2-week Intervals Research Articles

Long-term safety and efficacy of mavacamten in obstructive hypertrophic cardiomyopathy: up to 3.5-year follow-up results of the EXPLORER cohort of MAVA-Long-Term Extension study

Abstract Introduction Mavacamten safety and efficacy in patients with obstructive hypertrophic cardiomyopathy (HCM) was demonstrated in the phase 3 EXPLORER-HCM trial. Long-term safety and efficacy of mavacamten in patients with obstructive HCM is being studied in the MAVA-Long-Term Extension (LTE) study (NCT03723655). Purpose To present long-term safety and efficacy data from the EXPLORER cohort of MAVA-LTE up to week 180 (data cutoff: August 31, 2023). Methods Patients who completed EXPLORER-HCM could enroll in MAVA-LTE following washout. All patients received mavacamten 5 mg at baseline; dose titration to 2.5, 10, or 15 mg was based on site-read echocardiographic evaluation of Valsalva left ventricular outflow tract (LVOT) gradient and left ventricular ejection fraction (LVEF). Following titration, patients were assessed at 12-week intervals between weeks 24 to 156; week 180 was the first visit following a 24-week interval. Results At the data cutoff, 211 of 231 patients who enrolled in MAVA-LTE were on treatment; 185 and 99 patients had reached week 156 and 180, respectively (median [interquartile range (IQR)] time on study: 166 [160–189] weeks; total exposure: 739 patient-years). Sustained improvements from baseline to weeks 156 and 180 were observed in mean (standard deviation [SD]) resting LVOT gradient (−40.2 [32.8] mmHg, n=187; and −40.3 [32.7] mmHg, n=94; respectively), Valsalva LVOT gradient (−55.3 [37.3] mmHg, n=184; and −55.3 [33.7] mmHg, n=91) (Figure 1), and median (IQR) N-terminal pro B-type natriuretic peptide levels (−504 [−1160, −143] ng/L, n=179; and −562 [−1162.5, −209] ng/L, n=88). Improvements from baseline to weeks 144 and 180 were sustained in mean (SD) left atrial volume index (−3.5 [10.4] mL/m2, n=193; and −5.5 [9.7] mL/m2, n=62; respectively). At week 156 and 180, 53.5% and 66.3% of patients, respectively, were in New York Heart Association class I. Mean (SD) LVEF decreased from baseline to week 180 (−11.0% [8.9%]; n=93) but the mean (63.9%) remained within normal range. Overall, 33 patients (14.3%) experienced atrial fibrillation, 14 patients (6.1%) experienced cardiac failure episodes, 13 patients (5.6%) permanently discontinued treatment owing to adverse events and 20 patients (8.7%) experienced transient reductions in LVEF < 50% (range: 30–48%), of whom 6 (2.6%) experienced LVEF < 40% (Figure 2). Of these 20 patients (13 from the placebo group in EXPLORER-HCM), all recovered LVEF ≥ 50% following treatment interruption and 14 reinitiated medication. In total, 5 patients died during the study (all deaths unrelated to mavacamten). Conclusions Long-term mavacamten treatment in patients with obstructive HCM resulted in sustained improvements in echocardiographic measures, symptoms, and biomarkers. Treatment was well-tolerated; no new safety signals were observed. Transient and reversible reductions in LVEF were observed in a small proportion of patients during long-term therapy.

Psychometric Properties of the Chinese Version of the Psy-Flex Among Parents of Children with Autism Spectrum Disorder.

This research aimed to translate the original English version of the Psy-Flex, a scale of psychological flexibility, into Chinese and to test its psychometric properties among parents of children with autism spectrum disorder (ASD). Two phases were conducted: (1) translation from English to Chinese (Psy-Flex-C), followed by a semantic equivalence evaluation between two versions, a pre-test, and an evaluation of the Psy-Flex-C in terms of face validity with 20 parents of autistic children, and content validity of the Psy-Flex-C with eight experts. (2) A cross-sectional study with 248 parents of autistic children was conducted for validation, and a subgroup of 50 participants was randomly selected to assess the test-retest reliability at a 2-week interval. The Psy-Flex-C showed satisfactory semantic equivalence with the original version and demonstrated adequate internal consistency (Cronbach's α = 0.84) and test-retest stability (weighted kappa statistic = 0.88). Concurrent validity was supported by a moderate correlation between the Psy-Flex-C and the Comprehensive Assessment of Acceptance and Commitment Therapy Processes (Pearson's r = 0.54, p < 0.01). The Psy-Flex-C showed a significant mean score difference between parents with high and low parenting stress (t = 5.43, p < 0.001). Similar to the original scale, confirmatory factor analysis showed the best fitting one-factor structure of the Psy-Flex-C (X2/df = 1.62, p = 0.13, RMSEA = 0.05, GFI = 0.99, CFI = 0.99, TLI = 0.98, SRMR = 0.023). The Psy-Flex-C can be a reliable and valid instrument to self-report psychological flexibility in parents of children with ASD. Future research is recommended to test the Psy-Flex-C using diverse samples from different cultures and contexts to enhance its generalizability.

Effects of a 30-min rest with a nap chair on task performance, sleepiness, and neurophysiological measures in men with suspected brain fatigue: a randomized controlled crossover trial

BackgroundIt has been suggested that a short nap in the afternoon may improve sleepiness, alertness, and task performance. The present study evaluated the effects of a 30-min rest with a new nap chair on task performance, sleepiness, and neurophysiological measures.MethodsA randomized controlled crossover trial with a 1-week interval was carried out at the BOOCS Clinic Fukuoka in Japan. The subjects were male workers aged 20 to 64 years with suspected brain fatigue, which was defined by the Profile of Mood Status 2. The intervention was a 30-min rest with an office chair or a nap chair. The primary outcome was the performance in the Uchida-Kraepelin test. The secondary outcomes included the Karolinska Sleepiness Scale and 15-min heart rate variability (HRV). The changes after the nap-chair rest and office-chair rest were compared. Repeated measures analysis of variance with nesting was used in the statistical analysis.ResultsTwenty participants were eligible and entered the crossover trial. The overall 15-min score in the Uchida-Kraepelin test improved after the nap-chair rest and after the office-chair rest to almost the same extent (5.9 vs. 5.5 points, P = 0.68). The Karolinska Sleepiness score significantly decreased after the nap-chair rest, and the between-treatment difference in the decrease was highly significant (P = 0.0004). The average duration of sleep during rest was prominently longer in the nap-chair rest than in the office-chair rest (19.0 vs. 7.6 min, P = 0.002). No participants experienced REM sleep during the rest. LF and HF powers of the HRV were greater during the nap-chair rest than during the office-chair rest, the difference in the HF power being substantial.ConclusionA 30-min rest with the nap chair did not appreciably improve the performance in the Uchida-Kraepelin test as compared with the office-chair rest. The nap-chair rest induced a substantially longer sleep accompanied with a parasympathetic activation, thereby resulting in a material improvement in sleepiness after the rest.

The preoperative prediction of lymph node metastasis of resectable pancreatic ductal adenocarcinoma using dual-layer spectral computed tomography.

To investigate the value of dual-layer spectral computed tomography (DLCT) parameters derived from primary tumors in predicting lymph node metastasis (LNM) of resectable pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, patients with resectable PDAC who underwent DLCT within 2-week intervals before surgery were enrolled and randomly divided into training and validation sets at a 7:3 ratio. The patients' clinical data, CT morphological features, and DLCT parameters were analyzed. Univariate and multivariate logistic analyses were used to identify the predictors and construct a predictive model, and receiver operator characteristic (ROC) curves were programmed to evaluate the predictive efficacy. We enrolled 107 patients (44 patients with LNM and 63 patients without LNM). Among all variables, iodine concentration in the venous phase, extracellular volume, and tumor size were identified as independent predictors of LNM. The nomogram model, incorporating the two DLCT parameters and the morphological feature, achieved an area under the curve (AUC) of 0.877 (95% confidence interval [CI]: 0.803-0.952) and 0.842 (95% CI: 0.707-0.977) for predicting LNM in the training and validation sets, respectively. Furthermore, the AUC of the nomogram model was greater than that of morphological features of lymph nodes in the training (AUC = 0.877 vs. 0.570) and validation (AUC = 0.842 vs. 0.583) sets. DLCT has the potential to predict LNM in patients with resectable PDAC and show a better predictive value than morphological features of lymph nodes. Question Morphological features of lymph nodes are of limited value in detecting metastatic lymph nodes in pancreatic ductal adenocarcinoma (PDAC). Findings Dual-layer spectral computed tomography (DLCT) parameters and morphological features derived from PDAC lesions show good preoperatively predictive efficacy for lymph node metastasis. Clinical relevance The proposed DLCT-based nomogram model may serve as an effective and convenient tool for preoperatively predicting lymph node metastasis of resectable PDAC.

In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.

Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45-55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Evaluating the Psychometric Properties of a Physical Activity and Sedentary Behavior Identity Scale: Survey Study With Two Independent Samples of Adults in the United States.

Emerging evidence suggests a positive association between relevant aspects of one's psychological identity and physical activity engagement, but the current understanding of this relationship is primarily based on scales designed to assess identity as a person who exercises, leaving out essential aspects of physical activities (eg, incidental and occupational physical activity) and sedentary behavior. The goal of this study is to evaluate the validity of a new physical activity and sedentary behavior (PA/SB) identity scale using 2 independent samples of US adults. In study 1, participants answered 21 candidate items for the PA/SB identity scale and completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Study 2 participants completed the same PA/SB identity items twice over a 1-week interval and completed the IPAQ-SF at the end. We performed factor analyses to evaluate the structure of the PA/SB identity scale, evaluated convergent validity and test-retest reliability (in study 2) of the final scale scores, and examined their discriminant validity using tests for differences in dependent correlations. The final PA/SB identity measure was comprised of 3 scales: physical activity role identity (F1), physical activity belief (F2), and sedentary behavior role identity (F3). The scales had high test-retest reliability (Pearson correlation coefficient: F1, r=0.87; F2, r=0.75; F3, r=0.84; intraclass correlation coefficient [ICC]: F1: ICC=0.85; F2: ICC=0.75; F3: ICC=0.84). F1 and F2 were positively correlated with each other (study 1, r=0.76; study 2, r=0.69), while both were negatively correlated with F3 (Pearson correlation coefficient between F1 and F3: r=-0.58 for study 1 and r=-0.73 for study 2; F2 and F3: r=-0.46 for studies 1 and 2). Data from both studies also demonstrated adequate discriminant validity of the scale developed. Significantly larger correlations with time in vigorous and moderate activities and time walking and sitting assessed by IPAQ-SF with F1, compared with F2, were observed. Significantly larger correlations with time in vigorous and moderate activities with F1, compared with F3, were also observed. Similarly, a larger correlation with time in vigorous activities and a smaller correlation with time walking were observed with F2, compared with F3. This study provided initial empirical evidence from 2 independent studies on the reliability and validity of the PA/SB identity scales for adults.

Evaluating the efficacy of a cost-effective, fully three-dimensional-printed vertebra model for endoscopic spine surgery training for neurosurgical residents.

A fused deposition modeling three-dimensional (3D)-printed model of the L4-5 vertebra for lumbar discectomy was designed. The model included separately printed dura mater, spinal cord, ligamentum flavum, intervertebral disc (from thermoplastic polyurethane), and bony structures (from polylactic acid), and the material cost approximately US$ 1 per model. A simple plumbing endoscope was used for visualization. Dura mater injury was assessed by painting two layers on the dura mater, which peeled off with trauma. Endoscopic spine surgery is a subject of high interest in neurosurgery given its minimally invasive nature; however, it has a steep learning curve. This study evaluated the effectiveness of a cost-efficient 3D-printed model when teaching this technique to neurosurgery residents. Only a few studies have investigated the efficacy of such a model. Eight residents with >2 years of training participated. Residents performed the procedure bilaterally and twice at 1-week intervals. From the 32 surgeries, four were excluded because of facet removal (as it widened the surgical corridor), leaving 28 surgeries for analysis. Initial surgeries demonstrated a mean operation time of 21 minutes 18 seconds (standard deviation [SD], 2 minutes 32 seconds), which improved to a mean of 6 minutes 45 seconds (SD, 37 seconds) in the fourth surgery (F(3, 17)=19.18, p <0.0001), demonstrating a significant reduction in surgical time over successive surgeries. The median area with the paint removed decreased, from 161.80 (85.55-217.83) to 95.13 mm2 (12.62-160.54), (F(2.072, Inf)=2.04, p =0.128); however, this was not significant. Resident feedback indicated high satisfaction with the educational value of the model. The developed fully 3D-printed model provides a viable and scalable option for neurosurgical training programs, enhancing the learning experience while maintaining low costs. This model may be an excellent stepping stone for learning lumbar spine endoscopy, acclimating to the two-dimensional view, progressing to cadaver models, and, eventually, independent surgery.

Feasibility and Acceptability of a Self-Guided Digital Family Skills Management Intervention for Children Newly Diagnosed With Type 1 Diabetes: Pilot Randomized Controlled Trial.

Family dynamics play an important role in determining the glycemic outcomes of type 1 diabetes (T1D) in children. The time interval immediately following T1D diagnosis is particularly stressful for families, and interventions to support families in adjusting their family practices to support adjustment to and management of T1D in the months following diagnosis may improve glycemic outcomes. Self-guided digital interventions offer a sustainable model for interventions to support caregivers in learning evidence-based family management skills for adjustment to and management of T1D. We hypothesized that a self-guided, web-based, family skills management program (addressing caregiver social support as well as family problem-solving, communication, and supportive behavior change strategies) initiated at the time of T1D diagnosis would improve glycemic outcomes in children with T1D. In this study, we report on the feasibility and acceptability of this program. We prospectively evaluated a sample of 37 children newly diagnosed with T1D recruited from a pediatric endocrinology clinic. Parent participants were asked to complete web-based modules addressing social support, family problem-solving, communication, and supportive behavior change strategies. Module completion was analyzed for percentage completion, patterns of completion, and differences in completion rates by coparenting status. Qualitative open-ended feedback was collected at the completion of each module. A total of 31 (84%) of the 37 participants initiated the web-based program. Of those 31 participants, 25 (81%) completed some content and 15 (48%) completed all 5 modules. Completion rates were higher when coparenting partners engaged in the intervention together (P=.04). Of the 18 participants given a choice about the spacing of content delivery, 15 (83%) chose to have all sessions delivered at once and 3 (17%) chose to space sessions out at 2-week intervals. Qualitative feedback supported the acceptability of the program for delivery soon after T1D diagnosis. Families reported on positive benefits, including requesting future access to the program and describing helpful changes in personal or family processes for managing T1D. In this study, we found that a self-guided digital family support intervention initiated at the time of a child's T1D diagnosis was largely feasible and acceptable. Overall, rates of participation and module completion were similar to or higher than other self-guided digital prevention interventions for mental and physical health outcomes. Self-guided digital programs addressing family management skills may help prevent challenges common with T1D management and can decrease cost, increase access, and add flexibility compared to traditional interventions. ClinicalTrials.gov NCT03720912; https://clinicaltrials.gov/study/NCT03720912.

Family Functioning and Cohesion Scale: Validation of a Short Instrument for the Assessment of Intrafamily Relations.

Most available scales for assessing family relationships are lengthy. Our aim was to develop and validate the Family Functioning and Cohesion Scale (FFCS), a self-reported, short instrument consisting of 14 items. The FFCS was validated through its administration to 481 subjects via an online platform. Cronbach's alpha was 0.85 (ranging from 0.83 to 0.86 if any one item was deleted), signifying high internal consistency. The scale can be considered as a sole factor based on its high consistency, while factor analysis produced three factors corresponding to "communication", "anger/resentment/aggression", and "values and beliefs". The test-retest reliability correlation coefficient was found to be 0.88 at a 2-week interval. Regarding external validity, the correlation coefficient of the FFCS with the general functioning subscale of the McMaster Family Assessment Device (FAD) was 0.83. The high measures of consistency, reliability, and validity of the FFCS, combined with its short length, make it a most valuable tool for use by researchers as well as by professionals dealing with families in psychiatry, psychology, social work, or other related fields.

Differences in sex and age response to single pill combination based antihypertensive therapy reflecting in blood pressure and arterial stiffness.

There are noticeable sex differences in the treatment response to antihypertensives, with limited data on the response to single pill combinations. The aim of the PRECIOUS trial was to assess the treatment response to perindopril/amlodipine and perindopril/amlodipine/indapamide dual and triple single-pill combination in men and women. Four hundred and forty adults with essential hypertension were assessed in the 16-week interventional, open-label, prospective, international, multicentre trial. Based on the previous antihypertensive therapy, patients were assigned to either perindopril/amlodipine 4/5 mg or perindopril/amlodipine/indapamide 4/5/1.25 mg, with the initial dose up-titrated in 4-week intervals in case of uncontrolled blood pressure. An additional analysis was performed for sex- and age-related differences on the blood pressure response and arterial stiffness in men and women aged 35-74 years. Women achieved better overall blood pressure control in all age groups, except for the 35-44 age group. Women presented higher average 24 h aortic augmentation indexes than men, but had more pronounced decreasing trends. The pulse wave velocity was only age-dependent, with reductions slightly greater in women. Both the aortic augmentation index and pulse wave velocity were significantly decreased in all groups compared to baseline. The results of the PRECIOUS trial contribute significant data to the expanding body of evidence on sex differences in hypertension, including the aspect of age-related changes during the life course of women. The differences between same-aged men and women tend to be smaller with advancing age, but with a greater treatment response in women in all age groups for all observed blood pressure parameters and arterial stiffness. ClinicalTrials.gov identifier NCT03738761.

A Remote Behaviorally Designed Intervention to Promote Physical Activity in Patients With Knee Osteoarthritis: Results of a Pilot Randomized Clinical Trial.

We evaluated a behaviorally designed intervention utilizing gamification and social support to improve physical activity and reduce symptoms in patients with osteoarthritis of the knee (KOA). Veterans with KOA, aged 40-80 years, were enrolled in this randomized controlled trial. Participants received a Fitbit and completed a 2- to 4-week baseline period. A Web-based platform administered biweekly surveys after randomization and tracked physical activity. Participants selected a daily step goal that was 33%, 40%, or 50% above their baseline. The intervention arm received game playing aspects and a social support partner to advance weekly step performance while the control arm only received weekly updates. The primary outcome was the change in steps per day averaged over 2-week intervals. We used mixed effects regression, adjusting for baseline step count. Secondary outcomes assessed the change in KOOS (Knee Injury and Osteoarthritis Outcome Score) over 32 weeks. Thirty-one participants were included in the final analysis. Most participants were male (90.3%), Black (70.96%), had a mean (SD) age of 60 (13) years, and body mass index of 33.7 (5.9) kg/m2. Participants that received the intervention walked a total of 1119 (95% confidence interval: -562, 2799) more steps per day (p = 0.19). The effect was greatest in the first 6 months (1491 [-272, 3254], p = 0.10). Compared with controls, those that received the intervention had improvement over time in total KOOS (mean 2-week change +0.62 [0.031, 1.20] vs -0.38 [-1.04, 0.28], p = 0.02) and several subscales. This intervention demonstrated promise for promoting greater physical activity and improving symptoms in patients with KOA.

Autonomous nervous system responses to environmental-level exposure to 5G's first deployed band (3.5GHz) in healthy human volunteers.

Following the global progressive deployment of 5G networks, considerable attention has focused on assessing their potential impact on human health. This study aims to investigate autonomous nervous system changes by exploring skin temperature and electrodermal activity (EDA) among 44 healthy young individuals of both sexes during and after exposure to 3.5GHz antenna-emitted signals, with an electrical field intensity ranging from 1 to 2V/m. The study employed a randomized, cross-over design with triple-blinding, encompassing both 'real' and 'sham' exposure sessions, separated by a maximum interval of 1week. Each session comprised baseline, exposure and postexposure phases, resulting in the acquisition of seven runs. Each run initiated with a 150s segment of EDA recordings stimulated by 10 repeated beeps. Subsequently, the collected data underwent continuous decomposition analysis, generating specific indicators assessed alongside standard metrics such as trough-to-peak measurements, global skin conductance and maximum positive peak deflection. Additionally, non-invasive, real-time skin temperature measurements were conducted to evaluate specific anatomical points (hand, head and neck). The study suggests that exposure to 3.5GHz signals may potentially affect head and neck temperature, indicating a slight increase in this parameter. Furthermore, there was a minimal modulation of certain electrodermal metrics after the exposure, suggesting a potentially faster physiological response to auditory stimulation. However, while the results are significant, they remain within the normal physiological range and could be a consequence of an uncontrolled variable. Given the preliminary nature of this pilot study, further research is needed to confirm the effects of 5G exposure.

Matched-pair analysis of mCRPC patients receiving 177Lu-labeled PSMA-targeted radioligand therapy in a 4-week versus 6-week treatment interval

BackgroundThe optimal regimen for 177Lu-labeled prostate-specific membrane antigen-targeted radioligand therapy, including treatment intervals, remains under study, with evidence suggesting shorter intervals could benefit patients with high disease volume and rapid progression. This retrospective analysis evaluated treatment toxicity, PSA response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) in matched cohorts of mCRPC patients receiving 177Lu-PSMA-RLT at 4-week versus 6-week intervals.ResultsA PSA response (PSA decline ≥ 50%) was achieved in 47.8% and 21.7% of patients in the 4-week and 6-week treatment interval groups, respectively (p = 0.12). There was a trend towards longer PSA-PFS in the 4-week group compared to the 6-week group (median PSA-PFS, 26.0 weeks vs. 18.0 weeks; HR 0.6; p = 0.2). Although not statistically significant, there was a trend towards shorter OS in the 4-week group compared to the 6-week group (median OS, 15.1 months vs. 18.4 months; HR 1.3; p = 0.5). The 4-week group had a significantly greater decrease in leucocyte and platelet counts compared to the 6-week group (38.5% vs. 18.2% and 26.7% vs. 10.7%; p = 0.047 and p = 0.02). Severe adverse events were modest in both groups.ConclusionsIntensifying treatment intervals from 6 weeks to 4 weeks showed some improvements in PSA response and PSA-PFS for mCRPC patients, but did not significantly affect OS. Additionally, bone marrow reserve was significantly reduced with the intensified regimen. Therefore, the overall benefit remains uncertain, and further prospective studies are needed to compare 4-week and 6-week intervals regarding toxicity, treatment response, and outcome.

Efficacy of Food Industry By-Product β-Glucan/Chitin–Chitosan on Lipid Profile of Overweight and Obese Individuals: Sustainability and Nutraceuticals

Fat-binding nutraceutical supplements have gained considerable attention as potential cholesterol-lowering strategies to address dyslipidemia in overweight and obese individuals. This study aimed to evaluate the effects of a polysaccharide-rich compound containing β-glucan/chitin–chitosan (βGluCnCs) on lipid profiles and lipoprotein function. In a prospective, two-arm clinical trial, 58 overweight and obese individuals were randomized to receive either 3 g/day of βGluCnCs or a placebo (microcrystalline cellulose) for 12 weeks. Serum lipids and lipoprotein functions were assessed at baseline and at 4-week intervals throughout the study. The administration of βGluCnCs led to a significant increase in HDL cholesterol (HDLc) levels and improved HDLc/non-HDLc and HDLc/total cholesterol (TC) ratios, while reducing apolipoprotein B (ApoB) levels (p &lt; 0.05). However, the intervention did not affect HDL particle diameter, particle number, or lipoprotein functionality. Women demonstrated greater sensitivity to changes in HDLc during βGluCnCs supplementation, whereas men exhibited a significant reduction in ApoB levels. When stratified by baseline LDL cholesterol (LDLc) levels (cut-off: 130 mg/dL), the increase in HDLc and the ApoA1/ApoB ratio was found in the low-LDL group. In contrast, the high-LDL group experienced a significant reduction in atherogenic non-LDLc and LDLc, along with an improvement in HDL’s antioxidant capacity after βGluCnCs intervention. These changes were not statistically significant in the placebo group. In conclusion, our study demonstrated that daily supplementation with βGluCnCs significantly improved lipid profiles, with effects that varied based on sex and baseline LDLc levels.

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies.

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

Comparative study of microneedling monotherapy versus microneedling with autologous platelet-rich plasma for the treatment of stretch marks (striae distensae) and post-surgical scars: Clinical and dermoscopy outcomes

Objectives: Stretch marks and post-surgical scar marks may have negative cosmetic and psychological impacts.. Thus, this study aimed to compare the efficacy and safety of microneedling monotherapy versus microneedling in combination with autologous platelet-rich plasma (PRP) for the treatment of stretch marks and post-surgical scars. Material and Methods: This was a prospective randomized non-controlled study. A total of 30 study participants with stretch marks and post-surgery scars were enrolled and randomly divided into two groups, each with 15 study participants. All received three treatment sessions using microneedling monotherapy (Group A) or autologous PRP with microneedling (Group B) at 4-week intervals. Clinical response to treatment was assessed at the end of 20 weeks by comparing clinical photographs, Manchester Scar scale (MSS) score, dermoscopy images, and patient satisfaction scores. Results: At the end of the study, statistically significant esthetic improvement in terms of MSS scores was seen in Group B when compared to Group A. In Group A, 73.3% of the study participants were satisfied while in Group B, 86.6% were very satisfied with the results. Dermoscopy pictures substantiated the findings of clinical improvement. No major side effects were documented. Conclusion: PRP in combination with microneedling has a better outcome as compared to microneedling monotherapy. Furthermore, dermoscopy is a non-invasive tool that can be used to evaluate therapeutic response.

Timing of intravenous immunoglobulin treatment and outcome in Guillain-Barré syndrome: Is time nerve?

Despite treatment, a considerable proportion of patients with Guillain-Barré syndrome (GBS) experience poor recovery, highlighting a therapeutic need. There is a lack of evidence that treatment timing affects recovery. This study aims to investigate the effects of intravenous immunoglobulin (IVIg) timing on disability and speed of recovery in GBS. We performed a retrospective study of 136 IVIg-treated GBS patients admitted to two Korean centers between 2010 and 2021. We analyzed the effect of time to IVIg on the GBS disability scale (GBS-DS) and the degree of improvement from nadir (∆GBS-DS) at 1, 3, 6, and 12 months, as well as the time to regain the ability to walk or run unaided. Time to IVIg was treated either as a continuous variable or categorized into 1-week intervals to explore critical time windows. Known prognostic factors, the modified Erasmus GBS Outcome Scores on admission and pre-treatment serum albumin levels were adjusted as covariates. Shorter time to IVIg was independently associated with better GBS-DS, greater ∆GBS-DS, and shorter time to walk or run unaided at all time points. The therapeutic effect of IVIg was notably diminished when administered beyond the first 2 weeks of onset. Our study highlights the timing of IVIg as a modifiable prognostic factor in GBS. The earlier IVIg is initiated, the better the outcomes, with the ideal time window being within the first 2 weeks. These findings underscore the importance of prompt diagnosis and early intervention to optimize recovery in GBS patients.

Depressive symptoms and goal pursuit: Between-person and reciprocal within-person effects in a multi-wave longitudinal study.

Depressive symptoms, goal progress, and goal characteristics are interrelated, but the directionality of these relationships is unclear. In a 6-wave longitudinal study (N = 431; 2002 total surveys), we examine the bidirectionality of the relationships between depressive symptoms, goal characteristics (commitment, self-efficacy, and perception of other's support), and goal progress for academic and interpersonal goals at 2-week intervals. Separate random-intercept cross-lagged panel models were tested for each goal characteristic across both goals. At the within-person level, goal progress significantly positively predicted commitment, self-efficacy, and perception of others' support for the goal. Most of the other hypothesized paths were nonsignificant, including paths between depressive symptoms and progress. At the between-person level, all variables were significantly correlated, with some effects significantly larger for the interpersonal than the academic goal. The results suggest that when it comes to depressive symptoms and goal pursuit, general tendencies may be more important than variations over 2-week intervals.

Impact of Same Red Blood Cell Infusion at Different Intervals on Premature Infants' Hemoglobin Levels.

Blood transfusions are performed in small amounts in premature infants. Few studies have focused on the effect of the same red blood cell (RBC) package at different intervals on increasing hemoglobin(Hb) concentration. We aimed to determine the effect of infusion of the same RBC package at different time intervals on Hb levels in premature infants. Data were collected about premature infants who received the same package of RBC transfusion at two different intervals. Venous blood Hb levels before and within 24hours after transfusion were measured for the first and second transfusions. Overall, 196 premature infants with anemia were included in the study. The data were categorized into four groups (Group I, Group II, Group III and Group IV) based on the varying intervals between transfusions of the same red blood cells. Hb levels of the first and second transfusions with the same RBC package showed a significant difference pre and posttransfusion. Hb increments varied among groups: Group I (43.00 g/L), Group II (34.50 g/L), Group III (32.00 g/L), and Group IV (32.50 g/L), with Group I demonstrating a significant difference compared to Groups II, III, and IV (P<0.05), while no differences were noted among the latter groups. In premature infants with anemia, hemoglobin levels significantly increased after infusion of the same RBC package at different intervals. An interval of 1week had the most significant effect. There are differences in the effect of infusion of the same RBC at different time intervals on hemoglobin levels in premature infants. An interval of 1week had the most significant effect.

Influence of cocaine use reduction on markers of immune function

This study determined the effects of reduced cocaine use on immune function. Treatment seeking participants with Cocaine Use Disorder enrolled in a 12-week contingency management trial to reduce cocaine use. Participants were randomly assigned 1:1:1 to High Value Reinforcers (i.e., $55/negative urine sample) for cocaine abstinence (n = 41), Low Value Reinforcers (i.e., $13/negative urine sample) for cocaine abstinence (n = 33) or Non-Contingent Control (n = 33). Immune measures were collected at 6-week intervals. The High Value group had greatest use reductions, increased erythema and IL-6 and decreased IL-10 and CCL5, suggesting an activated immune response. Cocaine use reduction may promote changes in immune health.