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Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. [ABSTRACT FROM AUTHOR]

Poor vitamin D nutrition is linked with dementia, but vitamin D has not been tested in a randomized controlled trial (RCT) in Alzheimer's disease (AD). Nasal insulin acutely improves cognition and vitamin D upregulates insulin receptor expression and enhances insulin action. In an RCT we examined the effect of high-dose vitamin D followed by nasal insulin on memory and disability in mild-moderate AD. 63 community-dwelling individuals aged > 60 were recruited; 32 with mild-moderate disease (Folstein Mini-Mental State Examination [MMSE] score 12-24) met entry criteria and were randomized. All took low-dose vitamin D (1000IU/day) throughout. After run-in (8 weeks), they were randomized to additional high-dose D/placebo for 8 weeks, followed immediately by randomization to nasal insulin (60 IU qid)/placebo for 48 h. Primary outcome measures were Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and Disability Assessment in Dementia (after high-dose D) and ADAS-cog and Wechsler Memory Scale-Revised Logical memory (WMS-R LM) for immediate and delayed recall (after nasal insulin). Baseline median (interquartile range, IR) age, MMSE, and ADAS-cog were 77.5 (69-80), 19.5 (17-22), and 25.5 (20-31), respectively. Median 25OHD increased from 49 to 60 nM (p < 0.01) after run-in and was 187 nM after high-dose vitamin D and 72 nM after placebo (p < 0.001). Neither cognition nor disability changed significantly after high-dose D. ADAS-cog improved by a median (IR) of 9 (1-11) with nasal insulin after placebo high-dose vitamin D (p = 0.02), but may represent regression to the mean as WLS-R LM did not change. We conclude that high-dose vitamin D provides no benefit for cognition or disability over low-dose vitamin D in mild-moderate AD. [ABSTRACT FROM AUTHOR]

This Essay offers a utilitarian perspective on Martha Nussbaum's theory of justice. Nussbaum believes that society should guarantee to every individual a threshold level of central human capabilities. Although Nussbaum's approach has considerable appeal, it is implausible and unappealing when it diverges greatly from utilitarianism. Nussbaum's theory requires that enormous sums of money be devoted to people who receive very little benefit from efforts to raise them toward a capability threshold. Moreover, Nussbaum refuses to take a principled position on how conflicts among below-threshold interests should be resolved, even when one alternative would produce enormously more good than another alternative. Nussbaum mitigates these problems through an implicit incorporation of utilitarianism to address conflicts among below-threshold interests, but this partial adoption of utilitarianism cannot completely cure her theory. In addition to critiquing Nussbaum's theory, this Essay responds to some of Nussbaum's criticisms of utilitarianism. It rejects Nussbaum's claim that utilitarianism is wrong to give weight to adaptive preferences. It also demonstrates that Nussbaum misstates the relationship between her theory and the doctrine of incommensurability: features of her theory that she attributes to a denial of commensurability actually reflect a commitment to commensurability across the capability threshold. [ABSTRACT FROM AUTHOR]

Considers whether the conflation of many people into one can serve as a satisfactory theory of distributive justice. Argument that conflation is the way to treat people with equal respect; Comparison between conflation and utilitarianism; Implications on political science.

Utilitarianism is more convincing than resource egalitarianism or welfare egalitarianism as a theory of how resources should be distributed between disabled people and nondisabled people. Unlike resource egalitarianism, utilitarianism can redistribute resources to the disabled when they would benefit more from those resources than nondisabled people. Unlike welfare egalitarianism, utilitarianism can halt redistribution when the disabled would no longer benefit more than the nondisabled from additional resources. The author considers one objection to this view: it has been argued, by Sen and others, that there are circumstances under which utilitarianism would unfairly distribute fewer resources to the physically disabled than to nondisabled people, on the ground that the disabled would derive less benefit from those resources. In response, the author claims that critics of utilitarianism have fallaciously exaggerated the circumstances under which the disabled would benefit less than the nondisabled from additional resources. In those limited circumstances in which the disabled really would benefit less from resources, the author argues, it does not seem unfair to distribute fewer resources to them. [ABSTRACT FROM AUTHOR]

The article discusses the distribution of life of people suffering from disabilities under the concept of utilitarianism. The distribution issues involving people with disabilities have been a long-time subject of discussion in the field of sociology. The utilitarian distributive policy has apparent implications on the distribution of life between the disabled and the not disabled. According to utilitarian, the key divide is the division between the distribution of life-saving resources and of the non-life saving facility.

OBJECTIVE -- Latent autoimmune diabetes in adults (LADA) is defined as adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initially. Diagnosing LADA has treatment implications because of the high risk of progression to insulin dependency. Currently, there are no recommendations for islet antibody testing in adult-onset diabetes. In this study, we aimed to develop a clinical screening tool to identify adults at high risk of LADA who require islet antibody testing. RESEARCH DESIGN AND METHODS -- Subjects with LADA (n = 102, GAD antibody [GADA] +) and type 2 diabetes (n = 111, GADA-) (aged 30-75 years) were interviewed retrospectively. The clinical features documented were age of onset, acute symptoms of hyperglycemia, BMI, and personal and family history of autoimmune disease. Any clinical feature that was significantly more frequent in LADA was designated as a distinguishing clinical feature. In each subject, a "LADA clinical risk score," based on the total number of distinguishing features, was calculated. A prospective study of adults with newly diagnosed diabetes (n = 130) was used to determine whether the LADA clinical risk score could identify LADA. RESULTS -- In the retrospective study, five clinical features were more frequent in LADA compared with type 2 diabetes at diagnosis: 1) age of onset <50 years (P < 0.0001), 2) acute symptoms (P < 0.0001), 3) BMI <25 kg/m² (P = 0.0004), 4) personal history of autoimmune disease (P = 0.011), and 5) family history of autoimmune disease (P = 0.024). In the prospective study, the presence of at least two of these distinguishing clinical features (LADA clinical risk score ≥2) had a 90% sensitivity and 71% specificity for identifying LADA and a negative predictive value for a LADA clinical risk score ≤1 of 99%. CONCLUSIONS -- At least two distinguishing clinical features are found in a majority of patients with LADA at diagnosis and can be used to identify adults with diabetes at higher risk for LADA. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient. Design: Randomized, placebo-controlled double-blind, trial of 2 years' duration. Setting: Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia. Participants: Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. Intervention: Vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All subjects received 600 mg of elemental calcium daily as calcium carbonate. Measurements: Falls and fractures recorded prospectively in study diaries by care staff. Results: The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 (95% confidence interval (CI)=0.57–0.95). The odds ratio for ever falling was 0.82 (95% CI=0.59–1.12) and for ever fracturing was 0.69 (95% CI=0.40–1.18). An a priori subgroup analysis of subjects who took at least half the prescribed capsules (n=540), demonstrated an incident rate ratio for falls of 0.63 (95% CI=0.48–0.82), an odds ratio (OR) for ever falling of 0.70 (95% CI=0.50–0.99), and an OR for ever fracturing of 0.68 (95% CI=0.38–1.22). Conclusion: Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient. [ABSTRACT FROM AUTHOR]

A response to a letter to the editor about the article on the significance of poststroke urinary incontinence as a negative predictor of functional recovery on the basis of aging is presented.

To determine the prevalence of vitamin D deficiency in older people in residential care and the influence that the level of vitamin D may have on their incidence of falls. Prospective cohort. Residential care facilities for older people in several states of Australia. Six hundred sixty-seven women in low-level care and 952 women in high-level care, mean age 83.7 years. Serum 25-hydroxyvitamin D (25D) levels and recognized risk factors for falls including current medication use, a history of previous fractures, weight, tibial length (as a surrogate for height), cognitive function, walking ability, and frequency of going outdoors were determined. The women in low-level care and high-level care were followed for an average of 145 and 168 days, respectively. Falls were recorded prospectively in diaries completed monthly by residential care staff. Vitamin D deficiency (defined as a serum 25D level below 25 nmol/L) was present in 144 (22%) women in low-level care and 428 (45%) in high-level care. After excluding 358 bed-bound residents and adjusting for weight, cognitive status, psychotropic drug use, previous Colles fracture, and the presence of wandering behavior, log serum 25D level remained independently associated with time to first fall. The adjusted hazards ratio was 0.74 (95% confidence interval=0.59–0.94; P= .01), implying a 20% reduction in the risk of falling with a doubling of the vitamin D level. Vitamin D deficiency is common in residential care in Australia. A low level of serum vitamin D is an independent predictor of incident falls. [ABSTRACT FROM AUTHOR]