Dynamics of tuberculosis infection in various populations during the 19th and 20th century: The impact of conservative and pharmaceutical treatments.

Humans and Mycobacterium tuberculosis have co-evolved together for thousands of years. Many individuals are infected with the bacterium, but few show signs and symptoms of tuberculosis (TB). Pharmacotherapy to treat those who develop disease is useful, but drug resistance and non-adherence significantly impact the efficacy of these treatments. Prior to the introduction of antibiotic therapies, public health strategies were used to reduce TB mortality. This work shows how these strategies were able to reduce TB mortality in 19th and 20th century populations, compared with antibiotic treatments. Previously published mortality data from historical records for several populations (Switzerland, Germany, England and Wales, Scotland, USA, Japan, Brazil and South Africa) were used. Curvilinear regression was used to examine the reduction in mortality before and after the introduction of antibiotic treatments (1946). A strong decline in TB mortality was already occurring in Switzerland, Germany, England and Wales, Scotland and the USA prior to the introduction of antibiotic treatment. This occurred following many public health interventions including improved sanitation, compulsory reporting of TB cases, diagnostic techniques and sanatoria treatments. Following the introduction of antibiotics, mortality rates declined further, however, this had a smaller effect than the previously employed strategies. In Japan, Brazil and South Africa, reductions in mortality rates were largely driven by antibiotic treatments that caused rapid decline of mortality, with a smaller contribution from public health strategies. For the development of active disease, immune status is important. Individuals infected with the bacterium are more likely to develop signs and symptoms if their immune function is reduced. Effective strategies against TB can therefore include enhancing immune function of the population by improving nutrition, as well as reducing transmission by improving living conditions and public health. This has been effective in the past. Improving immunity may be an important strategy against drug resistant TB.

Repurposing a fracture risk calculator (FRAX) as a screening tool for women at risk for sarcopenia.

Osteoporosis and sarcopenia share risk profiles, so we tested a fracture risk assessment tool (FRAX) as a screening tool for sarcopenia. FRAX probabilities without bone mineral density predicted sarcopenia with high sensitivity and reasonable specificity. There is potential to use this FRAX as a screening tool for sarcopenia. PURPOSE: There is a need for simple screening tools for sarcopenia. As osteoporosis and sarcopenia share risk profiles, we tested the performance of a fracture risk assessment tool for discriminating individuals at risk for sarcopenia. METHODS: In this longitudinal study, FRAX (Australia) probabilities were calculated for 354 women (ages 40-90 years) in the Geelong Osteoporosis Study. Sarcopenia was assessed a decade later using DXA-derived low appendicular lean mass (Lunar; ALM/height2 < 5.5 kg/m2) and low handgrip strength (Jamar; HGS < 16 kg), according to EWGSOP2. We determined FRAX probabilities (%) for hip fracture (HF-FRAX) and major osteoporotic fracture (MOF-FRAX), with and without BMD. Area under the receiver operator characteristic (AUROC) curves quantified the performance of FRAX for predicting sarcopenia. RESULTS: Baseline median (IQR) values for HF-FRAX without BMD were 0.4 (0.1-1.3) and for MOF-FRAX without BMD, 2.4 (1.2-5.2); comparable figures for HF-FRAX with BMD were 0.2 (0.0-0.7) and for MOF-FRAX with BMD, 2.1 (1.1-4.4). At follow-up, sarcopenia was identified for 11 (3.1%) women. When FRAX was calculated without BMD, the AUROC was 0.90 for HF-FRAX and 0.88 for MOF-FRAX. Optimal thresholds were 0.9 for HF-FRAX (sensitivity 90.9%, specificity 62.4%) and 5.3 for MOF-FRAX (sensitivity 81.8%, specificity 71.7%). Calculating FRAX with BMD did not improve the predictive performance of FRAX for sarcopenia. CONCLUSION: Here we provide preliminary evidence to suggest that FRAX probabilities without BMD might predict sarcopenia with high sensitivity and reasonable specificity. Given that FRAX clinical risk factors are identified without equipment, there is potential to use this or a modified version of the FRAX tool to screen for individuals at risk of sarcopenia.

Bone mineral density in diabetes and impaired fasting glucose.

We report that compared with normoglycaemia, post-menopausal women (non-obese and obese) with diabetes had higher lumbar spine bone mineral density (LSBMD). Femoral neck bone mineral density (FNBMD) was higher in obese post-menopausal women with diabetes. Only non-obese post-menopausal women with impaired fasting glucose (IFG) had a higher LSBMD than normoglycaemia. No other associations with IFG were observed. INTRODUCTION: Individuals with diabetes have a higher or normal bone mineral density (BMD) compared with those without diabetes. However, paradoxically, they also have a higher fracture risk. It is not clear whether those with IFG also have altered BMD. This study aimed to determine whether individuals with IFG have elevated or normal BMD. METHODS: Women (n = 858) and men (n = 970) (aged 20-80 years) from the Geelong Osteoporosis Study were included. IFG was defined as fasting plasma glucose (FPG) 5.5-6.9 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, use of antihyperglycaemic medication and/or self-report. Using multivariable linear regression, the relationships between glycaemia and BMD at the femoral neck and lumbar spine were examined, and adjusted for age, body mass index (BMI), and other variables. In women, two interaction terms were identified: menopause × glycaemia and BMI × glycaemia, and thus, the analyses were stratified by menopause and obesity status (BMI cut point ≥ 30 kg/m2). RESULTS: There were no associations between glycaemic status and BMD for pre-menopausal women. For non-obese post-menopausal women, there was no association between FNBMD and glycaemic status, but women with IFG or diabetes had higher LSBMD than those with normoglycaemia (7.1% and 9.7%, respectively, both p < 0.01). Obese post-menopausal women with diabetes had a higher FNBMD (8.8%, p = 0.008) and LSBMD (12.2%, p < 0.001), but those with IFG were not different from the normoglycaemia group. There were no associations detected between glycaemic status and BMD in men. CONCLUSIONS: In this study, we report that compared with normoglycaemia, post-menopausal women (non-obese and obese) with diabetes had higher LSBMD. FNBMD was higher in obese post-menopausal women with diabetes. Only non-obese post-menopausal women with IFG had a higher LSBMD than normoglycaemia. No other associations with IFG were observed.

How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study reports that both FRAX and Garvan calculators underestimated fractures in Australian men and women, particularly in those with osteopenia or osteoporosis. Major osteoporotic fractures were poorly predicted, while both calculators performed acceptably well for hip fractures. INTRODUCTION: This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. METHODS: Women (n = 809) and men (n = 821) aged 50-90 years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAXBMD, FRAXnoBMD, GarvanBMD, GarvannoBMD). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10 years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. RESULTS: In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p < 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAXBMD and fragility fractures by GarvannoBMD, both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. CONCLUSIONS: Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that GarvanBMD performed better than GarvannoBMD for prediction of fragility fractures.

Vitamin D during pregnancy and offspring body composition: a prospective cohort study.

BACKGROUND: Evidence regarding the association between gestational vitamin D status and offspring body composition during childhood is inconsistent. Therefore, we aimed to determine the association between maternal vitamin D and offspring lean and fat mass in the Vitamin D in Pregnancy birth cohort. METHODS: Subjects were mother-child pairs recruited from the Australian-based Vitamin D in Pregnancy cohort study. Mothers were recruited before 16 weeks' gestation and provided a blood sample at both recruitment and at 28-32 weeks' gestation. Serum vitamin D [25(OH)D] was measured by radioimmunoassay (Tyne and Wear, UK). Offspring lean and fat mass were quantified by using dual-energy X-ray absorptiometry (GE Lunar Prodigy, Madison, WI, USA) at 11 years of age. RESULTS: Median maternal 25(OH)D levels were 55.9 (42.2-73.3) and 56.1 (43.6-73.9) at recruitment and 28-32 weeks' gestation, respectively. Maternal smoking was identified as an effect modifier in the association between maternal vitamin D status at recruitment and offspring body composition. In smokers, but not non-smokers, serum 25(OH)D status at recruitment was negatively associated with offspring fat mass percentage and positively associated with lean mass (both p < 0.05). There was no association with 25(OH)D status at 28-32 weeks' gestation. CONCLUSIONS: Maternal vitamin D status in early pregnancy, in smokers, is associated with offspring body composition. These important findings warrant confirmation in larger studies and trials.