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  1. Armijo-Olivo S, Barbosa-Silva J, de Castro-Carletti EM, de Oliveira-Souza AIS, Pelai EB, Mohamad N, et al.
    Am J Phys Med Rehabil, 2024 Sep 01;103(9):845-857.
    PMID: 38320245 DOI: 10.1097/PHM.0000000000002444
    This review presents a comprehensive summary and critical evaluation of intention-to-treat analysis, with a particular focus on its application to randomized controlled trials within the field of rehabilitation. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a methodological review that encompassed electronic and manual search strategies to identify relevant studies. Our selection process involved two independent reviewers who initially screened titles and abstracts and subsequently performed full-text screening based on established eligibility criteria. In addition, we included studies from manual searches that were already cataloged within the first author's personal database. The findings are synthesized through a narrative approach, covering fundamental aspects of intention to treat, including its definition, common misconceptions, advantages, disadvantages, and key recommendations. Notably, the health literature offers a variety of definitions for intention to treat, which can lead to misinterpretations and inappropriate application when analyzing randomized controlled trial results, potentially resulting in misleading findings with significant implications for healthcare decision making. Authors should clearly report the specific intention-to-treat definition used in their analysis, provide details on participant dropouts, and explain upon their approach to managing missing data. Adherence to reporting guidelines, such as the Consolidated Standards of Reporting Trials for randomized controlled trials, is essential to standardize intention-to-treat information, ensuring the delivery of accurate and informative results for healthcare decision making.
    Matched MeSH terms: Intention to Treat Analysis*
  2. Amir Faisal Mohd. Khairi, Hejar Abdul Rahman, Norsiah Ali
    MyJurnal
    Introduction: Methadone Maintenance Treatment (MMT) is the commonly used intervention for opioid dependents among Malays in FELDA settlements. However, relapse is common. Since majority of Malays are Muslims, Islamic Rehabilitation Intervention Module (ISRIM) using Health Belief Model (HBM) can be implemented as an intervention for reduction of relapse among opioid dependents in FELDA community. The objective of this study were to develop, implement and evaluate the effectiveness of ISRIM in the reduction of relapse among opioids dependent Malay males in FELDA communities in Jengka, Pahang. Methods: A single blind, cluster randomized controlled trial utilizing simple randomization was conducted, involving 10 MMT clinics. Intervention group received ISRIM for one session per week for four consecutive weeks, while control group were put on wait-list. Outcome was relapse, measured monthly for 6 months follow-up by the positive urine for drugs rapid test. Generalized Estimating Equations (GEE) was used as the main effectiveness analysis. Intention-to-treat (ITT), per protocol (PP) analysis, interaction terms, construct terms and key assumption terms were utilized. Results: Individual participation rate was 88.3%. All group comparisons at baseline were not significant (p>0.05). Cumulative relapse after 6-months follow-up for intervention and control group was 13.8% and 31.2%. There was significant difference in relapse between baseline, post-inter-vention and 6-months follow-up within intervention and control group (Q=29.06 vs 61.39,p
    Matched MeSH terms: Intention to Treat Analysis
  3. Hilwati, Hashim, Radhiana Hassan, Syazarina Sharis, Shahrul Azmin, Rabani Remli, Shahizon Azura Mukari, et al.
    Neurology Asia, 2013;18(4):355-360.
    MyJurnal
    Background and Objective: Intravenous thrombolysis service for stroke was introduced at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) in 2009, based on the recommendations of a multidisciplinary team of clinicians. We report the experience at our center in establishing a stroke protocol incorporating computed tomography perfusion (CTP) of the brain, to assess the feasibility of incorporating CTP in the stroke protocol.
    Methods: A retrospective review of all patients who had a CTP between January 2010 and December 2011 was performed. Results: Of 272 patients who were admitted with acute ischemic stroke, 44 (16.2%) arrived within 4.5 hours from symptom onset and had a CTP performed with the intention to treat. The median time for symptom-to-door, symptom-to-scan and door-to-scan was 90.0 minutes (62.5 – 146.3), 211.0 minutes (165.5 – 273.5) and 85.0 minutes (48.0 – 144.8) respectively. Eight patients (2.9%) were thrombolysed of whom five received IV thrombolysis and three underwent mechanical thrombolysis. The median symptom-to-needle and door-to-needle times were 290.5 minutes (261.3 – 405.0) and 225.0 minutes (172.5 – 316.8) respectively. Four patients were thrombolysed despite being outside the window of treatment based on the CTP findings. Six of the thrombolysed patients had a Modified Rankin Score (MRS) of 1-2 at 5 months post procedure.
    Conclusions: CTP provides a benefit to management decisions and subsequent patient outcome. It is feasible to incorporate CTP as a standard imaging modality in a stroke protocol. The delays in the time-dependent pathways are due to our work flow and organisational process rather than performing the CTP per se.
    Matched MeSH terms: Intention to Treat Analysis
  4. Mok WKH, Poh BK, Wee LH, Devanthini DG, Ruzita AT
    Med J Malaysia, 2018 04;73(2):100-105.
    PMID: 29703873
    INTRODUCTION: Obesity and physical inactivity among school children are among the most challenging health problems in Malaysia. The present study aimed to evaluate the sustained impact of Juara Sihat programme on physical activity level and anthropometric status at 18-month post-intervention.

    METHOD: Participants of Juara Sihat (n=55) were followed-up at 18 months after completion of the intervention. Juara Sihat intervention was implemented over 12 weeks and focused on four key components: (i) five one-hour nutrition education classes, (ii) four one-hour physical activity education sessions, (iii) family involvement, and (iv) empowerment of Parents and Teachers Association. Anthropometric variables (body mass index, body fat percentage and waist circumference) were measured and physical activity level was evaluated by using Physical Activity Questionnaire for Children (PAQ-C) at baseline (P0), immediately upon completion of intervention (P1), at three-month post-intervention (P2), and at 18-month postintervention (P3). Analyses of repeated measures analysis of covariance (ANCOVA) with intention-to-treat principle were applied.

    RESULTS: Sustained effects were found in BMI-for-age z-score which showed a reduction (P0 2.41±0.84 vs P3 2.27±0.81) and physical activity level which showed positive improvements (P0 2.46±0.62 vs P3 2.87±0.76) at 18 months after intervention was completed. Body fat and waist circumference had increased over the same time period.

    CONCLUSION: Overall, this study successfully demonstrated sustained intervention effects of Juara Sihat intervention on BMI-for-age z-score and physical activity, but not on body fat percentage and waist circumference.

    Matched MeSH terms: Intention to Treat Analysis
  5. Yahaya R, Zahary MN, Othman Z, Ismail R, Nik Him NAS, Abd Aziz A, et al.
    Heliyon, 2020 May;6(5):e03948.
    PMID: 32426546 DOI: 10.1016/j.heliyon.2020.e03948
    Introduction: Schizophrenia is a chronic mental illness with clusters of symptoms, including cognitive impairment. This study aimed to explore the effect of Tualang Honey (TH) on cognitive domains, especially as it pertained to the verbal memory of schizophrenia patients.

    Method: This was a cross-sectional study involved 80 individuals, diagnosed with schizophrenia. The Malay Version Auditory Verbal Learning Test (MVAVLT) was used. Data were analysed using SPSS 20.0 software. Intention to treat analysis was applied.

    Result: A comparison of the total learning score at eight weeks between the two groups based on time effect and time-treatment interaction favoured TH group.

    Conclusion: This study concludes that by supplementing schizophrenia patients with 8-week of TH did improve total learning performance across domains in the immediate memory among patients with schizophrenia.

    Matched MeSH terms: Intention to Treat Analysis
  6. Tan PC, Abdussyukur SA, Lim BK, Win ST, Omar SZ
    BJOG, 2020 10;127(11):1430-1437.
    PMID: 32356413 DOI: 10.1111/1471-0528.16290
    OBJECTIVE: To evaluate fasting for 12 hours compared with expedited oral feeding in hospitalised women with hyperemesis gravidarum (HG).

    DESIGN: Randomised trial.

    SETTING: University Hospital, Malaysia: April 2016-April 2017.

    POPULATION: One hundred and sixty women hospitalised for HG.

    METHOD: Women were randomised upon admission to fasting for 12 hours or expedited oral feeding. Standard HG care was instituted.

    MAIN OUTCOME MEASURE: Primary outcome was satisfaction score with overall treatment at 24 hours (0-10 Visual Numerical Rating Scale VNRS), vomiting episodes within 24 hours and nausea VNRS score at enrolment, and at 8, 16 and 24 hours.

    RESULTS: Satisfaction score, median (interquartile range) 8 (5-9) versus 8 (7-9) (P = 0.08) and 24-hour vomiting episodes were 1 (0-4) versus 1 (0-5) (P = 0.24) for 12-hour fasting versus expedited feeding, respectively. Repeated measures analysis of variance of nausea scores over 24 hours showed no difference (P = 0.11) between trial arms. Participants randomised to 12-hour fasting compared with expedited feeding were less likely to prefer their feeding regimen in future hospitalisation (41% versus 65%, P = 0.001), to recommend to a friend (65% versus 84%, P = 0.01; RR 0.8, 95% CI 0.6-0.9) and to adhere to protocol (85% versus 95%, P = 0.04; RR 0.9, 95% CI 0.8-1.0). Symptoms profile, ketonuria status at 24 hours and length of hospital stay were not different.

    CONCLUSION: Advisory of 12-hour fasting compared with immediate oral feeding resulted in a non-significant difference in satisfaction score but adherence to protocol and fidelity to and recommendation of immediate oral feeding to a friend were lower. The 24-hour nausea scores and vomiting episodes were similar.

    TWEETABLE ABSTRACT: Women hospitalised for hyperemesis gravidarum could feed as soon, as much and as often as can be tolerated compared with initial fasting.

    Matched MeSH terms: Intention to Treat Analysis
  7. Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al.
    J Clin Oncol, 2018 07 01;36(19):1913-1921.
    PMID: 29498924 DOI: 10.1200/JCO.2017.76.0892
    Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.
    Matched MeSH terms: Intention to Treat Analysis
  8. Chua CS, Yang KC, Chen JH, Liu YH, Hsu YH, Lee HC, et al.
    Int J Food Sci Nutr, 2016 Mar;67(2):177-83.
    PMID: 26883189 DOI: 10.3109/09637486.2016.1144716
    Helicobacter pylori is a major risk factor for gastritis, gastric ulcers and gastric cancer. Traditional therapy with proton pump inhibitor and antibiotics is regarded as optimal for H. pylori eradication whereas, the eradication rate is unsatisfactory. Studies have reported that cranberry may inhibit H. pylori adhesion to the human gastric mucus but lack of other berry extracts have been evaluated in clinical study. Thus, a 9-week add-on randomised controlled trial was conducted to explore the impact of blueberry and grape seed extract (BGE) combinations traditional therapy for H. pylori eradication. In results, we found that there was no significant difference of eradication rate between the berry extract group and placebo group in the intention-to-treat analysis and in the per-protocol analysis (94.64% versus 84.62%, p = 0.085). Diarrhoea, constipation and epigastric pain were observed increasing during ingestion of the berry extract in some cases. In conclusion, this study indicated that no significant difference existed between the BGE extract group and placebo group in eradication rate under triple therapy.
    Matched MeSH terms: Intention to Treat Analysis
  9. Gan KML, Oei JL, Quah-Smith I, Kamar AA, Lordudass AAD, Liem KD, et al.
    Front Pediatr, 2020;8:615008.
    PMID: 33425820 DOI: 10.3389/fped.2020.615008
    Background: Eye exam for Retinopathy of prematurity (ROP) is a painful procedure and pharmacological analgesia might be ineffective. We hypothesized that magnetic auricular acupuncture (MAA) compared to placebo will decrease pain during ROP exam in preterm infants. Methods: Multicentre randomized controlled trial conducted in three hospitals (Australia, Canada, and Malaysia). Eligibility: >32 weeks, ROP exam, not sedated, and parental consent. A total of 100 infants were randomized (1:1) to MAA (n = 50) or placebo (n = 50). MAA stickers or placebo were placed on both ears by an unblinded investigator. Pain was assessed using the Premature Infant Pain Profile. Primary analyses were by intention-to-treat. ClinicalTrials.gov:NCT03650621. Findings: The mean (standard deviation, SD) gestation, birthweight, and postnatal age were (MAA 28(3) vs. placebo 28(2) weeks; MAA 1,057(455) vs. placebo 952(273) g; MAA 7(3) vs. placebo 7(3) weeks. Placebo infants had significantly higher PIPP scores during [mean difference 1.6 points (95%CI 0.1-3.1)] and 1 h mean difference 1.5 points (95%CI 0.7-2.2) after the procedure (p < 0.03). Heart rate was lower (173(22) vs. 184(18)/min) and oxygen saturations were higher (93.8(6.2) vs. 91.7(6.1)%, p = 0.05) in MAA infants. No adverse effects. Interpretation: MAA may reduce physiological pain responses during and after ROP exam in preterm infants. Assessment of long-term effects are warranted. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03650621.
    Matched MeSH terms: Intention to Treat Analysis
  10. Mowla K, Rajai E, Ghorbani A, Dargahi-Malamir M, Bahadoram M, Mohammadi S
    J Clin Diagn Res, 2016 May;10(5):OC32-6.
    PMID: 27437268 DOI: 10.7860/JCDR/2016/16538.7814
    INTRODUCTION:
    HMG-CoA (3-hydroxy-3- methylglutary lcoenzyme A) reductase inhibitors (statins) have anti-inflammatory properties which may be particularly useful in rheumatoid arthritis to suppress disease activity and inflammatory factors.

    AIM:
    The purpose of this clinical trial was to determine anti-inflammatory properties of statins in rheumatoid arthritis.

    MATERIALS AND METHODS:
    Eighty Iranian patients with rheumatoid arthritis, aged between 19 to 75 years were recruited to take part in this randomized, double-blind placebo-controlled trial. Subjects were randomly allocated to two groups to take atorvastatin or placebo 40 mg daily as an adjunct to current disease-modifying anti-rheumatic drugs (DMARDs) treatment. Disease Activity Score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC) & tender joint count (TJC) were assessed before and after three months intervention.

    RESULTS:
    Analysis was based on intention to treat. DAS28 significantly declined in the atorvastatin group in comparison with placebo (p< 0.001). SJC, TJC, CRP and ESR also were significantly dropped in the atorvastatin group in comparison with placebo.

    CONCLUSION:
    It can be concluded that atorvastatin can suppress RA activity and inflmmatory factors in RA patients for high to moderate grade of inflmmation.

    KEYWORDS:
    Anti-inflammatory agents; Erythrocyte sedimentation rate; HMG-CoA; Swollen joint count; Tender joint count
    Matched MeSH terms: Intention to Treat Analysis
  11. Mohamed Rohani M, Ahmad Fuad N, Ahmad MS, Esa R
    Eur J Dent Educ, 2022 Nov;26(4):741-749.
    PMID: 34939257 DOI: 10.1111/eje.12756
    INTRODUCTION: Special Care Dentistry (SCD) education has been introduced in Malaysia, but there are limited number of studies about its impact to students. Thus, this study aimed to explore the level of students' readiness to treat people with learning disability (PWLD) based on their attitudes, self-efficacy and intention to treat.

    METHODS: A questionnaire was developed based on the Dental Student Attitude to the Handicapped Scale, Scale of Attitudes to the Disabled Persons and Health Action Process Approach. The self-administered, validated questionnaire was tested for reliability (Cronbach's alpha = .71-.81), before being distributed to clinical dental students of both genders from two universities (University A, n = 176 and University B, n = 175). Quantitative data were analysed via t test and ANOVA (p treat PWLD was not significantly influenced by university, gender or year of study.

    CONCLUSION: Incorporation of SCD education in the undergraduate curriculum, with hands-on clinical experience and exposure to DET, is recommended to equip students to be efficient oral healthcare providers for PWLD.

    Matched MeSH terms: Intention to Treat Analysis
  12. Flaherty K, Bath PM, Dineen R, Law Z, Scutt P, Pocock S, et al.
    Trials, 2017 Dec 20;18(1):607.
    PMID: 29262841 DOI: 10.1186/s13063-017-2341-5
    RATIONALE: Aside from blood pressure lowering, treatment options for intracerebral haemorrhage remain limited and a proportion of patients will undergo early haematoma expansion with resultant significant morbidity and mortality. Tranexamic acid (TXA), an anti-fibrinolytic drug, has been shown to significantly reduce mortality in patients, who are bleeding following trauma, when given rapidly. TICH-2 is testing whether TXA is effective at improving outcome in spontaneous intracerebral haemorrhage (SICH).

    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.

    TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN93732214 . Registered on 17 January 2013.

    Matched MeSH terms: Intention to Treat Analysis
  13. Yang HK, Ji J, Han SU, Terashima M, Li G, Kim HH, et al.
    Lancet Gastroenterol Hepatol, 2021 02;6(2):120-127.
    PMID: 33253659 DOI: 10.1016/S2468-1253(20)30315-0
    BACKGROUND: Peritoneal recurrence of gastric cancer after curative surgical resection is common and portends a poor prognosis. Early studies suggest that extensive intraoperative peritoneal lavage (EIPL) might reduce the risk of peritoneal recurrence and improve survival. We aimed to evaluate the survival benefit of EIPL in patients with gastric cancer undergoing curative gastrectomy.

    METHODS: In this open-label, phase 3, multicentre randomised trial, patients aged 21-80 years with cT3 or cT4 gastric cancer undergoing curative resection were enrolled at 22 centres from South Korea, China, Japan, Malaysia, Hong Kong, and Singapore. Patients were randomly assigned to receive surgery and EIPL (EIPL group) or surgery alone (standard surgery group) via a web-based programme in random permuted blocks in varying block sizes of four and six, assuming equal allocation between treatment groups. Randomisation was stratified according to study site and the sequence was generated using a computer program and concealed until the interventions were assigned. After surgery in the EIPL group, peritoneal lavage was done with 1 L of warm (42°C) normal 0·9% saline followed by complete aspiration; this procedure was repeated ten times. The primary endpoint was overall survival. All analyses were done assuming intention to treat. This trial is registered with ClinicalTrials.gov, NCT02140034.

    FINDINGS: Between Sept 16, 2012, and Aug 3, 2018, 800 patients were randomly assigned to the EIPL group (n=398) or the standard surgery group (n=402). Two patients in the EIPL group and one in the standard surgery group withdrew from the trial immediately after randomisation and were excluded from the intention-to-treat analysis. At the third interim analysis on Aug 28, 2019, the predictive probability of overall survival being significantly higher in the EIPL group was less than 0·5%; therefore, the trial was terminated on the basis of futility. With a median follow-up of 2·4 years (IQR 1·5-3·0), the two groups were similar in terms of overall survival (hazard ratio 1·09 [95% CI 0·78-1·52; p=0·62). 3-year overall survival was 77·0% (95% CI 71·4-81·6) for the EIPL group and 76·7% (71·0-81·5) for the standard surgery group. 60 adverse events were reported in the EIPL group and 41 were reported in the standard surgery group. The most common adverse events included anastomotic leak (ten [3%] of 346 patients in the EIPL group vs six [2%] of 362 patients in the standard surgery group), bleeding (six [2%] vs six [2%]), intra-abdominal abscess (four [1%] vs five [1%]), superficial wound infection (seven [2%] vs one [<1%]), and abnormal liver function (six [2%] vs one [<1%]). Ten of the reported adverse events (eight in the EIPL group and two in the standard surgery group) resulted in death.

    INTERPRETATION: EIPL and surgery did not have a survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for gastric cancer.

    FUNDING: National Medical Research Council, Singapore.

    Matched MeSH terms: Intention to Treat Analysis
  14. Katijjahbe MA, Granger CL, Denehy L, Royse A, Royse C, Bates R, et al.
    J Physiother, 2018 04;64(2):97-106.
    PMID: 29602750 DOI: 10.1016/j.jphys.2018.02.013
    QUESTION: In people who have undergone cardiac surgery via median sternotomy, does modifying usual sternal precautions to make them less restrictive improve physical function, pain, kinesiophobia and health-related quality of life?

    DESIGN: Two-centre, randomised, controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis.

    PARTICIPANTS: Seventy-two adults who had undergone cardiac surgery via a median sternotomy were included.

    INTERVENTION: Participants were randomly allocated to one of two groups at 4 (SD 1) days after surgery. The control group received the usual advice to restrict their upper limb use for 4 to 6 weeks (ie, restrictive sternal precautions). The experimental group received advice to use pain and discomfort as the safe limits for their upper limb use during daily activities (ie, less restrictive precautions) for the same period. Both groups received postoperative individualised education in hospital and via weekly telephone calls for 6 weeks.

    OUTCOME MEASURES: The primary outcome was physical function assessed by the Short Physical Performance Battery. Secondary outcomes included upper limb function, pain, kinesophobia, and health-related quality of life. Outcomes were measured before hospital discharge and at 4 and 12 weeks postoperatively. Adherence to sternal precautions was recorded.

    RESULTS: There were no statistically significant differences in physical function between the groups at 4 weeks (MD 1.0, 95% CI -0.2 to 2.3) and 12 weeks (MD 0.4, 95% CI -0.9 to 1.6) postoperatively. There were no statistically significant between-group differences in secondary outcomes.

    CONCLUSION: Modified (ie, less restrictive) sternal precautions for people following cardiac surgery had similar effects on physical recovery, pain and health-related quality of life as usual restrictive sternal precautions. Similar outcomes can be anticipated regardless of whether people following cardiac surgery are managed with traditional or modified sternal precautions.

    TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTRN12615000968572. [Katijjahbe MA, Granger CL, Denehy L, Royse A, Royse C, Bates R, Logie S, Nur Ayub MA, Clarke S, El-Ansary D (2018) Standard restrictive sternal precautions and modified sternal precautions had similar effects in people after cardiac surgery via median sternotomy ('SMART' Trial): a randomised trial. Journal of Physiotherapy 64: 97-106].

    Matched MeSH terms: Intention to Treat Analysis
  15. Mitra SR, Tan PY
    Br J Nutr, 2019 05;121(9):1002-1017.
    PMID: 30761964 DOI: 10.1017/S0007114519000345
    The aim of this study was to investigate the effectiveness of the Hipcref (high-protein, energy-restricted, high-vitamin E and high-fibre) diet in Malaysian adults on body composition and metabolic parameters after an intervention period of 6 months. Overweight/obese Malaysian adults (n 128; BMI≥23 kg/m2) were randomised to the Hipcref (n 65) or control diet (n 63). The intervention group received Hipcref diet charts based on their personal preferences. The control group followed a generalised dietary advice based on Malaysian Dietary Guidelines, 2010. All participants were responsible for preparing their own meals. There was a significant treatment group×time effect on anthropometric parameters (P<0·05) on an intention-to-treat basis. Pairwise comparisons revealed that Hipcref diet participants had significant reduction in weight, BMI, waist circumference, fat mass and percentage body fat at months 3 and 6 compared with baseline (P<0·001). The control group had significant increase in weight and BMI at months 3 and 6 compared with baseline (P<0·05). The Hipcref diet group had higher reduction in fasting insulin, insulin resistance and C-reactive protein levels compared with the control group at month 6 (P<0·05). Post-intervention, compared with the control group, the Hipcref diet group was found to consume significantly higher percentage energy from protein, and PUFA, higher energy-adjusted vitamin E (mg) and fibre (g), and lower total energy, lower percentage energy from fat and carbohydrate (P<0·05). The success of the Hipcref diet on overweight/obese Malaysian adults may be due to the combined effect of the nutrient composition of the Hipcref diet.
    Matched MeSH terms: Intention to Treat Analysis
  16. Katijjahbe MA, Denehy L, Granger CL, Royse A, Royse C, Bates R, et al.
    Trials, 2017 06 23;18(1):290.
    PMID: 28645301 DOI: 10.1186/s13063-017-1974-8
    BACKGROUND: The routine implementation of sternal precautions to prevent sternal complications that restrict the use of the upper limbs is currently worldwide practice following a median sternotomy. However, evidence is limited and drawn primarily from cadaver studies and orthopaedic research. Sternal precautions may delay recovery, prolong hospital discharge and be overly restrictive. Recent research has shown that upper limb exercise reduces post-operative sternal pain and results in minimal micromotion between the sternal edges as measured by ultrasound. The aims of this study are to evaluate the effects of modified sternal precautions on physical function, pain, recovery and health-related quality of life after cardiac surgery.

    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.

    TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry identifier: ACTRN12615000968572 . Registered on 16 September 2015 (prospectively registered).

    Matched MeSH terms: Intention to Treat Analysis
  17. Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, et al.
    N Engl J Med, 2019 Jun 27;380(26):2506-2517.
    PMID: 31112380 DOI: 10.1056/NEJMoa1904710
    BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied.

    METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days.

    RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group.

    CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).

    Matched MeSH terms: Intention to Treat Analysis
  18. Boo NY, Rohana J, Yong SC, Bilkis AZ, Yong-Junina F
    Singapore Med J, 2010 Feb;51(2):144-50.
    PMID: 20358154
    The aim of this study was to compare the response and survival rates of term infants with persistent pulmonary hypertension of the newborn (PPHN) on high frequency oscillatory ventilation (HFOV) treated with either inhaled nitric oxide (iNO) or intravenous magnesium sulphate (MgSO4).
    Matched MeSH terms: Intention to Treat Analysis
  19. Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF, et al.
    N Engl J Med, 2011 Dec 29;365(26):2463-72.
    PMID: 22204723 DOI: 10.1056/NEJMoa1111288
    BACKGROUND: Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, an associated reduction in the rate of death from any cause has not been shown.
    METHODS: We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo--both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression--on the rate of death from any cause among hospitalized, acutely ill medical patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. Inclusion criteria were an age of at least 40 years and hospitalization for acute decompensated heart failure, severe systemic infection with at least one risk factor for venous thromboembolism, or active cancer. The primary efficacy outcome was the rate of death from any cause at 30 days after randomization. The primary safety outcome was the rate of major bleeding during and up to 48 hours after the treatment period.
    RESULTS: A total of 8307 patients were randomly assigned to receive enoxaparin plus elastic stockings with graduated compression (4171 patients) or placebo plus elastic stockings with graduated compression (4136 patients) and were included in the intention-to-treat population. The rate of death from any cause at day 30 was 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (risk ratio, 1.0; 95% confidence interval [CI], 0.8 to 1.2; P=0.83). The rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group (risk ratio, 1.4; 95% CI, 0.7 to 3.1; P=0.35).
    CONCLUSIONS: The use of enoxaparin plus elastic stockings with graduated compression, as compared with elastic stockings with graduated compression alone, was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients. (Funded by Sanofi; LIFENOX ClinicalTrials.gov number, NCT00622648.).
    Note: Malaysia is a study site: participating investigators: Yaw Chong Hwa (WT Ma), Najihah I, SH How, Abdul Razak AM, Law WC (ST Tie), Bharathan T, Monniaty M, Aris Chandran, Ngau Yen Yew, Aziah AM, Irene Wong, CK Chuah, Rosemi S, KK Sia, Jeyaindran S, CY Leong
    Matched MeSH terms: Intention to Treat Analysis
  20. WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al.
    N Engl J Med, 2021 Feb 11;384(6):497-511.
    PMID: 33264556 DOI: 10.1056/NEJMoa2023184
    BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).

    METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.

    RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.

    CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

    Matched MeSH terms: Intention to Treat Analysis
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