Complex interventions for improving independent living and quality of life amongst community-dwelling older adults: a systematic review and meta-analysis.

BACKGROUND: community-based complex interventions for older adults have a variety of names, including Comprehensive Geriatric Assessment, but often share core components such as holistic needs assessment and care planning. OBJECTIVE: to summarise evidence for the components and effectiveness of community-based complex interventions for improving older adults' independent living and quality of life (QoL). METHODS: we searched nine databases and trial registries to February 2022 for randomised controlled trials comparing complex interventions to usual care. Primary outcomes included living at home and QoL. Secondary outcomes included mortality, hospitalisation, institutionalisation, cognitive function and functional status. We pooled data using risk ratios (RRs) or standardised mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: we included 50 trials of mostly moderate quality. Most reported using holistic assessment (94%) and care planning (90%). Twenty-seven (54%) involved multidisciplinary care, with 29.6% delivered mainly by primary care teams without geriatricians. Nurses were the most frequent care coordinators. Complex interventions increased the likelihood of living at home (RR 1.05; 95% CI 1.00-1.10; moderate-quality evidence) but did not affect QoL. Supported by high-quality evidence, they reduced mortality (RR 0.86; 95% CI 0.77-0.96), enhanced cognitive function (SMD 0.12; 95% CI 0.02-0.22) and improved instrumental activities of daily living (ADLs) (SMD 0.11; 95% CI 0.01-0.21) and combined basic/instrumental ADLs (SMD 0.08; 95% CI 0.03-0.13). CONCLUSIONS: complex interventions involving holistic assessment and care planning increased the chance of living at home, reduced mortality and improved cognitive function and some ADLs.

Podiatry interventions to prevent falls in older people: a systematic review and meta-analysis.

BACKGROUND: foot problems are independent risk factors for falls in older people. Podiatrists diagnose and treat a wide range of problems affecting the feet, ankles and lower limbs. However, the effectiveness of podiatry interventions to prevent falls in older people is unknown. This systematic review examined podiatry interventions for falls prevention delivered in the community and in care homes. METHODS: systematic review and meta-analysis. We searched multiple electronic databases with no language restrictions. Randomised or quasi-randomised-controlled trials documenting podiatry interventions in older people (aged 60+) were included. Two reviewers independently applied selection criteria and assessed methodological quality using the Cochrane Risk of Bias tool. TiDieR guidelines guided data extraction and where suitable statistical summary data were available, we combined the selected outcome data in pooled meta-analyses. RESULTS: from 35,857 titles and 5,201 screened abstracts, nine studies involving 6,502 participants (range 40-3,727) met the inclusion criteria. Interventions were single component podiatry (two studies), multifaceted podiatry (three studies), or multifactorial involving other components and referral to podiatry component (four studies). Seven studies were conducted in the community and two in care homes. Quality assessment showed overall low risk for selection bias, but unclear or high risk of detection bias in 4/9 studies. Combining falls rate data showed significant effects for multifaceted podiatry interventions compared to usual care (falls rate ratio 0.77 [95% CI 0.61, 0.99]); and multifactorial interventions including podiatry (falls rate ratio: 0.73 [95% CI 0.54, 0.98]). Single component podiatry interventions demonstrated no significant effects on falls rate. CONCLUSIONS: multifaceted podiatry interventions and multifactorial interventions involving referral to podiatry produce significant reductions in falls rate. The effect of multi-component podiatry interventions and of podiatry within multifactorial interventions in care homes is unknown and requires further trial data. PROSPERO REGISTRATION NUMBER: CRD42017068300.

Functional analysis of the Helicobacter pullorum N-linked protein glycosylation system.

N-linked protein glycosylation systems operate in species from all three domains of life. The model bacterial N-linked glycosylation system from Campylobacter jejuni is encoded by pgl genes present at a single chromosomal locus. This gene cluster includes the pglB oligosaccharyltransferase responsible for transfer of glycan from lipid carrier to protein. Although all genomes from species of the Campylobacter genus contain a pgl locus, among the related Helicobacter genus only three evolutionarily related species (H. pullorum, H. canadensis and H. winghamensis) potentially encode N-linked protein glycosylation systems. Helicobacter putative pgl genes are scattered in five chromosomal loci and include two putative oligosaccharyltransferase-encoding pglB genes per genome. We have previously demonstrated the in vitro N-linked glycosylation activity of H. pullorum resulting in transfer of a pentasaccharide to a peptide at asparagine within the sequon (D/E)XNXS/T. In this study, we identified the first H. pullorum N-linked glycoprotein, termed HgpA. Production of histidine-tagged HgpA in the background of insertional knockout mutants of H. pullorum pgl/wbp genes followed by analysis of HgpA glycan structures demonstrated the role of individual gene products in the PglB1-dependent N-linked protein glycosylation pathway. Glycopeptide purification by zwitterionic-hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry identified six glycosites from five H. pullorum proteins, which was consistent with proteins reactive with a polyclonal antiserum generated against glycosylated HgpA. This study demonstrates functioning of a H. pullorum N-linked general protein glycosylation system.

Serum sodium level variability as a prognosticator in older adults.

Our aim was to explore biological variation of serum sodium levels as a method of quantifying health risk in older adults. We investigated whether dynamic changes in serum sodium levels could provide additional prognostic information to standard predictors of mortality in older people. Analysis of routinely collected clinical datasets containing information on demographics, hospitalisation, biochemistry, haematology and physical function for Dundee in-patient rehabilitation services, between 1999 and 2011. Older people admitted to inpatient rehabilitation following an acute medical or surgical hospitalisation. Five dynamic measures of sodium levels homeostasis - minimum, maximum, standard deviation, and minimum and maximum deviation from mean - were derived for each individual, using biochemistry data from the year preceding their rehabilitation discharge. Cox regression models tested for associations with time to death. Covariates included age, sex, discharge Barthel score, co-morbid diagnoses, haemoglobin, albumin and eGFR. 3021 patients were included (mean age 84 years, 1776 (58.8%) females). 1651 (54.7%) patients experienced hyponatraemia and 446 (14.8%) became hypernatraemic. Mean sodium was correlated with all mean, minimum and SD of sodium. Kaplan-Meier survival curves showed that those without sodium perturbations had the best mortality outcomes, whilst those with both hyponatremia and hypernatremia had the worst. Multivariate Cox regression showed that standard deviation and hypernatraemia were significant predictors of death in non-adjusted models, but not fully adjusted models. All dynamic measures of dysnatraemia were associated with increased mortality risk, but failed to add predictive value to established static measures after adjusting for covariates.

Association between kidney function, rehabilitation outcome, and survival in older patients discharged from inpatient rehabilitation.

BACKGROUND: Chronic kidney disease (CKD) is common in older people, but it is unclear if it affects survival and rehabilitation outcomes independent of comorbid conditions and physical function in this population. STUDY DESIGN: Cohort analysis of prospective, routinely collected, linked clinical data sets. SETTING & PARTICIPANTS: Patients discharged from a single inpatient geriatric rehabilitation center over a 12-year period. PREDICTORS: Admission estimated glomerular filtration rate (eGFR) category as a predictor of improvement in the 20-point Barthel score (activities of daily living measure) during rehabilitation; discharge eGFR category and Barthel score as predictors of survival postdischarge. OUTCOMES: Survival postdischarge was modeled using Cox regression analyses, unadjusted and adjusted for age, sex, morbidities (ischemic heart disease, chronic obstructive pulmonary disease, stroke, diabetes, and heart failure), Barthel score and eGFR category on discharge, and serum calcium, hemoglobin, and albumin levels. The effect of admission eGFR category on change in Barthel score during admission was modeled using analysis of covariance, adjusted for admission, Barthel score, and comorbid conditions. RESULTS: 3,012 patients were included; mean age, 84 years. 2,394 patients died during a mean follow-up of 8.3 years. Compared with patients with eGFR of 60 to 89mL/min/1.73m(2), adjusted HRs for death were 1.26 (95% CI, 1.13-1.40), 1.45 (95% CI, 1.29-1.63), and 1.68 (95% CI, 1.42-1.99) for eGFR categories of 45 to 59, 30 to 44, and <30mL/min/1.73m(2), respectively. The relationship between discharge Barthel score and survival was similar within each discharge eGFR category (HRs of 0.95, 0.93, 0.92, 0.95, and 0.90 per Barthel score point within eGFR categories of ≥90, 60-89, 45-59, 30-44, and <30mL/min/1.73m(2); P for interaction = 0.2). Similar improvements in Barthel score between admission and discharge were seen for each admission eGFR category. LIMITATIONS: Single-center study using routinely collected clinical data. CONCLUSIONS: eGFR category and Barthel score are independent risk markers for survival in older rehabilitation patients, but advanced CKD does not preclude successful rehabilitation.

GP-led adapted comprehensive geriatric assessment for frail older people: a multi-methods evaluation of the 'Living Well Assessment' quality improvement project in Scotland.

BACKGROUND: Evidence to support comprehensive geriatric assessment (CGA) in primary care for frail older people is limited. AIM: To evaluate a GP-led adapted CGA quality improvement project. DESIGN & SETTING: Multi-methods evaluation in a large practice in Midlothian in Scotland. METHOD: The intervention was conducted by 10 GPs in a practice of approximately 11 000 patients, initially in the patient's home, and then remotely (by telephone or video consultation) during the COVID-19 pandemic. Evaluation included a patient questionnaire, and qualitative interviews with GPs delivering the Living Well Assessment (LWA), analysed by thematic analysis. RESULTS: A total of 165/220 (75%) patients responded to the survey, of which 86% reported a 'very good experience' of the LWA. The method of delivery did not significantly influence this although most (58%) stated a preference for face-to-face consultation. For the 31% who preferred remote LWA, most (23%) preferred telephone to video consultation (8%). Problems in remote consultations related to technical issues (video), poor vision (video), or deafness (telephone or video). GPs felt that home-based LWAs had real benefits but switching to remote during the pandemic had proven feasible. Concerns included potential increase in GP workload owing to the LWA and whether it was an efficient use of GPs' time. CONCLUSION: GP-led adapted CGA was feasible in a large practice, even during the pandemic, and highly valued by frail patients. Questions regarding efficient use of GPs' time, effectiveness in terms of important patient outcomes and impact, and cost-effectiveness, requires further investigation in a larger study.

A comparative overview of health and social care policy for older people in England and Scotland, United Kingdom (UK).

BACKGROUND: Responsibility for health and social care was devolved to Scotland in 1999 with evidence of diverging policy and organisation of care compared to England. This paper provides a comparative overview of major health and social care policies in England and Scotland published between 2011 and 2023 relating to the care of older people. METHODS: We searched United Kingdom (UK) and Scotland government websites for macro-level policy documents between 2011 and 2023 relating to the health and social care of older people (aged 65+). Data were extracted and emergent themes were summarised according to Donabedian's structure-process-outcome model. RESULTS: We reviewed 27 policies in England and 28 in Scotland. Four main policy themes emerged that were common to both countries. Two related to the structure of care: integration of care and adult social care reform. Two related to service delivery/processes of care: prevention and supported self-management and improving mental health care. Cross-cutting themes included person-centred care, addressing health inequalities, promoting use of technology, and improving outcomes. CONCLUSION: Despite differences in the structure of care, including more competition, financial incentivization, and consumer-based care in England compared to Scotland, there are similarities in policy vision around delivery/processes of care (e.g. person-centred care) and performance and patient outcomes. Lack of UK-wide health and social care datasets hinders evaluation of policies and comparison of outcomes between both countries.

Loneliness and social isolation causal association with health-related lifestyle risk in older adults: a systematic review and meta-analysis protocol.

BACKGROUND: The health impacts of loneliness and social isolation among older adults are widely acknowledged. Despite this, there is no consensus on the possible causal nature of this relationship, which could undermine effectiveness of interventions. One body of thought is that loneliness and social isolation affect health-related behaviours to indirectly damage health. However, there has not been any systematic assessment of the association between loneliness and social isolation and health-related behaviours which considers the possible impact from confounding factors and the causal direction of this association. METHODS/DESIGN: The research will comprise a systematic review and meta-analysis to address the evidence gap. EMBASE, MEDLINE, PSYCINFO, CINAHL, SocIndex, Scopus and Web of Science will be systematically searched for quantitative observational studies considering an association between loneliness/social isolation and key health-related behaviours in older adults. Two reviewers will independently check the study titles and abstracts for eligibility. Included studies will be critically appraised using Newcastle-Ottawa Scale by the lead author and checked by the second reviewer. Discrepancies in eligibility or quality assessment will be resolved via discussion or referral to a third reviewer. Results will be synthesised and reported in accordance with the Centre for Reviews and Dissemination (CRD) guidelines. This will be in the form of a descriptive summary, risk of bias assessment together with a meta-analysis and sub-group analyses (for covariate adjusted results) where sufficient heterogeneity of results is established. Finally, any associations identified will be analysed using the Bradford-Hill criteria to explore causal relationships which, if they exist, will be reported by means of a computed causations score. DISCUSSION: This review aims to assess the extent and causal nature of associations between loneliness/social isolation and health-related behaviours among older adults. This data will provide a comprehensive overview of the quality of the evidence base to inform stakeholders in tackling the growing public health challenges arising from loneliness/social isolation in ageing populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017020845.

Effectiveness of Motivational Interviewing on adult behaviour change in health and social care settings: A systematic review of reviews.

BACKGROUND: The challenge of addressing unhealthy lifestyle choice is of global concern. Motivational Interviewing has been widely implemented to help people change their behaviour, but it is unclear for whom it is most beneficial. This overview aims to appraise and synthesise the review evidence for the effectiveness of Motivational Interviewing on health behaviour of adults in health and social care settings. METHODS: A systematic review of reviews. Methods were pre-specified and documented in a protocol (PROSPERO-CRD42016049278). We systematically searched 7 electronic databases: CDSR; DARE; PROSPERO; MEDLINE; CINAHL; AMED and PsycINFO from 2000 to May 2018. Two reviewers applied pre-defined selection criteria, extracted data using TIDIER guidelines and assessed methodological quality using the ROBIS tool. We used GRADE criteria to rate the strength of the evidence for reviews including meta-analyses. FINDINGS: Searches identified 5222 records. One hundred and four reviews, including 39 meta-analyses met the inclusion criteria. Most meta-analysis evidence was graded as low or very low (128/155). Moderate quality evidence for mainly short term (<6 months) statistically significant small beneficial effects of Motivational Interviewing were found in 11 of 155 (7%) of meta-analysis comparisons. These outcomes include reducing binge drinking, frequency and quantity of alcohol consumption, substance abuse in people with dependency or addiction, and increasing physical activity participation. CONCLUSIONS: We have created a comprehensive map of reviews relating to Motivational Interviewing to signpost stakeholders to the best available evidence. More high quality research is needed to be confident about the effectiveness of Motivational Interviewing. We identified a large volume of low quality evidence and many areas of overlapping research. To avoid research waste, it is vital for researchers to be aware of existing research, and the implications arising from that research. In the case of Motivational Interviewing issues relating to monitoring and reporting fidelity of interventions need to be addressed.

Tumor endothelial marker 8 promotes cancer progression and metastasis.

Every year more than 8 million people suffer from cancer-related deaths worldwide [1]. Metastasis, the spread of cancer to distant sites, accounts for 90% of these deaths. A promising target for blocking tumor progression, without causing severe side effects [2], is Tumor Endothelial Marker 8 (TEM8), an integrin-like cell surface protein expressed predominantly in the tumor endothelium and in cancer cells [3, 4]. Here, we have investigated the role of TEM8 in cancer progression, angiogenesis and metastasis in invasive breast cancer, and validated the main findings and important results in colorectal cancer. We show that the loss of TEM8 in cancer cells results in inhibition of cancer progression, reduction in tumor angiogenesis and reduced metastatic burden in breast cancer mouse models. Furthermore, we show that TEM8 regulates cancer progression by affecting the expression levels of cell cycle-related genes. Taken together, our findings may have broad clinical and therapeutic potential for breast and colorectal primary tumor and metastasis treatment by targeting TEM8.

Association between bisphosphonate therapy and outcomes from rehabilitation in older people.

BACKGROUND: Bisphosphonate therapy may have actions beyond bone, including effects on cardiovascular, immune and muscle function. We tested whether bisphosphonate treatment is associated with improved outcomes in older people undergoing inpatient rehabilitation. METHODS: Analysis of prospectively collected, linked routine clinical datasets. Participants were divided into never users of bisphosphonates, use prior to rehabilitation only, use after rehabilitation only, and current users (use before and after rehabilitation). We calculated change in 20-point Barthel scores during rehabilitation, adjusting for comorbid disease and laboratory data using multivariable regression analysis. Cox regression analyses were performed to analyse the association between bisphosphonate use and time to death or hospitalisation. RESULTS: 2797 patients were included in the analysis. Current bisphosphonate users showed greater improvement in Barthel score during rehabilitation than non-users (5.0 points [95%CI 4.3-5.7] vs 3.8 [95%CI 3.6-3.9]), but no difference compared to those receiving bisphosphonates only after discharge (5.1 [95%CI 4.6-5.5]). Previous bisphosphonate use was significantly associated with time to death (adjusted hazard ratio 1.41 [95%CI 1.15-1.73]) but less strongly with time to combined endpoint of hospitalisation or death (adjusted hazard ratio 1.18 [95%CI 0.98-1.48]). Use after discharge from rehabilitation was associated with reduced risk of death (adjusted hazard ratio 0.64 [95%CI 0.55-0.73]; hazard ratio per year of bisphosphonate prescription 0.98 [95%CI 0.97-0.99]). CONCLUSION: Bisphosphonate use is unlikely to be causally associated with improved physical function in older people, but continuing use may be associated with lower risk of death.

Promotion of physical activity interventions for community dwelling older adults: A systematic review of reviews.

OBJECTIVES: While there is strong evidence that regular participation in physical activity (PA) brings numerous health benefits to older adults, and interventions to effectively promote PA are being developed and tested, the characteristics and components of the most effective interventions remain unclear. This systematically conducted review of systematic reviews evaluated the effects and characteristics of PA promotion interventions aimed at community dwelling people over 50 years old. METHODS: Major databases were searched for reviews from January 1990 to May 2015. TIDieR guidelines aided data extraction and the ROBIS tool was used to assess the risk of bias. Primary outcomes were objective and self-reported levels of PA. Indicators of psychological wellbeing and participation rates were secondary outcomes. RESULTS: Of 1284 records identified, 19 reviews met inclusion criteria and eight included meta-analyses. Interventions typically incorporated behaviour change techniques (BCTs) and were delivered as face-to-face, remote, group, individual or as combined interventions. Despite their heterogeneity, interventions often resulted in sustained improvements in PA over the study period, typically at 12 months, and led to improvements in general wellbeing. However, ways to ensure effective maintenance beyond one year are unclear. Certain intervention components were more clearly associated with positive effects (e.g. tailoring promotion strategy with combination of cognitive and behavioural elements, low to moderate intensity activity recommended). We found no evidence that certain other intervention characteristics were superior in achieving positive outcomes (e.g. mode of delivery, setting, professional background of the intervention provider, type of PA recommended). CONCLUSION: The evidence suggests that interventions to promote PA among older adults are generally effective but there is uncertainty around the most beneficial intervention components. There are indications that purely cognitive strategies and BCTs might be less suitable for older adults than motivators more meaningful to them, including social and environmental support, and enjoyment coming from being physically active. A whole system-oriented approach is required that is tailored to meet the needs of older adults and aligned with social, individual and environmental factors.

Association between allopurinol use and hip fracture in older patients.

BACKGROUND: Allopurinol reduces oxidative stress and interacts with purinergic signalling systems important in bone metabolism and muscle function. We assessed whether allopurinol use was associated with a reduced incidence of hip fracture in older people. METHODS: Analysis of prospective, routinely-collected health and social care data on patients undergoing health and social work assessment in a single geographical area over a 12year period. Exposure to allopurinol was derived from linked community prescribing data, and hospitalisation for hip fracture and comorbid disease was derived from linked hospitalisation data. Fine and Gray modelling was used to model time to hip fracture accounting for the competing risk of death, incorporating previous use of allopurinol, cumulative exposure to allopurinol as a time dependent variable, and covariate adjustments. RESULTS: 17,308 patients were alive at the time of first social work assessment without previous hip fracture; the mean age was 73years. 10,171 (59%) were female, and 1155 (8%) had at least one exposure to allopurinol. 618 (3.6%) sustained a hip fracture, and 4226 (24%) died during a mean follow-up of 7.2years. In fully-adjusted analyses, each year of allopurinol exposure conferred a hazard ratio of 1.01 (95% CI 0.99, 1.02; p=0.37) for hip fracture and 1.00 (0.99, 1.01; p=0.47) for death. Previous use of allopurinol conferred a hazard ratio of 0.76 (0.45, 1.26; p=0.28) for hip fracture and 1.13 (0.99, 1.29; p=0.07) for death. CONCLUSION: Greater cumulative use of allopurinol was not associated with a reduced risk of hip fracture or death in this cohort.

Interventions for sustained healthcare professional behaviour change: a protocol for an overview of reviews.

BACKGROUND: Failure to successfully implement and sustain change over the long term continues to be a major problem in health and social care. Translating evidence into routine clinical practice is notoriously complex, and it is recognised that to implement new evidence-based interventions and sustain them over time, professional behaviour needs to change accordingly. A number of theories and frameworks have been developed to support behaviour change among health and social care professionals, and models of sustainability are emerging, but few have translated into valid and reliable interventions. The long-term success of healthcare professional behavioural change interventions is variable, and the characteristics of successful interventions unclear. Previous reviews have synthesised the evidence for behaviour change, but none have focused on sustainability. In addition, multiple overlapping reviews have reported inconsistent results, which do not aid translation of evidence into practice. Overviews of reviews can provide accessible succinct summaries of evidence and address barriers to evidence-based practice. We aim to compile an overview of reviews, identifying, appraising and synthesising evidence relating to sustained social and healthcare professional behaviour change. METHODS: We will conduct a systematic review of Cochrane reviews (an Overview). We plan to systematically search the Cochrane Database of Systematic Reviews. We will include all systematic reviews of randomised controlled trials comparing a healthcare professional targeted behaviour change intervention to a standard care or no intervention control group. Two reviewers will independently assess the eligibility of the reviews and the methodological quality of included reviews using the ROBIS tool. The quality of evidence within each comparison in each review will be judged based on the GRADE criteria. Disagreements will be resolved through discussion. Effects of interventions will be systematically tabulated and the quality of evidence used to determine implications for clinical practice and make recommendations for future research. DISCUSSION: This overview will bring together the best available evidence relating to the sustainability of health professional behaviour change, thus supporting policy makers with decision-making in this field.

Slower Decline in C-Reactive Protein after an Inflammatory Insult Is Associated with Longer Survival in Older Hospitalised Patients.

BACKGROUND: Enhancing biological resilience may offer a novel way to prevent and ameliorate disease in older patients. We investigated whether changes in C-reactive protein (CRP), as a dynamic marker of the acute inflammatory response to diverse stressors, may provide a way to operationalize the concept of resilience in older adults. We tested this hypothesis by examining whether such changes could predict prognosis by identifying which individuals are at greater risk of 6-month mortality. METHODS: Analysis of prospective, routinely collected datasets containing data on hospitalization, clinical chemistry and rehabilitation outcomes for rehabilitation inpatients between 1999 and 2011. Maximum CRP response during acute illness and CRP recovery indices (time and slope of CRP decay to half maximum, and to <50mg/L if peak values were greater than 50mg/L) was derived from biochemistry data. 6-month survival plots were conducted on quartiles of CRP recovery indices. Cox proportional hazards models were used to test univariate and multivariate predictors of 6-month mortality. Covariates included age, sex, number of medications, serum calcium, haemoglobin level, renal function, and the presence of previous myocardial infarction, stroke, chronic heart failure, COPD and diabetes. RESULTS: 3723 patients, mean age 84 years, were included. 1535 (41%) were male and 733 (20%) died during six-month follow-up. The lower an individual's peak CRP reading, and the longer the time taken for their CRP to fall, the better their 6-month survival. The time for CRP to reach half of its maximum value was the best dynamic CRP index of survival (HR 0.93 per week, 95% CI 0.89 to 0.98; p = 0.004); this remained significant even after adjustment for maximum CRP level and covariates listed above. CONCLUSION: CRP recovery indices are associated with survival in older people; further work is required to explain differences in physiology between patients with a fast and slow CRP recovery.

Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection.

Cryptococcus neoformans is a significant fungal pathogen of immunocompromised patients. Many questions remain regarding the function of macrophages in normal clearance of cryptococcal infection and the defects present in uncontrolled cryptococcosis. Two current limitations are: 1) The difficulties in interpreting studies using isolated macrophages in the context of the progression of infection, and 2) The use of high resolution imaging in understanding immune cell behavior during animal infection. Here we describe a high-content imaging method in a zebrafish model of cryptococcosis that permits the detailed analysis of macrophage interactions with C. neoformans during infection. Using this approach we demonstrate that, while macrophages are critical for control of C. neoformans, a failure of macrophage response is not the limiting defect in fatal infections. We find phagocytosis is restrained very early in infection and that increases in cryptococcal number are driven by intracellular proliferation. We show that macrophages preferentially phagocytose cryptococci with smaller polysaccharide capsules and that capsule size is greatly increased over twenty-four hours of infection, a change that is sufficient to severely limit further phagocytosis. Thus, high-content imaging of cryptococcal infection in vivo demonstrates how very early interactions between macrophages and cryptococci are critical in the outcome of cryptococcosis.

"Horses for Courses": Comment on "Translating Evidence Into Healthcare Policy and Practice: Single Versus Multi-Faceted Implementation Strategies - Is There a Simple Answer to a Complex Question?".

This commentary considers the vexed question of whether or not we should be spending time and resources on using multifaceted interventions to undertake implementation of evidence in healthcare. A review of systematic reviews has suggested that simple interventions may be just as effective as those taking a multifaceted approach. Taking cognisance of the Promoting Action on Research Implementation in Health Services (PARIHS) framework this commentary takes account of the evidence, context and facilitation factors in undertaking implementation. It concludes that a 'horses for courses' approach is necessary meaning that the specific implementation approach should be selected to fit the implementation task in hand whether it be a single or multifaceted approach and reviewed on an individual basis.

Construction of a linked health and social care database resource--lessons on process, content and culture.

BACKGROUND: Combining routinely collected health and social care data on older people is essential to advance both service delivery and research for this client group. Little data is available on how to combine health and social care data; this article provides an overview of a successful data linkage process and discusses potential barriers to executing such projects. METHODS AND RESULTS: We successfully obtained and linked data on older people within Dundee from three sources: Dundee Social Work Department database (30,000 individuals aged 65 years and over), healthcare data held on NHS Tayside patients by the Health Informatics Centre (400,000 individuals), Dundee, and the Dundee of Medicine for the Elderly rehabilitation database (4300 individuals). Data were linked, anonymized and transferred to a Safe Haven environment to ensuring confidentiality and strict access control. Challenges were faced around workflows, culture and documentation. Exploiting the resultant data set raises further challenges centered on database documentation, understanding the way data were collected, dealing with missing data, data validity and collection at different time periods. CONCLUSION: Routinely collected health and social care data sets can be linked, but significant process barriers must be overcome to allow successful linkage and integration of data and its full exploitation.