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Needle-Free Jet Injector-Assisted Triamcinolone Treatment of Keloids and Hypertrophic Scars is Effective and Well Tolerated in Children 无针喷射器辅助曲安奈德治疗儿童瘢痕疙瘩和肥厚性疤痕有效且耐受性良好
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-13 DOI: 10.1007/s40261-023-01332-0
Vazula Zulfra Bekkers, Claire Van Eijsden, Qi Yin, Albert Wolkerstorfer, Errol Prospero Prens, Martijn Bastiaan Adriaan van Doorn

Background

Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia.

Objective

We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars.

Methods

A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction.

Results

Six female patients and five male patients aged 5–17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were ‘satisfied’ and five patients were ‘very satisfied’ with the treatment.

Conclusions

Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.

背景:瘢痕疙瘩和增生性疤痕可引起剧烈疼痛、瘙痒和心理困扰。传统的局部注射皮质类固醇治疗仍然具有挑战性,特别是对有针恐惧症的儿童。目的评价无针电子气动喷雾器在瘢痕疙瘩和增生性瘢痕患儿局部注射曲安奈德的疗效、耐受性和患者满意度。方法对瘢痕疙瘩和增生性瘢痕患儿应用电子气动喷雾器局部注射曲安奈德治疗的回顾性研究。使用患者和观察者疤痕评估量表和总体美学改善评分对随访和基线进行有效性评估。使用视觉模拟量表评估耐受性,报告不良反应和注射相关疼痛。采用满意度问卷评估与治疗相关的患者满意度。结果女性6例,男性5例,年龄5 ~ 17岁,共118例瘢痕疙瘩或增生性瘢痕。与基线相比,电子气动喷射器治疗导致患者和观察者疤痕评估量表的观察者和患者总得分显著降低,中位数分别降低28.9%和23.8% (p = 0.005;P = 0.009)。电子气动喷射器治疗的视觉模拟疼痛评分中位数明显低于针注射,分别为3.0分和7.0分(p = 0.027)。没有严重的不良反应报告。总体而言,6名患者对治疗“满意”,5名患者对治疗“非常满意”。结论电子气动喷雾器辅助局部注射曲安奈德是治疗儿童瘢痕肿和增生性瘢痕的有效方法。应考虑将其作为一种非创伤性分娩方法,特别是在以前针头注射时有针头恐惧症或剧烈疼痛的儿童中。
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引用次数: 0
Glucagon-Like Peptide-1 Receptor Agonist and Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials. 胰高血糖素样肽-1受体激动剂与2型糖尿病患者糖尿病视网膜病变的风险:随机安慰剂对照试验的系统评价和荟萃分析。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-08 DOI: 10.1007/s40261-023-01319-x
Xiaojuan Jiao, Ping Peng, Qin Zhang, Yunfeng Shen

Background: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) exhibit glucose-lowering, weight-reducing, and blood pressure-lowering effects. Nevertheless, a debate exists concerning the association between GLP-1RA treatment and the risk of diabetic retinopathy (DR) in patients diagnosed with type 2 diabetes mellitus (T2DM).

Objective: To ascertain the risk of DR in patients with T2DM undergoing GLP-1RA treatment, we conducted a meta-analysis utilizing data derived from randomized placebo-controlled studies (RCTs).

Methods: A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, and EMBASE. We focused on RCTs involving the use of GLP-1RAs in patients with T2DM. Utilizing R software, we compared the risk of DR among T2DM patients undergoing GLP-1RA treatment. The Cochrane risk of bias method was employed to assess the research quality.

Results: The meta-analysis incorporated data from 20 RCTs, encompassing a total of 24,832 T2DM patients. Across all included trials, randomization to GLP-1 RA treatment did not demonstrate an increased risk of DR (odds ratio = 1.17; 95% CI 0.98-1.39). Furthermore, no significant heterogeneity or publication bias was detected in the analysis.

Conclusion: The results of this systematic review and meta-analysis indicate that the administration of GLP-1 RA is not associated with an increased risk of DR. PROSPERO REGISTRATION IDENTIFIER: CRD42023413199.

背景:胰高血糖素样肽1受体激动剂(GLP-1RA)具有降血糖、减肥和降压作用。然而,关于GLP-1RA治疗与2型糖尿病(T2DM)患者糖尿病视网膜病变(DR)风险之间的关系仍存在争议,我们利用随机安慰剂对照研究(RCTs)的数据进行了荟萃分析。方法:使用PubMed、Cochrane Library、Web of Science和EMBASE进行全面的文献检索。我们重点研究了在T2DM患者中使用GLP-1RA的随机对照试验。利用R软件,我们比较了接受GLP-1RA治疗的T2DM患者发生DR的风险。采用Cochrane偏倚风险法评估研究质量。结果:荟萃分析纳入了20项随机对照试验的数据,共包括24832名T2DM患者。在所有纳入的试验中,随机分组接受GLP-1 RA治疗并未显示DR风险增加(比值比=1.17;95%CI 0.98-1.39)。此外,在分析中未检测到显著的异质性或发表偏倚。结论:这项系统综述和荟萃分析的结果表明,GLP-1 RA的给药与DR风险增加无关。PROSPERO注册标识符:CRD42023413199。
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引用次数: 0
Tauro-Urso-Deoxycholic Acid Trials in Amyotrophic Lateral Sclerosis: What is Achieved and What to Expect. 牛头-熊-脱氧胆酸治疗肌萎缩性侧索硬化症的试验:取得了什么成果?
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-16 DOI: 10.1007/s40261-023-01324-0
Maria Lo Giudice, Antoniangela Cocco, Giorgio Reggiardo, Stefania Lalli, Alberto Albanese

Phase II studies on tauro-urso-deoxycholic acid (TUDCA) raised the promise of safety and efficacy in patients with amyotrophic lateral sclerosis, a currently incurable and devastating disease. We review the available evidence on the efficacy and safety of TUDCA, administered alone or in combination, by analyzing and comparing published and ongoing studies on amyotrophic lateral sclerosis. Two independent phase II studies (using TUDCA solo or combined with sodium phenylbutyrate) showed similar efficacy in slowing disease progression measured by functional scales. One open-label follow-up TUDCA+sodium phenylbutyrate study suggested a benefit on survival. Two subsequent phase III studies with TUDCA (solo or combined with sodium phenylbutyrate) have been initiated and are currently ongoing. Their completion is expected by the end of 2023 and beginning of 2024. Evidence collected by phase II studies indicates that there are no safety concerns in patients with amyotrophic lateral sclerosis. The efficacy shown in phase II studies was considered sufficient to grant approval in some countries but not in others, owing to discrepant views on the strength of evidence. It will be necessary to wait for the results of ongoing phase III studies to attain a full appreciation of these data.

牛磺酸去氧胆酸(TUDCA)的II期研究为肌萎缩性侧索硬化症(一种目前无法治愈的毁灭性疾病)患者的安全性和有效性带来了希望。我们通过分析和比较已发表和正在进行的肌萎缩性侧索硬化症的研究,回顾了TUDCA单独或联合使用的有效性和安全性的现有证据。两项独立的II期研究(单独使用TUDCA或与苯丁酸钠联合使用)显示,通过功能量表测量,在减缓疾病进展方面具有相似的疗效。一项开放标签随访TUDCA+苯基丁酸钠研究表明其对生存有好处。随后的两项使用TUDCA(单用或联用苯丁酸钠)的III期研究已经启动,目前正在进行中。预计将于2023年底至2024年初完工。II期研究收集的证据表明,肌萎缩性侧索硬化症患者没有安全性问题。II期研究显示的疗效被认为足以在一些国家获得批准,但在其他国家则不然,因为对证据的强度有不同的看法。有必要等待正在进行的第三期研究的结果,以充分了解这些数据。
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引用次数: 0
Monotherapy Versus Combination Therapy in the Treatment of Painful Diabetic Neuropathy: A Systematic Review and Meta-analysis. 单药治疗与联合治疗疼痛性糖尿病神经病变:系统综述和荟萃分析。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-08 DOI: 10.1007/s40261-023-01318-y
Julyana Medeiros Dantas, Mariana de Jesus Oliveira, Luciana Alves Oliveira Silva, Sávio Batista, Caroline Serafim Dagostin, Daniel Campinho Schachter

Background and objective: Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy.

Methods: PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool.

Results: A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy.

Conclusion: In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.

背景与目的:疼痛性周围神经病变是糖尿病常见且具有挑战性的并发症。联合治疗被临床医生广泛使用,尽管缺乏有效性和安全性的有力证据。本研究的目的是比较一线药物联合治疗与单一治疗治疗周围型糖尿病神经病变的疗效和安全性。方法:2022年12月5日,检索PubMed、Embase、Cochrane Central和clinicaltrials.gov数据库,进行随机临床试验,比较加巴喷丁类药物和三环类抗抑郁药(TCAs)或血清素和去甲肾上腺素再摄取抑制剂(SNRIs)的联合治疗与任何这些药物的单一治疗。计算疼痛结果的合并平均差(MD)和95%置信区间(CI),在过去7天的平均疼痛评分的11点数字评分量表上进行测量。计算二元终点的风险比(RR)。使用偏差风险2工具进行风险评估。结果:共纳入5项随机研究和916名患者。随访时间为6-12周。联合治疗的平均疼痛减轻程度大于单一治疗(MD- 0.39;95%CI- 0.67至- 0.12;p=0.005)。同样,联合治疗的平均疼痛减轻≥30%也有改善(RR 1.16;95%CI 1.07-1.26;p<0.01)。相反,两组之间的平均疼痛减轻≥50%没有显著差异(RR 1.21;95%CI 0.99-1.49;p=0.06)。当比较联合治疗与加巴喷丁单药治疗时,平均疼痛也显著减轻(MD- 0.61;95%CI- 0.85至- 0.37;p<0.01)。结论:在疼痛的糖尿病周围神经病变患者中,与单药治疗相比,加巴喷丁类药物与TCAs或SNRIs的联合治疗可显著减轻疼痛,尽管这种差异可能不会转化为临床上重要的差异。
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引用次数: 0
Safety Concerns with Nusinersen, Risdiplam, and Onasemnogene Abeparvovec in Spinal Muscular Atrophy: A Real-World Pharmacovigilance Study. Nusinersen, Risdiplam和Onasemnogene abparvovec治疗脊髓性肌萎缩的安全性问题:一项真实世界药物警戒研究。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-23 DOI: 10.1007/s40261-023-01320-4
Wei Zhuang, Mei Lu, Ye Wu, Zhehui Chen, Minying Wang, Xudong Wang, Shaoxing Guan, Wanlong Lin
<p><strong>Background and objective: </strong>Spinal muscular atrophy (SMA) is a genetic disorder with limited treatment options. It is crucial to have a comprehensive understanding of drug safety in order to make informed clinical drug selections for patients with SMA. Assessing the safety profiles of therapeutic drugs for SMA has been challenging due to the limited number of patients included in clinical trials. This study aims to investigate and compare the potential safety concerns associated with three leading SMA therapeutic drugs: nusinersen, risdiplam, and onasemnogene abeparvovec.</p><p><strong>Methods: </strong>The FDA Adverse Event Reporting System database was used to analyze drug safety, and a case (SMA drug)/noncase (all other drugs in the database) approach was employed to estimate safety signals through disproportionality analysis and reporting odds ratio (ROR). Veen analysis was conducted to compare and select the idiosyncratic adverse events (AEs) associated with each drug.</p><p><strong>Results: </strong>The study included 5324 cases of nusinersen, 1184 cases of risdiplam, and 1277 cases of onasemnogene abeparvovec. Venn analysis revealed 27 common AEs among the three drugs, including cardiac, gastrointestinal, metabolism, musculoskeletal, renal, respiratory disorders, and infections. Additionally, 196 AEs exclusively found in nusinersen included post lumbar puncture syndrome [ROR (95% CI) = 6120.91 (5057.01-7408.64), n = 372], procedural pain [ROR (95% CI) = 54.86 (48.13-62.54), n = 234], idiopathic intracranial hypertension [ROR (95% CI) = 6.12 (2.29-16.33), n = 4], and hypokalemia [ROR (95% CI) = 2.02 (1.24-3.31), n = 16]. Additionally, transient deafness was identified as an unexpected and rare, yet severe, AE for nusinersen [ROR (95% CI) = 23.32 (8.71-62.44), n = 4]. Risdiplam exhibited 50 AEs exclusively, with notable idiosyncratic AEs including diarrhea [ROR (95% CI) = 4.55 (3.79-5.46), n = 121], fatigue [ROR (95% CI) = 2.03 (1.6-2.57), n = 70], photosensitivity reaction [ROR (95% CI) = 9.50 (4.25-21.13), n = 6], rash [ROR (95% CI) = 1.90 (1.36-2.67), n = 34], and [ROR (95% CI) = 4.3 (1.93-9.58), n = 6] in comparison with the other two drugs. Moreover, ileus [ROR (95% CI) = 11.11 (4.14-29.51), n = 4], gastrointestinal hemorrhage [ROR (95% CI) = 2.55 (1.15-5.69), n = 6], and hypoglycemic unconsciousness [ROR (95% CI) = 153.58 (62.98-374.54), n = 5] were rare but severe AEs associated with risdiplam. Onasemnogene abeparvovec had 143 exclusively identified AEs, with significant high signals for troponin I increase [ROR (95% CI) = 627.1 (492.2-798.99), n = 78], troponin T increase [ROR (95% CI) = 233.98 (153.29-357.15), n = 23], blood lactate dehydrogenase increase [ROR (95% CI) = 39.81 (28.88-54.87), n = 38], and transaminases increase [ROR (95% CI) = 36.88 (29.24-46.52), n = 73].</p><p><strong>Conclusions: </strong>This study highlights the importance of monitoring injection-related injuries and transient deafness events i
背景和目的:脊髓性肌萎缩症(SMA)是一种治疗选择有限的遗传性疾病。为了给SMA患者做出明智的临床药物选择,全面了解药物安全性是至关重要的。由于纳入临床试验的患者数量有限,评估SMA治疗药物的安全性一直具有挑战性。本研究旨在调查和比较三种主要SMA治疗药物:nusinersen、risdiplam和onasemnogene abparvovec的潜在安全性问题。方法:采用FDA不良事件报告系统数据库对药物安全性进行分析,采用病例(SMA药物)/非病例(数据库中所有其他药物)方法,通过歧化分析和报告优势比(ROR)估计安全性信号。进行了even分析来比较和选择与每种药物相关的特殊不良事件(ae)。结果:纳入nusinsen 5324例,risdiplam 1184例,onasemnogene abparvovec 1277例。Venn分析揭示了三种药物中27种常见ae,包括心脏、胃肠、代谢、肌肉骨骼、肾脏、呼吸系统疾病和感染。此外,在nusinersen中发现的196例ae包括腰椎穿刺后综合征[ROR (95% CI) = 6120.91 (5057.01-7408.64), n = 372],手术疼痛[ROR (95% CI) = 54.86 (48.13-62.54), n = 234],特发性颅内高压[ROR (95% CI) = 6.12 (2.29-16.33), n = 4]和低钾血症[ROR (95% CI) = 2.02 (1.24-3.31), n = 16]。此外,短暂性耳聋被认为是一种意想不到的、罕见但严重的耳聋[ROR (95% CI) = 23.32 (8.71-62.44), n = 4]。与其他两种药物相比,Risdiplam仅显示50个ae,显著的特异性ae包括腹泻[ROR (95% CI) = 4.55 (3.79-5.46), n = 121]、疲劳[ROR (95% CI) = 2.03 (1.6-2.57), n = 70]、光敏反应[ROR (95% CI) = 9.50 (4.25-21.13), n = 6]、皮疹[ROR (95% CI) = 1.90 (1.36-2.67), n = 34]和[ROR (95% CI) = 4.3 (1.93-9.58), n = 6]。此外,肠梗阻[ROR (95% CI) = 11.11 (4.14-29.51), n = 4]、胃肠道出血[ROR (95% CI) = 2.55 (1.15-5.69), n = 6]和低血糖性无意识[ROR (95% CI) = 153.58 (62.98-374.54), n = 5]是与瑞司哌仑相关的罕见但严重的ae。Onasemnogene abeparvovec共鉴定出143例ae,其中肌钙蛋白I升高[ROR (95% CI) = 627.1 (492.2 ~ 798.99), n = 78]、肌钙蛋白T升高[ROR (95% CI) = 233.98 (153.29 ~ 357.15), n = 23]、血乳酸脱氢酶升高[ROR (95% CI) = 39.81 (28.88 ~ 54.87), n = 38]、转氨酶升高[ROR (95% CI) = 36.88 (29.24 ~ 46.52), n = 73]具有显著高信号。结论:本研究强调了监测nusinsen治疗患者注射相关损伤和短暂性耳聋事件的重要性。对于onasemnogene abparvovec,仔细监测肾功能损害、肝损伤和心肌损伤是必要的。利斯地普兰需要注意罕见但严重的胃肠道损伤事件和低血糖的潜在风险。重要的是,利地普兰表现出较低的肝脏和肾脏毒性,使其成为肝脏或肾功能不全患者或与其他具有高肝脏或肾脏毒性的药物联合使用的潜在考虑因素。这些发现可为药物选择和进一步的前瞻性研究提供参考。
{"title":"Safety Concerns with Nusinersen, Risdiplam, and Onasemnogene Abeparvovec in Spinal Muscular Atrophy: A Real-World Pharmacovigilance Study.","authors":"Wei Zhuang, Mei Lu, Ye Wu, Zhehui Chen, Minying Wang, Xudong Wang, Shaoxing Guan, Wanlong Lin","doi":"10.1007/s40261-023-01320-4","DOIUrl":"10.1007/s40261-023-01320-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Spinal muscular atrophy (SMA) is a genetic disorder with limited treatment options. It is crucial to have a comprehensive understanding of drug safety in order to make informed clinical drug selections for patients with SMA. Assessing the safety profiles of therapeutic drugs for SMA has been challenging due to the limited number of patients included in clinical trials. This study aims to investigate and compare the potential safety concerns associated with three leading SMA therapeutic drugs: nusinersen, risdiplam, and onasemnogene abeparvovec.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The FDA Adverse Event Reporting System database was used to analyze drug safety, and a case (SMA drug)/noncase (all other drugs in the database) approach was employed to estimate safety signals through disproportionality analysis and reporting odds ratio (ROR). Veen analysis was conducted to compare and select the idiosyncratic adverse events (AEs) associated with each drug.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study included 5324 cases of nusinersen, 1184 cases of risdiplam, and 1277 cases of onasemnogene abeparvovec. Venn analysis revealed 27 common AEs among the three drugs, including cardiac, gastrointestinal, metabolism, musculoskeletal, renal, respiratory disorders, and infections. Additionally, 196 AEs exclusively found in nusinersen included post lumbar puncture syndrome [ROR (95% CI) = 6120.91 (5057.01-7408.64), n = 372], procedural pain [ROR (95% CI) = 54.86 (48.13-62.54), n = 234], idiopathic intracranial hypertension [ROR (95% CI) = 6.12 (2.29-16.33), n = 4], and hypokalemia [ROR (95% CI) = 2.02 (1.24-3.31), n = 16]. Additionally, transient deafness was identified as an unexpected and rare, yet severe, AE for nusinersen [ROR (95% CI) = 23.32 (8.71-62.44), n = 4]. Risdiplam exhibited 50 AEs exclusively, with notable idiosyncratic AEs including diarrhea [ROR (95% CI) = 4.55 (3.79-5.46), n = 121], fatigue [ROR (95% CI) = 2.03 (1.6-2.57), n = 70], photosensitivity reaction [ROR (95% CI) = 9.50 (4.25-21.13), n = 6], rash [ROR (95% CI) = 1.90 (1.36-2.67), n = 34], and [ROR (95% CI) = 4.3 (1.93-9.58), n = 6] in comparison with the other two drugs. Moreover, ileus [ROR (95% CI) = 11.11 (4.14-29.51), n = 4], gastrointestinal hemorrhage [ROR (95% CI) = 2.55 (1.15-5.69), n = 6], and hypoglycemic unconsciousness [ROR (95% CI) = 153.58 (62.98-374.54), n = 5] were rare but severe AEs associated with risdiplam. Onasemnogene abeparvovec had 143 exclusively identified AEs, with significant high signals for troponin I increase [ROR (95% CI) = 627.1 (492.2-798.99), n = 78], troponin T increase [ROR (95% CI) = 233.98 (153.29-357.15), n = 23], blood lactate dehydrogenase increase [ROR (95% CI) = 39.81 (28.88-54.87), n = 38], and transaminases increase [ROR (95% CI) = 36.88 (29.24-46.52), n = 73].&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study highlights the importance of monitoring injection-related injuries and transient deafness events i","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"949-962"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294847","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}
引用次数: 0
Is Alpelisib Plus Fulvestrant Cost-Effective for Treating PIK3CA-Mutation, HR+/HER2- Advanced Breast Cancer in the USA? 在美国,Alpelisib + Fulvestrant治疗pik3ca突变、HR+/HER2-晚期乳腺癌是否具有成本效益?
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-17 DOI: 10.1007/s40261-023-01325-z
Wenhua Wu, Huiting Lin, Jiaqin Cai, Hong Sun, Jia Liu, Congting Hu, Xiaoxia Wei

Background and objective: There is a considerable survival benefit of alpelisib in patients with PIK3CA-mutated, hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC), yet the financial burden may limit its use. Therefore, this study evaluated the cost-effectiveness of alpelisib plus fulvestrant in patients with PIK3CA-mutated, HR+/HER2- ABC in the USA.

Methods: A Markov model was constructed to simulate the progression of PIK3CA-mutated, HR+/HER2- ABC. Efficacy and safety data were derived from the SOLAR-1 trial. A parametric survival model was used to explore the long-term effect. From a US payer perspective, only direct medical costs were considered. The cost data were estimated based on local pricing and relevant literature. The health outcomes were expressed in quality-adjusted life years (QALYs). Model stability was assessed using one-way sensitivity analysis and probability sensitivity analysis. Subgroup analyses were performed to explore cost-effectiveness outcomes for patients with different clinical characteristics.

Results: The QALY increased by 0.28 with alpelisib plus fulvestrant with an additional cost of $94,345.87 compared with placebo plus fulvestrant, leading to an incremental cost-effectiveness ratio (ICER) of $340,153.30/QALY gained. Sensitivity analyses suggested that the model is most sensitive to the price of alpelisib. At a willingness-to-pay (WTP) threshold of $150,000/QALY, alpelisib plus fulvestrant was cost effective when the cost of alpelisib was less than $71 per 300 mg (36.5 % of the original price), whereas this cost would be less than $168 per 300 mg (86.5 % of the original price) at a WTP threshold of $300,000/QALY. In addition, alpelisib + fulvestrant was not cost effective in all subgroups compared with placebo + fulvestrant at the WTP threshold of $150,000/QALY. In contrast, at the WTP threshold of $300,000/QALY, alpelisib + fulvestrant was cost effective in nearly all subgroups except for endocrine-sensitive patients.

Conclusion: At current drug prices, alpelisib plus fulvestrant is not cost effective for patients with PIK3CA-mutated, HR+/HER2- ABC from a US payer perspective. Given the considerable progression-free survival (PFS) and overall survival (OS) benefits observed with alpelisib in this setting, further discussion and negotiation of the price of alpelisib are warranted to provide more favorable economic outcomes and thereby increase the value of the alpelisib plus fulvestrant regimen in patients.

背景与目的:在pik3ca突变、激素受体阳性和人表皮生长因子受体2阴性的晚期乳腺癌(HR+/HER2- ABC)患者中,alpelisib有相当大的生存获益,但经济负担可能限制了其使用。因此,本研究在美国评估了alpelisib加氟维司汀治疗pik3ca突变的HR+/HER2- ABC患者的成本-效果。方法:建立Markov模型,模拟pik3ca突变的HR+/HER2- ABC的进展。疗效和安全性数据来自SOLAR-1试验。采用参数生存模型探讨长期效果。从美国付款人的角度来看,只考虑直接医疗费用。成本数据是根据当地定价和相关文献估算的。健康结果以质量调整生命年(QALYs)表示。采用单向敏感性分析和概率敏感性分析对模型稳定性进行评价。进行亚组分析以探讨不同临床特征患者的成本-效果结果。结果:与安慰剂加氟维司汀相比,alpelisib加氟维司汀的QALY增加了0.28,额外的成本为94,345.87美元,导致增量成本-效果比(ICER)为340,153.30美元/QALY获得。敏感性分析表明,该模型对紫苏的价格最为敏感。在支付意愿(WTP)阈值为150,000美元/QALY时,当alpelisib的成本低于每300毫克71美元(原价的36.5%)时,alpelisib加氟维司汀具有成本效益,而在WTP阈值为300,000美元/QALY时,该成本将低于每300毫克168美元(原价的86.5%)。此外,在WTP阈值为15万美元/QALY时,与安慰剂+氟维司汀相比,alpelisib +氟维司汀并非在所有亚组中都具有成本效益。相比之下,在300,000美元/QALY的WTP阈值下,alpelisib + fulvestrant在除内分泌敏感患者外的几乎所有亚组中都具有成本效益。结论:从美国付款人的角度来看,以目前的药物价格,alpelisib加氟维司汀对pik3ca突变的HR+/HER2- ABC患者没有成本效益。鉴于alpelisib在这种情况下观察到的可观的无进展生存期(PFS)和总生存期(OS)益处,有必要对alpelisib的价格进行进一步讨论和谈判,以提供更有利的经济结果,从而提高alpelisib +氟维司汀方案对患者的价值。
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引用次数: 0
Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study. 日本肥胖2型糖尿病患者从西他列汀转为依普利洛嗪的疗效和安全性:一项单臂多中心介入研究。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1007/s40261-023-01317-z
Kentaro Watanabe, Susumu Yamaguchi, Yoshinori Kosakai, Tetsuya Ioji, Hisamitsu Ishihara

Background: Dipeptidyl peptidase-4 inhibitors have limited efficacy in improving glycemic control for obese Japanese patients with type 2 diabetes mellitus. Sodium-glucose co-transporter 2 inhibitors are recommended for use in patients with type 2 diabetes with obesity. Nevertheless, there has been no previously published study on the effect of switching from dipeptidyl peptidase-4 inhibitors to sodium-glucose co-transporter 2 inhibitors on the systemic and organic effects in obese Japanese patients with type 2 diabetes.

Objectives: We evaluated the efficacy and safety of switching from sitagliptin to ipragliflozin for 24 weeks in obese Japanese patients with inadequately controlled type 2 diabetes.

Methods: Fifty-one obese patients with type 2 diabetes (body mass index > 25 kg/m2) treated with sitagliptin (50 mg) and metformin but with inadequate glycemic control (glycosylated hemoglobin [HbA1c] > 7.5% and < 9.0%) were enrolled. After a 4-week observation period, sitagliptin was switched to ipragliflozin (50 mg) for 24 weeks. The primary outcome was the change in HbA1c from baseline to the end of treatment. The secondary outcomes were changes in clinical characteristics and other biochemical variables.

Results: Fifty-one patients with an average HbA1c of 8.37 ± 0.48% and body mass index of 28.8 ± 3.8 kg/m2 were enrolled. Fifty patients completed the study, one patient stopped ipragliflozin at 4 weeks because of the development of hyperosmolar hyperglycemic syndrome. No significant change in HbA1c from baseline to the end of treatment was observed (- 0.02 ± 0.75%). However, fasting plasma glucose was reduced (- 16.2 ± 28.4 mg/dL, p < 0.001), and biochemical variables associated with insulin resistance, oxidative stress, and hepatic and renal functions showed significant improvements. No severe adverse effects were observed, except in the one aforementioned case.

Conclusions: Switching from sitagliptin to ipragliflozin did not alter HbA1c in obese patients with type 2 diabetes, while improving parameters related to organ homeostasis. These data provide novel information useful for selecting oral anti-diabetic agents for patients with type 2 diabetes with obesity, a risk factor for developing various complications of diabetes.

Clinical trial registration: Japan Registry of Clinical Trials identifier: jRCT#031190022.

背景:二肽基肽酶-4抑制剂在改善肥胖日本2型糖尿病患者血糖控制方面的疗效有限。建议将钠-葡萄糖共转运蛋白2抑制剂用于2型糖尿病合并肥胖的患者。尽管如此,之前还没有发表过关于从二肽基肽酶-4抑制剂转换为钠-葡萄糖共转运蛋白2抑制剂对肥胖的日本2型糖尿病患者的全身和器质性影响的研究。目的:我们评估了在肥胖的日本2型糖尿病患者中,从西他列汀转为异丙列嗪治疗24周的疗效和安全性。方法:51名肥胖2型糖尿病患者(体重指数>25 kg/m2)接受西格列汀(50 mg)和二甲双胍治疗,但血糖控制不足(糖化血红蛋白[HbA1c]结果:51例患者的平均HbA1c为8.37±0.48%,体重指数为28.8±3.8kg/m2。50名患者完成了这项研究,其中一名患者在4周时因高渗性高血糖综合征而停止服用异丙列嗪。从基线到治疗结束,HbA1c没有观察到显著变化(-0.02±0.75%)。然而,空腹血糖降低(-16.2±28.4 mg/dL,p<0.001),与胰岛素抵抗、氧化应激以及肝肾功能相关的生化变量显示出显著改善。除上述一例外,未观察到严重不良反应。结论:在2型糖尿病肥胖患者中,从西他列汀转为异丙列嗪不会改变HbA1c,同时改善了与器官稳态相关的参数。这些数据提供了新的信息,有助于为患有肥胖的2型糖尿病患者选择口服抗糖尿病药物,肥胖是糖尿病各种并发症的风险因素。临床试验注册:日本临床试验注册处标识符:jRCT#03119022。
{"title":"Efficacy and Safety of Switching from Sitagliptin to Ipragliflozin in Obese Japanese Patients with Type 2 Diabetes Mellitus: A Single-Arm Multicenter Interventional Study.","authors":"Kentaro Watanabe, Susumu Yamaguchi, Yoshinori Kosakai, Tetsuya Ioji, Hisamitsu Ishihara","doi":"10.1007/s40261-023-01317-z","DOIUrl":"10.1007/s40261-023-01317-z","url":null,"abstract":"<p><strong>Background: </strong>Dipeptidyl peptidase-4 inhibitors have limited efficacy in improving glycemic control for obese Japanese patients with type 2 diabetes mellitus. Sodium-glucose co-transporter 2 inhibitors are recommended for use in patients with type 2 diabetes with obesity. Nevertheless, there has been no previously published study on the effect of switching from dipeptidyl peptidase-4 inhibitors to sodium-glucose co-transporter 2 inhibitors on the systemic and organic effects in obese Japanese patients with type 2 diabetes.</p><p><strong>Objectives: </strong>We evaluated the efficacy and safety of switching from sitagliptin to ipragliflozin for 24 weeks in obese Japanese patients with inadequately controlled type 2 diabetes.</p><p><strong>Methods: </strong>Fifty-one obese patients with type 2 diabetes (body mass index > 25 kg/m<sup>2</sup>) treated with sitagliptin (50 mg) and metformin but with inadequate glycemic control (glycosylated hemoglobin [HbA1c] > 7.5% and < 9.0%) were enrolled. After a 4-week observation period, sitagliptin was switched to ipragliflozin (50 mg) for 24 weeks. The primary outcome was the change in HbA1c from baseline to the end of treatment. The secondary outcomes were changes in clinical characteristics and other biochemical variables.</p><p><strong>Results: </strong>Fifty-one patients with an average HbA1c of 8.37 ± 0.48% and body mass index of 28.8 ± 3.8 kg/m<sup>2</sup> were enrolled. Fifty patients completed the study, one patient stopped ipragliflozin at 4 weeks because of the development of hyperosmolar hyperglycemic syndrome. No significant change in HbA1c from baseline to the end of treatment was observed (- 0.02 ± 0.75%). However, fasting plasma glucose was reduced (- 16.2 ± 28.4 mg/dL, p < 0.001), and biochemical variables associated with insulin resistance, oxidative stress, and hepatic and renal functions showed significant improvements. No severe adverse effects were observed, except in the one aforementioned case.</p><p><strong>Conclusions: </strong>Switching from sitagliptin to ipragliflozin did not alter HbA1c in obese patients with type 2 diabetes, while improving parameters related to organ homeostasis. These data provide novel information useful for selecting oral anti-diabetic agents for patients with type 2 diabetes with obesity, a risk factor for developing various complications of diabetes.</p><p><strong>Clinical trial registration: </strong>Japan Registry of Clinical Trials identifier: jRCT#031190022.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"927-937"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478814","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}
引用次数: 0
Correction: Pharmacokinetics and Safety of Erenumab after a Single Subcutaneous Injection Dose in Healthy Chinese Subjects. 修正:在中国健康受试者中单次皮下注射伊瑞那单抗后的药代动力学和安全性。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 DOI: 10.1007/s40261-023-01321-3
Qi Shen, Ying Jin, Xiangjie Di, Chao Hu, Runhan Liu, Ying Wang, Xiaohui Qi, Yongsheng Wang, Zhenlei Wang
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引用次数: 0
Clinical and Laboratory Factors Related to Seizure and Serotonin Toxicity in Tramadol Intoxication: An Egyptian Study. 曲马多中毒中癫痫发作和血清素毒性相关的临床和实验室因素:一项埃及研究。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-12-01 Epub Date: 2023-11-25 DOI: 10.1007/s40261-023-01326-y
Ahmed Amin Ali, Mahmoud Mohamed Abdeshafy, Khaled Abdelkawy, Ramy M Elsabaa, Fawzy Elbarbry

Background and objectives: Tramadol is a centrally acting analgesic with a lower risk of addiction compared to opioids. Tramadol overdose is becoming a health crisis in Egypt and is associated with serious and severe adverse effects. This study aims to identify clinical and laboratory findings associated with tramadol-induced seizure and serotonin toxicity in adult Egyptian patients with tramadol overdose.

Methods: This prospective study included adult patients admitted for tramadol overdose with or without symptoms of seizure or serotonin toxicity. Basic demographic information, clinical symptoms, laboratory measurements, and plasma tramadol concentrations were collected.

Results: A total of 71 patients (79% males) were included in the study. Seizure occurred in 38% of the subjects and was prevalent in male patients with metabolic acidosis or high tramadol concentrations. Serotonin toxicity occurred in 41% of the subjects and was prevalent in patients with hyperthermia, high pulse rate, and high tramadol levels.

Conclusion: Seizure and serotonin toxicity are severe adverse effects of tramadol overdose that occur in high frequency among young Egyptians. High tramadol concentrations in plasma seem to play a key role in prevalence of seizure and serotonin syndrome in tramadol-intoxicated adult Egyptians.

背景和目的:曲马多是一种中枢作用镇痛药,与阿片类药物相比,成瘾风险较低。曲马多过量正在成为埃及的一种健康危机,并与严重的不良反应有关。本研究旨在确定与曲马多过量埃及成年患者曲马多诱发癫痫和血清素毒性相关的临床和实验室结果。方法:这项前瞻性研究纳入了曲马多过量住院的成年患者,伴有或不伴有癫痫发作或血清素毒性症状。收集基本人口统计信息、临床症状、实验室测量和血浆曲马多浓度。结果:共纳入71例患者,其中79%为男性。38%的受试者发生癫痫发作,在代谢性酸中毒或曲马多浓度高的男性患者中普遍存在。41%的受试者出现血清素毒性,在高热、高脉搏率和高曲马多水平的患者中普遍存在。结论:癫痫发作和5 -羟色胺毒性是曲马多过量在埃及年轻人中高发的严重不良反应。血浆中高曲马多浓度似乎在曲马多中毒的埃及成人癫痫发作和血清素综合征的患病率中起关键作用。
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引用次数: 0
Acknowledgement to Referees. 给推荐人的确认函。
IF 3.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2023-11-28 DOI: 10.1007/s40261-023-01328-w
{"title":"Acknowledgement to Referees.","authors":"","doi":"10.1007/s40261-023-01328-w","DOIUrl":"https://doi.org/10.1007/s40261-023-01328-w","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444168","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}
引用次数: 0
期刊
Clinical Drug Investigation
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