Drugs - Real World Outcomes最新文献

Background: Topical ketoprofen gel (Fastum gel) is used for the treatment of rheumatic and traumatic musculoskeletal pain. Following reports of photosensitivity reactions, additional risk minimisation measures have been implemented in Europe to inform healthcare professionals (HCPs) and patients about this risk.

Objective: The main objectives of our survey were to assess both HCPs' awareness of the risk of photosensitivity associated with Fastum gel and their opinion on the usefulness of an annual direct healthcare professional communication (DHPC) in Belgium and Luxembourg.

Methods: A cross-sectional online survey was conducted between June and July 2023, approximately 1 month after the annual distribution of the DHPC. Targeted HCPs were asked about their awareness of the photosensitivity risk associated with Fastum gel, as well as their opinion on the usefulness of the annual DHPC. The study also explored the channels through which the information was received, along with awareness and use of educational materials. Frequencies and percentages were calculated both overall and by HCP category for each country.

Results: In Belgium, 569 HCPs responded to the survey. Almost all HCPs reported that they were aware of this risk (99%). More than half of pharmacists (58%) and half of physicians (50%) indicated that an annual DHPC is necessary. Around half of the respondents (49%) recalled receiving information about the risk in 2023, primarily through the DHPC (68%) while outlining other channels such as the logo on the packaging (42%) and the Summary of Product Characteristics (40%). Awareness of the patient card (32%) and the checklist (5%) was overall low, with very limited use in 2023. In Luxembourg, 190 HCPs responded to the survey. Almost all HCPs reported that they were aware of this risk (97%). The majority of pharmacists (70%) and more than half of physicians (52%) supported the annual DHPC distribution. Over two thirds of the respondents (68%) recalled receiving relevant information in 2023, mainly through the DHPC (70%) but also through the SmPC (30%). Awareness of the patient card (22%) and the checklist (13%) was overall low, with very limited use in 2023.

Conclusions: The results indicate a high level of awareness of the photosensitivity risk of Fastum gel among participating HCPs. Notably, a majority of HCPs expressed the need for an annual DHPC. This study also underscores the importance of using multiple channels of information to increase the opportunities for reaching HCPs. Nevertheless, the survey revealed limited use of the checklist and the patient card among HCPs.

Background and objective: Anticholinergic 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.

Methods: A 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.

Results: Among 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.

Conclusions: In 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.

Background: Limited research has addressed safety concerns related to vaccination against the human papillomavirus (HPV).

Objective: To investigate the association between receipt of HPV vaccination and autonomic dysfunction and menstrual irregularities in girls and young women.

Methods: Using a 25% random sample of IQVIA PharMetrics^® Plus for Academics claims database from 2016 to 2020, we conducted a self-controlled case series study in commercially insured girls and young women receiving their first HPV vaccine dose (analyses conducted between March 2024 and April 2025). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for two outcomes-autonomic dysfunction and menstrual irregularities. We conducted further analyses stratified by number of HPV vaccine doses received per beneficiary and by age (9-17 years vs. 18-26 years), as well as adjusted for age as a time-varying covariate. The IRRs were estimated over a maximum risk case post-vaccination period of 36 months compared to a 6-month within-person control pre-vaccination period.

Results: There were 1654 individuals in the autonomic dysfunction cohort and 3140 individuals in the menstrual irregularities cohort. When adjusted for age, HPV vaccination was associated with elevated IRRs for autonomic dysfunction (IRR 1.23; 95% CI 1.08-1.41) and menstrual irregularities (IRR 1.30; 95% CI 1.18-1.43). IRRs for individual outcomes varied by age group, with the younger cohort showing a significantly higher age-adjusted IRR than the older cohort for menstrual irregularities (IRR 1.51; 95% CI 1.33-1.72 vs. IRR 1.15; 95% CI 0.99-1.33, respectively). Although the risk of experiencing autonomic dysfunction was not significant in the adjusted younger cohort, young women aged 18-26 years had a heightened age-adjusted risk (IRR 1.40; 95% CI 1.12-1.75). Findings from the dose-response analysis were inconclusive.

Conclusions: HPV vaccination is associated with elevated risks of autonomic dysfunction and menstrual irregularities, which vary by age. Further research is needed to identify additional risk factors associated with HPV vaccination safety.

Background: Schizophrenia spectrum disorders (SSD) are chronic psychiatric conditions with high rates of medication nonadherence, relapse, and hospitalization. Long-acting injectable antipsychotics (LAIs) aim to improve adherence; their real-world use in inpatient settings is not yet well understood.

Objective: To investigate prescription patterns of LAI antipsychotics in a real-life setting among psychiatric inpatients with SSD in Australia.

Methods: This retrospective cross-sectional study was conducted at a major Australian tertiary center. It investigated prescription trends, demographics, hospitalization outcomes, and substance use among inpatients with SSD who received oral, LAI, or combined oral-LAI treatment. Readmission rates were also analyzed in patients with a history of medication nonadherence.

Results: Among the total of 510 inpatients with SSD, 26.6% received LAIs, 40% were treated with combined oral-LAI therapy, and 33.3% were prescribed oral antipsychotics alone. Second-generation LAIs were most prevalent (87.5%), with paliperidone being the most frequently used (53.7%). The combined oral-LAI therapy group had the highest rates of nonadherence (83.8%) and substance use (82.8%). Among patients with a history of medication nonadherence, those receiving LAIs had lower 30-day readmission rates compared with the oral antipsychotic treatment group.

Conclusions: Findings align with global trends favoring second-generation LAIs and highlight the rising yet understudied use of combined oral-LAI therapy. High nonadherence and substance use in the combined oral-LAI therapy group call for targeted interventions. While LAIs may reduce readmissions in nonadherent patients, further research is needed to assess combined therapy's effectiveness and optimize prescribing. These insights reinforce the role of LAIs in relapse prevention and the need for tailored adherence strategies.

Background: The optimal duration for thromboprophylaxis after colorectal cancer surgery remains uncertain. We sought to compare the effectiveness and safety of long-term thromboprophylaxis to that of short-term thromboprophylaxis in preventing venous thromboembolism (VTE) after colorectal cancer surgery.

Methods: In our retrospective study, patients undergoing colorectal cancer surgery were divided into the short-term (< 7 days) and long-term (≥ 7 days) thromboprophylaxis groups based on the low molecular weight heparin prophylaxis regimen. Propensity score matching was performed for both groups, and comparative analysis of the incidence of asymptomatic or symptomatic VTE and bleeding complications was conducted. Multivariable logistic regression analysis was performed in the unmatched cohort to explore the association of potential risk factors with postoperative VTE.

Results: A total of 140 patients undergoing colorectal cancer surgery were included. After matching, there were 57 patients in each group. VTE occurred in 18 patients (15.8%) within 6 months after surgery, with 12 cases (21.1%) in the short-term thromboprophylaxis group and six cases (10.5%) in the long-term thromboprophylaxis group (P = 0.123). There were no significant differences in the incidence of bleeding complications between the two groups. Multivariable logistic regression analysis indicated that long-term thromboprophylaxis can reduce the risk of postoperative VTE (odds ratio 0.34, 95% confidence interval 0.12-0.95; P = 0.039).

Conclusions: Long-term thromboprophylaxis (≥ 7 days) demonstrated comparable effectiveness and safety to shorter regimens (< 7 days) in preventing postoperative VTE in patients with colorectal cancer, while suggesting potential sustained protective benefits during extended follow-up periods exceeding 6 months. Whether VTE prophylaxis should be extended to 28 days post-surgery requires further research.

Background and objective: Nontuberculous 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.

Methods: This 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.

Results: Overall, 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.

Conclusion: Despite 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.

Background and objective: Sexual dimorphism in drug efficacy, beyond pharmacokinetics (PK), remains underexplored. Significant sex differences exist in drug metabolism and adverse events, highlighting the need for personalized medicine. The objective of our study was to assess whether there are sex differences in the pharmacodynamic (PD) response to valproic acid (VPA) in photosensitive epilepsy, focusing on electroencephalographic (EEG) biomarkers (e.g., photoparoxysmal response [PPR] raw data and transformed PPR data, the standardized photosensitivity range [SPR]) that cannot be attributed to pharmacokinetics alone. On the basis of some exploratory published evidence plus our own clinical observations of VPA treatment in patients with epilepsy plus photosensitivity over time, we hypothesized that an EEG pharmacodynamic difference might exist between females and males.

Methods: We conducted a retrospective, observational, single-center, within-patient EEG cohort study conducted on antiseizure medicine (ASM)-naïve photosensitive individuals before and after VPA treatment (nonrandomized). The data we reviewed had been collected from a referral hospital in the Netherlands from 1990 to 2000. Changes in EEG data, including raw PPR data (transformed into SPR), were analyzed before and after VPA therapy in 48 patients, including 27 females and 21 males, ranging in age from 8 to 50 years old for the entire cohort. Co-primary outcomes included a between-sex comparison in the distribution of within-patient SPR changes from pre-VPA to steady-state VPA therapy, and complete PPR elimination on EEG. Secondary outcomes included the comparison of percentage of males and females meaningfully responding to VPA across SPR change categories, VPA dose, potential impact of plasma [VPA] concentrations on SPR changes, and associaton of patient age with SPR values. Statistical analyses included univariate linear regression models, chi-squared tests, non-parametric Wilcoxon-Mann-Whitney tests, and Fisher's exact tests.

Results: Our first co-primary outcome revealed a statistically significant difference in the distribution of within-patient SPR changes from pre-VPA to steady-state VPA therapy. Males experienced a significantly greater reduction in SPR compared with females. The mean decrease in SPR was -7.0 ± 2.6 in males only versus -3.9 ± 3.3 in females only (p = 0.0018). The next co-primary outcome, the percent of patients with complete PPR elimination, or a SPR value = 0 on second EEG, was observed in ten (47.6%) males compared with four (14.8%) females, a 3.2-fold difference (p = 0.0237). One secondary outcome, the percentage of males with a VPA clinically meaningful to optimal response was 1.93-fold greater than females, at 100:51.8%, respectively (p < 0.0001). Between-sex VPA total daily milligram dose did not differ. Plasma [VPA] concentrations, although nearly twice as high in females, were not st

Background and objective: Hereditary angioedema presents as recurrent, unpredictable, and often debilitating attacks of cutaneous/submucosal swelling. This study assessed the characteristics and treatment patterns of patients receiving long-term prophylaxis with the plasma kallikrein inhibitor lanadelumab in US clinical practice.

Methods: This retrospective longitudinal study, based on a physician panel-based medical chart review, included patients with a diagnosis of hereditary angioedema due to C1 esterase inhibitor deficiency/dysfunction (HAE-C1INH-Type1/2), initiating lanadelumab in/after August 2018 (index date), and with ≥ 3 months' post-index follow-up (Part 1, N = 186) and, additionally, a dosing interval extension after initiating lanadelumab 300 mg every 2 weeks (Part 2, N = 75).

Results: Patients in Part 1 were predominantly aged ≥ 18 years (95.7%) with HAE-CINH-Type1 (90.3%); Part 2 included a higher proportion of patients with HAE-C1INH-Type2 (28.0% vs 9.7%). In Part 1, 115/165 (69.7%) patients with hereditary angioedema attack information experienced 371 attacks in the 3 months pre-index; these were mostly mild/moderate (60.4%) and most commonly affected the lips (38.0%) and hands (32.9%). In total, 19/155 (12.3%) patients had 39 attacks during the post-index period (mean ± standard deviation [interquartile range] attack rate: 0.1 ± 0.3 [0.0, 0.0] per month). In Part 2, a dosing interval extension was enabled by well-controlled disease (74/75, 98.7%); most patients (86.7%) transitioned from every 2 weeks to every 4 weeks dosing. Among patients with attack information, 7/72 (9.7%) experienced a hereditary angioedema attack while receiving an initial every 2 weeks dosing regimen and 4/75 (5.3%) after an extended-interval dosing regimen.

Conclusions: Lanadelumab dosing intervals can be individualized to maintain effective disease control. A dosing interval extension may be considered in well-controlled disease.

Background: In low- and middle-income countries, sulfonylureas are commonly prescribed due to cost-effectiveness. However, data comparing their real-world impact, especially when used alone versus in combination with metformin, remain limited.

Objective: This study aimed to assess the effectiveness of glipizide and glipizide plus metformin in individuals with type 2 diabetes (T2D) using real-world data.

Methods: Data was obtained from 11,949 individuals with T2D who were prescribed either glipizide or glipizide+metformin and had at least one follow-up within 1 year at a tertiary diabetes care centre in India. The primary outcome was the change in glycated hemoglobin (HbA1c) levels from baseline to follow-up. Secondary outcomes included changes in fasting plasma glucose (FPG), postprandial glucose (PPG), body mass index (BMI), and estimated glomerular filtration rate (eGFR).

Results: The mean age of participants was 56 ± 11 years, 59% (n = 7008) were male, and the mean diabetes duration was 10.2 ± 8 years. In the glipizide group (n = 6034), HbA1c decreased from 8.8% to 7.9% (p < 0.001), FPG decreased by 16 mg/dL (p < 0.001), and PPG decreased by 29 mg/dL (p < 0.001). In the glipizide + metformin group (n = 5915), HbA1c levels declined from 8.9% to 7.8% (p < 0.001), and FPG and PPG declined by 23 mg/dL and 44 mg/dL, respectively (p < 0.001). BMI remained stable in the glipizide group, while a reduction of 0.2 kg/m² was observed among overweight/obese individuals in the glipizide + metformin group. The use of glipizide and glipizide + metformin effectively improved glycemic control without adverse anthropometric changes. C-peptide levels were preserved across all treatment groups, demonstrating sustained β-cell function. HbA1c reductions were observed consistently across all eGFR categories. Furthermore, as glipizide plus metformin is one of the least expensive antidiabetic drugs in India (₹1460/year [$16.87]) it can help improve accessibility to treatment even among those in lower socio-economic statuses.

Conclusions: Glipizide as monotherapy or in combination with metformin, significantly improved glycemic control even in those with decreasing renal function, with no adverse effects on weight and with preservation of β-cell function. While long-term studies are needed to assess the sustainability of these benefits, glipizide can be considered a cost-effective therapeutic option for T2D in low- and middle-income countries.

Background: Previous 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.

Objective: The aim was to estimate average and annual opioid dispensing rate ratios (RRs) between lowest and highest income quintile geographic areas in Canada.

Methods: We 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.

Results: The 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.

Conclusion: Inequity 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.