Clinical therapeutics最新文献

{"title":"Understanding Variation Among Medical Device Reporting Sources: A Study of the MAUDE Database.","authors":"Meital Mishali, Nadav Sheffer, Oren Mishali, Maya Negev","doi":"10.1016/j.clinthera.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.10.004","url":null,"abstract":"<p><strong>Background: </strong>Increasing medical device usage raises concerns regarding unexpected, potentially life-threatening events that pose public health risks. Such events are reported to the Food and Drug Administration (FDA), and cataloged in the Manufacturer and User Facility Device Experience (MAUDE) database, a vital tool for post market surveillance that requires information of high quality and integrity, particularly concerning reporting sources.</p><p><strong>Purpose: </strong>To analyze reporting behavior among different reporters, including manufacturers, distributors, and user facilities, by examining differences in reported factors, namely: (1) device types, (2) product problem attribution, and (3) selection of Device Problem Codes (DPCs) associated with the root causes of events.</p><p><strong>Methods: </strong>Data spanning from 2005 to 2022 was retrieved from the MAUDE database using Python. Reports were grouped by reporter type and divided according to device type, and the reporter's indication of association with a product problem. Furthermore, events were classified by their respective DPCs, which were manually grouped into four categories: device issues, user issues, clinical issues, or unknown.</p><p><strong>Findings: </strong>The analysis revealed significant variations among reporters across all examined aspects (P < 0.00001 in all comparisons according to the proportion test). Manufacturers predominantly focused on infusion pumps (10.1%) and Implant, Endosseous, Root-Form (IER) devices (7.6%), with a product problem indication rate of 29.2% in their reports. Device issues codes were the most frequently observed category in their reports, comprising 36.3%, followed by unknown codes (32%) and clinical codes (19.3%). Distributors, on the other hand, primarily reported on IER devices (89%) and exhibited the lowest product problem indication rate at 2.7%. Clinical issues codes predominated in their reports, constituting 85.7%, followed by unknown codes (6.7%). User facilities concentrated on intravascular sets (4.7%), Electrosurgical, Cutting & Coagulation & Accessories (4.2%), and Ventricular (Assist) Bypass (4.1%). Remarkably, their product problem indication rate was the highest at 56.7%. They predominantly reported device issues codes (54.3%), followed by use codes (30.8%), and unknown codes (11.4%) IMPLICATIONS: The notable variation among different reporters underscores the importance of incorporating diverse sources when analyzing the database, particularly in cases where majority of reports originate from manufacturers. Decision-makers must approach database information comprehensively, considering data sources and diverse perspectives to inform regulatory decisions effectively. Developing strategies that encourage various reporters to contribute their unique and complementary viewpoints is advisable.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation Between Vitamin D, Inflammatory Markers, and T Lymphocytes With the Severity of Chronic Obstructive Pulmonary Disease and its Effect on the Risk of Acute Exacerbation: A Single Cross-sectional Study.","authors":"Yeqian Jiang, Mingzhu Li, Yan Yu, Hejun Liu, Qianbing Li","doi":"10.1016/j.clinthera.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.10.003","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic obstructive pulmonary disease (COPD) will become the fourth largest cause of death of chronic diseases in the world in 2030. The incidence of COPD ranked top among chronic diseases in the world. At present, there is a lack of simple and effective drugs for the treatment of COPD and for slowing the progression of the disease. The application of vitamin D as a drug in clinical treatment has been a research hotspot. In this study, we investigated the correlation between serum 25-hydroxyvitamin D (25(OH)D), inflammatory markers, and T lymphocytes with the severity of COPD and its effect on the risk of acute exacerbation.</p><p><strong>Methods: </strong>In this study, we recruited hospital inpatients and outpatient clinic patients with COPD. Their levels of 25(OH)D, inflammatory markers, and T lymphocytes were assessed. We built a nomogram model to evaluate the risk of acute exacerbation of COPD.</p><p><strong>Findings: </strong>The inflammatory mediators were higher in patients with acute exacerbation of COPD (AECOPD) than those in patients with COPD, but 25(OH)D showed the opposite phenomenon. In logistic regression analysis, high levels of neutrophil-lymphocyte ratio, C-reactive protein, and partial pressure of carbon dioxide and low levels of vitamin D, partial pressure of oxygen, and forced expiratory volume in the first as a percentage of predicted were regarded as independent risk factors for AECOPD. These variables were used for the construction of the nomogram model. The AUCs of the model were 0.971 (95% CI, 0.952-0.989), and 0.981 (95% CI, 0.959-1.000) in the training and testing set respectively, demonstrating that the model exhibited high accuracy for the prediction of the risk of acute exacerbation of COPD. The calibration curve of the nomogram found a high degree of consistency between the expected and actual values. The decision curve analysis and clinical impact curve indicated that the nomogram has clinical applicable for patients with COPD.</p><p><strong>Implications: </strong>A considerable percentage of patients with COPD were found to have insufficient vitamin D levels. Patients with AECOPD reported more symptoms than those with COPD. The variables neutrophil-lymphocyte ratio, C-reactive protein, partial pressure of carbon dioxide, 25(OH)D, partial pressure of oxygen, and forced expiratory volume in the first as a percentage of predicted can be used for the prediction of AECOPD. Accordingly, this study provided experimental rationales for the role of 25(OH)D in the prevention and the potential anti-inflammatory mechanisms involved in the control of the COPD process.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Burden and Health Care Resource Utilization Associated With Managing Sickle Cell Disease With Recurrent Vaso-occlusive Crises in England.","authors":"Chuka Udeze, Nelly F Ly, Fiona C Ingleby, Sophia D Fleming, Sarah C Conner, Jo Howard, Nanxin Li, Farrukh Shah","doi":"10.1016/j.clinthera.2024.09.023","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.023","url":null,"abstract":"<p><strong>Purpose: </strong>Sickle cell disease (SCD) is an inherited red blood cell disease caused by a mutation in the gene encoding the β-subunit of adult hemoglobin that leads to hemolysis, anemia, vaso-occlusive crises (VOCs), morbidity, and mortality. This study provides a real-world assessment of the clinical burden and health care resource utilization (HCRU) associated with SCD with recurrent VOCs in England.</p><p><strong>Methods: </strong>This retrospective study linked primary care records from the Clinical Practice Research Datalink database with secondary care records from the Hospital Episode Statistics database to identify patients with SCD with recurrent VOCs between July 1, 2008, and June 30, 2018. A VOC was defined as SCD with crisis, acute chest syndrome, or priapism. Eligible patients had SCD, ≥2 VOCs/year in any 2 consecutive years after a diagnosis of SCD, and ≥1 year of follow-up data from the index date. Patients were exact matched with 5 controls from the general population in the databases. Demographics were assessed at index. Mortality, clinical complications, and HCRU were summarized during follow-up.</p><p><strong>Findings: </strong>After applying eligibility criteria, 1117 patients with SCD with recurrent VOCs and 5585 controls were included in the study. Mean age at index was 25 years in both groups. The proportion of deaths (3.67% vs 0.68%; P < 0.001) and mortality rate (0.78 deaths per 100 person-years vs 0.16 deaths per 100 person-years) were substantially higher in patients with SCD with recurrent VOCs versus matched controls. Mean (standard deviation [SD]) age of death in patients with SCD with recurrent VOCs who died during the follow-up period was 40.17 (14.09) years. The mean (SD) rate of VOCs for patients with SCD with recurrent VOCs was 5.84 (12.50) per patient per year (PPPY) during follow-up. Compared with matched controls, patients with SCD with recurrent VOCs had substantially higher mean [SD] rates PPPY of inpatient hospitalizations (7.59 [14.50] vs 0.32 [2.71]), prescriptions (31.06 [60.62] vs 7.58 [27.77]), and outpatient visits (9.60 [10.69] vs 1.78 [4.18]). Older patients and those with increased numbers of VOCs had increased mortality, frequency of clinical complications, and HCRU.</p><p><strong>Implications: </strong>Despite currently available care, patients with SCD with recurrent VOCs in England have increased mortality, substantial clinical complications, and significant HCRU driven by VOCs and hospitalizations. Elevated mortality and clinical complications in patients with SCD with recurrent VOCs highlight the need for novel therapies in this space.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Prior Antiplatelet Therapy and Prognosis in Patients With Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis","authors":"Hanxu Zhang PhD ,&nbsp;Xiaoran Hou MS ,&nbsp;Yidan Gou MS ,&nbsp;Yanyan Chen MS ,&nbsp;Shuo An MD ,&nbsp;Yingsheng Wei MD ,&nbsp;Rongcai Jiang MD ,&nbsp;Ye Tian MD ,&nbsp;Hengjie Yuan PhD","doi":"10.1016/j.clinthera.2024.08.010","DOIUrl":"10.1016/j.clinthera.2024.08.010","url":null,"abstract":"<div><h3>Purpose</h3><div>Approximately 20% to 30% of intracerebral hemorrhage (ICH) patients were reported to be on antiplatelet therapy (APT), and association between prior APT and prognosis was unclear. We aimed to clarify the impact of APT on the prognosis of ICH through an updated systematic review and meta-analysis, and to further compare the risk of single APT (SAPT) or dual APT (DAPT) prior to ICH as well as the risk associated with various antiplatelet drugs.</div></div><div><h3>Methods</h3><div>EMBASE, MEDLINE via Ovid SP and Web of Science were searched from inception of each database to November 4, 2023. Included studies reported prognosis in both patients with prior APT and those without.</div></div><div><h3>Findings</h3><div>A total of 433,103 patients from 43 studies were included in the meta-analysis. Both univariate and multivariate analyses demonstrated a significant association between prior-APT and an increased mortality risk (odd ratio [OR] 1.43, 95% confidence interval [CI] 1.28–1.59; OR 1.20, 95%CI 1.10–1.30, respectively). The risk was higher in short term follow-up (Univariate OR 1.73, 95%CI 1.22–2.46; Multivariate OR 1.94, 95%CI 1.48–2.55). A notably increased risk of hematoma expansion was also observed in patients previously treated with APT (Univariate OR 1.47, 95%CI 1.12–1.94; Multivariate OR 1.88, 95%CI 1.30–2.71), which were mainly attributed to events within 24 hours. The impact of prior-APT on poor functional outcome was inconsistent between univariate and multivariate analyses. Both direct and indirect comparisons showed that SAPT significantly reduced the risk of mortality (OR 0.67, 95%CI 0.64–0.70; OR 0.84, 95%CI 0.71–0.99) and poor functional outcome (OR 0.84, 95%CI 0.72–0.98; OR 0.81, 95%CI 0.72–0.91) compared to DAPT.</div></div><div><h3>Implications</h3><div>Prior-APT increased the risk of mortality and hematoma expansion in patients with ICH. The increased risk of mortality and hematoma expansion was more obvious in the short term follow-up and within 24 hours, respectively. The effect of APT on poor functional outcome exhibited inconsistency between univariate and multivariate analyses, suggesting that further investigation is warranted to clarify this relationship. In comparison with DAPT, SAPT could decrease the risk of mortality and poor functional outcome. Further studies focusing on antiplatelet drug response, racial differences, and specific APT regimens may help verify the influence.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 905-915"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Cross-Sectional Analysis of the Humanistic and Economic Burden of Bipolar I Disorder","authors":"Larry Culpepper MD, MPH ,&nbsp;Ashley Martin PhD, MS ,&nbsp;Amanda Harrington PhD ,&nbsp;Sally W. Wade MPH ,&nbsp;Mousam Parikh MSc, BSc","doi":"10.1016/j.clinthera.2024.08.003","DOIUrl":"10.1016/j.clinthera.2024.08.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study quantified the burdens of bipolar I disorder (BP-I) by examining patient characteristics, health-related quality of life (HRQoL), health care resource utilization (HCRU), and costs of patients with versus without BP-I. Additionally, these outcomes were assessed across BP-I severity levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A retrospective, cross-sectional analysis of the 2020 National Health and Wellness Survey was conducted. Adults who self-reported a physician diagnosis of BP-I were assigned to the BP-I cohort, with severity-specific subgroups (mild, moderate, severe) created for analysis. A separate cohort of participants without BP-I or MDD was used for comparison. Exclusion criteria included a schizophrenia diagnosis. Bivariate analyses compared demographic and socioeconomic characteristics between cohorts. HRQoL (Short Form-36v2 Health Survey [SF36v2] mental and physical component scores, EuroQol Five-Dimension Visual Analogue Scale [EQ-5D VAS]), HCRU (health care provider visits, emergency department visits, hospitalizations), and annualized costs (direct and indirect) were evaluated for participants with versus without BP-I as well as across BP-I severity subgroups using multivariate analyses adjusted for key baseline differences. Because BP-I is often misdiagnosed as MDD, outcomes were evaluated in a subgroup of participants with MDD who according to the Mood Disorder Questionnaire screened as having probable BP-I (ie, potentially misdiagnosed BP-I) and were compared with the BP-I severity subgroups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Cohorts included 818 participants with BP-I (mild = 336, moderate = 285, severe = 197) and 53,021 participants without BP-I. Participants with BP-I reported significantly lower HRQoL scores on the SF-36v2 and EQ-5D VAS (all measures, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), and increasing BP-I severity was predictive of declining HRQoL. Participants with BP-I had significantly greater HCRU (all measures, &lt;em&gt;P&lt;/em&gt; &lt; 0.05) than participants without BP-I and increasing BP-I severity was associated with greater HCRU versus the mild BP-I cohort (all measures, &lt;em&gt;P&lt;/em&gt; &lt; 0.05). Participants with BP-I incurred significantly greater total direct (&lt;em&gt;P&lt;/em&gt; &lt; 0.01) and indirect (&lt;em&gt;P&lt;/em&gt; &lt; 0.001) costs versus participants without BP-I. Direct costs were incrementally higher across BP-I severity, while indirect costs were high across all groups but did not differ significantly. Participants with potentially misdiagnosed BP-I (n = 302) had similar HRQoL to those with mild-to-moderate BP-I and similar HCRU and direct costs to those with mild BP-I.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Implications&lt;/h3&gt;&lt;div&gt;These results demonstrate the substantial clinical and economic burdens associated with BP-I, and these negative impacts generally increase with BP-I severity. The study also suggests that despite not having the diagnosis of BP-I, burdens of potentially misdiagnosed patients are similar to ","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 855-864"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bariatric Surgery Underutilization in Young Postadolescent Population With Obesity","authors":"Ariana S. Ginsberg MD ,&nbsp;Artur Chernoguz MD, FACS","doi":"10.1016/j.clinthera.2024.08.012","DOIUrl":"10.1016/j.clinthera.2024.08.012","url":null,"abstract":"<div><h3>Purpose</h3><div>Bariatric surgery is an established treatment option for adolescent patients struggling with obesity, yet it remains underutilized. We aimed to gain insight into patients’ views of bariatric surgery and identify the strategies for improved utilization of the procedure in early postadolescence.</div></div><div><h3>Methods</h3><div>The electronic medical records of patients diagnosed with obesity at a tertiary medical center, ages 18–22 years old, were examined. Patients participated in a follow-up survey related to obesity treatment.</div></div><div><h3>Findings</h3><div>While 20% of patients had BMIs ≥ 35 kg/m² in adolescence, more than half (54%) of patients with obesity reached BMIs ≥ 35 kg/m² after 18 y/o, thus potentially qualifying for bariatric surgery. A minority of patients (6/280, 2%) underwent bariatric surgery and experienced substantial weight loss in early postadolescence. Most remaining surgery-eligible patients (141/152, 93%) noted a BMI increase (0.05–28.6 kg/m²) during the immediate young adult study period without surgical intervention. While 66.7% of patients who recall receiving surgery-specific counseling would consider surgery as a part of their treatment, only 4.6% of patients who did not recall counseling would consider undergoing bariatric surgery.</div></div><div><h3>Implications</h3><div>In the absence of provider referral during adolescence, bariatric surgery remains underutilized in early postadolescence. Provider counseling is an essential component of patients’ willingness to consider bariatric surgery.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages e29-e33"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Application of 0.05% Cyclosporine for the Treatment of Neurotrophic Keratopathy Secondary to Herpes Simplex Keratitis","authors":"Ruochen Liao ,&nbsp;Juan Li ,&nbsp;Yuqi Su ,&nbsp;Yu Tao ,&nbsp;Ruifeng Su ,&nbsp;Xiaobo Tan","doi":"10.1016/j.clinthera.2024.09.001","DOIUrl":"10.1016/j.clinthera.2024.09.001","url":null,"abstract":"<div><h3>Purpose</h3><div>The purpose of this study was to assess the effectiveness and tolerability of 0.05% cyclosporine A (CsA) eye drops for neurotrophic keratopathy (NK) secondary to herpes simplex keratitis (HSK).</div></div><div><h3>Methods</h3><div>Fifteen patients (15 eyes) with prior HSK and secondary NK, classified as stage 2 or 3 on the basis of the Mackie classification, were enrolled. All patients received a combined treatment regimen of 0.05% CsA eye drops (1 drop 4 times daily), a silicone hydrogel bandage contact lens, and 0.15% ganciclovir ophthalmic gel (1 drop 3 times daily). For patients achieving corneal healing, CsA was continued at a reduced dosage of twice daily for an additional 2 months and other treatments were discontinued. Follow-ups were scheduled at weeks 1, 2, 3, and 4 and at months 2 and 3 after treatment initiation, followed by a 3-month follow-up period. Key outcomes, including best-corrected visual acuity, Schirmer I test, and corneal sensitivity, were assessed at each visit before and after treatment.</div></div><div><h3>Findings</h3><div>Significant reductions were observed in the area of corneal defects, expressed as proportion of total corneal area, throughout follow-up period. Complete corneal healing was achieved by 13.3% of patients by week 2, 60.0% by week 3, 86.7% by week 4, and 100.0% by week 8, with the mean (SD) time to healing being 3.8 (1.8) weeks (range, 2–8 weeks). Additionally, significant improvements were noted in diseased eyes for best-corrected visual acuity, tear secretion (Schirmer I test values), and corneal sensitivity after treatment.</div></div><div><h3>Implications</h3><div>CsA eye drops, with bandage lenses and ganciclovir, effectively resolve NK from HSK, without adverse effects. This combination therapy shows promise for future clinical use and research.</div></div><div><h3>Clinical trial registration</h3><div>Our study is a retrospective observational study because it involves the analysis of previously collected data, so the study was not registered prior to its commencement. However, if it is necessary for publication, we are willing to proceed with retrospective registration.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 900-904"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Burden and Healthcare Resource Utilization Associated With Managing Transfusion-dependent β-Thalassemia in England.","authors":"Chuka Udeze, Nelly F Ly, Fiona C Ingleby, Sophia D Fleming, Sarah C Conner, Jo Howard, Nanxin Li, Farrukh Shah","doi":"10.1016/j.clinthera.2024.09.024","DOIUrl":"https://doi.org/10.1016/j.clinthera.2024.09.024","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with transfusion-dependent β-thalassemia (TDT) have reduced levels of β-globin, leading to ineffective erythropoiesis and iron overload. Patients with TDT depend on regular red blood cell transfusions (RBCTs) and iron chelation therapy for survival and management of disease- and treatment-related clinical complications. This study describes the clinical and economic burden in patients with TDT in England.</p><p><strong>Methods: </strong>This longitudinal, retrospective study linked the Clinical Practice Research Datalink (CPRD) database with secondary care data from the Hospital Episode Statistics database to identify patients with a diagnosis of β-thalassemia between July 1, 2008, and June 30, 2018. Included patients had a diagnosis of β-thalassemia prior to the index date, ≥8 RBCTs per year for ≥2 consecutive years, and ≥1 year of follow-up data available from the index date. Each eligible patient was exact matched with up to 5 controls in the CPRD. Proportions of deaths and rates of mortality, acute and chronic complications, and healthcare resource utilization (HCRU) were calculated during the follow-up period.</p><p><strong>Findings: </strong>Of 11,359 identified patients with β-thalassemia, 237 patients with TDT met the eligibility criteria and were matched with 1184 controls. The mean age at the index date was approximately 25 years in the patient and control groups. The proportion of deaths (7.17% vs 1.18%; P < 0.05) and mortality rate (1.19 deaths per 100 person-years vs 0.20 deaths per 100 person-years) were higher among patients with TDT compared to controls. Endocrine complications and bone disorders were the most prevalent complications among patients with TDT (58.23%) and included osteoporosis (29.11%), diabetes mellitus (28.27%), and hypopituitarism (28.27%). Patients with TDT had a mean of 13.62 RBCTs per patient per year (PPPY). HCRU was substantially higher among patients with TDT, wherein patients with TDT had higher rates of prescriptions recorded in primary care (24.09 vs 8.61 PPPY), outpatient visits (16.69 vs 1.31 PPPY), and inpatient hospitalizations (17.41 vs 0.24 PPPY) than controls. Inpatient hospitalizations were primarily <1 day, with 16.62 events PPPY lasting <1 day and 0.79 events PPPY lasting ≥1 day. Patients with TDT aged ≥18 years had increased rates of mortality, clinical complications, and HCRU than those aged <18 years.</p><p><strong>Implications: </strong>Patients with TDT in England have higher mortality than matched controls, substantial disease-related clinical complications, and substantial HCRU. High mortality and clinical complications highlight the need for additional innovative therapies for TDT.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newer Glucose-Lowering Drugs and Risk of Gout: A Network Meta-Analysis of Randomized Outcomes Trials","authors":"Aihua Wang ,&nbsp;Weilong Shi ,&nbsp;Ning Zhang ,&nbsp;Huilin Tang ,&nbsp;Xin Feng","doi":"10.1016/j.clinthera.2024.04.013","DOIUrl":"10.1016/j.clinthera.2024.04.013","url":null,"abstract":"<div><h3>Purpose</h3><div>Previous studies have shown that newer glucose-lowering drugs (GLDs), such as sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 (DPP-4) inhibitors, may decrease the risk of gout, however, the evidence remains inconclusive. This study aimed to assess the association between newer GLDs and risk of gout.</div></div><div><h3>Methods</h3><div>We systematically searched electronic databases up to August 2023 to include randomized, placebo-controlled outcome trials that reported gout-related outcomes in participants with and without type 2 diabetes. A random effects network meta-analysis was conducted to estimate the risk ratio (RR) with 95% confidence interval (CI) to compare the effects of SGLT2 inhibitors, GLP-1RAs, and DPP-4 inhibitors on risk of gout.</div></div><div><h3>Findings</h3><div>This study included 22 trials involving 173,498 patients. Compared with placebo, SGLT2 inhibitors were significantly associated with decreased risk of gout (RR, 0.51; 95% CI, 0.29–0.91) while both GLP-1RAs and DPP-4 inhibitors have no significant effects on gout risk. There were no significant differences between SGLT2 inhibitors and GLP-1RAs (RR, 0.75; 95%CI, 0.31–1.82) and between GLP-1RAs and DPP-4 inhibitors (RR, 0.39; 95%CI, 0.14–1.10).</div></div><div><h3>Implications</h3><div>SGLT2 inhibitors may potentially prevent the risk of gout, however, both GLP-1RAs and DPP-4 inhibitors have neutral effects.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Pages 851-854"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141129979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver Linings: Side Effects and Secondary Findings of Newly Emerging Therapies","authors":"Jill L. Maron MD, MPH","doi":"10.1016/j.clinthera.2024.10.002","DOIUrl":"10.1016/j.clinthera.2024.10.002","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"46 11","pages":"Page 825"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}