with activities of daily living disability, with a stronger gradient and better goodness of fit for CALS than ACB. During the 3-year follow-up, 25.3% of residents died. Cox regression analyses showed that residents with CALS or ACB ≥ 2 had significantly lower survival over 3 years. In fully adjusted Cox models, both CALS ≥ 2 (hazard ratio 1.93, 95% confidence interval 1.07–3.46) and ACB ≥ 2 (hazard ratio 1.69, 95% confidence interval 1.02–2.83) remained associated with increased mortality. Prognostic performance was similar (CALS C-index: 0.783; ACB: 0.781), but the model fit favored CALS.ConclusionsIn this cohort of nursing home residents, anticholinergic burden as measured by both CALS and ACB was associated with baseline physical impairment and 3-year mortality, but CALS showed a better goodness of fit. Between the two scales, CALS only was independently associated with baseline cognitive impairment. These findings support the clinical utility of CALS in assessing anticholinergic-related risk among frail older adults in institutional settings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-025-00509-7.

BackgroundPrevious research in Canada has examined opioids prescription dispensing at the population level but did not examine the potential relationship with area-level income and rates of opioid dispensing. ObjectiveThe aim was to estimate average and annual opioid dispensing rate ratios (RRs) between lowest and highest income quintile geographic areas in Canada.MethodsWe performed a population-based retrospective study using the National Prescription Drug Utilization Information System (NPDUIS) between 2010 and 2018 that contains prescription records for all public drug plan beneficiaries (65+) in all Canadian provinces, excluding Quebec, Nova Scotia, and New Brunswick. We used census median household income, calculated at the Forward Sortation Area (FSA—the first three letters of the postal code) to assign income quintiles. Morphine milligram equivalent (MME) was calculated for all opioid dispensing and was divided by population of the FSA quintile. Population census year 2016 was used for population and income estimations. We calculated the average and annual RR between lowest and highest quintiles and stratified them by patients’ sex. The significance of the trend of annual RR was tested by linear regression. ResultsThe average MME per capita for the 65+ population ranged from 2321.8 in quintile 1 to 5831.9 in quintile 5. The RR between highest and lowest quintile was 2.5 (95% confidence interval [CI] 1.3–3.7), and was more profound for males (3.2, 95% CI 1.4–4.9) than females (2.2, 95% CI 1.2–3.3). Over the study period, the RR reduced slightly from 2.7 to 2.3 (p < 0.01). However, this trend was only significant for females.ConclusionInequity in opioid prescriptions dispensing was persistent over time. Patients in the lowest income quintiles received higher amounts of opioids per capita, with some sex variation. Dispensing policies must take these equity issues into account.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-025-00498-7.

BackgroundAnaplastic thyroid carcinoma (ATC) is a highly aggressive cancer historically associated with a median survival of about 5 months. Recent advances in tumor genomic testing have identified targetable BRAF mutations in about 35–40% of ATC cases and have shown high levels of programmed death ligand-1 (PD-L1) expression in ATC. These observations have led to clinical trials showing favorable outcomes with targeted therapy and immunotherapy for ATC.ObjectiveWe aimed to evaluate treatments and outcomes of patients diagnosed with anaplastic thyroid cancer treated at our institution in order to determine the impact of targeted therapy and immunotherapy.MethodsA retrospective review of ATC patients at a single institution was performed. Data were collected from institutional electronic medical records, including demographic information, treatments administered, and outcomes including survival.ResultsA total of 28 patients were identified within the period under study. Systemic therapy was initiated in 61% of patients. The median overall survival for all patients was 7.3 months. There was a statistically significant improvement in overall survival for patients who received targeted therapy or immunotherapy compared to those who did not.ConclusionsIn this single-institution cohort of 28 patients with ATC, patients who received either targeted therapies or immunotherapy demonstrated markedly improved outcomes. Further clinical trials are required to determine the optimal systemic therapy for this patient population.