Systematic review of economic evaluations in pediatric ophthalmology and strabismus.

BACKGROUND: Economic evaluations in health care quantitatively compare interventions using cost and outcomes data. These evaluations can aid in the adoption of new surgical or medical treatments and inform policy decisions regarding healthcare spending. Several common types of economic analysis exist (cost-benefit, cost-analysis, cost-effectiveness, and cost-utility). We review all English-language economic evaluations in strabismus surgery and pediatric ophthalmology. METHODS: An electronic literature search of the PubMed and Health Economic Evaluations databases was conducted. Two reviewers independently reviewed the search string yield and assessed articles against inclusion and exclusion criteria. Outcome measures included journal of publication, year of publication, domain of ophthalmology, region/country of study, and type of economic evaluation. RESULTS: We identified 62 articles. Cost-utility studies comprised 30% of evaluations. The most studied domain was retinopathy of prematurity (33%), followed by amblyopia and vision screening (24%) and cataracts (14%). The Journal of the American Association for Pediatric Ophthalmology and Strabismus published the most economic evaluations (15%) followed by Ophthalmology and Pediatrics. The number of published economic evaluations did not increase over time. CONCLUSIONS: Economic evaluations in pediatric ophthalmology and strabismus have not increased over time. A minority (30%) of studies used cost utility-analysis, limiting comparisons to other domains of medicine. This suggests the need to alert pediatric ophthalmologists to the benefits of economic analysis, and cost-utility methodology specifically, to better inform and influence policy decisions regarding healthcare spending.

Assessment of Dietary Intake in Three Cohorts of Advanced Age in Two Countries: Methodology Challenges.

OBJECTIVES: Dietary intake information is key to understanding nutrition-related outcomes. Intake changes with age and some older people are at increased risk of malnutrition. Application, difficulties, and advantages of the 24-hour multiple pass recall (24hr-MPR) dietary assessment method in three cohorts of advanced age in the United Kingdom (UK) and New Zealand (NZ) is described. PARTICIPANTS: The Newcastle 85+ study (UK) recruited a single year birth cohort of people aged 85 years during 2006-7. LiLACS NZ recruited a 10-year birth cohort of Maori (indigenous New Zealanders) aged 80-90 years and a single year birth cohort of non-Maori aged 85 years in 2010. MEASUREMENTS: Two 24hr-MPR were conducted on non-consecutive days by trained assessors. Pictorial resources and language were adapted for the New Zealand and Maori contexts. Detailed methods are described. RESULTS: In the Newcastle 85+ study, 805 (93%) participants consented to the 24-MPR, 95% of whom completed two 24hr-MPR; in LiLACS NZ, 218 (82%) consented and 203 (76%) Maori and 353 (90%) non-Maori completed two 24hr-MPR. Mean time to complete each 24hr-MPR was 22 minutes in the Newcastle 85+ study, and 45 minutes for Maori and 39 minutes for non-Maori in LiLACS NZ. Dietary assessment of participants residing in residential care and those requiring proxy respondents were successfully included in both studies. Most participants (83-94%) felt that data captured by the 24hr-MPR reflected their usual dietary intake. CONCLUSIONS: Dietary assessment using 24hr-MPR was successful in capturing detailed dietary data including information on portion size and time of eating for over 1300 octogenarians in the UK and New Zealand (Maori and non- Maori). The 24hr-MPR is an acceptable method of dietary assessment in this age group.

Waardenburg syndrome-associated neurotrophic keratopathy in a child treated with neurotization surgery.

Waardenburg syndrome (WS) is a congenital developmental disorder characterized by congenital sensorineural hearing loss and pigmentary deficiencies in the iris, hair, and skin. Ocular associations of WS include choroidal and iris hypopigmentation and foveal hypoplasia. Possible associations include cataracts and retinal vein occlusion. We report the first case of neurotrophic cornea and relate our experience with neurotization surgery.

Quantitatively comparing weekly changes in retinal vascular characteristics of eyes eventually treated versus not treated for retinopathy of prematurity.

PURPOSE: To quantitatively compare retinal vascular characteristics over time in eyes eventually treated versus not treated for retinopathy of prematurity (ROP), using ROPtool analysis of narrow-field retinal images. METHODS: This longitudinal study used prospectively collected narrow-field retinal images of infants screened for ROP, prior to treatment, if needed. Images were analyzed using a methodology that combines quadrant-level measures from several images of the same eye. For the longitudinal analysis, one examination per postmenstrual age (PMA) was included per eye. We compared the following ROPtool indices and their change per week between eyes eventually treated versus not treated for ROP: tortuosity index (TI), dilation index (DI), sum of adjusted indices (SAI), and tortuosity-weighted plus (TWP). Analysis was performed on three levels: eye (mean value/eye), quadrant (highest quadrant value/eye), and blood vessel (highest blood vessel value/eye). RESULTS: Of 832 examinations (99 infants), 745 images (89.5%) had 3-4 quadrants analyzable by ROPtool. On the eye level, ROPtool indices differed between eyes eventually treated versus not treated at PMA of 33-35 and 37 weeks for TI, SAI, and TWP, and at PMA of 33-34 and 37 weeks for DI (P ≤ 0.0014), and change per week differed between eyes eventually treated versus not treated only for SAI at PMA of 32 weeks (P < 0.001). CONCLUSIONS: Quantitative analysis of retinal vascular characteristics using ROPtool can help predict eventual need for treatment for ROP as early as 32 weeks PMA. ROPtool index values were more useful than change in these indices to predict eyes that would eventually need treatment for ROP.

Delayed presentation of morning glory disc anomaly and transsphenoidal encephalocele: A management dilemma.

Background Morning glory disc anomaly (MGDA) is a rare developmental abnormality of the optic disc that is associated with many other neurological and vascular conditions. Most cases are diagnosed in childhood. Case Report We report a 57-year-old woman who presented to the ophthalmology department for assessment of long-standing poor vision in the left eye and exotropia. Examination showed a left MGDA and bitemporal hemianopsia. These findings prompted magnetic resonance imaging, revealing a transsphenoidal basal meningoencephalocele with herniation of the optic chiasm and inferior hypothalamus into the dural sac. Due to the eloquence of the neurovascular structures it contained, a decision was made not to reduce the meningoencephalocele. Instead, a ventriculoperitoneal shunt was placed. The patient's ophthalmologic examination remained stable over the following year. Conclusion While rare, MGDA can be first diagnosed in late adulthood and a thorough evaluation should be completed to assess for midline cranial defects, vascular abnormalities, and other associated abnormalities. Patients presenting late in life with basal encephalocele, herniation of the optic chiasm, and bitemporal hemianopsia present a management dilemma. In this case, a ventriculoperitoneal shunt was placed with the intention of lowering intracranial pressure to prevent further herniation and reduce the risk of cerebrospinal fluid leak.

Povidone-iodine concentration and dosing in cataract surgery.

Iodine has been recognized as an effective bactericide since the 1800s, and povidone-iodine (PI) solution has been applied to the ocular surface and periocular skin since the 1980s to prevent endophthalmitis in cataract surgery. In vitro, PI solution kills bacteria quickly at dilute concentrations (0.05%-1.0%). In many instances, PI kills bacteria more quickly at these dilute concentrations than more conventional (5%-10%) concentrations. This is due to greater availability of diatomic free iodine in dilute solution, the bactericidal component of PI. The toxicity of PI, both in vitro and clinically, has been shown to be related to concentration. Current American Academy of Ophthalmology and the European Society of Cataract and Refractive Surgeons recommendations regarding PI use suggest using 5% PI before surgery. An alternative dosing strategy uses dilute PI repetitively throughout cataract surgery (0.25% every 30 seconds). We review the povidone-iodine literature with attention to basic science and use of dilute PI.

Povidone-iodine concentration and in vitro killing time of bacterial corneal ulcer isolates.

Background: The concentration and dosing of povidone-iodine (PI) solution used in surgical site prophylaxis are variable. Prior in vitro work has demonstrated that dilute PI solutions (<1%) had greater bactericidal activity than stock solutions (10%). Studies using pathologic clinical isolates from the eye have yielded mixed results. The purpose of the current study was to evaluate the efficacy of different concentrations of PI on pathologic ocular surface isolates. Methods: We conducted an in vitro microbiology study using clinical isolates from corneal ulcers. Bacteria were recovered from trypticase soy agar with 5% sheep erythrocytes, chocolate agar, and thioglycollate broth media. A standardized concentration of each bacterial sample (1 × 108 cfu/ml) was exposed to various dilutions of PI. Quantitative cultures were performed to determine the number of organisms surviving PI exposure. Results: None of the isolates survived exposure to the PI 0.25% solution for 30 seconds. Micrococcus luteus and Staphylococcus aureus survived both 30-second and 1-minute exposure to PI 5% and 10%. The exposure time required to produce no growth was variable with concentrations of <0.25%. In some isolates, the 10% solution was faster than the more dilute solutions (0.1%, 0.05%). Conclusions: Our results are consistent with prior in vitro studies of PI, from nonocular sources, and suggest that PI has similar bactericidal action on pathologic bacteria from the ocular surface. In vitro exposure to dilute PI (0.25%) resulted in no growth after 30 seconds, whereas 10% and 5% solutions took longer to kill several of the isolates. Future investigations of PI use in ophthalmology as an antimicrobial agent should include the study of low-concentration PI (0.25%).

BMI and healthy life expectancy in old and very old women.

There is conflicting evidence for the effect of BMI on mortality at older ages, and little information on its effect on healthy life expectancy (HLE). Longitudinal data were from the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health (n 11 119), over 18 years of follow-up. Self-rated health status was measured at each survey, and BMI was measured at baseline. Multi-state models were fitted to estimate the effect of BMI on total life expectancy (TLE) and HLE. Compared with women of normal weight, overweight women at the age of 75 years had similar TLE but fewer years healthy (-0·79; 95 % CI -1·21, -0·37) and more years unhealthy (0·99; 95 % CI 0·56, 1·42). Obese women at the age of 75 years lived fewer years in total than normal-weight women (-1·09; 95 % CI -1·77, -0·41), and had more unhealthy years (1·46; 95 % CI 0·97, 1·95 years). Underweight women had the lowest TLE and the fewest years of healthy life. Women should aim to enter old age at a normal weight and in good health, as the slight benefit on mortality of being overweight is offset by spending fewer years healthy. All outcomes were better for those who began in good health. The relationship between weight and HLE has important implications for nutrition for older people, particularly maintenance of lean body mass and prevention of obesity. The benefit of weight loss in obese older women remains unclear, but we support the recommendation that weight-loss advice be individualised, as any benefits may not outweigh the risks in healthy obese older adults.

A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II.

Dramatic global increases in future numbers of people with dementia have been predicted. No multicentre population-based study powered to detect changes over time has reported dementia incidence. MRC Cognitive Function and Ageing Study (CFAS) undertook baseline interviews in populations aged 65+ years in England and Wales (1989-1994). Three areas (CFAS I) were selected for new sampling two decades later (2008-2011) with same geographical boundaries, sampling and approach methods (CFAS II). At 2 years CFAS I interviewed 5,156 (76% response) with 5,288 interviewed in CFAS II (74% response). Here we report a 20% drop in incidence (95% CI: 0-40%), driven by a reduction in men across all ages above 65. In the UK we estimate 209,600 new dementia cases per year. This study was uniquely designed to test for differences across geography and time. A reduction of age-specific incidence means that the numbers of people estimated to develop dementia in any year has remained relatively stable.

Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study.

SUMMARY: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown. INTRODUCTION: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N). METHODS: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models. RESULTS: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) µg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort. CONCLUSION: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

Magnitude of fragility fracture risk in the very old--are we meeting their needs? The Newcastle 85+ Study.

UNLABELLED: Fractures due to osteoporosis are common in older people. This study assessed the management of osteoporosis in a group of 85-year-olds and found both assessment and current treatment to be suboptimal. INTRODUCTION: Fragility fractures are a major cause of excess mortality, substantial morbidity, and health and social service expenditure in older people. However, much less is known about fracture risk and its management in the very old, despite this being the fastest growing age group of our population. METHODS: Cross-sectional analysis of people who reached the age of 85 during the year of 2006 was carried out. Data were gathered by general practice record review (GPRR) and a multidimensional health assessment (MDHA). RESULTS: Seven hundred thirty-nine individuals were recruited. Mean age was 85.55 years (SD 0.44), and 60.2% were female; 33.7% (n = 249) had experienced one or more fragility fractures (F 45.2% vs M 16.3% p < 0.001); in total, 332 fractures occurred in these 249 individuals. A formal documented diagnosis of osteoporosis occurred in 12.4%, and 38% of individuals had experienced a fall in the last 12 months. When the fracture risk assessment tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidelines were applied, osteoporosis treatment would be recommended in 35.0%, with a further 26.1% identified as needing bone mineral density (BMD) measurement and 38.9% not requiring treatment or BMD assessment. Women were more likely than men to need treatment (47.4 vs 16.3%, p < 0.001, odds ratio (OR) 4.62 (3.22-5.63)) and measurement of BMD (40.0 vs 5.1%, p < 0.001, OR 12.4 (7.13-21.6)). Of the 259 individuals identified as requiring treatment, only 74 (28.6%) were on adequate osteoporosis treatment. CONCLUSION: The prevalence of high fracture risk in the very old is much higher than the documented diagnosis of osteoporosis or the use of adequate treatments.

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.

25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study.

OBJECTIVE: To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years. DESIGN, SETTING AND SUBJECTS: Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D-containing supplements and medication) cohorts. RESULTS: For the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01-1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02) and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (≥75 nmol L(-1) ) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication.

Inpatient and emergency service utilization in patients with idiopathic intracranial hypertension.

BACKGROUND: Many patients with idiopathic intracranial hypertension (IIH) are diagnosed in the emergency department (ED) or visit the ED during the course of their illness. We studied the use of inpatient and emergency services, determined what procedures and tests were provided at those encounters, evaluated how these variables changed over the study period and examined the coding validity of the International Classification of Diseases (ICD)-9 code for IIH (348.2) for adult patients seen in our affiliated EDs and inpatient services. METHODS: Retrospective review of medical records over a 11-year period (2000-2011). RESULTS: We were able to analyze 137 encounters from 51 patients. Sixty-eight percent of encounters were to the ED and 40% of those patients were subsequently admitted to the hospital. The most common symptoms were headaches (96%), vision change (53%), and photophobia (27%). Recurrent symptoms accounted for 43% of encounters, followed by surgical complications (26%) and initial presentation (12%). Four patients (25% of the patients who received a diagnosis in the ED) were misdiagnosed at their initial presentation and correctly diagnosed on a subsequent ED visit. The number of ED visits more than doubled over the study period. The ICD-9 code had a low positive predictive value (55%) for identifying patients with IIH. CONCLUSIONS: The ED was commonly used by patients with IIH, with a mean of 2.7 visits per patient. The rate of a missed diagnosis was similar to another published series and is concerning for potentially permanent visual loss in undiagnosed patients. In our experience, the ICD-9 code vastly overestimated the number of ED and inpatient encounters attributable to IIH. This has important implications for research studies, particularly those relying on national inpatient databases.

Gender differences in health of EU10 and EU15 populations: the double burden of EU10 men.

This study compares gender differences in Healthy Life Years (HLY) and unhealthy life years (ULY) between the original (EU15) and new member states (EU10). Based on the number of deaths, population and prevalence of activity limitations from the Statistics of Living and Income Conditions Survey (SILC) survey, we calculated HLY and ULY for the EU10 and EU15 in 2006 with the Sullivan method. We used decomposition analysis to assess the contributions of mortality and disability and age to gender differences in HLY and ULY. HLY at age 15 for women in the EU10 were 3.1 years more than those for men at the same age, whereas HLY did not differ by gender in the EU15. In both populations ULY at age 15 for women exceeded those for men by 5.5 years. Decomposition showed that EU10 women had more HLY because higher disability in women only partially offset (-0.8 years) the effect of lower mortality (+3.9 years). In the EU15 women's higher disability prevalence almost completely offset women's lower mortality. The 5.3 fewer ULY in EU10 men than in EU10 women mainly reflected higher male mortality (4.5 years), while the fewer ULY in EU15 men than in EU15 women reflected both higher male mortality (2.9 years) and higher female disability (2.6 years). The absence of a clear gender gap in HLY in the EU15 thus masked important gender differences in mortality and disability. The similar size of the gender gap in ULY in the EU-10 and EU-15 masked the more unfavourable health situation of EU10 men, in particular the much stronger and younger mortality disadvantage in combination with the virtually absent disability advantage below age 65 in men.

Rehabilitation of older patients: day hospital compared with rehabilitation at home. A randomised controlled trial.

OBJECTIVES: To test the hypotheses that older people and their informal carers are not disadvantaged by home-based rehabilitation (HBR) relative to day hospital rehabilitation (DHR) and that HBR is less costly. DESIGN: Two-arm randomised controlled trial. SETTING: Four trusts in England providing both HBR and DHR. PARTICIPANTS: Clinical staff reviewed consecutive referrals to identify subjects who were potentially suitable for randomisation according to the defined inclusion criteria. INTERVENTIONS: Patients were randomised to receive either HBR or DHR. MAIN OUTCOME MEASURES: The primary outcome measure was the Nottingham Extended Activities of Daily Living (NEADL) scale. Secondary outcome measures included the EuroQol 5 dimensions (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Therapy Outcome Measures (TOMs), hospital admissions and the General Health Questionnaire (GHQ-30) for carers. RESULTS: Overall, 89 subjects were randomised and 42 received rehabilitation in each arm of the trial. At the primary end point of 6 months there were 32 and 33 patients in the HBR and DHR arms respectively. Estimated mean scores on the NEADL scale at 6 months, after adjustment for baseline, were not significantly in favour of either HBR or DHR [DHR 30.78 (SD 15.01), HBR 32.11 (SD 16.89), p = 0.37; mean difference -2.139 (95% CI -6.870 to 2.592)]. Analysis of the non-inferiority of HBR over DHR using a 'non-inferiority' limit (10%) applied to the confidence interval estimates for the different outcome measures at 6 months' follow-up demonstrated non-inferiority for the NEADL scale, EQ-5D and HADS anxiety scale and some advantage for HBR on the HADS depression scale, of borderline statistical significance. Similar results were seen at 3 and 12 months' follow-up, with a statistically significant difference in the mean EQ-5D(index) score in favour of DHR at 3 months (p = 0.047). At the end of rehabilitation, a greater proportion of the DHR group showed a positive direction of change from their initial assessment with respect to therapist-rated clinical outcomes; however, a lower proportion of HBR patients showed a negative direction of change and, overall, median scores on the TOMs scales did not differ between the two groups. Fewer patients in the HBR group were admitted to hospital on any occasion over the 12-month observation period [18 (43%) versus 22 (52%)]; however, this difference was not statistically significant. The psychological well-being of patients' carers, measured at 3, 6 and 12 months, was unaffected by whether rehabilitation took place at day hospital or at home. As the primary outcome measure and EQ-5D(index) scores at 6 months showed no significant differences between the two arms of the trial, a cost-minimisation analysis was undertaken. Neither the public costs nor the total costs at the 6-month follow-up point (an average of 213 days' total follow-up) or the 12-month follow-up point (an average of 395 days' total follow-up) were significantly different between the groups. CONCLUSIONS: Compared with DHR, providing rehabilitation in patients' own homes confers no particular disadvantage for patients and carers. The cost of providing HBR does not appear to be significantly different from that of providing DHR. Rehabilitation providers and purchasers need to consider the place of care in the light of local needs, to provide the benefits of both kinds of services. Caution is required when interpreting the results of the RCT because a large proportion of potentially eligible subjects were not recruited to the trial, the required sample size was not achieved and there was a relatively large loss to follow-up. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71801032.

Nutrition in advanced age: dietary assessment in the Newcastle 85+ study.

BACKGROUND/OBJECTIVES: Assessing food choice and/or nutrient intake in older people, particularly the oldest old (85 years and over), presents particular challenges. In some cases the respondent may have little or no involvement in food acquisition or preparation, in others, cognitive/memory impairment may restrict the ability to recall intake, or physical limitations may affect the ability to record intake. The assessment may therefore need to involve whoever provides care for the older person, of whom there may be more than one. For these reasons, there is a need for validated methods for dietary assessment in large populations within this age range. The need is particularly acute in view of the secular increase in the numbers of older people and the interest in the role of nutrition in maintaining health and ameliorating age-related decline. This paper describes a comparison of two different methods of dietary assessment within the Newcastle 85+ Study; a UK cohort study of health and ageing in the oldest old. METHODS: Two methods, the food frequency questionnaire (FFQ) (based on broad recall of the previous 12 months intake) and the repeated multiple pass recall (MPR) tool (based on detailed recall of the previous day's intake on two separate occasions), were applied in two different groups of approximately 85 individuals aged 85 years. FFQ data were collected during a pilot study conducted between 2003 and 2004, MPR data were collected in the main Newcastle study in 2006. Relative validity was measured by calculation of the ratio of reported energy intake to estimated basal metabolic rate (EI/BMR) and by comparison with dietary intakes reported for subjects of similar age in the UK National Diet and Nutrition Survey. RESULTS: EI/BMR ratios for MPR were 1.56 and 1.39 for men and women, respectively, and for FFQ were 2.18 and 2.14. The FFQ was found to overestimate energy and nutrient intake considerably. The MPR gave more realistic estimates of energy and nutrient intakes, and was found to be acceptable for use in this population group. However, use of this tool required greater investigator (nurse) time, extra resources for training and quality assurance and additional time and expertise in data processing. CONCLUSIONS: In the Newcastle 85+ Study, where the overall aims include detailed investigation of diet in relation to many variables describing biological, clinical and psychosocial status, we concluded that MPR was the preferable method, although there remains a need for non-subjective methods for assessing dietary intake, that is, biomarker approaches, which can give a comprehensive and objective assessment of dietary exposure.

Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial.

OBJECTIVES: To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. DESIGN: A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. SETTING: Five hospitals in England. PARTICIPANTS: Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). INTERVENTIONS: Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. MAIN OUTCOME MEASURES: The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. RESULTS: 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. CONCLUSIONS: Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

RATIONALE: High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. OBJECTIVE: The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. DESIGN: The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. SETTING: Acute stroke and medical units in teaching and district general hospitals, in the UK. PATIENTS: The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. STUDY OUTCOMES: The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Tumor necrosis factor-alpha mediates osteopenia caused by depletion of antioxidants.

We recently found that estrogen deficiency leads to a lowering of thiol antioxidant defenses in rodent bone. Moreover, administration of agents that increase the concentration in bone of glutathione, the main intracellular antioxidant, prevented estrogen-deficiency bone loss, whereas depletion of glutathione by buthionine sulfoximine (BSO) administration provoked substantial bone loss. It has been shown that the estrogen-deficiency bone loss is dependent on TNFalpha signaling. Therefore, a model in which estrogen deficiency causes bone loss by lowering antioxidant defenses predicts that the osteopenia caused by lowering antioxidant defenses should similarly depend on TNFalpha signaling. We found that the loss of bone caused by either BSO administration or ovariectomy was inhibited by administration of soluble TNFalpha receptors and abrogated in mice deleted for TNFalpha gene expression. In both circumstances, lack of TNFalpha signaling prevented the increase in bone resorption and the deficit in bone formation that otherwise occurred. Thus, depletion of thiol antioxidants by BSO, like ovariectomy, causes bone loss through TNFalpha signaling. Furthermore, in ovariectomized mice treated with soluble TNFalpha receptors, thiol antioxidant defenses in bone remained low, despite inhibition of bone loss. This suggests that the low levels of antioxidants in bone seen after ovariectomy are the cause, rather than the effect, of the increased resorption. These experiments are consistent with a model for estrogen-deficiency bone loss in which estrogen deficiency lowers thiol antioxidant defenses in bone cells, thereby increasing reactive oxygen species levels, which in turn induce expression of TNFalpha, which causes loss of bone.