Concomitant Medication Use Research Articles

Pre-exposure prophylaxis program in the Community of Madrid: Two years of experience

IntroductionPre-exposure prophylaxis (PrEP) against the human immunodeficiency virus (HIV) is an effective and safe preventive measure. However, it has not reached all target users who could benefit from it.The study aimed to understand the sociodemographic, clinical and behavioral baseline characteristics of PrEP users. As a secondary objective, the use of concomitant medication and drug consumption were described. MethodologyObservational, retrospective and descriptive study of the sociodemographic, clinical and behavioral characteristics of the users who were included in the PrEP program of the Community of Madrid during the first two years of experience. ResultsTwo thousand two hundred fifty-six PrEP users were included, 99.0% men, with a mean age of 36.9 years (SD 8.68). 33.1% presented a sexually transmitted infection (STI) on the first visit, highlighting chlamydiasis and rectal gonococci. 70.4% reported using drugs associated with sex, and 42.4% participated in chemsex sessions in the last 3 months. A high percentage of users with concomitant medication was observed (37.6%), highlighting drugs related to mental health and alopecia. ConclusionsA multidisciplinary approach is required to cover all the needs of PrEP users, including mental health evaluation measures and addiction treatment with the clinical approach.

#2338 Potassium-competitive acid blocker use is associated with a lower risk of renal function deterioration compared to proton pump inhibitor use

Abstract Background and Aims Proton pump inhibitors (PPI) are commonly used drugs worldwide and have been linked to worsening renal function and incident chronic kidney disease. Recently, potassium-competitive acid blockers (P-CAB) have emerged as alternative gastric acid-reducing agents with a comparable effect as PPIs. However, little is known about the renal safety of P-CAB. We aimed to compare the renal outcomes of patients treated with P-CAB and those treated with PPI. Method We retrospectively identified all patients who were prescribed P-CAB (tegoprazan) or PPI (esomeprazole) for 30 days or more in outpatient clinics of a tertiary care center between 2019 and 2023. Longitudinal serum creatinine data and various demographic and clinical variables were collected. Renal outcomes were defined as creatinine doubling or decline in estimated glomerular filtration rate (eGFR) of 30%. Patients with baseline eGFR < 15 mL/min/1.73 m2 and those who do not have sufficient creatinine measures to assess renal outcomes were excluded. Cox proportional hazard analyses were performed for renal outcomes with adjustment of multiple clinical covariates. Results Among 8 436 patients with a mean followup of 21 months, 2 214 and 6 222 patients were treated with P-CAB and PPI, respectively, for esophageal and gastric diseases. P-CAB group showed lower rates of creatinine doubling (Log-rank P = 0.001) and decline of eGFR (Log-rank P = 0.001) compared to PPI group. P-CAB use was associated with a 0.50-fold (95% confidence interval [CI] 0.33–0.75) lower risk for creatinine doubling and 0.58-fold (95% CI 0.42–0.81) lower risk for eGFR decline in unadjusted analysis. After adjusting multiple covariates including baseline eGFR, prescription days, major comorbidities, and concomitant use of other medications, hazard ratios for creatinine doubling and eGFR decline were 0.64 (95% CI 0.42–0.98) and 0.73 (95% CI 0.53–1.02), respectively. Conclusion Use of P-CAB is associated with a lower risk for renal function deterioration compared to PPI. Given the renal safety concerns of PPIs, using P-CAB could be a relatively safer strategy for preserving kidney function in patients who need long-term gastric acid suppression. Further studies with a larger cohort incorporating other P-CABs are required to validate this finding.

Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings

BackgroundTo evaluate the weight loss outcomes of the large US cohort of patients undergoing endoscopic sleeve gastroplasty (ESG) with or without concomitant anti-obesity (AOM) use. MethodsWe performed a retrospective analysis of adult patients who underwent ESG from seven different sites, from January 1, 2020 to November 30, 2022. Percent total body weight loss (%TBWL) and %excess weight loss (%EWL) were calculated based on baseline weight at the procedure. Medication use was considered if the subject received a prescribed AOM during the study period. SPSS (version 29.0) was used for statistical analyses. ResultsA total of 1506 patients were included (1359 (90.2 %) no AOM use and 147 (9.8 %) AOM use). Patients who were on an active AOM at the time of the procedure had a significantly lower TBWL% as compared to patients not on AOMs at 6 months. At the 24-month visit, patients who were prescribed AOMs after the 12-month visit had a significantly higher TBWL% and EWL% as compared to patients who were on active AOM at the time of the procedure. There was no significant difference between classes of medications at any time point, however, patients on a GLP-1RA had a trend towards improved weight loss at 18 and 24 months. ConclusionIn this large, real-world cohort of patients from the United States, data signal that with the use of pharmacotherapy at the appropriate time, patients can achieve optimal results.

Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: A population-based study

The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients. This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations. Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance. Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.

Proton pump inhibitors associated with severe COVID-19 among two-dose but not three-dose vaccine recipients.

Proton pump inhibitors (PPIs) may increase the risk of COVID-19 among non-vaccinated subjects via various mechanisms, including gut dysbiosis. We aimed to investigate whether PPIs also affect the clinical outcomes of COVID-19 among vaccine recipients. This was a territory-wide cohort study of 3272286 vaccine recipients (aged ≥18years) of ≥2 doses of either BNT162b2 or CoronaVac. Exclusion criteria included prior gastrointestinal surgery, immunocompromised status, and prior COVID-19. The primary outcome was COVID-19, and secondary outcomes included COVID-19-related hospitalization and severe infection (composite of intensive care unit admission, ventilatory support, and/or death). Covariates include age, sex, the Charlson Comorbidity Index, comorbidities, and concomitant medication use. Subjects were followed from index date (first dose of vaccination) until outcome occurrence, death, additional dose of vaccination, or March 31, 2022. Exposure was pre-vaccination PPI use (any prescription within 90days before the index date). Propensity score (PS) matching and a Poisson regression model were used to estimate the adjusted incidence rate ratio (aIRR) of outcomes with PPI use. Among 439154 PS-matched two-dose vaccine recipients (mean age: 65.3years; male: 45.7%) with a median follow-up of 6.8months (interquartile range: 2.6-7.9), PPI exposure was associated with a higher risk of COVID-19 (aIRR: 1.08; 95% confidence interval [95% CI]: 1.05-1.10), hospitalization (aIRR: 1.20; 95% CI: 1.08-1.33), and severe infection (aIRR: 1.57; 95% CI: 1.24-1.98). Among 188360 PS-matched three-dose vaccine recipients (mean age: 62.5years; male: 49.0%; median follow-up: 9.1months [interquartile range: 8.0-10.9]), PPIs were associated with higher infection risk (aIRR: 1.11; 95% CI: 1.08-1.15) but not other outcomes. Although PPI use was associated with a higher COVID-19 risk, severe infection was limited to two-dose but not three-dose vaccine recipients.

Abstract PO1-09-12: Cancer health disparities among patients with early-stage estrogen receptor-positive (ER+) breast cancer treated in public or private practices in Brazil

Abstract Background Cancer registries in Brazil are deficient and data about patients’ profiles and cancer treatment patterns are scarce in the country. Moreover, while 30% of population has access to private insurance, almost 70% of population uses publicly health services. The objective of this work was to describe the sociodemographic and clinicopathological characteristics of women with early-stage ER+ breast cancer on adjuvant ET in different regions of Brazil, and to describe treatment patterns for this disease according public and private institutions. Methodology: We performed a real-world data analysis in different institution regions of Brazil. Women with a history of early-stage ER+ invasive carcinoma of the breast on adjuvant endocrine therapy for at least 6 months were invited to participate of this study in 12 centers in four different regions in Brazil. Demographic and clinicopathologic information was retrieved from medical records. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. High education level was defined by completed high school. Data collection was done with RedCap software. Qualitative variables were compared between groups using the Chi-square or exact Chi-square test and for quantitative variables the non-parametric Mann-Whitney test was used. P < 0.05 was considered significant. Analyzes were performed in SAS 9.4; Results: From June 2021 to May 2023, a total of 461 women with ER+, early BC, were included in this analysis. A total of 233 (50.6%) came from private institutions, the mean age was 56.02 years (range 22-93), 47.69% were non-white, 61.3% were post-menopause, 61.7% lived with a partner, and 76.2% were highly educated and 66.81% had comorbidities. Tumor staging at diagnosis was classified as III, II and I respectively in 21.26%, 43.17% and 35.57% of all cases. Regarding treatment received, 62.4% of patients underwent lumpectomy, 32.2% had axillary dissection, 67.6% received (neo)adjuvant chemotherapy, 45.2% were on aromatase inhibitors and 14.19% were on ovarian function suppression plus ET . Median duration of ET use was 2.78 years (range 6 months- 9.61 years). Publicly health insurance was associated significantly associated with younger age at diagnosis (< 60 yo), premenopausal status, to live alone, lower educational level, more advanced tumors, prior mastectomy, prior axillary dissection, prior neo-adjuvant chemotherapy, prior radiotherapy, lower use of aromatase inhibitors, ovarian function suppression plus ET, and CDK4/6 inhibitors, while higher use of concomitant medications. Conclusion: The study shows significant health disparities among women with early-stage ER+ breast cancer treated in private versus public institutions in Brazil. Importantly, despite having more advanced tumors, women in public institution had less access to ovarian suppression, CDK4/6 inhibitors and were treated with more aggressive surgical procedures. A deep discussion involving government, lawmakers, health care providers and patients should be conducted to try to decrease the described disparities. Patient’s characteristic and patterns of treatment among patients with estrogen receptor-positive breast cancer on adjuvant therapy according to health insurance in Brazil ALND: axillary lymph node dissection; CDK4/6i: CDK4/6 inhibitors; ET: endocrine therapy; OS: ovary suppression. Citation Format: Romualdo Barroso-Sousa, Daniele Assad-Suzuki, Danielle Santos, Fernanda Moura, Sulene Oliveira, Anna Luiza Galvão, Bruno Souza, Amanda Castro, Monalisa Andrade, Andrea Shimada, Yuri Beckedorff, Maria Cristina Magalhães, Cristiano Souza, Carlos Paiva, Heloísa Resende, Daniela Pereira, Angelica Rodrigues, Daniela Rosa. Cancer health disparities among patients with early-stage estrogen receptor-positive (ER+) breast cancer treated in public or private practices in Brazil [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-12.

Abstract PO5-11-08: Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer

Abstract Background: Treatment with endocrine therapy such as tamoxifen has been identified as one of the most important variables linked with survival among women with hormone receptor-positive breast cancer (BC). There is significant risk reduction of BC recurrence and BC mortality at 15 years among patients treated with tamoxifen for 5 years compared to no endocrine therapy. Tamoxifen is metabolized in the liver via multiple cytochrome P (CYP) isoforms. To ensure optimal efficacy of tamoxifen, consideration must be given to concomitant use of other commonly prescribed drugs such as antidepressants. Some selective serotonin reuptake inhibitors (SSRIs) are potent inhibitors of CYP2D6, an enzyme that metabolizes tamoxifen into its active metabolite, endoxifen, which has anti-tumor effect. Such inhibition can reduce the plasma concentration of endoxifen which could lead to higher rates of BC recurrence. This resulted in an FDA black box warning discouraging concurrent prescriptions of tamoxifen and SSRIs, yet clinical data to support this warning is lacking. Our aim is to describe the practice patterns of concomitant use of tamoxifen and antidepressant medication at our institution. Methods: This is a single institution retrospective study that included adult women, ages 18-99, with stage I-IV BC, who received adjuvant tamoxifen and were taking an antidepressant medication between years 2016-2021. Patients were identified from a tumor registry database. Patient demographics and tumor characteristics were collected via electronic medical record. Results: A total of 419 patients met the inclusion criteria. At the start of tamoxifen therapy, 348 women were on at least one antidepressant, mostly for Major Depressive Disorder (86%). Of those women, 22% were prescribed a strong/moderately potent CYP inhibitor (paroxetine, fluoxetine, duloxetine, or bupropion) and 43% were prescribed weak or non-CYP inhibiting SSRIs (citalopram, escitalopram, fluvoxamine, and sertraline). The most commonly prescribed antidepressants at the start of tamoxifen, alone or in combination with a second antidepressant, were: venlafaxine (30%), escitalopram (17%), sertraline (13%), citalopram (12%) and duloxetine (10%). Main prescribers of antidepressants were primary care physicians (70%), psychiatrists (10%) followed by academic medical oncologists (7%) and regional medical oncologists (6%). Interestingly, the majority of women continued taking the same antidepressant after starting tamoxifen (76%) while, at least 10% of patients changed anti-depressant classes prior to starting tamoxifen, due to concern for drug-drug interaction. When a different class of antidepressant was chosen after starting tamoxifen (22%), serotonin and norepinephrine reuptake inhibitors (SNRIs) were the most frequent class (48%), followed by a different SSRI (42%). The time in which the antidepressant change occurred was variable, but most commonly prior to initiating tamoxifen. Conclusion: Concurrent use of tamoxifen and antidepressant medications is common. Theoretical risk of reduced efficacy of tamoxifen with inhibitors of CYP leads to medication changes for some but not all patients requiring tamoxifen and an antidepressant medication. This can have clinical implications as stability on a specific antidepressant is important for patients and adjustment may impact control of their mood disorder. In some cases, even if a drug-drug interaction was identified, some patients chose to continue their current antidepressant due to concerns of mood de-stabilization, and in other cases, aromatase inhibitors were started as an alternative. These findings highlight differences in practice patterns for which additional guidance may be helpful in bringing awareness and standardization to care. Citation Format: Mariah Ondeck, Bennett Osantowski, Nerea Lopetegui-Lia, Wei Wei, Alexandra Murray, Amanda Maggiotto, Halle Moore, Erin Roesch. Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-08.

Predictors of real-world response in adults treated with botulinumtoxin-A for upper limb spasticity

Background: To explore predictors of treatment response in adults receiving botulinumtoxin-A (BoNT-A) for upper limb spasticity (ULS) and to describe the association between response and concomitant medication, professional physical therapy, and quality of life (QoL). Methods: This was a secondary analysis of the longitudinal Upper Limb International Spasticity study (ULIS-III) data set. Eligible patients were adults receiving/initiating BoNT-A treatment for ULS in clinical practice. The treatment response was a goal attainment scaling (GAS) T score change of ≥10 points from baseline to follow-up for each cycle. Concomitant medication was recorded. Time spent on professional physical therapy and self-management was recorded using the Upper Limb Focal Spasticity Therapy Recording (ULSTR) schedule. QoL was assessed using the EQ-5D-5L questionnaire. Baseline patient and clinical characteristics were described. Factors predictive of treatment response were explored using stepwise multivariable regression modeling (linear or logistic as appropriate for the outcome) and backward elimination (α=0.1). Results: Overall, 828/981 patients had response data; 71.9% responded to BoNT-A therapy. Potential predictors of response identified were the use of injection guidance techniques (P=0.001), female sex (P=0.031), and abobotulinumtoxin-A therapy (vs. onabotulinumtoxin-A; P<0.001). Compared with nonresponders, responders had marginally lower use of concomitant medication, received marginally more professional physical therapy and (subgroup only) had improved QoL. Age, duration/distribution, severity of impairment, and previous BoNT-A had no predictive value. Conclusions: Future analyses of ULIS-III data will aim to validate these findings and further explore determinants of treatment response and the interplay between care modalities.

Levodopa-Carbidopa-Entacapone Intestinal Gel in Advanced Parkinson Disease: A Multicenter Real-Life Experience.

For Parkinson disease (PD) patients who have been diagnosed with advanced disease that can no longer be effectively controlled with optimized oral or transdermal medications, a range of device-aided therapies (DAT) are available, comprising either deep brain stimulation or infusion therapies providing continuous dopaminergic stimulation. Levodopa-entacapone-carbidopa intestinal gel (LECIG) infusion is the latest DAT for advanced PD (APD) that was approved in Romania in 2021. What is the experience to date in real-world clinical practice in Romania regarding the efficacy and tolerability of LECIG in APD? A retrospective evaluation of 74 APD patients treated with LECIG at 12 specialized APD centers in Romania. Demographic data and various clinical parameters were recorded, including Mini Mental State Evaluation score or Montreal Cognitive Assessment Test score. Levodopa-equivalent daily dose and the administered doses of levodopa and other PD medications were evaluated at baseline and after starting LECIG treatment. The efficacy of LECIG in reducing daily hours of off time, motor fluctuations, and dyskinesias were assessed. Any percutaneous endoscopic gastrojejunostomy system or device complications after starting LECIG treatment were noted. At baseline, patients were taking oral levodopa for a mean of 5.3 times per day, with a high proportion also taking concomitant add-on therapies (dopamine agonists, 86%, monoamine oxidase type-B inhibitors, 53%; catechol-O-methyltransferase inhibitors, 64%). LECIG treatment significantly reduced daily off time versus baseline from 5.7 h/d to 1.7 hours per day ( P < 0.01). Duration and severity of dyskinesias was also significantly reduced versus baseline, and improvements were observed in Hoehn and Yahr Scale scores. LECIG treatment also allowed a significant reduction in the use of concomitant oral medications. These findings suggest that LECIG treatment is an effective DAT option in APD that can simplify the treatment regimen.

Differences in Glutamate Dehydrogenase (GLDH) and Other Liver Biochemistry Levels before and after Remdesivir Treatment in COVID-19

Background: Remdesivir (RDV) is a broad-spectrum antiviral approved by the Food and Drug Administration (FDA) for the treatment of Covid-19 patients, known to have the potential to cause toxic effects on the liver. Routine monitoring of liver biochemical parameters such as AST, ALT, bilirubin, ALP and GGT, can help detect liver injury. Drug-induced liver injury, according to Hy's law, is characterized by an increase in ALT &gt; 5x ULN, or ALP &gt; 2x ULN, or an increase in ALT &gt; 3x and total bilirubin &gt; 2x ULN, simultaneously. Glutamate dehydrogenase (GLDH) is a sensitive and specific hepatic marker, which can detect liver injury and loss of mitochondrial integrity earlier than other liver biochemical parameters. This study aimed to analyze GLDH levels and liver biochemical parameters before and after RDV therapy in patients with Covid-19. We also analyze several factors that affect liver function and suggest renal function. Methods: This study used an observational analytical with a prospective cohort design, in a population of Covid-19 patients receiving RDV therapy at the infectious emergency department and isolation ward Dr. Soetomo Surabaya for September-November. Consecutive sampling was taken. The subject had drawn blood twice; once before therapy and 5 days after receiving intravenous RDV. GLDH examination is using sandwich ELISA method, while ALT, AST, ALP, GGT, direct and total bilirubin were determined spectrophotometrically. Mann-whitney, the Wilcoxon rank test and Spearman correlation test were used to analyze the data. Results: The number of samples was 34 participants with an average age of 52.47+15.21 years. Concomitant medications were dominated by n-acetylcysteine (94.1%), antioxidants (91.2%) and immunomodulators (82.4%). None of the subjects suffered liver injury induced by RDV according to Hy’s Law. Median GLDH serum levels before RDV treatment 1,14 U/L and after 5 days RDV administration 0,85 U/L (p=0,945), AST (36,4 U/L; 34, 00U/L; p=0,140), ALT (30,43 U/L; 30,20 U/L; p=0,301), DBI (0,15mg/dL; 0,24mg/dL; p=0,090), TBI (0,49mg/dL; 0,50mg/dL; p=0,567), ALP (85,0U/L; 87, 5 U/L; p=0,313) dan GGT (64,5U/L; 71,0U/L; p=0,871). The use of concomitant medication was thought to have protective properties against hepatocytes. Conclusion: After 5 days of RDV treatment, there is no evidence of liver injury. There are no significant differences in GLDH levels and other liver biomarker parameters compared to baseline. There is no difference in delta GLDH levels between groups with and without renal impairment.

Population Pharmacokinetic Modeling and Exposure-Efficacy and Body Weight-Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed the suitability of a fixed-dose regimen of tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients with asthma or healthy participants enrolled in 8 clinical studies (phases 1-3). Tezepelumab exposure-efficacy relationships were analyzed in the phase 3 NAVIGATOR study (NCT03347279), using asthma exacerbation rates over 52 weeks and changes in pre-bronchodilator forced expiratory volume in 1 s at week 52. Tezepelumab pharmacokinetics were well characterized by a 2-compartment linear disposition model with first-order absorption and elimination following subcutaneous and intravenous administration at 2.1-420 and 210-700 mg, respectively. There were no clinically relevant effects on tezepelumab pharmacokinetics from age (≥12 years), sex, race/ethnicity, renal or hepatic function, disease severity (inhaled corticosteroid dose level), concomitant asthma medication use, smoking history, or anti-drug antibodies. Body weight was the most influential covariate on tezepelumab exposure, but no meaningful differences in efficacy or safety were observed across body weight quartiles in patients with asthma who received tezepelumab 210 mg subcutaneously Q4W. There was no apparent relationship between tezepelumab exposure and efficacy at this dose regimen, suggesting that it is on the plateau of the exposure-response curve of tezepelumab. In conclusion, a fixed-dose regimen of tezepelumab 210 mg subcutaneously Q4W is appropriate for eligible adults and adolescents with severe, uncontrolled asthma.

Impact of Polypharmacy and Risk Factors for Exacerbation of Lower Urinary Tract Symptoms in Patients with Urological Conditions: A Retrospective Study in a Japanese Municipal Hospital.

Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.

Plasmapheresis in thyrotoxicosis: a single-center case series

BackgroundPlasmapheresis represent an alternative therapeutic option for hyperthyroidism with thyroid storm or refractory cases. It provides a rapid decrease in plasma thyroid hormones and anti-thyroid antibodies. The aim of this paper was to report our single center’s experience in managing particular situations of hyperthyroidism using apheresis.Cases presentationThe following case series describes three young African patients (two females, one male) aged 29, 37, and 25 years old, respectively, with Graves’ disease who presented with drug ineffectiveness, drug-induced agranulocytosis, and thyroid storm with multi-organ failure. The three patients underwent plasmapheresis sessions leading to effective decline of thyroid hormone levels and offering a window for processing total thyroidectomy.Discussion/conclusionThe standard management of thyrotoxicosis and thyroid storm was usually codified by the concomitant use of antithyroid medication, iodine, beta-blockers, and corticosteroids. This medical preparation can be effective in most cases. However, drug toxicity or ineffectiveness can limit the use of such therapeutics. Our paper supports the efficiency and safety of therapeutic plasma exchange in the preoperative management of thyrotoxicosis.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies

BackgroundAs the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years).MethodsWeek 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis.ResultsOf 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years.ConclusionsAmong individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities.Trial registration number: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Clinical Experience on the Use of a Single-day, Two-injection Start Initiation Regimen of Aripiprazole Once Monthly in Patients With Schizophrenia in Spain: SaTISfy Study.

The two-injection start (TIS) initiation regimen was recently approved for aripiprazole once monthly 400mg (AOM400), with potential benefits in adherence. The SaTISfy study described in this article analyzed Spanish psychiatrists' perspectives on hospitalization lengths of stay, schizophrenia management, and the use of AOM400-TIS. The authors describe an ecological study of aggregated data collected using a 41-question survey. Fifty psychiatrists were asked to provide their perceptions of their patients with schizophrenia and treatment with AOM400. The psychiatrists reported that lack of treatment adherence was the main reason for hospitalization for 58.3% of their patients diagnosed with schizophrenia. Aripiprazole, in any formulation, was the most commonly prescribed therapeutic option, being prescribed for a mean (SD) of 2.5 (0.9) out of 5 patients, while 98% of psychiatrists chose AOM400-TIS for patients who failed to adhere to previous treatments. Patients with schizophrenia, regardless of their treatment, were hospitalized for an average of 17.7 (3.93) days versus patients with schizophrenia treated with AOM400-TIS, who were hospitalized for an average of 14.2 (4.18) days, a reduction of 3.5 (3.86) days. Patients treated with AOM400-TIS showed a reduction of 5 (4.18) days compared with the mean national duration of hospitalization for acute patients in psychiatry units in Spain (19.18d). The surveyed psychiatrists reported that AOM400-TIS improved safety and tolerability. Most of the psychiatrists were satisfied with the administration and results of AOM400-TIS. Most of the psychiatrists (90%) also reported that fewer health care resources were consumed with AOM400-TIS, mainly due to a reduction in hospitalization days and in the use of concomitant medications. AOM400-TIS was considered to have a positive impact on the duration of hospitalization and thus on the use of health care resources. There was a positive perception of adherence, safety, and tolerability with the use of AOM400-TIS in patients with schizophrenia.

Risk of fall or fracture with concomitant use of prescription opioids and other medications in osteoarthritis patients.

Osteoarthritis (OA) patients taking prescription opioids for pain are at increased risk of fall or fracture, and the concomitant use of interacting drugs may further increase the risk of these events. To identify prescription opioid-related medication combinations associated with fall or fracture. We conducted a case-crossover-based screening of two administrative claims databases spanning 2003 through 2021. OA patients were aged 40 years or older with at least 365 days of continuous enrollment and 90 days of continuous prescription opioid use before their first eligible fall or fracture event. The primary analysis quantified the odds ratio (OR) between fall and non-opioid medications dispensed in the 90 days before the fall date after adjustment for prescription opioid dosage and confounding using a case-time-control design. A secondary analogous analysis evaluated medications associated with fracture. The false discovery rate (FDR) was used to account for multiple testing. We identified 41 693 OA patients who experienced a fall and 24 891 OA patients who experienced a fracture after at least 90 days of continuous opioid therapy. Top non-opioid medications by ascending p-value with OR > 1 for fall were meloxicam (OR 1.22, FDR = 0.08), metoprolol (OR 1.06, FDR >0.99), and celecoxib (OR 1.13, FDR > 0.99). Top non-opioid medications for fracture were losartan (OR 1.20, FDR = 0.80), alprazolam (OR 1.14, FDR > 0.99), and duloxetine (OR 1.12, FDR = 0.97). Clinicians may seek to monitor patients who are co-prescribed drugs that act on the central nervous system, especially in individuals with OA.

Comparison between sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors on the risk of incident cancer in patients with diabetes mellitus: A real-world evidence study.

Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT-2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan. This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT-2is during 2016-2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP-4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use. After controlling for relevant variables, the SGLT-2i cohort (aHR=0.90, 95% CI=0.87-0.93) had a significantly lower risk of developing cancer than the DPP-4i cohort, particularly when the SGLT-2i was dapagliflozin (aHR=0.91, 95% CI=0.87-0.95) or empagliflozin (aHR=0.90, 95% CI=0.86-0.94). Regarding cancer type, the SGLT-2i cohort's risk of cancer was significantly lower than that of the DPP-4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer. SGLT-2i use was associated with a significantly lower risk of cancer than DPP-4i use.

Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.

Real-world management of patients with neuromyelitis optica spectrum disorder using satralizumab: Results from a Japanese claims database

BackgroundSatralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database. MethodsWe used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study. ResultsOf the 131 patients included in the overall population, most were female (90.8 %), aged 18–65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0–351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date. ConclusionThese real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.