GPs' perspectives on the management of patients with multimorbidity: systematic review and synthesis of qualitative research.

OBJECTIVE: To synthesise the existing published literature on the perceptions of general practitioners (GPs) or their equivalent on the clinical management of multimorbidity and determine targets for future research that aims to improve clinical care in multimorbidity. DESIGN: Systematic review and metaethnographic synthesis of primary studies that used qualitative methods to explore GPs' experiences of clinical management of multimorbidity or multiple chronic diseases. DATA SOURCES: EMBASE, MEDLINE, CINAHL, PsycInfo, Academic Search Complete, SocIndex, Social Science Full Text and digital theses/online libraries (database inception to September 2012) to identify literature using qualitative methods (focus groups or interviews). REVIEW METHODS: The 7-step metaethnographic approach described by Noblit and Hare, which involves cross-interpretation between studies while preserving the context of the primary data. RESULTS: Of 1805 articles identified, 37 were reviewed in detail and 10 were included, using a total of 275 GPs in 7 different countries. Four areas of difficulty specific to the management of multimorbidity emerged from these papers: disorganisation and fragmentation of healthcare; the inadequacy of guidelines and evidence-based medicine; challenges in delivering patient-centred care; and barriers to shared decision-making. A 'line of argument' was drawn which described GPs' sense of isolation in decision-making for multimorbid patients. CONCLUSIONS: This systematic review shows that the problem areas for GPs in the management of multimorbidity may be classified into four domains. There will be no 'one size fits all' intervention for multimorbidity but these domains may be useful targets to guide the development of interventions that will assist and improve the provision of care to multimorbid patients

Use It or Lose It: Embodying Practice in Action Design Research (ADR)

This paper describes the adoption, implementation and empirical evaluation of Action Design Research (ADR) during an 18-month Industry-Academic research partnership. It details the theoretical basis for our research and the selection of ADR as the overarching approach. It describes our adoption of an explicitly interpretivist perspective to answer a broad research question which necessitate up-front exploratory research. It then traces the efficacy-in-use of the ADR approach for supporting our project, with its emphasis on interpretivist theory and research. The key contribution of this paper is an ADR variant suitable to projects of a similar nature to ours. Our findings are relevant to any discipline that engages in Industry-Academic collaboration, particularly with regard to socio-technical problems, including, for example, Information Systems (IS), Management and Organization Studies

Hypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo.

In mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother, and fetus are difficult to disentangle. Here, we used chronic hypoxia in the chicken embryo-an established model system that permits isolation of the direct effects of developmental hypoxia on the cardiovascular system of the offspring, independent of additional effects on the mother or the placenta. Fertilized chicken eggs were exposed to normoxia (N; 21% O2) or hypoxia (H; 13.5%-14% O2) from the start of incubation (day 0) until day 19 (hatching, ≈day 21). Following hatching, all birds were maintained under normoxic conditions until ≈6 months of adulthood. Hypoxic incubation increased hematocrit (+27%) in the chicken embryo and induced asymmetrical growth restriction (body weight, -8.6%; biparietal diameter/body weight ratio, +7.5%) in the hatchlings (all P<0.05). At adulthood (181±4 days), chickens from hypoxic incubations remained smaller (body weight, -7.5%) and showed reduced basal and stimulated in vivo NO bioavailability (pressor response to NG-nitro-L-arginine methyl ester, -43%; phenylephrine pressor response during NO blockade, -61%) with significant hypertension (mean arterial blood pressure, +18%), increased cardiac work (ejection fraction, +12%; fractional shortening, +25%; enhanced baroreflex gain, +456%), and left ventricular wall thickening (left ventricular wall volume, +36%; all P<0.05). Therefore, we show that chronic hypoxia can act directly on a developing embryo to program hypertension, cardiovascular dysfunction, and cardiac wall remodeling in adulthood in the absence of any maternal or placental effects.The British Heart Foundation The Wellcome Trus

Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H-Related Protein-5 (FHR5) Deposition

Introduction IgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury. Methods To elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN. Results M-ficolin, L-ficolin, mannan-binding lectin (MBL)–associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls. Progressive disease was associated with low plasma MASP-3 levels and increased glomerular staining for C3b/iC3b/C3c, C3d, C4d, C5b-9, and factor H–related protein 5 (FHR5). Glomerular FHR5 deposition positively correlated with glomerular C3b/iC3b/C3c, C3d, and C5b-9 deposition, but not with glomerular C4d. These observations, together with the finding that glomerular factor H (fH) deposition was reduced in progressive disease, are consistent with a role for fH deregulation by FHR5 in renal injury in IgAN. Conclusion Our data indicate that circulating MASP-3 levels could be used as a biomarker of disease severity in IgAN and that glomerular staining for FHR5 could both indicate alternative complement pathway activation and be a tissue marker of disease severity

O- and N-glycosylation of serum immunoglobulin A is associated with IgA nephropathy and glomerular function.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is a leading cause of renal failure. The disease mechanisms are not completely understood, but a higher abundance of galactose-deficient IgA is recognized to play a crucial role in IgAN pathogenesis. Although both types of human IgA (IgA1 and IgA2) have several N-glycans as post-translational modification, only IgA1 features extensive hinge-region O-glycosylation. IgA1 galactose deficiency on the O-glycans is commonly detected by a lectin-based method. To date, limited detail is known about IgA O- and N-glycosylation in IgAN. METHODS: To gain insights into the complex O- and N-glycosylation of serum IgA1 and IgA2 in IgAN, we used liquid chromatography-mass spectrometry (LC-MS) for the analysis of tryptic glycopeptides of serum IgA from 83 patients with IgAN and 244 age- and sex-matched healthy controls. RESULTS: Multiple structural features of N-glycosylation of IgA1 and IgA2 were associated with IgAN and glomerular function in our cross-sectional study. These features included differences in galactosylation, sialylation, bisection, fucosylation, and N-glycan complexity. Moreover, IgA1 O-glycan sialylation was associated with both the disease and glomerular function. Finally, glycopeptides were a better predictor of IgAN and glomerular function than galactose-deficient IgA1 levels measured by lectin-based ELISA. CONCLUSIONS: Our high-resolution data suggest that IgA O- and N-glycopeptides are promising targets for future investigations on the pathophysiology of IgAN and as potential noninvasive biomarkers for disease prediction and deteriorating kidney function

Identifying behavior change techniques for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia

Nursing home residents with dementia are commonly prescribed antipsychotics despite the associated increased risk of harms. Interventions to optimize prescribing practice have been found to be effective in the short term, but there is a lack of evidence to support sustainability of effects, along with a lack of theory, public involvement, and transparency in the intervention development process. Using theory has been advocated as a means of improving intervention sustainability. The aim of this study was, therefore, to identify behavior change techniques (BCTs) for inclusion in a complex intervention targeting antipsychotic prescribing to nursing home residents with dementia. A comprehensive approach to identifying a long list of all potential BCTs from three different sources was undertaken. The most appropriate BCTs were then selected through a two-round Delphi consensus survey with a broad range of experts (n = 18 panelists). Advisory groups of people with dementia, family carers, and professional stakeholders provided feedback on the final BCTs included. After two Delphi survey rounds, agreement was reached on 22 BCTs. Further refinement of the selected BCTs based on advisory group and panelists' feedback, along with use of the APEASE criteria (Affordability, Practicability, Effectiveness, Acceptability, Side effects/safety, and Equity) resulted in a final list of 16 BCTs. The next step in intervention development will be to identify the most appropriate mode of delivery of the 16 BCTs identified for inclusion. The study provides a case example of a systematic approach to incorporating evidence with stakeholder views in the identification of appropriate BCTs

Mapping the disease-specific LupusQoL to the SF-6D

Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

Association between somatic cell count during the first lactation and the cumulative milk yield of cows in Irish dairy herds

Reduced potential milk yield is an important component of mastitis costs in dairy cows. The first aim of this study was to assess associations between somatic cell count (SCC) during the first lactation, and cumulative milk yield over the first lactation and subsequent lifetime of cows in Irish dairy herds. The second aim was to assess the association between SCC at 5 to 30 d in milk during parity 1 (SCC1), and SCC over the entire first lactation for cows in Irish dairy herds. The data set studied included records from 51,483 cows in 5,900 herds. Somatic cell count throughout the first lactation was summarized using the geometric mean and variance of SCC. Data were analyzed using linear models that included random effects to account for the lack of independence between observations, and herdlevel variation in coefficients. Models were developed in a Bayesian framework and parameters were estimated from 10,000 Markov chain Monte Carlo simulations. The final models were a good fit to the data. A 1-unit increase in mean natural logarithm SCC over the first lactation was associated with a median decrease in first lactation and lifetime milk yield of 135 and 1,663 kg, respectively. A 1-unit increase in the variance of natural logarithm SCC over the first lactation was associated with a median decrease in lifetime milk yield of 719 kg. To demonstrate the context of lifetime milk yield results, microsimulation was used to model the trajectory of individual cows and evaluate the expected outcomes for particular changes in herd-level geometric mean SCC over the first lactation. A 75% certainty of savings of at least €199/heifer in the herd was detected if herd-level geometric mean SCC over the first lactation was reduced from ≥120,000 to ≤72,000 cells/mL. The association between SCC1 and SCC over the remainder of the first lactation was highly herd dependent, indicating that control measures for heifer mastitis should be preferentially targeted on an individual-herd basis toward either the pre- and peripartum period, or the lactating period, to optimize the lifetime milk yield of dairy cows