The Effect of Gua Sha Therapy on Pain in Parkinson's Disease: a Randomized Controlled Trial.

Purpose: Pain is a common yet undertreated symptom of Parkinson's disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD. Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I-III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10). Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred. Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.

Taking the edge off: a feasibility randomized controlled trial of an online mindfulness-based intervention to reduce suspiciousness/paranoia in high positive schizotypy.

Positive schizotypy can uniquely predict the development of psychosis with suspiciousness/paranoia having emerged as a key risk factor, pointing to significant worth in reducing this aspect in individuals with high positive schizotypy. Reduced paranoia in the general population following brief online mindfulness training has been previously reported. This study investigated the feasibility of a 40-day online mindfulness-based intervention (MBI) (n = 12) in the individuals with high positive schizotypy characterized by high suspiciousness/paranoia and to estimate its effect on paranoia as compared with an active control condition using reflective journaling (n = 12). The outcome measures were self-reported trait and VR-induced state paranoia, completed at baseline, after 10 days and post-intervention. The feasibility criteria included retention, adherence, engagement, and acceptability. There was 100% retention, excellent adherence to content and engagement, with an average MBI session completion rate of 91%. Acceptability, indexed by a self-rated motivation to continue practice post-intervention, was also high. No MBI effect on trait paranoia was observed; however, the MBI group showed a reduction in the VR-induced state paranoia with a medium-to-large effect (d = 0.63). The findings support conducting larger-scale randomized controlled trials to evaluate the effects of online MBIs on reducing suspiciousness/paranoia to mitigate psychosis risk in individuals with high positive schizotypy. Clinical Trial Registration:https://www.isrctn.com/, identifier ISRCTN78697391.

Optimizing Blood Pressure Management in Type 2 Diabetes: A Comparative Investigation of One-Time Versus Periodic Lifestyle Modification Counseling.

Background Type 2 diabetes mellitus (T2DM) often coexists with hypertension, significantly increasing cardiovascular risks. Lifestyle modification counseling has shown promise in managing T2DM and its comorbidities. However, the optimal frequency and structure of counseling for blood pressure control remain uncertain. Our study examines the best approach for managing blood pressure in T2DM patients by comparing the outcomes of two counseling strategies: a single session and periodic counseling over time. Methodology A total of 110 diabetic patients were enrolled, with 52 patients in each group after loss to follow-up. A randomized controlled trial compared one-time counseling (control) to six months of periodic counseling (intervention) on lifestyle modification. A weighing machine, stadiometer, 24-hour dietary recall, food frequency questionnaire, biochemical blood sugar level analysis, and telephonic follow-up were the essential tools used. The data were analyzed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA), employing descriptive statistics, including frequencies, percentages, graphs, mean, and standard deviation. Statistical significance at the 5% level was tested using probability (p) calculations. The Kolmogorov-Smirnov test confirmed normal distribution (p > 0.05). Parametric tests, specifically independent t-tests, were used for between-group comparisons of continuous variables, while categorical variables were analyzed using the chi-square test or Fisher's exact test. Intragroup comparisons over time employed repeated-measures analysis of variance for continuous variables. Changes within groups after six months were assessed using paired t-tests. All statistical analyses adhered to a significance level of p < 0.05. Results The gender distribution at baseline was similar between the control (55.8% male, 44.2% female) and intervention (46.2% male, 53.8% female) groups, with no significant differences (p = 0.327). The mean weight was 66.67 ± 11.51 kg in the control group and 67.14 ± 11.19 kg in the intervention group (p = 0.835), and the body mass index was 25.61 ± 4.09 kg/m² and 26.29 ± 6.01 kg/m², respectively (p = 0.503). Clinical parameters such as fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, and blood pressure showed no significant differences between the control and intervention groups at baseline (p > 0.05). After six months, the intervention group exhibited a trend toward lower blood pressure compared to the control group, but the differences were not statistically significant. The mean systolic blood pressure was 132.15 ± 14.867 mmHg in the control group and 129.15 ± 9.123 mmHg in the intervention group (p = 0.218). Changes in blood pressure over the six-month period showed significant decreases within the intervention group, while changes in the control group did not reach statistical significance. The mean difference in systolic blood pressure in the intervention group was 5.54 ± 9.77 mmHg (p = 0.0001), indicating a notable reduction, while the control group had a smaller and statistically insignificant increase of 2.308 ± 9.388 mmHg (p = 0.082). Conclusions This study addresses a significant gap in the literature by comparing the efficacy of one-time vs. periodic counseling in T2DM management. While periodic counseling shows promise in improving diastolic blood pressure, further research is needed to understand its nuanced effects and optimize lifestyle interventions for T2DM patients.

Reducing parenting stress in Chinese parents of children with learning disabilities with a mindful parenting program: A randomized controlled trial.

BACKGROUND: Parents raising children with Learning Disabilities (LDs) often face multiple challenges and high levels of parenting stress, especially in societies with intense academic competitions. Mindful parenting (MP) is an emerging approach that brings mindful awareness to parent-child interactions and is found effective in reducing parenting stress in various parent populations. AIMS: This study examined the effectivenesss of an 8-week online MP program on Chinese parents of children with LDs. METHODS AND PROCEDURES: A MP program was adapted and implemented in an online format with 69 parents of children with LDs. A randomized controlled trial design was used to examine the efficacy of the mindful parenting group compared with a wait-list control group. Parenting stress, mindful parenting and self-compassion were assessed pre- and post-intervention. OUTCOMES AND RESULTS: Compared with the wait-list control group, the MP group participants showed decreased parenting stress (d = 0.62, p < 0.05), improved mindful parenting (d = 0.63, p < 0.05), and increased self-compassion (d = 0.61, p < 0.05). CONCLUSIONS AND IMPLICATIONS: These findings support the effectiveness of an online MP intervention in reducing parenting stress and increasing mindful parenting and self-compassion among Chinese parents of children with LDs. The behavioral and intrapersonal aspects of MP are more amenable to improvement, whereas the attitudinal and interpersonal aspects, particularly non-judgmental acceptance and compassion towards the child, are resistant to change. Future studies should explore strategies to enhance these attitudinal aspects and interpersonal processes of MP.

Association between spontaneous breathing trial methods and reintubation in adult critically ill patients: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Reintubation is associated with higher risk of mortality. There is no clear evidence on the best spontaneous breathing trial (SBT) method to reduce the risk of reintubation. RESEARCH QUESTION: Are different methods of conducting SBT in critically ill patients associated with different risk of reintubation compared to T-tube? STUDY DESIGN AND METHODS: We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs) investigating the effects of different SBT methods on reintubation. We surveyed PubMed, MEDLINE, CINAHL and CENTRAL databases from inception to 26th January 2024. The Surface Under the Cumulative Ranking curve (SUCRA) was used to determine the likelihood that an intervention was ranked as the best. Pairwise comparisons were also investigated by frequentist meta-analysis. Certainty of the evidence was assessed according to the GRADE approach. RESULTS: A total of 22 RCTs were included, for a total of 6196 patients. The network included nine nodes, with 13 direct pairwise comparisons. About 71% of the patients were allocated to T-tube and PSV-ZEEP, with 2135 and 2101 patients, respectively. The only intervention with a significantly lower risk of reintubation compared to T-tube was high flow oxygen (HFO) (RR 0.23, CrI 0.09 to 0.51, moderate quality evidence). HFO was associated with the highest probability of being the best intervention for reducing the risk of reintubation (81.86%, SUCRA 96.42), followed by continuous positive airway pressure (11.8%, SUCRA 76.75). INTERPRETATION: HFO SBT was associated with a lower risk of reintubation in comparison to other SBT methods. The results of our analysis should be considered with caution due to the low number of studies that investigated HFO SBT, and potential clinical heterogeneity related to co-interventions. Further trials should be performed to confirm the results on larger cohorts of patients and assess specific subgroups.

Comparison of the efficacy and safety of vertebroplasty with different pedicle approaches for osteoporotic vertebral.

OBJECTIVE: To compare the efficacy and safety of vertebroplasty through different pedicle approaches in the treatment of osteoporotic vertebral compression fracture osteoporotic vertebral compression fractures (OVCF) by network meta-analysis. METHODS: Pubmed, Embase, Cochrane Library, Web of Science. Database for literature retrieval, retrieval time from the establishment of the database to April 2023, the randomized controlled trials of unilateral vertebroplasty (UVP), bilateral vertebroplasty (BVP), unilateral kyphoplasty (UKP), bilateral kyphoplasty (BKP), curved vertebroplasty (CVP) and curved kyphoplasty (CKP) were screened, evaluated and the data were extracted and included in the analysis. STATA 15.0 and ReMan 5.3 were used for data analysis. This study was registered in the National Institute for Health Research (NIHR) with the registration number CRD42023405181. RESULTS: This study included 16 articles with a total of 1712 patients. The order of visual analogue scale (VAS) improvement from good to bad is CVP > BVP > UVP > CKP > BKP > UKP. The order of kyphotic angles improvement from good to bad is CKP > UKP > UKP > UVP > BVP > CVP. The order of bone cement injection from less to more is UVP > CVP > UKP > CKP > BVP > BKP. The order of bone cement leakage rate from less to more is CKP > CVP > UKP > BKP > UVP > BVP. The order of X-ray exposure time from less to more is CKP > CVP > UVP > BVP > UKP > BKP. The order of operation time from less to more is CVP > UVP > UKP > CKP > BVP > BKP. CONCLUSION: For patients with kyphotic angles, kyphoplasty has unique advantages in improving kyphotic angles. But generally speaking, curved approach can optimize the distribution of bone cement through unilateral approach to achieve the orthopedic effect of bilateral approach, which is a minimally invasive technique with better curative effect and higher safety in the treatment of OVCF.

How much could anemia-related interventions reduce the HIV disparity in adverse birth outcomes?

Women and other people of childbearing potential living with HIV (WLHIV) have a higher risk of adverse birth outcomes than those without HIV (WWHIV). A higher risk of anemia in WLHIV could partially explain this disparity. Using a birth outcomes surveillance study in Botswana, we emulated target trials corresponding to currently available or feasible interventions on anemia. The first target trial evaluated two interventions: initiate multiple micronutrient supplementation (MMS), and MMS or iron and folic acid supplementation by 24 weeks gestation. The remaining target trials evaluated the interventions: eliminate anemia before pregnancy; and jointly eliminate anemia before pregnancy and initiate MMS. We estimated the observed disparity in adverse birth outcomes between WLHIV and WWHIV and compared the observed disparity measure (ODM) to the counterfactual disparity measure (CDM) under each intervention. Of 137,499 individuals (22% WLHIV), the observed risk of any adverse birth outcome was 26.0% in WWHIV and 34.5% in WLHIV (ODM, 8.5% [95% CI, 7.9-9.1%]). CDMs (95% CIs) ranged from 6.6% (4.8-8.4%) for the intervention to eliminate anemia and initiate MMS to 8.4% (7.7-9.1%) for the intervention to eliminate anemia only. Preventing anemia and expanding MMS may reduce HIV disparities in birth outcomes, but interventions with greater impact should be identified.

Comparison of Anti-Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight-Based Dosing of Polyvalent Immunoglobulin.

This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post-exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight). Quantitative serial serum hepatitis A antibody concentrations were measured at baseline and then on days 1, 3, 7, 28, and 50. Fifteen participants completed the trial. Serum hepatitis A antibody concentrations were not different between the study groups at any time point. Pharmacokinetic parameters estimated from participant data were not different between the study groups. The hepatitis A antibody level of all participants exceeded 10 mIU/mL at day 50. While no difference between dosing regimens was found in this study, further research should examine dosing at the lower limit of current Australian recommendations before making policy decisions.

Effects of a multidomain intervention against cognitive decline on dementia risk profiles - Results from the AgeWell.de trial.

INTRODUCTION: Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention. METHODS: Secondary analyses of the AgeWell trial, testing a multicomponent intervention (including optimization of nutrition, medication, and physical, social, and cognitive activity) in older adults with increased dementia risk. We analyzed data from n = 461 participants with complete information on risk/protective factors comprised by LIBRA at the 24-month follow-up. Intervention effects on LIBRA and LIBRA components were assessed using generalized linear models. RESULTS: The intervention reduced LIBRA scores, indicating decreased dementia risk at follow-up (b = -0.63, 95% confidence interval [CI]: -1.14, -0.12). Intervention effects were particularly due to improvements in diet (odds ratio [OR]: 1.60, 95% CI: 1.16, 2.22) and hypertension (OR: 1.61, 95% CI: 1.19, 2.18). DISCUSSION: The AgeWell.de intervention reduced dementia risk. However, several risk factors did not improve, possibly requiring more intensive interventions. HIGHLIGHTS: The AgeWell.de intervention reduced dementia risk according to LIfestyle for BRAin health (LIBRA) scores. Beneficial effects on LIBRA are mainly due to changes in diet and blood pressure. A pragmatic lifestyle intervention is apt to reduce dementia risk in an at-risk population.

POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients (POSITiVE) II-study protocol of a randomized clinical trial.

BACKGROUND: One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. METHODS: "POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. DISCUSSION: POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Effectiveness of a mobile application for independent computerized cognitive training in patients with mild cognitive impairment: study protocol for the NeNaE Study, a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. METHODS: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. DISCUSSION: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Silk-derived sericin/fibroin mixture drink fermented with plant-derived Lactococcus lactis BM32-1 improves constipation and related microbiota: a randomized, double-blind, and placebo-controlled clinical trial.

We previously showed through clinical trials that one plant-derived lactic acid bacteria (LAB) can improve constipation. We preliminarily found that the plant-derived LAB Lactococcus lactis BM32-1 can grow in a mixture of sericin and fibroin, which are extracted from silk and have been reported to help promote health. Thus, in the present study, we evaluated the favorable effect of a sericin/fibroin mixture (S/F-M), which was extracted from silk prepared from cocoons reared in an aseptic rearing system using an artificial diet, fermented with the BM32-1 strain through a clinical trial. The trial was conducted at Hiroshima University from June to October 2022 as a double-blind, placebo-controlled, randomized parallel-group comparative study with 50 eligible subjects (aged 23-71) who had an average defecation frequency of less than 5 times per week. The subjects were instructed to drink 100 mL of fermented S/F-M or placebo every day. After the 12 weeks of the clinical trial period, the average defecation frequency increased significantly-1.4 times higher than that at baseline in the test group-as compared with the placebo group. Furthermore, the fecal microbiota was also compared before and after treatment, revealing that intake of the fermented S/F-M significantly multiplied the relative abundance of the genera Enterococcus and Clostridium, which have been reported to contribute to the amelioration of constipation by improving the gut microbiota and producing butyric acid, respectively. In conclusion, the S/F-M fermented using the BM32-1 strain improves defecation frequency through alteration of the gut microbiota.

Using Flashcards and Descriptive Feedback to Teach Industrial Kitchen Equipment to a Student with Intellectual Disabilities in a Postsecondary Education Program.

With postsecondary education opportunities for adult students with intellectual and developmental disabilities (IDD) on the rise, it is important to find socially validated research-based methods that are appropriate for the university or other community-based postsecondary instructional settings. The present research examines the effects of using flashcards with descriptive feedback and opportunities to respond, to teach one student with intellectual disabilities, enrolled in a postsecondary education-training program, commonly used industrial kitchen equipment. Results showed that discrete trail instruction, which included an error correction strategy of descriptive feedback plus opportunities to correctly respond was highly effective in mastery and maintenance of kitchen equipment identification, and generalization when asked to locate those items in the university kitchen lab.

Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.

With the increase in life expectancy, aging has emerged as a significant health concern. Due to its various mechanisms of action, cardiometabolic drugs are often repurposed for other indications, including aging. This systematic review analyzed and highlighted the repositioning potential of cardiometabolic drugs to increase lifespan as an aging parameter in animal studies and supplemented by information from current clinical trial registries. Systematic searching in animal studies was performed based on PICO: "animal," "cardiometabolic drug," and "lifespan." All clinical trial registries were also searched from the WHO International Clinical Trial Registry Platform (ICTRP). Analysis of 49 animal trials and 10 clinical trial registries show that various cardiovascular and metabolic drugs have the potential to target lifespan. Metformin, acarbose, and aspirin are the three most studied drugs in animal trials. Aspirin and acarbose are the promising ones, whereas metformin exhibits various results. In clinical trial registries, metformin, omega-3 fatty acid, acarbose, and atorvastatin are currently cardiometabolic drugs that are repurposed to target aging. Published clinical trial results show great potential for omega-3 and metformin in healthspan. Systematic Review Registration: crd.york.ac.uk/prospero/display_record.php?RecordID=457358, identifier: CRD42023457358.

The effect of Phytopaj ) Ferula assa-foetida L. oleo gum resin and tragacanth( in patients with COVID-19: A randomized clinical trial.

Objective: Exogenous hydrogen sulfide (H2S) has a positive effect on respiratory diseases. Oleo-gum of Ferula assa-foetida contains this compound. This study assessed the effects of Ferula assa-foetida L. oleo gum resin and tragacanth (Phytopaj) on patients with COVID-19. Materials and Methods: A randomized, single-blinded, controlled trial (RCT) phase 2 was conducted in Mashhad on hospitalized COVID-19 patients. In this RCT, 122 patients were randomly assigned to either receive a 14-day oral phytopaj plus ordinary treatment or ordinary treatment only. Changes in peripheral blood lymphocyte count (LC) and blood oxygen saturation (PO2) were the endpoints. Results: Mean±SD of PO2 in Phytopaj comparison ordinary treatment before intervention was 91.86±4.62 and 91.41±9.18, after the intervention it was 93.22±4.26 and 91.91±5.92 mmHg; before intervention, mean±SD of peripheral blood lymphocyte count was 1015.90±500.55, and 1104.28±543.61, and after intervention, it was 1652.27±921.38 and 1326.12±719.28/µL respectively. Conclusion: Phyopaj is most useful in moderate stages of Covid19, and it is not recommended for elderly patients and patients with comorbidity until more insight is gained.

Chronic Kidney Disease Stage and Cardiovascular and Mortality Events Among Older Adults: The SPRINT Trial.

Rationale & Objective: The risk implications of the Kidney Disease: Improving Global Outcomes (KDIGO) chronic kidney disease classification in older adults are controversial. We evaluated the risk of adverse outcomes in this population across categories of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Study Design: Prospective cohort. Settings & Participants: In total, 2,509 participants aged ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT). Exposure: KDIGO eGFR and UACR categories. We combined KDIGO categories G1 and G2, G3b and G4, as well as A2 and A3. Outcomes: Primary SPRINT outcome (composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes), and all-cause death. Analytical Approach: Multivariable Cox proportional hazard models. Results: Mean age was 79.8 years, and 37.4% were female. The mean eGFR was 64.0 mL/min/1.73 m2, and the median UACR was 13.1 mg/g. In multivariable Cox proportional hazard analysis, compared with participants with eGFR ≥ 60 mL/min/1.73 m2 and UACR < 30 mg/g, there was no statistically significant difference in the risk of the primary outcome among participants with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR < 30 mg/g. However, those with eGFR 45-59 or 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g had higher risk of the primary outcome (HR [95% CI], 1.97 [1.27-3.04] and 3.32 [2.23-4.93], respectively). The risk for all-cause death was higher for each category of abnormal eGFR and UACR, with the highest risk observed among those with eGFR 15-44 mL/min/1.73 m2 and UACR ≥ 30 mg/g (3.34 [2.05-5.44]). Limitations: Individuals with diabetes and urine protein >1 g/day were excluded from SPRINT. Conclusion: Among older adults SPRINT participants, low eGFR without albuminuria was associated with higher mortality but not with increased risk of cardiovascular events. Additional studies are needed to evaluate an adapted chronic kidney disease stage-based risk stratification for older adults.

Using data from participants in the SPRINT trial, we evaluated the association of chronic kidney disease stage with adverse clinical outcomes among adults older than 75 years without diabetes. We found that low level of kidney function determined by a low estimated glomerular filtration rate with moderately or severely increased urine albumin excretion was associated with increased risk for cardiovascular events and all-cause mortality. However, low estimated glomerular filtration rate with normal or mildly increased urinary albumin excretion was not consistently associated with these adverse outcomes. This finding supports the need for additional studies to evaluate an age-adapted classification of chronic kidney disease to improve risk stratification among older adults.

Safety and Short-term Efficacy of a Single Dose of 2†mg Moxidectin in Loa loa-Infected Individuals: A Double-Blind, Randomized Ivermectin-Controlled Trial With Ascending Microfilarial Densities.

Background: In 2018, the US Food and Drug Administration approved the macrocylic lactone moxidectin (MOX) at 8 mg dosage for onchocerciasis treatment in individuals aged ≥12 years. Severe adverse reactions have occurred after ivermectin (IVM), also a macrocyclic lactone, in individuals with high Loa microfilarial density (MFD). This study compared the safety and efficacy of a 2 mg MOX dose and the standard 150 µg/kg IVM dose in individuals with low L loa MFD. Methods: A double-blind, randomized, ivermectin-controlled trial of a 2 mg moxidectin dose was conducted in Cameroon between May and July 2022. It enrolled 72 adult men with L loa MFD between 5 and 1000 microfilariae/mL. Outcomes were occurrence of adverse events (AEs) and L loa MFD reduction rate during the first month off treatment. Results: No serious or severe AEs occurred among the 36 MOX- or the 36 IVM-treated individuals. Forty-nine AEs occurred in the MOX arm versus 59 AEs in the IVM arm. Grade 2 AE incidence was higher among IVM- than MOX-treated participants (38.5% and 14.3%, respectively, P = .043). Median MFD reduction rates were significantly higher after IVM than MOX at day 3 (70.2% vs 48.5%), day 7 (76.4% vs 50.0%), and day 30 (79.8% vs 48.1%). Conclusions: A single 2 mg MOX dose is as safe as 150 µg/kg IVM in patients with low L loa MFD. Further studies with higher MOX doses and in patients with higher MFD are warranted. Clinical Trials Registration: NCT04049851.

Short- and long-term effects of imatinib in hospitalised COVID-19 patients: A randomised trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

Clinical trial designs to assess treatment effects on glomerular filtration rate decline.

Glomerular filtration rate (GFR) decline is used as surrogate endpoint for kidney failure. Interventions that reduce chronic kidney disease (CKD) progression often exert acute GFR reductions which differ from their long-term benefits and complicate the estimation of long-term benefit. Here, we assessed the utility of two alternative trial designs (wash-out design and active run-in randomized withdrawal design) that attempt to exclude the impact of acute effects. Post-hoc analyses of two clinical trials that characterized the effect of an intervention with acute reductions in GFR were conducted. The two trials included a wash-out period (EMPAREG-Outcome testing empagliflozin vs placebo) or an active run-in period with a randomized withdrawal (SONAR testing atrasentan vs placebo). We compared the drug effect on GFR decline calculated from the first on-treatment visit to the end-of-treatment (chronic effect in a standard randomized trial design) with GFR change calculated from randomization to end-of-wash-out, or GFR change from treatment specific baseline GFR values (GFR at start-of-run-in for placebo and end-of-run-in for atrasentan) until end-of-treatment. The effect of empagliflozin versus placebo on chronic GFR slope was 1.72 (95% confidence interval 1.49-1.94) mL/min/1.73m2 /year, similar to total GFR decline from baseline to the end of wash-out period using a linear mixed model 1.64 (1.44-1.85) mL/min/1.73m2 /year). The effect of atrasentan versus placebo on chronic GFR slope was 0.72 (0.32-1.11) mL/min/1.73m2 /year, similar to total slope from a single slope model when estimated from treatment specific baseline GFR values 0.77 (0.39-1.14) mL/min/1.73m2 /year). Statistical power of the two designs outperformed the standard randomized design. Thus, wash-out and active-run-in randomized-withdrawal trial designs are appropriate models to compute treatment effects on GFR decline.