Kara L. Holloway

Evolution of human tuberculosis: a systematic review and meta-analysis of paleopathological evidence

Tuberculosis is a re-emerging disease and is a major problem in both developing and developed countries today. An estimated one third of the worlds population is infected and almost two million people die from the disease each year. Bone lesions occur in 3-5% of active tuberculosis cases and can be used to diagnose the disease in ancient skeletal remains. A meta-analysis was conducted on 531 palaeopathological tuberculosis cases from 221 sites (7250 BCE to 1899) on all continents for the purpose of testing two hypotheses; (1) the frequency of bone lesions does not change through time and (2) the distribution of lesions throughout the skeleton does not change over time. The frequency of bone lesions was found to significantly decrease over time (P<0.05). The distribution of bone lesions was found to change from mainly spinal in earlier time periods to include more cases in other regions of the skeleton (long bones, joints, hands, feet) in later time periods. This difference in distribution was evaluated using a Chi-squared test and found to be significant (P<0.01). These findings are an important addition to the current knowledge of the evolution of the disease and the Mycobacterium tuberculosis.

Excessive daytime sleepiness and falls among older men and women: cross-sectional examination of a population-based sample

BackgroundExcessive daytime sleepiness (EDS) has been associated with an increased risk for falls among clinical samples of older adults. However, there is little detailed information among population-representative samples. The current study aimed to assess the relationship between EDS and falls among a cohort of population-based older adults.MethodsThis study assessed 367 women aged 60-93years (median 72, interquartile range 65-79) and 451 men aged 60-92years (median 73, interquartile range 66-80) who participated in the Geelong Osteoporosis Study between the years 2001 and 2008. Falls during the prior year were documented via self-report, and for men, falls risk score was obtained using an Elderly Fall Screening Test (EFST). Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and scores of ≥ 10 indicated EDS. Differences among those with and without EDS in regard to falls were tested using logistic regression models.ResultsAmong women, 50 (13.6 %) individuals reported EDS. Women with EDS were more likely to report a fall, and were more likely to report the fall occurring outside. EDS was similarly associated with an increased risk of a fall following adjustment for use of a walking aid, cases of nocturia and antidepressant medication use (adjusted OR = 2.54, 95 % CI 1.24-5.21). Multivariate modelling revealed antidepressant use (current) as an effect modifier (p < .001 for the interaction term). After stratifying the data by antidepressant medication use, the association between EDS and falls was sustained following adjustment for nocturia among antidepressant non-users (adjusted OR = 2.63, 95 % CI 1.31-5.30). Among men, 72 (16.0 %) individuals reported EDS. No differences were detected for men with and without EDS in regard to reported falls, and a trend towards significance was noted between EDS and a high falls risk as assessed by the EFST (p = 0.06), however, age explained this relationship (age adjusted OR = 2.20, 95 % CI 1.03-1.10).ConclusionsFor women, EDS is independently associated with at least one fall during the previous year, and this is more likely to occur whilst located outside. Amelioration of EDS may assist in improving functional outcomes among these individuals by reducing the risk for falls.

Skeletal Lesions in Human Tuberculosis May Sometimes Heal: An Aid to Palaeopathological Diagnoses

In three to five percent of active cases of tuberculosis, skeletal lesions develop. Typically, these occur on the vertebrae and are destructive in nature. In this paper, we examined cases of skeletal tuberculosis from a skeletal collection (Galler Collection) with focus on the manifestation of bony changes due to tuberculosis in various body regions in association with antibiotic introduction. This skeletal collection was created in 1925–1977 by a pathologist at the University Hospital in Zürich, Ernst Galler. It includes the remains of 2426 individuals with documented clinical histories as well as autopsies. It contained 29 cases of skeletal tuberculosis lesions. We observed natural healing of vertebral lesions through several processes including fusion of vertebrae, bone deposition and fusion of posterior elements. In these cases, we observed a higher frequency and proportion of bone deposition and fusion of posterior vertebral elements where pharmacological agents were used. There were also four cases of artificial healing through surgically induced posterior spinal fusion. With the introduction of pharmaceutical treatments, the number of individuals with multiple tuberculous foci decreased from 80% to 25% when compared to individuals who did not receive any drug therapy. Investigation of comorbidities showed that pneumonia, pleuritis and being underweight were consistently present, even with pharmaceutical treatment. Our results have applications in palaeopathological diagnoses where healing and consequent bone deposition may complicate differential diagnoses.

Sarcopenia and the Common Mental Disorders: a Potential Regulatory Role of Skeletal Muscle on Brain Function?

While it is understood that body composition impacts on physical conditions, such as diabetes and cardiovascular disease, it is only now apparent that body composition might play a role in the genesis of common mental disorders, depression and anxiety. Sarcopenia occurs in ageing and comprises a progressive decline in muscle mass, strength and function, leading to frailty, decreased independence and poorer quality of life. This review presents an emerging body of evidence to support the hypothesis that shared pathophysiological pathways for sarcopenia and the common mental disorders constitute links between skeletal muscle and brain function. Contracting skeletal muscle secretes neurotrophic factors that are known to play a role in mood and anxiety, and have the dual role of nourishing neuronal growth and differentiation, while protecting the size and number of motor units in skeletal muscle. Furthermore, skeletal muscle activity has important immune and redox effects that impact behaviour and reduce muscle catabolism.

FRAX (Aus) and falls risk: Association in men and women

PURPOSE The WHO fracture risk prediction tool (FRAX®) utilises clinical risk factors to estimate the probability of fracture over a 10-year period. Although falls increase fracture risk, they have not been incorporated into FRAX. It is currently unclear if FRAX captures falls risk and whether addition of falls would improve fracture prediction. We aimed to investigate the association of falls risk and Australian-specific FRAX. METHODS Clinical risk factors were documented for 735 men and 602 women (age 40-90 yr) assessed at follow-up (2006-2010 and 2000-2003, respectively) of the Geelong Osteoporosis Study. FRAX scores with and without BMD were calculated. A falls risk score was determined at the time of BMD assessment and self-reported incident falls were documented from questionnaires returned one year later. Multivariable analyses were performed to determine: (i) cross-sectional association between FRAX scores and falls risk score (Elderly Falls Screening Test, EFST) and (ii) prospective relationship between FRAX and time to a fall. RESULTS There was an association between FRAX (hip with BMD) and EFST scores (β = 0.07, p < 0.001). After adjustment for sex and age, the relationship became non-significant (β = 0.00, p = 0.79). The risk of incident falls increased with increasing FRAX (hip with BMD) score (unadjusted HR 1.04, 95% CI 1.02, 1.07). After adjustment for age and sex, the relationship became non-significant (1.01, 95% CI 0.97, 1.05). CONCLUSIONS There is a weak positive correlation between FRAX and falls risk score, that is likely explained by the inclusion of age and sex in the FRAX model. These data suggest that FRAX score may not be a robust surrogate for falls risk and that inclusion of falls in fracture risk assessment should be further explored.

LESSONS FROM HISTORY OF SOCIOECONOMIC IMPROVEMENTS: A NEW APPROACH TO TREATING MULTI-DRUG-RESISTANT TUBERCULOSIS

This study investigated the trends in tuberculosis mortality through time in Switzerland. Information on the decline in mortality before chemotherapies were introduced may be useful in developing countries where drug-resistant tuberculosis is now becoming a major problem. Swiss data were collected from historical records and comparative data were obtained from the literature for England and Wales, New York, Japan, Brazil and Sierra Leone. Logistic curves were fitted to examine the rate of decline before introduction of pharmacotherapies and these show that the decline would have continued without the introduction of chemical therapies, including antibiotics. In Switzerland, England and Wales and New York, the decline had occurred long before the introduction of specific anti-tuberculosis agents. In Brazil and Japan, chemical therapy was co-incident with the decline in tuberculosis mortality rates. Overall, it is suggested that the effective control of tuberculosis can be achieved through a combination of chemical interventions, conservative therapy (rest, good nutrition, ventilation, etc.) as well as public health interventions addressing hygiene, nutrition, reducing exposure to infections and educating the population about tuberculosis.

Dysglycaemia and Other Predictors for Progression or Regression from Impaired Fasting Glucose to Diabetes or Normoglycaemia.

Aims. Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. Methods. This study included 1167 women, aged 20–94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. Results. At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7–28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. Conclusions. Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes.

Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study

We aimed to examine the relationship between musculoskeletal deterioration and all‐cause mortality in a cohort of women studied prospectively over a decade.

Anxiety disorders and falls among older adults.

BACKGROUND Falls are common among older adults and can lead to serious injuries, including fractures. We aimed to determine associations between anxiety disorders and falls in older adults. METHODS Participants were 487 men and 376 women aged ≥60 years enrolled in the Geelong Osteoporosis Study, Australia. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition (SCID-I/NP), lifetime history of anxiety disorders was determined. Falls were determined by self-report. In men, a falls-risk score (Elderly Falls Screening Test (EFST)) was also calculated. RESULTS Among fallers, 24 of 299 (8.0%) had a lifetime history of anxiety disorder compared to 36 of 634 (5.7%) non-fallers (p=0.014). Examination of the association between anxiety and falls suggested differential relationships for men and women. In men, following adjustment for psychotropic medications, mobility and blood pressure, lifetime anxiety disorder was associated with falling (OR 2.96; 95%CI 1.07-8.21) and with EFST score (OR 3.46; 95%CI 1.13-10.6). In women, an association between lifetime anxiety disorder and falls was explained by psychotropic medication use, poor mobility and socioeconomic status. LIMITATIONS Sub-group analyses involving types of anxiety and anxiety disorders over the past 12-months were not performed due to power limitations. CONCLUSION Although anxiety disorders were independently associated with a 3-fold increase in likelihood of reported falls and high falls risk among men, an independent association was not detected among women. These results may aid in prevention of falls through specific interventions aimed at reducing anxiety, particularly in men.

Foot and Ankle Fracture Incidence in South-Eastern Australia: An Epidemiological Study

Objective: The aim of this study was to report the incidence of all foot and ankle fractures during 2006 and 2007 among residents from the Barwon Statistical Division, located in south-eastern Australia. Methods: Incident fractures were ascertained using X-ray reports from the imaging centres serving the region during the years 2006 and 2007. All fractures with ICD-9 code 824 (ankle) or 825 (foot) were included in this study. Age, proportions of left/right side fractures, cause of fracture and incidence rates (per 10,000 person-years) were all determined for foot and ankle fractures separately as well as for the two sites combined. Results: There were 312 males and 274 females identified with foot fractures and 344 males and 410 females with ankle fractures. The median age for both foot and ankle fracture was lower in males compared to females. The proportions of left and right side fractures were approximately equal; no sex or site (foot or ankle) showed higher proportions of either left or right side fractures. Among those for whom cause of fracture was known, most foot or ankle fractures (>75%) in both sexes were caused by an accidental fall. For both sexes, there was a bimodal pattern of incidence across the age groups, with peaks around adolescence/early adulthood and in the elderly. Incidence rates (per 10,000 person-years) for foot and ankle fractures combined were similar in both sexes; 25.85 and 25.88 for males and females, respectively. However, the incidence rate for foot/ankle fractures combined in those aged 50 years or over was lower in males than in females. Conclusion: Males sustained foot and ankle fractures at a lower median age than females and most fractures were the result of an accidental fall. Males sustain fractures mainly during adolescence and young adulthood, whereas fractures in females were sustained largely by individuals over 50 years of age. Despite this, the overall incidence rates were similar for both sexes.