Recent Randomized Controlled Trials Research Articles

Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS): development and validation of a novel outcome measure.

Recent randomised controlled trials (RCTs) in primary Sjögren's syndrome used the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) as their primary endpoint. Given the heterogeneous and complex nature of primary Sjögren's syndrome, it might be more appropriate to also assess other clinically relevant disease features. We aimed to develop a novel composite endpoint for assessing treatment efficacy in patients with primary Sjögren's syndrome: the Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS). A multidisciplinary expert team selected clinically relevant items and candidate measurements for inclusion in the composite score. For each measurement, cutoff points for response to treatment were chosen based on expert opinion, previously published data on minimal clinically important improvements, and trial data, primarily the week-24 data of the single-centre ASAP-III trial of abatacept versus placebo. CRESS was validated using data from three independent RCTs: one trial of rituximab (TRACTISS), one of abatacept (multinational trial), and one of tocilizumab (ETAP). We calculated the number and percentage of patients who were responders in the separate CRESS items, and the percentage of responders based on the total CRESS at the primary endpoint visits (week 48 for TRACTISS, week 24 for the other two trials). Patients with fewer than three items available for evaluating CRESS response were imputed as non-responders. Based on expert opinion, five complementary items were selected to assess response: (1) systemic disease activity by Clinical ESSDAI (less than 5 points); (2) patient-reported symptoms by EULAR Sjögren's Syndrome Patient Reported Index, assessed by a decrease of at least 1 point or at least 15% from baseline; (3) tear gland item by Schirmer's test and ocular staining score, assessed by an increase of at least 5 mm or decrease of at least 2 points, respectively, in patients with abnormal Schirmer's test or ocular staining score findings at baseline, or, in patients with normal baseline values, assessed by no change to abnormal for both; (4) salivary gland item, assessed by unstimulated whole saliva secretion (increase of at least 25%) and salivary gland ultrasonography (decrease of at least 25%); and (5) serology, assessed by rheumatoid factor (decrease of at least 25%) and IgG (decrease of at least 10%). Total CRESS response is defined as response on at least three of five items. Post-hoc assessment of phase 3 trial data showed that CRESS response rates at the primary endpoint visits were 60% (24 of 40) for abatacept versus 18% (seven of 39) for placebo (p<0·0001) in ASAP-III, 49% (33 of 67) for rituximab versus 30% (20 of 66) for placebo (p=0·026) in the TRACTISS trial, 45% (41 of 92) for abatacept versus 32% (30 of 95) for placebo (p=0·067) in the multinational abatacept trial, and 18% (10 of 55) for tocilizumab versus 24% (13 of 55) for placebo (p=0·48) in the ETAP trial. The CRESS is a feasible, well-balanced, composite endpoint for use in trials of primary Sjögren's syndrome. As a next step, the CRESS will require validation in a prospective RCT. None. For the Dutch translation of the abstract see Supplementary Materials section.

The Carbohydrate Threshold in Pregnancy and Gestational Diabetes: How Low Can We Go?

The original nutrition approach for the treatment of gestational diabetes mellitus (GDM) was to reduce total carbohydrate intake to 33–40% of total energy (EI) to decrease fetal overgrowth. Conversely, accumulating evidence suggests that higher carbohydrate intakes (60–70% EI, higher quality carbohydrates with low glycemic index/low added sugars) can control maternal glycemia. The Institute of Medicine (IOM) recommends ≥175 g/d of carbohydrate intake during pregnancy; however, many women are consuming lower carbohydrate (LC) diets (<175 g/d of carbohydrate or <40% of EI) within pregnancy and the periconceptual period aiming to improve glycemic control and pregnancy outcomes. This report systematically evaluates recent data (2018–2020) to identify the LC threshold in pregnancy in relation to safety considerations. Evidence from 11 reports suggests an optimal carbohydrate range of 47–70% EI supports normal fetal growth; higher than the conventionally recognized LC threshold. However, inadequate total maternal EI, which independently slows fetal growth was a frequent confounder across studies. Effects of a carbohydrate intake <175 g/d on maternal ketonemia and plasma triglyceride/free fatty acid concentrations remain unclear. A recent randomized controlled trial (RCT) suggests a higher risk for micronutrient deficiency with carbohydrate intake ≤165 g/d in GDM. Well-controlled prospective RCTs comparing LC (<165 g/d) and higher carbohydrate energy-balanced diets in pregnant women are clearly overdue.

Maintenance therapy after allogeneic hematopoietic transplant for acute myeloid leukemia: a systematic review and meta-analysis

Background For patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML), disease relapse remains the most common reason for transplant failure and patient death. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-transplant maintenance therapy. Methods We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with observation or placebo in patients with AML after allogeneic HSCT. We searched Cochrane Library, PubMed and conference proceedings up to Febuary 2021. Results Our search yielded five trials including 736 patients. Maintenance therapy consisted of tyrosine kinase inhibitors (TKIs) in 3 studies (sorafenib 2 studies; midostaurin 1 study) and hypomethylating agents (HMAs) in 2 studies (decitabine and azacytidine 1 study each). Maintenance therapy was associated with an improved overall survival (OS), HR = 0.61 (95% CI 0.47–0.80). Subgroup analysis revealed advantage in OS with either TKI or HMA maintenance. Relapse free survival (RFS) was also improved in the maintenance arm compared with the control arm HR = 0.51(95% CI 0.40 − 0.66). There was no difference between the two arms in overall grade 3/4 adverse events or overall infections, in grade 3/4 infections, or in acute and chronic graft versus host disease. Conclusions Our meta-analysis shows that post-transplant maintenance therapy in AML patients is effective in improving RFS and OS, with a satisfactory safety profile.

Beyond Causality: Additional Benefits of Randomized Controlled Trials for Improving Health Care Delivery.

Policy Points Policymakers at federal and state agencies, health systems, payers, and providers need rigorous evidence for strategies to improve health care delivery and population health. This is all the more urgent now, during the COVID-19 pandemic and its aftermath, especially among low-income communities and communities of color. Randomized controlled trials (RCTs) are known for their ability to produce credible causal impact estimates, which is why they are used to evaluate the safety and efficacy of drugs and, increasingly, to evaluate health care delivery and policy. But RCTs provide other benefits, allowing policymakers and researchers to: 1) design studies to answer the question they want to answer, 2) test theory and mechanisms to help enrich understanding beyond the results of a single study, 3) examine potentially subtle, indirect effects of a program or policy, and 4) collaborate closely to generate policy-relevant findings. Illustrating each of these points with examples of recent RCTs in health care, we demonstrate how policymakers can utilize RCTs to solve pressing challenges.

De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes

BackgroundBalancing the effects of dual antiplatelet therapy (DAPT) in the era of potent P2Y12 inhibitors has become a cornerstone of acute coronary syndrome (ACS) management. Recent randomized controlled trials (RCTs) have investigated DAPT de-escalation to decrease the risk of bleeding outcomes. ObjectivesThe aim of this study was to compare the efficacy and safety outcomes of various DAPT strategies in patients with ACS, including de-escalation from a potent P2Y12 inhibitor to clopidogrel or low-dose prasugrel. MethodsMEDLINE and EMBASE were searched through January 2021 for RCTs investigating the efficacy and safety of DAPT in patients with ACS, and a network meta-analysis was conducted. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding. ResultsOur search identified 15 eligible RCTs, including 55,798 patients with ACS. De-escalation therapy was associated with reduced risk of primary bleeding outcomes (HR: 0.48 [95% CI: 0.30-0.77] vs clopidogrel; HR: 0.32 [95% CI: 0.20-0.52] vs ticagrelor; HR: 0.36 [95% CI: 0.24-0.55] vs standard-dose prasugrel; and HR: 0.40 [95% CI: 0.22-0.75] vs low-dose prasugrel) without negatively affecting primary efficacy outcomes. There were no significant differences in ischemic or bleeding outcomes between de-escalation to clopidogrel or low-dose prasugrel. ConclusionsCompared with other established uses of DAPT, de-escalation was the most effective strategy for ACS treatment, resulting in fewer bleeding events without increasing ischemic events.

Comparative Efficacy and Safety of Gemtuzumab Ozogamicin (GO) Plus Daunorubicin-Cytarabine Combination and Comparators As Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia

Comparative Efficacy and Safety of Gemtuzumab Ozogamicin (GO) Plus Daunorubicin-Cytarabine Combination and Comparators As Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia

Catheter-Directed Thrombolysis for Acute Deep Vein Thrombosis: Experience from a Canadian Thrombosis Referral Centre

BACKGROUNDConventional management strategies for DVT with parenteral and/or oral anticoagulants are effective in the prevention of thrombus extension and embolization but do not actively eliminate thrombus. This poses ongoing risk of injury to the venous valves and consequently development of the post-thrombotic syndrome (PTS). Catheter-directed thrombolysis (CDT) involves the local delivery of a low dose of thrombolytic agent directly to the venous thrombus, resulting in acute reduction in clot burden while limiting the systemic thrombolytic effect.Recommendations from clinical practice guidelines differ dramatically on the use of CDT for lower limb DVTs. Results from recent prospective randomized control trials suggest that those individuals who derive benefit must be carefully selected. We describe the clinical features and outcomes of patients who received CDT for lower limb DVT management at a major referral centre for thromboembolic disease. Additionally, cross-sectional follow-up of these patients was performed to estimate the incidence and severity of PTS.METHODSWe conducted a retrospective cohort analysis on all adult patients who had undergone CDT for lower limb DVT management at St. Joseph's Healthcare Hamilton (SJHH), ON, Canada. Retrospective data were collected through use of electronic and chart-based medical records. The presence and severity of PTS was measured using the Villalta scale.RESULTSFrom 2011 to 2016, 15 patients underwent CDT at SJHH (Table 1).12/15 patients were female. Average patient age was 43.2 years (range 20 to 86 years). All patients had risk factors for venous thromboembolism (VTE); 7/15 patients had 2 risk factors. The most commonly identified transient risk factor was use of the oral contraception pill (5/15). May Thurner syndrome (5/15) was the most common permanent VTE risk factor. All patients were deemed to be at low risk of bleeding (platelets > 100,000, INR < 1.6, no known bleeding diathesis).All patients had DVTs that were iliofemoral in location; 2/15 presented with phlegmasia cerulea dolens. The average time between DVT diagnosis to CDT was 6.5 days. Prophylactic IVC filters were inserted prior to CDT in 3/15 patients. Pharmacomechanical thrombolysis with angioplasty was the most common form of CDT (6/15 patients).Complications from CDT were seen in 8/15 patients (Table 2). Recurrent VTE (3/15) and neurologic deficits in the affected leg (3/15) were the most common complications. There were no deaths attributable to CDT. All patients were managed with anticoagulant therapy post-procedure. The type and duration of anticoagulation was variable (Table 2). The Villalta score was calculated for 6/15 patients. Mild PTS was seen in 4/6 patients; 2/6 did not have PTS (average Villalta score 5.83).CONCLUSIONSCatheter-directed thrombolysis appears to be a well-tolerated treatment option for iliofemoral DVT. Complications were seen in 53% of patients and were frequently mild and self-resolving. The results of our study suggest that patients under 45 years of age who receive prompt thrombolysis, within 7-14 days of DVT diagnosis, are most likely to derive benefit from CDT. The clinical characteristics of patients described here are largely in accordance with those recommended by the 2016 CHEST guidelines.Due to the limited sample size in our study, it is unclear if CDT is beneficial in reducing rates of PTS. Additional studies are needed to clarify potential risks and benefits of this treatment approach. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Adequacy of Pelvic Lymphadenectomy During Radical Cystectomy for Carcinoma Urinary Bladder: A Narrative Review of Literature.

An adequate pelvic lymph node dissection (PLND) is an essential part of radical cystectomy for muscle invasive bladder cancer. However, the definition of what constitutes an adequate PLND is often shrouded in controversy. Various authors have defined different anatomic templates of PLND based on levels of pelvic lymph nodes. Some have suggested other surrogate markers of the adequacy of PLND, namely lymph node count and lymph node density. While individual studies have shown the efficacy and reliability of some of the above markers, none of them have been recommended forthright due to the absence of robust prospective data. The use of non-standardized nomenclature while referring to the above variables has made this matter more complex. Most of older data seems to favor use of extended template of PLND over the standard template. On the other hand, one recent randomized controlled trial (RCT) did not show any benefit of one template over the other in terms of survival benefit, but the study design allowed for a large margin of bias. Therefore, we conducted a systematic search of literature using EMBASE, Medline, and PubMed using PRISMA-P checklist for articles in English Language published over last 20 years. Out of 132 relevant articles, 47 articles were included in the final review. We have reviewed existing literature and guidelines and have attempted to provide a few suggestions toward a uniform nomenclature for the various anatomical descriptions and the extent of PLND done while doing a radical cystectomy. The results of another large RCT (SWOG S1011) are awaited and until we have a definitive evidence, we should adhere to these suggestions as much as possible and deal with each patient on a case to case basis.

Data Missing Not at Random in Mobile Health Research: Assessment of the Problem and a Case for Sensitivity Analyses.

BackgroundMissing data are common in mobile health (mHealth) research. There has been little systematic investigation of how missingness is handled statistically in mHealth randomized controlled trials (RCTs). Although some missing data patterns (ie, missing at random [MAR]) may be adequately addressed using modern missing data methods such as multiple imputation and maximum likelihood techniques, these methods do not address bias when data are missing not at random (MNAR). It is typically not possible to determine whether the missing data are MAR. However, higher attrition in active (ie, intervention) versus passive (ie, waitlist or no treatment) conditions in mHealth RCTs raise a strong likelihood of MNAR, such as if active participants who benefit less from the intervention are more likely to drop out.ObjectiveThis study aims to systematically evaluate differential attrition and methods used for handling missingness in a sample of mHealth RCTs comparing active and passive control conditions. We also aim to illustrate a modern model-based sensitivity analysis and a simpler fixed-value replacement approach that can be used to evaluate the influence of MNAR.MethodsWe reanalyzed attrition rates and predictors of differential attrition in a sample of 36 mHealth RCTs drawn from a recent meta-analysis of smartphone-based mental health interventions. We systematically evaluated the design features related to missingness and its handling. Data from a recent mHealth RCT were used to illustrate 2 sensitivity analysis approaches (pattern-mixture model and fixed-value replacement approach).ResultsAttrition in active conditions was, on average, roughly twice that of passive controls. Differential attrition was higher in larger studies and was associated with the use of MAR-based multiple imputation or maximum likelihood methods. Half of the studies (18/36, 50%) used these modern missing data techniques. None of the 36 mHealth RCTs reviewed conducted a sensitivity analysis to evaluate the possible consequences of data MNAR. A pattern-mixture model and fixed-value replacement sensitivity analysis approaches were introduced. Results from a recent mHealth RCT were shown to be robust to missing data, reflecting worse outcomes in missing versus nonmissing scores in some but not all scenarios. A review of such scenarios helps to qualify the observations of significant treatment effects.ConclusionsMNAR data because of differential attrition are likely in mHealth RCTs using passive controls. Sensitivity analyses are recommended to allow researchers to assess the potential impact of MNAR on trial results.

A Comprehensive Review of Almond Clinical Trials on Weight Measures, Metabolic Health Biomarkers and Outcomes, and the Gut Microbiota.

This comprehensive narrative review of 64 randomized controlled trials (RCTs) and 14 systematic reviews and/or meta-analyses provides an in-depth analysis of the effect of almonds on weight measures, metabolic health biomarkers and outcomes, and the colonic microbiota, with extensive use of figures and tables. Almonds are a higher energy-dense (ED) food that acts like a lower ED food when consumed. Recent systematic reviews and meta-analyses of nut RCTs showed that almonds were the only nut that had a small but significant decrease in both mean body mass and fat mass, compared to control diets. The biological mechanisms for almond weight control include enhanced displacement of other foods, decreased macronutrient bioavailability for a lower net metabolizable energy (ME), upregulation of acute signals for reduced hunger, and elevated satiety and increased resting energy expenditure. The intake of 42.5 g/day of almonds significantly lowered low-density lipoprotein cholesterol (LDL-C), 10-year Framingham estimated coronary heart disease (CHD) risk and associated cardiovascular disease (CVD) medical expenditures. Diastolic blood pressure (BP) was modestly but significantly lowered when almonds were consumed at >42.5 g/day or for >6 weeks. Recent RCTs suggest possible emerging health benefits for almonds such as enhanced cognitive performance, improved heart rate variability under mental stress, and reduced rate of facial skin aging from exposure to ultraviolet (UV) B radiation. Eight RCTs show that almonds can support colonic microbiota health by promoting microflora richness and diversity, increasing the ratio of symbiotic to pathogenic microflora, and concentrations of health-promoting colonic bioactives. Almonds are a premier healthy snack for precision nutrition diet plans.

Hybrid Systematic Review and Network Meta-Analysis of Randomized Controlled Trials of Interventions for Depressive Symptoms in Patients With Coronary Artery Disease.

Depression is common in patients with coronary artery disease (CAD) and is associated with poor outcomes. Although different treatments are available, it is unclear which are best or most acceptable to patients, so we conducted a network meta-analysis of evidence from randomized controlled trials (RCTs) of different depression treatments to ascertain relative efficacy. We searched for systematic reviews of RCTs of depression treatments in CAD and updated these with a comprehensive search for recent individual RCTs. RCTs comparing depression treatments (pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) were included. Primary outcomes were acceptability (dropout rate) and change in depressive symptoms 8 week after treatment commencement. Change in 26-week depression and mortality were secondary outcomes. Frequentist, random-effects network meta-analysis was used to synthesize the evidence, and evidence quality was evaluated following Grading of Recommendations, Assessment, Development and Evaluations recommendations. Thirty-three RCTs (7240 participants) provided analyzable data. All treatments were equally acceptable. At 8 weeks, combination therapy (1 study), exercise (1 study), and antidepressants (10 studies) yielded the strongest effects versus comparators. At 26 weeks, antidepressants were consistently effective, but psychotherapy was only effective versus usual care. There were no differences in treatment groups for mortality. Grading of Recommendations, Assessment, Development and Evaluations ratings ranged from very low to low. Overall, the evidence was limited and biased. Although all treatments for post-CAD depression were equally acceptable, antidepressants have the most robust evidence base and should be the first-line treatment. Combinations of antidepressants and psychotherapy, along with exercise, could be more effective than antidepressants alone but require further rigorous, multiarm intervention trials.Systematic Review Registration: CRD42018108293 (International Prospective Register of Systematic Reviews).

Antibiotics alone in the treatment of appendicitis.

The incidence of acute appendicitis is estimated to be 75 per 100 000 population per year, with the highest incidence in patients aged 10–19 years.[1][1] Overall, 67% of cases are nonperforated.[1][1] The findings of recent randomized controlled trials (RCTs) suggest that as many as 71% of

Leveraging water, sanitation and hygiene for nutrition in low- and middle-income countries: A conceptual framework.

In low‐ and middle‐income countries (LMICs), access to water, sanitation and hygiene (WASH) is associated with nutritional status including stunting, which affects 144 million children under 5 globally. Despite the consistent epidemiological association between WASH indicators and nutritional status, the provision of WASH interventions alone has not been found to improve child growth in recent randomized control trials. We conducted a literature review to develop a new conceptual framework that highlights what is known about the WASH to nutrition pathways, the limitations of certain interventions and how future WASH could be leveraged to benefit nutritional status in populations. This new conceptual framework will provide policy makers, program implementors and researchers with a visual tool to bring into perspective multiple levels of WASH and how it may effectively influence nutrition while identifying existing gaps in implementation and research.

Systematic review and network meta-analysis of randomised controlled trials of interventions for depressive symptoms in patients with coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Objective Depression is common in patients with coronary artery disease (CAD) and is associated with poor outcomes. Although different treatments are available, it is unclear which are best or most acceptable to patients, so we conducted a network meta-analysis of evidence from randomized controlled trials (RCTs) of different depression treatments to ascertain relative efficacy. Methods We searched for systematic reviews of RCTs of depression treatments in CAD and updated these with a comprehensive search for recent individual RCTs. RCTs comparing depression treatments (pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) were included. Primary outcomes were acceptability (dropout rate) and change in depressive symptoms 8-weeks post-treatment commencement. Change in 26-week depression and mortality were secondary outcomes. Frequentist, random effects network meta-analysis synthesized the evidence. GRADE was used to assess evidence quality. Results Thirty-three RCTs (7240 participants) provided analysable data. All treatments were equally acceptable. At 8-weeks, combination therapy (1 study), exercise (1 study), and antidepressants (10 studies) yielded the strongest effects versus comparators. At 26-weeks, antidepressants were consistently effective, but psychotherapy was only effective versus usual care. There were no differences in treatment groups for mortality. GRADE ratings ranged from very low to low. Conclusions All treatments were equally acceptable, while antidepressants appeared to have the most robust evidence base for post-CAD depression. The evidence base was limited and biased; conclusions based on this literature should be drawn cautiously and considered to be tentative. Rigorous, multi-arm intervention trials, including trials of combination therapies and exercise, are urgently needed.

RCTs for policy in India - Ethical Considerations, Methodological Concerns and Alternative Approaches

Randomised controlled trials (RCTs) have become a popular methodological choice for policy analysis in the developing world. This paper describes the various ethical and methodological considerations when choosing to adopt RCTs for policy decisions through a review of literature in multiple disciplines. Unlike previous critical analysis of RCTs, this paper contextualises its critique to India, a country that has been the site of well over a hundred RCTs. Through illustrations of recent Indian policy RCTs on corruption, livelihoods, Public Distribution System, conflict and others, the paper raises concern about violations of ethical requirements like equipoise, informed consent, data harms, human costs to research participants and research staff. The paper discusses methodological limitations of RCTs for Indian policy making including heterogeneity, researcher effects, generalisability, policy-relevant unobserved mechanisms and other socio-political considerations. The paper ends with a description of alternative approaches and a simple checklist for practitioners, specifically policy makers, to assess the feasibility of RCTs for informing decision making in their context.

Psychosocial Factors Mediating the Effect of the CHoBI7 Mobile Health Program on Handwashing With Soap and Household Stored Water Quality: A Randomized Controlled Trial

Household members of diarrhea patients are at higher risk of developing diarrheal diseases (>100 times for cholera) than the general population during the 7 days after the diarrhea patient is admitted at a health facility. There is growing evidence demonstrating that theory-driven water, sanitation, and hygiene (WASH) interventions are likely to yield greater behavior change than those based on health education alone. The Cholera Hospital-Based Intervention for 7-Days (CHoBI7) mobile health (mHealth) program is a theory-driven WASH intervention initially delivered to a diarrhea patient by a health promoter during a health facility visit and reinforced through weekly voice and text messages. In the recent randomized controlled trial (RCT) of the CHoBI7-mHealth program in Bangladesh, this intervention significantly reduced diarrheal disease and stunting, and increased handwashing with soap and stored drinking water quality over the 12-month program period. The aim of this study was to assess the underlying mechanism of change of this intervention. Handwashing with soap was measured by 5-hour structured observation. Stored drinking water quality was assessed by the presence of Escherichia coli during unannounced spot checks. Psychosocial factors were measured among 1,468 participants in the CHoBI7-mHealth RCT. Perceived susceptibility, response efficacy, self-efficacy, dirt reactivity, and diarrhea knowledge were mediators of the CHoBI7-mHealth program's effect on stored drinking water quality at the 1-week follow-up. Self-efficacy, response efficacy, and diarrhea knowledge were mediators of the intervention's effect on handwashing with soap habit maintenance and stored drinking water quality at the 12-month follow-up. This study demonstrates how theory-driven approaches for intervention design can facilitate WASH behavior change.

Efficacy of Green Tea Consumption on Reducing Body Mass Index and Insulin Resistance: A Meta‐Analysis

Introduction Obesity and diabetes are ongoing public health concerns in the United States, especially in rural communities. Obesity is a leading cause of many conditions such as cardiovascular diseases and diabetes. Diabetes, specifically Type 2 Diabetes Mellitus (T2DM), is a leading cause of many conditions such as heart disease and vision problems. Commercially available green tea (Camellia sinensis) products may promote weight loss and insulin sensitivity as indicated by change in Body Mass Index (BMI) and insulin-resistance markers, which could provide potential benefit in the adjunctive management of obesity and diabetes. We conducted a meta-analysis on recent randomized controlled trials (RCTs) to test the hypothesis that consumption of green tea (GT) or green tea extract (GTE) for over four weeks can lead to a decrease in BMI and/or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Our study results will provide updated guidance on dietary recommendations and offer insight into effect sizes translatable to the general population. Methods Electronic databases including PubMed were searched for parallel-designed and double-blinded RCTs published between 2010 and 2020 that examined the effect of GT and GTE on BMI and/or HOMA-IR Index. Two authors independently reviewed articles for inclusion with differences resolved by consensus. Three authors independently assessed studies to assign risk of bias scores. Heterogeneity of studies was evaluated through use of forest plots and the I2 statistic using RevMan5 software. When necessary, data of varying measurement units were synthesized by meta-analysis. Results Eleven studies involving over 800 subjects were included. Daily doses of green tea ranged from 379 mg standardized extract to 20 mg green tea solids. Duration of interventions ranged from 4 to 48 weeks. Preliminary analysis indicates a statistically significant (p<0.05) percentage change in BMI and HOMA-IR index with mean effect sizes of –2.29% (95% CI –4.45%, -0.13%, p=0.04) and –19.75% (95% CI -35.11%, -4.39%, p=0.01), respectively. Most included studies had unknown or high risk of bias. Conclusions Included studies were widely varied in patient selection, dosing, dosing strategy, and outcome measurements. However, these differences suggest broader applicability of the results. Adding green tea may be an accessible, inexpensive and well-tolerated dietary change that may reduce the risk of chronic diseases associated with obesity and diabetes. Future research opportunities include conducting large RCTs to address the public health concern of obesity, diabetes and preventive medicine.

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

Multi-Organ Protective Effects of Sodium Glucose Cotransporter 2 Inhibitors.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) block the reabsorption of glucose by inhibiting SGLT2, thus improving glucose control by promoting the renal excretion of glucose, without requiring insulin secretion. This pharmacological property of SGLT2i reduces body weight and improves insulin resistance in diabetic patients. Such beneficial metabolic changes caused by SGLT2i are expected to be useful not only for glucose metabolism, but also for the protection for various organs. Recent randomized controlled trials (RCTs) on cardiovascular diseases (EMPA-REG OUTCOME trial and CANVAS program) showed that SGLT2i prevented cardiovascular death and the development of heart failure. RCTs on renal events (EMPA-REG OUTCOME trial, CANVAS program, and CREDENCE trial) showed that SGLT2i suppressed the progression of kidney disease. Furthermore, SGLT2i effectively lowered the liver fat content, and our study demonstrated that SGLT2i reduced the degree of hepatic fibrosis in patients at high-risk of hepatic fibrosis. Such promising properties of SGLT2i for cardiovascular, renal, and hepatic protection provide us the chance to think about the underlying mechanisms for SGLT2i-induced improvement of multiple organs. SGLT2i have various mechanisms for organ protection beyond glucose-lowering effects, such as an increase in fatty acids utilization for hepatic protection, osmotic diuresis for cardiac protection, an improvement of insulin resistance for anti-atherogenesis, and an improvement of tubuloglomerular feedback for renal protection.

Neurocognitive Predictors of Response to Intervention With GraphoGame Rime

This study explores the neurocognitive predictors of response to intervention with GraphoGame Rime (GG Rime), an adaptive software game designed to aid the learning of English phonics. A cohort of 398 children (aged 6–7 years) who had participated in a recent randomised controlled trial (RCT) of GG Rime in the United Kingdom were studied. Half were randomly assigned to play GG Rime and the other half were assigned to Business As Usual (BAU). A series of pretests were given prior to the intervention to all participants, designed to measure phonological awareness skills, executive function (EF) skills and the ability to synchronise finger tapping to a rhythmic beat. Rhythmic synchronisation has been linked to reading readiness and early reading attainment, and is related to phonological awareness. Individual differences prior to the intervention in all three types of measure were significantly associated with progression through the game. Gender was also important for progression through the game, with boys progressing significantly further than girls. Vocabulary was not a predictor of progression through the game. Playing time, rhythmic synchronisation, phonological skills and EF skills did not differ by gender. Once playing time and non-verbal cognitive ability were controlled, phonological awareness, EF, rhythmic synchronisation and gender all remained significant predictors of progression through the game. In further analyses comparing these predictors, their interactions and controlling for the autoregressor of prior responsiveness to phonics instruction, phoneme awareness and EF skills were the strongest unique predictors. Analyses with the whole cohort (analysing BAU and GG children independently) showed that all neurocognitive measures contributed to progress in reading and spelling over the school year. We conclude that individual differences in phonological skills and EF skills predict which children will benefit most from computer assisted reading interventions like GG Rime. Further, boys respond better to this computerised intervention than girls. Accordingly, to be maximally beneficial to poor readers, the supplementary use of GG Rime in addition to ongoing classroom literacy instruction could be especially targeted to boys, but should be accompanied by a focus on developing both oral phonological awareness and EF skills.