Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.

OBJECTIVE: To demonstrate the importance of using a combined genetic and functional approach to correctly interpret a genetic test for monogenic diabetes. RESEARCH DESIGN AND METHODS: We identified three probands with a phenotype consistent with maturity-onset diabetes of the young (MODY) subtype GCK-MODY, in whom two potential pathogenic mutations were identified: [R43H/G68D], [E248 K/I225M], or [G261R/D217N]. Allele-specific PCR and cosegregation were used to determine phase. Single and double mutations were kinetically characterized. RESULTS: The mutations occurred in cis (double mutants) in two probands and in trans in one proband. Functional studies of all double mutants revealed inactivating kinetics. The previously reported GCK-MODY mutations R43H and G68D were inherited from an affected father and unaffected mother, respectively. Both our functional and genetic studies support R43H as the cause of GCK-MODY and G68D as a neutral rare variant. CONCLUSIONS: These data highlight the need for family/functional studies, even for previously reported pathogenic mutations

Variação diurna de parâmetros de função pulmonar e de força muscular respiratória em pacientes com DPOC Diurnal variations in the parameters of pulmonary function and respiratory muscle strength in patients with COPD

OBJETIVO: Avaliar a magnitude de mudanças diurnas em parâmetros de função pulmonar e de força e resistência dos músculos respiratórios em uma amostra de pacientes com DPOC. MÉTODOS: Um grupo com 7 pacientes foi submetido a espirometria e a determinação de PImáx e PEmáx em dois momentos (entre 8h00 e 8h30 e entre 16h30 e 17h00) em um único dia. Os pacientes permaneceram em repouso na área do laboratório entre as avaliações. RESULTADOS: De acordo com o sistema de estadiamento da Global Initiative for Chronic Obstructive Pulmonary Disease, a doença foi classificada em moderada, grave e muito grave em 1, 3 e 3 pacientes, respectivamente. Da primeira para a segunda avaliação, houve uma queda significativa em CVF, VEF1 e PEmáx (de 13%, 15% e 10%, respectivamente), bem como uma queda não significativa em PFE, PImáx e ventilação voluntária máxima (de 9%, 3% e 11%, respectivamente). CONCLUSÕES: Nesta amostra de pacientes com DPOC, houve variações diurnas nos parâmetros de função pulmonar e de força de músculos respiratórios. Os valores de VEF1, CVF e PEmáx foram significativamente menores à tarde do que de manhã.<br>OBJECTIVE: To evaluate the magnitude of diurnal changes in the parameters of pulmonary function and respiratory muscle strength/endurance in a sample of patients with COPD. METHODS: A group of 7 patients underwent spirometry, together with determination of MIP and MEP, at two distinct times (between 8:00 and 8:30 a.m. and between 4:30 and 5:00 p.m.) on a single day. Between assessments, the patients remained at rest in the laboratory. RESULTS: In accordance with the Global Initiative for Chronic Obstructive Pulmonary Disease staging system, COPD was classified as moderate, severe, and very severe in 1, 3, and 3 of the patients, respectively. From the first to the second assessment, there were significant decreases in FVC, FEV1, and MEP (of 13%, 15%, and 10%, respectively), as well as (less than significant) decreases in PEF, MIP, and maximal voluntary ventilation (of 9%, 3%, and 11%, respectively). CONCLUSIONS: In this sample of COPD patients, there were diurnal variations in the parameters of pulmonary function and respiratory muscle strength. The values of FEV1, FVC, and MEP were significantly lower in the afternoon than in the morning

Reduced risk of myocardial infarction related to active commuting: inflammatory and haemostatic effects are potential major mediating mechanisms

Background Regular physical activity is inversely associated with risk of coronary heart disease, but the precise mechanisms remain unclear. Active commuting is an environmental friendly way to achieve the recommended 30 min of daily physical activity. The aim of this study was to explore the relative contribution of markers from different potential mediating pathways on the association between active commuting and risk of myocardial infarction (MI) in a general population. Design Prospective incident nested case-control study. Methods Commuting habits, traditional risk factors and biomarkers were assessed at baseline and compared in 204 MI cases and 327 matched controls. Results Car commuting was significantly associated with MI risk, even after adjusting for potential confounders (odds ratio: 1.77, 95% confidence interval: 1.05-2.99). When potential mediators were included in the model, the risk was substantially attenuated. Among the traditional risk factors, apolipoprotein B/apolipoprotein A-1 ratio seemed to be the largest mediator (26.0%), followed by body mass index (18.7%). The inflammatory and haemostatic markers similarly dampened the effect, with tissue plasminogen activator/plasminogen activator inhibitor-1 complex and IL-6 explaining 33.6 and 27.6% of MI risk, respectively. Combined, the potential mediators investigated seemed to explain 40.1% of MI risk related to car commuting. Conclusion Overall, the traditional, inflammatory and haemostatic markers seemed to explain a substantial proportion of the reduction in MI risk related to active commuting in this study population. The predominant effect of the inflammatory and haemostatic markers supports the hypothesis that regular physical activity may work through additional biological mechanisms to reduce coronary risk beyond traditional risk factors. However, these findings need to be confirmed in larger studies. Eur J Cardiovasc Prev Rehabil 17:56-62 (C) 2010 The European Society of Cardiolog