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Although the research base on mental health in intellectual disabilities is advancing, there are long-standing barriers that hinder successful completion of funded studies. A variety of stakeholders hold the key to mitigating the challenges and arriving at sustainable solutions that involve researchers, experts by experience, clinicians and many others in the research pathway. Lessons learned during the COVID-19 pandemic can also contribute to improvements in the conduct of research in the medium to long term. People with an intellectual disability and mental health conditions deserve high standards of evidence-based care.
In the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to ‘use the lowest possible dose’ of antipsychotic drugs, but provide no information on optimal dosing.
This analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548).
A statistical model, which described the concentration–time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and ‘active moiety’ (combined concentrations) (n = 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS.
The model showed an age-related reduction in risperidone clearance (P < 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2) v. 7.6 (s.d. = 4.9) ng/mL per mg/day, Mann–Whitney U-test, P < 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P < 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P < 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance.
Our findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.
To evaluate the hypothesis that a perinatal educational dietary intervention focused on ‘eating for the gut microbiota’ improves diet quality of pregnant women pre- and postnatally.
The Healthy Parents, Healthy Kids study is a prospectively registered randomised controlled trial designed to evaluate the efficacy of a dietary intervention in altering the maternal and infant gut microbiota and improving perinatal diet quality. Eligible pregnant women were randomised to receive dietary advice from their healthcare provider or to additionally receive a three session dietary intervention. Dietary data were collected at gestation weeks 26, 31, 36 and postnatal week 4. Outcome measures were diet quality, dietary variety, prebiotic and probiotic food intakes, energy, fibre, saturated fat and discretionary food intakes. Between-group differential changes from baseline before and after birth in these dietary measures were assessed using generalised estimating equations.
Healthy pregnant women from gestation week 26.
Forty-five women were randomised (twenty-two control, twenty-three intervention). Compared with the control group, the intervention group improved diet quality prior to birth (5·66 (95 % CI 1·65, 9·67), Cohen’s d: 0·82 (se 0·33)). The intervention improved dietary variety (1·05 (95 % CI 0·17, 1·94), d: 0·66 (se 0·32)) and increased intakes of prebiotic (0·8 (95 % CI 0·27, 1·33), d: 0·91 (se 0·33)) and probiotic foods (1·05 (95 % CI 0·57, 1·53), d: 1·3(se 0·35)) over the whole study period compared with the control group.
A dietary intervention focused on ‘eating for the gut microbiota’ can improve aspects of perinatal diet quality during and after pregnancy.
To examine the impact of front-of-package (FOP) labels on perceived healthfulness, purchasing intentions and understanding of common FOP systems.
A parallel, open-label design randomised participants to different FOP labelling conditions: ‘high in’ warning labels (WL), multiple traffic light labelling (TLL), health star ratings (HSR) (all displayed per serving) or control with no interpretive FOP labelling. Participants completed a brief educational session via a smartphone application and two experimental tasks. In Task 1, participants viewed healthy or unhealthy versions of four products and rated healthiness and purchasing intention on a seven-point Likert-type scale. In Task 2, participants ranked three sets of five products from healthiest to least healthy.
Online commercial panel.
Canadian residents ≥ 18 years who were involved in household grocery shopping, owned a smartphone and met minimum screen requirements.
Data from 1997 participants (n 500/condition) were analysed. Task 1: across most product categories, the TLL and HSR increased perceived healthiness of healthier products. All FOP systems decreased perceived healthiness of less healthy products. Similar, albeit dampened, effects were seen regarding purchasing intentions. Task 2: participants performed best in the HSR, followed by the TLL, WL and control conditions. Lower health literacy was associated with higher perceived healthiness and purchasing intentions and poorer ranking task performance across all conditions.
All FOP labelling systems, after a brief educational session, improved task performance across a wide spectrum of foods. This effect differed depending on the nutritional quality of the products and the information communicated on labels.
Energy restriction (ER) has anti-ageing effects and probably protects from a range of chronic diseases including cancer, diabetes and chronic kidney disease (CKD). Specifically, ER has a positive impact on experimental kidney ageing, CKD (diabetic nephropathy, polycystic kidney disease) and acute kidney injury (nephrotoxic, ischaemia–reperfusion injury) through such mechanisms as increased autophagy, mitochondrial biogenesis and DNA repair, and decreased inflammation and oxidative stress. Key molecules contributing to ER-mediated kidney protection include adenosine monophosphate-activated protein kinase, sirtuin-1 and PPAR-γ coactivator 1α. However, CKD is a complex condition, and ER may potentially worsen CKD complications such as protein–energy wasting, bone–mineral disorders and impaired wound healing. ER mimetics are drugs, such as metformin and Na–glucose co-transporter-2 which mimic the action of ER. This review aims to provide comprehensive data regarding the effect of ER on CKD progression and outcomes.
This study investigated the impact of recipe and single-use herb/spice packet provision on egg intake and protein intake in community-dwelling individuals aged over 55 years.
Using a randomised-controlled intervention design, 100 older adults were randomised to receive (n 53) or not receive (n 47) high-protein egg-based recipes and herb/spice packets through the post for 12 weeks, from June to December 2016. Egg intake, protein intake, adverse events, lean body mass and functional measures of lean body mass were measured at baseline, after the 12 weeks and after a further 12 weeks.
Community-dwelling older adults.
Intention-to-treat data were analysed using regression, controlling for various demographic and lifestyle characteristics. Ninety-three individuals (intervention, n 50; control, n 43) completed assessments at all three time points. Egg intakes increased by end of intervention in both groups (mean: 4–5 eggs/month). After a further 12 weeks, higher egg intakes were sustained in the intervention group, while egg intakes in the control group returned to baseline levels (between-group difference: β = −0·124, P = 0·047). No differences were found in other measures (largest β = −0·106, P = 0·12).
The provision of high-protein egg-based recipes and single-use herb/spice packets over 12 weeks increased egg intakes up to 12 weeks after end of intervention. Other factors may explain increased egg intakes during the intervention, but the sustained effects most plausibly result directly from recipe provision. Limited effects in other measures suggest that the recipes may have replaced as opposed to added to existing protein intakes.
Polycystic ovary syndrome (PCOS) is defined as a reproductive endocrine disease that results in a low-grade inflammatory and pro-oxidant state. Dietary factors, including n-3 fatty acids, may have a key role in improving metabolic disorders in PCOS patients. The present study aimed to investigate the influence of n-3 fatty acid supplementation on inflammatory and oxidative stress (OS) markers in patients with PCOS. A systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus and Lilacs, until November 2019, was conducted. Randomised clinical trials that reported inflammatory and OS markers as endpoints in women with PCOS receiving n-3 fatty acid supplementation were included. The pooled estimates of the weighted mean differences (WMD) and the standard mean differences (SMD) were calculated. Random effects models were adopted to measure the pooled outcomes. Among the 323 studies retrieved, ten fulfilled the inclusion criteria for a meta-analysis. We founded a significant decrease in high-sensitivity C-reactive protein (hs-CRP) (SMD –0·29 (95 % CI –0·56, –0·02) mg/l) and an increase in adiponectin (WMD 1·42 (95 % CI 1·09, 1·76) ng/ml) concentrations in the intervention group when compared with the placebo group. No statistically significant results were found in the meta-analysis for visfatin, nitric oxide, GSH or malondialdehyde levels or total antioxidant capacity. The data suggest that supplementation of n-3 fatty acids could reduce the inflammatory state in women with PCOS, through a decrease in hs-CRP and an increase in adiponectin levels.
Dietary guidelines should be underpinned by the best available evidence on relationships between diet and health, including evidence from nutrient-based, food-based and dietary patterns research. The primary aim of the present study was to analyse the systematic reviews conducted to inform the 2013 Australian Dietary Guidelines according to dietary exposure. The secondary aim was to analyse the reviews by health outcome, and design of included studies. To identify the systematic reviews, the dietary guidelines report was used as a starting point and relevant references were retrieved. The evidence report contained the data used in this analysis. Descriptive statistics were used to analyse reviews according to exposure, outcome, and design of included studies. A total of 143 systematic reviews were included in this analysis. Foods were the most common exposure (86·7 % of reviews), followed by nutrients (10·5 %) and dietary patterns (2·8 %). Chronic disease morbidity and/or mortality was the most common outcome (80·4 %), followed by chronic disease risk factors (19·6 %). Most reviews included evidence from cohort or nested case–control studies (92·3 %), many included evidence from case–control studies (61·5 %) and some included evidence from randomised controlled trials (28·7 %). These results reflect the research questions that were asked, the systematic review methods that were used, and the evidence that was available. In developing future iterations of the Australian Dietary Guidelines, there is an opportunity to review the latest evidence from dietary patterns research.
Empirical evidence on the longer-term effectiveness of evidence-based treatments for adolescents with post-traumatic stress disorder (PTSD) in low-resource settings is needed. The aim of the study was to evaluate the maintenance of treatment gains achieved in a comparative study of effectiveness of prolonged exposure therapy for adolescents (PE-A) and supportive counselling (SC) in adolescents with PTSD up to 24-months post-treatment.
Sixty-three adolescents (13–18 years) with PTSD were randomly assigned to receive either of the interventions comprising 7–14 sessions of treatment provided by trained and supervised non-specialist health workers (NSHWs). The primary outcome measure was PTSD symptom severity, as independently assessed on the Child PTSD Symptom Scale, at pretreatment, post-treatment, and at 3-, 6-, 12- and 24-months post-treatment follow-up (FU) evaluations.
Participants in both the prolonged exposure and SC treatment groups attained a significant reduction in PTSD symptoms and maintained this reduction in PTSD symptoms at 12- and 24-month assessment. Participants receiving prolonged exposure experienced greater improvement on the PTSD symptom severity scale than those receiving SC at 12-months FU [difference in PE-A v. SC mean scores = 9.24, 95% CI (3.66–14.83), p < 0.001; g = 0.88] and at 24-months FU [difference in PE-A v. SC mean scores = 9.35, 95% CI (3.53–15.17), p = 0.002; g = 0.68].
Adolescents with PTSD continued to experience greater benefit from prolonged exposure treatment than SC provided by NSHWs in a community setting 12 and 24 months after completion of treatment.
While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48–96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.
Infants born preterm miss out on the peak period of in utero DHA accretion to the brain during the last trimester of pregnancy which is hypothesised to contribute to the increased prevalence of neurodevelopmental deficits in this population. This study aimed to determine whether DHA supplementation in infants born preterm improves attention at 18 months’ corrected age. This is a follow-up of a subset of infants who participated in the N3RO randomised controlled trial. Infants were randomised to receive an enteral emulsion of high-dose DHA (60 mg/kg per d) or no DHA (soya oil – control) from within the first days of birth until 36 weeks’ post-menstrual age. The assessment of attention involved three tasks requiring the child to maintain attention on toy/s in either the presence or absence of competition or a distractor. The primary outcome was the child’s latency of distractibility when attention was focused on a toy. The primary outcome was available for seventy-three of the 120 infants that were eligible to participate. There was no evidence of a difference between groups in the latency of distractibility (adjusted mean difference: 0·08 s, 95 % CI –0·81, 0·97; P = 0·86). Enteral DHA supplementation did not result in improved attention in infants born preterm at 18 months’ corrected age.
The burden of disease attributable to alcohol and other drug (AOD) use in young people is considerable. Prevention can be effective, yet few programs have demonstrated replicable effects. This study aimed to replicate research behind Climate Schools: Alcohol and Cannabis course among a large cohort of adolescents.
Seventy-one secondary schools across three States participated in a cluster-randomised controlled trial. Year 8 students received either the web-based Climate Schools: Alcohol and Cannabis course (Climate, n = 3236), or health education as usual (Control, n = 3150). Outcomes were measured via self-report and reported here for baseline, 6- and 12-months for alcohol and cannabis knowledge, alcohol, cannabis use and alcohol-related harms.
Compared to Controls, students in the Climate group showed greater increases in alcohol- [standardised mean difference (SMD) 0.51, p < 0.001] and cannabis-related knowledge (SMD 0.49, p < 0.001), less increases in the odds of drinking a full standard drink[(odds ratio (OR) 0.62, p = 0.014], and heavy episodic drinking (OR 0.49, p = 0.022). There was no evidence for differences in change over time in the odds of cannabis use (OR 0.57, p = 0.22) or alcohol harms (OR 0.73, p = 0.17).
The current study provides support for the effectiveness of the web-based Climate Schools: Alcohol and Cannabis course in increasing knowledge and reducing the uptake of alcohol. It represents one of the first trials of a web-based AOD prevention program to replicate alcohol effects in a large and diverse sample of students. Future research and/or adaptation of the program may be warranted with respect to prevention of cannabis use and alcohol harms.
Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is clinically effective and a commonly utilised approach in the management of functional symptoms in irritable bowel syndrome. Despite this, the low FODMAP diet has a number of challenges: it can alter the gut microbiota; impact nutrient intake and diet quality; is complex to understand; requires the patient to be adequately supported to follow the diet accurately and safely; and lastly, not all patients respond to the diet. The current review highlights the evidence for the clinical effectiveness of the low FODMAP diet, but focusses on the challenges associated with the diet to the patient, health professionals and the wider healthcare service. Finally, the review discusses research findings and practical guidance for how these challenges can be minimised and mitigated. The low FODMAP diet is a useful management strategy for irritable bowel syndrome, with data from clinical trials suggesting a 50–80% response rate, and when administered appropriately, the challenges to implementing the diet can be overcome so that these outcomes can be realised effectively and safely in clinical practice.
The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.
Around 100 000 people live in mental health supported accommodation in England, at considerable cost to the public purse, but there is little evidence to guide investment in the most effective models. We consider the various barriers to research in this field and offer suggestions on how to address them.
Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.
Test the efficacy and perceived effectiveness of nutrition labels on children’s menus from a full-service chain restaurant in an online study.
Using a between-groups experiment, parents were randomised to view children’s menus displaying one of five children’s nutrition labelling conditions: (i) No Nutrition Information (control); (ii) Calories Only; (iii) Calories + Contextual Statement (CS); (iv) Calories, Sodium + CS; or (v) Calories and Sodium in Traffic Lights + CS. Parents hypothetically ordered up to one entrée, side, beverage and dessert for their child, then rated and ranked all five labelling conditions on the level of perceived effectiveness.
998 parents with a 3–12 year old child.
Parents exposed to menus displaying ‘Calories, Sodium + CS’ selected significantly fewer calories ‘overall’ (entrées + side + dessert + beverage) compared to parents exposed to the control condition (−53·1 calories, P < 0·05). Parents selected ‘entrees’ with significantly fewer calories and lower sodium when exposed to menus with ‘Calories + CS’ (−24·3 calories, P < 0·05); ‘Calories, Sodium + CS’ (−25·4 calories, −56·1 mg sodium, P < 0·05 for both); and ‘Calories and Sodium in Traffic Lights + CS’ (−29·1 calories, −58·6 mg sodium, P < 0·05 for both). Parents exposed to menus with ‘Calories, Sodium + CS’ and ‘Calories and Sodium in Traffic Lights + CS’ were more likely to notice and understand nutrition information compared to other nuntrition labelling conditions. Parents perceived the menu with ‘Calories and Sodium in Traffic Lights + CS’ as most effective (P < 0·05).
Menus disclosing calories, sodium and a contextual statement increased the proportion of parents who noticed and understood nutrition information, and resulted in parents selecting lower calorie and sodium entrées for their children in the hypothetical purchase task.
In a RCT of family psychoeducation, 47 carers of 34 patients were allocated to one of three groups; Multifamily Group Psychoeducation, Solution Focussed Group Therapy or Treatment as Usual. Carers in both the MFGP intervention and the SFGP arm demonstrated greater knowledge and reduction in burden than those in the TAU arm.
The opioid system modulator nalmefeneis the first pharmacological therapy approved in the European Union for reduction of alcohol consumption.
To evaluate the clinical relevance of the reduction of alcohol consumption in patients with at least high drinking risk level at screening and randomisation from the two, identically designed, randomised controlled 6-month studies ESENSE1 (NCT00811720) and ESENSE2 (NCT00812461) of nalmefene versus placebo.
Study medication was taken as-needed. All patients received a motivational and adherence-enhancing intervention (BRENDA). Response criteria were based on alcohol consumption at month 6 and Clinical Global Impression – Severity of Illness/Improvement (CGI-S/I), Short Form Health Survey version 2 (SF-36) mental component summary(MCS) scores at week 24. Clinical relevance was also studied using the Drinker Inventory of Consequences (DrInC), Alcohol Dependence Scale (ADS), and liver function variables.
Pooled study population: 667 patients (placebo N=332; nalmefene N=335). The proportion of responders was higher in the nalmefene group than in the placebo group with odds ratios for response consistently significantly (p<0.05) in favour of nalmefene. The difference in the proportions of responders translated to numbers-needed-to-treat ranging from 6 to 10. Significant differences to placebo (p<0.05) in the SF-36 MCS and physical component summary score, ADS, DrInC, CGI-I/S and liver enzymes further supported the clinical relevance of the treatment effect.
In view of the immense alcohol-related burden to society, the harm to the individual and the large treatment gap partly due to a reluctance to engage in abstinence, the effect of nalmefene is clearly clinically relevant.
We conducted a meta-analysis of randomised controlled trials (RCT) to examine the effects of strawberry interventions on cardiovascular risk factors. We searched multiple databases including PubMed, Web of Science and Scopus to identify eligible studies published before 19 May 2019. The endpoints were blood pressure, total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, TAG, fasting blood glucose, endothelial function and inflammatory factors. Pooled analyses were performed using random- or fixed-effects models according to a heterogeneity test. We also conducted sub-group analyses by baseline endpoint levels. We included eleven RCT in this meta-analysis (six for blood pressure, seven for lipid profile, seven for fasting blood glucose and six for C-reactive protein (CRP)). Overall, the strawberry interventions significantly reduced CRP levels by 0·63 (95 % CI −1·04, −0·22) mg/l but did not affect blood pressure, lipid profile or fasting blood glucose in the main analyses. Our analysis stratified by baseline endpoint levels showed the strawberry interventions significantly reduced TC among people with baseline levels >5 mmol/l (−0·52 (95 % CI −0·88, −0·15) mmol/l) and reduced LDL-cholesterol among people with baseline levels >3 mmol/l (−0·31 (95 % CI −0·60, −0·02) mmol/l). There was little evidence of heterogeneity in the analysis and no evidence of publication bias. In summary, strawberry interventions significantly reduced CRP levels and may improve TC and LDL-cholesterol in individuals with high baseline levels.