Continuous positive airway pressure effect on visual acuity in patients with type 2 diabetes and obstructive sleep apnoea: a multicentre randomised controlled trial.

We sought to establish whether continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) in people with type 2 diabetes and diabetic macular oedema (DMO) improved visual acuity.We randomly assigned 131 eligible patients aged 30-85 years from 23 UK centres with significant DMO causing visual impairment (LogMAR letters identified ≥39 and ≤78, score 0.92-0.14) plus severe OSA on screening to either usual ophthalmology care (n=67) or usual ophthalmology care plus CPAP (n=64) for 12 months.Mean age of participants was 64 years, 73% male, mean body mass index 35.0 kg·m- 2 Mean 4% oxygen desaturation index was 36 events·h-1 There was no significant difference in the visual acuity at 12 months between the CPAP group and the control group (mean LogMAR 0.33 (95% CI 0.29-0.37) versus 0.31 (95% CI 0.27-0.35); p=0.39), and no significant correlation between change in LogMAR and average CPAP use. The median±sd (range) daily CPAP use was 3.33±2.25 (0-7.93) h at 3 months, 3.19±2.54 (0-8.07) h at 6 months and 3.21±2.70 (0-7.98) h at 12 months.CPAP therapy for OSA did not improve visual acuity in people with type 2 diabetes and DMO compared with usual care alone over 12 months.

Engaging the oldest old in research: lessons from the Newcastle 85+ study.

BACKGROUND: Those aged 85 and over, the oldest old, are now the fastest growing sector of the population. Information on their health is essential to inform future planning; however, there is a paucity of up-to-date information on the oldest old, who are often excluded from research. The aim of the Newcastle 85+ Study is to investigate the health of a cohort of 85-year-olds from a biological, medical and psychosocial perspective. This paper describes the methods employed for the successful recruitment, retention and evaluation of this cohort. METHODS: Participants were all individuals born in 1921 and registered with a participating general practice in Newcastle and North Tyneside, UK. Involvement comprised detailed health assessments, by a nurse, in their usual place of residence and/or review of their general practice medical records. RESULTS: Of the 1453 individuals eligible to participate, 72% (n = 1042) were recruited; 59% (n = 851) consented to both health assessment and review of general practice records. Key factors for successful involvement included protected time to engage with family and other key gatekeepers, minimising participant burden, through for example home based assessment, and flexibility of approach. Cognitive impairment is a significant issue; due consideration should be given to the ethical and legal issues of capacity and consent. Interim withdrawal rates at phase 2 (18 month post baseline), show 88 out of 854 participants (10%) had withdrawn with approval for continued use of data and materials and a further 2 participants (0.2%) had withdrawn and requested that all data be destroyed. Attrition due to death of participants within this same time frame was 135 (16%). CONCLUSION: Our recruitment rates were good and compared favourably with other similar UK and international longitudinal studies of the oldest old. The challenges of and successful strategies for involving, recruiting and retaining the oldest old in research, including those in institutions, are described to facilitate adequate representation of this growing population in future research into ageing.

Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism.

BACKGROUND: Meta-analyses predict that a 25% lowering of plasma homocysteine would reduce the risk of coronary heart disease by 11% to 16% and stroke by 19% to 24%. Individuals homozygous for the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism have reduced MTHFR enzyme activity resulting from the inappropriate loss of the riboflavin cofactor, but it is unknown whether their typically high homocysteine levels are responsive to improved riboflavin status. METHODS AND RESULTS: From a register of 680 healthy adults 18 to 65 years of age of known MTHFR 677C-->T genotype, we identified 35 with the homozygous (TT) genotype and age-matched individuals with heterozygous (CT, n=26) or wild-type (CC, n=28) genotypes to participate in an intervention in which participants were randomized by genotype group to receive 1.6 mg/d riboflavin or placebo for a 12-week period. Supplementation increased riboflavin status to the same extent in all genotype groups (8% to 12% response in erythrocyte glutathione reductase activation coefficient; P<0.01 in each case). However, homocysteine responded only in the TT group, with levels decreasing by as much as 22% overall (from 16.1+/-1.5 to 12.5+/-0.8 micromol/L; P=0.003; n=32) and markedly so (by 40%) in those with lower riboflavin status at baseline (from 22.0+/-2.9 and 13.2+/-1.0 micromol/L; P=0.010; n=16). No homocysteine response was observed in the CC or CT groups despite being preselected for suboptimal riboflavin status. CONCLUSIONS: Although previously overlooked, homocysteine is highly responsive to riboflavin, specifically in individuals with the MTHFR 677 TT genotype. Our findings might explain why this common polymorphism carries an increased risk of coronary heart disease in Europe but not in North America, where riboflavin fortification has existed for >50 years.

A novel postal-based approach to diagnosing obstructive sleep apnoea in a high-risk population.

OBJECTIVE: More than 50% of patients with diabetic macular oedema (DMO) have obstructive sleep apnoea (OSA), but the majority remain undiagnosed. We used a four-channel device (ApneaLink [AL], ResMed, UK) to establish a remote postal-based diagnostic service for patients with DMO. Here we describe our experience. METHODS: Patients with DMO were invited to participate. Interested patients returned a free-post reply slip to the study team, who posted an AL with pictorial and written instructions to them. Following a single night study, the AL was returned by a freepost service. RESULTS: Responses from 733 patients meeting the inclusion criteria were received, comprising 469 males and 264 females, mean age 64 years (standard deviation 10.4 years). ALs were issued to 718 patients, of whom 606 completed a diagnostic study. A total of 71 patients (12%) required a repeat study due to inadequacy of the first attempt. Completed sleep studies showed that 75% of respondents had sleep disordered breathing: 4% ODI 0-4/h, 24%; 5-9/h, 19%; 10-19/h, 23%; ≥20/h, 34%; and AHI 0-4/h, 25%; 5-14/h, 38%; 15-29/h, 20%; ≥30/h, 17%. Among 1592 postal events through the national post service, 20 ALs were lost. CONCLUSIONS: We have demonstrated that a remote postal-based diagnostic service for populations with a high risk of OSA can be successfully performed. This novel approach, which avoids clinic attendance, may be useful in clinical practice.

Sleepiness and Sleep-related Breathing Disorders in Myotonic Dystrophy and Responses to Treatment: A Prospective Cohort Study.

OBJECTIVE: We conducted prospective assessments in people with myotonic dystrophy type 1 (DM1) with daytime sleepiness, provided targeted therapies and assessed response. METHODS: Patients had overnight sleep assessments. Treatment with continuous positive airway pressure (CPAP) for OSA, non-invasive ventilation (NIV) for respiratory failure, modafinil for excessive daytime sleepiness were commenced. RESULTS: 120 people were studied: mean age 46.9 years (SD 13.2, range 18-74), body mass index 27.9 kg/m2 (7.2, 16-53), Epworth Sleepiness Score (ESS) 13.1 (4.7, 2-24). Twenty one people (18% of group) had OSA: mean age 49.6, BMI 31.1, ESS 14.3, ODI 22, pO2 11.3, pCO2 5.4. All were offered CPAP; seven continued with benefit but 14 had intolerance or no benefit. Thirty-three people (27%) had respiratory failure and abnormal sleep study: mean age 51.5, BMI 31.3, ESS 13.9, ODI 22.9, pO2 8.7, pCO2 6.8. All were offered NIV; 12 continued with benefit but 18 had intolerance or no benefit, 1 died and 2 declined commencement. Thirty-six people (30%) had predominantly sleepiness: mean age 44.8, BMI 24.6, ESS 14.1, ODI 9.2, pO2 11.7, pCO2 5.4. All were offered modafinil; 12 continued this with benefit but 10 had intolerance or no benefit, one was unkeen to start, 11 did not attend further clinic and two had other sleep disorders. Comparing means of treatment responders to non-responders showed no significant difference in any variable, except ESS: 15.9 vs.11.9 respectively, p < 0.0001. CONCLUSIONS: Causes of sleepiness are variable in DM1, but include obstructive sleep apnoea, respiratory failure and sleepiness with a normal sleep study; 29% of this studied cohort benefited from targeted sleep therapies.

Protocol for the production of concentrated extracts of food folate for use in human bioavailability studies.

To provide a tool to study folate bioavailability under controlled conditions, a methodology was developed to produce extracts representative of natural food folates but removed from their matrix and sufficiently concentrated so as to elicit a response in biomarkers of folate status without distorting usual dietary intake patterns. Egg, spinach, and yeast were selected to represent the wide range in extent of folate conjugation found in foods (0, 60, and 100% polyglutamyl folate, respectively). The protocol, which was based on extracting food folates using only reagents safe for human consumption, was optimized in the laboratory (thermal extraction for 10 min in a 2% ascorbate solution at pH 5) and then adapted for industrial scale production in a food-processing facility. Results showed that the extracts were 2.3-12 times more concentrated in folate compared with their corresponding food sources. Neither the mono- to polyglutamate ratio nor the distribution of the main folate derivatives was altered during processing, making these extracts suitable for use in human bioavailability studies.

Improving retention of very old participants in longitudinal research: experiences from the Newcastle 85+ study.

BACKGROUND: People aged 85 and over are often excluded from research on the grounds of being difficult to recruit and problematic to retain. The Newcastle 85+ study successfully recruited a cohort of 854 85-year-olds to detailed health assessment at baseline and followed them up over 3 phases spanning 5 years. This paper describes the effectiveness of its retention strategies. METHODS: Primary retention strategies involved meticulous management of contact information and active maintenance of contact with participants between research visits and between phases of the study. For statistical analysis, data on post-inclusion attrition over the 3 follow-up phases was separated into 'death' and 'withdrawal' categories, with sub-categories 'health' and 'non-health' reasons created for 'withdrawal'. Multinomial logistic regression was used to determine if particular socio-demographic and health characteristics were associated with post-inclusion attrition due to withdrawal at each of the 3 phase-to-phase transition points. RESULTS: For both sexes, at successive follow-up phases there was a decrease in attrition due to withdrawal and an increase due to death. Withdrawal was most prevalent between baseline and phase 2. Across the 5 years of the study total post-inclusion (post-baseline) attrition due to death accounted for a 40% (344/854) loss to cohort and total post-inclusion attrition due to withdraw a 19% (166/854) loss to cohort, with health reasons for withdrawal becoming more dominant over time. Adjusting for sex, parsimonious modelling showed only occupational class (National Statistics Socio-economic Classification) to be associated with withdrawal and only between baseline and phase 2 (routine/manual compared to managerial (OR 3.41; 95% CI [1.23 to 9.44]). CONCLUSION: Following successful recruitment, we retained a high proportion of participants from a very old age group over 5 years of longitudinal research. No strong predictors of post-inclusion attrition due to withdrawal were found, suggesting the general effectiveness of our retention strategies.

The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet.

Folate intake is strongly influenced by various methods of cooking that can degrade the natural forms of the vitamin in foods. The aim of the present study was to determine the effect of different cooking methods on folate retention in various foods that contribute to folate intake in the UK diet. Typical purchasing and cooking practices of representative food folate sources were determined from a questionnaire survey of local shoppers (n 100). Total folate was determined by microbiological assay (Lactobacillus casei NCIMB 10463) following thermal extraction and tri-enzyme (alpha-amylase, protease and conjugase) treatment in raw foods and after typical methods of cooking. Boiling for typical time periods resulted in only 49 % retention of folate in spinach (191.8 and 94.4 microg/100 g for raw and boiled spinach respectively; P<0.005), and only 44 % in broccoli (177.1 and 77.0 microg/100 g for raw and boiled broccoli respectively, P<0.0001). Steaming of spinach or broccoli, in contrast, resulted in no significant decrease in folate content, even for the maximum steaming periods of 4.5 min (spinach) and 15.0 min (broccoli). Prolonged grilling of beef for the maximum period of 16.0 min did not result in a significant decrease in folate content (54.3 and 51.5 microg/100 g for raw and grilled beef respectively). Compared with raw values, boiling of whole potatoes (skin and flesh) for 60.0 min did not result in a significant change in folate content (125.1 and 102.8 microg/100 g for raw and boiled potato respectively), nor was there any effect on folate retention whether or not skin was retained during boiling. These current results show that the retention of folate in various foods is highly dependent both on the food in question and the method of cooking. Thus, public health efforts to increase folate intake in order to improve folate status should incorporate practical advice on cooking.