Diabetes treatment satisfaction among a multi-ethnic Aotearoa New Zealand population with uncontrolled type 2 diabetes mellitus.

AIMS: To assess whether diabetes treatment satisfaction differs by ethnicity among participants with insufficient glycaemic control of type 2 diabetes mellitus in a clinical trial involving additional oral diabetes medications. Patient satisfaction is used as an indicator of healthcare quality. However, data on patients' diabetes treatment satisfaction in the context of insufficient glycaemic control is limited. METHODS: Individuals with type 2 diabetes and an HbA1c of 58-110mmol/mol (7.5-12.5%) were recruited across Aotearoa New Zealand to participate in an 8-month randomised crossover study of vildagliptin and pioglitazone as add-on therapy to metformin and/or sulfonylurea. Participants completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline pre-randomisation. Treatment satisfaction scores were compared between ethnic groups and other characteristics using the analysis of variance and linear regression. Perceived hyper- and hypoglycaemia were summarised separately. RESULTS: Between February 2019 and March 2020, 346 participants (41% women, 32% Pacific peoples, 23% Maori, 26% European) completed the DTSQ. Mean (SD) age was 57.5 (10.9) years, diabetes duration was 9 (6.3) years and HbA1c was 75 (12)mmol/mol (9.0[3.2]%). At study entry, 40% were receiving monotherapy for diabetes. Treatment satisfaction was rated highly, with a score of 29(6) (interquartile range 25-33). Pacific peoples and older people reported greater treatment satisfaction than other groups (p<0.001). CONCLUSIONS: Diabetes treatment satisfaction was high, particularly among Pacific peoples, despite suboptimal glycaemic control and insufficient glucose-lowering therapy.

--------Comparison of Hybrid-Simulation-Based Teaching with Traditional Teaching of Pharmacology.

OBJECTIVE: To compare the outcome of traditional teaching with hybrid simulation-based teaching for undergraduate medical students. Place and Duration of the Study: Department of Pharmacology, Jinnah Medical and Dental College, Karachi, Pakistan, from June to August 2023. STUDY DESIGN: Quasi-experimental study. METHODOLOGY: One hundred students from MBBS 3rd year were included in the study after taking the informed consent. Participants were divided into two cross-over groups and sampling was done randomly. Group A: (even roll numbers, n = 50) was the control group, taught by traditional lecture on positive inotropic medicines. Group B: (with odd roll numbers, n = 50) was the intervention group, taught the same topic by simulation-based teaching through 5 case scenarios. The teaching of this group was reinforced by role plays. Scores of post-test and retention test were compared by applying the Student's t-test. RESULTS: Students taught by traditional lectures i.e., Group A, their post-test mean scores were 30.7 ± 5.6, whereas Group B scored 45.7 ± 3.3, taught by hybrid stimulation (p <0.001). Retention test (MCQs based) was conducted after one month in which Group A obtained a mean score of 18.8 ± 9 with a passing percentage of approximately 30, whereas Group B obtained a score of 41.3 ± 5.6 (p <0.001). CONCLUSION: Hybrid-simulation-based teaching improved the immediate test scores as well as retention. KEY WORDS: Traditional teaching, Hybrid-simulation, MCQs, Retention test, Intervention group.

Randomized Trial of Transverse vs Vertical Extraction Site Incision After Robotic Radical Prostatectomy.

PURPOSE: Incisional hernias are a frequent complication following robotic radical prostatectomy. Observational data in men undergoing robotic prostatectomy suggest that transverse closure resulted in lower hernia rates than vertical closure. We sought to compare the incidence of incisional hernia after robotic radical prostatectomy after vertical and transverse extraction site closure. MATERIALS AND METHODS: We conducted a clinically integrated, crossover, cluster randomized trial at a single tertiary referral center (January 2016-September 2021) comparing the rate of hernia after transverse vs vertical extraction site excision in 1356 patients treated with minimally invasive radical prostatectomy. The primary outcome was between-group incidence of incisional hernia within 15 months of prostatectomy defined by physical examination and self-reported patient surveys. RESULTS: Overall, 197 (20%) patients developed an incisional hernia within 15 months, 797 did not have an incisional hernia within this period, and 362 had missing outcome data regarding incisional hernia. We found no significant difference in hernia rates between the 2 incision types (absolute between-group difference 1.8%; 95% CI -3.4%, 6.6%; P = .5) in the primary analysis or in the 3 sensitivity analyses. Notably, because of the inclusive definition of hernia used, these data cannot be used as an estimate of the true prevalence of incisional hernia. CONCLUSIONS: Surgeons should choose the incision and closure approach they are most comfortable with when extracting specimens. Studies of modifications to the surgical technique are best conducted as randomized comparisons, and the clinically integrated, crossover, cluster randomized trial allows large trials to be completed at a single center and at low cost. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407263.

Prevalent and new use of common drugs for the incidence of community-acquired acute kidney injury: cohort and case-crossover study.

Although community-acquired acute kidney injury (CA-AKI) represents a significant subset of all AKI incidence, evidence is limited due to the lack of comprehensive data prior to diagnosis. Here, we examined the risk of drug use for CA-AKI by using exhaustive pre-diagnostic prescription data. We included 78,754 working-age healthy individuals who underwent an annual health checkup program. We conducted a cohort study to assess the association between prevalent drug use and subsequent CA-AKI incidence using the Cox proportional hazard model. Subsequently, we conducted a case-crossover study to compare the new drug use in the case period directly before the CA-AKI incidence (- 3 to 0 months) with that in the control period far before the CA-AKI incidence (- 15 to - 12 months and - 9 to - 6 months) using the conditional Poisson regression model. The prevalent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with an increased CA-AKI incidence, but the new use was not. The new use of diuretics, anti-infectious drugs, and contrast medium was also associated with an increased CA-AKI incidence. These results suggest we need to pay attention for the incidence of AKI among the general population taking those common drugs.

Older adults exercising ON TIME: protocol for a randomized controlled cross-over study to assess the effect of physical activity timing on insomnia severity.

BACKGROUND: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function. METHODS: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock. DISCUSSION: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population. TRIAL REGISTRATION: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named ("Ouderen op tijd in beweging" or in English "Older adults exercising on time"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.

Oral hygiene changes & compliance with telemonitoring device in individuals with intellectual/developmental disabilities: a randomized controlled crossover trial.

OBJECTIVE: Advances in mobile technology are helping with health management practices, and smart toothbrushes provide proper dental care by collecting and analyzing users' toothbrushing data. The purpose of this study is to assess the effect of a telemonitoring device on oral hygiene management in individuals with intellectual or developmental disabilities and its role in promoting oral health. MATERIALS AND METHODS: Participants were split into two groups: one initially using the telemonitoring device (telemonitoring device/manual toothbrush) and the other using it later (manual toothbrush/telemonitoring device), with a one-month washout period. The study compared plaque index, halitosis, changes in oral microbiota, and guardian questionnaire responses between the groups. RESULTS: In period 1, the QHI index score significantly decreased from 1.93 to 0.83 in the group using the remote monitoring device, compared to an increase from 1.75 to 2.01 in the manual toothbrush group. Additionally, toothbrushing frequency, time, and cooperation increased by 0.82 ± 0.60, 0.82 ± 1.16, and 1.09 ± 0.94, respectively, with initial telemonitoring device use. However, these measures decreased by -1.45 ± 0.68, -1.09 ± 0.70, and - 1.00 ± 1.00 after switching to a manual toothbrush, and decreased by -0.64 ± 0.67, -0.27 ± 1.19, and 0.09 ± 0.94 overall, respectively. However, there were no significant differences in oral microbiota between the groups at these different time points. CONCLUSIONS: The study shows that telemonitoring devices effectively reduce plaque index and improve toothbrushing frequency, time, and cooperation. However, these benefits decrease after switching to a manual toothbrush. Follow-up is needed to assess satisfaction and compliance with telemonitoring device use. CLINICAL RELEVANCE: Using telemonitoring devices in the oral health management of individuals with intellectual and developmental disabilities can improve their oral health quality.

The Ex-Timing trial: evaluating morning, afternoon, and evening exercise on the circadian clock in individuals with type 2 diabetes and overweight/obesity-a randomized crossover study protocol.

BACKGROUND: Exercise is known to provide multiple metabolic benefits such as improved insulin sensitivity and glucose control in individuals with type 2 diabetes mellitus (T2DM) and those at risk. Beyond the traditional exercise dose, exercise timing is perceived as a contemporary hot topic, especially in the field of T2DM; however, the number of intervention studies assessing exercise timing and glucose metabolism is scarce. Our aim is to test the effect of exercise timing (i.e., morning, afternoon, or evening) on the inter-individual response variability in glycemic control and related metabolic health parameters in individuals with T2DM and those at risk during a 12-week intervention. METHODS: A randomized crossover exercise intervention will be conducted involving two groups: group 1, individuals with T2DM; group 2, age-matched older adults with overweight/obesity. The intervention will consist of three 2-week blocks of supervised post-prandial exercise using high-intensity interval training (HIIT). Between each training block, a 2-week washout period, where participants avoid structured exercise, will take place. Assessments will be conducted in both groups before and after each exercise block. The primary outcomes include the 24-h area under the curve continuous glucose monitoring-based glucose. The secondary outcomes include body composition, resting energy expenditure, insulin response to a meal tolerance test, maximal aerobic capacity, peak power output, physical activity, sleep quality, and insulin and glucose levels. All primary and secondary outcomes will be measured at each assessment point. DISCUSSION: Outcomes from this trial will provide us additional insight into the role of exercise timing on the inter-individual response variability in glycemic control and other related metabolic parameters in two distinct populations, thus contributing to the development of more effective exercise prescription guidelines for individuals with T2DM and those at risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT06136013. Registered on November 18, 2023.

Increasing coverage in cervical and colorectal cancer screening by leveraging attendance at breast cancer screening: A cluster-randomised, crossover trial.

BACKGROUND: Screening participation remains suboptimal in cervical cancer (CC) and colorectal cancer (CRC) screening despite their effectiveness in reducing cancer-related morbidity and mortality. We investigated the effectiveness of an intervention by leveraging the high participation rate in breast cancer (BC) screening as an opportunity to offer self-sampling kits to nonparticipants in CC and CRC screening. METHODS AND FINDINGS: A pragmatic, unblinded, cluster-randomised, multiple period, crossover trial was conducted in 5 BC screening units in the Central Denmark Region (CDR) between September 1, 2021 and May 25, 2022. On each of 100 selected weekdays, 1 BC screening unit was randomly allocated as the intervention unit while the remaining units served as controls. Women aged 50 to 69 years attending BC screening at the intervention unit were offered administrative check-up on their CC screening status (ages 50 to 64 years) and CRC screening status (aged 50 to 69), and women with overdue screening were offered self-sampling. Women in the control group received only standard screening offers according to the organised programmes. The primary outcomes were differences between the intervention group and the control group in the total screening coverage for the 2 programmes and in screening participation among women with overdue screening, measured 6 months after the intervention. These were assessed using intention-to-treat analysis, reporting risk differences with 95% confidence intervals (CIs). A total of 27,116 women were included in the trial, with 5,618 (20.7%) in the intervention group and 21,498 (79.3%) in the control group. Six months after the intervention, total coverage was higher in the intervention group as compared with the control group in CC screening (88.3 versus 83.5, difference 4.8 percentage points, 95% CI [3.6, 6.0]; p < 0.001) and in CRC screening (79.8 versus 76.0, difference 3.8 percentage points, 95% CI [2.6, 5.1]; p < 0.001). Among women overdue with CC screening, participation in the intervention group was 32.0% compared with 6.1% in the control group (difference 25.8 percentage points, 95% CI [22.0, 29.6]; p < 0.001). In CRC screening, participation among women overdue with screening in the intervention group was 23.8% compared with 8.9% in the control group (difference 14.9 percentage points, 95% CI [12.3, 17.5]; p < 0.001). Women who did not participate in BC screening were not included in this study. CONCLUSIONS: Offering self-sampling to women overdue with CC and CRC screening when they attend BC screening was a feasible intervention, resulting in an increase in participation and total coverage. Other interventions are required to reach women who are not participating in BC screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT05022511. The record of processing activities for research projects in the Central Denmark Region (R. No.: 1-16-02-217-21).

Healthy Dietary Patterns with and without Meat Improved Cardiometabolic Disease Risk Factors in Adults: A Randomized Crossover Controlled Feeding Trial.

We assessed the effects of consuming a U.S.-style healthy dietary pattern (HDP) with lean, unprocessed beef (BEEF) compared to a U.S.-style HDP without meat (vegetarian, VEG) on short-term changes in cardiometabolic disease (CMD) risk factors in adults classified as overweight or obese. Forty-one adults (22 females, 19 males; age 39.9 ± 8.0 y; BMI 29.6 ± 3.3 kg/m2; mean ± SD) completed two 5-week controlled feeding periods (randomized, crossover, controlled trial). For the BEEF HDP, two 3-oz (168-g) servings/d of lean, unprocessed beef were predominately substituted for some starchy vegetables and refined grains in the VEG HDP. Baseline and post-intervention measurements were fasting CMD risk factors, with serum low-density lipoprotein (LDL), total cholesterol (TC), and total apolipoprotein B as primary outcomes. VEG reduced LDL, insulin, and glucose compared to BEEF. Reductions did not differ between VEG vs. BEEF for TC, high-density lipoprotein (HDL), apolipoprotein A1, small, dense LDL IV, buoyant HDL2b, TC-to-HDL ratio, and systolic blood pressure. Total apolipoprotein B and all other CMD risk factors measured were not influenced by HDP type nor changed over time. Adopting a U.S.-style HDP that is either vegetarian or omnivorous with beef improved multiple cardiometabolic disease risk factors among adults classified as overweight or obese.

Genetic Factors Contributing to Interindividual Variability of α-Tocopherol Levels in Subcutaneous Adipose Tissue among Healthy Adult Males.

In humans, α-tocopherol (α-TOC) is mainly stored in adipose tissue, where it participates in preventing damages induced by inflammation and reactive oxygen species. Factors, including genetic ones, that explain adipose tissue α-TOC concentration remain poorly understood. This study, therefore, aimed to characterize the interindividual variability of adipose tissue α-TOC concentration in healthy individuals and to identify single nucleotide polymorphisms (SNPs) associated with it. The study used a randomized cross-over design with 42 healthy adult males. α-TOC concentration was measured in fasting plasma and periumbilical adipose tissue samples, both at fast and 8 h after consumption of three standard meals. Partial least squares (PLS) regression was performed to identify SNPs associated with the interindividual variability of adipose tissue α-TOC concentration. Adipose tissue α-TOC concentration was not associated with fasting plasma concentration (Pearson's r = 0.24, 95% CI: [-0.08, 0.51]). There was a high interindividual variability of adipose tissue α-TOC concentration (CV = 61%). A PLS regression model comprising 10 SNPs in five genes (PPARG, ABCA1, BUD13, CD36, and MGLL) explained 60% (adjusted R2) of the variability of this concentration. The interindividual variability of adipose tissue α-TOC concentration in humans is due, at least partly, to SNPs in genes involved in α-TOC and triglyceride metabolism.

Citrate Dialysate with and without Magnesium Supplementation in Hemodiafiltration: A Comparative Study Versus Acetate.

The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one.

A simple and effective method for simulating nested exchangeable correlated binary data for longitudinal cluster randomised trials.

BACKGROUND: Simulation is an important tool for assessing the performance of statistical methods for the analysis of data and for the planning of studies. While methods are available for the simulation of correlated binary random variables, all have significant practical limitations for simulating outcomes from longitudinal cluster randomised trial designs, such as the cluster randomised crossover and the stepped wedge trial designs. For these trial designs as the number of observations in each cluster increases these methods either become computationally infeasible or their range of allowable correlations rapidly shrinks to zero. METHODS: In this paper we present a simple method for simulating binary random variables with a specified vector of prevalences and correlation matrix. This method allows for the outcome prevalence to change due to treatment or over time, and for a 'nested exchangeable' correlation structure, in which observations in the same cluster are more highly correlated if they are measured in the same time period than in different time periods, and where different individuals are measured in each time period. This means that our method is also applicable to more general hierarchical clustered data contexts, such as students within classrooms within schools. The method is demonstrated by simulating 1000 datasets with parameters matching those derived from data from a cluster randomised crossover trial assessing two variants of stress ulcer prophylaxis. RESULTS: Our method is orders of magnitude faster than the most well known general simulation method while also allowing a much wider range of correlations than alternative methods. An implementation of our method is available in an R package NestBin. CONCLUSIONS: This simulation method is the first to allow for practical and efficient simulation of large datasets of binary outcomes with the commonly used nested exchangeable correlation structure. This will allow for much more effective testing of designs and inference methods for longitudinal cluster randomised trials with binary outcomes.

Effectiveness of a Virtual Reality Open-Air Bath Program in Reducing Loneliness and Improving Brain Function for Dementia Prevention in Older Adults: Protocol for a Prospective Randomized Crossover Study.

BACKGROUND: Older adults often face loneliness due to chronic illness or loss of close ones, a situation worsened by the COVID-19 pandemic. Increased loneliness heightens the risk of diseases, especially dementia, necessitating urgent action. OBJECTIVE: This study aims to assess the impact of a virtual reality (VR)-based open-air bath program on depression and loneliness in older individuals with subjective cognitive decline/mild cognitive impairment attending the Dementia Medical Center in Kyoto, Japan. We further aim to evaluate the feasibility of the program (participant recruitment and adherence) and to measure program enjoyment and satisfaction. METHODS: The study design is a crossover trial with a 1:1 ratio, wherein 12 participants will be randomly assigned to groups 1 and 2, with group 2 serving as a waitlist control and group 1 receiving the VR program from the onset for 6 months; the VR program will be conducted 6 times (monthly). Program completion for group 1 will be followed by an observation period from months 7 to 12. Group 2 will participate in the VR program from months 7 to 12, with an observation period from months 1 to 6. Cognitive tests, psychiatric assessments, and the University of California, Los Angeles Loneliness Scale will be conducted before the study, at 6 months, and at 12 months. Results will be analyzed using repeated-measures ANOVA. Head magnetic resonance imaging and single-photon emission computed tomography scans will be performed before and after the VR program to evaluate changes and effects on brain regions. RESULTS: Recruitment began in September 2023 and data collection is expected to be completed by March 2025. Complete study results will be published by September 2025. CONCLUSIONS: This study examines the preliminary effects of VR on loneliness in older adults with predementia through open-air bath simulations. VR experiences could benefit this population, particularly those with limited outdoor activities. Quantifying VR's impact will aid in determining the size for a larger clinical trial. Qualitative results will inform participation mechanisms and guide the implementation and design of future trials. TRIAL REGISTRATION: University hospital Medical Information Network UMIN000052667; https://tinyurl.com/3yaccay5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57101.

Impact of virtual reality on peri-interventional pain, anxiety and distress in a pediatric oncology outpatient clinic: a randomized controlled trial.

PURPOSE: Pain and anxiety-inducing interventions have a major impact on pediatric patients. Pain reduction by virtual reality (VR) during port and vein punctures is well studied. This study investigates peri-interventional reduction of pain, anxiety and distress using VR compared to the standard of care (SOC) in a pediatric oncology outpatient clinic. METHODS: In a randomized, controlled cross-over design, patients aged 6-18 years experience potentially painful interventions accompanied by VR. Observational instruments include NRS, FPS-r, BAADS, mYPAS-SF, PedsQL and SSKJ3-8R. All patients undergo two observations: SOC (A) and VR (B) in a randomized order. In addition, parents and staff are interviewed. Specific conditions for VR in an outpatient clinic setting derived from interprofessional focus group discussion are being explored. RESULTS: Between July 2021 and December 2022 57 eligible patients were included and randomized to the orders A/B (n = 28) and B/A (n = 29). Thirty-eight patients completed both observations. Characteristics in both groups did not differ significantly. More than half of the patients had no previous experience with VR, 5% decided to discontinue VR prematurely. Peri-interventional pain, anxiety and distress were significantly reduced by VR compared with SOC. 71% of patients and 76% of parents perceived punctures with VR to be more relaxed than previous ones. 95% of patients perceived fun with VR goggles. Detailed questionnaires on individual stress and anxiety were returned from 26 of 38 patients. Focus group discussion with staff yielded evidence for successful implementation of VR in an outpatient clinic. CONCLUSIONS: The present study shows that VR can be used for peri-interventional reduction of pain, anxiety, and distress in the special environment of a pediatric outpatient clinic. Specific conditions must be met for successful implementation. Further studies are needed to identify particularly susceptible patients and to illuminate alternatives for distraction that are feasible to implement with limited resources. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov ID): NCT06235723; 01/02/2024; retrospectively registered. This study adheres to the standard checklist of CONSORT guidelines.

Effects of a range of 6 prefabricated orthotic insole designs on plantar pressure in a healthy population: A randomized, open-label crossover investigation.

BACKGROUND: Prefabricated orthotic insoles are widely commercially available for self-selection to treat foot and lower-body musculoskeletal pain, without requiring advice from health care professionals. Although they are generally designed to mimic traditional design features of custom-made orthotics used in clinical practice, the effects of prefabricated insoles on plantar pressure distribution are poorly understood. OBJECTIVE: This investigation aimed to evaluate and directly compare the effects of a range of 6 different commercially available prefabricated orthotic insole designs on plantar pressure in healthy individuals. METHODS: This was a single-center, randomized, open-label, crossover investigation. In-shoe dynamic pressure (F-scan) was investigated in 24 healthy subjects with normal foot posture, wearing standard shoes alone and in combination with 6 different orthotic insoles, consecutively, measured on a single day. The biomechanical impact of each insole was determined by the statistical significance of changes from baseline measurements (standard shoe alone). RESULTS: Insoles with heel cups and medial arch geometries consistently increased contact area at medial arch and whole-foot regions and reduced both plantar peak pressure (PP) and pressure time integral at medial arch and heel regions. CONCLUSIONS: This investigation has aided in further understanding the mode of action of prefabricated insoles in a healthy population. The insoles in this study redistributed plantar pressure at key regions of the foot, based on design features common to prefabricated insoles. Prefabricated orthotic insoles represent an easily accessible means of reducing lower-body musculoskeletal stress for those who spend prolonged periods of time on their feet.

E-Cigarette Nicotine Delivery Among Young Adults by Nicotine Form, Concentration, and Flavor: A Crossover Randomized Clinical Trial.

Importance: Concerns have been raised about the abuse liability of modern e-cigarettes that use acidic additives to form nicotine salts, making the inhalation of nicotine smoother than freebase nicotine. Objective: To examine the effects of nicotine form and concentration and e-liquid flavor on subjective effects ratings, vaping behavior, and nicotine uptake among young adults who use e-cigarettes. Design, Setting, and Participants: In this single-blind, within-participant, crossover randomized clinical trial, a convenience sample of young adults aged 21 to 25 years who currently used e-cigarettes was recruited from December 2021 to August 2023, for in-person research laboratory visits in Columbus, Ohio. Interventions: Participants completed up to 9 vaping sessions, starting with their usual e-cigarette brand in the first session followed by 1 of 8 laboratory-prepared e-liquids in a randomly assigned order in each subsequent session. Prepared e-liquids varied by nicotine form (salt-based vs freebase), nicotine concentration (5% vs 1% weight per weight), and flavor (menthol vs tobacco). Each session included a 5-minute, 10-puff standardized vaping period followed by 30 minutes of ad libitum vaping. Main Outcomes and Measures: At 4 time points (0, 5, 10, and 35 minutes) during each vaping session, plasma samples were collected for assessing nicotine uptake, and self-reports of urges, craving, and withdrawal were collected via questionnaires. Positive subjective effects were self-reported after 35 minutes of vaping using a visual analog scale; urges and cravings were reported using the Questionnaire of Smoking Urges (QSU). Puff topography data were collected throughout each vaping session. Results: Seventy-two participants (mean [SD] age, 22.4 [1.4] years; 42 [58.3%] female) who sampled at least 1 laboratory-prepared e-liquid composed the analytic sample. Salt-based (vs freebase) nicotine e-liquids increased nicotine intake, with 5% salt-based e-liquids delivering the highest mean plasma levels of nicotine (11.2 ng/mL [95% CI, 9.3-13.2 ng/mL] at 5 minutes; 17.2 ng/mL [95% CI, 14.3-20.1 ng/mL] at 35 minutes) irrespective of flavors. Higher positive subjective effect ratings (eg, for liking) were received by salt-based (42.8; 95% CI, 39.4-46.1) vs freebase (32.0; 95% CI, 28.6-35.3) nicotine, 1% (43.4; 95% CI, 40.2-46.6) vs 5% (31.2; 95% CI, 27.7-34.6) nicotine, and menthol-flavored (43.2; 95% CI, 39.7-46.7) vs tobacco-flavored (31.5; 95% CI, 28.4-34.7) e-liquids. Salt-based and 1% but not menthol-flavored nicotine elicited more intense puffing (eg, 25% [95% CI, 12%-40%] more total puffs for nicotine salts vs freebase). All study e-liquids reduced urges and cravings, with 5% vs 1% nicotine being more effective (mean [SE] QSU-Desire score at 35 minutes, 15.4 [0.5] vs 16.7 [0.5]). Conclusions and Relevance: In this crossover randomized clinical trial among young adult e-cigarette users, salt-based (vs freebase) nicotine e-liquids increased nicotine intake and yielded more positive subjective effects ratings and intense puffing behaviors, suggesting higher abuse potential. Restricting the level of acidic additives and menthol flavoring may reduce the addictiveness of e-cigarettes. Trial Registration: ClinicalTrials.gov Identifier: NCT05458895.

Percutaneous Coracohumeral Release for Patients with Adhesive Capsulitis: Two-Year Results from a Randomized Control Crossover Study.

BACKGROUND: Adhesive capsulitis (AC) causes a variety of symptoms, including but not limited to pain, stiffness, and a gradual restriction of active and passive range of motion (ROM). The coracohumeral ligament (CHL) plays an important role in this disease process, and percutaneous CHL release (PCHLR) has demonstrated efficacy in treating manifestations of this disorder that are refractory to pain medication, physical therapy, and local injections. Our previous study demonstrated one-year efficacy and durability, and this study examines 2-year data from our original randomized control crossover cohort. OBJECTIVE: To highlight the importance of extended follow-ups evaluating PCHLR's efficacy in AC management. STUDY DESIGN: A prospective, randomized, controlled, cross-over trial. SETTING: An academic medical center. METHODS: Patients with AC refractory to oral medication, physiotherapy, and at least one local injection were included in our original study. In all, there were initially 40 patients (46 shoulders), including 6 patients who underwent bilateral PCHLR using the Tenex® system. In this prospective study, 2 groups, the experiment group (scheduled to receive PCHLR) and the control group (scheduled to receive a local anesthetic in the coracohumeral ligament [LACHL]) were determined through 2-to-1 block randomization. Of these 46 shoulders initially treated, 39 remained in the study at one year. Twenty-six of the 39 shoulders were assigned to the PCHLR group whereas 13 were assigned to the LACHL group. Nine out of 13 shoulders in the LACHL group crossed over to the PCHLR group. Ultimately, 31 shoulders remained in the PCHLR group for 2-year analysis. The effectiveness of these interventions was assessed using a variety of parameters. Pain scores, ROM, and the Oxford Shoulder Score (OSS) were evaluated before the procedure and at one-year and 2-year follow-up visits. RESULTS: In this 2-year follow-up study, a total of 31 shoulders were sampled, comprising 22 women and 5 men, with 4 patients undergoing bilateral procedures. The mean age of the patients was 65 years (± 11.48). Patients' mean body mass index (BMI) was 36.33 (± 6.55), and the mean CHL thickness was 38.5 (± 3.45). Osteoarthritis was present in 11 cases. The mean follow-up period for the study was 29.7 months (± 6.39). The baseline mean external rotation was 30° (± 8), which increased to 62° (± 18) at one year and 53° (± 18) at 2 years. The baseline mean abduction was 60° (± 16), which improved to 77° (± 21) at one year and 68° (± 20) at 2 years. The median NRS decreased from 8 (IQR: 8, 9) at baseline to 3 (IQR: 2, 7) at one year and 5 (IQR: 2, 7) at 2 years. The baseline median OSS was 7 (IQR: 3, 10), which increased to 32 at one year and 22 (IQR: 15, 35) at 2 years. LIMITATIONS: The present investigation has a limited sample size of patients who have ROM impairment caused by CHL thickening. CONCLUSIONS: While the algorithm for AC care has seen little change for several decades, the authors suggest that PCHLR is a safe, durable, and effective option for cases of AC that are refractory to traditional management.