Cross-over Randomised Controlled Trials Research Articles

Practical cooling interventions for preventing heat strain in indoor factory workers in Thailand.

Occupational heat stress, exacerbated by factors such as climate change and insufficient cooling solutions, endangers the health and productivity of workers, especially in low-resource workplaces. To evaluate the effectiveness of two cooling strategies in reducing physiological strain and productivity of piece-rate workers over a 9-h work shift in a southern Thailand sawmill. In a crossover randomized control trial design, 12 (33 ± 7 y; 1.58 ± 0.05 m; 51 ± 9 kg; n = 5 females) medically screened sawmill workers were randomly allocated into three groups comprising an established phase change material vest (VEST), an on-site combination cooling oasis (OASIS) (i.e., hydration, cold towels, fans, water dousing), and no cooling (CON) across 3 consecutive workdays. Physiological strain was measured via core temperature telemetry and heart rate monitoring. Productivity was determined by counting the number of pallets of wood sorted, stacked, and stowed each day. Relative to CON, OASIS lowered core temperature by 0.25°C [95% confidence interval = 0.24, 0.25] and heart rate by 7 bpm [6, 9] bpm, compared to 0.17°C [0.17, 0.18] and 10 [9,12] bpm reductions with VEST. It was inconclusive whether productivity was statistically lower in OASIS compared to CON (mean difference [MD] = 2.5 [-0.2, 5.2]), and was not statistically different between VEST and CON (MD = 1.4 [-1.3, 4.1]). Both OASIS and VEST were effective in reducing physiological strain compared to no cooling. Their effect on productivity requires further investigation, as even small differences between interventions could lead to meaningful disparities in piece-rate worker earnings over time.

Home versus in-centre haemodialysis for people with kidney failure.

Home versus in-centre haemodialysis for people with kidney failure.

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.

A systematic review on the effects of non-pharmacological interventions for fatigue among people with upper and/or lower limb osteoarthritis.

To identify non-pharmacological fatigue interventions and determine the effectiveness of these non-pharmacological interventions in reducing fatigue immediately and over time in OA. A review protocol (CRD42020163730) was developed and registered with the PROSPERO database. Included studies comprised peer-reviewed randomized controlled trials (RCTs) that examined the effects of conservative interventions on fatigue in people with upper and lower limb OA. Cochrane Collaboration's tool for assessing the risk of bias (ROB-2) was used to assess the quality of evidence of studies. Narrative synthesis was used to summarize the effectiveness of identified fatigue interventions. Out of 2644 citations identified from databases, 32 reports were included after screening for titles, abstracts and full texts. Of these reports, 30 parallel RCTs, one cluster and one cross-over RCT were included. 13 RCTs were of low ROB, 6 had some concerns and 13 had high ROB. The narrative synthesis identified interventions for fatigue including exercise, activity pacing, cognitive behavioural therapy, telerehabilitation and complementary alternative therapies. Exercise interventions showed the most significant beneficial effects on fatigue. Diverse interventions for fatigue management among individuals with upper and lower limb OA were identified. Of these, exercise interventions appear to be the most promising with the majority of these interventions favouring fatigue improvement. While cognitive behavioural therapy has limited evidence of beneficial effects, there is insufficient evidence regarding the effectiveness of other identified interventions, including complementary and alternative therapies, and telerehabilitation.

Effect of high-definition transcranial direct current stimulation among late-subacute and chronic stroke survivors with fatigue: A randomized-controlled crossover trial protocol

Post-stroke fatigue (PSF) is a commonly overlooked symptom that impacts daily functioning and quality of life. It is caused by altered functional connectivity within the brain networks, which can potentially be influenced by neuromodulation. Multiple cortical regions have been targeted to reduce PSF, but the most efficient ones remain uncertain. Therefore, we aim to identify the most appropriate cortical stimulation site to reduce PSF. Twenty participants with PSF will be included in this cross-over trial. Each participant will receive one session of active anodal high definition- transcranial direct current stimulation (HD-tDCS) over three different cortical areas and one session of sham tDCS in a cross-over manner, with a two-week of washout period in between. Pre- and post- fatigue will be assessed using Fatigue Severity Scale and fatigability using electromyography by determining the time to task failure. Resting-state electroencephalography will be performed before and after each stimulation session to determine the functional connectivity of the cortical areas stimulated.

Evaluating time until ligation in a novel tourniquet – A crossover randomized-controlled trial

Introduction and aimSevere external hemorrhage is a significant reason for morbidity and mortality in adults; thus, the swift and correct application of a tourniquet by laypersons can be lifesaving. We conducted this randomized-controlled cross-over study to investigate the use of a novel tourniquet. MethodsParticipants were recruited at the Heidelberg University Hospital. Eligible participants were ≥ 18 years old with a medical background but without prior experience in applying a tourniquet. Participants were 1:1 randomized to the intervention group (PAX tourniquet) or the control group (SAM or CAT tourniquet). In the control group, participants underwent another randomization to either the SAM or CAT tourniquet without a predefined allocation ratio. Hyperspectral measurements were undertaken (i) before ligation, (ii) 30 s after ligation, and (iii) 30 s after the reopening of the tourniquet. The primary outcome was time until ligation before crossover between the respective groups. The analysis of secondary endpoints included all attempts to assess a possible learning effect, intraoperator variability, and hyperspectral measurements. Participants were crossed to the other study group after a brief wash-out phase. ResultsIn total, 50 participants were recruited, resulting in 100 attempts. A success rate of 98% was observed across the study population. Time until ligation was 49 s and 56 s (p = 0.572) in the intervention and control group, respectively. However, there was a significant difference between the PAX and SAM (54 vs 75 s; p = 0.037) and the SAM and CAT tourniquet (75 vs. 47 s; p = 0.015). Further, we observed a significant learning effect in participants allocated to the control group first, with a median reduction of 9 s in the time until ligation. Hyperspectral measurements showed a significant decrease in perfusion and tissue oxygenation after ligation. Further, a significant increase in perfusion and tissue oxygenation was found after reopening the tourniquet compared to the baseline measurement. ConclusionThe novel PAX tourniquet can be applied quickly and effectively by medical personnel without prior experience in applying a tourniquet.

Efficacy of a smartphone-based Cognitive Bias Modification program for emotion regulation: A randomized-controlled crossover trial

Previous research has identified maladaptive emotion regulation as a key factor in psychopathology. Thus, addressing emotion regulation via scalable, low-threshold digital interventions – such as smartphone-based Cognitive Bias Modification (CBM) – holds important therapeutic potential. Using a randomized-controlled crossover trial, we tested the efficacy of an integrated CBM module within the Affect Regulation Training (ART, i.e., CBM-ART) that targeted emotion regulation through elements of appraisal-based and approach avoidance training.Undergraduate students reporting elevated stress were randomized to a one-week active intervention (Mindgames; including psychoeducation, a quiz, and CBM-ART; n = 40), active control training (Emo Shape; including placebo psychoeducation, a quiz, and a placebo swiping task; n = 36) or waitlist (n = 25). Before and after the intervention, we assessed emotion regulation, interpretation bias, stress and depression. We further tested post-training stress reactivity using an anagram task.Results indicated that the active intervention improved negative (OR = 0.35) and positive (OR = 2.40) interpretation biases and symptom measures (d = 0.52–0.87). However, active control training showed attenuated concurrent pre-post changes on interpretation biases (i.e., OR = 0.53 for negative, and OR = 1.49 for positive interpretations) and symptom measures (d = 0.26–0.91). The active intervention was rated positively in terms of acceptability and usability.These findings provide initial evidence for the efficacy and acceptability of an integrated app-based CBM intervention for emotion regulation in reducing interpretation biases and psychopathological symptoms, including stress. However, future studies should disentangle specific mechanisms underlying interventional effects.

Effect of optimized transcranial direct current stimulation on motor cortex activation in patients with sub-acute or chronic stroke: a study protocol for a single-blinded cross-over randomized control trial.

Transcranial direct current stimulation (tDCS) has shown positive but inconsistent results in stroke rehabilitation. This could be attributed to inter-individual variations in brain characteristics and stroke lesions, which limit the use of a single tDCS protocol for all post-stroke patients. Optimizing the electrode location in tDCS for each individual using magnetic resonance imaging (MRI) to generate three-dimensional computer models and calculate the electric field (E-field) induced by tDCS at a specific target point in the primary motor cortex may help reduce these inconsistencies. In stroke rehabilitation, locating the optimal position that generates a high E-field in a target area can influence motor recovery. Therefore, this study was designed to determine the effect of personalized tDCS electrode positions on hand-knob activation in post-stroke patients. This is a crossover study with a sample size of 50 participants, who will be randomly assigned to one of six groups and will receive one session of either optimized-active, conventional-active, or sham tDCS, with 24 h between sessions. The tDCS parameters will be 1 mA (5 × 5 cm electrodes) for 20 min. The motor-evoked potential (MEP) will be recorded before and after each session over the target area (motor cortex hand-knob) and the MEP hotspot. The MEP amplitude at the target location will be the primary outcome. We hypothesize that the optimized-active tDCS session would show a greater increase in MEP amplitude over the target area in patients with subacute and chronic stroke than conventional and sham tDCS sessions.Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007536.

Comparison of Static Stretching on Whole Body Vibration and Strength Training for Improving and Maintaining Hamstring Range of Motion

Background: Hamstring strains are prevalent among individuals engaged in sports and recreational activities. Addressing this, static stretching, whole-body vibrations (WBV), and strength training are recognized for enhancing range of motion (ROM) and reducing muscle injury risks. However, the comparative effectiveness of these modalities on hamstring flexibility and ROM requires further exploration. Objective: The primary objective of this study was to investigate the effects of static stretching combined with whole-body vibrations and strength training on improving and maintaining hamstring range of motion. Methods: This crossover randomized control trial in Karachi involved 44 participants aged 18-25 years, actively participating in various recreational activities. Participants were randomly divided into two groups: one underwent static stretching on whole-body vibration, and the other received strength training. The interventions lasted four weeks, with pre- and post-intervention assessments of active and passive range of motion (AROM and PROM). Data analysis was conducted using SPSS version 23.0. Results: The static stretching with whole-body vibration group showed an increase in AROM from a pre-intervention mean of 131.05° to a post-intervention mean of 136.55°, and in PROM from 131.67° to 137.41°. The strength training group exhibited an increase in AROM from a pre-intervention mean of 135.21° to 142.42°, and in PROM from 135.98° to 144.81°. Both interventions demonstrated statistically significant improvements in hamstring ROM. Conclusion: The study demonstrates that both static stretching on whole-body vibration and strength training are effective in enhancing the flexibility and range of motion of hamstrings. These findings suggest their beneficial incorporation in rehabilitation and athletic training programs.

Emergency front-of-neck access in infants: A pragmatic crossover randomized control trial comparing two approaches on a simulated rabbit model.

Rapid-sequence tracheotomy and scalpel-bougie tracheotomy are two published approaches for establishing emergency front-of-neck access in infants. It is unknown whether there is a difference in performance times and success rates between the two approaches. The aim of this cross-over randomized control trial study was to investigate whether the two approaches were equivalent for establishing tracheal access in rabbit cadavers. The underlying hypothesis was that the time to achieve the tracheal access is the same with both techniques. Between May and September 2022, thirty physicians (pediatric anesthesiologists and intensivists) were randomized to perform front-of-neck access using one and then the other technique: rapid-sequence tracheotomy and scalpel-bougie tracheotomy. After watching training videos, each technique was practiced four times followed by a final tracheotomy during which study measurements were obtained. Based on existing data, an equivalence margin was set at ∆ = ±10 s for the duration of the procedure. The primary outcome was defined as the duration until tracheal tube placement was achieved successfully. Secondary outcomes included success rate, structural injuries, and subjective participant self-evaluation. The median duration of the scalpel-bougie tracheotomy was 48 s (95% CI: 37-57), while the duration of the rapid-sequence tracheotomy was 59 s (95% CI: 49-66, p = .07). The difference in the median duration between the two approaches was 11 s (95% CI: -4.9 to 29). The overall success rate was 93.3% (95% CI: 83.8%-98.2%). The scalpel-bougie tracheotomy resulted in significantly fewer damaged tracheal rings and was preferred among participants. The scalpel-bougie tracheotomy was slightly faster than the rapid-sequence tracheotomy and favored by participants, with fewer tracheal injuries. Therefore, we propose the scalpel-bougie tracheostomy as a rescue approach favoring the similarity to the adult approach for small children. The use of a comparable equipment kit for both children and adults facilitates standardization, performance, and logistics. ClinicalTrials.gov identifier: NCT05499273.

Is older still good, or even better? Evaluation of possibility of using Miller laryngoscope for intubation in adults and comparison with the most widely used Macintosh laryngoscope. Protocol of a crossover randomized control trial

BackgroundMacintosh laryngoscope is the most widely used laryngoscope for intubation. In some patients, e.g. with flaccid, drooping, aplastic epiglottis, usage of this laryngoscope, or even videolaryngoscopes, may not provide visualization of a glottis. Elevation of the laryngopharynx, like in intubation with Miller laryngoscope, may significantly improve intubating conditions. MethodsAn anaesthesiologist with over 20 years of experience will perform direct laryngoscopy with randomly chosen Miller or Macintosh blade, evaluating the visibility of rima glottidis with Cormack-Lehane classification and POGO score with and without external laryngeal pressure. Then the second evaluation of glottis with other blade type will be obtained and the patient will be intubated. Comparison of the rima glottidis visibility when using both blades will be the primary endpoint of the study. The secondary endpoints consist of: demonstrating whether there is a group of adult patients in whom the use of the Miller blade associated with better vocal cord visibility may be predicted based on an anesthesiological examination, and whether external laryngeal pressure improves vocal cord visualization more when using the Miller blade compared with the Macintosh blade. Sample sizeWe performed minimal sample size calculations based on the data derived from the first 60 patients. We assessed the minimal sample size to obtain the alpha of 5 % and power of 90 %. We decide to enroll at least 286 patients. Discussionthis will be the first trial assessing Miller and Macintosh blades in the same population of adult patients. It will determine group of patients in whom Miller laryngoscope will provide better visualization of rima glottidis than Macintosh blade and associated technique, diminishing rate of prolonging intubations and reducing possible aftermaths of hypoxia.

13 Surgical Priming Improves Operative Performance in Surgical Trainees: A Crossover Randomised Control Trial

Abstract Aim The aim of this study was to evaluate the impact of a surgical warm-up using a virtual reality simulator on operative performance. Method This was a single-blinded cross-over randomised control trial in a single tertiary Orthopaedic training centre. Orthopaedic trainees were recruited, and each morning participants rostered to theatre were randomised to either undergo a simulated surgical procedure on a virtual reality simulation system prior to their first case as primary operator (priming arm), or to perform their usual preparatory routine for surgery (control arm). Consultant orthopaedic trainers were recruited within the orthopaedic unit to carry out subjective surgical performance assessments using a validated global rating scale tool on the first case the participant performed on 46 the list as primary operator. Results Over 3 study periods a total of 151 datapoints were collected, with 49 matched datapoints across priming status and procedural level of difficulty. Subjective assessment tools consistently demonstrated improved operative performance by participants following surgical priming (p = 0.001). Conclusions This study highlights that introduction of preoperative priming to improve operative preparation and optimises operative performance. This has not only implications for improved resident training, but also signals towards beneficial downstream effects on patient outcomes, and theatre list planning.

The Effect of Botulinum Toxin Type A Injection in the Rectus Femoris in Stroke Patients Walking With a Stiff Knee Gait: A Randomized Controlled Trial

Background Over activity of the rectus femoris is often cited as a main cause for stiff knee gait (SKG). Botulinum toxin (BoNT) can be used to reduce this over activity. Inconsistent results for the effect of BoNT injections were found in literature which can possibly be explained by the study design as these were uncontrolled or non-randomized studies. Objective To conduct a randomized controlled trial (RCT) to investigate the effect of botulinum toxin type A (BoNT-A) injections in the rectus femoris on gait kinematics and functional outcome in adult stroke patients. Methods Twenty-six participants were included in this triple-blind cross-over RCT. The intervention consisted of an injection with BoNT-A. Placebo is an injection with saline. Besides knee and hip kinematics, functional outcomes were measured. Results Comparison of the effect of BoNT-A injection to placebo injection showed a significant increase in peak knee flexion and knee range of motion of 6.7° and 4.8° respectively. There was no difference in hip kinematics. In functional outcomes, only the 6 Minute Walking Test showed a significant increase of 18.3 m. Conclusions BoNT-A injections in the rectus femoris is a valuable treatment option for stroke patients walking with a SKG to improve knee kinematics. To study the effect on functional outcome more research is necessary with different functional outcome measures that can capture the effect in kinematics. It is important to use kinematic measurements to demonstrate effects in quality of movement that are not captured by commonly used functional outcome measurements post stroke. Clinical Trial Registration: https://trialsearch.who.int/Trial2.aspx?TrialID=NTR2169

Addition of long-acting beta2 agonists or long-acting muscarinic antagonists versus doubling the dose of inhaled corticosteroids (ICS) in adolescents and adults with uncontrolled asthma with medium dose ICS: a systematic review and network meta-analysis.

Inhaled corticosteroids (ICS) are the mainstay treatment for persistent asthma. Escalating treatment is required when asthma is not controlled with ICS therapy alone, which would include, but is not limited to, adding a long-acting beta2-agonist (LABA) or a long-acting muscarinic antagonist (LAMA) or doubling the dose of ICS. To assess the efficacy and safety of adding a LABA or LAMA to ICS therapy versus doubling the dose of ICS in adolescents and adults whose asthma is not well controlled on medium-dose (MD)-ICS using a network meta-analysis (NMA), and to provide a ranking of these treatments according to their efficacy and safety. We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, Global Health, ClinicalTrials.gov, and the World Health Organization ICTRP for pre-registered randomised controlled trials (RCTs) from January 2008 to 19 December 2022. We searched for studies including adolescents and adults with uncontrolled asthma who had been treated with or were eligible for MD-ICS, comparing it to high-dose (HD)-ICS, ICS/LAMA, or ICS/LABA. We excluded cluster- and cross-over RCTs. Studies were of at least 12 weeks duration. We conducted a systematic review and network meta-analysis according to a previously published protocol. We used Cochrane's Screen4ME workflow to assess search results. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. The primary outcome is asthma exacerbations (moderate and severe). We included 38,276 participants from 35 studies (median duration 24 weeks (range 12 to 78); mean age 44.1; 38% male; 69% white; mean forced expiratory volume in one second 2.1 litres and 68% of predicted). MD- and HD-ICS/LABA likely reduce and MD-ICS/LAMA possibly reduces moderate to severe asthma exacerbations compared to MD-ICS (hazard ratio (HR) 0.70, 95% credible interval (CrI) 0.59 to 0.82; moderate certainty; HR 0.59, 95% CrI 0.46 to 0.76; moderate certainty; and HR 0.56, 95% CrI 0.38 to 0.82; low certainty, respectively), whereas HD-ICS probably does not (HR 0.94, 95% CrI 0.70 to 1.24; moderate certainty). There is no clear evidence to suggest that any combination therapy or HD-ICS reduces severe asthma exacerbations compared to MD-ICS (low to moderate certainty). This study suggests no clinically meaningful differences in the symptom or quality of life score between dual combinations and monotherapy (low to high certainty). MD- and HD-ICS/LABA increase or likely increase the odds of Asthma Control Questionnaire (ACQ) responders at 6 and 12 months compared to MD-ICS (odds ratio (OR) 1.47, 95% CrI 1.23 to 1.76; high certainty; and OR 1.59, 95% CrI 1.31 to 1.94; high certainty at 6 months; and OR 1.61, 95% CrI 1.22 to 2.13; moderate certainty and OR 1.55, 95% CrI 1.20 to 2.00; high certainty at 12 months, respectively). MD-ICS/LAMA probably increases the odds of ACQ responders at 6 months (OR 1.32, 95% CrI 1.11 to 1.57; moderate certainty). No data were available at 12 months. There is no clear evidence to suggest that HD-ICS increases the odds of ACQ responders or improves the symptom or qualify of life score compared to MD-ICS (very low to high certainty). There is no evidence to suggest that ICS/LABA or ICS/LAMA reduces asthma-related or all-cause serious adverse events (SAEs) compared to MD-ICS (very low to high certainty). HD-ICS results in or likely results in little or no difference in the included safety outcomes compared to MD-ICS as well as HD-ICS/LABA compared to MD-ICS/LABA. The pairwise meta-analysis shows that MD-ICS/LAMA likely reduces all-cause adverse events (AEs) and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.77 to 0.96; 4 studies, 2238 participants; moderate certainty; and RR 0.51, 95% CI 0.26 to 0.99; 4 studies, 2239 participants; absolute risk reduction 10 fewer per 1000 participants; moderate certainty, respectively). The NMA evidence is in agreement with the pairwise evidence on treatment discontinuation due to AEs, but very uncertain on all-cause AEs, due to imprecision and heterogeneity. The review findings suggest that MD- or HD-ICS/LABA and MD-ICS/LAMA reduce moderate to severe asthma exacerbations and increase the odds of ACQ responders compared to MD-ICS whereas HD-ICS probably does not. The evidence is generally stronger for MD- and HD-ICS/LABA than for MD-ICS/LAMA primarily due to a larger evidence base. There is no evidence to suggest that ICS/LABA, ICS/LAMA, or HD-ICS/LABA reduces severe asthma exacerbations or SAEs compared to MD-ICS. MD-ICS/LAMA likely reduces all-cause AEs and results in a slight reduction in treatment discontinuation due to AEs compared to MD-ICS. The above findings may assist in deciding on a treatment option during the stepwise approach of asthma management. Longer-term safety of higher than medium-dose ICS needs to be addressed in phase 4 or observational studies given that the median duration of included studies was six months.

Personalized digital behaviour interventions increase short-term physical activity: a randomized control crossover trial substudy of the MyHeart Counts Cardiovascular Health Study.

Physical activity is associated with decreased incidence of the chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity. We offered enrolment to community-living iPhone-using adults aged ≥18 years in the USA, UK, and Hong Kong who downloaded the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomized to four 7-day interventions. Interventions consisted of: (i) daily personalized e-coaching based on the individual's baseline activity patterns, (ii) daily prompts to complete 10 000 steps, (iii) hourly prompts to stand following inactivity, and (iv) daily instructions to read guidelines from the American Heart Association (AHA) website. After completion of one 7-day intervention, participants subsequently randomized to the next intervention of the crossover trial. The trial was completed in a free-living setting, where neither the participants nor investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis (modified in that participants had to complete 7 days of baseline monitoring and at least 1 day of an intervention to be included in analyses). This trial is registered with ClinicalTrials.gov, NCT03090321. Between 1 January 2017 and 1 April 2022, 4500 participants consented to enrol in the trial (a subset of the approximately 50 000 participants in the larger MyHeart Counts study), of whom 2458 completed 7 days of baseline monitoring (mean daily steps 4232 ± 73) and at least 1 day of one of the four interventions. Personalized e-coaching prompts, tailored to an individual based on their baseline activity, increased step count significantly (+402 ± 71 steps from baseline, P = 7.1⨯10-8). Hourly stand prompts (+292 steps from baseline, P = 0.00029) and a daily prompt to read AHA guidelines (+215 steps from baseline, P = 0.021) were significantly associated with increased mean daily step count, while a daily reminder to complete 10 000 steps was not (+170 steps from baseline, P = 0.11). Digital studies have a significant advantage over traditional clinical trials in that they can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we present a novel finding that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized. Further studies are needed to determine the effects of digital interventions on long-term outcomes.

Physical Exercise as a Potential Treatment for Fatigue in Parkinson's Disease? A Systematic Review and Meta-Analysis of Pharmacological and Non-Pharmacological Interventions.

Fatigue is one of the most common and debilitating non-motor symptoms among patients with Parkinson's disease (PD) and significantly impacts quality of life. Therefore, effective treatment options are needed. To provide an update on randomized controlled trials (RCTs) including pharmacological and non-pharmacological (but non-surgical) treatments that examine the effects of fatigue on PD patients. We searched the MEDLINE, EMBASE, PsycINFO, CENTRAL, and CINAHL databases for (cross-over) RCTs on pharmacological and non-pharmacological interventions for treating fatigue in PD patients until May 2021. Meta-analyses for random-effects models were calculated when two or more studies on the same treatment option were available using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Fourteen pharmacological and 16 non-pharmacological intervention RCTs were identified. For pharmacological approaches, a meta-analysis could only be performed for modafinil compared to placebo (n = 2) revealing a non-significant effect on fatigue (SMD = - 0.21, 95% CI - 0.74-0.31, p = 0.43). Regarding non-pharmacological approaches, physical exercise (n = 8) following different training approaches versus passive or placebo control groups showed a small significant effect (SMD = - 0.37, 95% CI - 0.69- - 0.05, p = 0.02) which could not be demonstrated for acupuncture vs. sham-acupuncture (SMD = 0.16, 95% CI - 0.19-0.50, p = 0.37). Physical exercise may be a promising strategy to treat fatigue in PD patients. Further research is required to examine the efficacy of this treatment strategy and further interventions. Future studies should differentiate treatment effects on physical and mental fatigue as the different underlying mechanisms of these symptoms may lead to different treatment responses. More effort is required to develop, evaluate, and implement holistic fatigue management strategies for PD patients.

Oestrogen therapy for treating pelvic organ prolapse in postmenopausal women.

Pelvic organ prolapse (POP) is the descent of a woman's uterus, bladder, or rectum into the vagina. It affects 50% of women over 50 years old who have given birth to at least one child, and recognised risk factors are older age, higher number of births, and higher body mass index. This review assesses the effects of oestrogen therapy, alone or in combination with other treatments, on POP in postmenopausal women. To assess the benefits and harms of local and systemic oestrogen therapy in the management of pelvic organ prolapse symptoms in postmenopausal women, and to summarise the principal findings of relevant economic evaluations. We searched the Cochrane Incontinence Specialised Register (up to 20 June 2022), which includes CENTRAL, MEDLINE, two trials registers, and handsearching of journals and conference proceedings. We also checked the reference lists of relevant articles for additional studies. We included randomised controlled trials (RCTs), quasi-RCTs, multi-arm RCTs, and cross-over RCTs that evaluated the effects of oestrogen therapy (alone or in combination with other treatments) versus placebo, no treatment, or other interventions in postmenopausal women with any grade of POP. Two review authors independently extracted data from the included trials using prespecified outcome measures and a piloted extraction form. The same review authors independently assessed the risk of bias of eligible trials using Cochrane's risk of bias tool. Had data allowed, we would have created summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE. We identified 14 studies including a total of 1002 women. In general, studies were at high risk of bias in terms of blinding of participants and personnel, and there were also some concerns about selective reporting. Owing to insufficient data for the outcomes of interest, we were unable to perform our planned subgroup analyses (systemic versus topical oestrogen, parous versus nulliparous women, women with versus without a uterus). No studies assessed the effects of oestrogen therapy alone versus no treatment, placebo, pelvic floor muscle training, devices such as vaginal pessaries, or surgery. However, we did identify three studies that assessed oestrogen therapy in conjunction with vaginal pessaries versus vaginal pessaries alone and 11 studies that assessed oestrogen therapy in conjunction with surgery versus surgery alone. There was insufficient evidence from RCTs to draw any solid conclusions on the benefits or harms of oestrogen therapy for managing POP symptoms in postmenopausal women. Topical oestrogen in conjunction with pessaries was associated with fewer adverse vaginal events compared with pessaries alone, and topical oestrogen in conjunction with surgery was associated with reduced postoperative urinary tract infections compared with surgery alone; however, these findings should be interpreted with caution, as the studies that contributed data varied substantially in their design. There is a need for larger studies on the effectiveness and cost-effectiveness of oestrogen therapy, used alone or in conjunction with pelvic floor muscle training, vaginal pessaries, or surgery, for the management of POP. These studies should measure outcomes in the medium and long term.

The feasibility of a randomized controlled crossover trial to assess the effect of probiotic and prebiotic supplementation on the health of elite wheelchair athletes

BackgroundGastrointestinal (GI) problems represent a health burden in Para athletes and can ultimately reduce athletic performance. This study aimed to evaluate the feasibility of a randomized controlled crossover trial (RCCT) assessing the effects of probiotic and prebiotic supplementation on the health of Swiss elite wheelchair athletes.MethodsThe RCCT was conducted between March 2021 and October 2021. Athletes were randomized to receive either a daily probiotic (3 g of probiotic preparation, including eight bacterial strains), or a daily prebiotic (5 g of oat bran) supplementation first. After the first supplementation phase (4 weeks), a washout period (4 weeks) and the second crossover supplementation phase (4 weeks) followed. Data were collected at four study visits (every 4 weeks) and included 3-day training and nutrition diaries, the Gastrointestinal Quality of Life Index (GIQLI) questionnaire, stool samples, and fasting blood samples. The study assessed the feasibility criteria such as recruitment rate, retention rate, success of data collection, adherence to the protocol, willingness to participate, and safety.ResultsThis pilot study met the majority of the predefined minimum requirements for the feasibility criteria. Out of 43 invited elite wheelchair athletes, 14 (33%) consented (mean (standard deviation) age: 34 (9) years, eight females, 11 with a spinal cord injury). The desired sample size was not reached, but the achieved recruitment rate was modest, especially considering the population studied. All participating athletes completed the study. With the exception of one missing stool sample and two missing diaries, data were successfully collected for all athletes at all four visits. Most athletes adhered to the daily intake protocol for at least 80% of the days, both for probiotics (n = 12, 86%) and prebiotics (n = 11, 79%). Ten (71%) athletes would be willing to participate in a similar study again. No serious adverse events occurred.ConclusionDespite the limited number of elite wheelchair athletes in Switzerland and the modest recruitment rate, the implementation of a RCCT in elite wheelchair athletes is feasible. The data collected in this study provide essential information for the design of the subsequent study which will include a larger cohort of physically active wheelchair users.Trial registrationSwiss Ethics Committee for Northwest/Central Switzerland (EKNZ), 2020–02337). ClinicalTrials.gov, NCT04659408.

Launching “methods and statistics tutorials”: A collection of resources for systematic reviewers

Robust and innovative methods are the lynchpin of Cochrane and remain the basis of its reputation as the home of high-quality systematic reviews. As methodology evolves to respond to the evidence needs of our stakeholders, it is crucial for Cochrane to be able to offer timely and clear advice to those working on our reviews. Cochrane's Methods Support Unit (MSU) was established in 2019 [1] to provide methodological and statistical support to authors and editors working on Cochrane protocols and reviews. A key challenge in the first 2 years of the Unit was the introduction of our new tool [2] to assess the risk of bias in randomized controlled trials (RCTs), but we have dealt with a multiplicity of different issues since being established. By March 2023, the Unit has dealt with over 1200 referrals relating to protocols, systematic reviews, updates of reviews, and statistical and methodological queries relating to reviews. Our work has ranged from full methodological and statistical reviews of research incorporating network meta-analyses to individual queries about the use of an intracluster correlation coefficient to adjust data from an individual study. It quickly became apparent that similar queries were often raised and we noticed common problems when working on reviews. Our monthly web clinic series was set up to allow authors and editors to raise questions and then later to provide guidance on a specific topic in addition [3]. However, we also felt that there is a need for accessible help with these issues which would be instantly available. Professor Doug Altman was a leader and pioneer in Cochrane and in the field of medical statistics [4]. One of Professor Altman's legacies was the Statistics Notes series in The BMJ, which provided clear advice on statistical concepts to medical researchers. Inspired by this work, former and current MSU managers (Dr Kerry Dwan and Rachel Richardson) are launching this series to provide easily accessible advice to the evidence synthesis community on the common methodological and statistical issues that we have observed within Cochrane. The hope is to make this as interactive and easy to understand as possible. In addition, the series will collaborate with Cochrane Training [5] to complement the articles in the series with visual learning, such as short videos or quick e-learning checks, to help those who learn better by doing or watching rather than reading. There are various sources of advice on methodological and statistical issues already available to reviewers, including the Cochrane Handbook for Systematic Reviews of Intervention [6] and resources from specialized Cochrane Methods Groups. This series will complement existing sources by responding to the day-to-day difficulties encountered by reviewers when implementing systematic review methods. The MSU is in a unique position to provide advice; having dealt with thousands of queries and requests for peer review since our inception, we know what reviewers find difficult and also why these issues cause confusion. We also believe that linking the articles with resources from Cochrane Training will make this series uniquely useful. dealing with data from crossover RCTs; the correct way to undertake and interpret subgroup analyses; inclusion of multiarm trials in meta-analysis; heterogeneity; the use of fixed versus random effects models in meta-analysis. Early articles in the series will focus on the use of effect measures in systematic reviews, specifically the standardized mean difference and the use of risk ratios versus odds ratios. These two topics often cause difficulties for authors and editors. Examples will be given in the articles of when to use these measures, how to calculate them and their interpretation. We will also cover cluster RCTs early in the series. We welcome proposals for this series from members across the evidence synthesis community on areas they see as methodological and statistical challenges for authors. Articles should be short tutorials, use the Commentary article type, and, in general, be less than 1000 words. Cochrane's mission is to produce trusted synthesized evidence, make it accessible to all, and advocate for its use. Ensuring that evidence synthesis methods are implemented wisely and accurately is foundational to us being able to achieve this mission. With the Methods and Statistics Tutorials series, we hope to support and onboard a wider and more diverse community of authors to produce the next generation of high-quality Cochrane Reviews and other evidence syntheses. Kerry Dwan: Conceptualization; writing—original draft; writing—review and editing. Rachel Richardson: Conceptualization; writing—review and editing. Kerry Dwan and Rachel Richardson are former and current employees, respectively, of Cochrane. None The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1002/cesm.12017. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Safety and Efficacy of Plaque Removal Using Manual and Powered Toothbrush in Cerebral Palsy Children by Parents/Caregivers: A Randomized Control Crossover Trial.

The aim of our study was to check the safety and efficacy of plaque removal using manual and powered toothbrush in cerebral palsy children by parents/caregivers. This was a single blinded, crossover randomized control trial conducted on 60 cerebral palsy children between the age of 6 to 14 years. They were randomly divided using a flip coin method into two groups: group A-manual toothbrush and group B-powered toothbrush. The plaque index (PI), gingival index (GI), and gingival abrasion (GA) score were measured at baseline, then at an interval of 3, 6, 9, and 12 weeks. This was followed by a crossover between two groups with a washout period of 1 week. Both manual and powered toothbrush showed a significant reduction in plaque and gingival score before and after crossover when compared to baseline (p < 0.05). The GA score was reduced to 100% in both groups. However, there was no statistically significant difference between both the groups before and after the crossover. Also, through the questionnaire it was observed that both child (86.6%) and parent (70%) showed positive feedback towards powered toothbrush. It can be concluded from the present study that the efficacy of a powered toothbrush is comparable to that of a manual toothbrush. Parents and caregivers, on the contrary, displayed a favorable attitude towards the use of powered toothbrushes due to their ease of use. Cerebral palsy is one of the most common neurological disorders among children. It is associated with poor motor skills and manual dexterity that hampers their ability to brush and thus leads to poor oral hygiene. A powered toothbrush seems more appealing and is specially designed for patients with poor neuromotor coordination. Deshpande AN, Naik K, Deshpande N, et al. Safety and Efficacy of Plaque Removal using Manual and Powered Toothbrush in Cerebral Palsy Children by Parents/Caregivers: A Randomized Control Crossover Trial. Int J Clin Pediatr Dent 2023;16(2):344-349.