METHODS: Patients with primary breast and colorectal cancer undergoing elective surgery are recruited from two tertiary hospitals. Eligible patients are assigned into one of the three intervention arms: (i) Group SS will receive ONS in addition to their normal diet up to 14 days preoperatively and postoperatively up to discharge; (ii) Group SS-E will receive ONS in addition to their normal diet up to 14 days preoperatively, postoperatively up to discharge and for an extended 90 days after discharge; and (iii) Group DS will receive ONS in addition to their normal diet postoperatively up to discharge from the hospital. The ONS is a standard formula fortified with lactium to aid in sleep for recovery. The primary endpoints include changes in weight, body mass index (BMI), serum albumin and prealbumin levels, while secondary endpoints are body composition (muscle and fat mass), muscle strength (handgrip strength), energy and protein intake, sleep quality, haemoglobin, inflammatory markers (transferrin, high sensitivity C-reactive protein, interleukin-6), stress marker (saliva cortisol), length of hospital stay and postoperative complication rate.
DISCUSSION: This trial is expected to provide evidence on whether perioperative supplementation in breast and colorectal cancer patients presenting with high BMI and not severely malnourished but undergoing the stress of surgery would be beneficial in terms of nutritional and clinical outcomes.
TRIAL REGISTRATION: ClinicalTrial.gov NCT04400552. Registered on 22 May 2020, retrospectively registered.
DATA SOURCES: We searched studies published between 1980 and 2014 on endometriosis and ART outcome. We searched MEDLINE, PubMed, ClinicalTrials.gov, and Cochrane databases and performed a manual search.
METHODS OF STUDY SELECTION: A total of 1,346 articles were identified, and 36 studies were eligible to be included for data synthesis. We included published cohort studies and randomized controlled trials.
TABULATION, INTEGRATION, AND RESULTS: Compared with women without endometriosis, women with endometriosis undertaking in vitro fertilization and intracytoplasmic sperm injection have a similar live birth rate per woman (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.84-1.06, 13 studies, 12,682 patients, I=35%), a lower clinical pregnancy rate per woman (OR 0.78, 95% CI 0.65-0.94), 24 studies, 20,757 patients, I=66%), a lower mean number of oocyte retrieved per cycle (mean difference -1.98, 95% CI -2.87 to -1.09, 17 studies, 17,593 cycles, I=97%), and a similar miscarriage rate per woman (OR 1.26, 95% CI (0.92-1.70, nine studies, 1,259 patients, I=0%). Women with more severe disease (American Society for Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy rate, and mean number of oocytes retrieved when compared with women with no endometriosis.
CONCLUSION: Women with and without endometriosis have comparable ART outcomes in terms of live births, whereas those with severe endometriosis have inferior outcomes. There is insufficient evidence to recommend surgery routinely before undergoing ART.
METHODS AND ANALYSIS: This randomised controlled trial will involve an intervention group receiving BRM and standard labour care, and a control group receiving only standard labour care. Primigravidae of 26-34 weeks of gestation without chronic diseases or pregnancy-related complications will be recruited from antenatal clinics. Eligible and consenting patients will be randomly allocated to the intervention or the control group stratified by intramuscular pethidine use. The BRM intervention will be delivered by a trained massage therapist. The primary outcomes of labour pain and anxiety will be measured during and after uterine contractions at baseline (cervical dilatation 6 cm) and post BRM hourly for 2 hours. The secondary outcomes include maternal stress hormone (adrenocorticotropic hormone, cortisol and oxytocin) levels, maternal vital signs (V/S), fetal heart rate, labour duration, Apgar scores and maternal satisfaction. The sample size is estimated based on the between-group difference of 0.6 in anxiety scores, 95% power and 5% α error, which yields a required sample size of 154 (77 in each group) accounting for a 20% attrition rate. The between-group and within-group outcome measures will be examined with mixed-effect regression models, time series analyses and paired t-test or equivalent non-parametric tests, respectively.
ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethical Committee for Research Involving Human Subjects of the Ministry of Health in the Saudi Arabia (H-02-K-076-0319-109) on 14 April 2019, and from the Ethics Committee for Research Involving Human Subjects (JKEUPM) Universiti Putra Malaysia on 23 October 2019, reference number: JKEUPM-2019-169. Written informed consent will be obtained from all participants. Results from this trial will be presented at regional, national and international conferences and published in indexed journals.
TRIAL REGISTRATION NUMBER: ISRCTN87414969, registered 3 May 2019.
COMMENT: Most non-randomized studies supported the use of montelukast for atopic dermatitis treatment. However, evidence from these studies should be interpreted with caution as it is relatively weak due to the absence of randomization, control groups and blinding processes, subjecting the results to high risk of selection and reporting biases. The inconsistent findings across RCTs may be related to the limited number of patients, nuances in study designs, varying severity of disease and the concomitant use of steroids in some of the studies.
WHAT IS NEW AND CONCLUSION: Current literature evidence is limited to rationally support the use of montelukast in atopic dermatitis treatment. For now, the conventional treatments should be preferred in the clinical setting.
METHODS: This is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.
RESULTS: Overall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3-19.6) kcal/kg and 0.6 (0.4-0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768-0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770-0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674-0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672-0.962) for protein delivery, respectively), but not in those > 2 mmol/L.
CONCLUSIONS: During the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.
TRIAL REGISTRATION: ISRCTN12233792, registered on November 24, 2017.
METHODS: A systematic search was conducted through Pubmed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials. Additional articles were located through cross-checking of the references list and bibliography citations of the included studies and previous review papers. We included intervention studies with controlled or baseline comparison groups that were conducted in primary care practices or the community, targeted at adult populations (randomized controlled trials, non-randomized trials with controlled groups and pre- and post-intervention studies). The interventions were targeted either at individuals, communities, health care professionals or the health-care system. The main outcome of interest was the relative risk (RR) of screening uptake rates due to the intervention.
RESULTS: We included 21 studies in the meta-analysis. The risk of bias for randomization was low to medium in the randomized controlled trials, except for one, and high in the non-randomized trials. Two analyses were performed; optimistic (using the highest effect sizes) and pessimistic (using the lowest effect sizes). Overall, interventions were shown to increase the uptake of screening for CVD risk factors (RR 1.443; 95% CI 1.264 to 1.648 for pessimistic analysis and RR 1.680; 95% CI 1.420 to 1.988 for optimistic analysis). Effective interventions that increased screening participation included: use of physician reminders (RR ranged between 1.392; 95% CI 1.192 to 1.625, and 1.471; 95% CI 1.304 to 1.660), use of dedicated personnel (RR ranged between 1.510; 95% CI 1.014 to 2.247, and 2.536; 95% CI 1.297 to 4.960) and provision of financial incentives for screening (RR 1.462; 95% CI 1.068 to 2.000). Meta-regression analysis showed that the effect of CVD risk factors screening uptake was not associated with study design, types of population nor types of interventions.
CONCLUSIONS: Interventions using physician reminders, using dedicated personnel to deliver screening, and provision of financial incentives were found to be effective in increasing CVD risk factors screening uptake.
METHODS AND ANALYSIS: This 12-week randomised double-blind, placebo-controlled, parallel-group study aims to evaluate the efficacy of the standardised water extract of EL known as Physta in increasing the quality of life of perimenopausal and postmenopausal women. The study involves 150 women aged 40-55 years who score more than 61 on the Menopause-Specific Quality of Life (MENQOL) assessment. These participants will be randomised into three groups, receiving Physta at either 50 mg or 100 mg or a placebo. The outcomes measures include mood state, quality of life, fatigue, sleep quality, sexual function and pain score assessed using Profile of Mood State, MENQOL, Chalder Fatigue Scale, Pittsburgh Sleep Quality Index, Female Sexual Function Index and the Brief Pain Inventory questionnaires, respectively. The secondary outcome of the study includes full blood analysis, urine analysis, female reproductive hormone profiling, inflammatory and oxidative stress biomarkers analysis.
ETHICS AND DISSEMINATION: The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2021-898). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications.
TRIAL REGISTRATION NUMBER: ACTRN12622001341718.
METHOD: This is a 6-month, single-center, prospective, randomized, two-arm, and parallel-group controlled trial. The trial recruits patients attending the otorhinolaryngology clinics of a tertiary referral hospital. Participants are randomized into control or intervention groups in a 1:1 ratio using permuted block randomization. The total number of participants estimated is 154, with each group requiring 77 participants. The control group receives standard pharmaceutical care, while the intervention group receives pharmacist-led education according to the AR-PRISE model. Both groups are assessed for middle turbinate endoscopy findings, disease severity, knowledge level, symptom control, medication adherence, and QoL at baseline and the end-of-study follow-up (day 180 ± 7). Depending on feasibility, intermediate follow-ups are conducted on days 60 ± 7 and 120 ± 7, either virtually or face-to-face. During intermediate follow-ups, participants are assessed for symptom control, medication adherence, and QoL. The intention-to-treat analysis includes all participants assigned to each group. An independent T-test compares the mean difference in knowledge level between the two groups. A two-way repeated measures ANOVA analysis is employed to determine between-group differences for scores of symptom control, adherence rate, and QoL. A P-value
METHODS: All randomized clinical trials (RCTs) and observational studies were systematically searched in the databases of CENTRAL, EMBASE and PubMed from their inception until January 2018. Case reports, case series and non-systematic reviews were excluded.
RESULTS: Seventy-three studies (6 RCTs and 67 observational studies) were eligible (n = 169,236) for inclusion in the data synthesis. In comparison with the CLS arm, RAS cohort was associated with a significant reduction in the incidence of conversion to open surgery (ρ
METHODS: PubMed, EMBASE, Medline, Cochrane Library, CINAHL, PEDro, and Airiti Library were searched from inception until May 5, 2023. Randomized controlled trials that examined exercise, vitamin D and protein supplementation effects on muscle mass, strength, and physical function. Quality assessment used the Cochrane risk of bias tool, and analysis employed Comprehensive Meta-Analysis version 2.0.
RESULTS: A total of 27 randomized controlled trials, involving 1,989 participants were identified. Meta-analysis results showed exercise improved lean body mass (SMD = 0.232, 95% CI: 0.097, 0.366), handgrip strength (SMD = 0.901, 95% CI: 0.362, 1.441), knee extension strength (SMD = 0.698, 95% CI: 0.384, 1.013). Resistance training had a small effect on lean body mass, longer exercise duration (> 12 weeks) and higher frequency (60-90 min, 3 sessions/week) showed small to moderate effects on lean body mass. Vitamin D supplementation improved handgrip strength (SMD = 0.303, 95% CI: 0.130, 0.476), but not knee extension strength. There was insufficient data to assess the impact of protein supplementation on muscle strength.
CONCLUSIONS: Exercise effectively improves muscle mass, and strength in menopausal women. Resistance training with 3 sessions per week, lasting 20-90 min for at least 6 weeks, is most effective. Vitamin D supplementation enhances small muscle group strength. Further trials are needed to assess the effects of vitamin D and protein supplementation on sarcopenia prevention.
REGISTRATION NUMBER: This review was registered on PROSPERO CRD42022329273.
STUDY QUESTION: Whether FDA death data in the PLATO trial matched the local site records.
STUDY DESIGN: The NDA spreadsheet contains 938 precisely detailed PLATO deaths. We obtained and validated local evidence for 52 deaths among 861 PLATO patients from 14 enrolling sites in 8 countries and matched those with the official NDA dataset submitted to the FDA.
MEASURES AND OUTCOMES: Existence, precise time, and primary cause of deaths in PLATO.
RESULTS: Discrepant to the NDA document, sites confirmed 2 extra unreported deaths (Poland and Korea) and failed to confirm 4 deaths (Malaysia). Of the remaining 46 deaths, dates were reported correctly for 42 patients, earlier (2 clopidogrel), or later (2 ticagrelor) than the actual occurrence of death. In 12 clopidogrel patients, cause of death was changed to "vascular," whereas 6 NDA ticagrelor "nonvascular" or "unknown" deaths were site-reported as of "vascular" origin. Sudden death was incorrectly reported in 4 clopidogrel patients, but omitted in 4 ticagrelor patients directly affecting the primary efficacy PLATO endpoint.
CONCLUSIONS: Many deaths were inaccurately reported in PLATO favoring ticagrelor. The full extent of mortality misreporting is currently unclear, while especially worrisome is a mismatch in identifying primary death cause. Because all PLATO events are kept in the cloud electronic Medidata Rave capture system, securing the database content, examining the dataset changes or/and repeated entries, identifying potential interference origin, and assessing full magnitude of the problem are warranted.
MATERIALS AND METHODS: Six electronic databases (Medline, Embase, PsycInfo, CINHAL, CENTRAL, International Pharmaceutical Abstracts) reference lists of retrieved articles and relevant websites were searched for randomized controlled trials published in the English language involving adults with chronic pain. Studies were included if one of the intervention arms had received pharmacist-led medication review independently or as part of a multidisciplinary intervention. Risk of bias was assessed for all the included studies.
RESULTS: The search strategy yielded 583 unique articles including 5 randomized controlled trials. Compared with control, meta-analysis showed that participants in the intervention group had: a 0.8-point reduction in pain intensity on a 0 to 10 numerical rating scale at 3 months [95% confidence interval (CI), -1.28 to -0.36] and a 0.7-point reduction (95% CI, -1.19 to -0.20) at 6 months; a 4.84 point (95% CI, -7.38 to -2.29) and -3.82 point (95% CI, -6.49 to -1.14) improvement in physical functioning on a 0- to 68-point function subscale of Western Ontario and McMaster Universities Osteoarthritis Index at 3 and 6 months, respectively; and a significant improvement in patient satisfaction equivalent to a "small to moderate effect."
DISCUSSION: Pharmacist-led medication review reduces pain intensity and improves physical functioning and patient satisfaction. However, the clinical significance of these findings remain uncertain due to small effect size and nature of reported data within clinical trials that limits recommendation of wider clinical role of pharmacist in chronic pain management.
METHODS: Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas.
RESULTS: Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%).
CONCLUSION: Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.
OBJECTIVES: To assess the effects of EMT on the healing of venous leg ulcers.
SEARCH METHODS: For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 30 January 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 12).
SELECTION CRITERIA: Randomised controlled trials comparing EMT with sham-EMT or other treatments.
DATA COLLECTION AND ANALYSIS: Standard Cochrane Collaboration methods were employed. At least two review authors independently scrutinised search results and obtained full reports of potentially eligible studies for further assessment. We extracted and summarised details of eligible studies using a data extraction sheet, and made attempts to obtain missing data by contacting study authors. A second review author checked data extraction, and we resolved disagreements after discussion between review authors.
MAIN RESULTS: Three randomised controlled trials (RCTs) of low or unclear risk of bias, involving 94 people, were included in the original review; subsequent updates have identified no new trials. All the trials compared the use of EMT with sham-EMT. Meta-analysis of these trials was not possible due to heterogeneity. In the two trials that reported healing rates; one small trial (44 participants) reported that significantly more ulcers healed in the EMT group than the sham-EMT group however this result was not robust to different assumptions about the outcomes of participants who were lost to follow up. The second trial that reported numbers of ulcers healed found no significant difference in healing. The third trial was also small (31 participants) and reported significantly greater reductions in ulcer size in the EMT group however this result may have been influenced by differences in the prognostic profiles of the treatment groups.
AUTHORS' CONCLUSIONS: It is not clear whether electromagnetic therapy influences the rate of healing of venous leg ulcers. Further research would be needed to answer this question.