Vitamin D Status and TB Treatment Outcomes in Adult Patients in Tanzania: A Cohort Study.

Vitamin D is an immunomodulator and can alter response to tuberculosis (TB) treatment, though randomised trials have been inconclusive to date. We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment, T-cell counts and nutritional outcomes by HIV status. Cohort study. Outpatient clinics in Tanzania. 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB (344 HIV infected) initiating anti-TB treatment at enrolment in a multivitamin supplementation (excluding vitamin D) trial (Clinicaltrials.gov identifier: NCT00197704). Information on treatment outcomes such as failure and relapse, HIV disease progression, T-cell counts and anthropometry was collected routinely, with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients, respectively. Cox and binomial regression, and generalised estimating equations were used to assess the association of vitamin D status with these outcomes. Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 (±21.5) nmol/L (27.9 (±8.6) ng/mL). Vitamin D insufficiency (<75 nmol/L) was associated with a 66% higher risk of relapse (95% CI 4% to 164%; 133% higher risk in HIV-uninfected patients). Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 (p=0.004) CD8 and 3 (p=0.01) CD3 T-cells/µL during follow-up in patients with HIV infection. Vitamin D insufficiency was also associated with a greater decrease of body mass index (BMI; -0.21 kg/m(2); 95% CI -0.39 to -0.02), during the first 8 months of follow-up. No association was observed for vitamin D status with mortality or HIV disease progression. Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB, with or without HIV infection. Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB

PREDICTING RISK FOR ADVERSE OUTCOMES FOLLOWING DISTAL RADIUS FRACTURE

Some individuals remain at risk for adverse outcomes such as chronic wrist/hand pain, falls, and fall-related osteoporotic fractures after distal radius fracture (DRF) remain. This thesis includes five studies that were conducted to establish prediction rules for assessing the risk of these adverse outcomes following DRF. The first manuscript outlines a theoretical framework (RACE - Reducing pain, Activating, Cognitive reshaping, Empowering) for managing the risk of adverse outcomes, mainly chronic pain, in individuals with DRF. The RACE is one of the first frameworks to suggest a risk-based management approach for individuals with DRF. The Patient-Rated Wrist Evaluation (PRWE) is a condition-specific measure for DRF used in research as well as clinical practice to measure pain and functions in individuals with different wrist/hand injuries. The second manuscript contributes to the literature by providing the first systematic literature review that synthesizes the evidence regarding the psychometric properties of the PRWE. The review determined that the PRWE has excellent reliability, construct validity, and responsiveness in individuals with DRF. The third manuscript indicates that the baseline pain intensity is an independent predictor of chronic pain in individuals with DRF. The results also suggest that the individuals who score ≥35/50 on the pain scale of the PRWE at baseline have 8 times greater risk for developing chronic wrist/hand pain compared to those who score The fourth and fifth manuscripts describe results of a two step study. The fourth manuscript is a structured literature synthesis that identified suitable measures for predicting the risk of falls and fall-related osteoporotic fractures following DRF. The fifth manuscript summarizes the results of preliminary analysis of psychometric properties of selected fall risk measures identified in the fourth manuscript. The fifth manuscript also provides feasibility and sample size requirements for conducting a fall prevention trial in individuals with DRF.Doctor of Philosophy (PhD

Palladium-catalyzed and electrophilic cyclization approaches to important heterocycles and carbocycles

Several new and synthetically useful approaches involving palladium catalysis and electrophilic cyclization have been described for the synthesis of potentially medicinally and industrially important heterocycles and carbocycles. The methods used are quite general and have been utilized to synthesize a wide variety of important heterocyclic and carbocyclic ring systems including isochromenes, cyclic imidates, as well as linear and fused polyheterocyclic compounds (PHCs) containing benzofurans, benzothiophenes, indoles, and isocoumarin subunits

Predicting Risk for Adverse Outcomes Following Distal Radius Fracture

Some individuals remain at risk for adverse outcomes such as chronic wrist/hand pain, falls, and fall-related osteoporotic fractures after distal radius fracture (DRF) remain. This thesis includes five studies that were conducted to establish prediction rules or assessing the risk of these adverse outcomes following DRF. The first manuscript outlines a theoretical framework (RACE - Reducing pain, Activating, Cognitive reshaping, Empowering) for managing the risk of adverse outcomes, mainly chronic pain, in individuals with DRF. The RACE is one of the first frameworks to suggest a risk-based management approach for individuals with DRF. The Patient-Rated Wrist Evaluation (PRWE) is a condition-specific measure for DRF used in research as well as clinical practice to measure pain and functions in individuals with different wrist/hand injuries. The second manuscript contributes to the literature by providing the first systematic literature review that synthesizes the evidence regarding the psychometric properties of the PRWE. The review determined that the PRWE has excellent reliability, construct validity, and responsiveness in individuals with DRF. The third manuscript indicates that the baseline pain intensity is an independent predictor of chronic pain in individuals with DRF. The results also suggest that the individuals who score ≥35/50 on the pain scale of the PRWE at baseline have 8 times greater risk for developing chronic wrist/hand pain compared to those who score \u3c 35/50. The fourth and fifth manuscripts describe results of a two step study. The fourth manuscript is a structured literature synthesis that identified suitable measures for predicting the risk of falls and fall-related osteoporotic fractures following DRF. The fifth manuscript summarizes the results of preliminary analysis of psychometric properties of selected fall risk measures identified in the fourth manuscript. The fifth manuscript also provides feasibility and sample size requirements for conducting a fall prevention trial in individuals with DRF

Vitamin D Status and its Association with Morbidity including Wasting and Opportunistic Illnesses in HIV-Infected Women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings

Systematic review of home physiotherapy after hip fracture surgery

OBJECTIVE: To compare the benefits of home physiotherapy, institution-based physiotherapy and no physiotherapy following hip fracture surgery. DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: Two reviewers independently extracted data from 5 included studies. Standardized mean differences were pooled for health-related quality of life and performance-based outcomes. Review Manager Version 5 was used for data analysis. RESULTS: Analysis of the 5 included studies indicated that home physiotherapy was better than no physiotherapy and similar to outpatient physiotherapy in improving patient-reported health-related quality of life. Performance-based outcomes were marginally better following outpatient physiotherapy compared with home physiotherapy 3 and 6 months after surgery. The risk of bias was high for most outcomes due to methodological issues in the included studies. Discussion: There was a trend of better results with increasing intensity of physiotherapy intervention, but this did not convert into significant effect sizes. The results of this review do not build a strong consensus for recommending one mode of physiotherapy over the others. The quality of evidence was low mainly due to the high risk of bias in the included studies. CONCLUSION: In light of no strong consensus, physiotherapists should continue to follow their current workplace practice policies for determining suitable discharge settings

Cross-cultural Adaptation and Psychometric Testing of the Hindi Version of the Patient-rated Wrist Evaluation

The purpose of this study was to perform cross-cultural adaptation and Hindi translation of the patient-rated wrist evaluation (PRWE) and assess psychometric properties of the PRWE-Hindi. Cross-cultural adaptation and Hindi translation of the PRWE was performed using standardized guidelines. Intraclass correlation coefficient (ICC) was used for assessing test–retest reliability, and Cronbach’s alpha (CA) was used for assessing the internal consistency of the PRWE-Hindi. Construct validity was assessed by examining the correlations between the PRWE-Hindi and grip strength, wrist range of movements, and self-reported pain and disability. A total of 50 patients with distal radius fracture were recruited and assessed three times (baseline, two to three days later, and four to five weeks later). PRWE-Hindi demonstrated excellent test–rest reliability (ICC=0.81) and internal consistency (CA=0.89). Moderate to low correlations (r\u3c0.7) were observed between the PRWE-Hindi and other measures of pain and disability. Our results indicated that PRWE-Hindi is a reliable and valid tool and can be used in patients with wrist/hand injuries whose primary language is Hindi

Matrix Free approach for Raviart-Thomas anisotropic Tensor Product Finite Elements

In this thesis, we develop techniques for fast, efficient cell based operator evaluation of Raviart-Thomas finite elements and thereby extend the existing implementation of matrix free framework in deal.ii. The extensions allow the framework to also support anisotropic vector-valued finite elements in addition to existing isotropic Lagrangian finite elements. Tests on finite element operators in divergence conforming spaces for Mixed diffusion equation and Stokes equations show that the method is sufficiently accurate (relative error 10e-16) and for RT2 is already twice as fast as corresponding sparse matrix based solution

The Implications of Chronic Pain Models for Rehabilitation of Distal Radius Fracture

Distal radius fracture (DRF) is the most common fracture and usually occurs as a result of a fall. Most patients recover following DRF with minimal residual pain or disability; however, a small subset of patients continue to experience pain and disability even one year after the injury. Currently, there are no practice guidelines for early identification and treatment of patients who are potentially at greater risk of developing these adverse outcomes. As a result, hand therapy management of patients following DRF does not incorporate screening of these at-risk patients. The objective of this paper is to apply constructs from learned helplessness and cognitive-behavioural models of chronic pain in assessing the psychosocial risk profile of patients following DRF. We have also integrated key findings derived from studies addressing personal and life-style factors in assessing this risk profile. This framework is proposed as a basis to categorize patients as higher or lower psychosocial risk for developing chronic pain and disability following DRF. We outline a model depicting the RACE approach (Reducing pain, Activating, Cognitive reshaping, Empowering) towards the management of patients following DRF. The model suggests that patients with minimal psychosocial risk factors are managed based on their injury profile and those with higher psychosocial risk are treated with the risk-based RACE approach. Using a biopsychosocial RACE approach to prognosis and treatment, hand therapy intervention can be customized for patients recovering from DRF. In future, researchers can conduct clinical trials to compare the RACE-based treatment approach to routine hand therapy in mitigating the risk of chronic pain and disability in patients with elevated risk profile for adverse outcomes following DRF

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved