Advances in Therapy最新文献

Sinonasal tumors with orbital involvement present significant management challenges due to the complex anatomy of the orbital and sinonasal complex and the potential for severe tumor- and treatment-related morbidities. This comprehensive review examines evidence-based decision-making guidelines in the context of treating sinonasal malignancies involving the orbit. We evaluate pre-treatment assessment strategies, discuss the indications for orbital preservation versus its exenteration, explore the role of neo-adjuvant therapies, and analyze reconstruction techniques with ensuing rehabilitation approaches and quality of life. Our review underscores the need for a patient-centered multidisciplinary approach that optimizes treatment outcomes and quality of life for patients suffering from such advanced sinonasal malignancies with orbital involvement.

Introduction

Patient adherence to regular controller medication is critical for improving clinical outcomes in asthma, which is consistently associated with underlying pathophysiological inflammation. This survey aimed to identify types of treatment nonadherence and associated factors, including patient characteristics that predict poor adherence, in patients with asthma.

Methods

This cross-sectional online survey involved patients with asthma and physicians managing such patients from Southeast Asia (Indonesia, Malaysia, Philippines, Thailand and Vietnam) and the Middle East (Saudi Arabia and United Arab Emirates) included in the Asthma Patients’ and Physicians’ Perspectives on the Burden and Management of Asthma (APPaRENT) 3 study. Patients and physicians shared their attitudes and beliefs regarding treatment and adherence in asthma management.

Results

Most patients (82%, 1108/1354) reported having ever received treatment with daily controller inhalers, whereas 38% used inhaled relievers at least once daily for symptomatic relief. Among those prescribed maintenance and reliever therapy, 93% were prescribed a separate inhaled reliever, with significant variation by country (P < 0.01). Erratic nonadherence (primary definition) was exhibited by 55% (462/845) of patients including those who reported at least sometimes forgetting inhaler use, with its prevalence increasing with worsening asthma severity. Nonerratic nonadherence was exhibited by 49% (415/847) of patients including those who reported using controller inhalers less than once daily. Physicians reported that 73% of patients adhered to the prescribed regular medication. Regression analysis examining both erratic (primary definition) and nonerratic nonadherence revealed that current inhaled reliever used was the only significant predictor of poor adherence (P = 0.04). Sensitivity analyses revealed that the predictors of poor adherence to controller inhaler varied depending on the definition of nonadherence employed in the study.

Conclusion

This study revealed high rates of erratic and nonerratic nonadherence to regular controller inhalers in patients with asthma as well as discordance between adherence rates reported by patients and physicians.

In the clinical care of people with disproportionate short stature, healthcare practitioners need to accurately collect anthropometric measurements over time, including height, weight, head circumference, and lengths of affected limb and body segments. Accurate anthropometric measurements are important for diagnostic evaluation, tracking growth, measuring response to pharmacologic therapies or surgeries, and monitoring for potential complications. However, for this clinical population, anthropometric measurements may need to be adjusted or modified to accommodate characteristics such as body disproportions, joint contractures, long bone deformities, spinal deformities, or muscle hypotonia. This article provides guidance for key anthropometric measurements in children and adults with disproportionate short stature, with a focus on people with achondroplasia. The measurements described in this article and illustrated in the infographics can be performed without expensive specialized equipment and are suitable for a variety of clinical settings.

Sandoz-adalimumab (SDZ-ADL; Hyrimoz^®, GP2017) is an adalimumab (ADL) biosimilar approved for the treatment of immune-mediated inflammatory diseases. Here, we review the available literature on SDZ-ADL from controlled and real-world evidence studies. A literature search was carried out to identify articles published up to July 2023 reporting data on efficacy, safety, immunogenicity, and treatment retention rates for SDZ-ADL. In randomized clinical trials, the efficacy, safety, and immunogenicity of SDZ-ADL were comparable to those observed for reference-adalimumab (ref-ADL) and not altered after single or multiple drug switches. Real-world studies confirmed the effectiveness and safety of treatment initiation with SDZ-ADL and of switching to SDZ-ADL from ref-ADL or from other ADL biosimilars. This literature review provides evidence that SDZ-ADL is as effective and safe as ref-ADL in both biologic-naïve and biologic-experienced patients.

Introduction

This study aimed to evaluate the pharmacokinetics (PK), safety, and local tolerability of local finasteride spray (0.25% solution in HPCH, once daily, volume 200 μL) after single and multiple doses in Chinese male volunteers with androgenetic alopecia.

Methods

Twelve male patients with androgenetic alopecia received once-daily scalp application of the solution for 7 days. Blood samples were collected at specified time points (on day 1, days 3–6, and day 7 of the trial) and plasma finasteride concentrations were determined by HPLC–MS.

Results

After single-dose administration, the C_max of finasteride was 15.2 ± 5.54 pg/mL, T_max was 11.00 (3.00, 20.00) h, AUC_0–24h was 263 ± 76.6 h·pg/mL, t_1/2 was 35.3 ± 47.7 h, and CL/F was 974 ± 518 L/h. After 7 days of multiple doses, C_max,ss was 29.7 ± 12.9 pg/mL, T_max,ss was 8.00 (3.00, 12.00) h, AUC_tau,ss was 530 ± 251 h·pg/mL, AUC_0–t,ss was 790 ± 464 h·pg/mL, t_1/2,ss was 22.6 ± 10.7 h, and CL/T_ss was 1080 ± 658 L/h. No clinically significant adverse events occurred during the study.

Conclusion

Compared to single-dose administration, multiple-dose administration of finasteride resulted in a stable half-life, minimal changes in clearance rate, and approximately twofold accumulation in exposure over 7 days. Multiple-dose administration of finasteride spray was well tolerated in Chinese male volunteers with androgenetic alopecia.

Introduction

Vigabatrin (VGB) is intended for use by caregivers of infants (1 month to 2 years old) diagnosed with infantile spasms (IS). Commercially available vigabatrin powders require caregiver reconstitution prior to oral administration. This study compared the ability of caregivers to accurately provide a targeted dose of vigabatrin using a ready-to-use (RTU) vigabatrin oral solution (VGB-RTU solution) and SABRIL^® (vigabatrin) powder for oral solution, Lundbeck LLC, (vigabatrin powder) without instruction from a healthcare professional.

Methods

A crossover comparative usability study with 30 lay users (15 caregivers with vigabatrin powder experience and 15 oral-syringe/medication preparation naïve users) which required users to deliver a single dose of both VGB-RTU surrogate solution and vigabatrin powder to a sample collection bottle was performed. Doses were measured analytically with a primary endpoint to deliver doses within ± 10% of the target dose of 1125 mg.

Results

All 30 participants administered VGB-RTU solution doses within ± 5% of the target, while only 23/30 of the vigabatrin powder doses were within ± 10%. All naïve users delivered vigabatrin doses using VGB-RTU solution within ± 5% of the target; whereas only 13/15 delivered doses within ± 10% for vigabatrin powder. All experienced vigabatrin users delivered calculated vigabatrin doses using VGB-RTU solution within ± 3%; whereas only 10/15 delivered doses within ± 10% for vigabatrin powder. Users were equally able to accurately deliver the prescribed volumes of both products. Calculated doses of VGB-RTU solution (mg) were significantly less variable (p < 0.0001) and more accurate (p < 0.01) than doses of vigabatrin powder.

Conclusion

Caregivers delivered more accurate and less variable doses of the ready-to-use solution compared to solutions prepared from vigabatrin powders for oral solution. These differences were shown to be due to caregiver errors in reconstituting vigabatrin powders for oral solution.

Introduction

Atrial fibrillation (AF), a common heart rhythm abnormality, is linked to a higher risk of stroke. Traditionally, warfarin has been the primary anticoagulation treatment for reducing the stroke risk. The new standard of treatment by direct oral anticoagulants (DOACs) offers greater benefits including improved efficacy and fewer adverse effects with reduced monitoring. This study aims to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB) among patients with AF who switched from warfarin to DOACs.

Methods

This study utilized Medicare data to conduct a retrospective analysis of patients with non-valvular atrial fibrillation (NVAF) who switched from warfarin to DOACs between January 1, 2012, and December 31, 2019. Patients with NVAF aged 65 and older who switched from warfarin and had continuous health plan enrollment were included. Descriptive statistics, propensity score matching (PSM), and Cox proportional hazard (PH) models were utilized to compare the outcomes and assess risks of SE and MB across the DOAC cohorts.

Results

Among 1,843,495 patients with NVAF on warfarin, 171,700 switched to DOACs within 90 days of discontinuation (apixaban: 90,850; rivaroxaban: 67,698; dabigatran: 12,900). The mean follow-up period across DOAC cohorts ranged from 552 to 628 days. After PSM, apixaban showed significantly lower rates of stroke/SE compared to dabigatran (2.99% vs. 3.98%, p < 0.0001) and rivaroxaban (3.08% vs. 3.80%, p < 0.0001). MB rates were also lower with apixaban versus dabigatran (4.29% vs. 5.57%, p < 0.0001) and rivaroxaban (4.07% vs. 6.35%, p < 0.0001). Cox PH models confirmed these findings, with apixaban demonstrating lower risks of stroke/SE [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.72–0.96 vs. dabigatran; HR 0.91, 95% CI 0.85–0.96 vs. rivaroxaban] and MB (HR 0.79, 95% CI 0.71–0.89 vs. dabigatran; HR 0.68, 95% CI 0.65–0.72 vs. rivaroxaban).

Conclusion

The risk of stroke/SE and MB varies significantly among patients with NVAF switching from warfarin to different DOACs, with apixaban presenting the lowest risk compared to dabigatran and rivaroxaban.

Introduction

This study explored the effects of four different surgical methods in the treatment of cesarean scar pregnancy (CSP).

Methods

In this multicenter retrospective analysis of 359 patients, the surgical indices, the time taken for the serum human chorionic gonadotropin level to return to normal, the recovery time of menstruation, and the incidence of postoperative adverse reactions were comparatively analyzed. The clinical efficacies of various preoperative treatment methods to block the blood supply to CSP tissues and those of four different surgical methods to treat CSP, namely, curettage, hysteroscopic surgery, laparoscopic surgery, and vaginal surgery, were evaluated in this study.

Results

Hysteroscopic pregnancy tissue removal in patients with type I CSP was found to be associated with low cost, rapid postoperative recovery, and a low incidence of postsurgical complications. Among patients with type II–III CSP, the operation success rate (96.97% for type II and 88.46% for type III) in those who underwent uterine artery embolization + curettage was lower than that in patients from the other groups (all 100%). Among patients with type III CSP who underwent transvaginal ligation of the descending uterine artery + hysteroscopic removal of the pregnancy tissues, three patients (12.5%) underwent hysteroscopic surgery under transumbilical single-port laparoscopic surveillance so as to avoid uterine perforation considering that the pregnancy tissue was only 1 mm away from the uterine plasma membrane layer.

Conclusion

Hysteroscopic surgery without pretreatment can be adopted for patients with type I CSP. In contrast, patients with type II and III CSP should be initially pretreated with vascular ligation to prevent intraoperative bleeding, followed by laparoscopic or vaginal surgery.

Trial Registry

Clinical Trial Registry Number ChiCTR2000040357.

Introduction

This retrospective claims analysis characterized contemporary ulcerative colitis (UC) treatment patterns and investigated the economic burden of UC in Japan.

Methods

This study used anonymized claims data in the Medical Data Vision database. Patients were included if they had a confirmed UC diagnosis and ≥ 1 claim of systemic treatment for UC (index date) between June 2018 and December 2022, in addition to continuous enrollment for ≥ 6 months before and ≥ 12 months after the index date. Patients were excluded if they were aged < 18 years at index or if they had claimed systemic UC treatment during the pre-index period, had a confirmed diagnosis of Crohn’s or Behçet’s disease, or had a record of colectomy during the pre-index period. Outcomes of interest were treatment patterns, healthcare resource utilization (HCRU), and UC-related costs per person per month (PPPM). Further exploratory analyses were conducted to understand whether real-world treatment patterns with conventional therapy were optimally aligned with guideline recommendations. Two definitions of suboptimal treatment with conventional therapies were identified: prolonged treatment with corticosteroids (i.e., consecutive use for  > 90 days) and corticosteroid cycling (i.e., three or more ≥ 30-day corticosteroid courses over 1 year, with a ≥ 60-day gap between courses).

Results

Overall, 15,429 patients were included. The most frequently observed class of first-line treatment was 5-aminosalicylic acid monotherapy (75.0%); treatment modification was observed in 39.7% of patients. Within 1 year of follow-up, patients had a mean (SD) of 9.8 (6.8) outpatient visits, and a hospital stay was reported in 23.9% of patients. Mean total cost PPPM was ¥76,374. Of patients with ≥ 1 course of corticosteroids, 39.8% received suboptimal treatment with conventional therapies. HCRU and total costs were higher for patients with versus without suboptimal treatment with conventional therapies.

Conclusions

Japanese patients with UC would benefit from treatment options that can reduce costs, HCRU, and suboptimal treatment with conventional therapies.