Systematic review of the impact of osteoarthritis on health outcomes for comorbid disease in older people.

OBJECTIVE: A systematic review was undertaken examining the impact of comorbid osteoarthritis on health outcomes for people aged 50 years or older with cardiovascular disease, diabetes or obesity. DESIGN: The protocol is registered in PROSPERO (CRD42015023417). Relevant electronic databases and grey literature were systematically searched for studies published in English between January 2005 and December 2016. Two reviewers independently screened studies for selection using predetermined inclusion and exclusion criteria, and independently completed methodological quality review. Data was extracted at study level by one reviewer and independently checked by a second reviewer, using a standardized form. The results across studies were qualitatively synthesized with outcomes described and summarized. RESULTS: Of 1456 articles, we identified 15 relevant studies, with nine good to high quality studies describing significant negative impact of osteoarthritis on outcomes for cardiovascular diseases. There were too few studies focussing on diabetes and obesity to make conclusions in regard to these diseases. CONCLUSIONS: This review provides evidence that osteoarthritis should not be overlooked when impacts of chronic disease on health outcomes and related health service use are considered. There is a clear need for more studies that consider the impacts of osteoarthritis on comorbid disease, especially those that consider the impact of osteoarthritis beyond the morbidity impacts. The management of comorbid osteoarthritis should be addressed for those with cardiovascular disease, and treatment choices considered given this association.

Anticholinergic medicines in an older primary care population: a cross-sectional analysis of medicines' levels of anticholinergic activity and clinical indications.

WHAT IS KNOWN AND OBJECTIVES: Adverse clinical outcomes have been associated with cumulative anticholinergic burden (to which low-potency as well as high-potency anticholinergic medicines contribute). The clinical indications for which anticholinergic medicines are prescribed (and thus the 'phenotype' of patients with anticholinergic burden) have not been established. We sought to establish the overall prevalence of prescribing of anticholinergic medicines, the prevalence of prescribing of low-, medium- and high-potency anticholinergic medicines, and the clinical indications for which the medicines were prescribed in an older primary care population. METHODS: This was a cross-sectional analysis of a cohort study of Australian early-career general practitioners' (GPs') clinical consultations - the Registrar Clinical Encounters in Training (ReCEnT) study. In ReCEnT, GPs collect detailed data (including medicines prescribed and their clinical indication) for 60 consecutive patients, on up to three occasions 6 months apart. Anticholinergic medicines were categorized as levels 1 (low-potency) to 3 (high-potency) using the Anticholinergic Drug Scale (ADS). RESULTS: During 2010-2014, 879 early-career GPs (across five of Australia's six states) conducted 20 555 consultations with patients aged 65 years or older, representing 35 506 problems/diagnoses. Anticholinergic medicines were prescribed in 10·4% [95% CIs 9·5-10·5] of consultations. Of the total anticholinergic load of prescribed medicines ('community anticholinergic load') 72·7% [95% CIs 71·0-74·3] was contributed by Level 1 medicines, 0·8% [95% CIs 0·5-1·3] by Level 2 medicines and 26·5% [95% CIs 24·8-28·1] by Level 3 medicines. Cardiac (40·0%), Musculoskeletal (16·9%) and Respiratory (10·6%) were the most common indications associated with Level 1 anticholinergic prescription. For Level 2 and 3 medicines (combined data), Psychological (16·1%), Neurological (16·1%), Musculoskeletal (15·7%) and Urological (11·1%) indications were most common. WHAT IS NEW AND CONCLUSION: Anticholinergic medicines are frequently prescribed in Australian general practice, and the majority of the 'community' anticholinergic burden is contributed by 'low'-anticholinergic potency medicines whose anticholinergic effects may be largely 'invisible' to prescribing GPs. Furthermore, the clinical 'phenotype' of the patient with high anticholinergic burden may be very different to common stereotypes (patients with urological, psychological or neurological problems), potentially making recognition of risk of anticholinergic adverse effects additionally problematic for GPs.

Factors associated with the health care cost in older Australian women with arthritis: an application of the Andersen's Behavioural Model of Health Services Use.

OBJECTIVE: Factors associated with the utilisation of health care have not been rigorously examined in people with arthritis. The objective of this study was to examine the determinants of health care utilisation and costs in older women with arthritis using the Andersen's behavioural model as a framework. STUDY DESIGN: Longitudinal cohort study. METHODS: Participants of Surveys 3 to 5 of the Australian Longitudinal Study on Women's Health who reported arthritis were included in the study. Information about health care utilisation and unit prices were based on linked Medicare Australia data, which included prescription medicines and health services. Total health care costs of participants with arthritis were measured for the years 2002 to 2003, 2005 to 2006, and 2008 to 2009, which corresponded to the survey years. Potential explanatory variables of the health care cost and other characteristics of the participants were collected from the health surveys. Explanatory variables were grouped into predisposing characteristics, enabling factors and need variables conforming to the Andersen's Behavioural Model of Health Services Use. Longitudinal data analysis was conducted using generalized estimating equations. RESULTS: A total of 5834 observations were included for the three periods. Regression analysis results show that higher health care cost in older Australian women with arthritis was significantly associated with residing in an urban area, having supplementary health insurance coverage, more comorbid conditions, using complementary and alternative medicine, and worse physical functioning. It was also found that predisposing characteristics (such as the area of residence) and enabling factors (such as health insurance coverage) accounted for more variance in the health care cost than need variables (such as comorbid conditions). CONCLUSION: These results may indicate an inefficient and unfair allocation of subsidised health care among older Australian women with arthritis, where individuals with less enabling resources and more socio-economic disadvantages have a lower level of health care utilisation. Future research may focus on evaluating the effectiveness of policies designed to reduce excessive out-of-pocket costs and to improve equity in health care access in the older population.

Serpina3n accelerates tissue repair in a diabetic mouse model of delayed wound healing.

Chronic, non-healing wounds are a major complication of diabetes and are characterized by chronic inflammation and excessive protease activity. Although once thought to function primarily as a pro-apoptotic serine protease, granzyme B (GzmB) can also accumulate in the extracellular matrix (ECM) during chronic inflammation and cleave ECM proteins that are essential for proper wound healing, including fibronectin. We hypothesized that GzmB contributes to the pathogenesis of impaired diabetic wound healing through excessive ECM degradation. In the present study, the murine serine protease inhibitor, serpina3n (SA3N), was administered to excisional wounds created on the dorsum of genetically induced type-II diabetic mice. Wound closure was monitored and skin wound samples were collected for analyses. Wound closure, including both re-epithelialization and contraction, were significantly increased in SA3N-treated wounds. Histological and immunohistochemical analyses of SA3N-treated wounds revealed a more mature, proliferative granulation tissue phenotype as indicated by increased cell proliferation, vascularization, fibroblast maturation and differentiation, and collagen deposition. Skin homogenates from SA3N-treated wounds also exhibited greater levels of full-length intact fibronectin compared with that of vehicle wounds. In addition, GzmB-induced detachment of mouse embryonic fibroblasts correlated with a rounded and clustered phenotype that was prevented by SA3N. In summary, topical administration of SA3N accelerated wound healing. Our findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of fibronectin that is essential for normal wound closure, and that SA3N promotes granulation tissue maturation and collagen deposition.

Neurofeedback facilitation of implicit motor learning.

BACKGROUND: Mu rhythm desynchronisation via EEG-neurofeedback (NFB) has been previously been shown to induce durable motor-cortical disinhibition for at least 20 min. It was hypothesised that the presentation of a novel procedural learning task immediately after this NFB protocol would boost motor performance. METHOD: The protocol consisted of firstly activating the right primary motor cortex with a single session of Mu (8-12 Hz) suppression via NFB for a total of 30 min. Shortly after, and with their non-dominant (left) hand, subjects (n=10) performed the serial reaction time task (SRTT), which is used to assess reaction time improvement over multiple trials. During another occasion (1 week before/after), the same subjects were tested on a different sequence without prior NFB, as part of a counterbalanced control condition. RESULTS: Compared to a "cross-over" condition without NFB, subjects who received NFB immediately prior to SRTT performance exhibited a significantly faster rate of learning, reflected in a greater reduction of reaction times across blocks (p=0.02). This occurred in the absence of explicit awareness of a repeating sequence. Moreover, no significant differences were observed between conditions in error rate or reaction time variability. CONCLUSION: Our results suggest that a single NFB session may be directly used to facilitate the early acquisition of a procedural motor task, and are the first to demonstrate that neurofeedback effects could be exploited immediately after individual training sessions so as to boost behavioural performance and learning.

A hypothesis and model of reduced fetal movement as a common pathogenetic mechanism in clubfoot.

BACKGROUND: Clubfoot or Talipes equinovarus is characterised by an adducted forefoot, hindfoot varus, and ankle equinus deformity, varying in severity and ease of correction. It is one of the most common congenital defects, with a prevalence of around 1 per 1000. Ambiguity still surrounds the classification and pathogenesis of clubfoot. METHODS: A literature search was performed using Pubmed, Ovid, and the Cochrane Databases, using search terms in isolation or combination: clubfoot, Talipes equinovarus, congenital foot deformities and joint development, identified articles were further hand searched and relevant references identified. CONCLUSION: We propose that the underlying unifying factor in all cases of clubfoot is a lack of fetal movement. Fetal movement is a key developmental signal in the development of joints, and we suggest that this applies to the morphogenesis of the forefoot. Theories exist to explain specific individual features of clubfoot in certain cases and to explain experimental studies, however no common final pathway has been described. We believe that our hypothesis brings together key elements of these and will simplify understanding and classification of clubfoot.

Mental health and other clinical correlates of euthanasia attitudes in an Australian outpatient cancer population.

A majority of patients with cancer have been reported to endorse euthanasia and physician assisted suicide (PAS) in general and a substantial proportion endorse these for themselves. However, the potential influence of mental health and other clinical variables on these decisions is not well understood. This study of 228 outpatients attending an oncology clinic in Newcastle, Australia used a cross-sectional design and logistic regression modelling to examine the relationship of demographic, disease status, mental health and quality of life variables to attitudes toward euthanasia and PAS. The majority reported support for euthanasia (79%, n=179), for PAS (69%, n=158) and personal support for euthanasia/PAS (68%, n=156). However, few reported having asked their doctor for euthanasia (2%, n=5) or PAS (2%, n=5). Three outcomes were modelled: support for euthanasia was associated with active religious belief (adjusted odds ratio (AOR) 0.21, 95% CI: 0.10-0.46); support for PAS was associated with active religious belief (AOR 0.35, 95% CI: 18-0.70) and recent pain (AOR 0.87, 95% CI: 0.0.76-0.99); and personal support for euthanasia/PAS was associated with active religious belief (AOR 0.26, 95% CI: 0.14-0.48). Depression, anxiety, recent suicidal ideation, and lifetime suicide attempt were not independently associated with any of the three outcomes modelled.

Developing a musculo-skeletal screening survey for Indigenous Australians living in rural communities.

INTRODUCTION: Indigenous Australians living in rural communities experience high levels of musculoskeletal conditions that significantly impair their daily activities. Aboriginal health workers (AHWs) have a close understanding of their communities' needs and play a central role in the assessment and management of these conditions. To assist in the musculoskeletal assessment process a screening survey was collaboratively developed, trialled and evaluated for use by AHWs. METHODS: A cross-sectional survey was developed following discussions with key community informants, and a literature review for relevant survey instruments. It was piloted before being administered by AHWs and the findings compared with those of a clinical assessment conducted by musculoskeletal health professionals. The participants included 189 members of an Australian rural Indigenous community. RESULTS: The screening survey achieved face and content validity. It provided high sensitivity (above 70%) and moderately high specificity (above 60%) for measuring musculoskeletal conditions in this community. It did not achieve high enough Kappa scores when measuring agreement between the screening tool and clinical assessment. A significant correlation was, however, obtained between the most prevalent musculoskeletal condition and between reported overall pain as assessed by AHWs and chiropractors. CONCLUSIONS: The screening survey has applicability in this community and has the potential to be adapted in similar settings. Incorporating a basic range of motion and palpation assessment to localise painful anatomical sites may help to further improve the sensitivity and specificity of this instrument.

Prevalence of musculoskeletal conditions, associated pain and disability and the barriers to managing these conditions in a rural, Australian Aboriginal community.

INTRODUCTION: Internationally, musculoskeletal conditions are a major morbidity issue for Indigenous populations and the social and economic burden imposed by musculoskeletal complaints is significant. However, little is known about the prevalence and associated pain and impairment of musculoskeletal conditions among rural Indigenous Australians. METHODS: The study was conducted between January 2001 and July 2002. DESIGN: A cross-sectional research design was used. SAMPLE: Participants included 189 Indigenous members of the community, 80 of whom were randomly selected and 109 were recruited using a convenience sample. The sample included 87 males (46%) and 102 females (53%). Participants' mean age was 44 years (+/-14.8). MEASURES: The main outcome measures were sites of current pain, self-reported levels of pain, limitations to activities of daily living, and barriers to managing these conditions. PROCEDURE: Following a screening survey participants underwent a clinical examination conducted by musculoskeletal health professional trained in standardised, clinical assessment procedures. RESULTS: Lower back pain, followed by neck, head and shoulder pain were the most common conditions. Approximately 57% of participants suffered from 2 to 4 musculoskeletal conditions. The most commonly endured level of pain was 'high'. There were no significant differences between male and female participants in terms of reported levels of pain. The level of pain reported was relatively high compared with the level of associated limitation of activities of daily living. A majority of participants had suffered from their principal condition for 7 weeks or more, indicating high levels of chronicity in the community. CONCLUSION: The majority of people living in this large rural, Indigenous community have learnt to live with chronic levels of pain affecting multiple anatomical sites. Strategies such as community musculoskeletal health promotion and appropriately trained community health workers can assist the community manage this chronic burden of disability. There is scope for further study into the musculoskeletal health of both rural and urban Indigenous populations.

Aboriginal health in Aboriginal hands: development, delivery and evaluation of a training programme for Aboriginal health workers to promote the musculoskeletal health of Indigenous people living in a rural community.

CONTEXT: Indigenous Australians living in rural communities suffer from multiple musculoskeletal problems that significantly impair their activities of daily living. They commonly report physical disability and 'having learned to live with their pain'. A pilot, accredited musculoskeletal training program in the form of a sports massage course was designed and implemented in an attempt to address modifiable, commonly-presenting musculoskeletal conditions in this community. ISSUE: Sports massage was taught to 20 participant Aboriginal Health workers (AHWs) and community Elders at Durri Aboriginal Corporation, New South Wales, Australia. Sports massage was chosen as the vehicle for skills development because sport was widely valued in the community. The participants were taught a variety of theoretical and massage skills in the 2 week course using the informal 'round table' techniques developed by Booroongen Djugun College, NSW, Australia. The course was evaluated positively by participants. Because the course was developed according to community guidelines it had high cultural acceptability. LESSONS: Sports massage skills have been adapted for treatment of patients with chronic illness and stress within the community. Development of the course according to community needs was essential for acceptance, as was the active involvement of AHWs in all phases. For sustainability, such courses require appropriate funding.

Medication use among older Australian veterans and war widows.

This study aimed to review the medications used by a group of Australian war veterans and widows, to identify type and number of medications used and potential inappropriate prescribing. Label details of 4304 medications used by 887 participants were recorded and classified according to the Anatomical Therapeutic Chemical code. The median number of regular medications being used was four (interquartile range 2-7), with a median of one other medication (interquartile range 1-2) being taken as needed. Over half (53%) the participants were taking four or more regular medications. There were 26 potential interactions among 25 people. Polypharmacy was a considerable problem for this group of older Australians.

Evaluating podiatry services: testing a treatment specific measure of health status.

This study reports on the preliminary testing of a new measure designed for use alongside EQ-5D in evaluating outcomes in podiatry: the Podiatry Health Questionnaire (PHQ). Individuals aged 18 years or more, receiving podiatry services in clinic or domicilliary locations across four NHS Trusts in Yorkshire and Humberside UK took part in a questionnaire survey. Respondents reported high levels of problems on all six PHQ dimensions. Correlations suggested that the PHQ and EQ-5D were measuring distinct constructs. The levels on each dimension were well defined in terms of self-rated morbidity on the PHQ visual analogue scale (PHQvas) and the EQ-5Dvas, although PHQvas appeared to be slightly more sensitive to changes in health on the dimensions. There was a strong relationship between clinicians' Podiatry Clinical Score rating and reported symptoms for four out of six PHQ dimensions and PHQvas. The PHQ was able to distinguish respondents in terms of their self-reported morbidity in EQ-5D and in terms of their morbidity as assessed by clinicians. It is suggested that the respondent completed PHQ appears to be a useful new measure for assessing foot-related health. However, further investigation of the psychometric properties of the measure is required.

The effect of HFE mutations on serum ferritin and transferrin saturation in the Jersey population.

High frequencies of the haemochromatosis-related HFE C282Y mutation have been reported in North European populations, in which a high proportion of patients with the disease are homozygotes. However, the degree of penetrance of this genotype is unknown. We determined the HFE C282Y and H63D genotypes of 411 consenting volunteer blood donors on Jersey, and the serum ferritin and transferrin saturation levels of 204 of these volunteers. The C282Y allele frequency was found to be 8.3% in 822 chromosomes, indicating a homozygote frequency of 1/145. Consistent with this, four C282Y homozygotes were detected in 411 volunteers. As there are only 18 patients presently receiving treatment for haemochromatosis on Jersey, out of a total population of about 85000, there is a large discrepancy between the number of haemochromatosis patients and the number of C282Y homozygotes in this population. In a preliminary study of 204 consenting volunteers we found a correlation between transferrin saturation and HFE H63D/ C282Y genotype (P=0.017) and between serum ferritin and genotype (P = 0.056). We also observed elevated values of transferrin saturation in the two C282Y homozygotes assayed. These results suggest that a large proportion of the many undetected C282Y homozygotes on Jersey and in similar populations could be in the preclinical stages of haemochromatosis, and warrant investigation. However, there may be a wide variation in the expression of the condition, and a more extensive study of the level of disease penetrance encompassing a large number of hitherto undetected C282Y homozygotes is therefore imperative.

Isolating the components of activity-density for the carabid beetle Pterostichus melanarius in farmland.

The activity and density of the carabid beetle, Pterostichus melanarius, were studied over 10 weeks in a continuous mark-recapture experiment using a grid of pitfall traps spanning a hedgerow and extending approximately 30 m into two cereal fields; 1777 beetles were individually marked. The recapture rate was approximately 60% and 40% for males and females, respectively. Activity-density rose and fell four times between early June and mid August. Jolly-Seber estimates of density showed population density increasing to a single peak in late July. The mean population density in late July and August was relatively stable at approximately 0.26 m-2. Activity varied over the 10 weeks and was significantly higher during August than in June or July. The daily displacement distance frequencies, calculated from 750 male and 485 female recaptures of individually marked beetles, were distributed exponentially. Mean displacement distances were approximately 2.6 m day-1 during June and July, and 5.3 m day-1 during August. A diffusion model provided diffusion coefficients of 23.7 and 27.9 m2 day-1 for female and male beetles, respectively. The spatial distribution of P. melanarius was aggregated in patches. Spatial analysis by distance indices showed the spatial distribution of counts between successive periods of activity-density to be significantly associated. Approximately 5.75% of recaptures were from releases on the opposite side of the hedgerow. Approximately 20% of recaptures were from releases in opposite halves of the grid within the same field. The hedgerow acted as a significant barrier to dispersal between fields, with implications for the metapopulation structure of the species.

A randomized controlled trial of sedation in the critically ill.

A randomized controlled trial comparing: a) a combination of oral chloral hydrate and promethazine to b) a continuous intravenous midazolam infusion, for maintenance sedation in critically ill children, was carried out. The level of sedation was assessed four hourly using a specifically devized sedation scale. Forty-four children entered the study of whom two were subsequently excluded. The number of satisfactory assessments (desired and actual levels of sedation equal) was significantly greater in the chloral hydrate and promethazine group (Chi-squared P < 0.01; confidence intervals of the difference 0.06 to 0.20). The number of assessments at level 5 on the sedation scale (patient restless/ distressed) was significantly greater in the midazolam group (Chi-squared P < 0.05). The total number of satisfactory assessments in the two groups were only 61 and 48% respectively, suggesting that sedation can be considerably improved. Chloral hydrate and promethazine are more effective than midazolam as maintenance sedation in critically ill children. It is possible to prospectively study the efficacy of sedative drugs in critically ill children.