Armando Teixeira-Pinto

C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study

IntroductionC-reactive protein (CRP) has been shown to be a valuable marker in the diagnosis of infection and in monitoring its response to antibiotics. Our objective was to evaluate serial CRP measurements after prescription of antibiotics to describe the clinical course of Community-Acquired Sepsis admitted to intensive care units (ICU).MethodsDuring a 12-month period a multi-center, prospective, observational study was conducted, segregating adults with Community-Acquired Sepsis. Patients were followed-up during the first five ICU days, day of ICU discharge or death and hospital outcome. CRP-ratio was calculated in relation to Day 1 CRP concentration. Patients were classified according to the pattern of CRP-ratio response to antibiotics: fast response if Day 5 CRP-ratio was < 0.4, slow response if Day 5 CRP-ratio was between 0.4 and 0.8, and no response if Day 5 CRP-ratio was > 0.8. Comparison between survivors and non-survivors was performed.ResultsA total of 891 patients (age 60 ± 17 yrs, hospital mortality 38%) were studied. There were no significant differences between the CRP of survivors and non-survivors until Day 2 of antibiotic therapy. On the following three days, CRP of survivors was significantly lower (P < 0.001). After adjusting for the Simplified Acute Physiology Score II and severity of sepsis, the CRP course was significantly associated with mortality (ORCRP-ratio = 1.03, confidence interval 95%= (1.02, 1.04), P < 0.001). The hospital mortality of patients with fast response, slow response and no response patterns was 23%, 30% and 41%, respectively (P = 0.001). No responders had a significant increase on the odds of death (OR = 2.5, CI95% = (1.6, 4.0), P < 0.001) when compared with fast responders.ConclusionsDaily CRP measurements after antibiotic prescription were useful as early as Day 3 in identification of Community-Acquired Sepsis patients with poor outcome. The rate of CRP decline during the first five ICU days was markedly associated with prognosis. The identification of the pattern of CRP-ratio response was useful in the recognition of the individual clinical course.

Shift in the composition of obesity in young adult men in Sweden over a third of a century.

Objective:To assess whether the composition of the obese category (body mass index (BMI)⩾30) has changed during the last one-third of a century in young adult men.Design:Retrospective study of 1 580 913 men (18.3±0.4 years) representing 82% of the Swedish male population at military conscription age between 1969 and 2005. Measured height and weight were used to define moderate and morbid obesity as BMI 30–34.9 and ⩾35, respectively. Data on socio-economic position (SEP), place of residence (urban, semi-urban and rural), age and test center were also collected.Results:From the period 1969–1974 to 2000–2005, the prevalence of moderate obesity almost quintupled (0.8–3.8%; P<0.0001), while morbid obesity increased 10-fold (0.1–1.3%; P<0.0001). The composition of the obese category changed from 12.9 to 25.1% morbidly obese during the same time, corresponding to an annual growth in the odds of 2.8% (CI95% 2.5–3.1%) per year within the obese category. Compared to 1969–1974, the odds ratios of obesity and morbid obesity, respectively, were 1.6 (1.6–1.7) and 1.9 (1.7–2.2) in 1980–1984, 2.8 (2.7–2.9) and 4.0 (3.5–4.5) in 1990–1994, and 6.0 (5.7–6.3) and 11.4 (10.1–12.9) in 2000–2005, after adjustment for SEP, urban/rural place of residence, age and test center. Extrapolation of the growth rate during the observation period resulted in an estimated 4% morbidly obese in 2020.Conclusion:Morbid obesity increased faster than moderate obesity during the last 35 years. As the health risks and costs of obesity-related morbidity increase disproportionately in the morbidly obese, it is important to assess morbid obesity in prevalence studies, and distinguish the morbidly from the moderately obese in cost analyses.

Erythrocyte density in sickle cell syndromes is associated with specific clinical manifestations and hemolysis.

Dense, dehydrated red blood cells (DRBCs) are a characteristic feature of sickle-cell disease (SCD). DRBCs play a role in the pathophysiology of SCD acute and chronic organ damage because of heightened tendency to undergo polymerization and sickling because of their higher hemoglobin S concentration. Relations between red cell density (assessed with phthalate density-distribution profile method) and several hematologic, biochemical, genetic parameters, and clinical manifestations were studied in a large cohort of homozygous patients. The percentage of DRBCs was significantly higher in patients who experienced skin ulcers, priapism, or renal dysfunction. Presence of α-thalassemia deletions was associated with fewer DRBCs. A multivariable analysis model showed DRBCs to be positively associated with hemolytic parameters such as lactate dehydrogenase and bilirubin and negatively with fetal hemoglobin. The percentage of DRBCs decreased by 34% at 6 months of hydroxycarbamide (xydroxyurea) therapy. Thus, DRBCs are associated with specific clinical manifestations and biologic markers and may be a useful addition to the biologic and clinical evaluation of patients with SCD, because they can easily be measured in a hematocrit tube.

Correlated Bivariate Continuous and Binary Outcomes: Issues and Applications

Increasingly multiple outcomes are collected in order to characterize treatment effectiveness or to evaluate the impact of large policy initiatives. Often the multiple outcomes are non-commensurate, e.g. measured on different scales. The common approach to inference is to model each outcome separately ignoring the potential correlation among the responses. We describe and contrast several full likelihood and quasi-likelihood multivariate methods for non-commensurate outcomes. We present a new multivariate model to analyze binary and continuous correlated outcomes using a latent variable. We study the efficiency gains of the multivariate methods relative to the univariate approach. For complete data, all approaches yield consistent parameter estimates. When the mean structure of all outcomes depends on the same set of covariates, efficiency gains by adopting a multivariate approach are negligible. In contrast, when the mean outcomes depend on different covariate sets, large efficiency gains are realized. Three real examples illustrate the different approaches.

A comparison of effects of fish and beef protein on satiety in normal weight men

Background:Previous studies have indicated that fish protein may have a greater effect on satiety compared to other protein sources of animal origin.Objective:To compare the effects of fish protein and beef protein meals on hunger and satiety.Design:Twenty-three normal non-smoking, healthy males aged 20–32 years, body mass index 22.5±1.8 (s.d.) kg/m2 participated in a study, with within-subjects design and 1 week between test days. In the morning of the test days, subjects received a standardized breakfast. Four hours after breakfast, subjects were served an iso-energetic protein-rich (40 energy % protein) lunch meal, consisting of either a fish protein dish or a beef protein dish. Four hours after the start of the lunch meals, an ad libitum standardized evening meal was served and the intake of food was measured. Appetite was rated by visual analogue scales (VAS) immediately before and after the meals, as well as every hour between the meals. After the evening meal until bedtime, subjects were asked to record in detail foods and drinks consumed.Results:The repeated VAS-ratings of hunger, satiety and prospective consumption were modelled in a random effects model, taking pre-lunch VAS-ratings into account. After the fish meal, the point estimates were lower for hunger (−2±4.8), higher for satiety (8.7±6.0) and lower for prospective consumption (−4.9±4.7), but they did not reach statistical significance (P satiety=0.88; P hunger=0.15; P prospective=0.30). However, the energy intake at the evening meal displayed significant differences with subjects eating less after the fish protein lunch (2765 vs 3080 KJ, P<0.01) without feeling less satiated. No later energy compensation after the evening meal was found on the test day.Conclusion:Although no significant differences in VAS-ratings of satiety or hunger were detected, subjects displayed an 11% reduction in energy intake at the subsequent evening meal.

Factors influencing hospital high length of stay outliers

BackgroundThe study of length of stay (LOS) outliers is important for the management and financing of hospitals. Our aim was to study variables associated with high LOS outliers and their evolution over time.MethodsWe used hospital administrative data from inpatient episodes in public acute care hospitals in the Portuguese National Health Service (NHS), with discharges between years 2000 and 2009, together with some hospital characteristics. The dependent variable, LOS outliers, was calculated for each diagnosis related group (DRG) using a trim point defined for each year by the geometric mean plus two standard deviations. Hospitals were classified on the basis of administrative, economic and teaching characteristics. We also studied the influence of comorbidities and readmissions. Logistic regression models, including a multivariable logistic regression, were used in the analysis. All the logistic regressions were fitted using generalized estimating equations (GEE).ResultsIn near nine million inpatient episodes analysed we found a proportion of 3.9% high LOS outliers, accounting for 19.2% of total inpatient days. The number of hospital patient discharges increased between years 2000 and 2005 and slightly decreased after that. The proportion of outliers ranged between the lowest value of 3.6% (in years 2001 and 2002) and the highest value of 4.3% in 2009. Teaching hospitals with over 1,000 beds have significantly more outliers than other hospitals, even after adjustment to readmissions and several patient characteristics.ConclusionsIn the last years both average LOS and high LOS outliers are increasing in Portuguese NHS hospitals. As high LOS outliers represent an important proportion in the total inpatient days, this should be seen as an important alert for the management of hospitals and for national health policies. As expected, age, type of admission, and hospital type were significantly associated with high LOS outliers. The proportion of high outliers does not seem to be related to their financial coverage; they should be studied in order to highlight areas for further investigation. The increasing complexity of both hospitals and patients may be the single most important determinant of high LOS outliers and must therefore be taken into account by health managers when considering hospital costs.

Cognitive reserve in multiple sclerosis: Protective effects of education.

Background: Recent data suggest that cognitive reserve modulates the adverse effects of multiple sclerosis (MS) pathology on cognitive functioning; however, the protective effects of education in MS are still unclear. Objective: To explore education as an indicator of cognitive reserve, while controlling for demographic, clinical and genetic features. Methods: A total of 419 MS patients and 159 healthy comparison (HC) subjects underwent a comprehensive neuropsychological (NP) assessment, and answered the Hospital Anxiety and Depression Scale. Based on the HC data, MS patients’ NP scores were adjusted for sex, age and education; and the estimated 5th percentile (or 95th percentile, when appropriate) was used to identify any deficits. Patients also performed the Mini-Mental State Examination (MMSE); and their human leucocyte antigen HLA-DRB1 and apolipoprotein E (ApoE) genotypes were investigated. Results: Patients with higher education were less likely (p < 0.05) to have cognitive deficits than those with lower education, even when controlling for other covariates. Other significant predictors of cognitive deficit were: age, Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), and a progressive course. No significant association was found with the HLA-DRB1*15:01 or ApoE ε4 alleles. Conclusions: These results provide support to the use of education as a proxy of cognitive reserve in MS and stress the need to take into account education when approaching cognition in MS.

Clinical assessment of pediatric obstructive sleep apnea: A systematic review and meta‐analysis

Clinical symptoms and signs are routinely used to investigate pediatric obstructive sleep apnea (OSA). This study aimed to systematically assess the evidence for the diagnostic accuracy of individual or combined clinical symptoms and signs in predicting pediatric OSA.

How different terminology for ductal carcinoma in situ impacts women's concern and treatment preferences: a randomised comparison within a national community survey

Objective There have been calls to remove ‘carcinoma’ from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as ‘abnormal cells’ versus ‘pre-invasive breast cancer cells’ on womens concern and treatment preferences. Setting and participants Community sample of Australian women (n=269) who spoke English as their main language at home. Design Randomised comparison within a community survey. Women considered a hypothetical scenario involving a diagnosis of DCIS described as either ‘abnormal cells’ (arm A) or ‘pre-invasive breast cancer cells’ (arm B). Within each arm, the initial description was followed by the alternative term and outcomes reassessed. Results Women in both arms indicated high concern, but still indicated strong initial preferences for watchful waiting (64%). There were no differences in initial concern or preferences by trial arm. However, more women in arm A (‘abnormal cells’ first term) indicated they would feel more concerned if given the alternative term (‘pre-invasive breast cancer cells’) compared to women in arm B who received the terms in the opposite order (67% arm A vs 52% arm B would feel more concerned, p=0.001). More women in arm A also changed their preference towards treatment when the terminology was switched from ‘abnormal cells’ to ‘pre-invasive breast cancer cells’ compared to arm B. In arm A, 18% of women changed their preference to treatment while only 6% changed to watchful waiting (p=0.008). In contrast, there were no significant changes in treatment preference in arm B when the terminology was switched (9% vs 8% changed their stated preference). Conclusions In a hypothetical scenario, interest in watchful waiting for DCIS was high, and changing terminology impacted womens concern and treatment preferences. Removal of the cancer term from DCIS may assist in efforts towards reducing overtreatment.

The Predisposition, Infection, Response and Organ Failure (Piro) Sepsis Classification System: Results of Hospital Mortality Using a Novel Concept and Methodological Approach

Introduction PIRO is a conceptual classification system in which a number of demographic, clinical, biological and laboratory variables are used to stratify patients with sepsis in categories with different outcomes, including mortality rates. Objectives To identify variables to be included in each component of PIRO aiming to improve the hospital mortality prediction. Methods Patients were selected from the Portuguese ICU-admitted community-acquired sepsis study (SACiUCI). Variables concerning the R and O component included repeated measurements along the first five days in ICU stay. The trends of these variables were summarized as the initial value at day 1 (D1) and the slope of the tendency during the five days, using a linear mixed model. Logistic regression models were built to assess the best set of covariates that predicted hospital mortality. Results A total of 891 patients (age 60±17 years, 64% men, 38% hospital mortality) were studied. Factors significantly associated with mortality for P component were gender, age, chronic liver failure, chronic renal failure and metastatic cancer; for I component were positive blood cultures, guideline concordant antibiotic therapy and health-care associated sepsis; for R component were C-reactive protein slope, D1 heart rate, heart rate slope, D1 neutrophils and neutrophils slope; for O component were D1 serum lactate, serum lactate slope, D1 SOFA and SOFA slope. The relative weight of each component of PIRO was calculated. The combination of these four results into a single-value predictor of hospital mortality presented an AUC-ROC 0.84 (IC95%:0.81–0.87) and a test of goodness-of-fit (Hosmer and Lemeshow) of p = 0.368. Conclusions We identified specific variables associated with each of the four components of PIRO, including biomarkers and a dynamic view of the patient daily clinical course. This novel approach to PIRO concept and overall score can be a better predictor of mortality for patients with community-acquired sepsis admitted to ICUs.