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  1. Loh SY, Lee SY, Quek KF, Murray L
    Asian Pac J Cancer Prev, 2012;13(12):6337-42.
    PMID: 23464455
    BACKGROUND: Clinical trials on cancer subjects have one of the highest dropout rates. Barriers to recruitment range from patient-related, through institutional-related to staff-related factors. This paper highlights the low response rate and the recruitment barriers faced in our Qigong exercises trial.

    MATERIALS AND METHOD: The Qigong trial is a three-arm trial with a priori power size of 114 patients for 80% power. The University Malaya Medical Centre database showed a total of 1,933 patients from 2006-2010 and 751 patients met our inclusion criteria. These patients were approached via telephone interview. 131 out of 197 patients attended the trial and the final response rate was 48% (n=95/197).

    RESULTS: Multiple barriers were identified, and were regrouped as patient- related, clinician-related and/or institutional related. A major consistent barrier was logistic difficulty related to transportation and car parking at the Medical Centre. conclusions: All clinical trials must pay considerable attention to the recruitment process and it should even be piloted to identify potential barriers and facilitators to reduce attrition rate in trials.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  2. Parthiban N, Esterman A, Mahajan R, Twomey DJ, Pathak RK, Lau DH, et al.
    J Am Coll Cardiol, 2015 Jun 23;65(24):2591-2600.
    PMID: 25983009 DOI: 10.1016/j.jacc.2015.04.029
    BACKGROUND: Remote monitoring (RM) of implantable cardioverter-defibrillators (ICD) is an established technology integrated into clinical practice. One recent randomized controlled trial (RCT) and several large device database studies have demonstrated a powerful survival advantage for ICD patients undergoing RM compared with those receiving conventional in-office (IO) follow-up.

    OBJECTIVES: This study sought to conduct a systematic published data review and meta-analysis of RCTs comparing RM with IO follow-up.

    METHODS: Electronic databases and reference lists were searched for RCTs reporting clinical outcomes in ICD patients who did or did not undergo RM. Data were extracted from 9 RCTs, including 6,469 patients, 3,496 of whom were randomized to RM and 2,973 to IO follow-up.

    RESULTS: In the RCT setting, RM demonstrated clinical outcomes comparable with office follow-up in terms of all-cause mortality (odds ratio [OR]: 0.83; p = 0.285), cardiovascular mortality (OR: 0.66; p = 0.103), and hospitalization (OR: 0.83; p = 0.196). However, a reduction in all-cause mortality was noted in the 3 trials using home monitoring (OR: 0.65; p = 0.021) with daily verification of transmission. Although the odds of receiving any ICD shock were similar in RM and IO patients (OR: 1.05; p = 0.86), the odds of inappropriate shock were reduced in RM patients (OR: 0.55; p = 0.002).

    CONCLUSIONS: Meta-analysis of RCTs demonstrates that RM and IO follow-up showed comparable overall outcomes related to patient safety and survival, with a potential survival benefit in RCTs using daily transmission verification. RM benefits include more rapid clinical event detection and a reduction in inappropriate shocks.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods
  3. Pui Kei C, Mohd Nordin NA, Abdul Aziz AF
    Medicine (Baltimore), 2020 Nov 20;99(47):e23296.
    PMID: 33217861 DOI: 10.1097/MD.0000000000023296
    INTRODUCTION: Stroke survivors are commonly at risk of functional decline following discharge from rehabilitation, which increase their susceptibility to falls, dependency in activities of daily living and emotional disturbances. To combat these, continued therapy is important. Home-based therapy (HBT) has been shown to be useful in maintaining functional performance and quality of life of chronic stroke survivors. However, evidence on its effectiveness remains limited, while no studies are available to date which report the benefit of HBT on stroke survivors self-efficacy and emotional status. Therefore, this study aims to assess the effectiveness of post-discharge HBT in comparison to usual practice on functional outcome (mobility and gait speed), self-efficacy and anxiety level among stroke survivors.

    METHODS: This is an assessor-blinded randomized control trial comparing 2 types of intervention which are HBT (experimental group) and usual practice (UP) (control group). Based on sample size calculation using GPower, a total number of 42 participants will be recruited and allocated into either the HBT or the UP group. Participants in HBT group will receive a set of structured exercise therapy consisting of progressive strengthening, balance and task-related exercises. While participants in UP group will receive a usual "intervention" practised by rehabilitation professional prior to discharging stroke patients from their care. Both groups are advised to perform the given interventions for 3 times per week for 12 weeks under the supervision of their caregiver. Outcomes of interventions will be measured using timed up and go test (for mobility), ten-meter walk test (for gait speed), stroke self-efficacy questionnaire (for self-efficacy) and hospital anxiety and depression scale (for anxiety level). All data will be analyzed using descriptive and inferential statistics.

    DISCUSSION: This study will provide the information on the effectiveness of HBT in comparison to UP among stroke population who are discharged from rehabilitation. Findings from the study will enable rehabilitation professionals to design effective discharge care plan for stroke survivors in combating functional decline when no longer receiving hospital-based therapy.

    TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001182189 (last updated 22/11/2019).

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  4. Sartini C, Lomivorotov V, Pieri M, Lopez-Delgado JC, Baiardo Redaelli M, Hajjar L, et al.
    J Cardiothorac Vasc Anesth, 2019 05;33(5):1430-1439.
    PMID: 30600204 DOI: 10.1053/j.jvca.2018.11.026
    The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.
    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  5. Bosch J, Eikelboom JW, Connolly SJ, Bruns NC, Lanius V, Yuan F, et al.
    Can J Cardiol, 2017 08;33(8):1027-1035.
    PMID: 28754388 DOI: 10.1016/j.cjca.2017.06.001
    BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy.

    METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo.

    RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD.

    CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  6. Vasu DT, Mohd Nordin NA, Ghazali SE
    Medicine (Baltimore), 2021 Aug 20;100(33):e26924.
    PMID: 34414949 DOI: 10.1097/MD.0000000000026924
    INTRODUCTION: The occurrence of post-stroke emotional problems is significant during the early post-stroke stage and affects the recovery of functionality among the survivors. Because stroke survivors require active engagement in rehabilitation to optimize the process of neuroplasticity in the initial stage of stroke, there is a need to integrate an intervention, preferably therapists-mediated during rehabilitation, which reduce emotional problems thus improve motivation level among the survivors. One such technique is autogenic relaxation training (ART). ART has been found to reduce anxiety and depression among patients with several medical conditions. However, its usage in stroke survivors during rehabilitation has been limited to date. Therefore, this study is intended to evaluate the effectiveness of ART in addition to usual physiotherapy in improving emotional state and functional level of stroke survivors during rehabilitation.

    METHODS: This is an assessor blinded randomized controlled trial comparing 2 intervention approaches namely ART-added physiotherapy (experimental group) and usual physiotherapy (control group). A total of 70 post-stroke patients will be recruited and allocated into either the ART-added physiotherapy or the usual physiotherapy group. The ART-added physiotherapy group will undergo a 20-minute ART session followed by 40 minutes of usual physiotherapy. While the usual physiotherapy group will receive usual physiotherapy alone for 60 minutes. All participants will be treated once a week and are required to carry out a set of home exercises for 2 times per week during the 12-week intervention. Assessment of emotional status and functional independence will be carried out at pre-intervention and week 13 of the intervention with the use of Hospital anxiety and depression scale, Barthel index, and EuroQol-5 dimensions-5 levels. All data will be analyzed using descriptive and inferential statistics.

    DISCUSSION: The expected main study outcome is an enhanced evidence-based physiotherapy program that may be used by physiotherapists in the rehabilitation of stroke patients with emotional disturbances.

    TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001664134 (last updated on 28/11/2019).

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  7. van Pelt BJ, Idris S, Jagersma G, Duvekot J, Maras A, van der Ende J, et al.
    BMC Psychiatry, 2020 06 01;20(1):274.
    PMID: 32487179 DOI: 10.1186/s12888-020-02650-9
    BACKGROUND: Social skills interventions are commonly deployed for adolescents with autism spectrum disorder (ASD). Because effective and appropriate social skills are determined by cultural factors that differ throughout the world, the effectiveness of these interventions relies on a good cultural fit. Therefore, the ACCEPT study examines the effectiveness of the Dutch Program for the Education and Enrichment of Relational Skills (PEERS®) social skills intervention.

    METHODS/DESIGN: This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28).

    CONCLUSION: This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect.

    TRAIL REGISTRATION: Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  8. Chin WK, Lee SWH
    Int J Clin Pharm, 2018 Oct;40(5):963-976.
    PMID: 29777328 DOI: 10.1007/s11096-018-0655-3
    Background Atopic dermatitis (AD) is the most common form of eczema. As leukotriene mediators are involved in the inflammatory phase of atopic dermatitis, montelukast has been suggested as a possible therapy. Aim of the review To evaluate the safety and efficacy of montelukast off-label use for the treatment atopic dermatitis. Method A search was performed from database inception until March 2018 in six electronic databases for randomized-controlled-trials examining the use of montelukast for AD. Results Among 301 articles screened, 11 studies met the inclusion criteria and were included in the review. The study populations consist of paediatric and adult subjects with moderate-to-severe AD. Montelukast use was shown to improve symptoms such as pruritus in four studies. Another 2 studies reported that montelukast could improve symptoms similar to the standard regimen of topical steroid and oral antihistamine. However, five studies reported that montelukast had no effects in symptoms alleviation. The use of montelukast was associated with a similar safety profile to placebo and well-tolerated with minimal adverse effects. Conclusion There is limited evidence to suggest that the off-label use of montelukast is effective in treating moderate-to-severe AD. Further research with larger study populations employing standardized endpoint measuring instrument is warranted to further investigate the off-label use of montelukast in AD treatment. Until then, the use of conventional treatments including optimal daily skin hydration should remain the mainstay in the management of atopic dermatitis. In fact, for moderate-to-severe condition, steroid sparing immune-suppressants should still be used clinically until more effective and safer alternative is discovered.
    Matched MeSH terms: Randomized Controlled Trials as Topic/methods
  9. Sartini C, Lomivorotov V, Pisano A, Riha H, Baiardo Redaelli M, Lopez-Delgado JC, et al.
    J Cardiothorac Vasc Anesth, 2019 Oct;33(10):2685-2694.
    PMID: 31064730 DOI: 10.1053/j.jvca.2019.03.022
    OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings.

    DESIGN: A systematic review of the literature followed by a consensus-based voting process.

    SETTING: A web-based international consensus conference.

    PARTICIPANTS: Two hundred fifty-one physicians from 46 countries.

    INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines.

    MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed.

    CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods*
  10. Ng SS, Lai NM, Nathisuwan S, Chaiyakunapruk N
    Clin Drug Investig, 2018 Jul;38(7):579-591.
    PMID: 29569095 DOI: 10.1007/s40261-018-0641-5
    INTRODUCTION: Anticoagulation therapy is the fundamental approach for stroke prevention in atrial fibrillation (AF) patients. Numerous systematic reviews comparing anticoagulation strategies have been published. We aim to summarize the efficacy and safety evidence of these strategies in AF patients from previously published systematic reviews.

    METHODS: We searched PubMed, EMBASE and Cochrane library from inception to Feb 24th, 2017, to identify systematic reviews and meta-analyses of randomized controlled trials that assessed interventions or strategies to improve oral anticoagulant use in AF patients.

    RESULTS: Thirty-four systematic reviews were eligible for inclusion but only 11 were included in the qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining systematic reviews had overlapping primary studies. There was insufficient evidence to support the efficacy of genotype-guided dosing and pharmacist-managed anticoagulation clinics for stroke prevention in AF patients. Conversely, patient's self-management and novel oral anticoagulants (NOACs), in general were superior to warfarin for preventing stroke and reducing mortality. All interventions showed comparable risk of major bleeding with warfarin.

    CONCLUSION: Findings from this overview support the superiority of NOACs and patient's self-management for preventing stroke in AF patients. However, uncertainties remain on the benefits of genotype-guided dosing and pharmacist-managed anticoagulation clinics due to poor quality evidence, and future research is warranted.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods
  11. Kua KP, Lee SWH
    Pharmacotherapy, 2017 Jun;37(6):755-769.
    PMID: 28423192 DOI: 10.1002/phar.1936
    BACKGROUND: Respiratory syncytial virus (RSV) is a common pathogen in infants with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection as the standard of care for infants with CF remains controversial.

    OBJECTIVE: To evaluate the efficacy of palivizumab in reducing the incidence of RSV hospitalization in children with CF who are younger than 2 years.

    METHODS: Four electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from inception until January 31, 2017, for clinical studies investigating the use of palivizumab in infants with CF aged less than 2 years. The primary outcome was hospitalization rate due to RSV infection. Secondary outcomes included hospitalization for respiratory illness, length of hospital stay, safety (adverse effects), and cost-effectiveness of palivizumab prophylaxis.

    RESULTS: The review included a total of 10 studies (six cohort studies, two before-and-after studies, one cross-sectional study, and one randomized controlled trial) involving 3891 patients with CF. Seven studies reported that palivizumab prophylaxis had a positive impact on the rate of RSV hospitalization. Five studies (n=3404) reported that palivizumab prophylaxis significantly reduced the rate of hospitalization due to RSV infection compared to no prophylaxis. One study (n=5) demonstrated patients with CF who received palivizumab had no RSV hospitalization. Another study showed infants with CF receiving palivizumab (n=117) had a lower risk of hospitalization for RSV infection compared with premature infants (gestational age < 35 completed weeks) who received palivizumab (n=4880).

    CONCLUSIONS: Evidence from the literature suggests that palivizumab may have a potential role in reducing RSV hospitalization in children aged less than 2 years with CF. Given the lack of overall data, additional research is warranted to better understand the efficacy and safety of prophylactic palivizumab in infants with CF.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods
  12. Kandiah N, Chan YF, Chen C, Dasig D, Dominguez J, Han SH, et al.
    CNS Neurosci Ther, 2021 Feb;27(2):149-162.
    PMID: 33352000 DOI: 10.1111/cns.13536
    BACKGROUND: Mild cognitive impairment (MCI) is a neurocognitive state between normal cognitive aging and dementia, with evidence of neuropsychological changes but insufficient functional decline to warrant a diagnosis of dementia. Individuals with MCI are at increased risk for progression to dementia; and an appreciable proportion display neuropsychiatric symptoms (NPS), also a known risk factor for dementia. Cerebrovascular disease (CVD) is thought to be an underdiagnosed contributor to MCI/dementia. The Ginkgo biloba extract, EGb 761® , is increasingly being used for the symptomatic treatment of cognitive disorders with/without CVD, due to its known neuroprotective effects and cerebrovascular benefits.

    AIMS: To present consensus opinion from the ASian Clinical Expert group on Neurocognitive Disorders (ASCEND) regarding the role of EGb 761® in MCI.

    MATERIALS & METHODS: The ASCEND Group reconvened in September 2019 to present and critically assess the current evidence on the general management of MCI, including the efficacy and safety of EGb 761® as a treatment option.

    RESULTS: EGb 761® has demonstrated symptomatic improvement in at least four randomized trials, in terms of cognitive performance, memory, recall and recognition, attention and concentration, anxiety, and NPS. There is also evidence that EGb 761® may help delay progression from MCI to dementia in some individuals.

    DISCUSSION: EGb 761® is currently recommended in multiple guidelines for the symptomatic treatment of MCI. Due to its beneficial effects on cerebrovascular blood flow, it is reasonable to expect that EGb 761® may benefit MCI patients with underlying CVD.

    CONCLUSION: As an expert group, we suggest it is clinically appropriate to incorporate EGb 761® as part of the multidomain intervention for MCI.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods
  13. Wilairat P, Kengkla K, Kaewpanan T, Kaewthong J, Ruankon S, Subthaweesin C, et al.
    Eur J Hosp Pharm, 2020 Mar;27(2):103-110.
    PMID: 32133137 DOI: 10.1136/ejhpharm-2018-001649
    OBJECTIVE: To examine the comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis (OM) in adult cancer patients.

    METHODS: We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489.

    RESULTS: A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance.

    CONCLUSIONS: This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.

    Matched MeSH terms: Randomized Controlled Trials as Topic/methods
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