Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals-a cluster randomised controlled trial.

BACKGROUND: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. METHODS: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. DISCUSSION: This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.

Microstructurally-based constitutive modelling of the skin - Linking intrinsic ageing to microstructural parameters.

A multiphasic constitutive model of the skin that implicitly accounts for the process of intrinsic (i.e. chronological) ageing via variation of the constitutive parameters is proposed. The structurally-motivated constitutive formulation features distinct mechanical contributions from collagen and elastin fibres. The central hypothesis underpinning this study is that the effects of ageing on the mechanical properties of the tissue are directly linked to alterations in the microstructural characteristics of the collagen and elastin networks. Constitutive parameters in the model, corresponding to different ages, are identified from published experimental data on bulge tests of human skin. The numerical results demonstrate that degradation of the elastin meshwork and variations in anisotropy of the collagen network are plausible mechanisms to explain ageing in terms of macroscopic tissue stiffening. Whereas alterations in elastin affect the low-modulus region of the skin stress-strain curve, those related to collagen have an impact on the linear region.

Thermoelastic modelling of the skin at finite deformations.

The modelling and computation of the coupled thermal and mechanical response of human skin at finite deformations is considered. The model extends current thermal models to account for thermally- and mechanically-induced deformations. Details of the solution of the highly nonlinear system of governing equations using the finite element method are presented. A representative numerical example illustrates the importance of considering the coupled response for the problem of a rigid, hot indenter in contact with the skin.

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.

The Long and Short of Genetic Counseling Summary Letters: A Case-control Study.

Genetic counseling summary letters are intended to reinforce information received during genetic counseling, but little information is available on patient/family responses to these letters. We conducted a case-control study to assess the effectiveness of two different letter formats. Parents of children receiving a new diagnosis were enrolled. The control group (n = 85) received a genetic counseling summary letter in a narrative format, 4-5 pages in length. After the control enrollment period, genetic counselors were trained by a professional medical writer to develop a concise letter format. The case group (n = 64) received a concise letter, approximately 1.5 pages in length, utilizing simple sentences, lay terms, and lists/bullet points. Parents completed a survey 4 weeks after the visit to rate the letter's format, usefulness, and their emotional reaction. Results show that parents in the case group rated the letter more highly (p = 0.023), particularly in the emotional response dimension (rating changes in anxiety, depression, fear, ability to cope, and confidence in response to the letter). Parents in the case group also rated the genetic counseling session more highly (p = 0.039). In the control group, parents without a college degree were more likely to rate the letter as too long and the level of medical detail as too high. In the case group, no significant differences were seen between parents with or without a college degree. These data suggest that a short genetic counseling summary letter is rated higher by parents, and is particularly associated with a more positive emotional reaction. A short letter format highlighting the basic facts related to the genetic condition may be more useful to parents of diverse educational backgrounds, and may support a positive emotional adaptation at the time of a new diagnosis. Genetic counselors may benefit from specific instruction in medical and educational writing.

Reliability of skin-type self-assessment: agreement of adolescents' repeated Fitzpatrick skin phototype classification ratings during a cohort study.

BACKGROUND: The Fitzpatrick Skin Phototype Classification (FSPC) is the most commonly used measure of skin type. In questionnaire-based surveys, self-rated FSPC is often used as a measure of respondents' skin type. OBJECTIVE: The objective of this analysis was to assess test-retest reliability of the self-rated FSPC within a 12-month cohort study that examined the psychological sequelae of acne. METHODS: Participants were students aged 14-17 years in four Australian secondary schools; two-government system schools and two private schools. The primary outcomes were a number of psychological measures. The FSPC was assessed by a single concise questionnaire item. Test-retest agreement (as measured by quadratic weighted kappa) of participants' self-rated FSPC at three time-points (baseline, 6 and 12 months) was calculated. RESULTS: Of the 244 participating students, 209 students (86%) completed all three rounds of data collection. A further 26 students (11%) completed two rounds. Quadratic weighted kappa for Rounds 1 and 2 was 0.757 (95% CI 0.663-0.831). For Rounds 2 and 3 it was 0.805 (95% CI 0.659-0.893). Between Rounds 1 and 3 it was 0.767 (95% CI 0.698-0.832). This represents good-to-very-good agreement. Skin type was retained as an independent variable in 8 of the 16 regression models built to explain psychological outcomes in this study. CONCLUSION: Skin type appears to be a significant factor in psychological morbidity in acne. The FSPC is a reliable method for assessing skin phenotype, even when elicited via a concise questionnaire item suitable for assessing skin type as a potential confounder in studies of other outcome factors.

Spatial and temporal operation of the Scotia Sea ecosystem: a review of large-scale links in a krill centred food web.

The Scotia Sea ecosystem is a major component of the circumpolar Southern Ocean system, where productivity and predator demand for prey are high. The eastward-flowing Antarctic Circumpolar Current (ACC) and waters from the Weddell-Scotia Confluence dominate the physics of the Scotia Sea, leading to a strong advective flow, intense eddy activity and mixing. There is also strong seasonality, manifest by the changing irradiance and sea ice cover, which leads to shorter summers in the south. Summer phytoplankton blooms, which at times can cover an area of more than 0.5 million km2, probably result from the mixing of micronutrients into surface waters through the flow of the ACC over the Scotia Arc. This production is consumed by a range of species including Antarctic krill, which are the major prey item of large seabird and marine mammal populations. The flow of the ACC is steered north by the Scotia Arc, pushing polar water to lower latitudes, carrying with it krill during spring and summer, which subsidize food webs around South Georgia and the northern Scotia Arc. There is also marked interannual variability in winter sea ice distribution and sea surface temperatures that is linked to southern hemisphere-scale climate processes such as the El Niño-Southern Oscillation. This variation affects regional primary and secondary production and influences biogeochemical cycles. It also affects krill population dynamics and dispersal, which in turn impacts higher trophic level predator foraging, breeding performance and population dynamics. The ecosystem has also been highly perturbed as a result of harvesting over the last two centuries and significant ecological changes have also occurred in response to rapid regional warming during the second half of the twentieth century. This combination of historical perturbation and rapid regional change highlights that the Scotia Sea ecosystem is likely to show significant change over the next two to three decades, which may result in major ecological shifts.

Definition of needle length required for intramuscular deltoid injection in elderly adults: an ultrasonographic study.

An ultrasound study in elderly patients (> or =65 years) showed that body mass index (BMI) was strongly correlated with deltoid subcutaneous layer thickness in males (r = 0.69 dominant arm, 0.71 non-dominant arm) and females (r = 0.79 both arms). Females with the same BMI as males had significantly thicker subcutaneous layers (p = 0.0001) and thinner muscle layers (p = 0.0003). Minimal needle length required for deltoid intramuscular injection where the needle was entered at 90 degrees to the long axis of the humerus was defined by BMI group. In all BMI males and females, BMI <35, intramuscular injection could be achieved with a 25 mm long needle, whilst in females BMI >35, a 32 mm long needle is required. These data will be used in studies to resolve the clinical equipoise regarding the optimal route of administration (intramuscular versus subcutaneous) of vaccines (e.g. influenza and pneumococcal vaccines), which are provided through public health programs for the elderly.

The effectiveness of nutrition counselling by Australian General Practitioners.

OBJECTIVE: To determine whether General Practitioners (GPs) consider or provide nutrition counselling for hypertension, diabetes, lipid disorders, ischaemic heart disease (IHD), overweight or obesity, and whether GPs include assessment of the patient's usual diet, assessment of the patient's readiness to change their diet, provision and discussion of nutrition leaflets when counselling. DESIGN: A self-completed questionnaire. SETTING: New South Wales, Australia. SUBJECTS: A total of 399 GPs were surveyed using a division mailing list. METHODS: Questionnaires were distributed in May 2004 with two reminders provided at four-weekly intervals. RESULTS: Of the 399 GPs, 28 no longer practiced at the address while nine were on extended leave. Of the remaining 362, 50% responded, 5% declining to participate, while 163 (45%) completed the questionnaire. GPs were less likely to strongly agree to consider nutrition for hypertension (37%), IHD (61%) and overweight (68%), than diabetes (86%), lipid disorders (82%) and obesity (83%). They were also less likely to strongly agree to provide nutrition for hypertension (22%), IHD (46%) and overweight (45%), than diabetes (79%), lipid disorders (71%) and obesity (68%). In total, 97% of GPs provided some nutrition counselling, with 66% 'often' assessing the patients diet and 59% 'often' assessing the patient's readiness to change their diet. In total, 45% were unaware of stage of change behaviour theory. A total of 85% used nutrition leaflets and 59% 'often' discussed these with their patients. CONCLUSIONS: Determining what are the barriers to nutrition counselling for hypertension, IHD and overweight is urgently needed. Educating GPs on stage of change behaviour theory could increase the efficacy of the counselling provided.

The management of dementia in general practice. A field test of guidelines.

INTRODUCTION: Guidelines for the management of dementia in non-institutionalized patients living in the community were developed by a broadly representative group. We assessed their usefulness. METHOD: The draft guidelines included emphasis on psychosocial issues. They were field tested by 17 general practitioners with 119 dementia patients. RESULTS: There was a high prevalence of comorbidity in the patients and frequent psychosocial issues in their management that were often not addressed. The guidelines were rated as very helpful for at least one aspect of care for 50% of the patients. DISCUSSION: The guidelines were found to be useful to GPs.

Research capacity building in general practice. The new Australian scene.

BACKGROUND: Primary care research needs strengthening. The Commonwealth Government Department of Health and Aged Care has recently funded the university departments of general practice and rural health to build research capacity in primary care. OBJECTIVE: To explore issues surrounding building primary care research capacity, as well as looking at barriers to research capacity building and ways of overcoming them. DISCUSSION: New funding provides many opportunities for increasing research capacity in primary health care areas. Different institutions will select those methods that are best suited to their skills and the requirements of their area.

Electromagnetic field-induced stimulation of Bruton's tyrosine kinase.

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-gamma 2 (PLC-gamma2), leading to increased inositol phospholipid turnover. PLC-gamma2 activation in EMF-stimulated cells is mediated by stimulation of the Bruton's tyrosine kinase (BTK), a member of the Src-related TEC family of protein tyrosine kinases, which acts downstream of LYN kinase and upstream of PLC-gamma2. B-cells rendered BTK-deficient by targeted disruption of the btk gene did not show enhanced PLC-gamma2 activation in response to EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) human btk gene into BTK-deficient B-cells restored their EMF responsiveness. Thus, BTK exerts a pivotal and mandatory function in initiation of EMF-induced signaling cascades in B-cells.

Stimulation of Src family protein-tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cgamma2 activation in lymphoma B cells exposed to low energy electromagnetic fields.

Here, we present evidence that exposure of DT40 lymphoma B cells to low energy electromagnetic field (EMF) results in a tyrosine kinase-dependent activation of phospholipase Cgamma2 (PLC-gamma2) leading to increased inositol phospholipid turnover. B cells rendered PLC-gamma2-deficient by targeted disruption of the PLC-gamma2 gene as well as PLC-gamma2-deficient cells reconstituted with Src homology domain 2 (SH2) domain mutant PLC-gamma2 did not show any increase in inositol-1,4,5-trisphosphate levels after EMF exposure, providing direct evidence that PLC-gamma2 is responsible for EMF-induced stimulation of inositol phospholipid turnover, and its SH2 domains are essential for this function. B cells rendered SYK-deficient by targeted disruption of the syk gene did not show PLC-gamma2 activation in response to EMF exposure. The C-terminal SH2 domain of SYK kinase is essential for its ability to activate PLC-gamma2. SYK-deficient cells reconstituted with a C-terminal SH2 domain mutant syk gene failed to elicit increased inositol phospholipid turnover after EMF exposure, whereas SYK-deficient cells reconstituted with an N-terminal SH2 domain mutant syk gene showed a normal EMF response. LYN kinase is essential for the initiation of this biochemical signaling cascade. Lymphoma B cells rendered LYN-deficient through targeted disruption of the lyn gene did not elicit enhanced inositol phospholipid turnover after EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) mouse fyn gene into LYN-deficient B cells restored their EMF responsiveness. B cells reconstituted with a SH2 domain mutant fyn gene showed a normal EMF response, whereas no increase in inositol phospholipid turnover in response to EMF was noticed in LYN-deficient cells reconstituted with a SH3 domain mutant fyn gene. Taken together, these results indicate that EMF-induced PLC-gamma2 activation is mediated by LYN-regulated stimulation of SYK, which acts downstream of LYN kinase and upstream of PLC-gamma2.

Stable-carbon-isotope composition of Fatty acids in hydrothermal vent mussels containing methanotrophic and thiotrophic bacterial endosymbionts.

Fatty acid biomarker analysis coupled with gas chromatography-isotope ratio mass spectrometry was used to confirm the presence of methanotrophic and thiotrophic bacterial endosymbionts in the tissues of a hydrothermal vent mussel (Bathymodiolus sp.), collected from the Menez Gwen vent field on the mid-Atlantic ridge. Monounsaturated (n-8) fatty acids, which are diagnostic of methanotrophic bacteria, were detected in all three types of tissues examined (gill, posterior adductor, and mantle), although levels were highest in gill tissues where the bacteria were found. Stable-carbon-isotope compositions (delta-C per mille relative to that of Peedee belemnite) of fatty acids for all three tissues ranged from -24.9 to -34.9 per thousand, which encompasses the range predicted for both thiotroph- and methanotroph-based nutrition. The data suggest that these thio- and methanotrophic bacterial endosymbionts are equally important in the nutrition of the vent mussel at this particular vent site.

News from the divisions: diabetes shared care.

It is not surprising that diabetes care has been a very active area for divisional projects and activities. Diabetes is prevalent in the community (up to one million Australians) and in general practice (1% of GP encounters). Optimal cost-effective diabetes management involves collaboration between general practice and public and private health services--one of the purposes for which divisions were created. Because diabetes is a multisystem chronic disease requiring multi-disciplinary interventions, it has also been a model for applying the health outcomes approach in general practice, especially in New South Wales.

Sleep-disordered breathing in elderly people and subjective sleep-wake disturbance.

Sleep-disordered breathing and subjective reports of sleep-wake disturbances are both common in elderly people but previous studies investigating the relationship between the two have produced uncertain results. We hypothesized that there is no relationship between sleep-disordered breathing and subjective reports of sleep-wake disturbance. Ninety-three random-sampled retirement-village residents, mean age 77.6 years, were monitored overnight with a portable microprocessor-based system. The respiratory disturbance index (RDI) was used as a measure of sleep-disordered breathing. Subjects were interviewed regarding sleep-wake patterns and snoring history and the Mini Mental State Examination, Geriatric Depression Scale and Nelson Adult Reading Test were administered. The sleep-wake responses were entered into a principal components analysis. Two components, reflecting night-time and daytime disturbance, accounted for 34% of the variance. Multiple regression analyses were performed using RDI as a continuous dependent variable, and three predictor variables, night-time, and daytime disturbance and history of snoring. Together, these variables accounted for only 2% of the variance. We conclude there is no relationship between mild and moderate sleep-disordered breathing and subjective sleep-wake disturbance in this population.