Current Medical Research and Opinion最新文献

Introduction: The purpose of this study was to describe the clinical burden and healthcare resource utilization (HCRU) among patients with sickle cell disease (SCD) and recurrent vaso-occlusive crises (VOCs) and patients with transfusion-dependent β-thalassemia (TDT) in the Netherlands.

Methods: This retrospective cohort study identified two patient populations, one cohort with SCD and recurrent VOCs and the other with TDT from the PHARMO Data Network (1 January 2014-31 December 2020). Key inclusion criteria were diagnosis of SCD and ≥2 VOCs per year for 2 consecutive years following the diagnosis for SCD; or diagnosis of β-thalassemia and ≥8 red blood cell transfusions (RBCTs) per year for 1 year following the diagnosis for β-thalassemia. Complications and HCRU were evaluated for each cohort.

Results: A total of 383 patients with SCD and recurrent VOCs and a total of 54 patients with TDT were identified with mean ages at index of 26.9 (standard deviation [SD]: 14.4) years and 17.7 (SD: 15.2) years, respectively. Patients with SCD and recurrent VOCs experienced an average of 7.0 VOCs per patient per year (PPPY). The most common acute complication was acute chest syndrome (34.9%), and the most common chronic complications were bone and joint complications (12.0%). Patients had a mean of 2.5 inpatient hospitalizations and 7.0 outpatient visits PPPY.Patients with TDT received an average of 13.0 RBCTs PPPY. The most common acute complication was infection (5.6%), and the most common chronic complication was transfusion-induced iron overload (33.3%). Patients had a mean of 11.3 inpatient hospitalizations, mainly driven by transfusion-related hospitalizations, and 8.4 outpatient visits PPPY.

Conclusion: Patients with SCD and recurrent VOCs and patients with TDT in the Netherlands sustain substantial clinical complications and HCRU mainly related to VOCs and regular RBCTs, respectively.

Objective: Forvisirvat (SP-624), an orally-administered epigenetic sirtuin 6 (SIRT6) activator with antidepressant effects in animal models, was well tolerated in three phase 1 trials. This phase 2 study, SP-624-201, evaluated the safety and efficacy of forvisirvat 20 mg daily for 4 weeks in participants with major depressive disorder (MDD).

Methods: SP-624-201 (NCT04479852) was a double-blind, placebo-controlled study. Participants were adults who met DSM-5 criteria for moderate to severe MDD and who discontinued psychoactive medications or supplements including antidepressants and mood stabilizers. Primary endpoint was change from baseline to Week 4 in Montgomery Asberg Depression Rating Scale score. Participants were randomized to forvisirvat 20 mg daily (N = 163) or placebo (N = 156).

Results: Of the 317 treated patients, 224 (70.7%) were White and 211 (66.6%) were female. No significant difference in the primary endpoint was observed between treatment groups. However, post-hoc analysis found that women treated with forvisirvat experienced significant overall improvement whereas men did not. The difference between sexes was also consistent for secondary efficacy measures. No serious adverse events were reported for forvisirvat-treated participants. The most frequent treatment-emergent event was headache (forvisirvat: 8.1%, placebo: 11.5%). Six of 161 forvisirvat-treated participants and 5 of 156 participants who received placebo discontinued due to adverse events.

Conclusions: The novel epigenetic mechanism of action of forvisirvat, favorable safety profile, and consistent post-hoc efficacy results in women observed in this study support further development of forvisirvat. A phase 2b/3 trial of forvisirvat in MDD (NCT06254612), to confirm these results, is ongoing.

Background: Evidence on the biochemical phenotypes of primary aldosteronism and their link to renal function in Chinese populations is limited. This study explored the associations of plasma aldosterone concentration (PAC), plasma renin concentration (PRC), and the aldosterone-to-renin ratio (ARR) with renal function.

Methods: In this cross-sectional study of 1700 participants from Southwest China, associations between PAC, PRC, ARR, and renal parameters (serum creatinine [SCR], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR]) were analyzed using a generalized linear mixed model. Dose-response relationships were assessed with P-trend and restricted cubic spline (RCS) analyses. A structural equation model evaluated the mediating effect of blood pressure.

Results: Higher log-transformed PAC was associated with elevated SCR (β = 0.451, 95% CI: 0.329, 0.573) and BUN (β = 0.370, 95% CI: 0.278, 0.462), and reduced eGFR (β = -0.263, 95% CI: -0.331, -0.194). RCS analyses confirmed linear dose-response relationships. These associations were more pronounced in males than females. Renin-Angiotensin-Aldosterone System (RAS) inhibitor use mitigated the positive association between PAC and BUN. Systolic blood pressure mediated a small proportion of the effect of PAC on SCR (2.4%) and eGFR (2.6%).

Conclusion: A continuous spectrum of PAC is associated with renal impairment in this Chinese cohort, with stronger effects observed in males. The use of RAS inhibitors may attenuate this aldosterone-related renal impairment.

Objectives: Quantify caregiver risk preferences to inform the "value of hope" for Duchenne muscular dystrophy (DMD) therapies affecting time to loss of ambulation (LoA).

Methods: Caregivers (medical decision-makers) of patients with DMD were surveyed to evaluate their preferences across 2 therapies with identical expected (average) time to LoA: 1 with variable (i.e. possibly longer or shorter than average) time to LoA and 1 with fixed (i.e. certain) time to LoA. Time to LoA with the fixed therapy was altered to determine the caregiver's indifference point. Study endpoints were (i) the share of caregivers who preferred the variable (vs fixed) time to LoA therapy; and (ii) the length of fixed time to LoA that would result in caregiver indifference between the variable and fixed therapies, calculated using parameter estimation by sequential testing. The base case examined therapy choice for a hypothetical ambulatory DMD patient aged 9 years; sensitivity analyses explored preferences for younger (aged 5) and older (aged 13) patients.

Results: Among 103 caregivers surveyed, 72 (69.9%) preferred the variable time to LoA therapy for a hypothetical 9-year-old patient with DMD (p < 0.001). Caregivers were willing to give up 11.5 months (p < 0.001) of certain time to LoA for a chance of longer time to LoA. Caregivers' preference for the variable therapy decreased with hypothetical patient age at treatment initiation, from 72.8% (75/103) for age 5 (p < 0.001) to 60.2% (62/103) for age 13 (p = 0.048).

Conclusions: Caregivers of patients with DMD demonstrated risk tolerance (positive value of hope) for therapies that could delay LoA.

Older adults are at increased risk of severe illness, hospitalization, and death due to influenza, making vaccination a key public health strategy. High-dose (HD) influenza vaccine has been recommended in several European countries to enhance protection in this vulnerable group. While clinical trials and observational studies have reported improved effectiveness of HD vaccine in preventing influenza-related outcomes, this advantage appears most consistent in individuals aged 75 and older. In contrast, evidence supporting the superiority of HD vaccine over standard-dose (SD) vaccines in the 65-74 age group (the "young-old") is limited and often not statistically significant. This review examined real-world effectiveness data comparing HD and SD influenza vaccines in elderly populations. While HD vaccines may provide added protection in the oldest age groups, SD vaccines continue to offer substantial and reliable protection, particularly among the 60-74 age range. HD vaccine is associated with higher rates of mild side effects and carries a significantly greater cost, which may limit its cost-effectiveness for broad use in the younger elderly population. Given that the majority of elderly individuals in developed countries fall within the 65-74 age group, a tailored vaccination approach may be more appropriate. Recommending HD vaccine primarily for those aged 75 and older, while offering SD vaccines to younger seniors, may help increase vaccine coverage without compromising protection. More real-world, age-stratified studies are needed to guide vaccination policies. Ultimately, any influenza vaccine is better than none, and SD vaccines remain an effective and accessible option for most older adults.

Background: Serum albumin is a well-known biomarker in sepsis, and several albumin-based ratios have been proposed to enhance its prognostic performance. However, it remains unclear whether these composite indices outperform serum albumin alone in predicting outcomes in septic patients.

Methods: We conducted a prospective observational study including 413 adult patients with sepsis admitted to the Intermediate Care Unit of Santorso Hospital, Italy, between January 2023 and June 2024. Clinical data, laboratory parameters, and six albumin-based ratios were collected at admission. The primary outcome was 30-day mortality. Prognostic performance was assessed using ROC curves, Brier Scores, and Decision Curve Analysis (DCA). Correlation with clinical severity was evaluated using Spearman's correlation with SOFA and APACHE II scores.

Results: Among the 413 patients enrolled, 30-day mortality was 16.9%. Serum albumin demonstrated the highest predictive value compared to all albumin-based ratios. DCA confirmed the superior net clinical benefit of serum albumin across a wide range of threshold probabilities, especially in early risk stratification. LAR showed comparable performance in AUC but lower clinical utility in DCA. Albumin also showed the strongest inverse correlation with SOFA (ρ = -0.276, p < 0.001) and APACHE II (ρ = -0.391, p < 0.001) scores.

Conclusions: Serum albumin is a strong, independent predictor of 30-day mortality in patients with sepsis and outperforms multiple albumin-based ratios in both statistical and clinical utility. Its use in early risk stratification should be encouraged in clinical practice. Further multicenter studies are warranted to confirm these findings and explore their generalizability.

Objective: We evaluated real-world treatment patterns and unmet needs associated with migraine preventive medications in Japan following the introduction of calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs), focusing on persistence, switching, and adherence rates.

Methods: This retrospective cohort study analyzed JMDC (previously Japan Medical Data Center) claims data (index date: April 2021 to January 2024) for treatment-naïve patients who initiated oral migraine preventive medications (OMPMs; n = 12,750) and patients initiating CGRP mAbs (n = 3,280). Persistence was defined as continuous therapy without a 60-day or longer gap. Treatment patterns were evaluated at 3, 6, and 12 months post-initiation.

Results: Most patients were female (74.1% OMPMs, 78.1% CGRP mAbs), over half of childbearing age. For OMPM initiators, persistence rates declined from 49.7% at 3 months to 21.7% at 12 months, with antiepileptics showing highest persistence (27.0%). CGRP mAb initiators demonstrated higher initial persistence (85.6% at 3 months), declining to 36.5% at 12 months. 22.9% of OMPM and 19.7% of CGRP mAb patients switched by 12 months. Among OMPM switchers, only 20% switched to CGRP mAbs. Both cohorts had a high prevalence of comorbidities, including non-migraine headaches (approx. 50%), mental health disorders (26-31%), and sleep disorders (approx. 29%).

Conclusion: Substantial unmet needs exist in migraine preventive treatment in Japan, as demonstrated by low 12-month persistence across all medication classes. Despite higher initial persistence, CGRP mAbs showed similar declining patterns over time, indicating most migraine patients do not remain on their index treatment and suggesting the need for additional options.

Patient engagement (PE) has evolved from an emerging concept to a fundamental ethos underpinning healthcare research and communication. In this commentary, we explore the historical evolution in medical research from patients being participants in clinical trials to becoming integral partners in communicating medical research findings. The progression from "why" to "how" PE should occur represents a fundamental shift in the medical publication landscape. We also highlight the International Society for Medical Publication Professionals' (ISMPP) journey in embracing and advancing PE within medical publications through ISMPP's initiatives and activities, including the establishment of its PE Task Force, patient membership, and support programs, while examining the cultural transformations occurring within the profession. Looking ahead, we discuss opportunities for expanding patient roles, improving accessibility to tools and frameworks, and integrating patient perspectives into leadership positions. This commentary serves as both a reflective narrative and a call to action for medical publication professionals to champion authentic and meaningful PE, ensuring publications truly engage and serve the patients at the heart of the research they describe, as exemplified by ISMPP.

Objective: This study aimed to report the 10-year experience of implantation, removal, and adjustment of a totally implantable venous access port (TIVAP) under the guidance of digital subtraction angiography (DSA) at a territory medical center.

Methods: The medical records of consecutive patients who underwent implantation, removal, and adjustment of the TIVAP under DSA guidance from January 2014 to March 2024 were retrospectively reviewed.

Results: In total, 290 consecutive patients who underwent TIVAP implantation were included, of which, 136 (46.9%) were men and 154 (53.1%) were women, with a mean age of 44.4 ± 16.5 years. The mean radiation dose was 4.9 ± 1.4 mGy. The operation time was 34.1 ± 3.8 min. The technical success rate was 100%. During a median follow-up of 239 days, 9 cases showed complications. No significant differences were found in age, sex, operation time, and radiation dose between the subclavian vein (SCV) and internal jugular vein (IJV) groups, while there were fewer complications in the IJV group (p = 0.039), and 114 consecutive patients who underwent TIVAP removal were included, of which, 49 (43.0%) were men and 65 (57.0%) were women, with a mean age of 44.3 ± 15.4 years. The median radiation dose was 3.8 (1.3-62.3) mGy. The median interval time from implantation to removal was 358.5 (2-3650) days. The operation time was 34.4 ± 6.1 min. The technical success rate was 100%. No significant differences were observed between the SCV and IJV groups. Cases with fracture and dislocation of the catheters were defined as the complicated group, while the others were defined as the uncomplicated group. The operation time (45.7 ± 12.4 vs. 33.7 ± 4.6 min) and radiation dose (45.4 ± 10.8 vs. 4.2 ± 2.2 mGy) between the above two groups were significantly different (both p < 0.05); A total of nine consecutive patients who underwent adjustment of the TIVAP were included, of which three patients had dislocation of the catheter and six patients had kinking of the catheters. They were all successfully adjusted using a pigtail catheter and/or gooseneck snare. The average operation time and radiation dose were 20.8 ± 5.6 min and 3.2 ± 1.3 mGy.

Conclusion: Implantation, removal, and adjustment of the venous port access under DSA guidance were safe and efficient. For the removal and adjustment of complicated cases, using the pigtail catheter and/or gooseneck snare under DSA guidance was efficient. In addition, the IJV seems to be a safer venous access site with a lower complication rate than the SCV.

Introduction: Diabetes Mellitus is a chronic disease characterised by elevated plasma glucose (PG) levels. HbA1c has been widely utilized for diabetes diagnosis. However, certain conditions restrict its use. In such cases, plasma glucose (PG) measurements and self-monitoring blood glucose (SMBG) are recommended. This case series highlights the importance of considering both HbA1c and PG or SMBG in the evaluation of patients with diabetes.

Case report: This case series presents three cases of patients with diabetes who exhibited a discrepancy between PG and HbA1c levels. Only one patient demonstrated isolated microcytosis, while the remaining two had completely normal hematologic profiles. Due to this discrepancy, hemoglobin electrophoresis was conducted, revealing various hemoglobinopathies in all cases.

Conclusion: For patients with discrepancies between PG levels and HbA1c, we suggest a thorough evaluation that includes consideration of potential hemoglobinopathies. These hemoglobin variants can present with isolated microcytosis or entirely normal hematologic parameters and may lead to falsely low HbA1c values. In cases of discordance between PG and HbA1c, hemoglobin electrophoresis can serve as a valuable diagnostic tool. Identifying hemoglobinopathies before determining treatment regimens can help mitigate the risk of complications from inadequate treatment, and awareness of HbA1c limitations allows clinicians to use both HbA1c and PG/SMBG to optimize diabetes management and minimize the risk of diabetic complications.