A Randomized Trial of Alerting to Hypocholesterolemia Results of the Low Indexes of Metabolism Intervention Trial-C (LIMIT-C)

ObjectivesThe benefit of alerting clinical staff to drug-induced hypocholesterolemia in patients aged 75 years and older remains uncertain.Design, setting, and participantsThe study included 1791 patients with serum cholesterol <160 mg/dL and on cholesterol-lowering drugs who were assigned to have an e-mail alert sent to their physician, and 1804 patients who were assigned to receive usual clinical care (control group). The primary outcome of the trial was annual death rate. Secondary outcomes included cholesterol-lowering drug dose reduction and emergency department (ED) visits.ResultsAt 1 year, 58 patients (3.2%) in the intervention group and 61 (3.4%) in the control group had died [relative risk 0.94, 95% confidence interval (CI) 0.66-1.34; P = .74]. Quarter-averaged cholesterol-lowering drug defined daily doses were reduced by −13.5 ± 47.0 (−17% ± 60%) in the intervention group and by −5.1 ± 42.2 (−6%±54%) in the control group (difference −8.5 ± 1.5, 95% CI –5.5 to −11.4; P < .0001). Annual ED visit rates per 1000 patients were 291 in the intervention group and 336 in the control group (45 fewer visits per 1000 patients in the intervention group, 95% CI –1 to −89; P = .04).Conclusions and implicationsIn this trial, alerting clinical staff to hypocholesterolemia in patients aged 75 years and older being treated with cholesterol-lowering drugs was associated with mildly reduced cholesterol-lowering drugs doses and marginally reduced ED visit rates. This e-mail alert intervention was not associated with a significant difference in 1-year survival rate compared with usual clinical care.     

Immunogenicity and Safety of Intradermal Trivalent Influenza Vaccination in Nursing Home Older Adults: A Randomized Controlled Trial

ObjectiveTo compare the immunogenicity and safety between full-dose (15 μg) intramuscular (IM) and full-dose (15 μg) intradermal (ID) immunization of the trivalent influenza vaccine in nursing home older adults.DesignA single-center, randomized, controlled, open-label, parallel group trial from October 2013 to April 2014.SettingNine nursing homes in Hong Kong.ParticipantsHundred nursing home older adults (mean age: 82.9 ± 7.4 years).InterventionFifty received ID (Intanza) and 50 received IM (Vaxigrip) vaccination.MeasurementsBaseline measurements included demographics, comorbidity, frailty and nutritional status. Day 21 and day 180 immunogenicity (seroconversion rate, seroprotection rate, geometric mean titer [GMT] fold increase in antibody titer) using hemagglutination-inhibition and adverse events were measured. Noninferiority and superiority of ID compared with IM vaccination in immunogenicity were analyzed. The study was registered on ClinicalTrials.gov; identifier: NCT 01967368.ResultsAt day 21, noninferiority in immunogenicity of the ID vaccination was demonstrated. The seroconversion rate of the H1N1 strain was significantly higher in the ID group. At day 180, immunogenicity of both groups fell but the GMT of all strains in ID group was higher and the difference was significant for H3N2 strain. The seroconversion rate and GMT fold increase of H3N2 strain was significantly higher in the ID group. Local adverse events was significantly more in ID group, but they were mild and resolved in 72 hours.ConclusionsID vaccination is noninferior, and even superior in some parts of immunogenicity assessment, to IM vaccination without compromising safety in nursing home older adults. ID vaccination is a good alternative to IM vaccination in this population.     

Post Hoc Analyses of a Randomized Controlled Trial for the Effect of Pharmacist Deprescribing Intervention on the Anticholinergic Burden in Frail Community-Dwelling Older Adults

ObjectivesAnticholinergic burden is detrimental to cognitive health. Multiple studies found that a high anticholinergic burden is associated with an increased risk for dementia, changes to the brain structure, function, and cognitive decline. We performed a post hoc analysis of a randomized controlled deprescribing trial. We compared the effect of the intervention on baseline anticholinergic burden across the treatment and control groups and the time of recruitment before and after a lockdown due to the COVID pandemic with subgroup analyses by baseline frailty index.DesignRandomized controlled trial.Settings and ParticipantsWe analyzed data from a de-prescribing trial of older adults (>65 years) previously conducted in New Zealand that was focused on reducing the Drug Burden Index (DBI).MethodsWe used the anticholinergic cognitive burden (ACB) to quantify the impact of the intervention on reducing the anticholinergic burden. Participants not taking anticholinergics at the start of the trial were excluded. The primary outcome for this subgroup analysis was a change in ACB, measured with the ĝ_Hedges statistic describing the difference in standard deviation units of this change between intervention and control. For this analysis, the trial participants were stratified into low, medium, and high frailty and timing into prior- and post-lockdown (public health measures for COVID-19).ResultsAmong the 295 participants in this analysis, the median (IQR) age was 79 (74, 85), and 67% were women. For the primary outcome ĝ_Hedges = −0.04 (95% CI −0.26 to 0.19) with a −0.23 mean reduction in ACB in the intervention arm and −0.19 in the control arm. Before lockdown ĝ_Hedges = −0.38 (95% CI −0.84 to 0.04) and post-lockdown ĝ_Hedges = 0.07 (95% CI −0.19 to 0.33). The mean change in ACB for each of the frailty strata was as follows: low frailty (−0.02; 95% CI −0.65 to 0.18); medium frailty (0.05; 95% CI −0.28 to 0.38); high frailty (0.08; 95% CI −0.40 to 0.56).Conclusions and ImplicationsThe study did not provide evidence for the effect of pharmacist deprescribing intervention on reducing the anticholinergic burden. However, this post hoc analysis examined the impact of COVID on the effectiveness of the intervention, and further research in this area may be warranted.     

The Effects of a Low Sodium Meal Plan on Blood Pressure in Older Adults: The SOTRUE Randomized Feasibility Trial

Reduced sodium meal plans are recommended by the Centers of Disease Control to lower blood pressure in older adults; however, this strategy has not been tested in a clinical trial. The Satter House Trial of Reduced Sodium Meals (SOTRUE) was an individual-level, double-blind, randomized controlled pilot study of adults living in a congregate living facility subsidized by the Federal Department of Housing and Urban Development (HUD). Adults over age 60 years ate 3 isocaloric meals with two snacks daily for 14 days. The meal plans differed in sodium density (<0.95 vs. >2 mg/kcal), but were equivalent in potassium and macronutrients. Seated systolic BP (SBP) was the primary outcome, while urine sodium-creatinine ratio was used to measure compliance. Twenty participants were randomized (95% women; 95% white; mean age 78 ± 8 years), beginning in 7 October 2019. Retention was 100% with the last participant ending 4 November 2019. Mean baseline SBP changed from 121 to 116 mmHg with the typical sodium diet (−5 mmHg; 95% CI: −18, 8) and from 123 to 112 mmHg with the low sodium diet (−11 mmHg; 95% CI: −15.2, −7.7). Compared to the typical sodium meal plan, the low sodium meal plan lowered SBP by 4.8 mmHg (95% CI: −14.4, 4.9; p = 0.31) and urine sodium-creatinine ratio by 36% (−36.0; 95% CI: −60.3, 3.4; p = 0.07), both non-significant. SOTRUE demonstrates the feasibility of sodium reduction in federally mandated meal plans. A longer and larger study is needed to establish the efficacy and safety of low sodium meals in older adults.     

Predictive Value of Different Expressions of Forced Expiratory Volume in 1 Second (FEV1) for Adverse Outcomes in a Cohort of Adults Aged 80 and Older

Objectives

Forced expiratory volume in 1 second (FEV₁) is proposed as a marker of healthy ageing and FEV₁ expressions that are independent of reference values have been reported to be better at predicting mortality in older adults. We assess and compare the predictive value of different FEV₁ expressions for mortality, hospitalization, and physical and mental decline in adults aged 80 and older.

Effects of Individual Dietary Intervention on Nutrient Intake in Postpartum Japanese Women: A Randomized Controlled Trial

No dietary intervention that focuses on the diet quality of postpartum women has been developed in Japan, although most postpartum women experience an insufficient intake of vitamins and minerals. We aimed to examine whether dietary intervention, based on the health belief model, at both 1 and 3 months postpartum affects nutrient intake and food group consumption at 6 months postpartum. A randomized controlled trial was conducted at a university hospital in Tokyo between 2015 and 2016. Healthy women at 1 month postpartum were randomly allocated to either an intervention group (n = 100) or a control group (n = 94). Dietary intervention included dietary assessment, individual feedback, and dietary guidance. The dietary intakes between the two groups were compared using the Mann-Whitney U test. At 6 months postpartum, the energy-adjusted intakes of protein, total dietary fiber, potassium, magnesium, phosphorus, zinc, vitamin B₆, and β-carotene were significantly higher in the intervention group than in the control group. The changes in energy-adjusted intakes of total dietary fiber and iron from 1 month postpartum to 6 months postpartum were significantly different between the two groups. Dietary intervention based on the health belief model improved nutrition at 6 months postpartum, although the impact was limited.     

Be Healthy in Pregnancy (BHIP): A Randomized Controlled Trial of Nutrition and Exercise Intervention from Early Pregnancy to Achieve Recommended Gestational Weight Gain

A randomized two-arm prospective superiority trial tested the efficacy of a novel structured and monitored nutrition (bi-weekly counselling for individualized energy and high dairy protein diet) and exercise program (walking goal of 10,000 steps/day) (intervention) compared to usual care (control) in pregnant women to achieve gestational weight gain (GWG) within current recommendations. Women recruited in communities in southern Ontario, Canada were randomized at 12–17 weeks gestation with stratification by site and pre-pregnancy BMI to intervention (n = 119) or control (n = 122). The primary outcome was the proportion of women who achieved GWG within the Institute of Medicine recommendations. Although the intervention compared to control group was more likely to achieve GWG within recommendations (OR = 1.51; 95% CI (0.81, 2.80)) and total GWG was lower by 1.45 kg (95% CI: (−11.9, 8.88)) neither reached statistical significance. The intervention group achieved significantly higher protein intake at 26–28 week (mean difference (MD); 15.0 g/day; 95% CI (8.1, 21.9)) and 36–38 week gestation (MD = 15.2 g/day; 95% CI (9.4, 21.1)) and higher healthy diet scores (22.5 ± 6.9 vs. 18.7 ± 8.5, p < 0.005) but step counts were similar averaging 6335 steps/day. Pregnancy and infant birth outcomes were similar between groups. While the structured and monitored nutrition with counselling improved diet quality and protein intake and may have benefited GWG, the exercise goal of 10,000 steps/day was unachievable. The results can inform future recommendations for diet and physical activity in pregnancy.     

Effect of Individual Nutrition Therapy and Exercise Regime on Gait Speed,Physical Function,Strength and Balance,Body Composition,Energy and Protein,in Injured,Vulnerable Elderly: A Multisite Randomized Controlled Trial (INTERACTIVE)

It is imperative that the surgical treatment of hip fractures is followed up with rehabilitation to enhance recovery and quality of life. This randomized controlled trial aimed to determine if an individualised, combined exercise–nutrition intervention significantly improved health outcomes in older adults, after proximal femoral fracture. We commenced the community extended therapy while in hospital, within two weeks post-surgery. The primary outcome was gait speed and secondary outcomes included physical function, strength and balance, body composition, energy and protein intake. Eighty-six and 89 participants were randomized into six months individualised exercise and nutrition intervention and attention-control groups, respectively. There were no statistically significant differences in gait speed between the groups at six and 12 months. There were no major differences between groups with respect to the secondary outcomes, except estimated energy and protein intake. This may be explained by the sample size achieved. Participants in the intervention group had greater increment in energy (235 kcal; 95% CI, 95 to 375; p = 0.01) and protein intake (9.1 g; 95% CI, 1.5 to 16.8; p = 0.02), compared with those in the control group at six months but not significant at 12 months. This study has demonstrated that providing early, combined exercise and nutrition therapy can improve dietary energy and protein intake in older adults with hip fractures.     

Feasibility and Acceptability of a Healthy Nordic Diet Intervention for the Treatment of Depression: A Randomized Controlled Pilot Trial

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and the acceptability of the intervention in preparation for an 8-week RCT in the future, which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n = 10) and non-depressed (n = 6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to their diet allocation and the study hypotheses. Health questionnaires were completed before and after the intervention and, throughout the study, questionnaires assessed participants’ liking for the meals, their sensory properties, adherence, and open-ended feedback. In the ND group, 75% of participants consumed only the provided foods, as instructed, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.     

Synbiotics Easing Renal Failure by Improving Gut Microbiology II (SYNERGY II): A Feasibility Randomized Controlled Trial

Synbiotics have emerged as a therapeutic strategy for modulating the gut microbiome and targeting novel cardiovascular risk factors, including uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS). This study aims to evaluate the feasibility of a trial of long-term synbiotic supplementation in adults with stage 3–4 chronic kidney disease (CKD). Adult participants with CKD and estimated glomerular filtration rate (eGFR) of 15–60 mL/min/1.73 m²) were recruited between April 2017 and August 2018 to a feasibility, double-blind, placebo-controlled, randomized trial of synbiotic therapy or matched identical placebo for 12 months. The primary outcomes were recruitment and retention rates as well as acceptability of the intervention. Secondary outcomes were treatment adherence and dietary intake. Exploratory outcomes were evaluation of the cardiovascular structure and function, serum IS and PCS, stool microbiota profile, kidney function, blood pressure, and lipid profile. Of 166 potentially eligible patients, 68 (41%) were recruited into the trial (synbiotic n = 35, placebo n = 33). Synbiotic and placebo groups had acceptable and comparable 12-month retention rates (80% versus 85%, respectively, p = 0.60). Synbiotic supplementation altered the stool microbiome with an enrichment of Bifidobacterium and Blautia spp., resulting in a 3.14 mL/min/1.73 m² (95% confidence interval (CI), −6.23 to −0.06 mL/min/1.73 m², p < 0.01) reduction in eGFR and a 20.8 µmol/L (95% CI, 2.97 to 38.5 µmol/L, p < 0.01) increase in serum creatinine concentration. No between-group differences were observed in any of the other secondary or exploratory outcomes. Long-term synbiotic supplementation was feasible and acceptable to patients with CKD, and it modified the gastrointestinal microbiome. However, the reduction in kidney function with synbiotics warrants further investigation.     

Feasibility and Clinical Efficacy of a Multidisciplinary Home-Telehealth Program to Prevent Falls in Older Adults: A Randomized Controlled Trial

Objectives

The aim of this study was to determine the feasibility and efficacy of a 6-month tele-rehabilitation home-based program, designed to prevent falls in older adults with 1 or more chronic diseases (cardiac, respiratory, neuromuscular or neurologic) returning home after in-hospital rehabilitation for their chronic condition. Patients were eligible for selection if they had experienced a fall during the previous year or were at high risk of falling.

Reducing the Burden of Complex Medication Regimens: SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) Cluster Randomized Controlled Trial

ObjectiveTo assess the application of a structured process to consolidate the number of medication administration times for residents of aged care facilities.DesignA nonblinded, matched-pair, cluster randomized controlled trial.Setting and ParticipantsPermanent residents who were English-speaking and taking at least 1 regular medication, recruited from 8 South Australian residential aged care facilities (RACFs).MethodsThe intervention involved a clinical pharmacist applying a validated 5-step tool to identify opportunities to reduce medication complexity (eg, by administering medications at the same time or through use of longer-acting or combination formulations). Residents in the comparison group received routine care. The primary outcome at 4-month follow-up was the number of administration times per day for medications charted regularly. Resident satisfaction and quality of life were secondary outcomes. Harms included falls, medication incidents, hospitalizations, and mortality. The association between the intervention and primary outcome was estimated using linear mixed models.ResultsOverall, 99 residents participated in the intervention arm and 143 in the comparison arm. At baseline, the mean resident age was 86 years, 74% were female, and medications were taken an average of 4 times daily. Medication simplification was possible for 62 (65%) residents in the intervention arm, with 57 (62%) of 92 simplification recommendations implemented at follow-up. The mean number of administration times at follow-up was reduced in the intervention arm in comparison to usual care (−0.36, 95% confidence interval −0.63 to −0.09, P = .01). No significant changes in secondary outcomes or harms were observed.Conclusions and ImplicationsOne-off application of a structured tool to reduce regimen complexity is a low-risk intervention to reduce the burden of medication administration in RACFs and may enable staff to shift time to other resident care activities.     

Randomized Controlled Trial of Hospital-Based Hygiene and Water Treatment Intervention (CHoBI7) to Reduce Cholera

The risk for cholera infection is >100 times higher for household contacts of cholera patients during the week after the index patient seeks hospital care than it is for the general population. To initiate a standard of care for this high-risk population, we developed Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7), which promotes hand washing with soap and treatment of water. To test CHoBI7, we conducted a randomized controlled trial among 219 intervention household contacts of 82 cholera patients and 220 control contacts of 83 cholera patients in Dhaka, Bangladesh, during 2013–2014. Intervention contacts had significantly fewer symptomatic Vibrio cholerae infections than did control contacts and 47% fewer overall V. cholerae infections. Intervention households had no stored drinking water with V. cholerae and 14 times higher odds of hand washing with soap at key events during structured observation on surveillance days 5, 6, or 7. CHoBI7 presents a promising approach for controlling cholera among highly susceptible household contacts of cholera patients.     

Lifestyle and Treatment Adherence Intervention after a Coronary Event Based on an Interactive Web Application (EVITE): Randomized Controlled Clinical Trial Protocol

Coronary heart disease is one of the main causes of morbimortality around the world. Patients that survive a coronary event suffer a high risk of readmission, relapse and mortality, attributed to the sub-optimal control of cardiovascular risk factors (CVRF), which highlights the need to improve secondary prevention strategies aimed at improving their lifestyle and adherence to treatment. Through a randomized controlled clinical trial, this study aims to evaluate the effect of an intervention involving an online health application supported by a mobile telephone or tablet (mHealth) on lifestyle (diet, physical activity, and tobacco consumption) and treatment adherence among people with coronary heart disease after percutaneous coronary intervention. The sample will comprise 240 subjects (120 in each arm: intervention and usual care). They are assessed immediately and nine months after their hospital discharge about sociodemographic, clinical, CVRF, lifestyle, and treatment adherence characteristics. The educative intervention, involving a follow-up and self-monitoring, will be performed using an online mHealth tool consisting of an application for mobile phones and tablets. The quantitative primary outcomes from the two groups will be compared using an analysis of covariance (ANCOVA) adjusted for age and gender. A multivariate analysis will be performed to examine the association of the intervention with lifestyle habits, the control of CVRFs, and outcomes after discharge in terms of the use of health services, emergency visits, cardiovascular events and readmissions.     

Efficacy of Cognitive Behavioral Therapy in Adherence to the Mediterranean Diet in Metabolic Syndrome Patients: A Randomized Controlled Trial

Objective

Verify the efficacy of cognitive behavioral therapy (CBT) in adherence to the Mediterranean diet (MedDiet) in metabolic syndrome (MetS) patients.