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Drugs : Real World Outcomes
Number of Followers: 1  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 2199-1154 - ISSN (Online) 2198-9788
Published by Springer-Verlag Homepage  [2467 journals]
  • CYP2D6 Substrate Dispensing Among Patients Dispensed Mirabegron: An
           Administrative Claims Analysis

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      Abstract: Background Overactive bladder (OAB) is characterized by the presence of bothersome urinary symptoms. Pharmacologic treatment options for OAB include anticholinergics and β3-adrenergic agonists. Use of β3-adrenergic agonists may result in similar treatment efficacy with a decreased side effect profile compared with anticholinergics because high anticholinergic burden is associated with cardiovascular and neurologic side effects. However, the β3-adrenergic agonist mirabegron, one of two approved drugs within this class, is a moderate cytochrome P450 (CYP) 2D6 inhibitor, and coadministration of drugs that are CYP2D6 substrates with mirabegron may lead to adverse drug effects. Objective The aim of this study was to quantify how often CYP2D6 substrates were dispensed in patients receiving mirabegron among adults of any age and among those ≥ 65 years of age. Methods In this retrospective descriptive analysis, a deidentified administrative claims database in the United States, IQVIA PharMetrics® Plus, was used to identify dispensing claims for CYP2D6 substrates and mirabegron from November 2012 to September 2019. Prevalence of CYP2D6 substrate dispensing was assessed in patients dispensed mirabegron among all adults ≥ 18 years old and additionally among a cohort of those ≥ 65 years old. Patient baseline profiles at the time of mirabegron and CYP2D6 substrate codispensing and at the time of mirabegron dispensing were compared. CYP2D6 substrates were categorized as those with the potential for increased risk of QT prolongation, with anticholinergic properties, with narrow therapeutic index (NTI), contraindicated or having a black box warning when used with CYP2D6 inhibitors, or used for depression or other psychiatric disease. Dispensing data and patient profiles were summarized descriptively. Results Overall, 68.5% of adults ≥ 18 years old dispensed mirabegron had overlapping dispensings for one or more CYP2D6 substrate; 60.6% and 53.6% had overlapping dispensings for CYP2D6 substrates with anticholinergic properties or risk of QT prolongation, respectively. CYP2D6 substrates with NTI, contraindicated with CYP2D6 inhibitors, or for psychiatric use were codispensed in 17.7%, 16.6%, and 38.0% of adult mirabegron users, respectively. Mirabegron users receiving one or more concurrent CYP2D6 substrate were more likely to be older, have more comorbidities and baseline polypharmacy, and have increased healthcare resource utilization compared with those without concurrent CYP2D6 substrates. Commonly codispensed CYP2D6 substrates included hydrocodone, oxycodone, tramadol, metoprolol, and tamsulosin. Findings were similar for patients in the older cohort (≥ 65 years old), with 72.1% receiving overlapping CYP2D6 substrates. Conclusions Codispensing of CYP2D6 substrates, especially those with anticholinergic properties or risk of QT prolongation, was common among adults and older adults receiving mirabegron. Results highlight the need for improved awareness of CYP2D6 substrate prescribing among patients receiving pharmacologic treatment for OAB that inhibits the CYP2D6 pathway.
      PubDate: 2022-12-02
       
  • Treatment Patterns, Clinical Outcomes and Health Care Resource Utilisation
           in Patients with EGFR-mutated Metastatic Non-Small Cell Lung Cancer: A
           Real-World Study in South Korea

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      Abstract: Background Despite the dynamic treatment landscape for EGFR mutant-positive metastatic non-small cell lung cancer (EGFRm+ mNSCLC), most of the earlier studies have focused on US or Western populations. Objective The objective of this study was to explore real-world treatment patterns and outcomes of South Korean patients with EGFRm+ mNSCLC. Methods Retrospective chart review of adult patients with EGFRm+ mNSCLC who received systemic treatment between January-2019 and June-2019. Results A total of 162 patients were included from 21 hospitals, with a median follow-up of 15.6 months. Median age was 65.0 years, 22% had central nervous system metastasis, and 57% and 38% had exon 19 deletion and exon 21 L858R, respectively. Among 144 patients (89%) who received first-line EGFR-tyrosine kinase inhibitor, afatinib was most the common (44%), followed by gefitinib (28%) and erlotinib (13%). First-line chemotherapy was more common when an EGFR-mutation was detected after versus before first-line treatment initiation (31% vs 5%). Discontinuation of first-line treatment was mostly due to disease-progression (81%) and toxicity (7%). Among 58 (78%) patients who received second-line treatment, osimertinib was the most common (40%). Most (60%) patients reported ≥1 Grade ≥3 adverse event during first-line treatment. Following initiation of first-line treatment, physician visits and chest X-rays were the most frequent healthcare utilisation events. Rates of emergency-room visits and hospitalization were 12% and 16%, respectively, with a mean length-of-stay of 10.4 days. At 12 months, overall survival rate was 95%, and numerically worse for patients with exon 21 versus 19 mutations. Conclusions Characteristics and clinical outcomes of Korean patients with EGFRm+ mNSCLC in real-world practice were comparable to those observed in clinical trials. As osimertinib was not reimbursed for first-line treatment before study completion, further investigation is warranted to explore evolving treatment practice.
      PubDate: 2022-12-02
       
  • Treatment Pathways and Health Outcomes of German Patients with Chronic
           Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell
           Transplantation: A Retrospective Health Claims Data Analysis

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      Abstract: Background Although chronic graft-versus-host-disease (cGvHD) is an important long-term complication after allogenic hematopoietic cell transplantation (allo-HCT) and is associated with increased healthcare resource utilization, real-world evidence is scarce. Objectives The aim of the study was to evaluate survival of patients with cGvHD in Germany and to analyze hospitalization and treatment patterns. Patients and Methods Based on a German claims database with 4.9 million enrollees, a retrospective longitudinal analysis covering a 6-year period between 2013 and 2018 was conducted. Patients with allo-HCT in 2014 or 2015 (index date) and no record of transplantation or documentation of GvHD 365 days prior to index were included. Patients who subsequently developed a cGVHD were compared with those who did not develop a cGVHD within 3 years after index date. cGVHD cases were identified based on documented International Classification of Diseases, Tenth Revision (ICD-10) diagnosis and treatment algorithms. Since the onset of cGvHD is defined at 100 days after allo-HCT, only those alive beyond day 100 were considered in the survival analysis. Patients who did not survive the first 100 days after allo-HCT were censored to prevent a selection bias due to early mortality within patients without GvHD. Survival rates were plotted using the Kaplan–Meier estimator. The number of hospitalizations and average lengths of stay as well as treatment patterns were descriptively examined. Results Overall, 165 cGvHD patients were identified and compared with 43 patients without cGVHD. Short-term survival rates were better for patients with cGvHD; the 6-month survival probability was 95.8% for patients with cGVHD and 83.7% for patients without cGVHD. However, long-term survival was better in patients without GvHD; The 30-month survival probability was 65.5% for patients with cGVHD and 76.7% for patients without cGVHD. While overall 90% of cGvHD patients were hospitalized at least once, the share was only half for patients without GvHD (44%). 78.2% of patients with cGVHD received corticosteroids in combination with other predefined immunosuppressants. Conclusion Findings from this study reveal a high disease burden associated with cGvHD. This underlines the high medical need for new interventional strategies to improve survival and morbidity after allo-HCT.
      PubDate: 2022-12-01
       
  • Drug-Induced QT Prolongation and Torsade de Pointes in Spontaneous Adverse
           Event Reporting: A Retrospective Analysis Using the Japanese Adverse Drug
           Event Report Database (2004–2021)

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      Abstract: Background Drugs with new mechanisms of action are continually being developed, but it is difficult to capture whether a drug induces QT prolongation/torsade de pointes (TdP) in preclinical and preapproval clinical trials. Objective To evaluate drugs associated with drug-induced QT prolongation/TdP using a real-world database in Japan. Patients and methods A search was performed in the Japanese Adverse Drug Event Report (JADER) database for QT prolongation and TdP. The reporting odds ratio (ROR) was calculated to identify potential drug-induced QT prolongation/TdP association. Results Among the reported 4,326,484 data entries, 3410 patients exhibited QT prolongation/TdP (2707 with QT prolongation, 703 with TdP) with the suspected drugs. Of these patients, 53.9% were females. The highest occurrence was in the 70- to 79-year-old age group (24.7%). The most common types of drugs involved were cardiovascular drugs, central nervous system (CNS) drugs, anticancer drugs, and anti-infective drugs; the rate of overdose was reportedly very low at 1.6%. The highest adjusted RORs were observed for nifekalant (351.41, 95% confidence interval (CI) 235.85–523.59), followed by vandetanib (182.55, 95% CI 108.11–308.24), evocalcet (181.59, 95% CI 132.96–248.01), bepridil (160.37, 95% CI 138.17–186.13), diarsenic trioxide (79.43, 95% CI 63.98–98.62), and guanfacine (78.29, 95% CI 58.51–104.74). Among the drugs launched in Japan during the last decade, vandetanib had the highest adjusted RORs. Conclusions This study using the JADER database showed that antiarrhythmic drugs, calcium-sensing receptor agonists, small-molecule targeted anticancer drugs, and CNS drugs are associated with QT prolongation/TdP. Further pharmacoepidemiological studies, such as cohort studies using large databases, are needed to prove these causal relationships.
      PubDate: 2022-12-01
       
  • Adverse Drug Events Related to Common Asthma Medications in US
           Hospitalized Children, 2000–2016

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      Abstract: Background The reduction in adverse drug events is a priority in healthcare. Medications are frequently prescribed for asthmatic children, but epidemiological trends of adverse drug events related to anti-asthmatic medications have not been described in hospitalized children. Objective The objective of this study was to report incidence trends, risk factors, and healthcare utilization of adverse drug events related to anti-asthmatic medications by major drug classes in hospitalized children in the USA from 2000 to 2016. Methods A population-based temporal analysis included those aged 0–20 years who were hospitalized with asthma from the 2000 to 2016 Kids Inpatient Database. Age-stratified weighted temporal trends of the inpatient incidence of adverse drug events related to anti-asthmatic medications (i.e., corticosteroids and bronchodilators) were estimated. Stepwise multivariate logistic regression models generated risk factors for adverse drug events. Results From 2000 to 2016, 12,640 out of 698,501 pediatric asthma discharges (1.7%) were associated with adverse drug events from anti-asthmatic medications. 0.83% were adverse drug events from corticosteroids, resulting in a 1.14-fold increase in the length of stay (days) and a 1.42-fold increase in hospitalization charges (dollars). The overall incidence (per 1000 discharges) of anti-asthmatic medication adverse drug events increased from 5.3 (95% confidence interval [CI] 4.6–6.1) in 2000 to 21.6 (95% CI 18.7–24.6) in 2016 (p-trend = 0.024). Children aged 0–4 years had the most dramatic increase in the incidence of bronchodilator adverse drug events from 0.2 (95% CI 0.1–0.4) to 19.3 (95% CI 15.2–23.4) [p-trend ≤ 0.001]. In general, discharges among asthmatic children with some comorbidities were associated with an approximately two to five times higher odds of adverse drug events. Conclusions The incidence of adverse drug events from common anti-asthmatic medications quadrupled over the past decade, particularly among preschool-age children who used bronchodilators, resulting in substantial increased healthcare costs. Those asthmatic children with complex medical conditions may benefit the most from adverse drug event monitoring.
      PubDate: 2022-12-01
       
  • Prophylactic Antimicrobial Prescribing in Australian Residential Aged-Care
           Facilities: Improvement is Required

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      Abstract: Background and Objective Inappropriate antimicrobial use can lead to adverse consequences, including antimicrobial resistance. The objective of our study was to describe patterns of prophylactic antimicrobial prescribing in Australian residential aged-care facilities and thereby provide insight into antimicrobial stewardship strategies that might be required. Methods Annual point prevalence data submitted by participating residential aged-care facilities as part of the Aged Care National Antimicrobial Prescribing Survey between 2016 and 2020 were extracted. All antimicrobials except anti-virals were counted; methenamine hippurate was classified as an antibacterial agent. Results The overall prevalence of residents prescribed one or more prophylactic antimicrobial on the survey day was 3.7% (n = 4643, 95% confidence interval 3.6–3.8). Of all prescribed antimicrobials (n = 15,831), 27.1% (n = 4871) were for prophylactic use. Of these prophylactic antimicrobials, 87.8% were anti-bacterials and 11.4% antifungals; most frequently, cefalexin (28.7%), methenamine hippurate (20.1%) and clotrimazole (8.8%). When compared with prescribing of all antimicrobial agents, prophylactic antimicrobials were less commonly prescribed for pro re nata administration (7.0% vs 20.3%) and more commonly prescribed greater than 6 months (52.9% vs 34.1%). The indication and review or stop date was less frequently documented (67.5% vs 73.8% and 20.9% vs 40.7%, respectively). The most common body system for which a prophylactic antimicrobial was prescribed was the urinary tract (54.3%). Of all urinary tract indications (n = 2575), about two thirds (n = 1681, 65.3%) were for cystitis and 10.6% were for asymptomatic bacteriuria. Conclusions Our results clearly identified immediate antimicrobial stewardship strategies that aim to improve prophylactic antimicrobial prescribing in Australian residential-aged care facilities are required.
      PubDate: 2022-12-01
       
  • Retrospective Cohort Evaluating the Comparative Effectiveness of
           Ceftaroline and Daptomycin as First-Line Therapies for Inpatient Treatment
           of Diabetic Foot Infection in the United States Veterans Health Care
           System

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      Abstract: Background Both ceftaroline and daptomycin are possible therapeutic options for diabetic foot infection (DFI) and both are active against methicillin-resistant Staphylococcus aureus (MRSA) infection; however, no previous studies have evaluated their effectiveness head-to-head. Objective This study compared hospital readmission and mortality proportions among patients receiving ceftaroline fosamil or daptomycin for DFI. Patients and Methods This was a retrospective cohort, comparative effectiveness study of adults (aged ≥ 18 years) admitted to United States Veterans Health Care System hospitals with a diagnosis code for DFI between 1 October 2010 and 30 September 2014 with an electronic order for ceftaroline or daptomycin as first-line therapy within 14 days of admission. Baseline characteristics were compared using Chi-square, Fisher's exact, and Wilcoxon rank-sum tests. Hospital readmission and patient mortality proportions were compared through multivariable logistic regression models with Hispanic ethnicity, prior hospitalization, dyslipidemia, and Charlson comorbidity score as covariates. Results In total, 223 patients were included (ceftaroline, n = 71; daptomycin n = 152). At baseline, ceftaroline patients were more likely to be Hispanic (18 vs. 6%, p < 0.01) and have been hospitalized in the past 90 days (34 vs. 19%, p = 0.02). Unadjusted 90-day hospital readmission proportions for ceftaroline versus daptomycin were 34 vs. 49%, and unadjusted 90-day mortality proportions were 1% vs. 8%. In multivariable models, ceftaroline patients were less likely to experience 90-day hospital readmission (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.25–0.85) and 90-day mortality (OR 0.14, 95% CI 0.01–0.77). Conclusions In this population, ceftaroline was associated with lower 90-day hospital readmission and 90-day mortality compared with daptomycin when used as first-line therapy for DFI.
      PubDate: 2022-12-01
       
  • Factors Associated with Discontinuation of Statin Therapy in Patients with
           Lymphoma Aged 80 Years and Older: A Retrospective Single-Institute Study

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      Abstract: Background There is little evidence to support or negate the benefits of statin therapy for primary prevention of cardiovascular disease (CVD) in lymphoma patients aged 80 years or older. Objective We evaluated comprehensive geriatric assessment (CGA) scores and previously reported risk factors for failure of statin therapy discontinuation in lymphoma patients aged 80 years and older with the aim of identifying those in whom discontinuation of statins for primary CVD prevention is indicated. Patients and methods Our study cohort comprised 50 patients aged 80 years and older treated with chemotherapy for lymphoma at our institute from January 2011 to July 2020. We retrospectively analyzed the associations between CGA, including Geriatric 8, instrumental activities of daily living, and Charlson comorbidity index, and previously reported factors associated with failure of statin therapy discontinuation, defined as reintroduction of statins after their discontinuation, in this patient cohort. Results Twenty years or less of statin therapy was an independent predictor of failure of statin therapy discontinuation (hazard ratio 8.240, 95% confidence interval 1.380–49.10). There were significant differences in the rate of failure of statin discontinuation between patients receiving statins for ≥ 20 years versus < 20 years (p = 0.010). Multivariate analysis of CGA-related scores identified no significant risk factors for failure of statin discontinuation. Conclusions Discontinuation of statin therapy may be indicated in lymphoma patients aged 80 years and older who have used statins for 20 years or more.
      PubDate: 2022-12-01
       
  • Increased Risk of Stroke Due to Non-adherence and Non-persistence with
           Direct Oral Anticoagulants (DOACs): Real-World Analyses Using a Nested
           Case–Control Study from The Netherlands, Italy and Germany

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      Abstract: Background A high degree of adherence to direct oral anticoagulants is essential for reducing the risk of ischaemic stroke and systemic embolism in patients with atrial fibrillation, owing to the rapid decline in anticoagulation activity when doses are omitted (i.e. rebound effect). Objective We aimed to assess the relationship between non-adherence and non-persistence with direct oral anticoagulants and the incidence of ischaemic stroke in patients with atrial fibrillation. Methods A nested case–control study was conducted in the Netherlands, Italy and Germany among patients with atrial fibrillation starting direct oral anticoagulants between the drug approval date and the end of database availability. Patients with an ischaemic stroke during the follow-up were selected as cases and compared with matched controls (matched on age ± 5 years, sex, year of cohort entry date and CHA2DS2-VASc-score at cohort entry date). The cohort entry date was the first dispensing date. Study patients were those aged ≥ 45 years, with ≥ 1 year database history, ≥ 1 year follow-up and at least two direct oral anticoagulant dispensings after the cohort entry date. Adherence and persistence to direct oral anticoagulant treatment were defined as the proportion of days covered ≥ 80% or direct oral anticoagulant continuous use between the cohort entry date and the index date (i.e. date of ischaemic stroke), respectively. Results In The Netherlands, Italy and Germany, 105 cases and 395 controls, 1580 cases and 6248 controls, and 900 cases and 3570 controls were included, respectively. Odds ratios (ORs) for stroke among current users who were non-adherent compared to adherent users were 0.43 (95% confidence interval [CI] 0.09–1.96) in The Netherlands, 1.11 (95% CI 0.98–1.26) in Italy and 1.21 (95% CI 1.01–1.45) in Germany. The risk of stroke was significantly higher among non-persistent users compared with persistent users in all three databases [OR 1.56 (95% CI 1.00–2.44), OR 1.48 (1.32–1.65) and OR 1.91 (95% CI 1.64–2.22), respectively]. In The Netherlands and Germany, the risk of stroke was higher the longer a patient had stopped using direct oral anticoagulants. Conclusions Both non-adherence (in Germany) and non-persistence increased the risk of stroke, either using a once-daily or twice-daily regime.
      PubDate: 2022-12-01
       
  • Osteonecrosis of the Jaw Caused by Denosumab in Treatment-Naïve and
           Pre-Treatment with Zoledronic Acid Groups: A Time-to-Onset Study Using the
           Japanese Adverse Drug Event Report (JADER) Database

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      Abstract: Background Medication-related osteonecrosis of the jaw is a serious adverse event associated with bone-modifying agents, such as injectable bisphosphonate (zoledronic acid) and the anti-receptor activator of nuclear factor-κB ligand antibody (denosumab). Objective This study aims to evaluate and compare the time-to-onset profile for medication-related osteonecrosis of the jaw associated with denosumab between treatment-naïve (naïve group) and pre-treatment with zoledronic acid (post-zoledronic acid group) patients using the Japanese Adverse Drug Event Report database. Methods Medication-related osteonecrosis of the jaw was defined according to the Medical Dictionary for Regulatory Activities. The medication-related osteonecrosis of the jaw onset profiles were evaluated using the Weibull shape parameter and the log-rank test. Results The Japanese Adverse Drug Event Report database contains 632,409 reports published between April 2004 and March 2020. In the time-to-onset analysis, after extracting the combinations with complete information for the treatment start date and the medication-related osteonecrosis of the jaw onset date, 272 reports of the naïve group and 86 reports of the post-zoledronic acid group were analyzed. The median onset in the naïve and post-zoledronic acid groups was 487.0 (25–75%: 274.0–690.8) and 305.5 (25–75%: 158.3–508.5) days, respectively. Medication-related osteonecrosis of the jaw occurred earlier in the post-zoledronic acid group than in the naïve group, and the log-rank test demonstrated a significant difference in their time transitions (p < 0.0001). Conclusions The results indicated a risk of medication-related osteonecrosis of the jaw in naïve and post-zoledronic acid groups and a shorter onset time in the latter than in the former. Thus, healthcare professionals should take the early risk of medication-related osteonecrosis of the jaw into account when switching patients from zoledronic acid to denosumab treatment.
      PubDate: 2022-12-01
       
  • Rituximab and Pyoderma Gangrenosum: An Investigation of Disproportionality
           Using a Systems Biology-Informed Approach in the FAERS Database

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      Abstract: Background Studies have found an increased risk of pyoderma gangrenosum associated with rituximab. The structural properties and pharmacological action of rituximab may affect the risk of pyoderma gangrenosum. Additionally, pyoderma gangrenosum is associated with autoimmune disorders for which rituximab is indicated. Objective We aimed to determine whether rituximab is disproportionally associated with pyoderma gangrenosum using a systems biology-informed approach. Methods Adverse event reports were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS, 2013–20). The Bayesian Confidence Propagation Neural Network Information Component was used to test for disproportionality. Comparators used to determine potential causal pathways included all other medicines, all medicines with a similar structure (monoclonal antibodies), all medicines with the same pharmacological target (CD20 antagonists) and all medicines used for the same indication(s) as rituximab. Results Thirty-two pyoderma gangrenosum cases were identified, 62.5% were female, with a median age of 48 years. There was an increased association of pyoderma gangrenosum with rituximab compared with all other medicines (exponentiated Information Component 6.75, 95% confidence interval (CI) 4.66–9.23). No association was observed when the comparator was either monoclonal antibodies or CD20 antagonists. Conditions for which an association of pyoderma gangrenosum with rituximab was observed were multiple sclerosis (6.68, 95% CI 1.63–15.15), rheumatoid arthritis (2.67, 95% CI 1.14–4.80) and non-Hodgkin’s lymphoma (2.94, 95% CI 1.80–3.73). Conclusions Pyoderma gangrenosum was reported more frequently with rituximab compared with all other medicines. The varying results when restricting medicines for the same condition suggest the potential for confounding by indication. Post-market surveillance of biologic medicines in  FAERS should consider a multi-faceted approach, particularly when the outcome of interest is associated with the underlying immune condition being treated by the medicine of interest.
      PubDate: 2022-12-01
       
  • Effect of Tolvaptan in Patients with Chronic Kidney Disease Stage G5, and
           Impact of Concomitant Use of Thiazide Diuretics: A Retrospective Cohort
           Study

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      Abstract: Background The diuretic effect of tolvaptan, a vasopressin V2 receptor antagonist, in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics reduce urinary volume (UV) in patients with nephrogenic diabetes insipidus, which lacks V2 receptor function. Objective This retrospective study investigated the acute urinary effects of tolvaptan in patients with stage G5 chronic kidney disease and congestive heart failure (CHF), and the impact of thiazide diuretics on the urinary effects of tolvaptan. Methods UVs 24 h before and after tolvaptan administration and 30-day dialysis initiation rate were compared between patients with and without thiazide diuretic administration. Results Thiazide diuretics were used in 26 of the 106 recruited patients (age 73.4 ± 13.0 years; estimated glomerular filtration rate 8.07 ± 3.13 mL/min/1.73 m2). The pre- and post-tolvaptan 24-h UVs were significantly higher in patients not administered thiazide diuretics (1043.4 ± 645.6 vs. 1422.2 ± 774.0 mL/day; p < 0.001) than in those administered thiazide diuretics (1177.3 ± 686.5 vs. 1173.1 ± 629.1 mL/day; p = 0.93). In a multivariate regression model, thiazide diuretic use was significantly associated with decreased 24-h UV (β coefficient − 486.7, 95% confidence interval [CI] − 674.5 to − 298.8); increased urine osmolality (β coefficient 37.7, 95% CI 17.1–58.4); increased body weight (β coefficient 0.62, 95% CI 0.31–0.92); and increased 30-day dialysis initiation rate (odds ratio 3.40, 95% CI 1.18–9.82) after tolvaptan administration. Conclusions Tolvaptan exhibited significant diuretic effects in patients with CHF, including those with severe renal dysfunction, which were diminished with concomitant thiazide diuretic use.
      PubDate: 2022-12-01
       
  • Impact of "time zero" of Follow-Up Settings in a Comparative
           Effectiveness Study Using Real-World Data with a Non-user Comparator:
           Comparison of Six Different Settings

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      Abstract: Background Time-related bias can lead to misleading conclusions. Properly setting the "time zero" of follow-up is crucial for avoiding these biases. However, the time-zero setting is challenging when comparing users and non-users of a study drug because the latter do not have a time point for starting treatment. Objective This methodological study aimed to illustrate the impact of different time-zero settings on effect estimates in a comparative effectiveness study using real-world data with a non-user comparator. Methods Data for type 2 diabetes patients were extracted from an administrative claims database, and the onset of diabetic retinopathy (study outcome) was compared between users (treatment group) and non-users (non-use group) of lipid-lowering agents. We applied six time-zero settings to the same dataset. The adjusted hazard ratio (HR) for the outcome was estimated using a Cox regression model in each time-zero setting, and the obtained results were compared among the settings. Results Of the six settings, three (study entry date [SED] vs SED [naïve approach], treatment initiation [TI] vs SED, TI vs Matched [random order]) showed that the treatment had a reduced risk of the outcome (HR [95% CI]: 0.65 [0.61–0.69], 0.92 [0.86–0.97], and 0.76 [0.71–0.82], respectively), one (TI vs Random) had an increased risk (HR [95% CI]: 1.52 [1.40–1.64]) , and two (SED vs SED [cloning method], and TI vs Matched [systematic order]) had neither increased nor decreased risk (HR [95% CI]: 0.95 [0.93–1.13], and 0.99 [0.93–1.07], respectively). Conclusions This study demonstrates that different time-zero settings can lead to different conclusions, even if the same dataset is analyzed for the same research question, probably because improper settings can introduce bias. To minimize such biases, researchers should carefully define time zero, particularly when designing a non-user comparator study using real-world data.
      PubDate: 2022-11-28
       
  • Identification of Potentially Inappropriate Medications in Frail Older
           Adults Residing in Long-Term Care: A Retrospective Chart Review Study

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      Abstract: Introduction Deprescribing is associated with positive health outcomes for older adults in long-term care (LTC), however deprescribing is not universally implemented. Objective The primary aim of this study was to estimate the prevalence of potentially inappropriate medications (PIMs) prescribed to frail older adults in Irish long-term care facilities (LTCFs), as identified by the Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy, version 2 (STOPPFrail v2). Methods A retrospective chart review was conducted in two publicly funded LTCFs in Ireland. Eligible participants were those (1) ≥ 65 years of age; (2) resident in a LTCF; (3) eligible as per the STOPPFrail v2 criteria by the site’s Medical Officer; and (4) receiving regular medication. Data collected included age, sex, drug, dose, frequency, regular/pro re nata prescribing and indication/relevant diagnoses. Rates of polypharmacy (taking five or more medications) and excessive polypharmacy (taking 10 or more medications) were calculated. STOPPFrail v2 was used to identify PIMs; however, clinical measurements were not taken. Descriptive and association statistics were calculated. Results Of the 103 residents, 89 were ≥ 65 years of age and categorised as frail and were therefore eligible for inclusion in the study. Of those eligible, 85 (95.5%) had polypharmacy and 57 (64%) experienced excessive polypharmacy. The mean number of regular medications was 10.8 (± 3.8), total medications 17.7 (± 5) and diagnoses 5.5 (± 2.5). The mean number of PIMs per resident was 4.8 (± 2.6). Of the eligible participants, 59.6% had at least one medicine without a documented indication, while 61.8%, 42.7% and 30.3% had at least one PIM from the vitamin D, antihypertensives and proton pump inhibitors drug classes, respectively. Conclusion Medication and PIM use was high among LTC residents, with inappropriate polypharmacy of concern. Lack of clear indication for prescribing medications appears to be an issue in LTC, potentially affecting healthcare professionals’ engagement with deprescribing. The prevalence of PIMs may be overestimated in the antihypertensives/antidiabetic classes due to the lack of clinical measurements.
      PubDate: 2022-11-27
       
  • Acknowledgement to Referees

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      PubDate: 2022-11-23
       
  • Trends in the Use of Sedative-Hypnotics, Opioids, and Neuromuscular
           Blockers in Hospitalized Patients During the COVID-19 Pandemic:
           Observational Retrospective Study

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      Abstract: Background The coronavirus disease 2019 (COVID-19) pandemic has increased the use of drugs administered for mechanical ventilation, leading to shortages in some countries. Objective The aim was to identify trends in the consumption of sedatives, hypnotics, neuromuscular blockers, and opioids used for anesthetic induction and deep sedation in hospitals in Colombia. Method This was a descriptive, longitudinal, and retrospective study with monthly follow-up of sedative, hypnotic, opioid, and neuromuscular blocker dispensing in 20 clinics and hospitals from January to November 2020. The frequencies of use of each drug and variations in the institutions and intensive care units (ICUs) were identified. Results A total of 1,252,576 units of the analyzed drugs were delivered to 79,094 treated patients, 55.0% of whom were women (n = 43,521). The drugs with the greatest increase in consumption were rocuronium (1058% variation in March–November) and propofol (511%). The consumption of midazolam and vecuronium initially increased, but by the end of the study period, it decreased. Among drugs dispensed only in ICUs, 920,170 units were delivered (73.5% of the drugs dispensed during the study), and the most often dispensed drugs were fentanyl (n = 251,519; 27.3% of the drugs used in the ICU) and midazolam (5 mg/5 mL) solution (n = 188,568; 20.5%). Specifically in the ICU, the drugs with the greatest increase in use were rocuronium (19,709%), propofol (2622%), and ketamine (2591%). Conclusion Rapid changes in the use of drugs were evident, which demonstrates the need for closer cooperation among treating physicians, service providers, pharmaceutical managers, and state institutions to maintain a sufficient and timely supply of critical drugs in this type of contingency.
      PubDate: 2022-11-03
       
  • Clinical Characteristics of Registry Participants with Psoriatic Arthritis
           Initiating Guselkumab: An Analysis from the CorEvitas Psoriatic
           Arthritis/Spondyloarthritis Registry

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      Abstract: Background The monoclonal antibody guselkumab is the first selective inhibitor of the interleukin-23 p19 subunit approved to treat adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). Given its recent approval for active PsA, data describing patients with PsA initiating guselkumab outside of clinical trials are limited. Objective This analysis describes characteristics of patients with rheumatologist-diagnosed PsA initiating guselkumab in the US-based, prospective, observational CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. Methods Demographics, lifestyle/disease characteristics, comorbidities, prior treatment, and disease activity were summarized for patients with PsA initiating guselkumab from registry inception through 30 September, 2021. Results Of 113 patients initiating guselkumab, the majority were female (63%), obese (67%), had psoriasis (89%), and initiated guselkumab as monotherapy (81%). Common comorbidities were hypertension (32%), depression (30%), and diabetes mellitus (26%). Mean tender (6.8) and swollen (2.0) joint counts, clinical Disease Activity Index for PsA score (19.1), and 57% of participants with ≥ 3% body surface area affected by psoriasis indicated moderate disease activity. Axial involvement was identified in 49% of patients. Median patient-reported pain and fatigue visual analog scale scores (0–100) were 60 and 59, respectively. Prior to guselkumab, 76% of patients had received two or more biologic disease-modifying antirheumatic drugs; the last therapy prior to guselkumab was a biologic disease-modifying antirheumatic drug in 81% of patients. Conclusions Registry participants with PsA initiating guselkumab had active peripheral joint and skin disease, with substantial pain and fatigue; a considerable proportion had axial involvement. Future studies will evaluate the effectiveness of guselkumab in this population.
      PubDate: 2022-10-15
       
  • A Review of Research Studies Using Data from the Administrative Claims
           Databases in Japan

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      Abstract: Background In Japan, several research studies have used administrative claims databases. However, no study has compared the studies conducted in each database. Objective We assessed the type, design, and research area of each research study using the administrative databases in Japan to illustrate the suitability of the database used for the types of research studies. Methods We reviewed studies from four administrative claims databases (the Japanese National Database of Health Insurance Claims and Specific Health Checkups [NDB]; the DPC Study Group database [DPC]; Japan Medical Data Center [JMDC]; and Medical Data Vision [MDV]). The PubMed database was searched from January 2015 to October 2020. We assessed the type, design, and research area of the abstract or full text of each research study. Results Overall, 643 studies were included. The number of studies increased from 59 in 2015 to 171 in 2020. Descriptive studies accounted for 62.7% (42 studies) of the studies from the NDB, while the treatment effectiveness studies accounted for 81.7% (211 studies) of the studies from the DPC database and were the most common in the JMDC and MDV. Cohort studies accounted for only 17.9% of the studies on NDB but 45.5% on DPC. The most common research area was medicine, general, and internal medicine (53 studies, 8.4%). Conclusions The type and design of the studies conducted differed in each database and were influenced by the characteristics of the database used. In the future, it may be necessary to integrate various real-world data databases to increase their comprehensiveness.
      PubDate: 2022-09-15
      DOI: 10.1007/s40801-022-00331-5
       
  • Real-World Patient Characteristics, Utilization Patterns, and Outcomes of
           US Patients with HR+, HER2− Metastatic Breast Cancer Treated with
           Abemaciclib

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      Abstract: Background Abemaciclib is the most recent oral cyclin-dependent kinase 4 and 6 inhibitor (CDK4 & 6i) to receive US Food and Drug Administration (FDA) approval to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer (MBC). Administrative claims data were used to describe patient characteristics and select clinical and economic outcomes in US patients treated in routine clinical practice. Prior analyses from electronic health records data indicate approximately 25% of patients received either palbociclib or ribociclib for MBC before initiating abemaciclib treatment; this work further explored these findings and associated outcomes. Methods This retrospective study analyzed medical and pharmacy claims from the IBM® MarketScan® Research Databases between 1 January 2007 to 31 January 2020. Patients with HR+, HER2− MBC newly initiating abemaciclib between 1 September 2017 and 31 October 2019 were included and grouped by concomitant therapy (+aromatase inhibitor (AI), +fulvestrant (F), 200 mg abemaciclib monotherapy (Mono), or +other), and outcomes were analyzed by prior CDK4 & 6i use. Patient and treatment characteristics were summarized with descriptive statistics. Kaplan–Meier methods assessed time-to-discontinuation (TTD; i.e., persistency) and time-to-chemotherapy (TTC). Adherence (defined by the medication possession ratio) and drug wastage were determined. Results This analysis included 454 patients (mean age 57.7 years), with 35.0% (n = 159) in the +F group, 29.3% (n = 133) in the +AI group, 10.4% (n = 47) in the 200 mg Mono group, and 25.3% (n = 115) in the +other group. Prior chemotherapy and CDK 4 & 6i use were present in 23.8% and 49.8% of all patients, respectively. Visceral metastases were present at abemaciclib initiation in 50.4% in the +AI group; 49.7% in the +F group; and 55.3% in the 200 mg Mono group. Liver metastases were present in 33.7% of the overall population. Among patients without prior CDK4 & 6i use, the median TTD for patients receiving abemaciclib + AI was not reached [95% CI 430–not reached (NR) days], abemaciclib + F [531 days (95% CI 281–NR)], and abemaciclib mono [141 days (95% CI 80–NR)]. Median TTC for abemaciclib + AI and abemaciclib + F groups were not reached and the median TTC for abemaciclib mono was 535 days (95% CI 181–NR). Medication adherence was 88.7% and medication wastage costs among those with at least one dose modification were $808.12 and $452.2 per patient per month based on amount paid and wholesale acquisition cost (WAC), respectively. Mean length of follow-up for all patients was 350 days (SD 187). Conclusion These real-world data complement clinical trial results by examining abemaciclib use among patients treated in routine clinical practice. The sizeable number of patients treated with prior CDK4 & 6i, chemotherapy, and/or visceral metastases at abemaciclib initiation suggest that many patients had very advanced disease and/or were in later stages of their treatment. These data confirm a higher percentage of patients treated with previous CDK4 & 6i than reported previously, reinforcing the importance of the ongoing, prospective clinical trials evaluating outcomes following progression on CDK4 & 6i.
      PubDate: 2022-09-12
      DOI: 10.1007/s40801-022-00327-1
       
  • Effectiveness and Safety of Filgrastim (Neupogen™) versus
           Filgrastim-aafi (Nivestim™) in Primary Prophylaxis of
           Chemotherapy-Induced Febrile Neutropenia: An Observational Cohort Study

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      Abstract: Background Despite the demonstrated efficacy and safety of biosimilar filgrastim-aafi (Nivestim™), few studies have compared its use in real-life clinical practice to the originator filgrastim (Neupogen™). Objectives This study aimed to compare the effectiveness and safety of filgrastim and filgrastim-aafi for the primary prophylaxis of chemotherapy induced-febrile neutropenia in the real-life setting. Patients and methods A retrospective cohort study included all adult cancer patients at the King Hussein Cancer Centre requiring primary prophylaxis for chemotherapy-induced febrile neutropenia between 2014 and 2016. Two cohorts were selected: patients who received filgrastim and those who received filgrastim-aafi. The primary endpoint was the incidence of febrile neutropenia; the secondary endpoints were the incidence of adverse drug reactions (ADRs), hospital admissions due to febrile neutropenia, and the mean length of hospitalization. Chi-squared tests were performed to evaluate differences between groups. Logistic regression was conducted to adjust for confounding factors. Results A total of 268 patients were identified, with 88 in the filgrastim cohort and 180 in the filgrastim-aafi cohort; 64%were females. The mean age was 47 (±15) years. The incidence of febrile neutropenia was 21.6% in the filgrastim cohort and 15% in the filgrastim-aafi cohort (P = 0.179). No statistically significant differences were detected in the incidence of hospital admission (P = 0.551) or ADRs (P = 0.623) between the two cohorts. Upon adjusting for the confounding factors, results remained statistically insignificant. Conclusion Filgrastim and filgrastim-aafi had comparable effectiveness and safety as primary prophylaxis for chemotherapy-induced febrile neutropenia. More extensive prospective studies with additional insight on the cost implications are required.
      PubDate: 2022-09-07
      DOI: 10.1007/s40801-022-00312-8
       
 
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