METHODS: This is a pragmatic randomized control trial study where elective admitted patients will be randomly divided into the intervention (SS) or control (NN) group. All data will be collected during a face-to-face interview, anthropometric measurement, blood sampling (albumin, white blood count, hemoglobin, and c-reactive protein), handgrip strength, and postoperative complications. Group SS will be receiving a tailored lifestyle and intensively supplemented with oral nutrition support as compared to Group NN that will receive standard medical care. The primary outcome for this study is the length of stay in the hospital. Additional outcome measures are changes in biochemical profile and nutritional and functional status. The effects of intervention between groups on the outcome parameters will be analyzed by using the SPSS General Linear Model (GLM) for the repeated measure procedure.

DISCUSSION: The intervention implemented in this study will serve as baseline data in providing appropriate nutritional management in patients undergoing gastrointestinal and oncological surgery.

METHODS: This study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants' self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis.

DISCUSSION: This is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants' preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind.

METHODS: We chose a double-blinded pragmatic randomized-controlled with factorial design for this investigation. The trial is going to recruit 1648 hypertensive patients with coronary artery disease at the age of 21 to 70 years. All participants will already be on anti-hypertensive medication and own a smartphone. They will be randomized into four groups with each having 412 participants. The first group will only receive standard care; while the second group, in addition to standard care, will receive monthly Ed-counselling (educational booklets with animated infographics and peer counseling); the third group will receive daily written and voice reminders and an education-led video once weekly together with standard care; while the fourth one gets both interventions given to second and third groups respectively. All groups will be followed-up for 1 year (0, 6, and 12 months). The primary outcome will be the change in systolic blood pressure while secondary outcomes include health-related quality of life and changes in medication adherence. For measuring changes in systolic blood pressure (SBP) and adherence scores difference at 0, 6, and 12 months between and within the group, parametric (ANOVA/repeated measure ANOVA) and non-parametric tests (Kruskal-Wallis test/Friedman test) will be used. By using the general estimating equation (GEE) with negative binomial regression, at 12 months, the covariates affecting primary and secondary outcomes will be determined and controlled. The analysis will be intention-to-treat. All the outcomes will be analyzed at 0, 6, and 12 months; however, the final analysis will be at 12 months from baseline.

TRIAL DESIGN: The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial.

PARTICIPANTS: All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan).

INTERVENTION AND COMPARATOR: In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan.

MAIN OUTCOMES: Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization.

RANDOMISATION: Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure.

BLINDING (MASKING): Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking.

NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 1000 participants will be enrolled in the study with 1:1 allocation.

TRIAL STATUS: The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022.

TRIAL REGISTRATION: Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087 .

METHODS: PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel-Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity.

DISCUSSION: Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases.

METHODS/DESIGN: This protocol describes our randomised controlled trial that tests whether a breastfeeding meditation audio reduces maternal stress in mothers of late preterm infants in London. Home visits will be conducted at 2-3 and 6-8 weeks post-delivery. Participants will be randomised to a control group or an intervention group, where mothers will be asked to listen to a meditation tape on a daily basis while breastfeeding. The main outcomes of the intervention will be maternal stress markers and infant weight Z-score. Potential mediators will be the secondary outcomes and include breast milk macronutrient and hormone levels (ghrelin, leptin, cortisol, and adiponectin), milk volume assessed by 48-h test-weighing, and maternal engagement with the infant. Infant behaviour, including crying and sleeping, and infant appetite will be evaluated. Data about other mediators such as maternal perception of milk supply and salivary oxytocin will be collected.

DISCUSSION: We hypothesise that the use of the breastfeeding meditation will reduce maternal stress and consequently improve infant growth mediated by changes in milk composition and volume and maternal behaviour. This study will allow us to understand the mother-infant factors that influence breastfeeding in late preterm infants and potentially identify a method that could improve mother, infant, and breastfeeding outcomes.

METHODS/DESIGN: The study will be a prospective randomized controlled trial comparing an intensive tobacco-related education program versus non-tobacco-related training on pharmacists' tobacco-use-related knowledge, attitudes, self-efficacy, and skills. Community pharmacists practicing in Qatar will be eligible for participation in the study. A random sample of pharmacists will be selected for participation. Consenting participants will be randomly allocated to intervention or control groups. Participants in the intervention group will receive an intensive education program delivered by a multi-disciplinary group of educators, researchers, and clinicians with expertise in tobacco cessation. A short didactic session on a non-tobacco-related topic will be delivered to pharmacists in the control group. The study has two primary outcomes: post-intervention tobacco-related knowledge and post-intervention skills for tobacco cessation assessed using a multiple-choice-based evaluation instrument and an Objective Structured Clinical Examination (OSCE), respectively. The secondary study outcomes are post-intervention attitudes towards tobacco cessation and self-efficacy in tobacco-cessation interventions assessed using a survey instrument. An additional secondary study outcome is the post-intervention performance difference in relation to tobacco-cessation skills in the practice setting assessed using the simulated client approach.

DISCUSSION: If demonstrated to be effective, this education program will be considered as a model that Qatar and the Middle East region can apply to overcome the burden of tobacco-use disorder.

METHODS AND DESIGN: TICH-2 is a pragmatic, phase III, prospective, double-blind, randomised placebo-controlled trial. Two thousand adult (aged ≥ 18 years) patients with an acute SICH, within 8 h of stroke onset, will be randomised to receive TXA or the placebo control. The primary outcome is ordinal shift of modified Rankin Scale score at day 90. Analyses will be performed using intention-to-treat.

RESULTS: This paper and its attached appendices describe the statistical analysis plan (SAP) for the trial and were developed and published prior to database lock and unblinding to treatment allocation. The SAP includes details of analyses to be undertaken and unpopulated tables which will be reported in the primary and key secondary publications. The database will be locked in early 2018, ready for publication of the results later in the same year.

DISCUSSION: The SAP details the analyses that will be done to avoid bias arising from prior knowledge of the study findings. The trial will determine whether TXA can improve outcome after SICH, which currently has no definitive therapy.

METHODS/DESIGN: This open-labelled, randomised controlled trial (RCT) will randomly allocate patients into intervention and control groups. Ambulated Malaysian aged over 18 years and scheduled for elective surgery for (suspected) GC, will be included in this study. The intervention group will be given whey-protein-infused carbohydrate-loading drinks on the evening before their operation and 3 h before their operation as well as started on early oral feeding 4 h post-operatively. The control group will be fasted overnight pre-operation and only allowed plain water, and return to a normal diet is allowed when bowel sounds return post-operatively. The primary outcomes of study are length of post-operative hospital stay, length of clear-fluid tolerance, solid-food tolerance and bowel function. Additional outcome measures are changes in nutritional status, biochemical profile and functional status. Data will be analysed on an intention-to-treat basis.

METHODS: The DROP-Asian ACS is a prospective, stepped wedge, cluster-randomized trial enrolling 4260 participants presenting with chest pain to the ED of 12 acute care hospitals in five Asian countries (UMIN; 000042461). Consecutive patients presenting with suspected acute coronary syndrome between July 2022 and Apr 2024 were included. Initially, all clusters will apply "usual care" according to local standard operating procedures including hs-cTnT but not the 0/1-h algorithm. The primary outcome is the incidence of major adverse cardiac events (MACE), the composite of all-cause death, myocardial infarction, unstable angina, or unplanned revascularization within 30 days. The difference in MACE (with one-sided 95% CI) was estimated to evaluate non-inferiority. The non-inferiority margin was prespecified at 1.5%. Secondary efficacy outcomes include costs for healthcare resources and duration of stay in ED.

METHODS/DESIGN: This study is a phase II, double-blind, randomised controlled trial with concealed allocation, blinding of patients and assessors, and intention-to-treat analysis. Patients (n = 72) will be recruited following cardiac surgery via a median sternotomy. Sample size calculations were based on the minimal important difference (two points) for the primary outcome: Short Physical Performance Battery. Thirty-six participants are required per group to counter dropout (20%). All participants will be randomised to receive either standard or modified sternal precautions. The intervention group will receive guidelines encouraging the safe use of the upper limbs. Secondary outcomes are upper limb function, pain, kinesiophobia and health-related quality of life. Descriptive statistics will be used to summarise data. The primary hypothesis will be examined by repeated-measures analysis of variance to evaluate the changes from baseline to 4 weeks post-operatively in the intervention arm compared with the usual-care arm. In all tests to be conducted, a p value <0.05 (two-tailed) will be considered statistically significant, and confidence intervals will be reported.

DISCUSSION: The Sternal Management Accelerated Recovery Trial (S.M.A.R.T.) is a two-centre randomised controlled trial powered and designed to investigate whether the effects of modifying sternal precautions to include the safe use of the upper limbs and trunk impact patients' physical function and recovery following cardiac surgery via median sternotomy.

METHODS/DESIGN: The CROSSSD study adopts an international two-round online modified Delphi survey followed by a stakeholder consensus meeting to identify a patient-centred core outcome domain set for SSD based on what is considered critical and important for assessing whether an intervention for SSD has worked.

METHODS: Records were identified by searching MEDLINE, EMBASE, PubMed, CINAHL, ClinicalTrials.gov, ISRCTN, CENTRAL, WHO ICTRP and the NIHR UK clinical trials gateway. The search included records published from 1946 to March 2020. Included studies were those as follows: (a) recruiting adults aged 18 years or older diagnosed with SSD of average threshold severity worse than 70 dB HL in the worse-hearing ear and normal (or near-normal) hearing in the better-hearing ear, (b) evaluating interventions to restore bilateral and/or binaural hearing and (c) enrolling those adults in a controlled trial, before-and-after study or cross-over study. Studies that fell just short of the participant eligibility criteria were included in a separate sensitivity analysis.

RESULTS: Ninety-six studies were included (72 full inclusion, 24 sensitivity analysis). For fully included studies, 37 exclusively evaluated interventions to re-establish bilateral hearing and 29 exclusively evaluated interventions to restore binaural hearing. Overall, 520 outcome domains were identified (350 primary and 170 secondary). Speech-related outcome domains were the most common (74% of studies), followed by spatial-related domains (60% of studies). A total of 344 unique outcome instruments were reported. Speech-related outcome domains were measured by 73 different instruments and spatial-related domains by 43 different instruments. There was considerable variability in duration of follow-up, ranging from acute (baseline) testing to 10 years after the intervention. The sensitivity analysis identified no additional outcome domains.

CONCLUSIONS: This review identified large variability in the reporting of outcome domains and instruments in studies evaluating the therapeutic benefits and harms of SSD interventions. Reports frequently omitted information on what domains the study intended to assess, and on what instruments were used to measure which domains.

METHODS: The study is being conducted as a randomized controlled intervention trial. Adult participants with unipolar depression are being randomized into three groups (BPT, MMT, or CG), and the first two groups are undergoing a 10-week treatment phase. CG follows their individual standard treatment as usual. A priori power analysis revealed that about 120 people should be included to capture a moderate effect. The primary outcome of the study is depression rated with the Montgomery and Asberg Depression Rating Scale (MADRS) before (t0), directly after (t1), and 12 months after the intervention phase (t2). Data are being collected via questionnaires, computer-assisted video interviews, and physical examinations. The primary hypotheses will be statistically analyzed by mixed model ANOVAs to compare the three groups over time. For secondary outcomes, further multivariate methods (e.g., mixed model ANOVAs and regression analyses) will be conducted. Qualitative data will be evaluated on the basis of the qualitative thematic analysis.

DISCUSSION: This study is investigating psychological and physical effects of BPT and MMT and its factors of influence on outpatients suffering from depression compared with a CG in a highly naturalistic design. The study could therefore provide insight into the modes of action of group therapy for depression and help to establish new short-term group treatments. Methodological limitations of the study might be the clinical heterogeneity of the sample and confounding effects due to simultaneous individual psychotherapy.

METHODS: A two-round online survey will be conducted, followed by a stakeholder consensus meeting to identify a Core Domain Set. Participants will belong to one of two stakeholder groups: healthcare users with lived experience of tinnitus, and professionals with relevant clinical, commercial, or research experience.