Docosahexaenoic Acid Slows Visual Field Progression in X-Linked Retinitis Pigmentosa: Ancillary Outcomes of the DHAX Trial.

PURPOSE: Docosahexaenoic acid (DHA) was supplemented in a single-site, placebo-controlled, randomized clinical trial designed to slow vision loss associated with X-linked retinitis pigmentosa (XLRP); the DHAX Trial. We previously reported no significant differences between supplemented and placebo groups in intent-to-treat analysis of primary ERG outcomes. Assessed herein are hypothesis-generating measures of ancillary visual function outcomes in participants fully adhering to trial protocol. METHODS: Male participants with XLRP (range, 7-31 years) received 30 mg DHA/kg/d (n = 29) or placebo (n = 22) for 4 years. Visual outcomes were measured annually and red blood cell (RBC) DHA determined every 6 months. RESULTS: Oral DHA supplementation increased mean RBC-DHA levels by 4-fold (P < 0.0001) over placebo. No group differences in progression were found for visual acuity (P = 0.11), shape discrimination (P = 0.18), or fundus appearance (P = 0.70). Optical coherence tomography (OCT) became available during year 2 of the trial; no group differences were seen in ellipsoid zone constriction (P = 0.87) over 2 years. Yearly rates of progression were reduced for dark-adapted thresholds (P = 0.06) and visual field sensitivity for foveal, macular, peripheral, total, and ellipsoid zone regions by DHA supplementation (P = 0.039, P = 0.031, P < 0.0001, P < 0.0001, and P = 0.033). Rates of visual field sensitivity decline were dependent on RBC-DHA (P = 0.046 to <0.0001). CONCLUSIONS: Supplementation of DHA significantly elevated blood DHA levels and reduced the rate of progression in final dark-adapted thresholds and visual field sensitivity. From the relationship between RBC-DHA and the rate of field sensitivity loss, we can extrapolate that an RBC-DHA level of 17% could minimize the decline in field sensitivity. (ClinicalTrials.gov number, NCT00100230.)

Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: the 4-year DHAX trial.

PURPOSE: Docosahexaenoic acid (DHA) continues to be evaluated and recommended as treatment and prophylaxis for various diseases. We recently assessed efficacy of high-dose DHA supplementation to slow vision loss in patients with X-linked retinitis pigmentosa (XLRP) in a randomized clinical trial. Because DHA is a highly unsaturated fatty acid, it could serve as a target for free-radical induced oxidation, resulting in increased oxidative stress. Biosafety was monitored during the 4-year trial to determine whether DHA supplementation was associated with identifiable risks. METHODS: Males (n = 78; 7-31 years) meeting entry criteria were enrolled. The modified intent-to-treat cohort (DHA = 33; placebo = 27) adhered to the protocol ≥ 1 year. Participants were randomized to an oral dose of 30 mg/kg/d DHA or placebo plus a daily multivitamin. Comprehensive metabolic analyses were assessed for group differences. Treatment-emergent adverse events including blood chemistry metabolites were recorded. RESULTS: By year 4, supplementation elevated plasma and red blood cell-DHA 4.4- and 3.6-fold, respectively, compared with the placebo group (P < 0.00001). Over the trial duration, no significant differences between DHA and placebo groups were found for vitamin A, vitamin E, platelet aggregation, antioxidant activity, lipoprotein cholesterol, or oxidized LDL levels (all P > 0.14). Adverse events were transient and not considered severe (e.g., gastrointestinal [GI] irritability, blood chemistry alterations). One participant was unable to tolerate persistent GI discomfort. CONCLUSIONS: Long-term, high-dose DHA supplementation to patients with XLRP was associated with limited safety risks in this 4-year trial. Nevertheless, GI symptoms should be monitored in all patients taking high dose DHA especially those with personal or family history of GI disturbances. (ClinicalTrials.gov number, NCT00100230.).

Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial.

IMPORTANCE: X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100,000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. OBJECTIVE: To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). DESIGN, SETTING, AND PARTICIPANTS: A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non-X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). INTERVENTIONS: All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. RESULTS: Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse events were found. CONCLUSIONS AND RELEVANCE: Long-term DHA supplementation was not effective in slowing the loss of cone or rod ERG function associated with X-linked retinitis pigmentosa. Participant dropout and lower-than-expected disease event rate limited power to detect statistical significance. A larger sample size, longer trial, and attainment of a target blood DHA level (13%) would be desirable. While DHA supplementation at 30 mg/kg/d does not present serious adverse effects, routine monitoring of gastrointestinal tolerance is prudent. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00100230.

Complementary nutrient effects of separately collected human faeces and urine on the yield and nutrient uptake of spinach (Spinacia oleracea).

A glasshouse experiment was conducted to evaluate the combined use of separately collected human faeces and urine as fertilizer for spinach (Spinacia oleracea) production. Seven human faeces N : urine N combinations (1 : 7 to 7 : 1) each supplying 200 kg N ha(-1) were evaluated along with sole human faeces, sole urine, inorganic fertilizer and an unamended control. Complementary application of the two resources, human faeces and urine, increased fresh and dry matter yields only in treatments having high proportions of urine. Nitrogen uptake followed the same trend but the opposite trend occurred for P uptake indicating that urine was a better source of N whereas human faeces were the better source of P. Potassium uptake was not influenced by the two resources. The minimal improvement observed in the fertilizer value of human faeces when co-applied with urine suggested that co-application of the two resources may not give an added yield advantage when compared with sole human faeces.

Dental health and treatment needs among a sample of Bangladeshi medical users aged 40 years and over living in Tower Hamlets, UK.

AIM: To assess the dental health status and treatment needs of Bangladeshi medical care users aged 40 years and over and to explore the relationship of oral disease status, tobacco usage and paan (betel quid) chewing. DESIGN: Multi-centre cross-sectional study. SETTING: General medical practitioners' waiting areas in Tower Hamlets, UK. SUBJECTS: 185 Bangladeshi adults aged 40 years and over. INTERVENTION: A clinical examination and an interview schedule. MEASURES: Dental status, periodontal status, dental plaque, calculus and denture status. Tobacco smoking and paan chewing behaviour. RESULTS: The response rate was 74%. 85% of participants were dentate with an average number of 24 (SD +/- 5.4) standing teeth. The mean DMFT score was 5.38, with missing teeth (3.81) being the major component. The decayed component was 0.43 and the filled was 1.14. 46% of participants were assessed as being free from gingivitis. Significant relationships between chewing paan and aspects of dental and periodontal status were found. Impacts of oral health were reported by 45% of the respondents. The normative need for dental treatment was 96% with a perceived need of 48%. CONCLUSION: There was considerable normative dental need. Whilst caries experience was low, there were high levels of periodontal treatment needs. Paan chewing was related to aspects of dental and periodontal status.

Prevalence of oral lesions among a sample of Bangladeshi medical users aged 40 years and over living in Tower Hamlets, UK.

AIM: To collect data on the prevalence of oral mucosal lesions among Bangladeshi medical care users aged 40 years and over and to explore the relationship of oral disease status and tobacco smoking and paan (betel quid) chewing. DESIGN: Multi-centre cross-sectional study. SETTING: General medical practitioners' waiting areas in Tower Hamlets, UK. SUBJECTS: 185 Bangladeshi adults aged 40 years old and over. METHOD: An oral mucosal examination, based on WHO criteria and an interview. Information on tobacco smoking and paan chewing behaviour was collected during the interview. RESULTS: Out of 185 adults there was a response rate of 74%. Oral mucosal lesions were observed in 40% of participants. The most common lesion was found to be leukoplakia with a prevalence of 25%. Significant relationships were found between smoking and the presence of oral pathology and between paan chewing with tobacco and the presence of leukoplakia. CONCLUSION: In this study of older Bangladeshi medical care users there was a high prevalence of oral mucosal lesions. Sensitively tailored health promotion interventions, which aim to reduce tobacco use, should be developed for this population.

Dental service use and the implications for oral cancer screening in a sample of Bangladeshi adult medical care users living in Tower Hamlets, UK.

AIM: To assess the use of dental services, barriers to uptake of dental care and attitudes to regular dental examinations and the prevalence of tobacco and paan chewing habits in a group of Bangladeshi medical care users. DESIGN: Multi-centre cross-sectional study. SETTING: Four general medical practices' waiting areas in Tower Hamlets. SUBJECTS: Bangladeshi adults aged 40 years and over. INTERVENTION: An interview schedule. MAIN OUTCOME MEASURES: The prevalence of tobacco smoking and paan chewing with or without the addition of tobacco. The use of dental services, barriers to the use of dental services and attitudes to regular dental examinations. RESULTS: Results were obtained from 158 subjects (response rate 85%). 25% of the whole sample had never visited a dentist. These were significantly (P < 0.05) more likely to be women, who also thought regular check-ups were of little value. In their use of health services 73% experienced language difficulties. 33% of the sample were tobacco smokers. Paan was chewed by 78% of the sample with significantly (P < 0.05) more females than males adding tobacco to their quid and chewing more frequently than males. CONCLUSION: There are considerable barriers to be overcome if dental practices are to be the site for oral cancer screening and oral health promotion in this population. There are sex differences in reported behaviour and attitudes about use of dental services and in tobacco and paan use in this Bangladeshi sample. Further research is needed to establish why this ethnic minority attend general medical practices but not general dental practices.

Impairment of the visuo-spatial sketch pad.

A case study is presented of a female patient, ELD, who has difficulty in the immediate recall of short sequences of visuo-spatial material following a right-hemisphere aneurysm. Despite poor performance on tasks such as the Brooks Matrix and the Corsi Blocks, ELD is good at the immediate serial recall of letters even when presentation modality is visual and shows effects of phonological similarity and articulatory suppression. This pattern of performance represents a double dissociation from that which has been observed with the short-term memory patient PV (Vallar & Baddeley, 1984), who is extremely poor at serial recall of verbal material but shows no visual memory impairment. It is argued that ELD has an impairment to the visuo-spatial component of working memory (Baddeley, 1986) in the absence of any phonological loop deficit. Further investigation reveals that ELD performs poorly on mental rotation tasks and finds it difficult to use imagery mnemonics, but has no difficulty in retrieving visuo-spatial information from long-term memory so long as it was learnt before her illness.