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Randomized controlled trial to test the efficacy of a brief, communication-based, substance use preventive intervention for parents of adolescents: Protocol for the SUPPER Project (Substance Use Prevention Promoted by Eating family meals Regularly).
Skeer, MR, Sabelli, RA, Rancaño, KM, Lee-Bravatti, M, Ryan, EC, Eliasziw, M, Spirito, A
PloS one. 2022;(2):e0263016
Abstract
BACKGROUND Substance use among adolescents in the U.S. is associated with adverse physical and mental health outcomes in the long-term. Universal youth-focused substance use prevention programs have demonstrated effectiveness but are often not sustainable due to the significant amount of time, effort, and resources required. We describe a trial protocol for a brief, low-participant-burden intervention to improve substance use-specific parent-child communication through the promotion of family meals and increased parental engagement. METHODS This study is a parallel-group randomized controlled trial designed to assess the efficacy of a 13-week intervention. A total of 500 dyads of parents and their 5th-7th grade children are recruited from across Massachusetts. Dyads are randomized to the intervention or attention-control condition using block urn randomization, based on child grade, gender, and school. Parents/guardians in the substance use preventive intervention arm receive a short handbook, attend two meetings with an interventionist, and receive two SMS messages per week. Parents/guardians in the control arm receive the same dose but with content focused on nutrition, physical activity, and weight stigma. Participant dyads submit videos of family meals, audio recordings of prompted conversations, and quantitative surveys over an 18-month period (baseline, 3, 6, 12, 18 months post-intervention). The primary outcomes measure the quantity and quality of parent-child substance use conversations and proximal child indicators (i.e., substance use attitudes and expectancies, affiliation with substance-using peers, and intentions and willingness to use substances). The secondary outcome is child substance use initiation. DISCUSSION This is a novel, brief, communication-focused intervention for parents/guardians that was designed to reduce participant burden. The intervention has the potential to improve parent-child engagement and communication and conversations about substance use specifically and decrease child substance use risk factors and substance use initiation. TRIAL REGISTRATION ClinicalTrials.gov NCT03925220. Registered on 24 April 2019.
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Vitamin C and scar strength: analysis of a historical trial and implications for collagen-related pathologies.
Hujoel, PP, Hujoel, MLA
The American journal of clinical nutrition. 2022;(1):8-17
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Abstract
A double-blind controlled trial initiated in 1944 has led to the common narrative that a 10-mg daily vitamin C intake is adequate to prevent and treat impaired wound healing, and by inference, other collagen-related diseases such as heart disease or stroke. The WHO relies on this narrative to set the recommended nutrient intake for vitamin C. This narrative, however, is based on what is known as the eyeball method of data assessment. The 1944 trial published individual participant data on scar strength providing an opportunity to statistically probe the validity of the 10-mg narrative, something which has not yet been done. The findings show that a vitamin C intake that averages to 10 mg/d over a mean follow-up of 11.5 mo was associated with a 42% weakened scar strength when compared with 80 mg vitamin C intake/d (P < 0.001). The observed dose-response curve between scar strength and vitamin C intake suggests that the daily vitamin C intake needed to prevent collagen-related pathologies is in the range recommended by the National Academy of Medicine and the European Food Safety Authority (75 to 110 mg/d), not the WHO recommendation (45 mg/d). The findings also show that a vitamin C intake that averages to 65 mg/d over a mean follow-up of 6.5 mo failed to restore the normal wound-healing capacity of vitamin C-depleted tissues; such tissues had a 49% weaker scar strength when compared with nondepleted tissues (P < 0.05). Thus, average daily vitamin C intakes ∼50% higher than the WHO recommends may fail to treat existing collagen-related pathologies. It is concluded that the prior lack of statistical analyses of a landmark trial may have led to a misleading narrative on the vitamin C needs for the prevention and treatment of collagen-related pathologies.
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Prevention of Urinary Stones With Hydration (PUSH): Design and Rationale of a Clinical Trial.
Scales, CD, Desai, AC, Harper, JD, Lai, HH, Maalouf, NM, Reese, PP, Tasian, GE, Al-Khalidi, HR, Kirkali, Z, Wessells, H, et al
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(6):898-906.e1
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Abstract
RATIONALE & OBJECTIVE Although maintaining high fluid intake is an effective low-risk intervention for the secondary prevention of urinary stone disease, many patients with stones do not increase their fluid intake. STUDY DESIGN We describe the rationale and design of the Prevention of Urinary Stones With Hydration (PUSH) Study, a randomized trial of a multicomponent behavioral intervention program to increase and maintain high fluid intake. Participants are randomly assigned (1:1 ratio) to the intervention or control arm. The target sample size is 1,642 participants. SETTING & PARTICIPANTS Adults and adolescents 12 years and older with a symptomatic stone history and low urine volume are eligible. Exclusion criteria include infectious or monogenic causes of urinary stone disease and comorbid conditions precluding increased fluid intake. INTERVENTIONS All participants receive usual care and a smart water bottle with smartphone application. Participants in the intervention arm receive a fluid intake prescription and an adaptive program of behavioral interventions, including financial incentives, structured problem solving, and other automated adherence interventions. Control arm participants receive guideline-based fluid instructions. OUTCOMES The primary end point is recurrence of a symptomatic stone during 24 months of follow-up. Secondary end points include changes in radiographic stone burden, 24-hour urine output, and urinary symptoms. LIMITATIONS Periodic 24-hour urine volumes may not fully reflect daily behavior. CONCLUSIONS With its highly novel features, the PUSH Study will address an important health care problem. FUNDING National Institute of Diabetes and Digestive and Kidney Diseases. TRIAL REGISTRATION Registered at ClinicalTrials.gov with study number NCT03244189.
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Effects of cashew nut consumption on body composition and glycemic indices: A meta-analysis and systematic review of randomized controlled trials.
Jamshidi, S, Moradi, Y, Nameni, G, Mohsenpour, MA, Vafa, M
Diabetes & metabolic syndrome. 2021;(2):605-613
Abstract
BACKGROUND AND AIMS Present meta-analysis and systematic review was conducted to synthesis a definitive conclusion from previous randomized controlled clinical trials (RCTs). METHODS A comprehensive search was done up to July 2020, in order to extract RCTs which investigated the effect of cashew nut on weight, body mass index (BMI), waist circumference (WC), fasting blood sugar (FBS), insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate effect size. Meta regression analysis was done to identify probable sources of heterogeneity. RESULTS Six clinical trials with 521 participants were included. Combined effect sizes demonstrated no effect of cashew consumption on weight (WMD): 0.02, 95% CI: -1.04, 1.09, P > 0.05), BMI (WMD: 0.1, 95% CI: -0.72, 0.74, P > 0.05), and WC (WMD: -0.13, 95% CI: -1.97, 1.70, P > 0.05). Results were also not significant for FBS (WMD: 3.58, 95% CI: -3.92, 11.08, P > 0.05), insulin (WMD: -0.19, 95% CI: -1.63, 1.25, P > 0.05), and HOMA-IR (WMD: 0.25, 95% CI: -0.55, 1.06, P > 0.05). CONCLUSION The sum up, incorporating cashew into the diet has no significant effect on body composition or modifying glycemic indices.
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The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials.
Abdollahi, H, Abdolahi, M, Sedighiyan, M, Jafarieh, A
Endocrine, metabolic & immune disorders drug targets. 2021;(4):673-681
Abstract
BACKGROUND Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and meta-analysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients. METHODS A systematic search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to the random effects model. RESULTS Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, L-carnitine supplementation may not have clinically a significant effect on mortality rate. CONCLUSION L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using a dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients.
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Blinding and expectancy confounds in psychedelic randomized controlled trials.
Muthukumaraswamy, SD, Forsyth, A, Lumley, T
Expert review of clinical pharmacology. 2021;(9):1133-1152
Abstract
Introduction: There is increasing interest in the potential for psychedelic drugs such as psilocybin, LSD and ketamine to treat several mental health disorders, with a growing number of randomized controlled trials (RCTs) being conducted to investigate the therapeutic effectiveness of psychedelics.Areas covered: We review previous literature on expectancy effects and blinding in the context of psychedelic RCTs - literature which strongly suggest that psychedelic RCTs might be confounded by de-blinding and expectancy. We conduct systematic reviews of psychedelic RCTs using Medline, PsychInfo and EMBASE (Jan 1990 - Nov 2020) and show that currently reported psychedelic RCTs have generally not reported pre-trial expectancy, nor the success of blinding procedures.Expert opinion: While psychedelic RCTs have generally shown promising results, with large effect sizes reported, we argue that treatment effect sizes in psychedelic RCTs are likely over-estimated due to de-blinding of participants and high levels of response expectancy. We suggest that psychedelic RCTs should routinely measure de-blinding and expectancy. Careful attention should be paid to clinical trial design and the instructions given to participants to allow these confounds to be reduced, estimated and removed from effect size estimates. We urge caution in interpreting effect size estimates from extant psychedelic RCTs.
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Individual Patient Data from the Pivotal Randomized Controlled Trials of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (COMBINE AF): Design and Rationale: From the COMBINE AF (A Collaboration between Multiple institutions to Better Investigate Non-vitamin K antagonist oral anticoagulant use in Atrial Fibrillation) Investigators.
Carnicelli, AP, Hong, H, Giugliano, RP, Connolly, SJ, Eikelboom, J, Patel, MR, Wallentin, L, Morrow, DA, Wojdyla, D, Hua, K, et al
American heart journal. 2021;:48-58
Abstract
BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date. DESIGN COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771). CONCLUSION In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.
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Cardiovascular Outcomes with SGLT-2 inhibitors in patients with heart failure with or without type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.
Singh, AK, Singh, R
Diabetes & metabolic syndrome. 2021;(1):351-359
Abstract
BACKGROUND AND AIMS We conducted a systematic review and meta-analysis of all the randomized controlled trials (RCTs) with SGLT-2 inhibitors (SGLT-2i) in patients with known heart failure (HF) with or without type 2 diabetes (T2DM), that have studied the outcomes of cardiovascular (CV) death, hospitalization due to HF (HHF), and composite of CV death or HHF. METHODS A systematic search in PubMed, Embase and Cochrane Library database were made up till November 20, 2020 using specific keywords. RCTs that qualified underwent a meta-analysis by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio (HR) using both random- and fixed-effects model. RESULTS This meta-analysis of 9 RCTs (N = 19,741) have found a significant 26% relative risk reduction in composite of CV death or HHF (HR 0.74; 95% CI, 0.69-0.79; p < 0.001) with SGLT-2i in patients with HF. The meta-analysis of 8 RCTs (N = 16,460) also showed a significant reduction in CV death (HR 0.86; 95% CI, 0.78-0.95; p = 0.003) and HHF (HR 0.68; 95% CI, 0.62-0.74; p < 0.001) outcomes with SGLT-2i in patients with HF. Subgroup analysis stratified on baseline ejection fraction (EF) showed a similar benefit in the composite of CV death or HHF in patients with HF with reduced EF (HFrEF) or preserved EF (HFpEF). CONCLUSIONS SGLT-2i significantly reduces the composite of CV death or HHF, CV death, and HHF in patients with HF. Although subgroup analysis suggested an insignificant Pheterogenity for these outcomes irrespective of the types of HF, however, reduction in both CV death and HHF were more pronounced in patients with HFrEF.
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The effect of N-acetylcysteine on bipolar depression: a systematic review and meta-analysis of randomized controlled trials.
Pittas, S, Theodoridis, X, Haidich, AB, Bozikas, PV, Papazisis, G
Psychopharmacology. 2021;(7):1729-1736
Abstract
RATIONALE The current pharmacotherapy of bipolar depression often presents limited efficacy and increased risk for adverse events. N-acetylcysteine (NAC) has been suggested as potentially effective and well-tolerated adjunctive treatment for bipolar disorder (BD). OBJECTIVES This systematic review and meta-analysis aimed to examine the efficacy of N-acetylcysteine, as an adjunctive therapy, for treating bipolar depression. METHODS PubMed, Cochrane Library, Scopus databases, and grey literature were searched for studies retrieval. Randomized controlled trials including patients with a diagnosed bipolar disorder and a current depressive episode were included in the analysis. The measured variables included symptoms, functioning, and quality of life scales. The mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) was set as the primary outcome. RESULTS A total of five studies were included in the analysis. A significant improvement was not observed from the addition of NAC to standard therapy in symptomatology [MADRS (MD = -3.32; 95% CI = -12.79 to 6.16), Young Mania Rating Scale (MD = -0.7; 95% CI = -2.15 to 0.75), Bipolar Depression Rating Scale (MD = -3.19; 95% CI = -15.48 to 9.1), and Clinical Global Impression for severity (MD = -0.13; 95% CI = -0.33 to 0.08)], functioning, [Global Assessment of Functioning Scale (MD = 3.21; 95% CI = -12.55 to 18.97), Social and Occupational Functioning Assessment Scale (MD = 0.47; 95% CI = -4.60 to 5.53), or quality of life [Quality of Life Enjoyment and Satisfaction Questionnaire (MD = 2.27; 95% CI = -9.13 to 13.67)]. CONCLUSIONS There is no evidence indicating that NAC has beneficial effects as an adjunctive treatment for bipolar depression. Future trials with improved methodological design and efficient sample sizes are required to draw safer conclusions.
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Adenoma and Advanced Adenoma Detection Rates of Water Exchange, Endocuff, and Cap Colonoscopy: A Network Meta-Analysis with Pooled Data of Randomized Controlled Trials.
Shao, PP, Bui, A, Romero, T, Jia, H, Leung, FW
Digestive diseases and sciences. 2021;(4):1175-1188
Abstract
BACKGROUND AND AIMS A network meta-analysis showed that low-cost optimization of existing resources was as effective as distal add-on devices in increasing adenoma detection rate (ADR). We assessed the impacts of water exchange (WE), Endocuff, and cap colonoscopy on ADR and advanced adenoma detection rate (AADR). We hypothesized that WE may be superior at improving ADR and AADR. METHODS The literature was searched for all randomized controlled trials (RCTs) that reported ADR as an outcome and included the keywords colonoscopy, and water exchange, Endocuff, or cap. We performed traditional network meta-analyses with random effect models comparing ADR and AADR of each method using air insufflation (AI) as the control and reported the odds ratios with 95% confidence interval. Performances were ranked based on P-score. RESULTS Twenty-one RCTs met inclusion criteria. Fourteen RCTs also reported AADR. Both WE [1.46 (1.20-1.76)] and Endocuff [1.39 (1.17-1.66)] significantly increase ADR, while cap has no impact on ADR [1.00 (0.82-1.22)]. P-scores for WE (0.88), Endocuff (0.79), cap (0.17), and AI (0.17) suggest WE has the highest ADR. WE [1.38 (1.12-1.70)], but not Endocuff [0.96 (0.76-1.21)] or cap [1.06 (0.85-1.32)], significantly increases AADR. P-scores for WE (0.98), cap (0.50), AI (0.31), and Endocuff (0.21) suggest WE is more effective at increasing AADR. The results did not change after adjusting for age, proportion of males, and withdrawal time. CONCLUSION WE may be the modality of choice to maximally improve ADR and AADR.