Direct analysis in real time mass spectrometry (DART-MS/MS) for rapid urine opioid detection in a clinical setting.

BACKGROUND AND AIMS: Current laboratory methods for opioid detection involve an initial screening with immunoassays which offers efficient but non-specific results and a subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmation which offers accurate results but requires extensive sample preparation and turnaround time. Direct Analysis in Real Time (DART) tandem mass spectrometry is evaluated as an alternative approach for accurate opioid detection with efficient sample preparation and turnaround time. MATERIALS AND METHODS: DART-MS/MS was optimized by testing the method with varying temperatures, operation modes, extraction methods, hydrolysis times, and vortex times. The method was evaluated for 12 opioids by testing the analytical measurement range, percent carryover, precision studies, stability, and method-to-method comparison with LC-MS/MS. RESULTS: DART-MS/MS shows high sensitivity and specificity for the detection of 6-acetylmorphine, codeine, hydromorphone, oxymorphone, hydrocodone, naloxone, buprenorphine, norfentanyl, and fentanyl in urine samples. However, its performance was suboptimal for norbuprenorphine, morphine and oxycodone. CONCLUSION: In this proof-of-concept study, DART-MS/MS is evaluated for its rapid quantitative definitive testing of opioids drugs in urine. Further research is needed to expand its application to other areas of drug testing.

Prevalence of early initiation of breastfeeding and its associated factors among women in Mauritania: evidence from a national survey.

BACKGROUND: Timely initiation of breastfeeding is crucial for positive health outcomes for babies and mothers. Understanding the factors influencing timely initiation of breastfeeding is vital for reducing child morbidities and mortalities in Mauritania. This study, therefore, assessed the prevalence of early initiation of breastfeeding and its associated factors among women in Mauritania, providing significant insights for improving maternal and child health in the country. METHODS: We performed a secondary analysis of the 2019-2021 Mauritania Demographic and Health Survey data. A weighted sample of 4,114 mother-child pairs was included in the study. We used percentage to present the prevalence of early initiation of breastfeeding. A four-modelled multilevel binary logistic regression was used to examine the factors associated with early initiation of breastfeeding. The regression results were presented using adjusted odds ratio (aOR) with their respective 95% confidence interval (CI). Stata software version 17.0 was used to perform all the analyses. RESULTS: The prevalence of early initiation of breastfeeding was 57.3% (95% CI 54.5, 60.00). Birth order was associated with early initiation of breastfeeding with the highest odds among those in the fourth birth order (aOR 1.61; 95% CI 1.08, 2.39). Mothers who practiced skin-to-skin contact were more likely to initiate breastfeeding early than those who did not (aOR 1.46; 95% CI 1.14, 1.87). There were regional disparities in the early initiation of breastfeeding. The odds of timely initiation of breastfeeding was lower among women who were delivered by caesarean section (aOR 0.22; 95%CI 0.14, 0.36), those who were working (aOR 0.57; 95% CI 0.45, 0.73), those who had four or more antenatal care visits (aOR 0.67; 95%CI 0.47, 0.94)], and those in the richest wealth quintile (aOR 0.61; 95% CI 0.38, 0.98) compared to those who had normal delivery, those who were not working, those who had zero antenatal care visits, and those in the poorest wealth quintile households, respectively. CONCLUSION: Our study found a relatively low prevalence of early initiation of breastfeeding among women in Mauritania. Factor such as birth order, region of residence, mother and newborn skin-to-skin contact after birth, antenatal care visits, caesarean delivery, employment status, and wealth index were associated with early initiation of breastfeeding. Improving optimal breastfeeding practices, such as early initiation of breastfeeding in Mauritania, should be given adequate attention. There is a need for interventions such as baby-friendly facilities, providing an enabling environment for mothers to breastfeed their newborns early. Addressing regional health access disparities is important to improve early initiation of breastfeeding and other maternal, newborn, and child health interventions.

The influence of simultaneous posterior colporrhaphy and perineoplasty on the efficiency and safety of mesh-augmented sacrospinal fixation (apical sling) in advanced POP repair.

BACKGROUND: Pelvic organ prolapse (POP) is one of the most common pathologies of the pelvic floor, and it can be found among 40-60% of women who have given birth. Correction of the defect of the DeLancey level II without reconstruction of the apical defect is doomed to failure. Also, in the structure of pelvic floor defects, there is often an incompetency of the perineal body, as a consequence of traumatic delivery. Perineoplasty is considered to be the main method of correction for perineal body incompetency. However, it is worth mentioning that there are no randomized trials, which estimate the influence of simultaneous correction of the perineal body on the effectiveness of transvaginal apical fixation. METHODS: It is planned to include 310 patients in this trial. Patients who met the inclusion/exclusion criteria will be randomized into 2 groups: 1st group-patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy without perineoplasty, 2nd group-patients who will undergo mesh-augmented sacrospinal fixation with anterior and posterior colporrhaphy and perineoplasty. Patients will be called to an appointment 6, 12, and 24 months after discharge. DISCUSSION: The aim of this trial is to evaluate the efficiency and safety of simultaneous perineoplasty on the clinical and anatomical efficacy of mesh-augmented sacrospinal fixation in advanced pelvic organ prolapse repair. Based on previous studies, it was difficult to estimate and comprehend whether colpoperinoplasty actually reduces the risk of prolapse recurrence. TRIAL REGISTRATION: NCT05422209. Registered on 18 May 2022.

Influence of curing mode and aging on the bonding performance of universal adhesives in coronal and root dentin.

BACKGROUND: This study aims to evaluate the microtensile bond strength (µTBS) of different resin composite restorations bonded to mid-coronal dentin and proximal root dentin using light-cured, chemical-cured, and dual-cured adhesives immediately and after aging. Nanoleakage and degree of cure were also assessed. METHODS: Eighty-four molars were divided into mid-coronal dentin and proximal root dentin. Each group was further subdivided into three subgroups based on the restorative systems used, which involved the utilization of light-cured, chemical-cured, and dual-cured adhesives. Half of the specimens underwent µTBS testing after 24 h, while the other half after aging. Representative specimens were analyzed for nanoleakage. The degree of cure of the tested adhesive systems was also assessed. RESULTS: Aging showed a significant negative effect on µTBS results and led to increased nanoleakage (p < 0.001). Furthermore, in all subgroups, the µTBS values of proximal root dentin were lower compared to mid-coronal dentin, except in the aged subgroup for the system utilizing the dual-cured adhesive. The restorative systems with chemical and dual-cured adhesives demonstrated comparable bonding properties. However, the system with the light-cured adhesive exhibited the worst bonding properties after aging when bonded to proximal root dentin and cured at a large distance (p < 0.05). CONCLUSIONS: All tested restorative systems were negatively affected by aging, and the regional dentin had variable effects on the bonding properties. Clinicians should exercise caution when using the tested light-cured adhesive in areas where the curing distance exceeds 3 mm.

Relationship between longer sleep and serum neurofilament light chain in american adults: evidence from the 2013-2014 US national health and nutrition examination survey.

BACKGROUND: Sleep disturbance is linked to neurodegenerative diseases and the related brain pathophysiology. Serum neurofilament light chain (NfL) is a reliable biomarker for neurological disorders. This study examined the association between sleep characteristics and serum NfL levels in American adults. METHODS: In this cross-sectional study, data from the 2013-2014 US National Health and Nutrition Examination Survey were utilized. Participants were categorized into short (≤ 6 h), normal (7-8 h), and long (≥ 9 h) sleep groups based on their self-reported sleep durations. Sleep duration, trouble sleeping, and diagnosed sleep disorders were queried, forming "sleep pattern (healthy, moderate, and poor)." The association between sleep characteristics and serum NfL levels was assessed using multivariate linear regression models. Stratification and sensitivity analyses were conducted to determine the stability of results. RESULTS: Overall, 1637 participants were included; among them, 48.2% were male and 51.8% were female (mean ± SD, age: 46.9 ± 15.5 years) and 38.8% reported sleeping for ≤ 6 h, 54.4% for 7-8 h, and 6.8% for ≥ 9 h. Participants with longer sleep duration, poor sleep pattern, diagnosed sleep disorders, or trouble sleeping exhibited higher serum NfL levels. A positive correlation was found between extended sleep and elevated serum NfL levels (Adjusted ß = 4.82, 95%CI: 2.2, 7.44, P < 0.001), with no significant correlation observed in the short-sleep group or those with poor sleep pattern. Stratified and sensitivity analyses confirmed the robustness of the relationship between longer sleep and elevated serum NfL levels. CONCLUSIONS: A long sleep duration is associated with higher serum NfL levels than a normal sleep duration in American adults.

DepActive: study protocol for a randomised controlled multicentre trial of telephone-delivered behavioural activation for the treatment of depression in older adults in primary care.

BACKGROUND: Depression is common in older adults and is related to reduced quality of life and functional ability as well as increased mortality and morbidity. Current guidelines recommend psychological treatments for the treatment of depression in adults. Studies show that about 30% of older adults with depression in Sweden receive pharmacological treatment and about 3% receive psychological treatment. However, a majority receive no treatment at all. There is a need for effective and scalable psychological treatment options for older adults with depression in primary care. Behavioural activation is an extensively evaluated, effective, and relatively simple treatment for depression that can be delivered by health care professionals without comprehensive training in psychological treatment. METHODS: We will conduct a randomised controlled 2-armed parallel group multicentre trial comparing treatment as usual in primary care to a five-session telephone-delivered behavioural activation treatment as add on to treatment as usual. The current trial is open labelled. In all, 250 older adults (≥ 65 years) with depression will be recruited from primary healthcare centres in three Swedish regions. The primary outcome is depressive symptoms measured with the Montgomery Åsberg Depression Rating Scale - Self rating version (MADRS-S) after treatment and at 3- and 6-month follow-up. Secondary outcomes include depression diagnoses, activity level (self-rated and measured with accelerometer), and self-rated anxiety, daily functioning, quality of life, self-efficacy, and loneliness. DISCUSSION: There is a need for fully powered studies of brief behavioural activation for older adults with depression delivered by telephone in a primary care context. This study has the potential to improve first-line treatment of depression in older adults in primary care, consequently reducing morbidity and mortality within this population. Increasing the availability and accessibility to effective psychological treatment for depression in older adults is needed to meet future demographic changes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06284889 . Registered February 28, 2024.

The effect of MIND diet on sleep status, anxiety, depression, and cardiometabolic indices in obese diabetic women with insomnia: study protocol for a randomized controlled clinical trial {1}.

BACKGROUND: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is a plant-based and anti-inflammatory diet that has the ability to protect and manage cardiovascular and nervous system diseases. Regarding that insomnia and cardiovascular problems are x`common in type 2 diabetes mellitus (T2DM), the present study will assess the effectiveness of the MIND dietary pattern on sleep quality, cardiometabolic indicators, and other psychological indicators. METHODS: Forty-four overweight/obese T2DM women with insomnia, aged 30-65 years, will voluntarily participate in this randomized controlled trial and will be randomized to receive either a MIND low-calorie diet (MLCD) or a low-calorie diet (LCD) over a 3-month period. Before and after the study, sleep quality, some biochemical and cardiometabolic indices, cortisol, brain-derived neurotrophic factor (BDNF), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress indicators will be assessed. DISCUSSION: The use of dietary interventions in the management of T2DM complications is practical and safe. This research seeks to investigate the capacity of the MIND diet in the management of insomnia and cardiovascular problems of DM. It is expected that the results of this research will provide new perspectives on using an ideal dietary regimen to treat these health conditions. TRIAL REGISTRATION: IRCT20181111041611N8. Registered on August 7, 2023. https://www.irct.ir/trial/71772.

Sleeping <6.55 h per day was associated with a higher risk of low back pain in adults aged over 50 years: a Korean nationwide cross-sectional study.

Background: Patients with low back pain (LBP) often suffer from sleep disorder, and insufficient sleep duration was recognized as a potential risk factor for LBP. Our aim was to explore the exact effect of sleep duration on LBP and the optimal sleep duration to reduce the risk of LBP. Methods: Analyzing data from the Korean National Health and Nutrition Examination Survey (KNHANES), we investigated the association between sleep duration and LBP in individuals aged 50 years and older. We used logistic regression models, interaction stratification analysis, and threshold effect assessment to analyze the relationship between sleep duration and LBP. Results: A total of 6,285 participants, comprising 3,056 males and 3,229 females with a median age of 63.1 years, were enrolled in the study. The association between sleep duration and LBP risk exhibited an L-shaped curve (p < 0.015) in RCS analysis. In the threshold analysis, the OR of developing risk of LBP was 0.864 (95% CI:0.78-0.957, p = 0.005) in participants with sleep duration <6.55 h. Each additional hour of sleep was associated with a 13.6% decrease in the risk of LBP. No significant association was observed between sleep duration ≥6.55 h and the risk of LBP. The risk of LBP did not decrease further with increasing sleep duration. Results remain robust across subgroups. Conclusion: Our findings indicate that shorter sleep duration is a risk factor for LBP in adults aged over 50 years. We revealed an L-shaped association between sleep duration and LBP, with an inflection point at approximately 6.55 h per day. These results underscore the significance of sleep duration as a factor in the risk assessment for LBP.

Elevated Triglyceride-Glucose (TyG) Index Predicts Poor Clinical Outcomes in Critically Ill AECOPD Patients: A Retrospective Study.

Purpose: The triglyceride-glucose (TyG) index is a surrogate biomarker of insulin resistance which has been widely used in intensive care unit (ICU) to predict prognosis. However, its role in critically ill acute exacerbation of COPD (AECOPD) patients remains largely unknown. Material and methods: A total of 645 AECOPD patients were induced in this retrospective cohort study, which extracted data from the eICU Collaborative Research Database (eICU-CRD). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). The primary endpoint includes in-hospital mortality and ICU mortality. The secondary endpoint was sepsis, acute kidney injury (AKI), and acute respiratory failure (ARF). Results: Multivariable Cox regression analysis revealed that the TyG index was independently associated with an increased risk of in-hospital mortality (hazard ratio, HR: 1.45, 95% CI: 1.04-2.01, P = 0.028) and ICU mortality (HR: 2.13, 95% CI: 1.28-3.54, P = 0.004). Moreover, the TyG index was independently associated with an increased risk of sepsis (odds ratio, OR: 1.54, 95% CI: 1.24-1.93, P < 0.001), AKI (OR: 1.57, 95% CI: 1.26-2.02, P < 0.001) and ARF (OR: 1.50, 95% CI: 1.20-1.87, P < 0.001). Kaplan-Meier survival analysis revealed that higher TyG indexes were also related to increased in-hospital mortality and ICU mortality. In addition, the restricted cubic splines regression model demonstrated that the in-hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.897, P for non-linearity = 0.897, respectively). Conclusion: Elevated TyG index was independently associated with an increased risk of poor clinical outcomes in critically ill AECOPD patients. A prospective study to define TyG as a biomarker for prognosis prediction in critically ill AECOPD patients is warranted.

Association Between Opioid and Benzodiazepine Use and All-Cause Mortality in Individuals with Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study.

Background: Opioids and benzodiazepines are frequently prescribed for managing pain and anxiety in chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine whether opioid use, with or without benzodiazepine use, is associated with increased all-cause mortality in COPD patients. Methods: This prospective cohort study included adults aged ≥20 years with COPD from the US National Health and Nutrition Examination Survey 2007-2012. The primary outcome was all-cause mortality, which were obtained through linkage to registries. Weighted Cox proportional hazards regression models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Additionally, subgroup and sensitivity analyses were used to evaluate the robustness of our findings. Results: This study enrolled 811 participants, representing 10.84 million COPD individuals in the United States (mean [standard error] age, 58.7 [0.6] years). During a median follow-up of 9.6 years, mortality rates were 57.8 per 1000 person-years in patients using only opioids, 41.3 per 1000 person-years in patients using only benzodiazepines, 45.7 per 1000 person-years in patients using both opioids and benzodiazepines, and 27.0 per 1000 person-years in patients using neither. In the fully adjusted model, COPD patients prescribed both opioids and benzodiazepines (HR: 1.76; 95% CI: 1.11-2.78) and those prescribed opioids only (HR: 1.68; 95% CI: 1.13-2.49) had significantly higher all-cause mortality compared to non-users. After adjusting for propensity scores, the mortality risk for opioid-only users slightly increased (HR: 1.87; 95% CI: 1.25-2.81). Further, subgroup analysis revealed an elevated mortality risk in patients over 60 years receiving coprescriptions or opioids only, but not in younger participants. In contrast, benzodiazepine-only users aged 60 or younger showed increased mortality risk. Conclusion: Opioid use, with or without benzodiazepine use, was associated with higher mortality in COPD patients over 60, while benzodiazepine-only use was associated with higher mortality aged 60 or younger.

Indirect costs assessment and intangible costs description of rheumatoid arthritis patients with biological therapy in Morocco: ECORAM Study.

INTRODUCTION: The aims of study are to estimate the indirect costs and intangible costs of RA in Morocco and to identify the factors likely to influence these costs among suffering patients. METHODS: In the current study, data were collected by face-to-face interviews using a questionnaire in addition to the patient's files. Indirect costs including productivity losses and formal care, and intangible costs such as the cessation of physical and leisure activities, family care and divorce or remaining single until menopause's age for women due to the disease were reported for 110 RA patients. RESULTS: The results show that among patients who lost totally or partially their salary, the annual average costs is $2337.73 ± 1649.80 per patient, with a minimum and a maximum of $600 and $9630 respectively. As regards formal care, only 13 patients reported that they paid for care services; the annual average cost was $421.84 ± 261.34 with a minimum of $252 and a maximum of $1200. Statistical analysis revealed significant differences between annual lost salary and gender (p = .04) disease duration (p = .016) and sport/leisure activities cessation (p = .08). CONCLUSION: Besides the burden in terms of productivity loss and caregivers' costs, the intangible costs are considerable, especially those related to divorce and spinsterhood. These conclusions may contribute to the understanding of the socio-economic impact of the disease and to the development of strategies for better governance of RA in Morocco.

Correlation Fuzzy measure of multivariate time series for signature recognition.

Distinguishing different time series, which is determinant or stochastic, is an important task in signal processing. In this work, a correlation measure constructs Correlation Fuzzy Entropy (CFE) to discriminate Chaos and stochastic series. It can be employed to distinguish chaotic signals from ARIMA series with different noises. With specific embedding dimensions, we implemented the CFE features by analyzing two available online signature databases MCYT-100 and SVC2004. The accurate rates of the CFE-based models exceed 99.3%.

Low- And Middle-Income Countries Experienced Delays Accessing New Essential Medicines, 1982-2024.

Little is known about how long it takes for new medicines to reach countries with different income levels. We analyzed data, sourced from IQVIA, on the timing of new drug launches in seventy-five low-, middle-, and high-income markets from 1982 to 2024. The sample captured the majority of essential medicines (as designated by the World Health Organization in the twenty-third Model List of Essential Medicines) that first came into medical use anywhere globally from 1982 onward. Kaplan-Meier estimates were used to quantify delays in launches across countries. Our analysis comprised 119 medicines with 6,871 observed launches. Nearly three-quarters (74 percent) of first launches occurred in just eight countries (in order of the most first launches, the US, the Netherlands, Sweden, Switzerland, the United Kingdom, France, Germany, and Japan). From the first launch globally, the median time to availability was 2.7 years for high-income countries, 4.5 years for upper-middle-income countries, 6.9 years for lower-middle-income countries, and 8.0 years for low-income countries. The gap between richer (high- and upper-middle-income) and poorer (lower-middle- and low-income) countries remained largely unchanged over time. Strategies to address the disparities highlighted by this analysis are urgently needed.

Psychological distress and trajectories of sleep duration among Australian adolescents: a prospective cohort study.

OBJECTIVES: This study investigated the association between indicators of psychological distress and well-being and trajectories of sleep duration among a cohort of Australian adolescents. DESIGN: A prospective cohort of adolescents was followed over 27 weeks (8 November 2019-14 May 2020). Data on sleep duration and psychological distress were collected via smartphones, based on ecological momentary assessments. SETTING: Sydney population catchment, Australia. PARTICIPANTS: Young people aged 13-19 years were recruited via social media (Instagram or Facebook). PRIMARY OUTCOME MEASURE: Self-reported sleep duration in the past 24 hours. Sleep duration was dichotomised into 'less than 8 hours' and 'at least 8 hours', to represent those participants not meeting the recommended minimum amount of daily sleep. RESULTS: Participants with high psychological distress had higher odds of sleeping less than 8 hours (OR 1.51 (95% CI 1.17 to 1.96)), compared with those with low psychological distress. Social media use (OR 1.34 (95% CI 1.01 to 1.79)) and longer periods spent on homework (OR 1.37, (95% CI 1.07 to 1.75)) were also associated with a sleep duration of less than 8 hours. Also, decreasing sleep trajectories were associated with increased psychological distress (ß=0.069, (95% CI -0.010 to 0.149)) and increased homework hours (ß=0.078 (95% CI 0.036 to 0.120)). CONCLUSION: Findings highlight the adverse impact of psychological distress and high levels of social media use on sleep duration among adolescents. Longitudinal studies with longer follow-up periods are warranted to further explore the temporal associations between sleep duration and different health outcomes among varying populations.

Protocol for a randomized controlled trial: exercise-priming of CBT for depression (the CBT+ trial).

BACKGROUND: Depression is a leading cause of disability worldwide, and treatments could be more effective. Identifying methods to improve treatment success has the potential to reduce disease burden dramatically. Preparing or "priming" someone to respond more effectively to psychotherapy (e.g., cognitive behavioral therapy [CBT]) by preceding sessions with aerobic exercise, a powerful neurobiological activator, could enhance the success of the subsequently performed therapy. However, the success of this priming approach for increasing engagement of working mechanisms of psychotherapy (e.g., increased working alliance and behavioral activation) has yet to be formally tested. METHODS: The CBT + trial will be a parallel-arm randomized controlled trial that will recruit 40 adult participants with DSM-5 diagnosed depression (verified with clinical interview) via referrals, mass emails, local flyers, and social media posts. Participants will be randomized to an ActiveCBT or CalmCBT condition. The ActiveCBT group will receive an 8-week CBT intervention primed with 30 min of moderate-intensity aerobic exercise (cycling on a stationary bike at a 13 rating of perceived exertion). The CalmCBT group will receive the same 8-week CBT intervention while resting for 30 min before CBT (i.e., cycling vs no cycling is the only difference). The primary outcome measures will be mean working alliance (assessed with the client version of the Working Alliance Inventory-Short Revised) and mean behavioral activation (self-reported Behavioral Activation for Depression Scale) recorded at each of the 8 therapy sessions. Secondary outcomes include evaluation of state anhedonia and serum brain-derived neurotrophic factor before the active/calm conditions, between the condition and therapy, and after the therapy. Additional exploratory analyses will evaluate group differences in algorithm-generated ratings of therapist-participant interactions via the Lyssn platform. DISCUSSION: The novel approach of priming CBT with moderate-intensity aerobic exercise evaluated in a randomized controlled trial (CBT + trial) has the potential to demonstrate the usefulness of exercise as an augmentation strategy that improves working mechanisms of therapy and overall treatment outcomes for adults with depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT06001346 . Registered on August 21, 2023.

Effects and mechanisms of supramaximal high-intensity interval training on extrapulmonary manifestations in people with and without chronic obstructive pulmonary disease (COPD-HIIT): study protocol for a multi-centre, randomized controlled trial.

BACKGROUND: Beyond being a pulmonary disease, chronic obstructive pulmonary disease (COPD) presents with extrapulmonary manifestations including reduced cognitive, cardiovascular, and muscle function. While exercise training is the cornerstone in the non-pharmacological treatment of COPD, there is a need for new exercise training methods due to suboptimal adaptations when following traditional exercise guidelines, often applying moderate-intensity continuous training (MICT). In people with COPD, short-duration high-intensity interval training (HIIT) holds the potential to induce a more optimal stimulus for training adaptations while circumventing the ventilatory burden often associated with MICT in people with COPD. We aim to determine the effects of supramaximal HIIT and MICT on extrapulmonary manifestations in people with COPD compared to matched healthy controls. METHODS: COPD-HIIT is a prospective, multi-centre, randomized, controlled trial with blinded assessors and data analysts, employing a parallel-group designed trial. In phase 1, we will investigate the effects and mechanisms of a 12-week intervention of supramaximal HIIT compared to MICT in people with COPD (n = 92) and matched healthy controls (n = 70). Participants will perform watt-based cycling two to three times weekly. In phase 2, we will determine how exercise training and inflammation impact the trajectories of neurodegeneration, in people with COPD, over 24 months. In addition to the 92 participants with COPD performing HIIT or MICT, a usual care group (n = 46) is included in phase 2. In both phases, the primary outcomes are a change from baseline in cognitive function, cardiorespiratory fitness, and muscle power. Key secondary outcomes include change from baseline exercise tolerance, brain structure, and function measured by MRI, neuroinflammation measured by PET/CT, systemic inflammation, and intramuscular adaptations. Feasibility of the interventions will be comprehensively investigated. DISCUSSION: The COPD-HIIT trial will determine the effects of supramaximal HIIT compared to MICT in people with COPD and healthy controls. We will provide evidence for a novel exercise modality that might overcome the barriers associated with MICT in people with COPD. We will also shed light on the impact of exercise at different intensities to reduce neurodegeneration. The goal of the COPD-HIIT trial is to improve the treatment of extrapulmonary manifestations of the disease. TRIAL REGISTRATION: Clinicaltrials.gov: NCT06068322. Prospectively registered on 2023-09-28.

Consideration of factors of low accrual and methods for setting appropriate accrual periods: Japan Clinical Oncology Group study.

BACKGROUND: Poor patient accrual can delay reporting of clinical trials and, consequently, the development of new treatments. For reducing the risk of additional resource requirements, a method for setting planned accrual periods with minimal deviation from the actual accrual periods is desirable. Risk factors for poor patient accrual and the appropriate method of estimating the required accrual period for timely completion of clinical trials were evaluated using the data of trials conducted by the Japan Clinical Oncology Group. METHODS: The study included 199 trials that started patient accrual between January 1, 1990, and June 30, 2021. The explanatory variables included factors that could be evaluated prior to trial commencement. We also evaluated whether the estimation methods for accrual pace could lead to completion within the planned accrual period. RESULTS: Approximately 23.6% of trials were completed within the planned accrual period. The risk factors for trial extension included planned accrual periods > 3 years (reference group: ≤ 3 years, odds ratio [OR] 0.37, 95% confidence interval [CI]: 0.15-0.92, P = 0.033) and stratified trial design (reference group: nonrandomized phase II trials, nonrandomized phase III trial [OR: 3.28, 95% CI: 0.99-10.9, P = 0.051], randomized phase II trial [OR: 3.91, 95% CI: 0.75-20.30, P = 0.105], and randomized phase III trial [OR: 9.29, 95% CI: 3.39-25.40, P < 0.001]). The method of estimating the accrual pace based on past clinical trials facilitated timely completion of the trial (OR: 3.51; 95% CI: 1.73-7.10, P < 0.001), unlike the estimation method based on survey evaluation of the accrual pace for participating institutions (OR: 1.12, 95% CI: 0.56-2.26, P = 0.751). Furthermore, the discrepancy between planned and actual accrual periods was minimal when using the methods of considering the accrual pace of past clinical trials. CONCLUSIONS: Considering the accrual pace of past clinical trials is useful for estimating the required accrual period if data from past trials are available. When conducting a survey, it is necessary to be cautious of overestimating the cases at each facility.

Does Sperm DNA Fragmentation Index Continuously Decrease Over Time After Varicocelectomy in Varicocele-Induced Infertility? A Systematic Review and Meta-Analysis.

Varicocele (VC) is the most frequent and reversible cause of male infertility. One of the preferred management strategies to alleviate this problem is varicocelectomy. However, there are no researchers who have explored the relationship between better timing and postoperative sperm DNA fragmentation index (DFI) improvement in patients. We conducted this meta-analysis by enrolling published studies to find out the best waiting time after varicocelectomy to wait for better improvement of sperm DFI. A literature search was conducted using PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases. The data from the pooled analysis were presented as mean difference (MD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Four studies were included after screening relevant literature. Statistical analysis revealed that after varicocelectomy, follow-up results within 3 months showed a significant improvement in sperm DFI compared with the preoperative period (MD: -3.66, 95% CI = [-5.17, -2.14], p < .00001), and follow-up results with 6 months showed a significant improvement in sperm DFI compared with the postoperative 3 months as well (MD: -1.51, 95% CI = [-2.73, -0.29], p = .02). Notably, no further improvement in sperm DFI was observed when the follow-up period reached 12 months (MD: -1.59, 95% CI = [-3.22, 0.05], p = .06). Six months after varicocelectomy may be the optimal time for sperm DFI compared with 12 months or even longer, which means it is also the preferable time for conception. However, more well-designed prospective studies are needed in the future to validate our conclusion.

Beyond graft function impairment after liver transplantation: the prolonged cold ischemia time impact on recurrence of hepatocellular carcinoma after liver transplantation-a single-center retrospective study.

Purpose: Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. Patients and Methods: This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. Results: A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p < 0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p < 0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p = 0.012), and the incidence of early allograft dysfunction (EAD) (p = 0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p = 0.02), and the time of mechanical ventilation postoperative was longer (p = 0.045). Conclusion: An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.