Incorporating parent, former patient, and clinician perspectives in the design of a national UK double-cluster, randomised controlled trial addressing uncertainties in preterm nutrition

Background: Comparative effectiveness randomised controlled trials are powerful tools to resolve uncertainties in existing treatments and care processes. We sought parent and patient perspectives on the design of a planned national, double-cluster randomised controlled trial (COLLABORATE) to resolve two longstanding uncertainties in preterm nutrition. Methods: We used qualitative focus groups and interviews with parents, former patients and clinicians. We followed the Consolidated Criteria for Reporting Qualitative Research checklist and conducted framework analysis, a specific methodology within thematic analysis. Results: We identified support for the trial’s methodology and vision, and elicited themes illustrating parents’ emotional needs in relation to clinical research. These were: relieving the pressure on mothers to breastfeed; opt-out consent as reducing parent stress; the desire for research to be a partnership between clinicians, parents and researchers; the value of presenting trial information in a collaborative tone; and in a format that allows assimilation by parents at their own pace. We identified anxiety and cognitive dissonance among some clinicians in which they recognised the uncertainties that justify the trial but felt unable to participate because of their strongly held views. Conclusions: The early involvement of parents and former patients identified the centrality of parents’ emotional needs in the design of comparative effectiveness research. These insights have been incorporated into trial enrolment processes and information provided to participants. Specific outputs were a two-sided leaflet providing very brief as well as more detailed information, and use of language that parents perceive as inclusive and participatory. Further work is warranted to support clinicians to address personal biases that inhibit trial participation

Improving the management of non-ST elevation acute coronary syndromes: systematic evaluation of a quality improvement programme European QUality Improvement Programme for Acute Coronary Syndrome: The EQUIP-ACS project protocol and design

Acute coronary syndromes, including myocardial infarction and unstable angina, are important causes of premature mortality, morbidity and hospital admissions. Acute coronary syndromes consume large amounts of health care resources, and have a major negative economic and social impact through days lost at work, support for disability, and coping with the psychological consequences of illness. Several registries have shown that evidence based treatments are under-utilised in this patient population, particularly in high-risk patients. There is evidence that systematic educational programmes can lead to improvement in the management of these patients. Since application of the results of important clinical trials and expert clinical guidelines into clinical practice leads to improved patient care and outcomes, we propose to test a quality improvement programme in a general group of hospitals in Europe

Respiratory symptoms and chronic bronchitis in people with and without HIV infection

Objectives High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV‐negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. Methods Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George’s Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann–Whitney U tests and Spearman’s rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV‐related parameters, and with depressive symptoms and quality of life. Results Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV‐negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty‐three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV‐negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV‐negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. Conclusions Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle‐similar HIV‐negative people and are associated with poorer mental health and quality of life

A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects

BACKGROUND: Weight loss has been shown to reduce risk factors associated with cardiovascular disease and diabetes; however, successful maintenance of weight loss continues to pose a challenge. OBJECTIVE: The present study was designed to assess whether changes in subcutaneous adipose tissue (scAT) gene expression during a low-calorie diet (LCD) could be used to differentiate and predict subjects who experience successful short-term weight maintenance from subjects who experience weight regain. DESIGN: Forty white women followed a dietary protocol consisting of an 8-wk LCD phase followed by a 6-mo weight-maintenance phase. Participants were classified as weight maintainers (WMs; 0-10% weight regain) and weight regainers (WRs; 50-100% weight regain) by considering changes in body weight during the 2 phases. Anthropometric measurements, bioclinical variables, and scAT gene expression were studied in all individuals before and after the LCD. Energy intake was estimated by using 3-d dietary records. RESULTS: No differences in body weight and fasting insulin were observed between WMs and WRs at baseline or after the LCD period. The LCD resulted in significant decreases in body weight and in several plasma variables in both groups. WMs experienced a significant reduction in insulin secretion in response to an oral-glucose-tolerance test after the LCD; in contrast, no changes in insulin secretion were observed in WRs after the LCD. An ANOVA of scAT gene expression showed that genes regulating fatty acid metabolism, citric acid cycle, oxidative phosphorylation, and apoptosis were regulated differently by the LCD in WM and WR subjects. CONCLUSION: This study suggests that LCD-induced changes in insulin secretion and scAT gene expression may have the potential to predict successful short-term weight maintenanc

Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial

Background Parenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations. Objective To confirm the safety and demonstrate efficacy of the immediate introduction of the recommended daily intake of amino acids (Imm-RDI) and soya bean oil, medium-chain triglycerides, olive oil and fish oil lipid in PN to increase non-adipose (lean) body mass and decrease intrahepatocellular lipid (IHCL) content. Design Multicentre, double-blind, 2 × 2 factorial and randomised controlled trial (RCT). Setting Neonatal units in London and south-east England, UK. Participants Extremely preterm infants born before 31 weeks of gestation without major congenital or life-threatening abnormalities who could to be randomised to receive PN within 24 hours of birth. Interventions Infants were randomised within 24 hours of birth to receive PN containing either high [RDI of amino acids (Imm-RDI)] or low [incremental amino acids (Inc-AA) control] levels of amino acids. In addition, infants were randomised to receive either 20% SMOFlipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) or 20% Intralipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) (control). This resulted in four groups: (1) Inc-AA/Intralipid, (2) Inc-AA/SMOFlipid, (3) Imm-RDI/Intralipid and (4) Imm-RDI/SMOFlipid. The intervention was continued until infants were receiving 150 ml/kg/day of enteral feeds for 24 hours. Primary outcome measure For the amino acid intervention, this was non-adipose or lean body mass measured by magnetic resonance imaging. For the lipid composition intervention, this was IHCL content as measured by hepatic magnetic resonance spectroscopy. Primary outcomes were measured at term age equivalent, between 37 and 44 weeks postmenstrual age. Results We randomised 168 infants born before 31 weeks of gestation. We evaluated outcomes, at term, in 133 infants. There were no significant differences in non-adipose mass between the Imm-RDI and Inc-AA groups [adjusted mean difference 1.0 g, 95% confidence interval (CI) –108 to 111 g] or in levels of IHCLs between the SMOFlipid and Intralipid groups (adjusted mean SMOFlipid to Intralipid ratio 1.1, 95% CI 0.8 to 1.6). Infants receiving the Imm-RDI were more likely than Inc-AA infants to have blood urea nitrogen levels > 7 mmol/l [75% vs. 49% (p  10 mmol/l [49% vs. 18% (p < 0.01)]. Furthermore, head circumference at term was smaller in the Imm-RDI group (mean difference –0.8 cm, 95% CI –1.5 to –0.1 cm; p = 0.02). There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, weight, length and mortality. Limitations Not all eligible babies were available for recruitment, as pharmacy staff trained in clinical trial procedures were unavailable at weekends in three of the four centres. We were able to assess brain volumes in only one-third of participants, as imaging was carried out while the participants were sleeping naturally and we measured primary outcomes first and continued to brain imaging only if the infant remained asleep. Conclusions Immediate delivery of the recommended daily intake of parenteral amino acids does not benefit body composition or growth to term and may be harmful; SMOFlipid does not affect IHCL content. Future work The long-term functional outcomes of early administration of RDI of amino acids and the use of SMOFlipid, including neurodevelopment, body composition and metabolic health, should be evaluated. Trial registration Current Controlled Trials ISRCTN29665319 and EudraCT 2009-016731-34. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership

Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake

BACKGROUND: The mechanisms underlying body weight evolution after diet-induced weight loss are poorly understood. OBJECTIVE: We aimed to identify and characterize differences in the subcutaneous adipose tissue (SAT) transcriptome of subjects with different weight changes after energy restriction-induced weight loss during 6 mo on 4 different diets. DESIGN: After an 8-wk low-calorie diet (800 kcal/d), we randomly assigned weight-reduced obese subjects from 8 European countries to receive 4 diets that differed in protein and glycemic index content. In addition to anthropometric and plasma markers, SAT biopsies were taken at the beginning [clinical investigation day (CID) 2] and end (CID3) of the weight follow-up period. Microarray analysis was used to define SAT gene expression profiles at CID2 and CID3 in 22 women with continued weight loss (successful group) and in 22 women with weight regain (unsuccessful group) across the 4 dietary arms. RESULTS: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather than to differences in dietary macronutrient content. An analysis of covariance with total energy intake as a covariate identified 1338 differentially expressed genes. Cellular growth and proliferation, cell death, cellular function, and maintenance were the main biological processes represented in SAT from subjects who regained weight. Mitochondrial oxidative phosphorylation was the major pattern associated with continued weight loss. CONCLUSIONS: The ability to control body weight loss independent of energy intake or diet composition is reflected in the SAT transcriptome. Although cell proliferation may be detrimental, a greater mitochondrial energy gene expression is suggested as being beneficial for weight control

Cognitive function, depressive symptoms and syphilis in HIV-positive and HIV-negative individuals

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53–63) and 58 (53–63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders