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• Randomized controlled trials of non-pharmacological interventions following concussion demonstrate moderate to good completeness. • Missing key components, particularly modifications, motivational strategies, and qualified supervisor limit accurate replication. • Reporting completeness has improved since Template for Intervention Description and Replication and Consensus on Exercise Reporting Template publication. • Publication in highly cited journals and low risk of bias do not guarantee reporting completeness. The study aimed to examine the reporting completeness of randomized controlled trials (RCTs) of non-pharmacological interventions following concussion. We searched MEDLINE, Embase, PsycInfo, CINAHL, and Web of Science up to May 2022. Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication (TIDieR), Consensus on Exercise Reporting Template (CERT), and international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) checklists. Additional information was sought my study authors where reporting was incomplete. Risk of bias (ROB) was assessed with the Cochrane ROB-2 Tool. RCTs examining non-pharmacological interventions following concussion. We included 89 RCTs (n = 53 high ROB) examining 11 different interventions for concussion: sub-symptom threshold aerobic exercise, cervicovestibular therapy, physical/cognitive rest, vision therapy, education, psychotherapy, hyperbaric oxygen therapy, transcranial magnetic stimulation, blue light therapy, osteopathic manipulation, and head/neck cooling. Median scores were: TIDieR 9/12 (75%; interquartile range (IQR) = 5; range: 5–12), CERT 17/19 (89%; IQR = 2; range: 10–19), and i-CONTENT 6/7 (86%; IQR = 1; range: 5–7). Percentage of studies completely reporting all items was TIDieR 35% (31/89), CERT 24% (5/21), and i-CONTENT 10% (2/21). Studies were more completely reported after publication of TIDieR (t 87 = 2.08; p = 0.04) and CERT (t 19 = 2.72; p = 0.01). Reporting completeness was not strongly associated with journal impact factor (TIDieR: r s = 0.27; p = 0.01; CERT: r s = –0.44; p = 0.06; i-CONTENT: r s = –0.17; p = 0.48) or ROB (TIDieR: r s = 0.11; p = 0.31; CERT: r s = 0.04; p = 0.86; i-CONTENT: r s = 0.12; p = 0.60). RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness, but are often missing key components, particularly modifications, motivational strategies, and qualified supervisor. Reporting completeness improved after TIDieR and CERT publication, but publication in highly cited journals and low ROB do not guarantee reporting completeness. [Display omitted] [ABSTRACT FROM AUTHOR]

To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression. A randomized controlled trial design was employed. From June to August, 2022, 4,460 rescuers were screened using the Self-Rating Depression Scale (SDS), and 1,615 positive cases were identified. Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group. The intervention group received health education and nutritional intervention (a compound paste therapy primarily composed of red roses and Seville orange flowers), while the control group received psychological education. SDS scores were assessed before and after the intervention. There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention (P < 0.05). Furthermore, the SDS scores of the intervention group were significantly lower than those of the control group, both before and after the intervention (P < 0.05). No severe adverse reactions were observed during safety evaluation. The nutritional intervention effectively reduced the depression scores in rescuers. Early nutritional intervention is recommended for rescuers who initially screen positive for depression. [ABSTRACT FROM AUTHOR]

Gum chewing has been found to improve oral function. Nevertheless, few randomized controlled trials have investigated the effects of gum-chewing exercises on oral function in older adults. This study aimed to examine the effect of gum-chewing exercises on oral function in older adults. This was a single-blind, randomized controlled trial, conducted from November 2021 to January 2022. A total of 130 participants were divided randomly into the intervention and control groups. The intervention group was told to chew experimental gums for one month, while the control group was instructed to chew experimental tablets for one month. Maximum bite force, occlusal contact areas, oral dryness, tongue pressure, tongue and lip functions (number of times each of the following syllables is pronounced per second:/pa/,/ta/, and/ka/), masticatory function, subjective masticatory function, and gum-chewing time were measured at baseline and one month following intervention to assess outcomes. One month following the intervention, tongue pressure was significantly higher in the intervention group than in the control group (P = 0.027). In the within-group comparisons, maximum bite force (P < 0.001), unstimulated saliva flow (P < 0.001), tongue and lip functions (/pa/: P < 0.001;/ta/: P < 0.001;/ka/: P < 0.001), color scale value (P = 0.019), and ΔE value (P = 0.024) were significantly increased in the intervention group. The results suggest that gum-chewing exercises can improve oral functions in older adults, although additional increases in masticatory load may be necessary to establish a more effective oral function training method using gum-chewing exercises in older adults. [ABSTRACT FROM AUTHOR]

Cognitive-behavioral therapy (CBT) and biofeedback therapy are commonly regarded as effective treatment modalities for panic disorder. The aim of this study was to establish a Taiwanese version of an integrated cognitive-behavioral and biofeedback therapy (ICB) and examine its effects on panic disorder using psychological and physiological indicators. Thirty patients with panic disorder were enrolled in this study. They were randomly assigned to either the ICB group (n = 15) or the treatment as usual (TAU) group (n = 15). The intervention consisted of six sessions, conducted once a week. Psychological indicators were measured at baseline (prior to intervention), week 3, and week 6, while physiological indicators were measured at baseline and week 6. The psychological indicators included five scales, with the Panic Disorder Severity Scale (PDSS) being the primary measure. The physiological indicators included respiratory sinus arrhythmia (RSA) and skin conductance, which respectively represent parasympathetic and sympathetic activity. Considering all participants, PDSS scores significantly decreased over time, but the difference between the ICB and TAU groups did not reach statistical significance. Among the physiological indicators, resting-state RSA and RSA under relaxation showed significant between-group differences over time, with the ICB group demonstrating a more pronounced improvement in RSA. In the context of existing pharmacological treatments, the benefits of ICB for panic disorder may not be observable through psychological indicators. However, it can lead to enhancement of parasympathetic activity as evidenced by the physiological indicators. [ABSTRACT FROM AUTHOR]

To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities. Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events. A total of 6112 participants with a median age of 69 years (interquartile range, 65–74) and median of 2 (interquartile range, 1–3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87–1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46–1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35–1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66–1.28). BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs. [ABSTRACT FROM AUTHOR]

We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, −2.0, (95% CI, −10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effects of a mindfulness-based psychosomatic intervention on depression, anxiety, fear of childbirth (FOC), and life satisfaction of pregnant women in China. Women experiencing first-time pregnancy (n = 104) were randomly allocated to the intervention group or a parallel active control group. We collected data at baseline (T0), post-intervention (T1), 3 days after delivery (T2), and 42 days after delivery (T3). The participants completed questionnaires for the assessment of the levels of depression, anxiety, FOC, life satisfaction, and mindfulness. Differences between the two groups and changes within the same group were analyzed at four time points using repeated-measures analysis of variance. Compared with the active control group, the intervention group reported lower depression levels at T2 (P = 0.038) and T3 (P = 0.013); reduced anxiety at T1 (P = 0.001) and T2 (P = 0.003); reduced FOC at T1 (P < 0.001) and T2 (P = 0.04); increased life satisfaction at T1 (P < 0.001) and T3 (P = 0.015); and increased mindfulness at T1 (P = 0.01) and T2 (P = 0.006). The mindfulness-based psychosomatic intervention effectively increased life satisfaction and reduced perinatal depression, anxiety, and FOC. [ABSTRACT FROM AUTHOR]

This study aimed to conduct a scoping review of randomized controlled trials (RCTs) and investigate which work productivity loss outcomes were measured in these RCTs, how each outcome was measured and analyzed, and how the results for each outcome were presented. A systematic search was conducted from January 2010 to April 2020 from 2 databases: PubMed and Cochrane Central Register of Controlled Trials. Data on country, study population, disease focus, sample size, work productivity loss outcomes measured (absenteeism, presenteeism, employment status changes), and methods used to measure, report, and analyze each work productivity loss outcome were extracted and analyzed. We found 435 studies measuring absenteeism or presenteeism, of which 155 studies (35.6%) measured both absenteeism and presenteeism and were included in our final review. Only 9 studies also measured employment status changes. The most used questionnaire was the Work Productivity and Activity Impairment Questionnaire. The analysis of absenteeism and presenteeism data was mostly done using regression models (n = 98, n = 98, respectively) for which a normal distribution was assumed (n = 77, n = 89, respectively). Absenteeism results were most often presented in time whereas presenteeism was commonly presented using a percent scale or score. There is a lack of consensus on how to measure, analyze, and present work productivity loss outcomes in RCTs published in the past 10 years. The diversity of measurement, analysis, and presentation methods used in RCTs may make comparability challenging. There is a need for guidelines providing recommendations to standardize the comprehensiveness and the appropriateness of methods used to measure, analyze, and report work productivity loss in RCTs. • Increasingly, randomized controlled trials (RCTs) are incorporating work productivity loss as a patient-centered outcome. Previous literature has focused on assessing measurement properties of various questionnaires used to measure work productivity loss. Nevertheless, little is known about current research practices in terms of which work productivity loss outcomes are measured (absenteeism, presenteeism, and employment status changes) and how they are measured, analyzed, and presented in RCTs among broader populations including employees, patients, and caregivers. • We found 435 studies measuring absenteeism or presenteeism. Among them, 155 (35.6%) measured both, and only 9 studies also measured employment status changes. The most used questionnaire was the Work Productivity and Activity Impairment Questionnaire. Despite their skewed distribution with many zeros, absenteeism and presenteeism were commonly analyzed with models that assume they follow a normal distribution. Absenteeism results were most often presented in time, whereas presenteeism was commonly presented using a percent scale or score. • RCTs are measuring work productivity loss as a patient-centered outcome or a cost component for economic evaluations. The results of RCTs and economic evaluations are critical in informing healthcare decision makers for their funding decisions. Our review suggests that most RCTs partially measured work productivity loss and may not analyze the data with statistically appropriate methods, which may result in reporting underestimated loss and biased treatment effects. The diverse methods used in RCTs make comparability challenging. [ABSTRACT FROM AUTHOR]

Background Probiotics may alleviate lactose maldigestion. Objectives The objective was to select a probiotic with high lactase activity and compare it with lactase and placebo in clinical trials. Methods Bacterial cultures were screened for lactase activity in a model of the upper gastrointestinal (GI) tract. Bifidobacterium animalis subsp. lactis Bi-07 (Bi-07) counts were adjusted in subsequent experiments to correspond to 4500 Food Chemicals Codex (FCC) units of lactase, the amount in the European Food Safety Authority (EFSA)-approved health claim. Two crossover clinical trials, Booster Alpha and Booster Omega, were performed in participants with lactose intolerance, where 2 × 1012 CFUs Bi-07, 4662 FCC lactase, or placebo was consumed simultaneously with a lactose challenge, with 1-wk washouts between challenges. The trial designs were identical except for the source of lactose. Breath hydrogen concentration (BHC) was measured to assess the effect of the investigational products on lactose digestion, for which incremental area under the curve (iAUC) was the primary outcome. Peak BHC, cumulative BHC, and GI symptoms were secondary outcomes. Results Bi-07 was superior to placebo in reducing BHC [iAUC, parts per million (ppm) ∙ h] in both trials (Booster Alpha: geometric least square mean ratio: 0.462; 95% CI: 0.249, 0.859; P =  0.016; Booster Omega: 0.227; 95% CI: 0.095, 0.543; P  = 0.001). Lactase was superior to placebo in Booster Alpha (0.190; 95% CI: 0.102, 0.365; P  < 0.001) but not Booster Omega (0.493; 95% CI: 0.210, 1.156; P  = 0.102). Noninferiority of Bi-07 compared with lactase was observed in Booster Omega (0.460; 95% CI: 0.193, 1.096; P  = 0.079; CI upper limit < 1.25 noninferiority margin). Odds of abdominal pain (compared with placebo: 0.32, P  = 0.036) and flatulence (compared with placebo: 0.25, P  = 0.007) were lower with lactase in Booster Alpha. Increased odds of nausea were seen with Bi-07 (compared with placebo: 4.0, P  = 0.005) in Booster Omega. Conclusions Bi-07 has high lactase activit y , and in 2 clinical trials, it supported lactose digestion in individuals with lactose intolerance. These trials were registered at clinicaltrials.gov as NCT03659747 (Booster Alpha) and NCT03814668 (Booster Omega). [ABSTRACT FROM AUTHOR]

Background: Vitamin D status and requirements of infants of women with gestational diabetes mellitus (GDM) are unclear.Objectives: The objectives were to assess vitamin D status in infants of mothers with GDM and compare vitamin D status in response to 400 vs. 1000 IU/d vitamin D supplementation in infants born with serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L.Methods: Women with GDM delivering full-term infants (n = 98; March 2017-2019, Montreal, Canada) were surveyed for demographic and lifestyle factors. Pregnancy history was obtained from medical records. Newborn serum 25(OH)D was measured (immunoassay) and categorized as <30 (deficient) or ≥40 nmol/L (adequate). Breastfed neonates (n = 16) with serum 25(OH)D <50 nmol/L at birth were randomly assigned to 400 or 1000 IU/d of supplemental cholecalciferol (vitamin D3), and serum 25(OH)D was measured at baseline (≤1 mo) and 3, 6, and 12 mo of age. Groups were compared using a linear mixed-effects model and Tukey-Kramer post hoc tests.Results: Mean newborn serum 25(OH)D was 46.4 (95% CI: 43.9, 49.9) nmol/L, with 15.3% (95% CI: 8.2%, 22.4%) <30 nmol/L and 61.2% (95% CI: 51.6%, 70.9%) ≥40 nmol/L. During the trial, most infants were breastfed to 3 mo (400 IU/d: 87.5%; 1000 IU/d: 75.0%). Mean (± SEM) infant serum 25(OH)D was higher in the 1000-IU/d group at 3 mo (79.9 ± 5.9 vs. 111.5 ± 15.2 nmol/L; P = 0.0263), and although not different at 6-12 mo, was maintained at >50 nmol/L.Conclusions: Most infants of women with GDM had adequate vitamin D status in this study. In those born with serum 25(OH)D <50 nmol/L, vitamin D status was corrected by 3 mo of age in response to 400 or 1000 IU/d of supplemental vitamin D. Dietary guidance should continue to recommend that all women who could become pregnant take a multivitamin supplement and that breastfed infants receive 400 IU/d of supplemental vitamin D. This study and ancillary trial were registered at clinicaltrials.gov (https://www.clinicaltrials.gov/ct2/show/NCT02563015) as NCT02563015. [ABSTRACT FROM AUTHOR]

• Treatment with camostat did not affect the cycle threshold change in the early phase of COVID-19 disease. • Clinical improvement was similar in patients with COVID-19 treated with camostat or a placebo. • Treatment with camostat did not affect the SARS-CoV-2 neutralizing antibody response. • This randomized controlled trial showed the safe use of 300 mg camostat three times daily in patients with COVID-19. • Camostat mesylate is not effective as an antiviral drug for ambulatory patients with COVID-19. This study aimed to assess the efficacy and safety of 300 mg camostat mesylate three times daily in a fasted state to treat early phase COVID-19 in an ambulatory setting. We conducted a phase II randomized controlled trial in symptomatic (maximum 5 days) and asymptomatic patients with confirmed COVID-19 infection. Patients were randomly assigned in a 2:1 ratio to receive either camostat mesylate or a placebo. Outcomes included change in nasopharyngeal viral load, time to clinical improvement, the presence of neutralizing antibodies, and safety. Of 96 participants randomized between November 2020 and June 2021, analyses were performed on the data of 90 participants who completed treatment (N = 61 camostat mesylate, N = 29 placebo). The estimated mean change in cycle threshold between day 1 and day 5 between the camostat and placebo group was 1.183 (P = 0.511). The unadjusted hazard ratio for clinical improvement in the camostat group was 0.965 (95% confidence interval, 0.480-1.942, P = 0.921 by Cox regression). The percentage distribution of the 50% neutralizing antibody titer at day 28 visit and frequency of adverse events were similar between the two groups. Under this protocol, camostat mesylate was not found to be effective as an antiviral drug against SARS-CoV-2. Trial registration: ClinicalTrials.gov NCT04625114 ; November 12, 2020. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78–1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72–1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99–1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19. [ABSTRACT FROM AUTHOR]

Background: The purpose of this meta-analysis is to compare the merits and drawbacks between reamed intramedullary nailing (RIN) and unreamed intramedullary nailing (URIN) among adults.Methods: We comprehensively searched PubMed, MEDLINE database through the PubMed search engine, Google Scholar, Cochrane Library, Embase, VIPI (Database for Chinese Technical Periodicals), and CNKI (China National Knowledge Infrastructure) from inception to March 2020. Outcomes of interest included nonunion rates, implant failure rates, secondary procedure rates, blood loss, acute respiratory distress syndrome (ARDS) rates, and pulmonary complications rates.Results: Eight randomized controlled trials were included. The result of nonunion rates shows that the nonunion rate is significantly lower in the RIN group (RR = 0.20, 95% CI = 0.09-0.48, Z = 3.63, P = 0.0003). There were no significant differences for the risk of implant failure rates (RR = 0.55, 95% CI = 0.18-1.69, Z = 1.04, P = 0.30). The secondary procedure rates were significantly lower in the RIN group (RR = 0.28, 95% CI = 0.12-0.66, Z = 2.91, P = 0.004). The result shows that the blood loss of URIN group is significantly lower (RR = 145.52, 95% CI = 39.68-251.36, Z = 2.69, P = 0.007). The result shows that there was no significant difference in the ARDS rates (RR = 1.53, 95% CI = 0.37-6.29, Z = 0.59, P = 0.55) and the pulmonary complications rates between RIN group and URIN group (RR = 1.59, 95% CI = 0.61-4.17, Z = 0.94, P = 0.35).Conclusions: Reamed intramedullary nailing would lead to lower nonunion rate, secondary procedure rate and more blood loss. Unreamed intramedullary nailing is related to a higher nonunion rate, secondary procedure rate and less blood loss. No significant difference is found in implant failure rate, ARDS rate and pulmonary complication rate between the two groups. [ABSTRACT FROM AUTHOR]

To assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. COVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. The analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59–68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3–5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%–18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4–21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. Our findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: The use of guideline-directed medical therapy (GDMT) is underprescribed in patients with heart failure with reduced ejection fraction (HFrEF).Objectives: This study sought to examine whether targeted and tailored electronic health record (EHR) alerts recommending GDMT in eligible patients with HFrEF improves GDMT use.Methods: PROMPT-HF (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure) was a pragmatic, EHR-based, cluster-randomized comparative effectiveness trial. A total of 100 providers caring for patients with HFrEF were randomized to either an alert or usual care. The alert notified providers of individualized GDMT recommendations along with patient characteristics. The primary outcome was an increase in the number of GDMT classes prescribed at 30 days postrandomization. Providers were surveyed on knowledge of guidelines and user experience.Results: The study enrolled 1,310 ambulatory patients with HFrEF from April to October 2021. Median age was 72 years; 31% were female; 18% were Black; and median left ventricular ejection fraction was 32%. At baseline, 84% of participants were receiving β-blockers, 71% received a renin-angiotensin-aldosterone system inhibitor, 29% received a mineralocorticoid receptor antagonist, and 11% received a sodium-glucose cotransporter-2 inhibitor. The primary outcome occurred in 176 of 685 (26%) participants in the alert arm vs 117 of 625 (19%) in the usual care arm, thus increasing GDMT class prescription by >40% after alert exposure (adjusted relative risk: 1.41; 95% CI: 1.03-1.93; P = 0.03). The number of patients needed to alert to result in an increase in addition of GDMT classes was 14. A total of 79% of alerted providers agreed that the alert was effective at enabling improved prescription of medical therapy for HF.Conclusions: A real-time, targeted, and tailored EHR-based alerting system for outpatients with HFrEF led to significantly higher rates of GDMT at 30 days when compared with usual care. This low-cost intervention can be rapidly integrated into clinical care and accelerate adoption of high-value therapies in heart failure. (PRagmatic trial Of Messaging to Providers about Treatment of Heart Failure [PROMPT-HF; NCT04514458]). [ABSTRACT FROM AUTHOR]

Background The obesogenic environment of Western countries raises questions about its current management. Some clinical studies have explored hypnosis, although the current state of knowledge does not lead to definitive conclusions about its efficacy. Objectives We assessed the impact of Ericksonian hypnosis and self-hypnosis on disinhibition of eating in adults with obesity and high food impulsivity levels, compared with standard nutritional education. Methods From September 2014 to July 2015, adults with BMI (in kg/m2) of 30–40 and a high disinhibition score [>8 on the Three Factor Eating Questionnaire (TFEQ-51)] were included in a randomized controlled trial. The control and hypnosis groups received the same standard nutrition education in 8 workshops. In the hypnosis group, subjects had 8 sessions of hypnosis combined with training in self-hypnosis. Disinhibition (primary outcome) and other scores from the TFEQ-51 as well as anthropometric, food intake, cardiometabolic, and physical activity variables were collected at inclusion and at 8 mo. Results Of 82 randomly assigned adults, 70 participated in all sessions; 80 participated in ≥1 session and were included in the main analysis (hypnosis group, n  = 41; control group, n  = 39). After 8 mo of follow-up, disinhibition scores adjusted for baseline values were lower in the hypnosis group, with a mean between-group difference of 4.2 (95% CI: 2.8, 5.5; P  < 0.001); 67.7% of adults in the hypnosis group had normalized their disinhibition (compared with 11.1% in control; P  < 0.0001). Differences for weight (1.8 kg; 95% CI: −0.1, 3.7 kg; P  = 0.052), BMI (0.8; 95% CI: 0.1, 1.4; P  = 0.028), susceptibility to hunger score (2.2; 95% CI: 1.0, 3.3; P  < 0.001), and its 2 subscales also favored the hypnosis group. Conclusions In the management of adults with obesity and a high disinhibition score, hypnosis and self-hypnosis can significantly improve the deep mechanisms of eating behaviors and seem to have a beneficial effect on weight loss. This trial was registered at clinicaltrials.gov as NCT02292108. [ABSTRACT FROM AUTHOR]

Background Intrauterine exposure to maternal vitamin D status <50 nmol/L of serum 25-hydroxyvitamin D [25(OH)D] may adversely affect infant body composition. Whether postnatal interventions can reprogram for a leaner body phenotype is unknown. Objectives The primary objective was to test whether 1000 IU/d of supplemental vitamin D (compared with 400 IU/d) improves lean mass in infants born with serum 25(OH)D <50 nmol/L. Methods Healthy, term, breastfed infants (Montréal, Canada, March 2016–2019) were assessed for serum 25(OH)D (immunoassay) 24–36 h postpartum. Infants with serum 25(OH)D <50nmol/L at 24–36 h were eligible for the trial and randomly assigned at baseline (1 mo postpartum) to 400 (29 males, 20 females) or 1000 IU/d (29 males, 20 females) of vitamin D until 12 mo. Infants (23 males, 18 females) with 25(OH)D ≥50 nmol/L (sufficient) formed a nonrandomized reference group provided 400 IU/d. Anthropometry, body composition (DXA), and serum 25(OH)D concentrations were measured at 1, 3, 6, and 12 mo. Results At baseline, mean ± SD serum 25(OH)D concentrations in infants allocated to the 400 and 1000 IU/d vitamin D groups were 45.8 ± 14.1 and 47.6 ± 13.4, respectively; for the reference group it was 69.2 ± 16.4 nmol/L. Serum 25(OH)D concentration increased on average to ≥50 nmol/L in the trial groups at 3–12 mo. Lean mass varied differently between groups over time; at 12 mo it was higher in the 1000 IU/d vitamin D group than in the 400 IU/d group (mean ± SD: 7013 ± 904.6 compared with 6690.4 ± 1121.7 g, P = 0.0428), but not the reference group (mean ± SD: 6715.1 ± 784.6 g, P = 0.19). Whole-body fat mass was not different between the groups over time. Conclusions Vitamin D supplementation (400 or 1000 IU/d) during infancy readily corrects vitamin D status, whereas 1000 IU/d modestly increases lean mass by 12 mo. The long-term implications require further research. This trial was registered at clinicaltrials.gov as NCT02563015. [ABSTRACT FROM AUTHOR]

Evaluate and compare the efficacy and safety of molnupiravir and favipiravir in outpatients with mild to moderate COVID-19 and at risk of severe COVID-19. In an open-label, parallel-group, multicenter trial in Thailand, participants with moderate COVID-19 and at least one factor associated with severe COVID-19 were randomly assigned 1:1 to receive oral molnupiravir or oral favipiravir (standard of care). Phone calls for remote symptom assessment were made on Days 6, 15, and 29. Participants with worsening symptoms were instructed to return to the hospital. The primary endpoint was pulmonary involvement by Day 29, as evidenced by ≥2 of the following: dyspnea, oxygen saturation <92% or imaging. Nine hundred seventy-seven participants (487 molnupiravir, 490 favipiravir) were enrolled from 8 July 2022 to 19 January 2023. 98% had received ≥1 dose of COVID-19 vaccine and 83% ≥3 doses. By Day 29, pulmonary involvement occurred in 0% (0/483) in molnupiravir arm versus 1% (5/482) in favipiravir arm (−1.0%; Newcombe 95.2% CI: −2.4% to −0.0%; P = 0.021); all-cause death in 0% (0/483) and <1% (1/482); COVID-19 related hospitalization in <1% (1/483) and 1% (3/482); treatment-related adverse event in 1% (5/483) and 1% (4/486); and serious adverse event in 1% (4/483) and 1% (4/486). Favipiravir and molnupiravir had a similar efficacy and safety profile. Whether either of the two reduced the risk of complications during the omicron era in this population with a low risk of pulmonary involvement and a high vaccine coverage remains unclear. There were no differences in any of the safety endpoints. TCTR20230111009. [ABSTRACT FROM AUTHOR]

Background Consumption of sugar-sweetened beverages, including fruit drinks (i.e. fruit-flavored drinks containing added sugar), contributes to childhood obesity. Objectives We aimed to examine whether nutrition-related claims on fruit drinks influence purchasing among parents and lead to misperceptions of healthfulness. Methods We conducted an experiment in a virtual convenience store with 2219 parents of children ages 1–5 y. Parents were randomly assigned to view fruit drinks displaying 1 of 3 claims ("No artificial sweeteners," "100% Vitamin C," and "100% All Natural") or no claim (i.e. control group). Parents selected among each of 2 drinks for their young child: 1) a fruit drink or 100% juice (primary outcome), and 2) a fruit drink or water. Results When choosing between a fruit drink and 100% juice, 45% of parents who viewed the fruit drink with the "No artificial sweeteners" claim, 51% who viewed the "100% Vitamin C" claim, and 54% who viewed the "100% All Natural" claim selected the fruit drink, compared with 32% in the no-claim control group (all P  < 0.001). "No artificial sweeteners" (Cohen's d  = 0.13, P  < 0.05) and "100% All Natural" (d  = 0.15, P  < 0.05) claims increased the likelihood of parents choosing the fruit drink instead of water but "100% Vitamin C" did not (P  = 0.06). All claims made parents more likely to incorrectly believe that the fruit drinks contained no added sugar and were 100% juice than the control (d ranged from 0.26 to 0.84, all P  < 0.001), as assessed in a posttest survey. The impact of claims on selection of the fruit drink (compared with 100% juice) did not vary by any of the moderators examined (e.g. race/ethnicity, income; all moderation P  > 0.05). Conclusions Nutrition-related claims led parents to choose less healthy beverages for their children and misled them about the healthfulness of fruit drinks. Labeling regulations could mitigate misleading marketing of fruit drinks. This trial was registered at clinicaltrials.gov as NCT04381481. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is frequent among patients undergoing bariatric surgery. Beyond weight reduction, dietary supplements like micronutrients or probiotics that modify insulin resistance and lipotoxicity can be used to prevent or delay the progression of liver disease.Objectives: We evaluated the effect of a dietary approach with a specifically tailored multistrain probiotic and micronutrient mixture compared with a basic care micronutrient supplement on serum alanine aminotransferase (ALAT) in obese patients after mini gastric bypass (MGB) surgery.Methods: This randomized, double-blind, controlled trial included 60 obese patients (age: 40 ± 10 y; BMI: 44 ± 3 kg/m²). Patients received a combination of specifically tailored multistrain probiotic powder and a specific micronutrient mixture (Pro+SM) or a control treatment consisting of a placebo and a basic care micronutrient mixture (Con+BM), with some micronutrients in lower doses than SM, for 12 wk after hospital discharge. Primary (serum ALAT) and secondary outcomes [serum aspartate aminotransferase (ASAT), fatty liver index, NAFLD fibrosis score, glucose metabolism, blood pressure (BP), heart rate] were assessed at week 0 and week 12. Data were analyzed using unpaired Student's t-tests or Mann-Whitney U tests to compare the changes due to each treatment to one another.Results: A total of 48 patients were included in the analyses. Changes in serum ALAT concentrations did not differ between groups. Compared with Con+BM, Pro+SM improved serum ASAT (difference: -8.0 U/L, 95% CI: -17.0, -4.0; P = 0.043), NAFLD fibrosis score (difference: -0.39; 95% CI: -0.78, 0; P = 0.048), serum triglycerides (difference: -22.8 mg/dL; 95% CI: -45.6, -0.1; P = 0.049) and the visceral adiposity index (difference: -0.70; 95% CI: -1.31, -0.08; P = 0.027).Conclusion: Supplementation with a specifically tailored probiotic and micronutrient mixture improved NAFLD-related markers more than a basic micronutrient mixture in obese patients following MGB surgery. The trial was registered under clinicaltrials.gov as NCT03585413. [ABSTRACT FROM AUTHOR]

Background: The glycemic effects of peanuts are not well studied and no trials have been conducted in adults with elevated fasting plasma glucose (FPG). Furthermore, intake of peanuts as a nighttime snack, an eating occasion affecting FPG, has not been examined.Objectives: The aim was to determine the effect of consuming 28 g/d of peanuts as a nighttime snack for 6 wk on glycemic control and cardiovascular disease risk factors, compared with an isocaloric lower fat, higher carbohydrate (LFHC) snack (whole grain crackers and low-fat cheese), in adults with elevated FPG.Methods: In a randomized crossover trial, 50 adults (FPG 100 ± 8 mg/dL) consumed dry roasted, unsalted peanuts [164 kcal; 11% energy (E) carbohydrate, 17% E protein, and 73% E fat] or a LFHC snack (164 kcal; 54% E carbohydrate, 17% E protein, and 33% E fat) in the evening (after dinner and before bedtime) for 6 wk with a 4-wk washout period. Primary (FPG) and secondary end points [Healthy Eating Index-2015 (HEI-2015), weight, insulin, fructosamine, lipids/lipoproteins, central and peripheral blood pressure, and pulse wave velocity] were evaluated at the beginning and end of each condition. Linear mixed models were used for data analysis.Results: FPG was not different between the peanut and LFHC conditions (end point mean difference: -0.6 mg/dL; 95% CI: -2.7, 1.6; P = 0.67). There were no between-condition effects for secondary cardiometabolic endpoints. The HEI-2015 score was not different between the conditions (3.6 points; P = 0.19), although the seafood/plant protein (2.0 points; P < 0.01) and added sugar (0.8 points; P = 0.04) components were improved following peanut intake. The whole grain component was lower with peanuts compared with LFHC (-2.6 points; P < 0.01).Conclusions: In adults with elevated FPG, peanuts as a nighttime snack (28 g/d) did not affect FPG compared with an isocaloric LFHC snack after 6 wk.This trial was registered at clinicaltrials.gov as NCT03654651. [ABSTRACT FROM AUTHOR]

Previous research has identified key factors associated with improved average daily gain (ADG) in preweaning dairy calves and these factors have been combined to create a web app–based calf health plan (www.nottingham.ac.uk/herdhealthtoolkit). A randomized controlled trial was conducted to determine the effect of implementing this evidence-based calf health plan on both productivity and health outcomes for calves reared on British dairy farms. Sixty dairy farms were randomized by location (North, South, and Midlands) to either receive the plan at the beginning (INT) or after the end of the trial (CON) and recorded birth and weaning weights by weigh tape, and cases of morbidity and mortality. Calf records were returned for 3,593 calves from 45 farms (21 CON, 24 INT), with 1,760 calves from 43 farms having 2 weights recorded >40 d apart for ADG calculations, with 1,871 calves from 43 farms born >90 d before the end of the trial for morbidity and mortality calculations. Associations between both intervention group and the number of interventions in place with ADG were analyzed using linear regression models. Morbidity and mortality rates were analyzed using beta regression models. Mean ADG was 0.78 kg/d, ranging from 0.33 to 1.13 kg/d, with mean rates of 20.12% (0–96.55%), 16.40% (0–95.24%), and 4.28% (0–18.75%) for diarrhea, pneumonia, and mortality. The INT farms were undertaking a greater number of interventions (9.9) by the end of the trial than CON farms (7.6). Mean farm ADG was higher for calves on INT farms than CON farms for both male beef (MB, +0.22 kg/d) and dairy heifer (DH, +0.03 kg/d) calves. The MB calves on INT farms had significantly increased mean ADG (0.12 kg/d, 95% confidence interval: 0.02–0.22) compared with CON farms. No significant differences were observed between intervention groups for morbidity or mortality. Implementing one additional intervention from the plan, regardless of intervention group, was associated with improvements in mean ADG for DH calves of 0.01 kg/d (0.01, 0–0.03) and MB calves of 0.02 kg/d (0.00–0.04). Model predictions suggest that a farm with the highest number of interventions in place (15) compared with farms with the lowest number of interventions in place (4) would expect an improvement in growth rates from 0.65 to 0.81 kg/d for MB, from 0.73 to 0.88 kg/d for DH, a decrease in mortality rates from 10.9% to 2.8% in MB, and a decrease in diarrhea rates from 42.1% to 15.1% in DH. The calf health plan tested in this study represents a useful tool to aid veterinarians and farmers in the implementation of effective management interventions likely to improve the growth rates, health, and welfare of preweaning calves on dairy farms. [ABSTRACT FROM AUTHOR]

Background A large proportion of infants in low- and middle-income countries are stunted. These infants are often fed complementary foods that are low-quality, primarily in terms of protein and micronutrients. Objectives We aimed to test 2 milk–cereal mixes supplemented with modest and high amounts of protein during 6–12 mo of age, compared with no supplementation, for their effect on length-for-age z score (LAZ) at 12 mo of age. Methods Eligible infants (6 mo plus ≤29 d) were randomly assigned to either of the 2 interventions (modest- and high-protein) or a no supplement group. The milk–cereal mixes provided ∼125 kcal, 30%–45% energy from fats, and 80%–100% RDA of multiple micronutrients (MMN). The modest-protein group received 2.5 g protein [protein energy ratio (PER): 8%; 0.75 g from milk source] and the high-protein group received 5.6 g protein (PER: 18%, 1.68 g from milk source). One packet was given daily for 180 d. Counseling on continued breastfeeding and optimal infant-care practices was provided to all. Results We enrolled 1548 infants (high-protein: n  = 512; modest-protein: n  = 519; and no supplement: n  = 517). Compared with the no supplement group, there was an improvement in LAZ [adjusted mean difference (MD): 0.08; 95% CI: 0.01, 0.15], weight-for-age z score (MD: 0.12; 95% CI: 0.06, 0.19), weight-for-length z score (MD: 0.11; 95% CI: 0.02, 0.19), and midupper arm circumference z score (MD: 0.10; 95% CI: 0.02, 0.18) in the high-protein group at 12 mo of age. No significant differences for these anthropometric indicators were noted between the modest-protein and no supplement groups or between the high- and modest-protein groups. Conclusions Cereal mixes with higher amounts of milk-based protein and MMN may lead to improvement in linear growth and other anthropometric indexes in infants, compared with no supplementation. This trial was registered at ctri.nic.in as CTRI/2018/04/012932. [ABSTRACT FROM AUTHOR]

We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir–interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. The intention-to-treat population included 583 participants—lopinavir/ritonavir (n = 145), lopinavir/ritonavir–IFN–β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)—among whom 418 (71.7%) were male, the median age was 63 years (IQR 54–71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55–1.26, p 0.39), lopinavir/ritonavir–IFN–β-1a versus control, aOR 0.69 (95%CI 0.45–1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62–1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir–IFN–β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens. [ABSTRACT FROM AUTHOR]

Background Limited evidence supports the common public health guideline that children >2 y of age should consume dairy with reduced fat content. Objectives We aimed to investigate the effects of whole-fat compared with reduced-fat dairy intake on measures of adiposity and biomarkers of cardiometabolic risk in healthy 4- to 6-y-old children. Methods The Milky Way Study enrolled 49 children (mean ± SD age: 5.2 ± 0.9 y; 47% girls) who were habitual consumers of whole-fat dairy, then randomly assigned them in a double-blind fashion to remain on whole-fat dairy or switch their dairy consumption to reduced-fat products for 3 mo. Primary endpoints included measures of adiposity, body composition, blood pressure, fasting serum lipids, blood glucose, glycated hemoglobin (HbA1c), and C-reactive protein (CRP) and were assessed at baseline and study end. Pre- and postintervention results were compared using linear mixed models, adjusted for growth, age, and sex. Results Dairy fat intake was reduced by an adjusted (mean ± SEM) 12.9 ± 4.1 g/d in the reduced-fat compared with the whole-fat dairy group (95% CI: –21.2, –4.6 g/d; P  = 0.003), whereas dietary energy intakes remained similar (P  = 0.936). We found no significant differential changes between dairy groups in any measure of adiposity, body composition, blood pressure, or fasting serum lipids, glucose, HbA1c, and CRP. Conclusions Our results suggest that although changing from whole-fat to reduced-fat dairy products does reduce dairy fat intake, it does not result in changes to markers of adiposity or cardiometabolic disease risk in healthy children. This trial was registered at www.anzctr.org.au as ACTRN12616001642471. [ABSTRACT FROM AUTHOR]

Background/purpose: Edentulous ridges with height discrepancies (RHDs) could jeopardize the outcome of implant placement. This study aimed at evaluating the outcomes of placing regular- and slope-configured implants in RHDs.Methods: Patients with >1 mm RHDs requesting implant rehabilitation were recruited and randomly assigned to regular- (control) or slope-configured (test) implant treatment using a submerged installation protocol. Thread exposure (TE) and implant stability quotient (ISQ) were evaluated during implant installation (S1) and uncovered surgery (S2), and marginal bone level (MBL) was evaluated after implant installation (T1) and uncovery (T3), and one year after implant placement (T4). Periodontal status and gingival crevicular fluid (GCF) biomarkers of adjacent teeth were evaluated before implant installation (T0), before uncovery (T2), and at T4. Peri-implant clinical status and peri-implant crevicular fluid (PICF) biomarkers of examined implants were evaluated at T4.Results: Nineteen patients with 17 control and 13 test implants were included. All of the implants survived with acceptable peri-implant health, and PICF biomarkers were at equivalent levels as GCF biomarkers of the adjacent teeth at T4. Compared with the control group, the test group showed reduced TE and equivalent ISQ at S1 and S2, and the loss of MBL was reduced at T4. Regarding the adjacent teeth, all periodontal parameters and GCF biomarkers were slightly decreased from T0 to T2, and the reductions in probing pocket depth and clinical attachment level were slightly greater at T4.Conclusion: Slope-configured implants maintained the implant-supporting structures and minimally altered periodontal status of the adjacent teeth in RHDs. [ABSTRACT FROM AUTHOR]

Background Studies suggest that Schisandra chinensis Baillon (Sc) may enhance muscle strength and mass because of its anti-inflammatory and antioxidant properties. Objectives We aimed to examine the effects and safety of consumption of Sc extract (SCe) for 12 wk on muscle strength and mass in older adults with relatively low muscle mass who do low-intensity exercise. Methods A randomized, double-blind, placebo-controlled trial was performed in adults >50 y of age. Fifty-four participants were randomly assigned into 2 groups and, for 12 wk, received either 1 g SCe/d or a placebo. All participants were required to walk for 30–60 min/d for >3 d/wk during the trial period. At baseline and at 4 and 12 wk after treatment, the participants were examined for knee extension strength using Biodex isokinetic dynamometers, handgrip strengths, and body composition, and blood tests were performed. The Euro-QoL-5D (EQ-5D) questionnaire and the FFQ were administered at baseline and at 12 wk after treatment. Physical activity was assessed using a self-recorded daily exercise log and an accelerometer during the study. Results SCe supplementation over 12 wk caused a higher increase in right knee extensor strength by 10.2 Nm (95% CI: 3.7, 16.8 Nm; P  = 0.003) and left knee extensor strength by 6.7 Nm (95% CI: 0.3, 13.1 Nm; P  = 0.041) than did the placebo. However, no differences were observed in the muscle mass, anti-inflammatory markers, antioxidative markers, and EQ-5D score between the groups. None of the participants experienced adverse events. Conclusions SCe supplementation may enhance skeletal muscle strength but not mass in older adults who perform low-intensity exercise. This trial was registered at clinicaltrials.gov as NCT03402308. [ABSTRACT FROM AUTHOR]

Background Although there is growing evidence on the role of preconception nutrition for birth outcomes, very few studies have evaluated the long-term effects of nutrition interventions during the preconception period on offspring cognitive outcomes. Objective We evaluate the impact of preconception weekly multiple micronutrients (MMs) or iron and folic acid (IFA) supplementation compared with folic acid (FA) alone on offspring intellectual functioning at age 6–7 y. Methods We followed 1599 offspring born to women who participated in a double-blinded randomized controlled trial of preconception supplementation in Vietnam. Women received weekly supplements containing either 2800 μg FA only, 60 mg iron and 2800 μg FA, or MMs (15 micronutrients including IFA) from baseline until conception, followed by daily prenatal IFA supplements until delivery. We used the Wechsler Intelligence Scale for Children to measure full-scale IQ (FSIQ) and 4 related domains of intellectual functioning [Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores] at 6–7 y. Group comparisons were done using ANOVA tests for all children and the subgroup born to women who consumed the supplements ≥26 wk before conception (per-protocol analyses). Results The final sample with data at 6–7 y (n  = 1321) was similar for baseline maternal and offspring birth characteristics and age at follow-up by treatment group. Compared with the offspring in the FA group, those in the MM group had higher FSIQ (β = 1.7; 95% CI: 0.1, 3.3), WMI (β = 1.7; 95% CI: 0.2, 3.2), and PSI (β = 2.5; 95% CI: 0.9, 4.1). Similar findings were observed in the per-protocol analyses. There were no significant differences by treatment group for VCI and PRI. Conclusions Preconception supplementation with MMs improved certain domains of intellectual functioning at age 6–7 y compared with FA. These findings suggest the potential for preconception micronutrient interventions to have long-term benefits for offspring cognition. [ABSTRACT FROM AUTHOR]

A novel antibody–drug conjugate, trastuzumab deruxtecan is a combination of a human epidermal growth factor receptor 2 (HER2)-targeting antibody and DNA topoisomerase I inhibitor used to treat HER2-low/positive advanced breast cancer. To determine its safety and efficacy in treating HER2-low/positive advanced breast cancer, we performed a meta-analysis of several randomized clinical trials (RCTs) including DESTINY-Breast02 (NCT03523585), DESTINY-Breast03 (NCT03529110), and DESTINY-Breast04 (NCT03734029). We searched PubMed, Embase, and the Cochrane Library for RCTs on the efficacy and safety of trastuzumab deruxtecan that were published before May 2023. The efficacy endpoints included median progressive-free survival (PFS), overall survival (OS), duration of response (DOR), overall response rate (ORR), and clinical benefit rate (CBR). The safety endpoints included treatment-related adverse events. Statistical analyses were performed using RevMan 5.4 software. To ensure transparency, this study was registered on the International Prospective Register of Systematic Reviews website (CRD42023414170). Three RCTs involving 1689 patients were included. Compared with physician-recommended and conventional treatments, trastuzumab deruxtecan exhibited statistically significant improvements in PFS, ORR, and CBR. The median OS and DOR failed to be combined; however, the analyzed studies showed that they were longer. The incidence of adverse events was generally higher with trastuzumab deruxtecan than with physician-recommended or conventional treatments. The results of this study suggest that trastuzumab deruxtecan is more effective in treating HER2-low/positive advanced breast cancer than physician-recommended or conventional treatments. However, trastuzumab deruxtecan-related adverse drug reactions should be closely monitored because of its higher incidence of adverse events. • HER2-targeted therapy is ineffective in locally advanced or metastatic disease. • Trastuzumab deruxtecan may improve function compared to traditional treatments. • We included 1689 breast cancer patients from three randomized clinical studies. • Verification of trastuzumab deruxtecan's efficacy and safety is needed. [ABSTRACT FROM AUTHOR]

Background: The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown.Objectives: The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides.Methods: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time.Results: Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1.Conclusions: Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210. [ABSTRACT FROM AUTHOR]

Background In lower-middle-income settings, growth faltering in the first 6 mo of life occurs despite exclusive breastfeeding. Objective The aim was to test the efficacy of an approach to improve the dietary adequacy of mothers during lactation and thus improve the growth of their infants. Methods Eligible mother–infant dyads (infants ≤7 d of age) were randomly assigned to either intervention or control groups. Mothers in the intervention group received snacks that were to be consumed daily, which provided 600 kcal of energy—with 25–30% of energy derived from fats (150–180 kcal) and 13% of energy from protein (80 kcal). Micronutrients were supplemented as daily tablets. We provided counseling on breastfeeding and infant-care practices to mothers in both groups. The primary outcome was attained infant length-for-age z scores (LAZ) at 6 mo of age. Secondary outcomes included exclusive breastfeeding proportion reported by the mother, maternal BMI and midupper arm circumference (MUAC), hemoglobin concentrations in mothers and infants, and the proportion of anemic infants at 6 mo of age. Results We enrolled 816 mother–infant dyads. The intervention did not achieve a significant effect on LAZ at 6 mo (adjusted mean difference: 0.09; 95% CI: −0.03, 0.20). Exclusive breastfeeding at 5 mo was higher (45.1% vs. 34.5%; RR: 1.31; 95% CI: 1.04, 1.64) in the intervention group compared with the controls. There were no significant effects on mean hemoglobin concentration or the proportion of anemic infants at 6 mo of age compared with the control group. We noted significant effects on maternal nutritional status (BMI, MUAC, hemoglobin concentration, and proportion anemic). Conclusions Postnatal supplementation of 600 kcal energy, 20 g protein, and multiple micronutrients daily to lactating mothers did not affect infant LAZ at age 6 mo. Such supplementation may improve maternal nutritional status. This trial was registered at Clinical Trials Registry–India as CTRI/2018/04/013095. [ABSTRACT FROM AUTHOR]

Context: People with spasticity that occurred between 30 days and one year after stroke onset with a baseline Modified Ashworth Scale (MAS) ≥1.Objectives: To determine the practicality of a pragmatic parallel-group open-labeled randomized controlled trial and to collect preliminary data of effectiveness and safety of electroacupuncture (EA) for poststroke spasticity.Methods: Eligible participants were randomly allocated to the intervention group (EA plus usual care) or the control group (usual care alone) at a 1:1 ratio with block sizes of six. Participants received EA three times a week for four weeks, then were followed up for another four weeks. Participants' retention and adherence in the trial were assessed to determine the practicality of trial design. Clinical outcome measures were the change scores of MAS, Fugl-Meyer Assessment of motor performance and Barthel Index, and adverse events.Results: Seventy-two people were screened for eligibility, and 30 of them were recruited and randomized. At the end, 25 participants followed the trial protocol and were included in our final data analyses using an intention-to-treat approach. No significant between-group difference was detected for the change scores of MAS, Fugl-Meyer Assessment, or Barthel Index at the end of treatment or end of follow-up. Eighteen participants reported 37 adverse events, but none of the participants was deemed related to EA.Conclusion: It is feasible to conduct a full-scale trial to precisely evaluate the effectiveness and safety of EA for treating poststroke spasticity; however, longer treatment and follow-up phases should be considered in the full-scale trial. [ABSTRACT FROM AUTHOR]

Background There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. Objectives The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. Methods Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. Results Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: −57.0 g/d; 95% CI: −77.9, −39.5 g/d; and −38.8 μmol/d; 95% CI: −91.2, −10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P  < 0.001 and P  = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: −0.7% point, 95% CI: −2.0, −0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. Conclusions Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group. This trial was registered at clinicaltrials.gov as NCT03067428. [ABSTRACT FROM AUTHOR]

Background Observational studies have suggested that intake of nuts is associated with lower risk of cardiometabolic diseases, whereas refined grain consumption has been linked to higher risk. Little is known about whether substituting white rice, a refined grain, with nuts may confer benefit among adults at high risk of cardiometabolic diseases. Objectives We aimed to evaluate isocaloric substitution of peanuts for white rice bars as snacks on changes in fasting glucose, lipid profile, body weight, as well as changes in metabolic syndrome (MetS) status among participants with MetS or at risk of MetS. Methods This parallel-arm randomized controlled trial included 224 participants either with MetS (according to the International Diabetes Federation criteria for Chinese adults, n  = 163) or at risk of MetS (central obesity plus 1 additional MetS risk factor, n  = 61). Participants were randomly assigned to either the peanut arm (56 g/d as snacks, n  = 113) or the control arm (isocaloric white rice bars, n  = 111) for 12 wk. Results A total of 209 participants (93.3%) completed the 12-wk intervention with a compliance rate > 85% among all participants. No between-group differences were found for improvements in fasting glucose, HDL cholesterol, waist circumference, and body weight. Participants in the peanut group had a significantly higher MetS reversion rate (no longer meeting MetS criteria after the 12-wk trial) than those in the control group (RR: 2.33; 95% CI: 1.10, 4.89; P  = 0.026). Conclusions Including peanuts as a snack in the habitual diet in place of a refined-grain snack did not significantly change glycemic or lipid parameters, but improved overall MetS risk without promoting weight gain among Chinese adults at high risk of cardiometabolic diseases. Further larger-scale trials are needed to confirm these findings and elucidate underlying biological mechanisms. This trial was registered at clinicaltrials.gov as NCT03194152. [ABSTRACT FROM AUTHOR]

Background: Obesity accelerates age-related cognitive decline, which is partly mediated by vascular dysfunction.Objective: The aim was to test the hypothesis that supplementation with fish oil and curcumin can enhance cognitive performance by improving cerebral circulatory function in overweight or obese middle-aged to older adults.Methods: In a 16-wk double-blind, placebo-controlled intervention trial, adults [50-80 y; BMI (kg/m2): 25-40] were randomly assigned to either fish oil (2000 mg/d DHA + 400 mg/d EPA), curcumin (160 mg/d), or a combination. Effects on cerebrovascular function (primary outcome) and cardiovascular risk factors were reported previously. Effects on cognitive performance and cerebrovascular responsiveness (CVR) to cognitive stimuli are reported herein. One-factor ANOVA with post hoc analyses was conducted between groups in the whole cohort and in males and females separately. Two-factor ANOVA was conducted to assess independent effects of fish oil and curcumin and a potential interaction. Correlations between outcomes (those obtained herein and previously reported) were also examined.Results: Compared with placebo, fish oil improved CVR to a processing speed test (4.4% ± 1.9% vs. -2.2% ± 2.1%; P = 0.023) and processing speed in males only (Z-score: 0.6 ± 0.2 vs. 0.1 ± 0.2; P = 0.043). Changes in processing speed correlated inversely with changes in blood pressure (R = -0.243, P = 0.006) and C-reactive protein (R = -0.183, P = 0.046). Curcumin improved CVR in a working memory test (3.6% ± 1.2% vs. -0.2% ± 0.2%, P = 0.026) and, in males only, performance of a verbal memory test compared with placebo (Z-score: 0.2 ± 0.1 vs. -0.5 ± 0.2, P = 0.039). Combining fish oil with curcumin did not produce additional benefits.Conclusions: Improvements in processing speed following fish-oil supplementation in middle-aged to older males might be mediated by improvements in circulatory function. Mechanisms underlying the cognitive benefit seen with curcumin are unknown. As cognitive benefits were found in males only, further evaluation of sex differences in responsiveness to supplementation is warranted. This trial was registered at the Australian and New Zealand Clinical Trial Register at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370788 as ACTRN12616000732482p. [ABSTRACT FROM AUTHOR]

Background Despite the rising popularity of plant-based alternative meats, there is limited evidence of the health effects of these products. Objectives We aimed to compare the effect of consuming plant-based alternative meat (Plant) as opposed to animal meat (Animal) on health factors. The primary outcome was fasting serum trimethylamine-N-oxide (TMAO). Secondary outcomes included fasting insulin-like growth factor 1, lipids, glucose, insulin, blood pressure, and weight. Methods SWAP-MEAT (The Study With Appetizing Plantfood—Meat Eating Alternatives Trial) was a single-site, randomized crossover trial with no washout period. Participants received Plant and Animal products, dietary counseling, lab assessments, microbiome assessments (16S), and anthropometric measurements. Participants were instructed to consume ≥2 servings/d of Plant compared with Animal for 8 wk each, while keeping all other foods and beverages as similar as possible between the 2 phases. Results The 36 participants who provided complete data for both crossover phases included 67% women, were 69% Caucasian, had a mean ± SD age 50 ± 14 y, and BMI 28 ± 5 kg/m2. Mean ± SD servings per day were not different by intervention sequence: 2.5 ± 0.6 compared with 2.6 ± 0.7 for Plant and Animal, respectively (P  = 0.76). Mean ± SEM TMAO concentrations were significantly lower overall for Plant (2.7 ± 0.3) than for Animal (4.7 ± 0.9) (P  = 0.012), but a significant order effect was observed (P  = 0.023). TMAO concentrations were significantly lower for Plant among the n  = 18 who received Plant second (2.9 ± 0.4 compared with 6.4 ± 1.5, Plant compared with Animal, P  = 0.007), but not for the n  = 18 who received Plant first (2.5 ± 0.4 compared with 3.0 ± 0.6, Plant compared with Animal, P  = 0.23). Exploratory analyses of the microbiome failed to reveal possible responder compared with nonresponder factors. Mean ± SEM LDL-cholesterol concentrations (109.9 ± 4.5 compared with 120.7 ± 4.5 mg/dL, P  = 0.002) and weight (78.7 ± 3.0 compared with 79.6 ± 3.0 kg, P  < 0.001) were lower during the Plant phase. Conclusions Among generally healthy adults, contrasting Plant with Animal intake, while keeping all other dietary components similar, the Plant products improved several cardiovascular disease risk factors, including TMAO; there were no adverse effects on risk factors from the Plant products. This trial was registered at clinicaltrials.gov as NCT03718988. [ABSTRACT FROM AUTHOR]

Objectives: We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.Methods: The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.Results: We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.Conclusions: Atorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. [ABSTRACT FROM AUTHOR]

Background: This study demonstrated the safety and effectiveness of baroreflex activation therapy (BAT) in patients with heart failure with reduced ejection fraction (HFrEF).Objectives: The BeAT-HF (Baroreflex Activation Therapy for Heart Failure) trial was a multicenter, prospective, randomized, controlled trial; subjects were randomized 1:1 to receive either BAT plus optimal medical management (BAT group) or optimal medical management alone (control group).Methods: Four patient cohorts were created from 408 randomized patients with HFrEF using the following enrollment criteria: current New York Heart Association (NYHA) functional class III or functional class II (patients who had a recent history of NYHA functional class III); ejection fraction ≤35%; stable medical management for ≥4 weeks; and no Class I indication for cardiac resynchronization therapy. Effectiveness endpoints were the change from baseline to 6 months in 6-min hall walk distance (6MHW), Minnesota Living with HF Questionnaire quality-of-life (QOL) score, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. The safety endpoint included the major adverse neurological or cardiovascular system or procedure-related event rate (MANCE).Results: Results from, timeline and rationale for, cohorts A, B, and C are presented in detail in the text. Cohort D, which represented the intended use population that reflected the U.S. Food and Drug Administration-approved instructions for use (enrollment criteria plus NT-proBNP <1,600 pg/ml), consisted of 245 patients followed-up for 6 months (120 in the BAT group and 125 in the control group). BAT was safe and significantly improved QOL, 6MHW, and NT-proBNP. In the BAT group versus the control group, QOL score decreased (Δ = -14.1; 95% confidence interval [CI]: -19 to -9; p < 0.001), 6MHW distance increased (Δ = 60 m; 95% CI: 40 to 80 m; p < 0.001), NT-proBNP decreased (Δ = -25%; 95% CI: -38% to -9%; p = 0.004), and the MANCE free rate was 97% (95% CI: 93% to 100%; p < 0.001).Conclusions: BAT was safe and significantly improved QOL, exercise capacity, and NT-proBNP. (Baroreflex Activation Therapy for Heart Failure [BeAT-HF]; NCT02627196). [ABSTRACT FROM AUTHOR]

• We will monitor compliance with the intervention and adverse events. • Data will be analyzed following intention-to-treat principles. • A cost-effectiveness analysis will be performed. This a priori statistical analysis plan describes the methods of analysis for the Trial Of Prevention Strategies for low back pain (TOPS). TOPS aimed to investigate the effectiveness and cost-effectiveness of exercise and education classes compared with a minimal intervention control in preventing recurrence of low back pain (LBP) in people who have recently recovered from an episode of LBP. TOPS is a superiority, pragmatic, parallel-group randomized controlled trial with allocation concealment, blinded outcome assessors, and intention-to-treat analysis. Participants were randomized to a physical therapist-led exercise and education program for 12 weeks or minimal intervention. The primary outcome was days to recurrence of an episode of LBP. The three key secondary outcomes were days to recurrence of an episode of LBP resulting in (1) activity limitation, (2) care seeking for LBP; and (3) work absence of at least 1 day. Differences in survival curves for the primary (days to recurrence) and secondary outcome (days to LBP with activity limitation, days to care seeking due to LBP, and days to work absence due to LBP) will be compared using Cox regression. Hazard ratios (HRs) and median survival times with 95% confidence intervals (CI) will be calculated. The number of adverse events, including serious adverse events will be reported and the proportion of adverse events between groups will be compared using a Chi-squared test. This paper will provide a detailed description of the planned analyses for the TOPS trial. Australian New Zealand Clinical Trials Registry (ACTRN12615000939594). [ABSTRACT FROM AUTHOR]

Background: Postprandial inflammation that occurs concurrently with hyperglycemia and hyperlipidemia after ingestion of a high-saturated-fat, high-carbohydrate meal (HFCM) is a risk factor for cardiovascular disease (CVD). Numerous preclinical and clinical studies demonstrate anti-inflammatory effects of individual spices. However, the effect of consumption of a spice blend on inflammatory mediators has not been examined in a randomized controlled trial.Objectives: The objective of this study was to investigate the postprandial effect of a blend of spices in a HFCM on inflammatory cytokine responses.Methods: Nonsmoking men (40-65 y old) with overweight/obesity (25 ≤ BMI ≤ 35 kg/m2), elevated waist circumference (≥ 94 cm), and ≥ 1 CVD risk factor were recruited for a 3-period crossover study ( n = 12). In random order, participants consumed the following: a HFCM (∼1000 kcal, 33% kcal from saturated fat and 36% kcal from carbohydrate), a HFCM containing 2 g spice blend, or an HFCM containing 6 g spice blend. The spice blend consisted of basil, bay leaf, black pepper, cinnamon, coriander, cumin, ginger, oregano, parsley, red pepper, rosemary, thyme, and turmeric. Blood was collected before, and hourly for 4 h after the HFCM. Peripheral blood mononuclear cells (PBMCs) were isolated, and the percentage of CD14 +/Human Leukocyte Antigen-DR isotype + (HLA-DR +) monocytes and proinflammatory cytokine concentrations in plasma and LPS-stimulated PBMCs were quantified as secondary outcomes.Results: There was a significant spice-by-time interaction on IL-1β (P < 0.001), IL-8 (P = 0.020), and TNF-α (P = 0.009) secretion from LPS-stimulated PBMCs. IL-1β secretion from LPS-stimulated PBMCs was significantly reduced (1314%) at 240 min after HFCM consumption containing 6 g, but not 2 g, of spice blend compared with 0 g spice blend.Conclusions: A HFCM containing 6 g spice blend attenuated HFCM-induced postprandial IL-1β secretion in men with overweight/obesity.This trial was registered at clinicaltrials.gov as NCT03064958. [ABSTRACT FROM AUTHOR]

Background: Effects of very low carbohydrate (VLC) diets on appetite response in individuals with type 2 diabetes remain unclear.Objective: A secondary analysis was conducted to determine appetite responses to an energy-restricted [30% of energy (%E) deficit] very low carbohydrate (VLC) diet compared with a higher carbohydrate (HC) diet in adults who were overweight or obese with type 2 diabetes.Methods: Forty-four men and 40 women (mean ± SD, age: 58.7 ± 6.6 y; weight: 100.4 ± 15.5 kg; BMI: 34.5 ± 4.1 kg/m2; glycated hemoglobin: 7.3 ± 1.0%; duration of diabetes: 6.7 ± 5.6 y) were randomly assigned to diets categorized as VLC [14%E carbohydrate (<50 g/d), 28%E protein, 58%E fat (<10%E saturated fat)], or energy-matched HC [53%E carbohydrate, 17%E protein, 30%E fat (<10%E saturated fat)] combined with progressive multicomponent exercise (60 min; 3 d/wk). Body weight, average weekly "daily fasting" and "daily overall" appetite perceptions (hunger, fullness, prospective consumption, and desire to eat-visual analog scales) were assessed at baseline and after 4 and 16 wk. Changes between diets over time were assessed using repeated measures ANOVA.Results: Significant decreases in body weight did not differ between groups (VLC: -11.0 ± 5.4 kg/16 wk compared with HC: -10.1 ± 4.3 kg/16 wk, P = 0.40). Compared with HC, VLC had greater decreases in "daily overall" ratings of fullness (P time × diet < 0.01), such that scores were higher in HC at Week 4 (VLC:48 ± 3 vs HC:56 ± 3 mm, P = 0.001) and 16 (VLC:51 ± 2 vs HC:57 ± 3 mm, P = 0.019). Compared with HC, VLC had greater increases in prospective consumption ratings (P time × diet = 0.03), such that scores were lower in HC at Week 4 (VLC:33 ± 2 vs HC:28 ± 2 mm, P = 0.008), but not at Week 16 (VLC:33 ± 2 vs HC 31 ± 2 mm, P = 0.289).Conclusions: In the context of energy restriction, both HC and VLC energy-matched diets promoted comparable effects on fasting perceptions of appetite, but the HC diet resulted in greater "daily overall" fullness and reduced prospective consumption. Further research is required to evaluate the effects of ad libitum diets differing in amounts of carbohydrate on appetite response in populations with type 2 diabetes. This trial was registered at www.anzctr.org.au as ACTRN12612000369820. [ABSTRACT FROM AUTHOR]

Context: Chronic breathlessness is a clinical syndrome that results in significant distress and disability. Morphine can reduce chronic breathlessness when the contributing etiologies are optimally treated.Objectives: Does oxycodone reduce chronic breathlessness compared with placebo?Methods: A multisite, randomized, placebo-controlled, double-blind, parallel-arm, fixed-dose trial of oral controlled-release oxycodone 15 mg (5 mg, eight hourly) or placebo (ACTRN12609000806268 at www.anzctr.org.au). As-needed immediate-release morphine (2.5 mg per dose; six and less doses/day) was available for both arms as required by one ethics committee overseeing the trial. Recruitment occurred from 2010 to 2014 in 14 inpatient and outpatient respiratory, cardiology, and palliative care services across Australia. Participants were adults, with chronic breathlessness (modified Medical Research Council Scale 3 or 4), who were opioid naive. The primary end point was the proportion of people with greater than 15% reduction from baseline in the intensity of breathlessness now (0-100 mm visual analogue scale) comparing arms Days 5-7. Secondary end points were average and worst breathlessness, quality of life, function, and harms.Results: Of 157 participants randomized, 155 were included (74 oxycodone and 81 placebo), but the study did not reach target recruitment. There was difference in neither between groups for the primary outcome (P = 0.489) nor any of the prespecified secondary outcomes. Placebo participants used more as-needed morphine (mean 7.0 vs. 4.2 doses; P ≤ 0.001). Oxycodone participants reported more nausea (P < 0.001).Conclusion: There was no signal of benefit from oxycodone over placebo. Future research should focus on investigating the existence of an opioid class effect on the reduction of chronic breathlessness. [ABSTRACT FROM AUTHOR]

Background Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. Objectives A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterranean-style diet on indices of inflammation and changes in nutritional status. Methods Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65–79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. Results Estimated selenium intakes increased significantly with the intervention group (P  < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P  < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P  = 0.04) and France (P  = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P  < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P  < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P  = 0.01) and body iron (P  = 0.01), but not sTfR (P  = 0.73); there were no study center × selenium status interactions for the iron biomarkers. Conclusions Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012. [ABSTRACT FROM AUTHOR]

Background Comparative studies suggest that DHA may have stronger serum triglyceride–lowering effects than EPA; however, the molecular basis for this differential effect remains unexplored in humans. Differential regulation of lipogenesis and triglyceride clearance are 2 possible mechanisms of action. Objectives We compared the effects of EPA and DHA supplementation on serum triglycerides, markers of lipogenesis, and lipoprotein lipase (LPL) activity in adults participating in a double-blind, multiarm, placebo-controlled parallel-group randomized trial. Lipogenesis was assessed with the lipogenic index and compound specific isotope analysis (CSIA). Methods Young, healthy normolipidemic men and women (n  = 89; 21.6 ± 0.23 y; mean ± SEM) were randomly allocated into 1 of 3 supplement groups for 12 wk: 1) olive oil, 2) ∼3 g EPA/d, and 3) ∼3 g DHA/d. Omega-3 supplements were provided in triglyceride form. Blood was collected before and after supplementation for the analysis of fatty acids and preheparin LPL activity. Variations in the 13C:12C ratio (δ13C) of palmitate (16:0) and linoleate (18:2n–6) were measured by CSIA. Results DHA supplementation reduced blood triglycerides (0.85 ± 0.04 mmol/L to 0.65 ± 0.03 mmol/L; P  < 0.01), with no change seen with EPA supplementation. DHA supplementation did not change the lipogenic index or δ13C-16:0, whereas EPA supplementation increased the lipogenic index by 11% (P  < 0.01) and δ13C-16:0 (P  = 0.03) from −23.2 ± 0.2 to −22.8 ± 0.2 milliUrey ± SEM. Conclusions Reduced triglyceride concentrations after DHA supplementation are associated with increased LPL activity, whereas the null effect of EPA supplementation on blood triglycerides may stem from the concomitant increases in lipogenesis and LPL activity. Further investigation of the differential triglyceride-lowering effects of EPA and DHA is warranted in both normolipidemic and hyperlipidemic individuals. This trial was registered at clinicaltrials.gov as NCT03378232. [ABSTRACT FROM AUTHOR]

Background Thiamin, a water-soluble B-complex vitamin, functions as a coenzyme in macronutrient oxidation and in the production of cellular ATP. Data suggest that thiamin depletion occurs in heart failure (HF). Therefore, thiamin supplementation in HF patients may improve cardiac function. Objective We sought to determine whether oral thiamin supplementation improves left ventricular ejection fraction (LVEF), exercise tolerance, and quality of life among patients with HF and reduced LVEF. Methods In this prospective, multicenter, double-blind, placebo-controlled randomized trial, eligible ambulatory patients with HF and reduced LVEF were recruited from 4 academic and community hospitals between 2010 and 2015. Participants were randomly assigned to receive either 200 mg oral thiamin mononitrate per day or placebo for 6 mo. Results Sixty-nine patients (mean ± SD age: 64 ± 12 y; 83% men; LVEF: 37% ± 11%) were randomly assigned: 34 received placebo and 35 received thiamin supplementation. Erythrocyte thiamin pyrophosphate and urine thiamin concentrations were significantly higher in the supplemented group than in the placebo group at 6 mo (P  = 0.02 and <0.001, respectively). At 6 mo, LVEF was significantly higher in the placebo group than in the thiamin group (38%; 95% CI: 36%, 39% compared with 35%; 95% CI: 33%, 37%, P  = 0.047) after adjusting for baseline measurements. There were no significant differences in Minnesota Living with Heart Failure score, distance walked in 6 min, and N-terminal prohormone of brain natriuretic peptide concentrations between the 2 groups. One patient (2.9%) in the thiamin-supplemented group and none in the control group died at 6 mo. Conclusions In ambulatory patients with HF and reduced LVEF, thiamin supplementation for 6 mo did not improve LVEF, quality of life, or exercise capacity, despite increases in thiamin concentrations. These findings do not support routine thiamin supplementation in the treatment of HF and reduced LVEF. This trial was registered at clinicaltrials.gov as NCT00959075. [ABSTRACT FROM AUTHOR]

Context: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined.Objectives: We examined the effect of two doses of prophylactic FSS on exertional dyspnea.Methods: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%-45% (high dose) or 15%-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function.Results: Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected.Conclusion: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials. [ABSTRACT FROM AUTHOR]

Context: Although opioids and pregabalin are widely used for cancer-related neuropathic pain (CNP), no clinical trials exist to determine which medications are effective when an opioid-pregabalin combination therapy fails.Objectives: We investigated the efficacy of duloxetine for CNP nonresponsive or intolerant to opioid-pregabalin combination therapy.Methods: A multicenter, randomized, double-blind, placebo-controlled trial was performed at 12 specialized palliative care services in Japan. Patients with CNP average pain scores (Brief Pain Inventory [BPI]-Item 5) ≥ 4 in the previous 24 hours and nonresponsive or intolerant to opioid-pregabalin combination therapy were eligible. Patients with chemotherapy-induced peripheral neuropathies were excluded. Patients were administered duloxetine 20 mg/day titrated to 40 mg/day or placebo for 10 days. The primary endpoint was BPI-Item 5 on Day 10. Responder analysis measured proportions of patients with 30% and 50% pain decreases.Results: Seventy patients were enrolled. Complete case analysis revealed mean BPI-Item 5 on Day 10 of 4.03 for Group D vs. 4.88 for Group P (P = 0.053). Baseline observation carried forward analysis revealed mean BPI-Item 5 on Day 10 of 4.06 and 4.91 for Groups D and P, respectively (P = 0.048). Clinically meaningful pain improvement (≥30%) was reported by 44.1% (n = 15) of patients in Group D vs. 18.2% (n = 6) in Group P (P = 0.02); 32.4% (n = 11) vs. 3.0% (n = 1) of patients in Groups D and P, respectively, reported pain reduction ≥ 50% (P = 0.002).Conclusion: Adding duloxetine to opioid-pregabalin therapy might have clinical benefit in alleviating refractory CNP. Further studies are needed to conclude the efficacy of adding duloxetine. [ABSTRACT FROM AUTHOR]

Background: The preferred macronutrient dietary composition, and the health consequences of dietary fat reduction specifically, have been debated for decades. Here we provide a comprehensive overview of long-term health outcomes in the Women's Health Initiative Dietary Modification (DM) trial.Objective: The DM trial aimed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer, colorectal cancer, and, secondarily, coronary heart disease (CHD), with various other health outcomes also considered.Methods: The DM trial is a randomized controlled trial conducted at 40 centers in the US, among 48,835 postmenopausal women aged 50-79 y with baseline intake of ≥32% energy from fat. Participants were randomly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group, during 1993-1998. Intervention goals were to reduce fat intake from ∼35% to 20% of total energy, in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d.Results: Over an 8.5-y (median) intervention period, intervention and comparison group differences included lower fat by 8-10%, and higher carbohydrate by 8-10%, of total energy, in conjunction with higher consumption of vegetables, fruit, and grains. Time-to-outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer, colorectal cancer, or CHD, either over the intervention period or over longer-term cumulative follow-up. Additional analyses showed significant intervention group benefits related to breast cancer, CHD, and diabetes, without adverse effects. Over a 19.6-y (median) follow-up period, HRs (95% CIs) were 0.84 (0.74, 0.96) for breast cancer followed by death, and 0.87 (0.77, 0.98) for diabetes requiring insulin.Conclusions: Reduction in dietary fat with corresponding increase in vegetables, fruit, and grains led to benefits related to breast cancer, CHD, and diabetes, without adverse effects, among healthy postmenopausal US women.This trial was registered at clinicaltrials.gov as NCT00000611. [ABSTRACT FROM AUTHOR]