6-month Study Research Articles

Standing balance test for fall prediction in older adults: a 6-month longitudinal study.

A core component of older adult health care assessment includes identifying fall risk, which also includes identifying those with subtle balance deficits. To compare body displacement of the Center of Pressure (CoP) and time held during the balance test. Also, to examine whether balance tests at baseline can predict falls after 6months. A longitudinal study with 153 community-dwelling older adults, between 60-89years old. Anteroposterior (AP) and mediolateral (ML) amplitude and velocity CoP displacements were assessed in four upright positions using a force platform: double-leg, semi-tandem, tandem, and single-leg stances, with a maximum duration of 30s each. Adjusted repeated measures ANOVA were used to compare the differences among the balance positions. Comparisons between males and females were also conducted. Logistic regression adjusted for confounders was performed to verify whether upright balance tests can predict future falls. As the base of support narrows, body sway increases. A decrease in stance time was observed across the balance stages, i.e., double-leg/semi-tandem versus tandem versus single-leg stances. The mean duration held in the single-leg stance was 14.8s and for tandem was 22.2s. Similar stance durations were observed for double-leg and semi-tandem stances. Males were able to maintain balance positions longer than females even with greater CoP displacement. ML amplitude of CoP displacement and the time held during tandem and single-leg positions were able to predict falls after 6months (p < 0.05). In clinical practice in which only stance time is recorded, it is possible to interchangeably use the double-leg or semi-tandem stance. To identify early signs of imbalance, we suggest setting a time limit for the balance test equal to or greater than 23s, as 10s appear to be insufficient to detect subtle balance deficits. The time maintenance on tandem and single-leg positions was able to predict future falls.

Long-term outcome of transanal irrigation for individuals with spina bifida: a 12-year experience study.

Transanal irrigation (TAI) effectively addresses fecal incontinence and improves quality of life in individuals with spina bifida. Given the scarcity of follow-up studies lasting > 5years and reports of numerous TAI discontinuations, we assessed the enduring effectiveness and impact of TAI > 10years after its initiation on the quality of life in individuals with spina bifida. We recruited individuals with spina bifida enrolled in a bowel management program who initiated TAI in 2010 and participated in 4-month and 3-year follow-up studies at a spina bifida clinic. Raw data on bowel-related characteristics at baseline and after 4months and 3years of TAI were collected, and new survey-based demographic information, bowel-related characteristics, and the Fecal Incontinence Quality of Life scale scores were analyzed alongside extant datasets. Among 34 participants (age, mean [standard deviation] 17.7 [3.2] years), the mean follow-up was 11.8 (0.3) years; 21 participants persistently used TAI (persistent users), 12 discontinued TAI (discontinued users), and 1 used TAI and antegrade continence enema at the time of analysis. The fecal incontinence rate among persistent users decreased from 76.2% at baseline to 14.3% at the time of analysis; 11 (91.7%) discontinued users had fecal incontinence before TAI initiation, and the majority of discontinued users (66.7%) discontinued TAI because of improved bowel function. The fecal incontinence rate and quality of life did not differ significantly between discontinued users and persistent users. TAI effectively alleviated fecal incontinence among persistent users. One-third of users discontinued TAI but had improved fecal continence. We recommend periodic bowel function evaluation in TAI users and to reevaluate the necessity for TAI maintenance.

Relationship between reticulospinal system sensitization and proprioceptive pathways in the development of dynamic spasticity (ReProDS) post-spinal cord injury: protocol for a prospective, observational cohort study.

Dynamic spasticity (DS) is a common complication post-spinal cord injury (SCI), marked by intermittent increases in muscle tone during postural transitions or movement. Despite its prevalence, high-quality research on DS incidence, risk factors, and underlying mechanisms in SCI patients remains limited. With the growing application of spinal cord stimulation (SCS) for spasticity control, the role of proprioception in DS development has garnered attention. Additionally, advances in diffusion tensor imaging (DTI) allow for the analysis of the reticulospinal tract's (RST) role in postural control among SCI patients. However, the impact of microstructural changes in RST and proprioception on DS following SCI remains unclear. To investigate the relationship between microstructural changes in the RST and proprioceptive circuits in SCI patients, exploring their association with DS and potential predictive factors that influence recovery. This is a 12-month prospective cohort study. The neurophysiological and global functional status of the participants will be assessed. Primary outcomes include DTI indices of RST and proprioception, and spasticity assessment. Secondary outcomes include auditory startle reflex (ASR), H-reflex, shear wave velocity (SWV), overall functional status including spinal cord independence measure, gait analysis, modified Barthel Index, and the 36-item short form health survey. Data will be collected at 1, 3, 6, and 12 months after enrolment. Matched healthy controls will be measured during the same period after recruitment. This study is the first to explore the role of microstructural changes in the RST and proprioception in the assessment and prediction of DS following SCI. The findings aim to enhance theoretical understanding of SCS in spasticity management and to establish pre-treatment criteria for SCS interventions targeting motor function recovery in SCI. ChiCTR2400090724.

A phase 4, multicenter, global clinical study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib.

Pexidartinib is effective in patients with tenosynovial giant cell tumor (TGCT) for whom surgery is not feasible. Durability of response after discontinuation of pexidartinib and the safety and efficacy of restarting pexidartinib have not been previously recorded. This phase 4 study was designed to mimic the real-world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug. This was a global, multicenter, phase 4 study that enrolled patients with TGCT who were experiencing clinical benefit from pexidartinib in one of four prior phase 1 or phase 3 studies investigating pexidartinib in the disease. Patients could choose to continue pexidartinib at the same dose (the treatment-continuation cohort) or discontinue treatment with the option to restart pexidartinib (the treatment-free/retreatment cohort). Tumor progression determined by Response Evaluation Criteriain Solid Tumors (RECIST) version 1.1, patient-reported outcomes (the Patient-Reported Outcomes Measurement Information System-Physical Function [PROMIS-PF] questionnaire and the EuroQol 5-dimension, 5-level [EQ-5D-5L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment-free/retreatment cohort who remained treatment-free at month 12 and 24; this did not depend on disease progression. Thirty-two patients were enrolled: 21 chose to enter the treatment-continuation cohort, and 11 entered the treatment-free/retreatment cohort. During the treatment-free period, six of 11 (54.5%) patients in the treatment-free/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment-continuation cohort had disease progression. Over the 24-month study, three of 11 (27.3%) patients in the treatment-free/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (n=1 each). The probability of remaining treatment-free in the treatment-free/retreatment cohort was 73% (95% confidence interval, 37%-90%). In the treatment-free/retreatment cohort, the median progression-free survival of the treatment-free period was 22.8 months (95% confidence interval, 1.6 months to not estimable). By 6 months of retreatment, all retreated patients achieved new disease stabilization with no new safety concerns; two patients had clinically significant improvements in PROMIS-PF and EQ-5D-5L visual analog scale scores. The mean PROMIS-PF and EQ-5D-5L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort. In this small phase 4 study designed to evaluate outcomes in patients who stopped and restarted pexidartinib, 54.5% of patients who discontinued pexidartinib showed PD, with a median progression-free survival of 22.8 months. Each of the three patients who restarted pexidartinib stopped progressing, and some reported a new gain in physical function. No PD was detected in patients who remained on treatment, and the safety profile did not indicate long-term hepatotoxicity or any new safety concerns. Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended. This study examined what happens when patients stop taking pexidartinib (after it has helped them) to see whether it is safe and effective to restart if needed. Thirty-two patients were followed for 2 years: 21 chose to continue pexidartinib and did not experience disease progression, while 11 chose to stop pexidartinib; 54.5% of them had disease progression within 2 years. Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened. Restarting pexidartinib was safe and effective in these patients.

Study of Knowledge, Attitudes and Practices of Family Planning: Case of Female Staff of the Communal Medical Center (CMC) of Flamboyants, Conakry, Guinea

&amp;lt;i&amp;gt;Introduction:&amp;lt;/i&amp;gt; The aim was to assess the knowledge, attitudes and practices of female staff on family planning at the Flamboyants Communal Medical Center. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; This was a 3-month cross-sectional, prospective, descriptive and analytical study involving women (doctors, midwives, laboratory technicians and nurses) working at the Flamboyants CMC and agreeing to participate in the study. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; The contraceptive prevalence was 61.9%. All respondents were aware of FP (100%). The most commonly cited contraceptive methods were: the intrauterine device (IUD) at 85.7%, the Jadelle implant (79.4%) and the contraceptive pill (68.3%). More than 8 out of 10 respondents (81.0%) were in favor of using family planning. Most of the respondents, 74.5%, discussed family planning with their spouses and 70.2% of the spouses were in favor of FP. The most frequently used method was the pill (59.0%). The factors associated with the use of FP were: dialogue with the spouse on contraception (p = 0.018), marriage (p = 0.012) and good attitude of the spouse towards FP (p = 0.000). &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Improving this prevalence would require the involvement of spouses and midwives during counseling during antenatal and postpartum follow-up.

Machine learning-based crop type detection and vegetation mon-itoring using Sentinel-1 SAR and Landsat 8

This study explores the use of machine learning for crop type detection and vegetation monitoring in arid and semi-arid regions, specifically in Biskra and Khenchela, Algeria. Traditional field-based agricultural monitoring is labor-intensive and limited in spatial coverage, prompting the need for more efficient and scalable methods. The research integrates Synthetic Aperture Radar (SAR) data from Sentinel-1 and optical imagery from Landsat 8 to enhance the classification of different crop types and track vegetation dynamics. Key metrics such as radar backscatter and Normalized Difference Vegetation Index (NDVI) are employed to distinguish between irrigated and rainfed crops. The Random Forest algorithm is utilized for classification, with training data derived from field surveys, high-resolution satellite imagery, and existing land cover maps. The Google Earth Engine (GEE) platform facilitates large-scale data processing, providing real-time agricultural analysis. Over the 12-month study period (January to December 2020), the integrated approach demonstrated high accuracy, achieving over 85% precision in classifying key crops such as date palms, cereals, and vegetables. Results indicate that SAR and NDVI data provide complementary insights into vegetation health, phenology, and agricultural practices in different climatic zones. This methodology offers a promising solution for improving agricultural monitoring and resource management in arid and semi-arid regions, enhancing food security and optimizing water usage. The study’s findings also underscore the value of satellite-based remote sensing for large-scale, real-time agricultural analysis.

Adiponectin may play a crucial role in the metabolic effects of GLP-1RAs treatment in patients with Type 2 Diabetes Mellitus: a preliminary longitudinal study.

Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk. We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide. In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p < 0.05); a significant decrease in LDL cholesterol levels (p < 0.05) and triglycerides (p < 0.01); and a significant increase in serum adiponectin levels (p < 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p < 0.05). In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.

Plasma Rich in Growth Factors Compared to Xenogenic Bone Graft in Treatment of Periodontal Intra-Osseous Defects—A Prospective, Comparative Clinical Study

Background: Periodontal intra-bony defects are challenging conditions in dental practice, often requiring regenerative approaches for successful treatment. This clinical study aimed to compare the effectiveness of plasma rich in growth factors (PRGF) versus xenogenic bone graft (BXG) in addressing intra-bony defects. Methods: Forty patients aged between 30 and 50 years presenting with generalized periodontitis were included. The study assessed various parameters, including relative attachment level (RAL); probing pocket depth (PPD); gingival marginal level (GML); intra-bony defect depth (IBDD) at baseline, 3, and 6 months; and level of pain, post-operative bleeding, and swelling, as patient-reported outcomes during the first seven days post operation. Results: The results revealed that both PRGF and BXG treatments led to significant reductions in IBDD over the 6-month study period. PRGF demonstrated significant advantages in GML enhancement and post-operative pain management during the initial post-treatment days. However, BXG showed a significantly greater reduction in IBDD compared to PRGF. Post-operative bleeding and swelling levels were comparable between the two treatments. Conclusions: These findings underscore the efficacy of both PRGF and BXG in periodontal regeneration, with treatment decisions guided by patient-specific factors and clinical goals.

Assessment of Cardiac Autonomic Function by Short-Term Sensor-Based and Long-Term Heart Rate Variability Analyses in Individuals with Spinal Cord Injury After Long-Term Table Tennis Training

This study aimed to examine the acute and chronic effects of an exercising table tennis program on cardiac Autonomic Nervous System (ANS) and functional capacity in people with tetraplegia. Twenty males with tetraplegia (C6–C7), with a mean age of 38.50 ± 4.04 years old, were randomly assigned into two equal groups: A, who followed a 6-month exercise training program with table tennis 3 times per week, and B, who remained untrained. Additionally, 11 healthy sedentary men (group C) with a mean age of 39.71 ± 5.87 years old participated in the study as healthy controls. At baseline, all participants underwent a short-term (5 min) and a long-term (24 h ambulatory) ECG monitoring to evaluate the heart rate variability (HRV) indices and a maximal arm ergometric and dynamometric testing of the upper limbs. Moreover, the acute cardiac autonomic responses to maximal arm cycle exercise test were evaluated by Polar S810i sensor chest strap. At the end of the 6-month study, all parameters were revaluated only in groups A and B. At baseline, there was no statistically significant difference between the two patient groups. However, intra-group changes at the end of the 6-month study regarding the 24-h HRV monitoring indicated that group A statistically increased the standard deviation of R-R intervals (SDNN) by 13.9% (p = 0.007), the standard deviation of R-R intervals calculated every 5 min (SDANN) by 8.4% (p = 0.007), the very low frequency (VLF) by 7.1% (p = 0.042), and the low frequency [LF (ms2)] by 10.5% (p = 0.009), which almost reached the levels of group C. Favorable improvements were also noticed at the end of the study for group A in maximal exercise time of the upper limbs by 80.4% (p &lt; 0.001) and maximal strength of the right hand by 27.8% (p &lt; 0.001). Linear regression analysis after training showed that maximal exercise time was positively correlated with SDNN (r = 0.663, p = 0.036) and with LF (ms2) (r = 0.623, p = 0.045). Our results indicate that a 6-month table tennis training program is efficient and can improve cardiac ANS activity mainly by increasing sympathovagal balance.

Predictors of consistent condom use among male construction workers who have engaged in concurrent sex with regular sex partners, casual sex partners, and sex workers over a 3-month period

ABSTRACT This study investigates the predictors of consistent condom use among male construction workers in South Africa who reported concurrent sexual relationships with regular partners, casual partners, and sex workers over a 3-month period. A cross-sectional survey was used to collect data from a convenience sample of 450 male workers across 18 construction work sites in the Western Cape province. Of these, 245 (54%) indicated that they had engaged in sex with all three partner types during the 3-month study period. Hierarchical multiple linear regression was then used to assess consistent condom use as a function of demographic, experiential, behavioural and cognitive characteristics. Three statistically significant predictors of consistent condom use were identified: perceived control over condom use (β = 0.252, p < 0.001), positive attitude toward condom use (β = 0.154, p < 0.05) and fear of HIV infection (β = 0.121, p < 0.05). These findings highlight the high prevalence of sexual concurrency among study participants. It also suggests that amid declining condom use, interventions which focus on enhancing an individuals’ condom application skills and efficacy, that foster positive attitudes toward condom use and that strategically incorporate fear-based messaging within a multilevel framework may potentially increase condom use among individuals in concurrent sexual relationships.

The Algorithm and the Org Chart: How Algorithms Can Conflict with Organizational Structures

Algorithms are introducing changes to individuals? jobs, but do algorithms also lead to changes in the structures of organizations themselves? Organizational structures, as often formalized into organization (org) charts, are meant to facilitate coordinated decision-making. Yet our 10-month ethnographic study of a large online retail company reveals why the organizational structures that facilitate effective decision-making by humans may be in tension with the organizational structures that facilitate effective decision-making using algorithms. Our findings show that the human decision-makers needed small, divided-up sets of decisions, and they had previously accomplished this through how they structured individuals' roles and teams in the org chart. In contrast, when data scientists developed a new algorithm and first deployed it within organizational structures meant to support human decision-making, they realized that these small divided-up decision spaces were arbitrarily constraining the algorithm's search space. When not constrained in this manner, the algorithm could identify and recommend better solutions, but those optimal solutions did not always align with the structure of roles and teams in the org chart. This study suggests that as algorithms are integrated into the workplace, organization designs may begin to more explicitly reflect the contours of those algorithms' behaviors.

Maternal and neonatal risks and outcomes after bariatric surgery: a comparative population based study across BMI categories in Qatar

The impact of Bariatric Surgery (BS) on maternal and neonatal outcomes among pregnant women is not fully understood, especially in comparison to different weight categories. The primary aim of this study is to assess the factors associated to women who have undergone BS. The study also investigates the maternal and neonatal outcomes amongst this group in comparison to the three Body Mass Index (BMI) groups (women with obesity, overweight and normal weight). A 12-month population-based retrospective study was conducted using registry data from the PEARL-Peristat Study at the Women's Wellness and Research Center (WWRC) in Qatar from January 1, 2017, through December 31, 2017. Both univariate and multivariable regression analyses were employed to scrutinize risk factors and maternal and neonatal outcomes. The study included 6212 parturient women, of which 315 had a history of BS, while 5897 with no BS history. Qatari women, aged 35 and higher, with parity > 1, diabetes, and hypertension were more likely to be in the post-BS group. Women in the post-BS group were found to be more likely to have a cesarean delivery (37.5% vs. 24%, Adjusted Odds Ratio (aOR) = 1.59, CI 1.18–2.14), preterm babies (10% vs. 7%, aOR = 1.66, CI 1.06–2.59), and stillbirth (1.6% vs. 0.4%, aOR = 4.53, CI 1.33–15.50) compared to the normal weight women group. Moreover, post-BS women had a higher risk of low-birth-weight neonates than women with obesity (15% vs. 8%, aOR = 1.77, CI 1.153–2.73), overweight (15% vs. 7%, aOR = 1.63, CI 1.09–2.43), and normal weight (15% vs. 8%, aOR = 1.838, CI 1.23–2.75). Finally, women in the post-BS group were more likely to have low-birth-weight neonates amongst term babies than women with obesity and overweight. Pregnancies with post-BS should be considered a high-risk group for certain medical outcomes and should be monitored closely. These findings may guide the future clinical decisions of antenatal and postnatal follow-up for post-BS women.

Nonclinical Similarity of the Biosimilar Candidate ABP 938 with Aflibercept Reference Product.

ABP 938 is being developed as a biosimilar to Eylea® (aflibercept reference product [RP]), an anti-vascular endothelial growth factor (VEGF) drug used in the management of retinal diseases. Previously, a comparative analytical similarity assessment demonstrated that ABP 938 and aflibercept RP have the same amino acid sequence and exhibit similar higher-order structure and biological activity. The nonclinical studies described here were designed to assess the in vitro pharmacology and the in vivo pharmacokinetics (PK), toxicokinetics (TK), and safety profiles of ABP 938 compared to aflibercept RP. In vitro target-binding kinetics and affinity for VEGF-A and placental growth factor (PIGF) isoforms were evaluated using surface plasmon resonance (SPR). Effector functions were assessed by cell-based assays. PK was evaluated in a nonterminal intravitreal (IVT) ocular distribution study in rabbits. Safety was assessed in a 1-month IVT study in cynomolgus monkeys. SPR results demonstrated that ABP 938 is similar to aflibercept RP in binding kinetics and affinity for VEGF-A111, VEGF-A121, VEGF-A165, VEGF-A189, PlGF-1, and PlGF-2 isoforms. No antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity was observed with ABP 938 and aflibercept RP. Results from thenonterminal ocular distribution study in rabbits indicated that there were no meaningful differences in the distribution kinetics between intravitreally injected ABP 938 and aflibercept RP. Additionally, there was no evidence of ocular or systemic toxicity associated with IVT administration of ABP 938 in a repeat-dose, 1-month toxicology study in cynomolgus monkeys; toxicokinetic and toxicology profiles were similar to aflibercept RP. This integrated assessment of results from the in vitro pharmacology assessment and in vivo PK and TK/toxicology profiles formed the nonclinical portion of the totality of evidence demonstrating ABP938 is a biosimilar to aflibercept RP.

Comparing fermented food and vitamin E on exercise-mediated Nrf2/ARE activation in middle-aged/ elderly: A randomized, double-blind clinical study

Objective: This study investigated the effects of fermented papaya preparation (FPP®) and vitamin E on gene expression in middle-aged/elderly individuals, leveraging FPP’s established antioxidant and immune-regulatory benefits. Methods: Graded Exercise Walking Test was administered twice weekly for 6 months. Total Antioxidant capacity (TAC) and gene expression (Nrf2, NQO1, HO-1) in PBMC were measured monthly. Results: Throughout the 6-month study, routine biochemistry and BMI remained stable. Both treatments significantly improved Total Antioxidant Capacity (TAC), Vitamin E exhibiting earlier effects (3 months). Notably, FPP® supplementation led to sustained over-expression of nuclear Nrf2 in all subjects, surpassing Vitamin E’s effects. NQO1 gene expression was rapidly and consistently upregulated in the FPP group, exceeding baseline and Vitamin E levels throughout the study. HO-1 gene expression was upregulated by FPP at 1 month in younger age quartiles (Q1-2) and at 3 and 6 months in all subjects, regardless of age and gender. In contrast Vitamin E did not significantly impact Nrf2, NQO1, or HO-1 gene expression. Conclusion: These findings demonstrate that FPP, unlike Vitamin E, potentiates Nrf2 signaling, triggering a downstream epigenetic cascade. Notably, our clinical data reveal that physical exercise combined with functional food supplementation partially restores impaired Nrf2 signaling in elderly individuals.

Chronic pain in older adults with disabilities is associated with cognitive impairment-a prospective cohort study.

Chronic pain may be an important factor influencing cognitive impairment; however, there is limited research on that link in older adults with disabilities. We aimed to determine the association between chronic pain and cognitive impairment in older adults with disabilities. This 24-month prospective cohort study involved 143 Japanese older adults (≥65 years of age) with long-term care insurance. Chronic pain was defined as pain persisting for ≥3 months, and cognitive impairment was defined as a Mini-Mental State Examination score ≤ 23. We employed logistic regression analysis with chronic pain as the independent variable and cognitive impairment as the dependent variable after propensity score matching (PSM). Sixty-six participants were selected using PSM, and logistic regression analysis showed that chronic pain was significantly associated with cognitive impairment (odds ratio: 4.103, 95% confidence interval: 1.455-11.567, P = 0.008). To prevent cognitive impairment in older adults with disabilities, the management of chronic pain should be considered, as they are related.

Treatment satisfaction and effectiveness of Lurasidone on quality of life and functioning in adult patients with schizophrenia in the real-world Italian clinical practice: a prospective 3-month observational study.

Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. NCT06527885 retrospectively registered (01/08/2024).

Pharmacokinetic/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham.

Pegcetacoplan is a complement C3/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham-treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose-response and PK/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15 mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear-with-time over the 24-month maximal study duration. Disease-specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and >20 intermediate or large drusen groups (≥63 μm) at baseline. The dose-response model estimated 0.80-fold (95% CI: 0.75, 0.84) and 0.83-fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log-transformed vitreous pegcetacoplan concentration in the PK/PD model. PK/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.

Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist.

GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non-clinical and first-in-human (FIH) evaluation of ECC5004/AZD5004, an oral small-molecule GLP-1 RA. ECC5004 was profiled in cell lines overexpressing human GLP-1R, in glucose-stimulated insulin secretion (GSIS) assays in a human β-cell line and non-human primates (NHPs). To evaluate safety, ECC5004 was orally administered to NHPs for 9 months and a phase I, double-blind, placebo-controlled FIH study was conducted. This study evaluated single doses of ECC5004 (1-300 mg) in healthy volunteers, and multiple daily doses (5, 10, 30 and 50 mg) in patients with T2DM for 28 days. ECC5004 bound to the hGLP-1R (IC50 = 2.4 nM) augmented cAMP signalling without β-arrestin-2 recruitment or receptor internalization. ECC5004 potentiated GSIS in both EndoC-βH5 cells (EC50 = 5.9 nM) and in vivo in NHPs (EC50 = 0.022 nM). Dose-dependent body weight changes compared to control were seen in the 9-month NHP toxicity study. In the first-in-human study, ECC5004 was well tolerated with no serious adverse events. Dose-dependent reductions in glucose and body weight were observed with a dose-proportional exposure at doses ≥25 mg. ECC5004 engaged the GLP-1R across the therapeutic dose range tested and had a safety and tolerability profile consistent with other GLP-1 RAs, along with a pharmacokinetic profile compatible with once-daily oral dosing. These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity. NCT05654831.

Patients with Opioid Use Disorder Choosing Treatment with Extended-Release Naltrexone: A 6-Month Naturalistic Study

Plain Language SummaryThis study looked at the effectiveness of a drug called extended-release naltrexone (XR-NTX) for treating opioid addiction. The study was conducted in Norway, where patients could freely choose this treatment over other options. The study lasted 24 weeks and involved 161 participants aged 18–65 years. The participants were given injections of XR-NTX every 4 weeks. The researchers measured how long the participants stayed in treatment; their use of opioids, alcohol, and other drugs; their cravings for heroin; their satisfaction with the treatment; and any side effects. The results showed that most participants (about 61%) completed the full 24 weeks of treatment. There was a significant decrease in opioid use, and the use of alcohol and other drugs was low. The participants reported high satisfaction with the treatment and low cravings for heroin. Those who completed the full treatment used fewer opioids and were more satisfied with the treatment than those who stopped early. No serious side effects were directly related to XR-NTX use. In conclusion, the study found that XR-NTX treatment resulted in high retention rates, decreased opioid use, and low use of other drugs and alcohol. Participants also reported minimal cravings for heroin and high treatment satisfaction. Those who completed the full 24-week treatment had better outcomes than those who stopped early. This success may be due to the participants’ strong motivation to stop using opioids, facilitated by the XR-NTX treatment.

How initial perceptions of the effectiveness of mind and body complementary and integrative health therapies influence long-term adherence in a pragmatic trial.

Beliefs and perceptions about pain intervention effectiveness when initiating a therapy may influence long-term engagement. This study examines how early perceived effectiveness of complementary and integrative health therapies impacts long-term engagement in a pragmatic trial context. Veterans with chronic musculoskeletal pain participating in a pragmatic trial of provider-delivered complementary and integrative health therapies (acupuncture, chiropractic care, or massage therapy) used alone compared to combining those therapies with self-care therapies (yoga, Tai Chi/Qigong, or meditation). This analysis focuses on 1713 participants using self-care therapies at baseline. 18 Veterans Healthcare Administration Medical Facilities. Prospective cohort study. Predictors of total self-care complementary and integrative health therapy sessions over a 6-month assessment period were assessed using linear regression to determine how strongly perceptions of initial therapy effectiveness was associated with total utilization. Perception of initial therapy effectiveness was assessed at study entry across four domains (pain, mental health, fatigue, and general well-being). In total, 56% (1032/1713) of Veterans reported a positive perceived effectiveness of their recent complementary and integrative health therapy use at study initiation. Older individuals and those using meditation were more likely to report early positive perceptions. Mean number of therapy sessions over the 6-month study was 11 (range 1 to 168). Early positive perceptions had a small effect on overall use, increasing mean sessions by 2.5 (1.3 to 3.6). Other factors such as recent physical therapy use and distance to primary care explained more variation in total utilization. Pragmatic pain trials should examine factors associated with engagement across assigned treatment protocols, especially if any of the treatment protocols being tested are sensitive to long-term engagement.