Pub Date : 2022-01-01DOI: 10.1177/20420986221118143
Mary T Antonelli, John S Cox, Cassandra Saphirak, Jerry H Gurwitz, Sonal Singh, Kathleen M Mazor
<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
{"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}
Pub Date : 2021-12-16eCollection Date: 2021-01-01DOI: 10.1177/20420986211065215
Hideyuki Kondo, Ken Masamune
<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
{"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}
Pub Date : 2021-12-16eCollection Date: 2021-01-01DOI: 10.1177/20420986211062965
Gualtiero Palareti, Cristina Legnani, Emilia Antonucci, Benilde Cosmi, Anna Falanga, Daniela Poli, Daniela Mastroiacovo, Vittorio Pengo, Walter Ageno, Sophie Testa
<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
{"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}
Pub Date : 2021-10-22eCollection Date: 2021-01-01DOI: 10.1177/20420986211052343
Shakti Shrestha, Arjun Poudel, Magnolia Cardona, Kathryn J Steadman, Lisa M Nissen
<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
对临床医生来说，决定取消既用于疾病预防又用于症状控制的药物(双重用途药物或dpm)通常是具有挑战性的。我们的目标是确定处方dpm对接近生命末期(EOL)的老年人患者相关结果的影响。方法:本系统评价按照PRISMA(系统评价和荟萃分析首选报告项目)指南进行。截至2019年12月，在PubMed、EMBASE、CINAHL、PsycINFO和Google Scholar上检索有关对照组(随机化或不随机化)的处方性干预研究的文献;针对小于或等于65岁的人，在EOL，至少有一种限制生命的疾病和至少一种可能不适当的DPM。我们对任何与患者相关的结果都感兴趣。具有类似结果评估标准的研究进行meta分析和叙事综合。分别使用Cochrane risk of bias和ROBINS-I工具对随机对照试验(rct)和准实验非随机对照研究进行偏倚风险评估。结果:5项研究纳入689名参与者，平均年龄81.6-85.7岁，其中大多数(74.6-100%)为痴呆患者。偏倚风险为中到低。dpm的处方降低了死亡风险(风险比(RR) = 0.59, 95%可信区间(CI) = 0.44-0.79)和转诊到急症护理机构的风险(RR = 0.40, 95% CI = 0.22-0.73)，但对跌倒、非椎体骨折、急诊、计划外住院或全科医生就诊的风险没有显著影响。干预组和对照组在生活质量、身体和认知功能方面没有观察到显著差异。结论:有一些证据表明，对接近EOL的老年人开dpm处方可以降低死亡率和转诊到急性护理机构的风险，但没有足够的高质量研究来证实在生活质量、身体或认知功能、卫生服务利用和不良事件方面的益处。简单的语言总结:在接近生命末期的老年人中，用于疾病预防和症状控制的药物停药或剂量减少对健康的影响是什么?引言:患有癌症、痴呆和器官衰竭等晚期疾病的老年人(年龄大于或等于65岁)的预期寿命往往有限。随着这些疾病向生命末期发展，日常支持性护理的强度变得越来越必要。使用药物进行症状管理是此类护理的关键部分，但由于预期寿命已经缩短，使用药物进行长期疾病预防可能变得无关紧要，并且可能由于与年龄和虚弱相关的生理和药理学改变而变得有害。这就需要停药或减少不适当药物的剂量，这一过程被称为去处方化。在这一人群中，决定取消用于疾病预防和症状控制(DPMs)的药物通常对临床医生具有挑战性。在这种情况下，dpm的处方是否可以改善患者相关的健康结果是未知的。方法:对文献证据进行回顾和分析，并对研究质量进行评价。五项研究确定了689名参与者，他们的平均年龄在80岁以上，大多数患有痴呆症。结果:对这些研究的分析表明，在12个月时，减少dpm的处方降低了死亡和转诊到急性护理机构的风险，但对跌倒、非椎体骨折、急诊表现、计划外住院、全科医生就诊、生活质量、身心功能没有显著影响。结论:总而言之，目前没有足够的高质量研究来证实处方dpm是否能减少不良事件、减少医疗服务的使用，或改善接近生命终点的老年人的生活质量或功能。
{"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}
Pub Date : 2021-10-22eCollection Date: 2021-01-01DOI: 10.1177/20420986211052344
Patrick Russell, Udul Hewage, Cameron McDonald, Campbell Thompson, Richard Woodman, Arduino A Mangoni
<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
{"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}
Pub Date : 2021-09-24eCollection Date: 2021-01-01DOI: 10.1177/20420986211042517
Chenchula Santenna, Kota Vidyasagar, Krishna Chaitanya Amarneni, Sai Nikhila Ghanta, Balakrishnan Sadasivam, Saman Pathan, R Padmavathi
<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
{"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}
Pub Date : 2021-09-20eCollection Date: 2021-01-01DOI: 10.1177/20420986211042208
Sarah Hall
{"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}
<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
{"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}
Pub Date : 2021-08-24eCollection Date: 2021-01-01DOI: 10.1177/20420986211043303
[This corrects the article DOI: 10.1177/2042098616646726.].
[这更正了文章DOI: 10.1177/2042098616646726.]。
{"title":"Corrigendum.","authors":"","doi":"10.1177/20420986211043303","DOIUrl":"https://doi.org/10.1177/20420986211043303","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/2042098616646726.].</p>","PeriodicalId":23012,"journal":{"name":"Therapeutic Advances in Drug Safety","volume":"12 ","pages":"20420986211043303"},"PeriodicalIF":4.4,"publicationDate":"2021-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/13/10.1177_20420986211043303.PMC8388215.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39366979","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}
Pub Date : 2021-08-05eCollection Date: 2021-01-01DOI: 10.1177/20420986211038436
Marco Sardella, Glyn Belcher, Calin Lungu, Terenzio Ignoni, Manuela Camisa, Doris Irene Stenver, Paolo Porcelli, Margherita D'Antuono, Nicola Gian Castiglione, Anna Adams, Giovanni Furlan, Ilaria Grisoni, Sarah Hall, Laura Boga, Valentina Mancini, Mircea Ciuca, David Chonzi, Brian Edwards, Arduino A Mangoni, Marco Tuccori, Elena Prokofyeva, Fabio De Gregorio, Mario Bertazzoli Grabinski Broglio, Bert van Leeuwen, Paola Kruger, Christian Rausch, Hervé Le Louet
<p><p>The collection and assessment of individual case safety reports (ICSRs) is important to detect unknown adverse drug reactions particularly in the first decade after approval of new chemical entities. However, regulations require that these activities are routinely undertaken for all medicinal products, including older medicines such as generic medicinal products with a well-established safety profile. For the latter, the risk management plans no longer contain important risks, considered important safety concerns, on the basis that routine pharmacovigilance activity would not allow their further characterisation. Society assumes that unexpected adverse reactions causally related to pharmacological activity are very unlikely to be detected for such well-established medicines, but important risks can still occur. For these products, a change in the safety profile which is brand or source specific and usually local in nature, associated with failures with the adequate control of quality of manufacturing or distribution are important safety issues. These may be the consequence of manufacturing and pharmacovigilance quality systems that are not fully integrated over the product life cycle (e.g. inadequate control of quality defects affecting one or multiple batches; inadequate impact assessment of change/variation of manufacturing, quality control testing, storage and distribution processes; inadequate control over the distribution channels including the introduction of counterfeit or falsified products into the supply chain). Drug safety hazards caused by the above-mentioned issues have been identified with different products and formulations, from small molecules to complex molecules such as biological products extracted from animal sources, biosimilars and advanced therapy medicinal products. The various phases of the drug manufacturing and distribution of pharmaceutical products require inputs from pharmacovigilance to assess any effects of quality-related issues and to identify proportionate risk minimisation measures that often have design implications for a medicine which requires a close link between proactive vigilance and good manufacturing practice. To illustrate our argument for closer organisational integration, some examples of drug safety hazards originating from quality, manufacturing and distribution issues are discussed.</p><p><strong>Plain language summary: </strong><b>Monitoring the manufacturing and quality of medicines: the fundamental task of pharmacovigilance</b> Pharmacovigilance is the science relating to the collection, detection, assessment, monitoring, and prevention of adverse reactions with pharmaceutical products. The collection and assessment of adverse reactions are particularly important in the first decade after marketing authorisation of a drug as the information gathered in this period could help, for example, to identify complications from its use which were unknown before its commercialization. However, wh
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