The long-term survival of single or dual kidney grafts from donors older than 60 years of age is excellent, provided that the grafts are evaluated histologically before implantation. This approach may help to expand the donor-organ pool for kidney transplantation.

BackgroundThe Alvarado score can be used to stratify patients with symptoms of suspected appendicitis; the validity of the score in certain patient groups and at different cut points is still unclear. The aim of this study was to assess the discrimination (diagnostic accuracy) and calibration performance of the Alvarado score.MethodsA systematic search of validation studies in Medline, Embase, DARE and The Cochrane library was performed up to April 2011. We assessed the diagnostic accuracy of the score at the two cut-off points: score of 5 (1 to 4 vs. 5 to 10) and score of 7 (1 to 6 vs. 7 to 10). Calibration was analysed across low (1 to 4), intermediate (5 to 6) and high (7 to 10) risk strata. The analysis focused on three sub-groups: men, women and children.ResultsForty-two studies were included in the review. In terms of diagnostic accuracy, the cut-point of 5 was good at 'ruling out' admission for appendicitis (sensitivity 99% overall, 96% men, 99% woman, 99% children). At the cut-point of 7, recommended for 'ruling in' appendicitis and progression to surgery, the score performed poorly in each subgroup (specificity overall 81%, men 57%, woman 73%, children 76%). The Alvarado score is well calibrated in men across all risk strata (low RR 1.06, 95% CI 0.87 to 1.28; intermediate 1.09, 0.86 to 1.37 and high 1.02, 0.97 to 1.08). The score over-predicts the probability of appendicitis in children in the intermediate and high risk groups and in women across all risk strata.ConclusionsThe Alvarado score is a useful diagnostic 'rule out' score at a cut point of 5 for all patient groups. The score is well calibrated in men, inconsistent in children and over-predicts the probability of appendicitis in women across all strata of risk.

BackgroundMultimorbidity defined as the “the coexistence of two or more chronic diseases” in one individual, is increasing in prevalence globally. The aim of this study is to compare the prevalence of multimorbidity across low and middle-income countries (LMICs), and to investigate patterns by age and education, as a proxy for socio-economic status (SES).MethodsChronic disease data from 28 countries of the World Health Survey (2003) were extracted and inter-country socio-economic differences were examined by gross domestic product (GDP). Regression analyses were applied to examine associations of education with multimorbidity by region adjusted for age and sex distributions.ResultsThe mean world standardized multimorbidity prevalence for LMICs was 7.8 % (95 % CI, 7.79 % - 7.83 %). In all countries, multimorbidity increased significantly with age. A positive but non–linear relationship was found between country GDP and multimorbidity prevalence. Trend analyses of multimorbidity by education suggest that there are intergenerational differences, with a more inverse education gradient for younger adults compared to older adults. Higher education was significantly associated with a decreased risk of multimorbidity in the all-region analyses.ConclusionsMultimorbidity is a global phenomenon, not just affecting older adults in HICs. Policy makers worldwide need to address these health inequalities, and support the complex service needs of a growing multimorbid population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2008-7) contains supplementary material, which is available to authorized users.

BackgroundAsthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear.ObjectiveWe performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients.MethodsSixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed.ResultsSignificant heterogeneity of T-cell phenotypes was observed, with levels of IL-13–secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased mast cell mediator levels in patients with severe asthma both in its atopic (type 2 cytokine–high) and nonatopic forms.ConclusionThe evidence for a role for TH17 cells in patients with severe asthma is limited. Severe asthma is associated with a striking deficiency of MAIT cells and high mast cell mediator levels. This study provides proof of concept for disease mechanistic networks in asthmatic patients with clusters that could inform the development of new therapies.

Symptoms of primary ciliary dyskinesia (PCD) are nonspecific and guidance on whom to refer for testing is limited. Diagnostic tests for PCD are highly specialised, requiring expensive equipment and experienced PCD scientists. This study aims to develop a practical clinical diagnostic tool to identify patients requiring testing.Patients consecutively referred for testing were studied. Information readily obtained from patient history was correlated with diagnostic outcome. Using logistic regression, the predictive performance of the best model was tested by receiver operating characteristic curve analyses. The model was simplified into a practical tool (PICADAR) and externally validated in a second diagnostic centre.Of 641 referrals with a definitive diagnostic outcome, 75 (12%) were positive. PICADAR applies to patients with persistent wet cough and has seven predictive parameters: full-term gestation, neonatal chest symptoms, neonatal intensive care admittance, chronic rhinitis, ear symptoms, situs inversus and congenital cardiac defect. Sensitivity and specificity of the tool were 0.90 and 0.75 for a cut-off score of 5 points. Area under the curve for the internally and externally validated tool was 0.91 and 0.87, respectively.PICADAR represents a simple diagnostic clinical prediction rule with good accuracy and validity, ready for testing in respiratory centres referring to PCD centres.

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Background-The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws.The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined. Methods and Results-Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA. Conclusions-Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice. Clinical Trial Registration-URL: http://www.clinicaltrial.gov. Unique identifier: NCT01070771.(Circ Cardiovasc Interv. 2014;7:248-255.)

Microalbuminuria is a risk factor for renal and cardiovascular disease. A role for insulin resistance in the pathogenesis of microalbuminuria has been suggested but is still unproven. In this case-control, cross-sectional study, we compared glucose disposal rate (GDR), measured by hyperinsulinemic-euglycemic clamp, in 50 pairs of matched type 2 diabetic patients with micro-or normoalbuminuria (main study) and in 29 matched pairs of diabetic patients with macro-or microalbuminuria (substudy). In the main study, GDR was ϳ25% lower in micro-than in normoalbuminuric patients (5.20 ؎ 1.91 vs. 6.86 ؎ 2.88 mg ⅐ kg ؊1 ⅐ min ؊1 , P < 0.05) and was independently associated with microalbuminuria (P ‫؍‬ 0.002), with each 1 mg ⅐ kg ؊1 ⅐ min ؊1 decrease predicting ϳ40% increased prevalence (odds ratio 1.37 [95% CI 1.14 -1.70]). Microalbuminuria was threefold more frequent in patients with GDR <7.50 ؎ 2.56 mg ⅐ kg ؊1 ⅐ min ؊1 than in those with higher GDR (60% vs. 20%, P < 0.005). In the substudy, GDR in macro-and microalbuminuric patients was comparable (5.52 ؎ 2.56 vs. 5.16 ؎ 1.61 mg ⅐ kg ؊1 ⅐ min ؊1 ) and independent of macroalbuminuria. GDR was significantly correlated with urinary albumin excretion rate in the main study (P ‫؍‬ 0.004) but not in the substudy (P ‫؍‬ 0.60). In type 2 diabetes, more severe insulin resistance is independently associated with microalbuminuria. Longitudinal studies are needed to clarify the role of insulin resistance in the pathogenesis of microalbuminuria and related complications.