Vitamin D Supplementation improves Bone Mineral Density in Patients with Hyperthyroidism

Background: Diseases of the thyroid gland are a common occurrence in India. Thyrotoxicosis causes acceleration of bone remodeling and even though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone is a little- discussed subject.Materials & Methods: 70 consecutive patients with hyperthyroidism attending endocrine clinic of Maulana Azad Medical College. Serum total calcium, phosphorous, urinary creatinine and alkaline phosphatase were measured by standard methods. Serum T4, serum 25(OH)D estimations were done by radioimmunoassay assay. Serum intact PTH and TSH concentration was measured by immune-radiometric assay using commercial kits. Bone mineral density was measured using Hologic DR 4500A densitometer. Bone mineral density was measured at both hips, and lumbar spine (L2-L4) using anteroposterior view. 50% of the patients were randomized for vitamin D supplementation.Results: The mean age of the patients was 39±10.01 years. The baseline vitamin D of the patients was 19.24±10.15 ng/ml. The values of vitamin D in randomized and non-randomized patients were 27.82±16.43 vs 11.82±6.58 ng/ml (p>0.0001) respectively. Patients who received vitamin D had acquired optimum level of vitamin significantly, whereas, BMD at lumbar spine was also found increased after post treatment of vitamin D. However, it was not significantly raised when compared with the pre treatment. BMD at hip region was found elevated after post-treatment. There was an improvement noticed in total body BMD as well.Conclusion: Patients with active thyrotoxicosis, acquired optimum vitamin D levels, elevated lumbar spine and hip BMD after one year of vitamin D supplementation. Vitamin D supplementation is necessary to be advocated in patients with hyperthyroidism

Mood instability : significance, definition and measurement

Mood instability is common, and an important feature of several psychiatric disorders. We discuss the definition and measurement of mood instability, and review its prevalence, characteristics, neurobiological correlates and clinical implications. We suggest that mood instability has underappreciated transdiagnostic potential as an investigational and therapeutic target

Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy

Objectives: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. Methods: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffPoeso), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5±2 months. Results: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59±26 to 23±13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57±0.62 to 2.94±0.60 l), forced expiratory volume in the first second (2.21±0.49 to 2.45±0.47 l), total lung capacity (3.57±1.19 to 4.1±1.12 l), diaphragmatic movement during deep respiration (5.5±1.0 to 6.6±1.1 cm) and SniffPoeso (68.7±23 to 93.1±25.2 cmH2O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffPoeso. Conclusions: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis

Bone mineral parameters in healthy young Indian adults with optimal vitamin D availability

Background: Several recent studies indicate a marked prevalence of vitamin D deficiency in asymptomatic, apparently healthy urban subjects from different socioeconomic groups in north India. Methods: To further examine this trend, we studied 40 men and 50 women, 20–30 years of age, from the Indian paramilitary forces. These individuals consume a nutritious, high-protein diet, have optimal exposure to sunlight and undertake strenuous outdoor physical exercise. Results: The mean serum calcium, phosphorus and alkaline phosphatase levels were normal in both men and women. The mean (SD) serum intact parathyroid hormone and 25-hydroxy-vitamin D3 levels were 19.3 (8.2) pg/ml and 18.4 (5.3) ng/ml in men, and 11.9 (6.6) pg/ml and 25.3 (7.4) ng/ml in women. Bone mineral density estimated in 20 men and 22 women revealed that in comparison with white Caucasians, 35%–50% of men and 14%–32% of women were osteopenic at different sites, while an additional 10% of men had osteoporosis of the lumbar spine. Conclusion: We found that with optimal nutrition, good sunlight exposure and regular physical exercise, healthy young individuals have normal bone and mineral biochemical values. The reasons for the abnormalities detected in bone mineral density in them needs further study. The impact of childhood nutrition on accumulation of peak bone mass may contribute to our findings. There is a need for establishing normative bone mineral density data for Indians

Web based software for the study of USDA soil taxonomy and classification of newly found soil

United States Department of Agriculture (USDA) Soil Taxonomy is based on soil properties that can be objectively observed and measured in the natural conditions as they exist today. There are many soil classification systems but USDA Soil Taxonomy is most accepted worldwide. Ontologies are the new form of knowledge representation that acts in synergy with agents and Semantic Web Architecture. Soil ontology developed for USDA soil taxonomy has been used to develop a query interface that will help in detailed study of soil taxonomy, classification of new soil as well as exchange knowledge between software agents and systems. This is a web based application having N-tier architecture. Application development environment is NetBeans 6.9 editor and Protégé. Web development technology is Java Server Pages (JSP). Programming languages JAVA and SPARQL are used for querying. Client interface is developed with Hyper Text Markup Language (HTML), Cascading Style Sheet (CSS) and JavaScript. Third tier of software consist of database which is in MS-SQL server 2005. Other two layers are Web Ontology Language (OWL) Ontology layer and Semantic Web Framework layer. OWL layer contains soil taxonomy information in the form of Ontology. Semantic Web Framework layer is implemented using JENA. In the search panel user can search anything related to USDA Soil Taxonomy, which comprises of twelve orders. However, this software contains information about seven soil orders reported in India. Domain experts can see and edit the knowledge base (i.e. Soil Ontology) or can suggest anything related to the creation of Soil Taxonomy Ontology through WebProtégé

A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes

Aim We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia. Methods We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: i) 45mg loading-weeks 0/4/16, ii) 45mg maintenance-weeks 0/4/16/28/40, iii) 90mg loading-weeks 0/4/16 and iv) 90mg maintenance-weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses. Results Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90mg maintenance dosing cohort had the smallest mean decline in C-peptide AUC (0.1pmol/mL). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1 and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A. Conclusion Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response

Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial

Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis. CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at least one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045. Five hundred fifty-one participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99, 382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group; however, the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group. Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered

Cognitive Remediation in Bipolar (CRiB2): study protocol for a randomised controlled trial assessing efficacy and mechanisms of cognitive remediation therapy compared to treatment as usual

\ua9 2023, The Author(s).Background: A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects. Methods: CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30–40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models. Discussion: This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action. Trial registration: Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting