Therapeutic Advances in Drug Safety最新文献

{"title":"Analysis of drug-induced hand-foot syndrome using a spontaneous reporting system database.","authors":"Yu Yoshida, Sayaka Sasaoka, Mizuki Tanaka, Kiyoka Matsumoto, Misaki Inoue, Riko Satake, Kazuyo Shimada, Ririka Mukai, Takaaki Suzuki, Mari Iwata, Fumiya Goto, Takayuki Mori, Koki Mori, Tomoaki Yoshimura, Mitsuhiro Nakamura","doi":"10.1177/20420986221101963","DOIUrl":"https://doi.org/10.1177/20420986221101963","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of our study was to assess the clinical features of hand-foot syndrome (HFS) associated with certain systemic chemotherapeutic drugs in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database.</p><p><strong>Methods: </strong>HFS was defined using the preferred terms from the Medical Dictionary for Regulatory Activities. We used several indices, such as the reporting odds ratios (RORs) at 95% confidence interval (CI), the time-to-onset profile of HFS, and cluster analysis.</p><p><strong>Results: </strong>Of 646,779 reports (submission period: April 2004 to September 2020), 1814 reported HFS events. The RORs (95% CI) for axitinib, capecitabine, lapatinib, regorafenib, sorafenib, and sunitinib were 14.9 (11.1-20.1), 54.6 (49.2-60.6), 130.4 (110.7-153.6), 63.3 (55.2-72.6), 29.0 (25.8-32.7), and 13.9 (11.7-16.5), respectively. The analysis of time-to-onset profiles revealed that the median values (interquartile range: 25.0-75.0%) of drug-induced HFS caused by capecitabine, cisplatin, docetaxel, everolimus, regorafenib, sorafenib, and trastuzumab were 21.0 (13.0-42.0), 15.0 (10.0-82.0), 6.0 (3.0-25.0), 86.5 (67.0-90.5), 9.0 (6.0-14.0), 9.0 (6.0-14.0), and 70.0 (15.0-189.0) days, respectively. The number of clusters was set to 4. Among these, one cluster, which included capecitabine, regorafenib, and lapatinib, exhibited a higher reporting ratio and ROR of drug-induced HFS than other drugs.</p><p><strong>Conclusions: </strong>The RORs and results of time-to-onset analysis obtained in this study indicated the potential risk of HFS associated with chemotherapeutic drugs. Our results suggest that health care professionals must be aware of the potential onset of drug-induced HFS with docetaxel, regorafenib, and sorafenib for at least 4 weeks; therefore, careful observation is recommended.</p><p><strong>Plain language summary: </strong><b>Elucidation of the relationship between cancer drugs and risk of hand-foot syndrome:</b> <b>Purpose:</b> Hand-foot syndrome (HFS) is an adverse effect of some cancer drugs, which is characterized by symptoms such as redness, swelling, blistering, and pain in the area of palms and soles. HFS reduces the quality of life of patients and can sometimes interfere with anticancer treatment plans. It is important to understand the clinical manifestations of HFS and gain knowledge that will allow for early intervention by clinicians.<b>Methods:</b> In this study, we used a large-scale side effect database of real-world cases for a comprehensive investigation of anticancer-drug-induced HFS. The database contained 646,779 adverse event reports from April 2004 to September 2020; among which, we identified 1814 HFS events. Using these data, we could obtain information on the relationship between 19 types of anticancer drugs and HFS, and the onset time of HFS and HFS prognosis related to each anticancer drug. <b>Results:</b> Our results suggest that clinicians should monitor","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"13 ","pages":"20420986221101963"},"PeriodicalIF":4.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/5d/10.1177_20420986221101963.PMC9136434.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10619326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescription for COVID-19 by non-medical professionals during the pandemic in Colombia: a cross-sectional study","authors":"María José Niño-Orrego, Daniela Baracaldo-Santamaría, Claudia Patricia Ortiz, Heyde Patricia Zuluaga, Sthefany Alejandra Cruz-Becerra, F. Soler, Andrés M. Pérez-Acosta, Daniel Ricardo Delgado, C. Calderón-Ospina","doi":"10.1177/20420986221101964","DOIUrl":"https://doi.org/10.1177/20420986221101964","url":null,"abstract":"Background: The COVID-19 pandemic has led to an increase in the behavior of self-medication (SM). Given the massive release of misleading information during the pandemic, some pharmacies recommend drugs such as ivermectin, azithromycin, and hydroxychloroquine that are not useful for preventing or treating COVID-19 and could expose patients to unnecessary adverse drug reactions (ADRs), drug-drug interactions (DDIs), disease masking, and antibiotic resistance. Rationale: SM with drugs advertised for COVID-19 can have consequences, and people should be aware of approved uses, potential contraindications, and ADRs. Thus, the aim of this study was to know the drug therapies including natural products and homeopathic drugs offered by Colombian pharmaceutical establishments for the prevention and treatment of COVID-19, as well as the information provided on the safe use of the product. Methods: An observational, cross-sectional mystery shopping study was carried out to determine the pharmaceutical alternatives for the management of COVID-19 offered by pharmaceutical establishments (drugstores, pharmacies, homeopathic pharmacies, and nutritional supplements stores) in Colombia, and information related to the safe use of the product. The study included 482 pharmaceutical establishments from 16 Colombian departments. Data collection was done through telephone calls to each of the establishments following an interview protocol pretending to be a patient who presents symptoms related to COVID-19. Results: About 57.3% (276) of the establishments recommended a product for the treatment of COVID-19 infection, 66.6% (321) asked whether the caller had COVID-19 symptoms and what they are, and 44.2% (213) suggested taking a COVID-19 test. Of 59 drugs suggested by pharmacies, the most recommended were azithromycin, ivermectin, acetaminophen, ibuprofen, and ASA (aspirin). From the establishments that recommended a product, dosage was indicated in 85.5% (236) of the pharmaceutical establishments and 14.5% (40) of the establishments reported the most common adverse effects of this substance. About 9.4% (26) of the establishments reported possible interactions of the recommended drugs and substances with food, beverages, or supplements.Conclusion: Pharmaceutical establishments in Colombia seem to have significantly contributed to self-medication for COVID-19 in Colombia during the pandemic. This behavior is inappropriate, since the mild forms of the disease do not have a specific treatment. Plain Language Summary Self-medication induced by pharmaceutical establishments in Colombia during the COVID-19 pandemic Background: The COVID-19 pandemic has led to an increase in the behavior of self-medication (SM). Given the massive release of misleading information during the pandemic, some pharmacies recommend drugs such as ivermectin, azithromycin, hydroxychloroquine among others, which are not useful for preventing or treating COVID-19 and could expose patients to unnecessary","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49320233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motivating deprescribing conversations for patients with Alzheimer's disease and related dementias: a descriptive study.","authors":"Mary T Antonelli, John S Cox, Cassandra Saphirak, Jerry H Gurwitz, Sonal Singh, Kathleen M Mazor","doi":"10.1177/20420986221118143","DOIUrl":"https://doi.org/10.1177/20420986221118143","url":null,"abstract":"<p><strong>Introduction: </strong>Older adults with Alzheimer's disease and related dementias (ADRD) are at increased risk of harm due to prescribing of potentially inappropriate medications. Encouraging patients and caregivers to talk with their providers about potentially inappropriate medications could stimulate deprescribing. Our objective was to explore whether mailing educational materials to patients with ADRD might activate patients or caregivers to initiate a conversation with their provider about potentially inappropriate medications.</p><p><strong>Methods: </strong>We conducted semi-structured interviews with patients with ADRD, caregivers of patients with ADRD, and healthcare providers. All participants were shown educational materials referencing potentially inappropriate medications and suggestions to promote deprescribing. Interviews explored reactions to the materials, the idea of patients and caregivers initiating a conversation about deprescribing, and the deprescribing process. Interview transcripts were analyzed using inductive thematic analysis.</p><p><strong>Results: </strong>We conducted a total of 27 interviews: 9 with caregivers only, 2 with patients only, 3 with patient-caregiver dyads, and 13 with providers. Patients and caregivers reported that if a medication might cause harm, it would motivate them to talk to their provider about the medication. Trust in the provider could facilitate or inhibit such conversations; conversations would be more likely if there were prior positive experiences asking questions of the provider. Providers were receptive to patients and caregivers initiating conversations about their medications, as they valued deprescribing as part of their clinical practice and welcome informed patients and caregivers as participants in decision-making about medication.</p><p><strong>Conclusion: </strong>Mailing educational materials about potentially inappropriate medications to community-dwelling patients with ADRD may promote deprescribing conversations. Ongoing pragmatic trials will determine whether such interventions stimulate deprescribing conversations and achieve reductions in prescribing of inappropriate medications.</p><p><strong>Plain language summary: </strong><b>Encouraging patients with Alzheimer's disease to talk with their providers about medications that may cause harm</b> <b>Introduction:</b> Older adults with Alzheimer's disease and related dementias (ADRD) are sometimes prescribed medications that may cause harm, especially when taken for extended periods of time. Patients and their caregivers may not know about the risks. Doctors know of the risks but may not address them due to competing priorities or other challenges in providing care to these patients with complex needs. Encouraging the patient or their caregiver to talk to their doctor about their medications might help to reduce the use of medications that are not beneficial. This study's goal was to explore whether sending educa","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"13 ","pages":"20420986221118143"},"PeriodicalIF":4.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/00/10.1177_20420986221118143.PMC9425903.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9952417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of drug postmarketing all-case surveillance as a safety measure in Japan.","authors":"Hideyuki Kondo, Ken Masamune","doi":"10.1177/20420986211065215","DOIUrl":"https://doi.org/10.1177/20420986211065215","url":null,"abstract":"<p><strong>Introduction: </strong>The drug pharmacovigilance system in Japan is similar to those in the European Union (EU) and the United States. As a unique Japanese pharmacovigilance program, postmarketing all-case surveillance (PMACS) is required. PMACS plays a key role for postmarketing activities, but there are challenges that place much burden on PMACS conduct. This study investigates the impact of PMACS on postmarketing activities in Japan and proposes its potential improvement. This study also seeks the possibility to expand PMACS beyond Japan.</p><p><strong>Materials and methods: </strong>Reexamination reports issued from 2017 to 2019 were identified in September 2020 by searching 'reexamination report' and '201701' to '201912' on the Pharmaceuticals and Medical Devices Agency website. The corresponding Package Insert (PI) change orders and premarketing review reports were also identified. Reviewing these regulatory documents allowed for investigation of the PMACS impact on postmarketing activities.</p><p><strong>Results: </strong>More than half (57%) of the drugs with PMACS had 'Limited dosing experience in Japan' as a reason for the PMACS requirement. As a safety measure, no PI change orders were imposed on 33% and 28% of drugs with and without PMACS, respectively. The means of the number of PI change orders were 2.23 and 2.14 for drugs with and without PMACS, respectively. There were no reexamination reports mentioning any concerns related to efficacy.</p><p><strong>Discussion and conclusion: </strong>PMACS should not be imposed only because of limited dosing experience in Japan at the premarketing stage. Rather, PMACS should focus on (1) collection of safety data (not efficacy), (2) necessity of distribution control, and/or (3) collection of case details for drugs with a limited treated population. PMACS also has the potential to be utilized in the EU and the United States, as their regulatory frameworks are acceptable for PMACS. Naglazyme (galsulfase) is a case where the PMACS-like studies have been required in each region.</p><p><strong>Plain language summary: </strong><b>Effectiveness of data collection for all patients who receive a new drug as a safety measure in Japan:</b> <b>Introduction::</b> In Japan, a drug company is obligated to conduct data collection after a new drug launch as an approval condition. The obligation is a unique Japanese requirement where a company must collect data from all patients receiving the drug in Japan in cooperation with hospitals. This is expected to contribute to intensive data collection and better drug distribution control and could potentially be useful in countries beyond Japan. However, no clear criteria have been established for decision making, despite the significant burden for companies and hospitals. Therefore, this study aimed to investigate the impact of the obligation on safety measures and efficacy data collection and propose a potentially improved drug scope to impose the obliga","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211065215"},"PeriodicalIF":4.4,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/97/10.1177_20420986211065215.PMC8689626.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do women with venous thromboembolism bleed more than men during anticoagulation? Data from the real-life, prospective START-Register.","authors":"Gualtiero Palareti, Cristina Legnani, Emilia Antonucci, Benilde Cosmi, Anna Falanga, Daniela Poli, Daniela Mastroiacovo, Vittorio Pengo, Walter Ageno, Sophie Testa","doi":"10.1177/20420986211062965","DOIUrl":"https://doi.org/10.1177/20420986211062965","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) is a frequent and serious disease that requires immediate and long-term anticoagulant treatment, which is inevitably associated with a risk of bleeding complications. Some studies, though not all, reported a higher risk of bleeding in female patients treated with either old anticoagulants [vitamin k antagonists (VKAs)] or recent anticoagulants [direct oral anticoagulants (DOACs)]. Furthermore, analyses of clinical trials reported an abnormal vaginal bleeding in women of reproductive age treated with DOACs. This study aimed at comparing the risk of bleeding in an inception cohort of VTE women and men included in a prospective observational registry.</p><p><strong>Methods: </strong>Baseline characteristics and bleeding events occurring during anticoagulation in patients of both sexes, included in the START-Register after a first VTE, were analyzed.</p><p><strong>Results: </strong>In all, 1298 women were compared with 1290 men. Women were older and more often had renal diseases; their index events were often provoked (often by hormonal contraception and pregnancy), and more frequently presented as isolated pulmonary embolism (PE). The rate of bleeding was similar in women (2.9% patient-years) and men (2.1% patient-years), though it was higher when uterine bleeds were included (3.5% patient-years, <i>p</i> = 0.0141). More bleeds occurred in VKA- than DOAC-treated patients (6.4% <i>versus</i> 2.6%, respectively; <i>p</i> = 0.0013). At multivariate analysis, age ⩾ 75 years was associated with higher prevalence of bleeds.</p><p><strong>Conclusion: </strong>The occurrence of bleeding was not different between women and men during anticoagulation after VTE. Only after inclusion of vaginal/uterine bleeds, the rate of bleeding was higher in women. The incidence of bleeding was higher in women treated with VKAs.</p><p><strong>Plain language summary: </strong><b>The risk of bleeding in women anticoagulated for deep vein thrombosis or pulmonary embolism is not higher than that in men, except for vaginal bleeding:</b> <b>Background::</b> The occurrence of a venous thromboembolic event (VTE, including deep vein thrombosis and pulmonary embolism) necessarily requires a period of at least 3-6 months of treatment with anticoagulant drugs [either vitamin k antagonists (VKA) or, more recently, direct oral anticoagulants (DOACs)]. Anticoagulation therapy, however, is associated with a risk of bleeding that is influenced by several factors. Sex is one of these factors as some authors have hypothesized that women are at higher risk than men. Furthermore, some studies have recently found more vaginal bleeding in VTE women treated with a DOAC compared with those who received VKAs.<b>Methods::</b> The present study aimed to compare the frequency of bleeds occurring in women and in men who were treated with DOACs or VKAs for a first VTE event and followed in real-life conditions. Since the beginning of their antic","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211062965"},"PeriodicalIF":4.4,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/a3/10.1177_20420986211062965.PMC8689616.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39789873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of deprescribing dual-purpose medications on patient-related outcomes for older adults near end-of-life: a systematic review and meta-analysis.","authors":"Shakti Shrestha, Arjun Poudel, Magnolia Cardona, Kathryn J Steadman, Lisa M Nissen","doi":"10.1177/20420986211052343","DOIUrl":"https://doi.org/10.1177/20420986211052343","url":null,"abstract":"<p><strong>Introduction: </strong>The decision to deprescribe medications used for both disease prevention and symptom control (dual-purpose medications or DPMs) is often challenging for clinicians. We aim to establish the impact of deprescribing DPMs on patient-related outcomes for older adults near end-of-life (EOL).</p><p><strong>Methods: </strong>This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Literature was searched on PubMed, EMBASE, CINAHL, PsycINFO and Google Scholar until December 2019 for studies on deprescribing intervention with a control group (with or without randomisation); targeting ⩾65-year olds, at EOL, with at least one life-limiting illness and at least one potentially inappropriate DPM. We were interested in any patient-related outcomes. Studies with similar outcome assessment criteria were subjected to meta-analysis and narrative synthesis otherwise. The risk of bias was assessed using Cochrane Risk of Bias and ROBINS-I tools for randomised controlled trials (RCTs) and quasi-experimental non-randomised controlled studies, respectively.</p><p><strong>Results: </strong>Five studies covering 689 participants with mean age 81.6-85.7 years, the majority (74.6-100%) with dementia were included. The risk of bias was moderate to low. The deprescribing of DPMs lowered the risk of mortality (risk ratio (RR) = 0.59, 95% confidence interval (CI) = 0.44-0.79) and referral to acute care facilities (RR = 0.40, 95% CI = 0.22-0.73), but did not have a significant impact on the risk of falls, non-vertebral fracture, emergency presentation, unplanned hospital admission, or general practitioner visits. No significant difference was observed in the quality of life, physical and cognitive functions between the intervention and control groups.</p><p><strong>Conclusion: </strong>There is some evidence that deprescribing of DPMs for older adults near the EOL can lower the risk of mortality and referral to acute care facilities, but there are insufficient good-quality studies powered to confirm a benefit in terms of quality of life, physical or cognitive function, health service utilisation and adverse events.</p><p><strong>Plain language summary: </strong><b>What is the health impact of withdrawal or dose reduction of medication used for disease prevention and symptom control in older adults near end-of-life?</b> <b>Introduction:</b> Older adults (aged ⩾ 65 years) with advanced diseases such as cancer, dementia, and organ failure tend to have a limited life expectancy. With the progression of these diseases towards the end-of-life, the intensity for day-to-day supportive care becomes increasingly necessary. The use of medications for symptom management is a critical part of such care, but the use of medications for long-term disease prevention can become irrelevant due to the already shortened life expectancy and may become harmful due to alterations in phys","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211052343"},"PeriodicalIF":4.4,"publicationDate":"2021-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/df/10.1177_20420986211052343.PMC8543710.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39567009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective cohort study of nonspecific deprescribing in older medical inpatients being discharged to a nursing home.","authors":"Patrick Russell, Udul Hewage, Cameron McDonald, Campbell Thompson, Richard Woodman, Arduino A Mangoni","doi":"10.1177/20420986211052344","DOIUrl":"https://doi.org/10.1177/20420986211052344","url":null,"abstract":"<p><strong>Background: </strong>Older patients from nursing homes are commonly exposed to polypharmacy before a hospital admission. Deprescribing has been promoted as a solution to this problem, though systematic reviews have not found benefit. The aim of this study was to understand if in-hospital deprescribing of certain classes of medications is associated with certain benefits or risks.</p><p><strong>Methods: </strong>We conducted a prospective, multicentre, cohort study in 239 medical inpatients ⩾75 years (mean age 87.4 years) who were exposed to polypharmacy (⩾5 medications) prior to admission and discharged to a nursing home for permanent placement. Patients were categorised by whether deprescribing occurred, mortality and readmissions were assessed 30 and 90 days after hospital discharge. The EQ-5D-5 L health survey assessed changes in health-related quality of life (HRQOL) at 90 days, with comparison to EQ-5D-5 L results at day 30. Latent class analysis (LCA) was used to investigate associations between patterns of prescribed and deprescribed medications and mortality.</p><p><strong>Results: </strong>Patients for whom deprescribing occurred had a higher Charlson Index; there were no differences between the groups in principal diagnosis, total or Beers list number of medications on admission. The number of Beers list medications increased in both groups before discharge. Patients who had medications deprescribed had nonsignificantly greater odds of dying within 90 days [odds ration (OR) = 3.23 (95% confidence interval (CI): 0.68, 14.92; p = 0.136]. Deprescribing of certain classes was associated with higher 90-day mortality: antihypertensives (OR = 2.27, 95% CI: 1.004, 5; <i>p</i> = 0.049) and statins (OR = 5, 95% CI: 1.61, 14.28; <i>p</i> = 0.005). Readmissions and 1-year mortality rates were similar. There was no deterioration in HRQOL when medications were deprescribed. LCA showed that patients with the least medication changes had the lowest mortality.</p><p><strong>Conclusion: </strong>Deprescribing certain classes of medications during hospitalisation was associated with worse mortality, but not readmissions or overall HRQOL. Larger controlled deprescribing studies targeting specific medications are warranted to further investigate these findings.This study was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN1 2616001336471.</p><p><strong>Plain language summary: </strong><b>Background:</b> When an older person living in a nursing home is admitted to hospital, does stopping long-term medications help them?Many older people from nursing homes take a large number of medications each day to treat symptoms and prevent adverse events. \"Polypharmacy\" is a term used to describe taking multiple long-term medications, and it is associated with many negative outcomes such as increased number of falls, cognitive decline, hospital readmission, even death. Deprescribing of nonessential medications - whether stopping ","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211052344"},"PeriodicalIF":4.4,"publicationDate":"2021-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/eb/10.1177_20420986211052344.PMC8543714.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39567010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The safety, tolerability and mortality reduction efficacy of remdesivir; based on randomized clinical trials, observational and case studies reported safety outcomes: an updated systematic review and meta-analysis.","authors":"Chenchula Santenna, Kota Vidyasagar, Krishna Chaitanya Amarneni, Sai Nikhila Ghanta, Balakrishnan Sadasivam, Saman Pathan, R Padmavathi","doi":"10.1177/20420986211042517","DOIUrl":"10.1177/20420986211042517","url":null,"abstract":"<p><strong>Introduction: </strong>Remdesivir, an experimental antiviral drug has shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both <i>in vitro</i> and <i>in vivo</i>. The present systematic review and meta-analysis were performed to quantify the safety and tolerability of remdesivir, based on safety outcome findings from randomized controlled trials, observational studies and case reports of remdesivir in coronavirus disease 2019 (COVID-19) patients.</p><p><strong>Methods: </strong>We have performed a systematic search in the PubMed, Google Scholar and Cochrane Library using specific keywords such as 'COVID-19' OR 'SARS CoV-2' AND 'Remdesivir'. The study endpoints include total adverse events (AEs), serious adverse events (SAEs), grade 3 and grade 4 AEs, mortality and drug tolerability. Statistical analysis was carried out by using Revman 5.4 software.</p><p><strong>Results: </strong>Total 15 studies were included for systematic review, but only 5 randomized clinical trials (RCTs) (<i>n</i> = 13,622) were included for meta-analysis. Visual inspection of the forest plots for remdesivir 10-day <i>versus</i> placebo and remdesivir 10-day <i>versus</i> 5-day groups revealed that there is a significant difference in SAEs [10-day remdesivir <i>versus</i> control (odds ratio [OR] = 0.55, 0.40-0.74) <i>p</i> = 0.0001; <i>I</i> <sup>2</sup> = 0%; 10-day remdesivir <i>versus</i> 5-day remdesivir (OR = 0.56, 0.38-0.84) <i>p</i> = 0.005; <i>I</i> <sup>2</sup> = 13%]. In grade 4 AEs, there is a significant difference in 10-day remdesivir <i>versus</i> control (OR = 0.32, 0.19-0.54) <i>p</i> = 0.0001; <i>I</i> <sup>2</sup> = 0%, but not in comparison to 5-day remdesivir (OR = 0.95, 0.59-1.54) <i>p</i> = 0.85; <i>I</i> <sup>2</sup> = 0%. But there is no significant difference in grade 3 AEs [remdesivir 10 day <i>versus</i> control (OR = 0.81, 0.59-1.11) <i>p</i> = 0.19; <i>I</i> <sup>2</sup> = 0%; 10-day remdesivir <i>versus</i> 5-day remdesivir (OR = 1.24, 0.86-1.80) <i>p</i> = 0.25; <i>I</i> <sup>2</sup> = 0%], in total AEs [remdesivir 10 day <i>versus</i> control (OR = 1.07, 0.66-1.75) <i>p</i> = 0.77; <i>I</i> <sup>2</sup> = 79%; remdesivir 10 day <i>versus</i> 5 day (OR = 1.08, 0.70-1.68) <i>p</i> = 0.73; <i>I</i> <sup>2</sup> = 54%)], in mortality [10-day remdesivir <i>versus</i> control (OR = 0.93, 0.80-1.08) <i>p</i> = 0.32; <i>I</i> <sup>2</sup> = 0%; 10-day remdesivir <i>versus</i> 5-day remdesivir (OR = 1.39, 0.73-2.62) <i>p</i> = 0.32; <i>I</i> <sup>2</sup> = 0%)] and tolerability [remdesivir 10 day <i>versus</i> control (OR = 1.05, 0.51-2.18) <i>p</i> = 0.89; <i>I</i> <sup>2</sup> = 65%, 10-day remdesivir <i>versus</i> 5-day remdesivir (OR = 0.86, 0.18-4.01) <i>p</i> = 0.85; <i>I</i> <sup>2</sup> = 78%].</p><p><strong>Discussion & conclusion: </strong>Ten-day remdesivir was a safe antiviral agent but not tolerable over control in the hospitalized COVID-19 patients with a need of administration cautiousness for grad","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211042517"},"PeriodicalIF":4.4,"publicationDate":"2021-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/15/10.1177_20420986211042517.PMC8477695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39476403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in pharmacovigilance following the end of the Brexit transition.","authors":"Sarah Hall","doi":"10.1177/20420986211042208","DOIUrl":"https://doi.org/10.1177/20420986211042208","url":null,"abstract":"","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211042208"},"PeriodicalIF":4.4,"publicationDate":"2021-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/a7/10.1177_20420986211042208.PMC8458674.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39452378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of potential drug interactions between repurposed COVID-19 and antitubercular drugs: an integrational approach of drug information software and computational techniques data.","authors":"Levin Thomas, Sumit Raosaheb Birangal, Rajdeep Ray, Sonal Sekhar Miraj, Murali Munisamy, Muralidhar Varma, Chidananda Sanju S V, Mithu Banerjee, Gautham G Shenoy, Mahadev Rao","doi":"10.1177/20420986211041277","DOIUrl":"https://doi.org/10.1177/20420986211041277","url":null,"abstract":"<p><strong>Introduction: </strong>Tuberculosis is a major respiratory disease globally with a higher prevalence in Asian and African countries than rest of the world. With a larger population of tuberculosis patients anticipated to be co-infected with COVID-19 infection, an ongoing pandemic, identifying, preventing and managing drug-drug interactions is inevitable for maximizing patient benefits for the current repurposed COVID-19 and antitubercular drugs.</p><p><strong>Methods: </strong>We assessed the potential drug-drug interactions between repurposed COVID-19 drugs and antitubercular drugs using the drug interaction checker of IBM Micromedex®. Extensive computational studies were performed at a molecular level to validate and understand the drug-drug interactions found from the Micromedex drug interaction checker database at a molecular level. The integrated knowledge derived from Micromedex and computational data was collated and curated for predicting potential drug-drug interactions between repurposed COVID-19 and antitubercular drugs.</p><p><strong>Results: </strong>A total of 91 potential drug-drug interactions along with their severity and level of documentation were identified from Micromedex between repurposed COVID-19 drugs and antitubercular drugs. We identified 47 pharmacodynamic, 42 pharmacokinetic and 2 unknown DDIs. The majority of our molecular modelling results were in line with drug-drug interaction data obtained from the drug information software. QT prolongation was identified as the most common type of pharmacodynamic drug-drug interaction, whereas drug-drug interactions associated with cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) inhibition and induction were identified as the frequent pharmacokinetic drug-drug interactions. The results suggest antitubercular drugs, particularly rifampin and second-line agents, warrant high alert and monitoring while prescribing with the repurposed COVID-19 drugs.</p><p><strong>Conclusion: </strong>Predicting these potential drug-drug interactions, particularly related to CYP3A4, P-gp and the human Ether-à-go-go-Related Gene proteins, could be used in clinical settings for screening and management of drug-drug interactions for delivering safer chemotherapeutic tuberculosis and COVID-19 care. The current study provides an initial propulsion for further well-designed pharmacokinetic-pharmacodynamic-based drug-drug interaction studies.</p><p><strong>Plain language summary: </strong><b>Introduction::</b> Tuberculosis is a major respiratory disease globally with a higher prevalence in Asian and African countries than rest of the world. With a larger population of tuberculosis patients predicted to be infected with COVID-19 during this period, there is a higher risk for the occurrence of medication interactions between the medicines used for COVID-19 and tuberculosis. Hence, identifying and managing these interactions is vital to ensure the safety of patients undergoing COVID-19 and t","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211041277"},"PeriodicalIF":4.4,"publicationDate":"2021-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/f8/10.1177_20420986211041277.PMC8404633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39375805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}