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JAMA Internal Medicine Nov 2020The efficacy and safety of time-restricted eating have not been explored in large randomized clinical trials. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The efficacy and safety of time-restricted eating have not been explored in large randomized clinical trials.
OBJECTIVE
To determine the effect of 16:8-hour time-restricted eating on weight loss and metabolic risk markers.
INTERVENTIONS
Participants were randomized such that the consistent meal timing (CMT) group was instructed to eat 3 structured meals per day, and the time-restricted eating (TRE) group was instructed to eat ad libitum from 12:00 pm until 8:00 pm and completely abstain from caloric intake from 8:00 pm until 12:00 pm the following day.
DESIGN, SETTING, AND PARTICIPANTS
This 12-week randomized clinical trial including men and women aged 18 to 64 years with a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 to 43 was conducted on a custom mobile study application. Participants received a Bluetooth scale. Participants lived anywhere in the United States, with a subset of 50 participants living near San Francisco, California, who underwent in-person testing.
MAIN OUTCOMES AND MEASURES
The primary outcome was weight loss. Secondary outcomes from the in-person cohort included changes in weight, fat mass, lean mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure.
RESULTS
Overall, 116 participants (mean [SD] age, 46.5 [10.5] years; 70 [60.3%] men) were included in the study. There was a significant decrease in weight in the TRE (-0.94 kg; 95% CI, -1.68 to -0.20; P = .01), but no significant change in the CMT group (-0.68 kg; 95% CI, -1.41 to 0.05, P = .07) or between groups (-0.26 kg; 95% CI, -1.30 to 0.78; P = .63). In the in-person cohort (n = 25 TRE, n = 25 CMT), there was a significant within-group decrease in weight in the TRE group (-1.70 kg; 95% CI, -2.56 to -0.83; P < .001). There was also a significant difference in appendicular lean mass index between groups (-0.16 kg/m2; 95% CI, -0.27 to -0.05; P = .005). There were no significant changes in any of the other secondary outcomes within or between groups. There were no differences in estimated energy intake between groups.
CONCLUSIONS AND RELEVANCE
Time-restricted eating, in the absence of other interventions, is not more effective in weight loss than eating throughout the day.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT03393195 and NCT03637855.
Topics: Adult; Blood Glucose; Body Mass Index; Caloric Restriction; Diet Therapy; Fasting; Female; Humans; Male; Middle Aged; Obesity; Patient Compliance; Weight Loss; Young Adult
PubMed: 32986097
DOI: 10.1001/jamainternmed.2020.4153 -
The New England Journal of Medicine Aug 2023Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia.
METHODS
We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants.
RESULTS
A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups.
CONCLUSIONS
Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).
Topics: Aged; Aged, 80 and over; Humans; Brain; Cognition; Cognitive Dysfunction; Dementia; Diet, Mediterranean; Diet, Sodium-Restricted; Caloric Restriction
PubMed: 37466280
DOI: 10.1056/NEJMoa2302368 -
The New England Journal of Medicine Jan 2023Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including... (Clinical Trial)
Clinical Trial
BACKGROUND
Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a KRAS G12C inhibitor with an epidermal growth factor receptor antibody could be an effective clinical strategy.
METHODS
In this phase 1-2, open-label, nonrandomized clinical trial, we assigned heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C to receive adagrasib monotherapy (600 mg orally twice daily) or adagrasib (at the same dose) in combination with intravenous cetuximab once a week (with an initial loading dose of 400 mg per square meter of body-surface area, followed by a dose of 250 mg per square meter) or every 2 weeks (with a dose of 500 mg per square meter). The primary end points were objective response (complete or partial response) and safety.
RESULTS
As of June 16, 2022, a total of 44 patients had received adagrasib, and 32 had received combination therapy with adagrasib and cetuximab, with a median follow-up of 20.1 months and 17.5 months, respectively. In the monotherapy group (43 evaluable patients), a response was reported in 19% of the patients (95% confidence interval [CI], 8 to 33). The median response duration was 4.3 months (95% CI, 2.3 to 8.3), and the median progression-free survival was 5.6 months (95% CI, 4.1 to 8.3). In the combination-therapy group (28 evaluable patients), the response was 46% (95% CI, 28 to 66). The median response duration was 7.6 months (95% CI, 5.7 to not estimable), and the median progression-free survival was 6.9 months (95% CI, 5.4 to 8.1). The percentage of grade 3 or 4 treatment-related adverse events was 34% in the monotherapy group and 16% in the combination-therapy group. No grade 5 adverse events were observed.
CONCLUSIONS
Adagrasib had antitumor activity in heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C, both as oral monotherapy and in combination with cetuximab. The median response duration was more than 6 months in the combination-therapy group. Reversible adverse events were common in the two groups. (Funded by Mirati Therapeutics; KRYSTAL-1 ClinicalTrials.gov number, NCT03785249.).
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Piperazines; Proto-Oncogene Proteins p21(ras); Antineoplastic Agents
PubMed: 36546659
DOI: 10.1056/NEJMoa2212419 -
JAMA Internal Medicine Mar 2022Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been...
IMPORTANCE
Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders.
OBJECTIVE
To determine the association between LTL and overall as well as disease-specific mortality and morbidity.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021.
MAIN OUTCOMES AND MEASURES
Hazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity.
RESULTS
This study included a total of 472 432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR, 1.08; 95% CI, 1.07-1.09), cardiovascular (HR, 1.09; 95% CI, 1.06-1.12), respiratory (HR, 1.40; 95% CI, 1.34-1.45), digestive (HR, 1.26; 95% CI, 1.19-1.33), musculoskeletal (HR, 1.51; 95% CI, 1.35-1.92), and COVID-19 (HR, 1.15; 95% CI, 1.07-1.23) mortality, but not cancer-related mortality. A total of 214 disorders were significantly overrepresented and 37 underrepresented in participants with shorter LTL. Respiratory (11%), digestive/liver-related (14%), circulatory (18%), and musculoskeletal conditions (6%), together with infections (5%), accounted for most positive associations, whereas (benign) neoplasms and endocrinologic/metabolic disorders were the most underrepresented entities. Malignant tumors, esophageal cancer, and lymphoid and myeloid leukemia were significantly more common in participants with shorter LTL, whereas brain cancer and melanoma were less prevalent. While smoking and alcohol consumption were associated with shorter LTL, additional adjustment for both factors, as well as cognitive function/major comorbid conditions, did not significantly alter the results.
CONCLUSIONS AND RELEVANCE
This cohort study found that shorter LTL was associated with a small risk increase of overall mortality, but a higher risk of mortality was associated with specific organs and diseases.
Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Leukocytes; Longitudinal Studies; Male; Middle Aged; Mortality; Risk; Telomere; United Kingdom
PubMed: 35040871
DOI: 10.1001/jamainternmed.2021.7804 -
JAMA Network Open Oct 2023Time-restricted eating (TRE) has become increasingly popular, yet longer-term randomized clinical trials have not evaluated its efficacy and safety in patients with type... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Time-restricted eating (TRE) has become increasingly popular, yet longer-term randomized clinical trials have not evaluated its efficacy and safety in patients with type 2 diabetes (T2D).
OBJECTIVE
To determine whether TRE is more effective for weight reduction and glycemic control than daily calorie restriction (CR) or a control condition in adults with T2D.
DESIGN, SETTING, AND PARTICIPANTS
This 6-month, parallel-group, randomized clinical trial was performed between January 25, 2022, and April 1, 2023, at the University of Illinois Chicago. Participants were aged 18 to 80 years with obesity and T2D. Data analysis was based on intention to treat.
INTERVENTIONS
Participants were randomized to 1 of 3 groups: 8-hour TRE (eating 12 to 8 pm only, without calorie counting), CR (25% energy restriction daily), or control.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was change in body weight by month 6. Secondary outcomes included changes in hemoglobin A1c (HbA1c) levels and metabolic risk factors.
RESULTS
Seventy-five participants were enrolled with a mean (SD) age of 55 (12) years. The mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39 (7) and the mean (SD) HbA1c level was 8.1% (1.6%). A total of 53 participants (71%) were women. One participant (1%) was Asian, 30 (40%) were Hispanic White, 40 (53%) were non-Hispanic Black, and 4 (5%) were non-Hispanic White. Participants in the TRE group were adherent with their eating window on a mean (SD) of 6.1 (0.8) days per week, and 17 (68%) in the CR group were adherent with their prescribed calorie goals over 6 months. The mean (SD) reduction in energy intake was -313 (509) kcal/d for TRE, -197 (426) kcal/d for CR, and -16 (439) kcal/d for controls. By month 6, body weight decreased significantly in the TRE group (-3.56% [95% CI, -5.92% to -1.20%]; P = .004) but not the CR group (-1.78% [95% CI, -3.67% to 0.11%]; P = .06), relative to controls. Levels of HbA1c decreased in the TRE (-0.91% [95% CI, -1.61% to -0.20%]) and CR (-0.94% [95% CI, -1.59% to -0.30%]) groups, relative to controls, with no differences between the TRE and CR groups. Time in euglycemic range, medication effect score, blood pressure, and plasma lipid levels did not differ among groups. No serious adverse events were reported.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that a TRE diet strategy without calorie counting was effective for weight loss and lowering of HbA1c levels compared with daily calorie counting in a sample of adults with T2D. These findings will need to be confirmed by larger RCTs with longer follow-up.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05225337.
Topics: Adult; Female; Humans; Male; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Obesity; Risk Factors; Weight Loss; Middle Aged; Aged
PubMed: 37889487
DOI: 10.1001/jamanetworkopen.2023.39337 -
Medicine Sep 2021The most challenging aspect of rehabilitation is the high costs of in-patient rehabilitation programs and poor continuity of care while patients are transferred to home.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The most challenging aspect of rehabilitation is the high costs of in-patient rehabilitation programs and poor continuity of care while patients are transferred to home. In this regard, numerous home-based rehabilitation programs have been developed. The purpose of this study was to investigate the effects of home-based rehabilitative programs on postural balance, walking, and quality of life in individuals with chronic hemiparetic stroke.
DESIGN
A CONSORT-compliant randomized controlled trial.
METHODS
Seventeen community-dwelling people diagnosed with a first stroke participated in this study. They randomly divided the home-based rehabilitative program (HBP) group (n = 9) and control group (n = 8). The HBP group received coordination exercises at home and the control group received clinic-based exercises. This study measured postural balance, walking, and quality of life using four outcome measures: 10-meter walk test, figure of 8 walk test, four-square step test, and 36 item short-form survey.
RESULTS
After analysis, it was found that the HBP improved postural balance, comfortable speed, and fast speed walking, and straight and curved walking for chronic stroke. Second, clinic-based rehabilitation services improved postural balance, comfortable speed, and fast speed walking abilities in patients with chronic stroke.
CONCLUSION
The results of this study suggest that the HBP group received positive benefits with regard to the postural balance and walking abilities of chronic hemiparetic stroke patients compared to the clinical setting exercise program.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Postural Balance; Quality of Life; Stroke Rehabilitation; Walking
PubMed: 34477171
DOI: 10.1097/MD.0000000000027154 -
JAMA Network Open Mar 2023Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and...
IMPORTANCE
Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts.
OBJECTIVES
To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups.
DESIGN, SETTING, AND PARTICIPANTS
This survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022.
EXPOSURES
National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018.
MAIN OUTCOMES AND MEASURES
Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis.
RESULTS
This study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend).
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.
Topics: Male; Adult; Humans; Female; Obesity, Metabolically Benign; Nutrition Surveys; Cross-Sectional Studies; Prevalence; Obesity; Triglycerides
PubMed: 36892842
DOI: 10.1001/jamanetworkopen.2023.2145