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- Olaparib First-Line Maintenance Monotherapy in BRCA-Mutated Epithelial
Ovarian Cancer: Descriptive Analysis of the First French Real-World Data
Study-
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Abstract: Background Olaparib, a poly(ADP-ribose) polymerase inhibitor, was approved by the European Commission in June 2019, following the results of the SOLO-1/GOG 3004 trial as maintenance monotherapy in adult patients with BRCA-mutated epithelial ovarian cancer. Objective This study aimed to provide a descriptive analysis of the first real-world data from patients with BRCA-mutated ovarian cancer who received olaparib as first-line maintenance monotherapy in the French cohort Temporary Authorisation for Use (Autorisation Temporaire d’Utilisation de cohorte, ATUc) programme from 11 March, 2019 to 16 January, 2020. Methods Eligible patients were aged 18 years and over with confirmed epithelial ovarian, primary peritoneal or Fallopian tube cancer and a deleterious or suspected deleterious germline or somatic BRCA 1/2 mutation. Patients were in complete or partial clinical response at the end of first-line platinum-based chemotherapy. Olaparib maintenance therapy was initiated within 8 weeks of the patients’ last dose of chemotherapy. Real-world data were collected through treatment access request forms completed by physicians. Clinical and safety data were collected monthly until the end of the ATUc programme. Results A total of 107 centres in metropolitan France and the French Overseas Departments and Territories requested the inclusion for 238 patients, of whom 194 received maintenance olaparib. In total, 87.6% of the primary tumour locations were ovary, the most common histology was high-grade serous (93.0%) and the most common International Federation of Gynaecology and Obstetrics (Fédération Internationale de Gynécologie et d’Obstétrique) stage was IIIC (56.8%). BRCA testing was performed in routine practice, prior to inclusion into the ATUc programme. All patients had a BRCA mutation: 52.5% had a somatic mutation, 38.4% had a germinal mutation and 9.1% had germinal and somatic mutations. Twenty-four (12%) patients experienced serious adverse drug reactions at the last safety follow-up (17 February, 2020). The most common were anaemia (12 [6%] patients), neutropenia (3 [2%] patients) and thrombocytopenia (3 [2%] patients). Conclusions The rapid enrolment into the ATUc programme highlighted the strong unmet need for patients with ovarian cancer and a BRCA mutation in first-line maintenance treatment. Olaparib was well tolerated and no new safety signals were observed in this real-world patient population.
PubDate: 2023-06-01
- Validation of Algorithms to Identify Bone Metastases Using Administrative
Claims Data in a Japanese Hospital-
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Abstract: Background Validated coding algorithms are essential to generate high-quality, real-world evidence from claims data studies. Objective We aimed to evaluate the validity of the algorithms to identify patients with bone metastases using claims data from a Japanese hospital. Patients and Methods This study used administrative claims data and electronic medical records at Juntendo University Hospital from April 2017 to March 2019. We developed two candidate claims-based algorithms to detect bone metastases, one based on diagnosis codes alone (Algorithm 1) and the other based on the combination of diagnosis and imaging test codes (Algorithm 2). Of the patients identified by Algorithm 1, 100 patients were randomly sampled. Among these 100 patients, 88 patients met the conditions of Algorithm 2; further, 12 additional patients were randomly sampled from those identified by Algorithm 2, thus obtaining a total of 100 patients for Algorithm 2. They were evaluated for their true diagnosis using the patient chart review as the gold standard. The positive predictive value (PPV) was calculated to assess the accuracy of each algorithm. Results For Algorithm 1, 82 patients were analyzed after excluding 18 patients without diagnostic imaging reports. Of these, 69 patients were true positive by chart review, resulting in a PPV of 84.1% (95% confidence interval (CI) 74.5–90.6). For Algorithm 2, 92 patients were analyzed after excluding eight patients whose diagnoses were not judged by chart review. Of these, 76 patients were confirmed positive by chart review, yielding a PPV of 82.6% (95% CI 73.4–89.1). Conclusion Both claims-based algorithms yielded high PPVs of approximately 85%, with no improvement in PPV by adding imaging test conditions. The diagnosis code-based algorithm is sufficient and valid for identifying bone metastases in this Japanese hospital.
PubDate: 2023-06-01
- Retrospective Observational Study of Outcomes in HER2-Positive Metastatic
Breast Cancer (mBC) Patients Treated with Ado-Trastuzumab Emtansine
(T-DM1) and Subsequent Treatments After T-DM1 in the United States-
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Abstract: Background Limited evidence exists on real-world outcomes with ado-trastuzumab emtansine (T-DM1) treatment and the effectiveness of subsequent therapies. Objective This study evaluated treatment patterns and outcomes of patients treated with T-DM1 and post-T-DM1 therapy in the United States. Patients and methods Adult patients with HER2-positive (HER2+) metastatic breast cancer (mBC) initiating treatment with T-DM1 between 1/1/2013 and 9/30/2018 were included and followed through 12/31/2018. Data were obtained from the iKnowMed electronic health record. Demographic, clinical, and pre- and post-T-DM1 treatment characteristics were described. The Kaplan-Meier method was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). Results Of 318 patients treated with T-DM1, 184 (57.9%) had prior treatment with pertuzumab. The median age was 58 years. Most patients had visceral disease (93.4%), and 62.3% had two or more prior treatments for mBC before T-DM1 (range 0–9). The most common subsequent regimens were trastuzumab + vinorelbine (22.5%), HER2-targeted monotherapy (22.5%), and trastuzumab + other chemotherapy (19.6%). Median TTD with T-DM1 was 5.9 months (95% confidence interval [CI] 4.6–6.9); median OS from the start of T-DM1 therapy was 19.2 months (95% CI 16.8–24.5). Conclusions Patients treated with T-DM1 in this study appeared to have more advanced disease than patients in clinical trials and were treated in later lines of therapy. Variability was observed across subsequent therapy selections. Treatment patterns and outcomes appeared comparable for patients who received prior pertuzumab. The short treatment durations and survival with T-DM1 therapy in the real-world setting underscore the need for effective post-trastuzumab therapies.
PubDate: 2023-06-01
- Myopericarditis Associated with the Novavax COVID-19 Vaccine
(NVX-CoV2373): A Retrospective Analysis of Individual Case Safety Reports
from VigiBase-
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Abstract: Background Myocarditis and pericarditis have been associated most notably with mRNA vaccines, but the association with a recently authorized adjuvated vaccine (NVX-CoV2373) is controversial. Objective The aim was to analyze the cases of myocarditis and pericarditis in association with NVX-CoV2373 reported to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase), applying disproportionality analyses. Patients and methods The main characteristics of the ICSRs reporting myopericarditis with NVX-CoV2373 have been summarized. Reporting odds ratios (RORs) as a measure of disproportionality for reported myopericarditis (November 1967–August 2022) have been calculated for NVX-CoV2373; mRNA and adenoviral vector-based vaccines were also included as a reference. Results In total, 61 ICSRs included NVX-CoV2373. Most of the reports originated in Australia (50; 82.0%); 24 (39.3%) were considered serious. None of them were fatal. The median age of individuals was 35.5 years old, and most were males (38; 62.3%). Chest pain was the most common co-reported event 43 (70.5%). The median induction period was 3 days after immunization. Increased disproportionality for myopericarditis was found for NVX-CoV2373 (ROR 14.47, 95% confidence interval [CI] 11.22–18.67) and mRNA vaccines: BNT162b2 (ROR 17.15, 95% CI 16.88–17.42) and mRNA-1273 (ROR 6.92, 95% CI 6.77–7.08). Higher values were found in males. The adenoviral vector-based vaccine Ad26.COV2.S showed slightly increased disproportionality (ROR 1.83, 95% CI 1.70–1.98), whereas no increased disproportionality was found for ChAdOx1. Conclusions NVX-CoV2373 vaccine showed a similar increased disproportionality as mRNA vaccines. More evidence from controlled studies is necessary; however, a precautionary approach is warranted. Healthcare professionals should be aware of the potential occurrence of myopericarditis with this new vaccine.
PubDate: 2023-06-01
- Safety and Effectiveness of Lenvatinib in Patients with Unresectable
Hepatocellular Carcinoma in Real-World Clinical Practice: An Observational
Post-Marketing Study in Japan-
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Abstract: Background Lenvatinib was approved for use in unresectable hepatocellular carcinoma (uHCC) in Japan in 2018. Patients with diverse clinical characteristics receive lenvatinib treatment in clinical practice. Thus, it is crucial to evaluate the safety and effectiveness of lenvatinib in real-world clinical settings. Objective This study aimed to evaluate the real-world safety and effectiveness of lenvatinib for uHCC in clinical practice in Japan. Patients and Methods Between July 2018 and January 2019, patients with uHCC who were administered lenvatinib for the first time were enrolled in this prospective, multicenter, observational post-marketing study (NCT03663114). Patients were orally administered lenvatinib and followed up for 12 months. For safety, adverse drug reactions (ADRs) were evaluated. For effectiveness, the objective response rate (ORR) was calculated to evaluate tumor response. Overall survival (OS) was estimated using the Kaplan–Meier method. Results Data of 703 patients (median age, 73 years; 80.2% males) were analyzed. The median (range) treatment duration was 25.3 (0.3–68.9) weeks. The mean ± standard deviation initial dose was 7.37 ± 1.65 mg in patients with body weight < 60 kg and 10.43 ± 2.49 mg in those with body weight ≥ 60 kg. ADRs (any grade) were reported in 84.9% of the patients, with Grade ≥ 3 ADRs reported in 42.5% of the patients. The most common ADRs (> 10%) were decreased appetite, fatigue, hypertension, proteinuria, palmar-plantar erythrodysesthesia, hypothyroidism, and diarrhea. The median OS of the 703 patients was 498.0 days. In 494 patients assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the ORR was 39.5% (95% confidence interval: 35.1–43.9%). Patients with better liver or renal function at baseline achieved significantly higher ORR than those with worse liver or renal function. Conclusions In patients with uHCC in real-world clinical practice in Japan, treatment with lenvatinib was generally well tolerated, and no new safety concerns were identified. The ORR and median OS were similar to or better than the results of the Japanese subset of the global Phase III REFLECT trial. Our results demonstrated that clinically meaningful treatment responses were achieved with lenvatinib in real-world clinical practice.
PubDate: 2023-06-01
- Time Trends in Patient Characteristics of New Rivaroxaban Users with
Atrial Fibrillation in Germany and the Netherlands-
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Abstract: Background Use of the direct oral anticoagulant rivaroxaban has strongly increased in Europe since its market approval for non-valvular atrial fibrillation in 2011. Patients characteristics of rivaroxaban initiators may have changed over time but this has not been investigated so far. Objective We aimed to describe time trends of patient baseline characteristics among new rivaroxaban users with non-valvular atrial fibrillation from 2011 to 2016/17 in two European countries. Methods We used data from Germany (German Pharmacoepidemiological Research Database) and the Netherlands (PHARMO Database Network). We included new rivaroxaban users with (i) a first dispensing between 2011 and 2016/17, (ii) ≥ 2 years of age, and (iii) a diagnosis of non-valvular atrial fibrillation and described their baseline medication and comorbidity prior to starting rivaroxaban stratified by year of inclusion. Results Overall, 130,652 new rivaroxaban users were included during the study period (Germany: N = 127,743, the Netherlands: N = 2909). The sex ratio and median age remained relatively stable over time. The proportion of patients without prior use of oral anticoagulants before initiation of rivaroxaban increased in both countries between 2011 and 2016/17 (Germany: from 51 to 76%, the Netherlands: from 57 to 85%). In Germany, we observed a relative decrease by 27% in the proportion of new rivaroxaban users with a history of ischemic stroke and by 18% in the proportion with a transient ischemic attack at baseline. No such a pattern was observed in the Netherlands. The proportion of patients with heart failure at baseline showed a three-fold increase in the Netherlands, while there was a relative decrease by 12% in Germany. Conclusions Patient characteristics of new rivaroxaban users with non-valvular atrial fibrillation changed between 2011 and 2016/17, but changes differed between countries. These patterns have methodological implications. They have to be considered in the interpretation of observational studies comparing effectiveness and safety of oral anticoagulants, especially regarding potential bias due to unmeasured confounding.
PubDate: 2023-06-01
- An Attempt to Replicate Randomized Trials of Diabetes Treatments Using a
Japanese Administrative Claims and Health Checkup Database: A Feasibility
Study-
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Abstract: Background Use of real-world evidence (RWE) has been limited for evaluating effectiveness because of the lack of confidence in its reliability. Examining whether a rigorously designed observational study using real-world data (RWD) can reproduce the results of a randomized controlled trial (RCT) will provide insights into the implementation of high-quality RWE studies that can produce valid conclusions. Objective We aimed to replicate published RCTs using a Japanese claims and health checkup database and examine whether the emulated RWE studies’ results agree with those of the original RCTs. Methods We selected three RCTs on diabetes medications for replication in patients with type 2 diabetes. The study outcome was either the change or percentage change in HbA1c levels from baseline. We designed three observational studies using the RWD to mimic the critical study elements of the respective RCTs as closely as possible. We performed 1:1 propensity score nearest-neighbor matching to balance the groups for potential confounders. The differences in outcomes between the groups and their 95% confidence intervals (CIs) were calculated in each RWE study, and the results were compared with those of the RCT. Results Patient characteristics, such as age, sex, and duration of diabetes, differed between the RWE studies and RCTs. In Trial 1 emulation, the percentage changes in HbA1c levels were larger in the treatment group than in the comparator group (difference −6.21, 95% confidence interval (CI) −11.01 to −1.40). In Trial 2, the change in HbA1c level was larger in the treatment group (difference −0.01; 95% CI −0.25 to 0.23), and in Trial 3, it was smaller in the treatment group (difference 0.46; 95% CI −0.01 to 0.94). These results did not show regulatory or estimate agreement with the RCTs. Conclusions None of the three emulated RWE studies using this claims and health checkup database reproduced the same conclusions as the RCTs. These discrepancies could largely be attributed to design differences between RWE studies and RCTs, primarily due to the lack of necessary data in the database. This particular RWD source may not be the best fit for evaluating treatment effects using laboratory data as the study outcome.
PubDate: 2023-06-01
- Evidence of Accidental Dosing Errors with Immediate-Release Sodium
Oxybate: Data from the US Food and Drug Administration Adverse Event
Reporting System-
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Abstract: Introduction Sodium oxybate has been approved by the US Food and Drug Administration (FDA) to treat narcolepsy for 20 years; however, the only available products have been immediate-release (IR) formulations given twice nightly—once at bedtime and a second dose 2.5–4 h later—creating inherent risks with dosing administration errors. Objectives Evidence and risks associated with accidental ingestion of the second IR oxybate dose < 2.5 h after the first dose were examined. Methods The FDA Adverse Event Reporting System database was searched for “inappropriate schedule of product administration” with IR sodium oxybate or calcium/magnesium/potassium/sodium oxybates; reports classified as serious and with IR oxybate as the suspect product were further analyzed. Results Of 541 reports meeting the search criteria, 178 were classified as serious: accidental early administration of the second dose resulting in adverse events (AEs; n = 41); “near miss” (no harm reported following early dosing; n = 9); intentionally taking second dose early (n = 25); other inappropriate use (late dosing/not taking daily; n = 102); and one duplicate report. Of the 41 reports of taking the second dose too early resulting in AEs, 22% (9/41) used emergency services and 27% (11/41) resulted in hospitalizations. AEs reported with accidentally taking the second dose too early included CNS depression, bradycardia, respiratory depression, dizziness, seizure, confusion, delirium, difficulty awakening, drowsiness, falls, nausea, vomiting, and enuresis. Conclusions Patients, caregivers, clinicians, and Poison Control Centers should be aware of the risk of accidentally dosing twice-nightly IR oxybates earlier than 2.5 h after the first dose and the subsequent harm that may occur with early dosing.
PubDate: 2023-06-01
- Dermatology Life Quality Index in Patients with Psoriasis Treated with
Biologic Versus Non-biologic Treatment in Malaysia: A Retrospective
Cross-Sectional Study-
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Abstract: Background Psoriasis imposes a substantial burden on patients’ social, emotional, physical, and family life. Although psoriasis has no complete cure, various treatments are available to control its symptoms and improve a patients’ quality of life. Objective We aimed to compare the effectiveness of biologic versus non-biologic treatments on health-related quality of life among patients with psoriasis in Malaysia. Methods This retrospective cross-sectional study evaluated data of adult patients diagnosed with psoriasis during 2007–18 from the Malaysian Psoriasis Registry. Baseline demographics, disease, and treatment characteristics were described. For a subset of patients treated with biologics and non-biologics who had baseline and 6-month follow-up data available, changes in the mean Dermatology Life Quality Index scores and the proportion of patients with a clinically relevant improvement (≥ 4 points) post-treatment were assessed. Results Overall, 15,238 adult patients with psoriasis from the Malaysian Psoriasis Registry were included in the analysis. Patients receiving biologics showed a statistically significant reduction in the mean Dermatology Life Quality Index scores after 6 months compared with those receiving non-biologic treatment (− 5.7 vs − 0.8%; p < 0.001). The proportion of patients who achieved a ≥ 4-point improvement in Dermatology Life Quality Index scores was approximately two times greater in the biologic-treated group versus the non-biologic-treated group (56.4 vs 27.7%). Conclusions Biologic treatment showed a greater reduction in the Dermatology Life Quality Index scores of patients with psoriasis versus non-biologic treatment. These results highlight the importance of early treatment with more efficacious treatment options, such as biologic therapies, to improve the overall health-related quality of life of patients with psoriasis.
PubDate: 2023-06-01
- Risk Factors Associated With Polypharmacy and Potentially Inappropriate
Medication Use in Ambulatory Care Among the Elderly in the United States:
A Cross-Sectional Study-
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Abstract: Introduction Polypharmacy, defined as the concurrent use of multiple (commonly five or more) prescription drugs, is widely prevalent among the elderly. It is a preventable and significant contributor to morbidity and mortality among older people. It is linked to prescribing potentially inappropriate medications (PIMs), which have been shown to be associated with an increased risk of adverse drug interactions and reduced compliance, and in some cases result in prescribing cascades where more drugs are prescribed to manage adverse outcomes. This study aimed to examine risk factors associated with polypharmacy and PIMs among elderly patients in outpatient settings in the US. Methods We conducted a cross-sectional analysis using the nationally representative National Ambulatory Medical Care Survey, between 2010 and 2016. We extracted data from all people aged 65 years or older and evaluated factors associated with polypharmacy and PIMs using multivariable logistic regression. Weights were applied to obtain national estimates. Results During the study period, there were a total of 81,295 ambulatory visits among adults 65 years and older. Being a woman (compared with a man) was more likely to be associated with greater prevalence of PIMs (OR: 1.31, 95% CI 1.23–1.40), and living in rural areas were more likely to be associated with both polypharmacy (OR: 1.15, 95% CI 1.07–1.23) and PIMs (OR: 1.19, 95% CI 1.09–1.29), compared with living in urban areas. Older age was positively associated with polypharmacy (OR: 1.08, 95% CI 1.06–1.10), but negatively associated with PIMs (OR: 0.97, 95% CI 0.95–0.99). Conclusions Our study suggests age, being a woman, and living in rural areas are risk factors for both polypharmacy and PIMs usage. Aside from primary care providers’ roles in managing polypharmacy, collaborative care with other specialty providers, such as clinical pharmacists, should also be considered as an approach to improving the quality of prescribing in geriatric patients. Future research should further explore reasons for polypharmacy and focus on deprescribing and quality improvement initiatives in primary care to lower polypharmacy among the elderly
PubDate: 2023-05-26
- Assessment of Codispensing Patterns of Mirabegron and Prespecified CYP2D6
Substrates in Patients with Overactive Bladder-
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Abstract: Background Patients with overactive bladder (OAB) experience sudden, intense urges to urinate, which may include urge urinary incontinence and nocturia. Pharmacotherapy includes β3-adrenergic receptor agonists such as mirabegron; however, mirabegron contains a label warning for cytochrome P450 (CYP) 2D6 inhibition, making coadministration with CYP2D6 substrates require monitoring and dose adjustment to avoid unintended increases in substrate concentration. Objective To understand the codispensing patterns of mirabegron among patients using ten predefined CYP2D6 substrates with and before mirabegron dispensing. Methods This retrospective claims database analysis used the IQVIA PharMetrics® Plus Database to assess codispensing of mirabegron with ten predefined CYP2D6 substrate groups identified on the basis of medications most frequently prescribed in the United States, those with high susceptibility to CYP2D6 inhibition, and those with evidence for exposure-related toxicity. Patients had to be ≥ 18 years old before initiation of the CYP2D6 substrate episode that overlapped with mirabegron. The cohort entry period was November 2012 to September 2019, and the overall study period was 1 January 2011 to 30 September 2019. Comparisons of patient profiles at dispensing were made between time periods with and before mirabegron use in the same patient. Descriptive statistics were used to assess the number of exposure episodes, total duration of exposure, and median duration of exposure of CYP2D6 substrate dispensing with and before mirabegron. Results CYP2D6 substrate exposure periods totaling ≥ 9000 person-months were available before overlapping exposure to mirabegron for all ten CYP2D6 substrate cohorts. Median codispensing duration for chronically administered CYP2D6 substrates was 62 (interquartile range [IQR] 91) days for citalopram/escitalopram, 71 (105) days for duloxetine/venlafaxine, and 75 (115) days for metoprolol/carvedilol; median codispensing duration for acutely administered CYP2D6 substrates was 15 (33) days for tramadol and 9 (18) days for hydrocodone. Conclusions In this claims database analysis, the dispensing patterns of CYP2D6 substrates with mirabegron displayed frequent overlapping of exposure. Thus, a need exists to better understand the outcomes experienced by patients with OAB who are at increased risk for drug‒drug interactions when taking multiple CYP2D6 substrates concurrently with a CYP2D6 inhibitor.
PubDate: 2023-05-23
- Strategies to Address Current Challenges in Real-World Evidence Generation
in Japan-
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Abstract: The generation of real-world evidence (RWE), which describes patient characteristics or treatment patterns using real-world data (RWD), is rapidly growing more popular as a tool for decision-making in Japan. The aim of this review was to summarize challenges to RWE generation in Japan related to pharmacoepidemiology, and to propose strategies to address some of these challenges. We first focused on data-related issues, including the lack of transparency of RWD sources, linkage across different care settings, definitions of clinical outcomes, and the overall assessment framework of RWD when used for research purposes. Next the study reviewed methodology-related challenges. As lack of design transparency impairs study reproducibility, transparent reporting of study design is critical for stakeholders. For this review, we considered different sources of biases and time-varying confounding, along with potential study design and methodological solutions. Additionally, the implementation of robust assessment of definition uncertainty, misclassification, and unmeasured confounders would enhance RWE credibility in light of RWD source-related limitations, and is being strongly considered by task forces in Japan. Overall, the development of guidance for best practices on data source selection, design transparency, and analytical methods to address different sources of biases and robustness in the process of RWE generation will enhance credibility for stakeholders and local decision-makers.
PubDate: 2023-05-13
- Analysis of Adverse Events of Cholinesterase Inhibitors and NMDA Receptor
Antagonists on Arrhythmias Using the Japanese Adverse Drug Event Report
Database-
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Abstract: Background The association between anti-dementia drugs and arrhythmia is uncertain. In addition, the effects of certain drug combinations are not yet well known. Objective We investigated the association between anti-dementia drugs and arrhythmia. Furthermore, we investigated the effects of anti-dementia drugs both alone and in combination on the likelihood of arrhythmia in patients with dementia. Methods We examined the Japanese Adverse Drug Event Report database (JADER) from April 2004 to May 2022 for dementia drug users aged ≥ 60 years. We calculated the unadjusted reported odds ratio (ROR) and adjusted ROR for confounding factors. Furthermore, we examined the association of various combinations of anti-dementia drugs with the development of arrhythmias. Results There were 6718 arrhythmia cases identified out of 333,702 reported cases. The unadjusted ROR results were as follows: donepezil alone (ROR 4.39, 95% confidence interval [CI] 3.89–4.95), rivastigmine alone (2.10, 1.53–2.87), galantamine alone (3.87, 3.04–4.94), memantine alone (2.25, 1.59–3.20), and combination of choline esterase inhibitor and memantine (2.56, 1.84–3.57). In a multivariate analysis, the RORs remained significant. Conclusions Regardless of whether anti-dementia drugs were used alone or in combination, attention should be paid to the occurrence of arrhythmias.
PubDate: 2023-04-22
- A Retrospective Real-World Observational Study Assessing the Evolution of
Bisacodyl Prescriptions in Patients with Constipation During Long-Term
Treatment-
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Abstract: Background Potential habituation could be a safety concern associated with the long-term use of bisacodyl in patients with constipation. Objective In this study, we evaluated whether patients with constipation who require long-term treatment with bisacodyl will remain on a stable dose when treated for ≥ 28 days. Methods In this retrospective, population-based, observational cohort study, electronic medical record data of adult patients with constipation between January 1, 2011, and December 31, 2019, were collected from The Health Improvement Network French database. Total bisacodyl exposure during the long-term (≥ 28 days) and follow-up (12 months) periods was evaluated. The primary endpoint was the dose change status of bisacodyl during the follow-up period from the initial dose in the long-term cohort. Results Out of 5725 bisacodyl users in the database, 218 patients qualified to be part of the long-term cohort. A total of 166 (76.1%), 37 (17%), and 15 (6.9%) patients were initiated on bisacodyl at 5, 7.5, and 10 mg, respectively. During the follow-up, most (94%) of the patients remained on the same dose as initially prescribed for the first year. In contrast, only seven (3.2%) patients had their dose increased (from the initial prescribed dose of 5 mg), and the remaining six (2.8%) patients decreased their dose (four patients from the 7.5 mg group and two from the 10 mg group). Conclusion Bisacodyl can be prescribed at a stable dose for > 28 days as most patients remained on their initial prescribed dose during the follow-up period. No signs of habituation were observed in this real-world study.
PubDate: 2023-04-08
- Patients’ Perceived Importance of Medication and Adherence in
Polypharmacy, a Quantitative, Cross-Sectional Study Using a Questionnaire
Administered in Three Doctors’ Private Practices in France-
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Abstract: Background Among the determinants of nonadherence, polypharmacy (common in people with multiple pathologies and especially in elderly patients), plays a major role. Objective In patients who are subject to polypharmacy involving different classes of medications, the first aim is to assess the impact of medication importance given by patients on (i) medication adherence and (ii) the respective effect of intentionality and habit in medication importance and medication adherence. The second objective is to compare the importance given to medication and adherence in the different therapeutic classes. Patients and Methods Patients taking 5–10 different medications for at least 1 month were included in a cross-sectional survey in three private practices in one region in France. Results This study included 130 patients (59.2 % female) with 851 medications in total. The mean ± standard deviation (SD) age was 70.5 ± 12.2 years. The mean ± SD of medications taken was 6.9 ± 1.7. Treatment adherence had a strong positive correlation with the patient-perceived medication importance (p < 0.001). Counter-intuitively, taking a large number of medications (≥7) was associated with being fully adherent (p = 0.02). A high intentional nonadherence score was negatively associated with high medication importance (p = 0.003). Furthermore, patient-perceived medication importance was positively associated with taking treatment by habit (p = 0.03). Overall nonadherence more strongly correlated with unintentional nonadherence (p < 0.001) than with intentional nonadherence (p = 0.02). Compared to the antihypertensive class, a decrease in adherence by medication was observed in psychoanaleptics (p < 0.0001) and drugs used in diabetes class (p = 0.002), and a decrease in importance in lipid-modifying agents class (p = 0.001) and psychoanaleptics (p < 0.0001). Conclusion The perception of the importance of a medicine is associated with the place of intentionality and habit in patient adherence. Therefore, explaining the importance of a medicine should become an important part of patient education.
PubDate: 2023-03-30
- Perioperative Analgesics and Anesthesia as Risk Factors for Postoperative
Chronic Opioid Use in Patients Undergoing Total Knee Arthroplasty: A
Retrospective Cohort Study Using Japanese Hospital Claims Data-
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Abstract: Background Patients with chronic postsurgical pain are commonly prescribed opioids chronically because of refractory pain although chronic opioid use can cause various severe problems. Objective We aimed to investigate postoperative chronic opioid use and its association with perioperative pain management in patients who underwent a total knee arthroplasty in a Japanese real-world clinical setting. Methods We conducted a retrospective cohort study using an administrative claims database. We used a multivariate logistic regression analysis to examine the association between perioperative analgesic and anesthesia prescriptions and postoperative chronic opioid use. We calculated all-cause medication and medical costs for each patient. Results Of the 23,537,431 patient records, 14,325 patients met the criteria and were included in the analyses. There were 5.4% of patients with postoperative chronic opioid use. Perioperative prescriptions of weak opioids, strong and weak opioids, and the α2δ ligand were significantly associated with postoperative chronic opioid use (adjusted odds ratio [95% confidence interval], 7.22 [3.89, 13.41], 7.97 [5.07, 12.50], and 1.45 [1.13, 1.88], respectively). Perioperative combined prescriptions of general and local anesthesia were also significantly associated with postoperative chronic opioid use (3.37 [2.23, 5.08]). These medications and local anesthesia were more commonly prescribed on the day following surgery, after routinely used medications and general anesthesia were prescribed. The median total direct costs were approximately 1.3-fold higher among patients with postoperative chronic opioid use than those without postoperative chronic opioid use. Conclusions Patients who require supplementary prescription of analgesics for acute postsurgical pain are at high risk of postoperative chronic opioid use and these prescriptions should be given careful consideration to mitigate the patient burden.
PubDate: 2023-03-28
- The Association of Pre-operative Serum Albumin Levels and Post-operative
In-Hospital Death in Patients Undergoing Gastrointestinal Surgeries in
Thailand: A Retrospective Cohort Study-
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Abstract: Background Pre-operative hypoalbuminemia is known to predict negative outcomes for patients undergoing major surgeries. However, various cut-off points for starting exogenous albumin have been recommended. Objective This study investigated the association between pre-operative severe hypoalbuminemia, in-hospital death, and length of hospital stay in patients undergoing gastrointestinal surgery. Methods A retrospective cohort study using a database analysis was undertaken on hospitalized patients who underwent major gastrointestinal surgery. The pre-operative serum albumin level was classified into three groups: severe hypoalbuminemia (< 2.0 mg/dL) and non-severe hypoalbuminemia (≥ 2.0–3.4 g/dL) and normal level (3.5–5.5 g/dL). To compare between different cut-offs, a sensitivity analysis using another albumin level classification as severe hypoalbuminemia (< 2.5 mg/dL) and non-severe hypoalbuminemia (≥ 2.5–3.4 g/dL) and normal level (3.5–5.5 g/dL) was applied. The primary outcome was post-operative in-hospital death. Propensity-score adjusted regression analyses were applied. Results A total of 670 patients were included. Their average age was 57.4 ± 16.3 years, and 56.1% were men. Only 59 patients (8.8%) had severe hypoalbuminemia. Overall, a total of 93 in-hospital deaths (13.9%) occurred among all included patients, but there were 24/59 (40.7%) deaths among patients with severe hypoalbuminemia, 59/302 (19.5%) deaths among patients with non-severe hypoalbuminemia, and 10/309 (3.2%) deaths among patients with normal albumin level. The adjusted odds ratio for post-operative in-hospital death comparing patients with severe hypoalbuminemia and patients with normal albumin level was 8.11 (3.31–19.87; p < 0.001), while the odds ratio for in-hospital death comparing patients with non-severe and patients with normal albumin level was 3.89 (1.87–8.10; p < 0.001). A sensitivity analysis showed similar findings, the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as < 2.5 g/dL) was 7.44 (3.38–16.36; p < 0.001), while the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as 2.5–3.4 g/dL) was 3.02 (1.40–6.52; p = 0.005). Conclusions Severe pre-operative hypoalbuminemia in patients undergoing gastrointestinal surgery was associated with an increased risk of in-hospital mortality. The risk of death for patients with severe hypoalbuminemia was relatively similar when using different cut-offs such as < 2.0 and <2.5 g/dL.
PubDate: 2023-03-27
- Digoxin and Standard-of-Care Therapy for Heart Failure Patients with
COVID-19: Analysis of Data from the US Military Health System (MHS) Data
Repository-
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Abstract: Background Cardiac glycosides such as digoxin, digitoxin and ouabain are still used around the world to treat patients with chronic heart failure with reduced ejection fraction (HFrEF) and/or atrial fibrillation (AF). However, in the US, only digoxin is licensed for treating these illnesses, and the use of digoxin for this group of patients is increasingly being replaced in the US by a new standard of care with groups of more expensive drugs. However, ouabain and digitoxin, and less potently digoxin, have also recently been reported to inhibit SARS-CoV-2 virus penetration into human lung cells, thus blocking COVID-19 infection. COVID-19 is known to be a more aggressive disease in patients with cardiac comorbidities, including heart failure. Objective We therefore considered the possibility that digoxin might provide at least a measure of relief from COVID-19 in digoxin-treated heart failure patients. To this end, we hypothesized that treatment with digoxin rather than standard of care might equivalently protect heart failure patients with regard to diagnosis of COVID-19, hospitalization and death. Methods To test this hypothesis, we conducted a cross-sectional study by using the US Military Health System (MHS) Data Repository to identify all MHS TRICARE Prime and Plus beneficiaries aged 18–64 years with a heart failure (HF) diagnosis during the period April 2020 to August 2021. In the MHS, all patients receive equal, optimal care without regard to rank or ethnicity. Analyses included descriptive statistics on patient demographics and clinical characteristics, and logistic regressions to determine likelihood of digoxin use. Results We identified 14,044 beneficiaries with heart failure in the MHS during the study period. Of these, 496 were treated with digoxin. However, we found that both digoxin-treated and standard-of-care groups were equivalently protected from COVID-19. We also noted that younger active duty service members and their dependents with HF were less likely to receive digoxin compared with older, retired beneficiaries with more comorbidities. Conclusion The hypothesis of equivalent protection by digoxin treatment of HF patients in terms of susceptibility to COVID-19 infection appears to be supported by the data.
PubDate: 2023-03-18
DOI: 10.1007/s40801-023-00360-8
- Drug Burden Index in Older Adults with Psychiatric Illnesses: A
Cross-Sectional Study-
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Abstract: Background Medications with anticholinergic and/or sedative properties are commonly used in the management of psychiatric illnesses. The burden of anticholinergic and sedative medication use has been measured by the Drug Burden Index (DBI) score tool. A higher DBI score has been associated with increased risk of falls, bone and hip fractures, and functional and cognitive impairment, among other serious health outcomes, especially in older adults. Objectives We aimed to describe the drug burden in older adults with psychiatric illnesses using DBI, determine the factors that are associated with the drug burden measured by DBI, and examine the association between DBI score and Katz for activities of daily living (ADL) index. Methods A cross-sectional study was conducted in the psychogeriatric division of an aged-care home. The study sample comprised all inpatients, aged ≥ 65 years, diagnosed with psychiatric illness. The data obtained included demographic characteristics, duration of hospital stay, primary psychiatric diagnosis and comorbidities, functional status using the Katz ADL index, and cognitive status using the Mini-Mental State Examination (MMSE) score. DBI score was calculated for each anticholinergic and sedative medication used. Results Of the 200 patients eligible for analysis, 106 (53.1%) were females and the mean age was 76 ± 9 years. The most commonly encountered chronic disorders were hypertension 102 (51%) and schizophrenia 94 (47%). The use of drugs with anticholinergic and/or sedative effects was seen in 163 (81.5%) patients; the mean DBI score was 1.25 ± 1. The results of the multinomial logistic regression showed that schizophrenia (odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.57–4.45), p = 0.01), level of dependency (OR = 3.50 (95% CI 1.38–5.70), p = 0.001), and polypharmacy (OR = 2.99 (95% CI 2.15–4.29), p = 0.003) were significantly associated with DBI score ≥ 1 compared to DBI score 0. Conclusions The study showed that anticholinergic and sedative medication exposure measured by DBI was associated with higher levels of dependency on the Katz ADL index in a sample of older adults with psychiatric illnesses from an aged-care home.
PubDate: 2023-03-13
DOI: 10.1007/s40801-023-00357-3
- Factors Associated with Prescriptions for an Orexin Receptor Antagonist
Among Japanese Patients with Insomnia: Analysis of a Nationwide Japanese
Claims Database-
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Abstract: Background Few studies have examined the prescribing patterns of orexin receptor antagonists (ORAs) in the real-world clinical setting in Japan. Objective We sought to analyze the factors associated with ORA prescriptions for patients with insomnia in Japan. Methods Outpatients (aged ≥ 20 to < 75 years old) prescribed one or more hypnotic for insomnia between April 1, 2018 and March 31, 2020 with continuous enrollment for ≥ 12 months were extracted from the JMDC Claims Database. We performed multivariable logistic regression to identify factors (patient demographics and psychiatric comorbidities) associated with ORA prescription in new or non-new users of hypnotics (patients without or with hypnotics prescription history, respectively). Results Of 58,907 new users, 11,589 (19.7%) were prescribed ORA at the index date. Male sex (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.12–1.22) and presence of bipolar disorders (OR 1.36, 95% CI 1.20–1.55) were associated with greater odds of ORA prescription. Among 88,611 non-new users, 15,504 (17.5%) were prescribed ORA at the index date. Younger age and several psychiatric comorbidities, such as neurocognitive disorders (OR 1.64, 95% CI 1.15–2.35), substance use disorders (OR 1.19, 95% CI 1.05–1.35), bipolar disorders (OR 1.14, 95% CI 1.07–1.22), schizophrenia spectrum disorders (OR 1.07, 95% CI 1.01–1.14), and anxiety disorders (OR 1.05, 95% CI 1.00–1.10), were associated with greater odds of ORA prescription. Conclusion This is the first study to determine the factors associated with ORA prescriptions in Japan. Our findings could help guide appropriate insomnia treatment using ORAs.
PubDate: 2023-03-03
DOI: 10.1007/s40801-023-00356-4
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