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Optimising the Therapeutic Window: A Systematic Review and Network Meta-Analysis of Pregabalin Dosing Strategies for Painful Diabetic Neuropathy

2026-04-01T00:00:00Z

Title: Optimising the Therapeutic Window: A Systematic Review and Network Meta-Analysis of Pregabalin Dosing Strategies for Painful Diabetic Neuropathy Authors: Kwon, Doyun; Jung, Hee‐Jae; Nam, Junho; Kim, Jonghae; Jeon, Eonju; Kwak, Sanggyu Abstract: Aims Although pregabalin is a first-line therapy for painful diabetic polyneuropathy (PDPN), its optimal dose-response relationship remains unclear. We conducted a network meta-analysis to evaluate the efficacy and safety of fixed pregabalin dosages in PDPN patients.Materials and Methods We systematically searched major databases through October 2025 comparing various doses of pregabalin (75, 150, 300, and 600 mg/day) with placebo in adults with PDPN. The outcomes were short- and long-term changes in the average daily pain score, patient/clinician global impression of change, and adverse events (AEs) including dizziness, somnolence, headache, and peripheral oedema.Results Twelve RCTs were eligible. In the short term, pregabalin 300 (Standardised Mean Difference [SMD], 1.09; 95% CI, 0.69-1.50) and pregabalin 600 mg/day (SMD, 0.90; 95% CI, 0.24-1.55) produced significant pain reduction compared with placebo. In the long term, both pregabalin 300 (SMD, 0.12; 95% CI, 0.06-0.17) and 600 mg/day (SMD, 0.31; 95% CI, 0.23-0.38) remained effective, whereas pregabalin 75 and 150 mg/day did not demonstrate superiority over placebo. Regarding safety, both pregabalin 300 and 600 mg/day were associated with greater risks of dizziness, somnolence, and peripheral oedema compared with pregabalin 75 mg/day, pregabalin 150 mg/day, and placebo.Conclusion Pregabalin doses <= 150 mg/day demonstrated no clinical benefit over placebo. Conversely, both pregabalin 300 and 600 mg/day showed a pain reduction effect at short- and long-term follow-up. Given that pregabalin 600 mg/day was associated with a higher incidence of AEs, pregabalin 300 mg/day appears to offer a more favourable balance, aligning potent efficacy with a manageable safety profile.

Trends in Acute Care and Rehabilitation for First-Ever Stroke Patients: A 12-Year Perspective, the KOSCO Study

2026-04-01T00:00:00Z

Title: Trends in Acute Care and Rehabilitation for First-Ever Stroke Patients: A 12-Year Perspective, the KOSCO Study Authors: Kim, Dae Hyun; Sohn, Min Kyun; Lee, Jongmin; Kim, Deog Young; Shin, Yong-Il; Oh, Gyung-Jae; Lee, Yang-Soo; Joo, Min Cheol; Lee, So Young; Song, Min-Keun; Han, Junhee; Ahn, Jeonghoon; Lee, Ho Seok; Kim, Yun-Hee; Chang, Won Hyuk Abstract: Background: Updated data on stroke care trends are crucial for advancing stroke treatment. This study aimed to assess trends in inpatient care for first-ever stroke patients in South Korea over a 12-year period, focusing on demographic shifts and acute treatments including rehabilitation. Methods: This multicenter cohort study analyzed first-ever stroke patients admitted to three representative hospitals in South Korea during 2008 (n = 911), 2014 (n = 1,489), and 2020 (n = 1,434). The 2008 data were collected retrospectively, while 2014 and 2020 data were obtained from a prospective cohort study. Data included demographics, risk factors, stroke characteristics, hospital course, and rehabilitation treatments. Results: From 2008 to 2020, the mean age of stroke patients increased from 62.0 to 66.2 years. The proportion of ischemic stroke cases increased markedly from 47.3% to 74.5% while risk factors such as diabetes mellitus and hyperlipidemia showed increasing prevalence. Mechanical thrombectomy increased from 0% to 3.3%. Mean hospital stay decreased from 25.2 to 14.9 days, while in-hospital mortality declined from 5.9% to 3.7%. Rehabilitation consultations increased from 27.8% to 80.6%, occurring earlier during hospitalization. Rehabilitation therapy during hospitalization increased from 23.7% to 55.8%, and transfers to rehabilitation medicine rose from 12.8% to 19.1%. Home discharge increased from 34.8% to 60.0%.Conclusion: Management of first-ever stroke patients in Korea improved substantially over 12 years, reflecting positive impacts of national quality initiatives and advancing stroke care.

In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression

2026-04-01T00:00:00Z

Title: In vivo adenine base editing of mutant Galc gene ameliorates Krabbe disease progression Authors: Nam, Bae-Geun; Seo, Jung Hwa; Hong, Sung-Ah; Kim, Ju-Hee; Kang, Minju; Notario, Geneva Rose; Hong, Yoontaik; Cho, Seunghee; Bae, Sangsu; Cho, Sung-Rae Abstract: Background Krabbe disease (KD) is caused by mutation of the galactosylceramidase (GALC) gene, leading to deficient sphingolipid metabolism, which is essential for functional myelination. The twitcher (Galc(twi/twi)) mouse, a KD model with a premature termination codon (PTC) caused by a single-nucleotide G-to-A substitution at the 355th codon of the Galc gene, is a model candidate for treatment with adenine base editors (ABEs). ABEs have emerged exclusively among genome editing systems as viable therapeutic candidates to correct mutant genes. Methods To confirm base editing efficiency of ABEs, mouse embryonic fibroblasts (MEFs) or mutant GALC HEK293T cells treated with three ABE variants (ABEmax, ABE8eWQ, ABE8e) were assessed using targeted deep sequencing. Each split-ABE8e vector was packaged into a dual-vector adeno-associated virus serotype 9 (AAV9) system and delivered to twitcher mice via intracerebroventricular injection on postnatal day 1. Thereafter, motor functions and survival rate were evaluated by rotarod test, clasping test and lifespan analysis. Various methods, including next-generation sequencing (NGS), qRT-PCR, enzyme activity assay, and flow cytometry, were used to measure the base correction rate of the target gene and verified restoration of GALC enzyme activity in the brain of ABE8e-treated mice. Additionally, myelin recovery was evaluated in the brain using histological analysis, magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and transmission electron microscopy (TEM). Results The ABE8e-treated MEFs and mutant GALC HEK293T cells showed the most effective editing among the ABE variants tested. Three weeks after dual-AAV9 injection, the PTC was corrected in approximately 0.5% of genomic DNA and 5% of mRNA in twitcher mice. ABE8e treatment restored GALC enzymatic activity to approximately 5% of wild-type (WT) levels, while reducing the accumulation of psychosine-a major neurotoxic metabolite-by approximately 47% relative to WT. Moreover, histological analysis, TEM and, DTI and T2-weighted MRI showed preserved myelination and axonal integrity, along with amelioration of myelin deficits in the corpus callosum of ABE-treated twitcher mice. Five weeks after ABE8e administration, body weight recovered to approximately 64% of WT levels, accompanied by an extension of lifespan. In addition, clasping scores and rotarod performance improved to approximately 23% and 64% of WT levels, respectively. Conclusions These data demonstrate a reliable application of base editing technology using ABEs as a potential treatment option for KD, progressing the development of therapeutics treating various genetic diseases. [GRAPHICS]

Association between instrumental activities of daily living and incidence of Parkinson's disease: a nationwide population-based cohort study

2026-03-01T00:00:00Z

Title: Association between instrumental activities of daily living and incidence of Parkinson's disease: a nationwide population-based cohort study Authors: Park, You Hyun; Lee, Hyo Jeong; Kim, Yong Wook; Lee, Sang Chul; Yoon, Seo Yeon Abstract: Several studies have investigated the prodromal factors for early diagnosis of Parkinson's disease (PD). Instrumental activities of daily living (IADL) involve both motor and non-motor functions, and has been used as a screening tool for dementia. This study aimed to examine the association between IADL dependency and PD incidence and identify specific IADL items linked to an increased likelihood of developing PD. This population-based cohort study used data from the Korean National Health Insurance Service database, that contains information on long-term care services. Individuals who underwent at least one health screening and completed the geriatric assessment sheet between 2009 and 2021 were included in this study. Information on IADL was extracted from the geriatric assessment sheet. The Fine-Gray subdistribution hazard model was used to assess the association between IADL dependency and PD incidence. During a mean follow-up period of 3.78 +/- 3.34 years, 308 of the 21,662 participants developed PD. The highest IADL dependency was significantly associated with an increased incidence of PD (adjusted hazard ratio [aHR] = 1.458, 95% confidence interval [CI] 1.037-2.050), particularly among women or >= 75 years. Among the 10 IADL items, dependency in financial management (aHR 1.420, 95% CI 1.057-1.909, p = 0.0201) or telephone use was significantly associated with an increased incidence of PD (aHR 1.536, 95% CI 1.204-1.961, p = 0.0006). Our results suggests that IADL dependency is a potential prodromal indicator of PD. Further research on other ethnicities that considers sociocultural differences is required to confirm this association.