Participant Withdrew Research Articles

The effectiveness of a problem-solving intervention with workplace involvement on self-reported sick leave, psychological symptoms and work ability: a cluster randomised clinical trial.

Problem-solving interventions with workplace involvement (PSI-WPI) have been shown to reduce sick leave and increase return to work in an occupational health services context. However, many employees struggle with reduced work functioning, anxiety-, and depressive symptoms up to 12months after a sick leave episode, and it is unclear if the intervention affects outcomes other than sick leave. The aim of this study is to investigate if a PSI-WPI added to care as usual (CAU) is superior to CAU with respect to self-reported sick leave, psychological symptoms, work ability, work performance, and health after RTW when provided in primary care. Employed individuals aged 18-59years on sick leave (2 to 12weeks) diagnosed by a physician at a primary care center with mild to moderate depression, anxiety, or adjustment disorder were enrolled in a two-armed cluster-randomised trial evaluating the effectiveness of a PSI-WPI. Multiple outcomes were recorded at baseline, six months, 12months, and every fourth week during the study period. Outcomes were categorised into psychological symptoms, health, work ability, work performance, and self-reported sick leave. Data were analysed using MANOVA, GEE (Generalized Estimating Equations), and cox regression. One hundred ninety-nine individuals responded to the invitation to participate; one participant withdrew, one was excluded as the employment ended, nine did not answer the baseline survey, and three were removed from the analysis due to missing data. The analysis included 81 subjects who received the intervention and 104 subjects who received the control. Baseline characteristics were similar across both groups. No differences between the groups were found among either variables except one. There was a significant difference between the groups in self-rated health (EQ5D) in favour of the CAU group from baseline to six-month follow-up, with a mean difference of -8.44 (-14.84, -2.04). A problem-solving intervention with workplace involvement added to CAU did not result in statistically significant reductions in outcomes. Further research is needed to understand why problem-solving interventions appear to have an effect on sick leave in an occupational health services context and not in a primary care context. NCT3346395, registration date 2017-11-17.

The financial impact of participant attrition from randomised trials: a case-study from the Occupational Therapist Intervention Study (OTIS).

Loss to follow-up of participants can compromise the statistical validity of randomised trials. Moreover, it can have financial consequences for trial teams and funders. This study explores the Occupational Therapist Intervention Study (OTIS) where, despite a withdrawal rate of less than 10%, the trial team incurred opportunity costs related to participants who were initially recruited but subsequently decided to withdraw from the trial. To estimate the cost of participant losses to follow-up in the OTIS trial and thus introduce a costing framework to research teams on how they could estimate the opportunity costs of participant withdrawal from their randomised trials. The participants lost to follow-up are differentiated by (1) the time point at which they were lost to follow-up; (2) the treatment group they were allocated to; (3) their response patters to follow-up questionnaires; these elements were considered to identify the relevant types of attrition. Protocol-driven costs of trial materials, including administration, print, and shipping, were gathered. We calculated unit costs for each type of attrition by multiplying protocol-driven and intervention costs with the relevant number of participants. Summing up unit costs by type of loss to follow-up yields aggregate figures, enabling the estimation of aggregate and average opportunity costs of attrition. The average cost per participant loss to follow-up in the OTIS trial is £98.41. The aggregate cost of participant loss to follow-up is £10,234.90 from the economic perspective of the trial team. Therefore, 1.42% of the allocated funding has been misallocated because of participant loss to follow-up. Despite the low attrition rate of the OTIS trial, loss to follow-up has still generated considerable opportunity costs. It is recommended that decision makers focus on identifying strategies which could improve participant retention in randomised trials to optimise their budget.

Fasting as an intervention to alter the impact of simulated night-shift work on glucose metabolism in healthy adults: a cluster randomised controlled trial.

Night-shift work causes circadian misalignment and impairs glucose metabolism. We hypothesise that food intake during night shifts may contribute to this phenomenon. This open-label, multi-arm, single-site, parallel-group controlled trial involved a 6 day stay at the University of South Australia's sleep laboratory (Adelaide, SA, Australia). Healthy, non-shift-working adults without obesity (N=55; age 24.5 ± 4.8 years; BMI 24.8 ± 2.8 kg/m2) were assigned to the next available run date and cluster randomised (1:1:1) to fasting-at-night (N=20), snack-at-night (N=17), or meal-at-night (N=18) conditions. One participant withdrew from each group, prior to starting the study. Due to study design, neither participants nor people collecting their measurements could be blinded. Statistical and laboratory staff were concealed to study allocation. Participants were fed at calculated energy balance, with the macronutrient composition of meals being similar across conditions. The primary outcomes were a linear mixed-effects model of glucose, insulin and NEFA AUC in response to a 75 g OGTT that was conducted prior to and after 4 consecutive nights of shift work plus 1 night of recovery sleep. Insulin sensitivity, insulinogenic and disposition indexes were also calculated. Night-shift work impaired insulin sensitivity, as measured by insulin AUC (p=0.035) and the insulin sensitivity index (p=0.016) across all conditions. Insulin secretion, as measured by the insulinogenic index, was increased in the fasting-at-night condition only (p=0.030), resulting in a day×condition interaction in glucose AUC (p<0.001) such that glucose tolerance was impaired in the meal-at night (+2.00 [95% CI 1.45, 2.56], p<0.001) and snack at-night (+0.96 [0.36, 1.56], p=0.022) conditions vs the fasting-at-night (+0.34 [-0.21, 0.89]) condition. A day×condition interaction was also observed in NEFA AUC (p<0.001), being higher in the meal-at-night (+0.07 [0.03, 0.10]. p=0.001) and snack-at-night (0.01 [-0.03, 0.05], p=0.045) conditions vs the fasting-at-night condition (-0.02 [-0.06, 0.01]). No adverse events occurred. The timing of food intake has a critical effect on glucose metabolism during simulated night-shift work, which was readily amendable to a meal re-timing intervention. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001556437 FUNDING: This work was funded by the National Health and Medical Research Council (NHMRC), APP1099077.

Blood pressure targets for hypertension in people with chronic renal disease.

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown. Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target. We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions. We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure. We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding. We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups. Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future.

Poly-Ether-Ether-Ketone versus dead-soft coaxial bonded retainers: a randomized clinical trial. Part 2: periodontal health and microbial biofilm assessment.

Retainers have the potential to detrimentally impact periodontal health and contribute to tooth decay. To investigate periodontal health and bacterial biofilm related to Poly-Ether-Ether-Ketone (PEEK) fixed retainers as compared to Dead-soft coaxial fixed retainer (DSC). A two-arm parallel groups single-centre randomized clinical trial. The trial included patients whose orthodontic treatment was completed and required retainers. Participants were randomly assigned into two retainer groups: PEEK retainers, prepared by computer-aided design and manufacturing into 0.8mm wire form, and DSC retainers. The objectives included assessing periodontal health through plaque accumulation index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD), gingival index (GI), calculus index (CI), and alveolar bone height (ABH) assessment. Biofilm assessment involved bacteriological screening of aerobic, facultative anaerobic, mutans streptococci, and lactobacilli. The periodontal indices and microbiological screening as well as were assessed at the debonding stage (T0), 1-month (T1), 3-month (T3), and 6-month (T6) after the commencement of the trial, except for the ABH, which was recorded using periapical radiograph at T0 and T6. Single blinding of participants in addition to the bacteriological specialist. Initially, the trial enrolled 46 participants, aged between 12 and 28 years, and were randomly assigned to two groups, with 23 participants in each group. Subsequently, one participant withdrew from the trial, resulting in a total of 45 participants whose data were analysed. Assessment of the periodontal indices, excluding the CI (P = .480), revealed statistically but not clinically significant differences between groups after 6-month of retention (P = .016 of PI, P = .020 of BOP, P = .05 of PPD, and P = .01 of GI). There was slight plaque accumulation, normal PPD (approximately 1mm), healthy to mild gingivitis with a GI of less than 1 and BOP was around 10%. Concerning the ABH, there was a noticeable reduction in its score after 6 months, particularly in the PEEK group, although the difference was not statistically significant (P = .102). Furthermore, the bacteriological viable count did not show any significant difference between the groups during the recall visits. There have been no reported negative consequences. Blinding the assessor of periodontal indices was not feasible due to the nature of the intervention. The trial follow-up duration was limited. Both the PEEK and DSC retainers have comparable impacts on periodontal health and bacterial accumulation and composition during the retention period. NCT05557136.

Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials.

Psychedelic agents have regained the attention of pharmaceutical companies as promising treatments for depressive episodes. 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), an atypical psychedelic, is emerging as a potentially effective, novel rapid-acting antidepressant. In this systematic review, we analyze the safety and tolerability evidence from clinical trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, electronic databases (PubMed, SCOPUS, Web of Science, EMBASE, and EBSCO) were searched from inception until 15 May 2024 to identify clinical trials (regardless of phase) reporting on short-term safety and tolerability profile of 5-MeO-DMT using the following keywords in various combinations: 5-methoxy-N, N-dimethyltryptamine, 5-MeO-DMT, safety, adverse, adverse reaction, side effects, tolerability, dropout, healthy volunteer, healthy participant, depression, major depressive disorder. Only studies written in English were considered. Initial search yielded 100 records, out of which 3 met the inclusion criteria. These studies reported on the results from clinical trial phases I and I/II, with a total of 78 participants included; two studies involved healthy volunteers, and one included patients with treatment-resistant depression. Although the data is limited, it confirms a good short-term safety and tolerability profile for 5-MeO-DMT, with no serious adverse events (SAEs) reported. Furthermore, no drop-outs were reported. 5-MeO-DMT administration in human subjects presents favorable short-term safety and tolerability profile. Importantly, no SAEs have been documented, and no adverse events led to participant withdrawal from the studies There is a need for future randomized, double-blind, placebo-controlled trials with larger samples and follow-up to assess potential chronic adverse events.

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis.

In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years). Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool. Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events. For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

Exploring the feasibility of heart rate variability biofeedback for individuals with tetraplegia: A pilot clinical trial.

This study aimed to determine the feasibility of using commercially available heart rate variability (HRV) biofeedback training to improve physiological and self-reported stress and anxiety among adults with tetraplegia. HRV biofeedback teaches individuals to effectively modify their HRV levels in synchronization with their respiration rate and amplitude. Thirty participants with tetraplegia were enrolled and allocated into one of two study arms: biofeedback or control. The study was conducted remotely from June 2022 through February 2023. Participants in the biofeedback arm received eight HRV training sessions with physiological monitoring, while participants in the control arm received physiological monitoring only. Outcome measures included feasibility, percentage of time spent in the low-frequency range, the Depression Anxiety Stress Scale-21, the Subjective Units of Distress Scale, and the State-Trait Anxiety Inventory-Y Form. Feasibility was demonstrated with 100% completion of the protocol and no participant withdrawals due to adverse events. The biofeedback arm showed a greater percentage of time spent in the low-frequency range and reported greater improvement in anxiety from baseline to Session 8 on the Subjective Units of Distress Scale compared to the control arm. However, no differences were found between study arms on the Depression Anxiety Stress Scale-21 and State-Trait Anxiety Inventory-Y Form. This study demonstrated that a remotely delivered, self-administered HRV biofeedback intervention could feasibly be delivered to individuals with tetraplegia who report moderate-to-high levels of anxiety. Trends in the reduction of physiological and self-reported anxiety were observed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Safety of acamprosate for alcohol use disorder after liver transplant: A pilot randomized controlled trial.

Acamprosate is a therapy for alcohol use disorder, but data on feasibility and safety in recipients of liver transplants are lacking. This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18y) with liver transplant for alcohol-associated liver disease enrolled between 2021 and 2023, who were randomized 2:1 to the intervention of acamprosate (666mg dose 3 times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety (prevalence of adverse events [AEs]), feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use >60%), and efficacy (reduction in Penn Alcohol Craving Scale), and relapse-blood phosphatidylethanol (≥20ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention-to-treat (excluding withdrawals before medication administration) and per-protocol population (excluding withdrawals/<4 weeks participation). Of 78 participants who were approached, 30 enrolled (19 acamprosate and 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate before medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p > 0.99), including grade 3 AEs (53.9% vs. 60.0%, p > 0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate versus SOC groups (61.0% vs. 76.0%, p = 0.19), and 69.0% were acamprosate adherents. Baseline Penn Alcohol Craving Scale values were low with no difference by the group in median absolute change in Penn Alcohol Craving Scale for intention-to-treat (0, IQR: -4 to 0 vs. 0, IQR: 0-0, p = 0.32), and per-protocol analyses (-1, IQR: -6 to 0 vs. 0, IQR: -0 to 0, p = 0.36). There was no reported or biochemical evidence of alcohol relapse. In this pilot study, preliminary data suggest that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-liver transplant care (ClinicalTrials.gov, Number: NCT06471686).

Use of the PRECEDE-PROCEED Model in Piloting Vaccine Promotion and Infection Self-Protection: Intervention Development and Effectiveness Examination.

This study aimed to tailor and pilot a health education program using the PRECEDE-PROCEED model to promote vaccination and enhance self-protective behaviors against COVID-19 in Hong Kong populations. Quasi-experimental study. Phases 1-4 of the PRECEDE-PROCEED model were used to identify the needs for COVID-19 prevention. Strategies to address predisposing, reinforcing, and enabling factors in the PRECEDE-PROCEED model were developed, and an intervention package was generated thereafter. A pre-post experimental study was conducted among 50 participants to preliminarily assess the effects of the intervention based on Phases 5 and 8 of the PRECEDE-PROCEED model. The 3-month intervention package contained 16 health education videos, 36 health tips, individual consultations, regular reminders of vaccination, incentive of anti-epidemic packages, and vaccine booking services. By the third month, 33 participants took a new dose of COVID-19 vaccine, and 5 participants withdrew. The vaccination rate for new dose achieved 73.3% (95% CI: 58.06-85.40%). Compared with the Hong Kong population in the same period, our study demonstrated higher increase in vaccination rate (9.97 vs. 1.36 doses per 1000 person-days). The percentage of early testing in personal and family level increased to 86.7% and 84.4%, respectively (both p < 0.05). For correct mask wearing and hand washing, the scores increased from a baseline score of 9.1 ± 1.6 and 4.9 ± 1.3 to 9.5 ± 1.0 and 5.3 ± 1.2, respectively (both p < 0.05). The application of the PRECEDE-PROCEED model effectively facilitated the stepwise development, implementation, and evaluation of a health education program for improving vaccination rates and fostering self-protective behaviors against infections.

Repetitive transcranial magnetic stimulation to treat chronic tinnitus: a feasibility study

ABSTRACT This study aimed to evaluate the feasibility, safety and preliminary efficacy of high-frequency repetitive transcranial magnetic stimulation for treating chronic subjective tinnitus. Eleven adults (8 males; age: 56.70 ± 11.42 years, tinnitus duration: 12.43 ± 7.43 years) were recruited to participate in a pre-registered study. Six treatments were provided over two weeks. Feasibility was determined against pre-specified criteria addressing recruitment, adherence (protocol, 2-week follow-up, 4-week follow-up), and perceived usefulness, helpfulness and acceptability. Adverse events were recorded and preliminary efficacy was assessed using the Tinnitus Handicap Inventory. Five out of seven feasibility criteria were met and no serious adverse events occurred. One participant withdrew from the study due to stimulation being uncomfortable. Preliminary efficacy data indicated a significant effect of Time on tinnitus (p < 0.001). Compared to baseline, tinnitus reduced at mid-treatment (t (9) = −3.47, p = 0.028) and 4-weeks post treatment (t (9) = −3.62, p = 0.024). A repetitive transcranial magnetic stimulation protocol to manage chronic subjective tinnitus appears feasible, safe, and may have preliminary evidence of effectiveness. The recommendation is to proceed to trial with minor adjustments to gain further insight into the patient experience.

Vestibular Rehabilitation Using Dynamic Posturography: Objective and Patient-Reported Outcomes from a Randomized Trial.

Balance deficits are common and debilitating. Standard treatments have limitations in addressing symptoms and restoring dynamic balance function. This study compares a rehabilitative computerized dynamic posturography (CDP) protocol, computerized vestibular retraining therapy (CVRT), with a home exercise program (HEP) for patients with objectively confirmed unilateral vestibular deficits (UVDs). Single-center, randomized, interventional trial, with 1-sided crossover. A tertiary neurotology clinic. Patients with UVDs and Dizziness Handicap Inventory (DHI) score >30 were randomized to receive either CVRT or HEP. After completion of treatment, the HEP group was crossed over to CVRT. Outcome measures were the sensory organization test (SOT) and 3 participants reported dizziness disability measures: the DHI, Activity-Specific Balance Confidence Scale (ABC) scale, and Falls Efficacy Score-International (FES-I). We enrolled 37 patients: 18 participants completed CVRT and 12 completed HEP, 11 of whom completed the crossover. Seven participants withdrew. The CVRT group demonstrated a greater improvement in SOT composite score than the HEP group (P = .04). Both groups demonstrated improvement in participant-reported measures but there were no differences between groups (DHI: P = .2604; ABC: P = .3627; FES-I: P = .96). Following crossover to CVRT after HEP, SOT composite (P = .002), DHI (P = .03), and ABC (P = .006) improved compared to HEP alone. CVRT and HEP were both associated with improved participant-reported disability outcomes. CVRT was associated with greater improvement in objective balance than HEP. Adding CVRT after HEP was superior to HEP alone. Multimodal CDP-based interventions, such as CVRT, should be considered as an adjunct to vestibular physiotherapy for patients with UVD.

Anakinra in Sanfilippo syndrome: a phase 1/2 trial

Sanfilippo syndrome is a fatal childhood neurodegenerative disorder involving neuroinflammation among multiple pathologies. We hypothesized that anakinra, a recombinant interleukin-1 receptor antagonist, could improve neurobehavioral and functional symptoms owing to its capacity to treat neuroinflammation. This phase 1/2 trial aimed to test the safety, tolerability and effects of anakinra on neurobehavioral, functional and quality-of-life outcomes in patients and their caregivers. The primary outcome was the percent of participants requiring a dose increase at week 8 or week 16. Secondary efficacy outcomes included a multi-domain responder index (MDRI). Twenty-three participants (6–26 years of age) were enrolled. Twenty continued treatment to week 8, and 15 (75%) required an increased dose at week 8 or week 16. There was an improvement in at least one domain in the MDRI in 18 of 21 (86%) at week 8 and in 15 of 16 (94%) at week 36. Seven participants withdrew (intolerability of daily injections and lost to follow-up) before week 36. Adverse events occurred in 22 of 23 (96%) participants, most commonly mild injection site reactions. No serious adverse events were related to anakinra. In conclusion, anakinra was safe and associated with improved neurobehavioral and functional outcomes, supporting continued investigation of anakinra in Sanfilippo syndrome and other mucopolysaccharidoses. ClinicalTrials.gov identifier: NCT04018755.

Assessing sleep in primary brain tumor patients using smart wearables and patient-reported data: Feasibility and interim analysis of an observational study.

Sleep-wake disturbances are common and disabling in primary brain tumor (PBT) patients but studies exploring longitudinal data are limited. This study investigates the feasibility and relationship between longitudinal patient-reported outcomes (PROs) and physiologic data collected via smart wearables. Fifty-four PBT patients ≥ 18 years wore Fitbit smart-wearable devices for 4 weeks, which captured physiologic sleep measures (eg, total sleep time, wake after sleep onset [WASO]). They completed PROs (sleep hygiene index, PROMIS sleep-related impairment [SRI] and Sleep Disturbance [SD], Morningness-Eveningness Questionnaire [MEQ]) at baseline and 4 weeks. Smart wearable use feasibility (enrollment/attrition, data missingness), clinical characteristics, test consistency, PROs severity, and relationships between PROs and physiologic sleep measures were assessed. The majority (72%) wore their Fitbit for the entire study duration with 89% missing < 3 days, no participant withdrawals, and 100% PRO completion. PROMIS SRI/SD and MEQ were all consistent/reliable (Cronbach's alpha 0.74-0.92). Chronotype breakdown showed 39% morning, 56% intermediate, and only 6% evening types. Moderate-severe SD and SRI were reported in 13% and 17% at baseline, and with significant improvement in SD at 4 weeks (P = .014). Fitbit-recorded measures showed a correlation at week 4 between WASO and SD (r = 0.35, P = .009) but not with SRI (r = 0.24, P = .08). Collecting sleep data with Fitbits is feasible, PROs are consistent/reliable, > 10% of participants had SD and SRI that improved with smart wearable use, and SD was associated with WASO. The skewed chronotype distribution, risk and impact of sleep fragmentation mechanisms warrant further investigation. NCT04 669 574.

Nonalcoholic Fatty Liver Disease in Shift Workers and Its Effect on Peripheral Nerve Conduction: A Cross-Sectional Study.

Introduction Nonalcoholic fatty liver disease (NAFLD) presents as a multisystem disorder, heightening the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Occupation emerges as a significant factor influencing the occurrence of NAFLD. Research indicates that individuals engaged in shift work face an elevated risk of NAFLD, alongside obesity and T2DM, attributed to disruptions in their circadian rhythm, which precipitate hepatic steatosis and inflammation. Remarkably, peripheral neuropathy has been observed in conjunction with advanced liver disorders and NAFLD in the general population. However, the correlation between NAFLD and peripheral neuropathy remains unestablished in shift workers. Objective To identify NAFLD in seemingly healthy rotating shift workers and assess any potential impact of NAFLD on nerve function in this demographic. Methods This cross-sectional study involved 73 apparently healthy nonalcoholic security guards (aged 35 to 60 years) working in rotating shifts. The study included a comprehensive assessment, beginning with a medical history, an evaluation of physical activity, and anthropometric measurements. Confirmation of NAFLD was achieved through abdominal ultrasonography (USG), followed by the analysis of biochemical parameters. Motor and sensory nerve conduction studies (NCS) were conducted on participants with normal vitamin B12 levels using the Aleron electromyograph (EMG) machine (Recorders and Medicare Systems Private Ltd, Budanpur, India). The evaluation encompassed the Median and Common Peroneal motor nerves, as well as Median and Sural sensory nerves. Recorded parameters for motor nerves included distal motor latency (DML), compound muscle action potential (CMAP) amplitude, conduction velocity (CV), and F-wave minimum latency (F-wave), while sensory nerve parameters comprised sensory onset latency (SOL), sensory nerve action potential (SNAP) amplitude, and CV. Results Among 73 healthy security guards working in rotating shifts, 76.1% were diagnosed with NAFLD through abdominal ultrasound. Following participant withdrawals and exclusions due to vitamin B12 deficiency, a comparison of NCS parameters between NAFLD (n=24) and Non-NAFLD (n=12) groups revealed no significant disparities in motor or sensory parameters, except for a slightly diminished CMAP amplitude in the peroneal nerve of NAFLD subjects (8.21±2.83mV vs ±10.22±2.30 mV, p< 0.040). However, these differences fell within normal ranges, indicating no notable impact on peripheral nerve conduction in the presence of NAFLD. Conclusion The results indicate a high prevalence of NAFLD among individuals working rotating shifts. Moreover, the investigation suggests that despite the presence of NAFLD, there is no discernible influence on motor and sensory peripheral nerve conduction, particularly in common peroneal, median, and sural nerves.

Formative research to adapt a cardiac rehabilitation program to breast cancer survivors: the heart health after cancer treatment (HEART-ACT) study.

Breast cancer survivors are disproportionately at risk for cardiovascular disease; exercise-based interventions may improve cardiovascular health. The objective of this formative research is to better understand the needs of patients and barriers to participation in an adapted cardiac rehabilitation program for diverse breast cancer survivors in an urban safety net setting. We recruited 30 participants (10 English-speaking, 10 Spanish-speaking, and 10 Cantonese-speaking) who had received treatment with curative intent for breast cancer from an urban safety net hospital between November 9, 2021, to August 30, 2022. Participants completed surveys and interviews about perspectives on health behaviors and participating in an adapted cardiac rehabilitation program. Interviews were qualitatively analyzed using rapid template analysis with pre-selected constructs from the Theory of Planned Behavior, Unified Theory of Acceptance and Use of Technology, and Consolidated Framework for Implementation Research, as well as emergent codes. We developed a Participant User Journey for a program based on responses and conducted human-centered design sessions with 8 participants to iteratively revise the Participant User Journey. Among 30 participants, mean age was 56.7 years (standard deviation [SD] 10.2) with 100% female sex assigned at birth; 1 participant withdrew before completing study procedures. Most participants had limited health literacy (18/29, 62%). Mean body mass index was 31.4 (SD 8.3), 21/29 (72%) had blood pressure below 140/90 mmHg, and 12/29 (41%) had blood pressure below 130/80. Mean 6-minute walk distance was 384.9 meters (SD 78.3). The desired benefits of a program included healthy living and prevention of cancer recurrence. Barriers to participation included motivation, social support, transportation, and concerns about exercise safety. Participants emphasized the need for practicality, such as fitting physical activity into daily life and nutrition support, including recipes and shopping lists. Trusted experts and cultural and language concordance were viewed as important aspects of the program. Through participant interviews and human-centered design sessions, we developed the HEART-ACT program, a 12-week multi-disciplinary program addressing physical activity, nutrition, emotional well-being, cardiovascular risk, survivorship, and other components if indicated (e.g., tobacco cessation). Future research will test the effects of this program on patient-centered outcomes.

Abstract PO1-28-08: The Efficacy and Safety Results of Neoadjuvant Phase II study of Anlotinib plus Sintilimab Combined with Chemotherapy in Triple-negative Breast Cancer (NeoSACT)

Abstract Background: In triple-negative breast cancer (TNBC), the co-administration of programmed mortality 1 (PD-1) inhibitors and chemotherapy has demonstrated enhanced pathological complete response (pCR) rates and improved event-free survival (EFS). Previous research has suggested that antiangiogenic agents possess the ability to normalize aberrant tumor vasculature, thereby converting the immune-suppressive tumor microenvironment into an immune-supportive one. This study aims to assess the effectiveness and safety of combining the neoadjuvant small-molecule antiangiogenic drug Antilotinib with the PD-1 inhibitor Sintilimab and chemotherapy. Methods: In this study, a single-arm, open-label, phase II trial was conducted to evaluate the effectiveness of Anlotinib plus Sintilimab, in conjunction with nab-paclitaxel and carboplatin, followed by epirubicin and cyclophosphamide, in eligible patients with stage II-III TNBC. The treatment regimen consisted of four cycles of nab-paclitaxel (100 mg/m² on day 1, 8 and 15) plus carboplatin (AUC 5) every 21 days, followed by four cycles of epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) every 21 days. Additionally, patients received Sintilimab (200mg) every 21 days and Antilotinib (12mg, po on day 1-14, every 21 days) for eight cycles. Patient enrollment was conducted according to a Simon two-stage design. The primary endpoint was the rate of pCR based on the definition of ypT0/Tis ypN0. Secondary endpoints included residual cancer burden (RCB), EFS, overall survival (OS), adverse events (AE), and immune response biomarkers. Results: Between September 2021 and August 2023, a cohort of 31 patients was enrolled, with a median age of 48 years (range: 30-70 years). Among the participants, 21 out of 31 (67.8%) presented with clinical stage II disease, 23 out of 31 (74.2%) had T2 tumors, and 19 out of 31 (61.3%) exhibited clinically positive lymph nodes. In the initial phase of the study, a total of 11 patients were evaluated, out of which 7 patients achieved a pathological complete response (pCR) after surgery. Consequently, 20 patients were included in the subsequent stage, and among the 19 patients who were evaluable, 13 achieved pCR. One participant withdrew from the study prematurely following the third cycle due to grade 3 liver impairment, resulting in the discontinuation of study therapy as well as subsequent surgery. In the intention-to-treat (ITT) population, the overall pCR rate was determined to be 64.5% (20/31, 95% CI 45.4% - 80.8%). Additionally, 80.6% (25/31, 95%CI 62.5% - 92.5%) of the patients were assessed as having a RCB score of 0 or 1. A total of 31 patients were subjected to adverse event assessment. Among them, 12 patients (38.7%) experienced one or more grade 3/4 adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The grade 3/4 AEs encompassed rash (7 patients, 22.6%), anemia (4 patients, 12.9%), thrombocytopenia (3 patients, 9.7%), neutropenia (2 patients, 6.4%), leukopenia (2 patients, 6.4%), hypothyroidism (2 patients, 6.4%), and elevated AST/ALT (1 patient, 3.2%). Conclusions: The neoadjuvant regimen comprising the combination of Anlotinib and Sintilimab alongside chemotherapy demonstrated a pCR rate of 64.5%, with no observed emergence of novel toxicity signals. Ongoing investigations encompass biomarker assessments and survival analyses. Pertinent clinical trial details can be found under the identifier NCT04877821. Citation Format: Liulu Zhang, Mei Yang, Ciqiu Yang, Teng Zhu, Hong-Fei Gao, Kun Wang. The Efficacy and Safety Results of Neoadjuvant Phase II study of Anlotinib plus Sintilimab Combined with Chemotherapy in Triple-negative Breast Cancer (NeoSACT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-08.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial

The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. For the Chinese translation of the abstract see Supplementary Materials section.

High-flow nasal cannula during pulmonary rehabilitation for people with chronic obstructive pulmonary disease: Asystematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is an increasingly concerning global public health issue due to its high burden of morbidity and mortality. Pulmonary rehabilitation (PR) is a comprehensive intervention to improve patients' physical and psychological conditions, commonly involving oxygen supplementation. The potential benefits of high-flow nasal cannula (HFNC) have recently sparked interest as oxygen therapy. In this context, this study aims to assess the effects of HFNC during the exercise training component of a PR program in people with COPD. Systematic review (CRD42022330929). We included randomised controlled trials (RCTs), including crossover RCTs with adults with stable COPD. We included trials using oxygen therapy with HFNC during the exercise training component of a PR programme. disease-specific health-related quality of life (HRQoL), exercise capacity (EC) and adverse events. treatment adherence, breathlessness and future exacerbations. We included five studies with 300 participants with moderate to severe COPD. The certainty of the evidence was primarily low or very low for all outcomes of interest due to risk of bias, inconsistency or imprecision. HFNC has little to no difference in HRQoL (4 studies, 129 participants, MD 0.17, 95% CI -1.20 to 1.54; I2 50%). HFNC may result in little to no difference in EC (3 studies, 212 participants, mean difference 18.73, 95% CI -20.49 to 28.94; I2 56%), and we are uncertain about the effect of HFNC on breathlessness (4 studies; 244 participants, MD of -0.07, 95% CI -0.4 to 0.26; I2 63%). Only one study with 44 participants reported a participant's withdrawal because of progressive dyspnoea during lower limb exercise. We are uncertain about the effect of HFNC during the exercise component of a PR programme in HRQoL, EC or dyspnoea compared to usual care or conventional supplementary oxygen. Non-domiciliary oxygen patients showed improvements in HRQoL, EC and dyspnoea.

Acceptability and Feasibility of the Telehealth Bariatric Behavioral Intervention to Increase Physical Activity Before Bariatric Surgery: A Single-Case Experimental Study (Part I).

Physical activity (PA) can play an important role in optimizing metabolic/bariatric surgery (MBS) outcomes. However, many MBS patients have difficulty increasing PA, necessitating the development of theory-driven counseling interventions. This study aimed to (1) assess the feasibility and acceptability of the TELEhealth BARIatric behavioral intervention (TELE-BariACTIV) trial protocol/methods and intervention, which was designed to increase moderate-to-vigorous intensity physical activity (MVPA) in adults awaiting MBS and (2) estimate the effect of the intervention on MVPA. This trial used a repeated single-case experimental design. Twelve insufficiently active adults awaiting MBS received 6 weekly 45-min PA videoconferencing counseling sessions. Feasibility and acceptability data (i.e., refusal, recruitment, retention, attendance, and attrition rates) were tracked and collected via online surveys, and interviews. MVPA was assessed via accelerometry pre-, during, and post-intervention. Among the 24 patients referred to the research team; five declined to participate (refusal rate = 20.8%) and seven were ineligible or unreachable. The recruitment rate was 1.2 participants per month between 2021-09 and 2022-07. One participant withdrew during the baseline phase, and one after the intervention (retention rate = 83.3%). No participant dropouts occurred during the intervention and 98.6% of sessions were completed. Participants' anticipated and retrospective acceptability of the intervention was 3.2/4 (IQR, 0.5) and 3.0/4 (IQR, 0.2), respectively. There was a statistically significant increase in MVPA [Tau-U = 0.32(0.11; 0.51)] from pre- to post-intervention. Despite a low recruitment rate, which could be explained by circumstances (COVID-19 pandemic), results support feasibility, acceptability, and preliminary efficacy of the TELE-Bari-ACTIV intervention for increasing MVPA in patients awaiting MBS.