Clinical, Economic, and Humanistic Impact of Short-Bowel Syndrome/Chronic Intestinal Failure in Portugal (PARENTERAL Study).

Introduction: This study aimed to assess the clinical, economic, and humanistic impact of short-bowel syndrome/chronic intestinal failure (SBS/CIF) in Portugal. Methods: This is a retrospective multicenter cohort chart review study, with a cross-sectional component for quality-of-life (QoL) evaluation. Inclusion criteria comprised patients with SBS/CIF, aged ≥1 year, with stable parenteral nutrition (PN). Data collection included patient chart review over a 12-month period and patient/caregiver self-report and SF-36/PedsQL™ questionnaires. Main endpoints comprised clinical and PN characterization, healthcare resource use (HRU), direct costs, and patient QoL. Results: Thirty-one patients were included (11 adults and 20 children). Patients' mean age (standard deviation [SD]) was 57.9 (14.3) years in adults and 7.5 (5.0) years in children, with a mean time since diagnosis of 10.2 (5.9) and 6.6 (4.2) years, respectively. PN was administered for a mean of 5.2 and 6.6 days/week in adults and children, respectively; home PN occurred in 81.8% of adults and 90.0% of children for a mean of 9.6 and 10.8 months/year, respectively. The mean annual number of hospitalizations was 1.9 and 2.0 which lasted for a mean of 34.0 and 29.4 days in adults and children, respectively. Twenty-one and forty hospitalization episodes were reported in adults and children, respectively, of which 71.4% and 85.0% were due to catheter-related complications. Mean annual direct costs per patient amounted to 47,857.53 EUR in adults and 74,734.50 EUR in children, with PN and hospitalizations as the main cost-drivers. QoL assessment showed a clinically significant impaired physical component in adults and a notable deterioration in the school functioning domain in children. Conclusion: In Portugal, SBS/CIF patient management is characterized by a substantial therapeutic burden and HRU, translating into high direct costs and a substantial impairment of the adults' physical function and children's school functioning.

Introdução: Este estudo teve como objetivo avaliar o impacto clínico, económico e social da síndrome do intestino curto/falência intestinal crónica (SIC/FIC) em Portugal. Métodos: Estudo de coorte retrospectivo e multicêntrico de revisão dos processos clínicos incluindo uma componente transversal para avaliação da qualidade de vida (QV). Os critérios de elegibilidade incluíram doentes com SIC/FIC, idade ≥1 ano, em nutrição parenteral (NP) e clinicamente estáveis. A recolha de dados incluiu a revisão dos processos clínicos ao longo de um período de 12 meses e a aplicação de questionários auto-administrados a doentes e cuidadores e de questionários de QV (SF-36/PedsQL™). Os indicadores principais foram a caracterização clínica e da NP, a utilização de recursos de saúde, custos diretos e QV dos doentes. Resultados: Foram incluídos 31 doentes (11 adultos e 20 crianças). A idade média (desvio padrão: DP) foi de 57.9 (14.3) anos nos adultos e de 7.5 (5.0) nas crianças com um tempo médio desde o diagnóstico de 10.2 (5.9) e 6.6 (4.2) anos, respetivamente. A NP foi administrada durante uma média de 5.2 e 6.6 dias por semana, em adultos e crianças respetivamente, em 81.8% e 90.0% dos adultos/crianças foi feita em casa durante uma média de 9.6 ou 10.8 meses por ano, respetivamente. O número médio anual de hospitalizações foi de 1.9 (1.6) e 2.0 (1.5) com uma duração média de 34.0 (47.4) e 29.4 (32.3) dias, em adultos e crianças, respetivamente. Foram reportados 21 e 40 episódios de hospitalização em adultos/crianças, dos quais 71.4% e 85.0% foram devido a complicações relacionadas ao uso de cateter. Os custos diretos anuais médios por doente ascenderam a 47,857.53 EUR nos adultos e a 74,734.50 EUR nas crianças, sendo que os maiores responsáveis foram a NP e as hospitalizações. A avaliação da QV mostrou um comprometimento clinicamente significativo da componente física nos adultos e uma deterioração relevante da dimensão escolar nas crianças. Conclusões: A gestão dos doentes com SIC/FIC em Portugal é caracterizada por uma sobrecarga substancial a nível terapêutico e de utilização de recursos de saúde, o que se traduz em elevados custos diretos e comprometimento substancial da componente física nos adultos e do desempenho escolar nas crianças.

Quality of life and informal care burden associated with duchenne muscular dystrophy in Portugal: the COIDUCH study.

BACKGROUND: To describe the reduced health-related quality of life (HRQoL) of duchenne muscular dystrophy (DMD) patients and their caregiver burden and to present its relationship with disease progression. METHODS: This cross-sectional study assessed patient HRQoL with the 3-level version of the EuroQol-5D (EQ-5D-3L) and caregiver burden with the Work Productivity and Activity Impairment: General Health questionnaire. DMD patients and their caregivers were identified through Portuguese Neuromuscular Association (APN). RESULTS: A total of 46 DMD main caregivers, of eight ambulant and 38 non-ambulant patients, completed the questionnaires. Over half (58.7%) of all non-ambulant patients were on ventilation support, either full-time (15.2%) or non full-time (43.5%). Non-ambulant patients had a lower mean utility scores than ambulant patients (- 0.05 versus 0.51, p value < 0.001). Caregivers of non-ambulant patients reported a significant mean daily activity impairment as compared to caregivers of ambulant patients (68% versus 23%, p value < 0.001). Among non-ambulant patients, both utility scores and caregiver impairment appeared to deteriorate according to a higher need for ventilation support, however, these results were not statistically significant. CONCLUSIONS: These results emphasise the significant negative impact that DMD progression has on the patient HRQoL, as well as caregivers' ability to conduct their daily activities. Therapeutic options that stop or slow the disease progression could have a beneficial impact for both patients and caregivers.

Cost of Illness in Patients with Duchenne Muscular Dystrophy in Portugal: The COIDUCH Study.

OBJECTIVE: The aim of this study was to estimate the cost of illness (COI) of Duchenne muscular dystrophy (DMD) and its relation to disease progression, using age as a proxy, and according to the ambulatory status of patients. METHODS: We conducted a cross-sectional study of patients diagnosed with DMD identified through the Portuguese Neuromuscular Patients Association (APN). Data regarding patient and caregiver demographics, patient health status, resource utilization and cost, and informal care were collected using a custom semistructured questionnaire. Labor productivity and absenteeism losses were captured using the Work Productivity and Activity Impairment questionnaire. Costs were valued using a societal perspective. RESULTS: A total of 46 patient-caregiver pairs were included, of which eight of the patients were ambulant and 38 were nonambulant. Age had a decreasing effect on COI, independent of the patient's disease stage. Annualized lifetime costs were at their highest in nonambulant patients around the mean age of loss of ambulation (10 years of age). The mean per patient stage-specific costs (year 2019 values) of DMD were estimated at €48,991 in the nonambulant stage and €19,993 in the ambulant stage. Direct nonmedical costs were the main cost drivers, followed by indirect costs. CONCLUSIONS: Our results indicate a close relation between overall disease costs and disease progression. DMD is associated with a substantial economic burden, which appears to be larger around the time ambulation is lost (10 years of age). The availability of new therapeutic options that delay disease progression, especially loss of ambulation, may prove to be highly beneficial for not only patients with DMD but also their families and society.

Matching-Adjusted Indirect Comparison of Efficacy and Consumption of rVIII-SingleChain Versus Two Recombinant FVIII Products Used for Prophylactic Treatment of Adults/Adolescents with Severe Haemophilia A.

INTRODUCTION: Given the relatively small number of patients with haemophilia A, head-to-head comparisons between recombinant FVIII (rFVIII) products are difficult to conduct. This study compared the efficacy and consumption of rVIII-SingleChain (lonoctocog alfa, AFSTYLA®) with rAHF-PFM (octocog alfa, Advate®) and rFVIIIFc (efmoroctocog alfa, Elocta®), for the prophylaxis and treatment of bleeding episodes in previously treated adolescents/adults with severe haemophilia A, through a matching-adjusted indirect comparison (MAIC). METHODS: A systematic literature review identified published clinical trials for rAHF-PFM and rFVIIIFc. Individual patient data for rVIII-SingleChain were used to match baseline patient characteristics to those from published trials, using an approach similar to propensity score weighting. After matching, annualized bleeding rates (ABR), percentage of patients with zero bleeds, and rFVIII consumption were compared across trial populations. RESULTS: Published data were identified from two rAHF-PFM trials and one rFVIIIFc trial. rVIII-SingleChain had similar ABR (risk ratio [RR]: 0.74 [0.16; 3.48]; RR: 1.18 [0.85; 1.65]) and percentage of patients with zero bleeds (odds ratio [OR]: 1.34 [0.56; 3.22]; OR: 0.78 [0.47; 1.31]) versus rAHF-PFM and rFVIIIFc, respectively. Annual rVIII-SingleChain consumption was significantly lower than rAHF-PFM (mean difference: - 1507.66 IU/kg/year [- 2011.71; - 1003.61]) and equivalent to rFVIIIFc (RR: 0.96 [0.62; 1.49]). CONCLUSION: Although limited to published information for comparator trials, these results suggest that with an annualized rFVIII consumption comparable to rFVIIIFc, but significantly lower than rAHF-PFM, routine prophylaxis with rVIII-SingleChain is able to maintain a similar ABR and percentage of patients with zero bleeds, attesting to the long-acting nature of rVIII-SingleChain.

It is difficult to directly compare different recombinant FVIII products in head-to-head studies because there are few patients with haemophilia A. This study aimed to indirectly compare the efficacy and consumption of different recombinant FVIII products in the prophylactic treatment of haemophilia A using published clinical data. A proven method for performing indirect comparisons of products is referred to as a matching-adjusted indirect comparison. Using this approach, we were able to compare rVIII-SingleChain with two other recombinant FVIII products (rAHF-PFM and rFVIIIFc). Our results suggest that annual FVIII consumption with rVIII-SingleChain is comparable to rFVIIIFc, but is significantly lower than rAHF-PFM, while maintaining a similar bleeding rate. These results highlight the long-acting nature of the product.

Predictors for incomplete response to ursodeoxycholic acid in primary biliary cholangitis. Data from a national registry of liver disease.

BACKGROUND: The current standard of treatment in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although a considerable proportion of patients show incomplete response resulting in disease progression. OBJECTIVE: This study aimed to assess the prevalence of incomplete response to UDCA and determine associated patients' characteristics. METHODS: Patients with PBC as main diagnosis were included from a national multicentric patient registry-Liver.pt. Main endpoints included incomplete response to UDCA treatment according to Barcelona, Paris I and Paris II criteria, Globe and UK PBC scores and the association between baseline characteristics and incomplete response according to Paris II criteria. RESULTS: A total of 434 PBC patients were identified, with a mean age of 55 years and 89.2% females. Nearly half of patients were asymptomatic at diagnosis and 93.2% had positive anti-mitochondrial antibodies. Almost all patients (95.6%) had been prescribed at least one drug for PBC treatment. At the last follow-up visit, 93.3% were under treatment of which 99.8% received UDCA. Incomplete response to UDCA was observed in 30.7%, 35.3%, 53.7% and 36.4% of patients according to Barcelona, Paris I, Paris II criteria and Globe score, respectively. After adjusting for age and sex, and accordingly to Paris II criteria, the risk for incomplete biochemical response was 25% higher for patients with cirrhosis at diagnosis (odds ratio [OR] = 1.25; 95% confidence interval [95%CI]: 1.02-1.54; p = 0.033) and 35% (95%CI:1.06-1.72; p = 0.016) and 5% (OR = 1.05; 95%CI:1.01-1.10; p = 0.013) for those with elevated gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP). CONCLUSION: A considerable proportion of patients showed incomplete biochemical response to UDCA treatment according to Paris II criteria. Cirrhosis, elevated GGT and ALP at diagnosis were identified as associated risk factors for incomplete response. Early identification of patients at risk of incomplete response could improve treatment care and guide clinical decision to a more careful patient monitorization.

Joint analysis of longitudinal and survival AIDS data with a spatial fraction of long-term survivors: A Bayesian approach.

A typical survival analysis with time-dependent covariates usually does not take into account the possible random fluctuations or the contamination by measurement errors of the variables. Ignoring these sources of randomness may cause bias in the estimates of the model parameters. One possible way for overcoming that limitation is to consider a longitudinal model for the time-varying covariates jointly with a survival model for the time to the event of interest, thereby taking advantage of the complementary information flowing between these two-model outcomes. We employ here a Bayesian hierarchical approach to jointly model spatial-clustered survival data with a fraction of long-term survivors along with the repeated measurements of CD4+ T lymphocyte counts for a random sample of 500 HIV/AIDS individuals collected in all the 27 states of Brazil during the period 2002-2006. The proposed Bayesian joint model comprises two parts: on the one hand, a flexible model using Penalized Splines to better capture the nonlinear behavior of the different CD4 profiles over time; on the other hand, a spatial cure model to cope with the set of long-term survivor individuals. Our findings show that joint models considering this set of patients were the ones with the best performance comparatively to the more traditional survival approach. Moreover, the use of spatial frailties allowed us to map the heterogeneity in the disease risk among the Brazilian states.

Bayesian joint modeling of longitudinal and spatial survival AIDS data.

Joint analysis of longitudinal and survival data has received increasing attention in the recent years, especially for analyzing cancer and AIDS data. As both repeated measurements (longitudinal) and time-to-event (survival) outcomes are observed in an individual, a joint modeling is more appropriate because it takes into account the dependence between the two types of responses, which are often analyzed separately. We propose a Bayesian hierarchical model for jointly modeling longitudinal and survival data considering functional time and spatial frailty effects, respectively. That is, the proposed model deals with non-linear longitudinal effects and spatial survival effects accounting for the unobserved heterogeneity among individuals living in the same region. This joint approach is applied to a cohort study of patients with HIV/AIDS in Brazil during the years 2002-2006. Our Bayesian joint model presents considerable improvements in the estimation of survival times of the Brazilian HIV/AIDS patients when compared with those obtained through a separate survival model and shows that the spatial risk of death is the same across the different Brazilian states. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacoeconomics of ruxolitinib therapy in patients with myelofibrosis.

BACKGROUND: Overall survival (OS) and other important clinical trial end-points seem increasingly more elusive in supporting rapid and efficient incorporation of innovative cancer drugs in clinical practice. This study proposes a clinical trial based pharmacoeconomic framework to assess the therapeutic and economic value of ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. METHODS: Individual patient level 144 week follow-up data from the COMFORT-II trial was used to account for the crossover effect on overall survival. Lifetime treatment benefits and costs were estimated considering detailed patterns of both ruxolitinib dose adjustments and blood transfusion needs. RESULTS: The authors estimate a 3.3 years increment in life expectancy (HR = 0.30; 95% CI = 0.17-0.55; p-value <0.001) and an incremental cost-effectiveness ratio of €40,000 per life year gained with the use of ruxolitinib. CONCLUSION: This study also demonstrates how valuable information from clinical trials can be used to support informed decisions about the early incorporation of innovative drugs.

Maternal child-feeding practices and dietary inadequacy of 4-year-old children.

This study aimed to evaluate the association between maternal perceived responsibility and child-feeding practices and dietary inadequacy of 4-year-old children. We studied 4122 mothers and children enrolled in the population-based birth cohort - Generation XXI (Porto, Portugal). Mothers self-completed the Child Feeding Questionnaire and a scale on covert and overt control, and answered to a food frequency questionnaire in face-to-face interviews. Using dietary guidelines for preschool children, adequacy intervals were defined: fruit and vegetables (F&V) 4-7 times/day; dairy 3-5 times/day; meat and eggs 5-10 times/week; fish 2-4 times/week. Inadequacy was considered as below or above these cut-points. For energy-dense micronutrient-poor foods and beverages (EDF), a tolerable limit was defined (<6 times/week). Associations between maternal perceived responsibility and child-feeding practices (restriction, monitoring, pressure to eat, overt and covert control) and children's diet were examined by logistic regression models. After adjustment for maternal BMI, education, and diet, and children's characteristics (sex, BMI z-scores), restriction, monitoring, overt and covert control were associated with 11-18% lower odds of F&V consumption below the interval defined as adequate. Overt control was also associated with 24% higher odds of their consumption above it. Higher perceived responsibility was associated with higher odds of children consuming F&V and dairy above recommendations. Pressure to eat was positively associated with consumption of dairy above the adequate interval. Except for pressure to eat, maternal practices were associated with 14-27% lower odds of inadequate consumption of EDF. In conclusion, children whose mothers had higher levels of covert control, monitoring, and restriction were less likely to consume F&V below recommendations and EDF above tolerable limits. Higher overt control and pressure to eat were associated, respectively, with higher possibility of children consuming F&V and dairy above recommendations.

Social inequalities in BMI trajectories: 8-year follow-up of the Pró-Saúde study in Rio de Janeiro, Brazil.

OBJECTIVE: In a cohort of government employees in Rio de Janeiro, Brazil, we investigated prospectively, sex-specific associations between education and BMI trajectories and their potential effect modification by race. DESIGN: Of the 4030 participants in Phase 1 (1999), 3253 (81 %) participated in Phase 2 (2003) and 3058 (76 %) participated in Phase 3 (2006). Education was categorized as elementary, high school or college graduate. Study participants self-identified as White, Black or Pardo. BMI was calculated from measured weight and height. BMI trajectories were modelled using a generalized additive regression model with mixed effects (GAMM). SETTING: The Pro-Saúde Study, a longitudinal investigation of social determinants of health. SUBJECTS: Women (n 1441) and men (n 1127) who participated in the three phases of data collection and had complete information for all study variables. RESULTS: Women and men with less than high school, or only a high school education, gained approximately 1 kg/m(2) more than college graduates (women: 1·06 kg/m(2) (P<0·001) and 1·06 kg/m(2) (P<0·001), respectively; men: 1·04 kg/m(2) (P=0·013) and 1·01 kg/m(2) (P=0·277), respectively). For women only, race was independently associated with weight gain. Women identifying as Pardo or Black gained 1·03 kg/m(2) (P=0·01) and 1·02 kg/m(2) (P=0·10), respectively, more than Whites. No effect modification by race was observed for either men or women. CONCLUSIONS: While both lower education and darker race were associated with greater weight gain, gender similarities and differences were observed in these associations. The relationship between weight gain and different indicators of social status are therefore complex and require careful consideration when addressing the obesity epidemic.

Analysis of HIV/AIDS DRG in Portugal: a hierarchical finite mixture model.

Inpatient length of stay (LOS) is an important measure of hospital activity, but its empirical distribution is often positively skewed, representing a challenge for statistical analysis. Taking this feature into account, we seek to identify factors that are associated with HIV/AIDS through a hierarchical finite mixture model. A mixture of normal components is applied to adult HIV/AIDS diagnosis-related group data (DRG) from 2008. The model accounts for the demographic and clinical characteristics of the patients, as well the inherent correlation of patients clustered within hospitals. In the present research, a normal mixture distribution was fitted to the logarithm of LOS and it was found that a model with two-components had the best fit, resulting in two subgroups of LOS: a short-stay subgroup and a long-stay subgroup. Associated risk factors for both groups were identified as well as some statistical differences in the hospitals. Our findings provide important information for policy makers in terms of discharge planning and the efficient management of LOS. The presence of "atypical" hospitals also suggests that hospitals should not be viewed or treated as homogenous bodies.

Prognostic value of a new cardiopulmonary exercise testing parameter in chronic heart failure: oxygen uptake efficiency at peak exercise - comparison with oxygen uptake efficiency slope.

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.

Análise de sobrevivência: teoria e aplicações em saúde / Survival analysis: theory and applications in health

O objetivo apoiar o desenvolvimento metodológico em análise de dados longitudinais, através da aplicação, teste e disseminação de métodos estatísticos inovadores no contexto da saúde, particularmente os voltados para a análise de sobrevida

Combining ventilatory efficiency and peak oxygen consumption in the prognostic assessment of patients with chronic heart failure.

UNLABELLED: Cardiopulmonary exercise testing (CPET) is an objective method for assessment of functional capacity and for prognostic stratification of patients with chronic heart failure (CHF). In this study, we analyzed the prognostic value of a recently described CPET-derived parameter, the minute ventilation to carbon dioxide production slope normalized for peak oxygen consumption (VE/VCO2 slope/pVO2). METHODS: We prospectively studied 157 patients with stable CHF and dilated cardiomyopathy who performed maximal CPET using the modified Bruce protocol. The prognostic value of VE/VCO2 slope/pVO2 was determined and compared with traditional CPET parameters. RESULTS: During follow-up 37 patients died and 12 were transplanted. Mean follow-up in surviving patients was 29.7 months (12-36). Cox multivariate analysis revealed that VE/VCO2 slope/pVO2 had the greatest prognostic power of all the parameters studied. A VE/VCO2 slope/pVO2 of > or = 2.2 signaled cases at higher risk. CONCLUSION: Normalization of the ventilatory response to exercise for peak oxygen consumption appears to increase the prognostic value of CPET in patients with CHF.

Predictors of mortality in HIV-associated hospitalizations in Portugal: a hierarchical survival model.

BACKGROUND: The beneficial effects of highly active antiretroviral therapy, increasing survival and the prevention of AIDS defining illness development are well established. However, the annual Portuguese hospital mortality is still higher than expected. It is crucial to understand the hospitalization behaviour to better allocate resources. This study investigates the predictors of mortality in HIV associated hospitalizations in Portugal through a hierarchical survival model. METHODS: The study population consists of 12,078 adult discharges from patients with HIV infection diagnosis attended at Portuguese hospitals from 2005-2007 that were registered on the diagnosis-related groups' database.We used discharge and hospital level variables to develop a hierarchical model. The discharge level variables were: age, gender, type of admission, type of diagnoses-related group, related HIV complication, the region of the patient's residence, the number of diagnoses and procedures, the Euclidean distance from hospital to the centroid of the patient's ward, and if patient lived in the hospital's catchment area. The hospital characteristics include size and hospital classification according to the National Health System. Kaplan-Meier plots were used to examine differences in survival curves. Cox proportional hazard models with frailty were applied to identify independent predictors of hospital mortality and to calculate hazard ratios (HR). RESULTS: The Cox proportional model with frailty showed that male gender, older patient, great number of diagnoses and pneumonia increased the hazard of HIV related hospital mortality. On the other hand tuberculosis was associated with a reduced risk of death. Central hospital discharge also presents less risk of mortality.The frailty variance was small but statistically significant, indicating hazard ratio heterogeneity among hospitals that varied between 0.67 and 1.34, and resulted in two hospitals with HR different from the average risk. CONCLUSION: The frailty model suggests that there are unmeasured factors affecting mortality in HIV associated hospitalizations. Consequently, for healthcare policy purposes, hospitals should not all be treated in an equal manner.

Serial changes in oxidized low-density lipoprotein associated with culprit vessel in ST-elevation myocardial infarction--a promising marker?

The aim of the present study was to investigate variations in oxidized LDL (oxLDL) at the onset of acute myocardial infarction (AMI) and over the recovery period, exploring their relationship with coronary disease severity. A follow-up of 50 AMI patients was evaluated against 25 healthy volunteers (reference group). The AMI patients were evaluated at three time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, and two and 40 days after intervention. Plasma oxLDL concentrations were measured by ELISA. oxLDL was found to be significantly higher in AMI patients in the acute phase relative to reference levels, decreasing progressively over the recovery period. The results also demonstrated that oxLDL levels were decreased in patients with the left circumflex artery (LCX) as culprit vessel compared to the left anterior descending coronary (LAD) or right coronary artery (RCA). The results highlight a significant increase in oxLDL concentration related to coronary artery disease severity, as conditions such as LCX lesions are usually associated with a favorable prognosis, contrasting with LAD-associated conditions that can compromise large areas of myocardium. The results thus suggest that oxLDL may constitute a promising marker in assessment of AMI evolution.

[Risk factors for respiratory morbidity at 12 to 36 months in very low birth weight premature infants previously admitted to a public neonatal intensive care unit]. / Fatores associados à morbidade respiratória entre 12 e 36 meses de vida de crianças nascidas de muito baixo peso oriundas de uma UTI neonatal pública.

The aim of this paper was to estimate respiratory morbidity and its determinants for premature infants aged 12 to 36 months. The population comprised 84 infants from a cohort of very low birth weight premature infants. The outcome was the respiratory morbidity incidence rate. The relationship between the independent variables and respiratory morbidity was estimated using a Poisson regression model. From 12 to 24 months of age, 56.3% of children had experienced at least one episode of respiratory disease. >From 24 to 36 months, 38.1% of children were affected. Variables significantly associated with respiratory morbidity were bronchopulmonary dysplasia (RR = 1.9; 95%CI: 1.2-2.9), abnormal lung compliance (RR = 1.6; 95%CI: 1.1-2.3), neonatal pneumonia (RR = 2.8; 95%CI: 1.9-4.0), patent ductus arteriosus (RR = 1.6; 95%CI: 1.1-2.5), and respiratory morbidity in the first year of life (RR = 1.7; 95%CI: 1.2-2.5). The incidence of respiratory morbidity remains high in this group of high-risk infants, which calls for regular follow-up and effective interventions to prevent respiratory disease and to improve the quality of life of these children and their families.

Fatores associados à morbidade respiratória entre 12 e 36 meses de vida de crianças nascidas de muito baixo peso oriundas de uma UTI neonatal pública / Risk factors for respiratory morbidity at 12 to 36 months in very low birth weight premature infants previously admitted to a public neonatal intensive care unit

O objetivo do estudo foi estimar a morbidade respiratória entre 12 e 36 meses em crianças prematuras e identificar os fatores associados. A população compreendeu 84 crianças de uma coorte de prematuros de muito baixo peso. O desfecho foi a taxa de incidência de morbidade respiratória. A associação entre as variáveis independentes e morbidade respiratória foi verificada por modelo linear generalizado. Entre 12 e 24 meses, 56,3 por cento das crianças apresentaram morbidade respiratória. Entre 24 e 36 meses, 38,1 por cento das crianças foram acometidas. As variáveis associadas à morbidade respiratória foram: displasia broncopulmonar (RT = 1,9; IC95 por cento: 1,2-2,9), complacência pulmonar alterada (RT = 1,6; IC95 por cento: 1,1-2,2), pneumonia neonatal (RT = 2,8; IC95 por cento: 2,0-4,0), persistência do canal arterial (RT = 1,6; IC95 por cento: 1,1-2,4) e morbidade respiratória no primeiro ano de vida (RT = 1,8; IC95 por cento: 1,3-2,6). A incidência de morbidade respiratória entre 12 e 36 meses se manteve elevada neste grupo de crianças de alto risco, o que reforça a necessidade de acompanhamento e de intervenções efetivas na prevenção do adoecimento e na melhora da qualidade de vida destas crianças e suas famílias.

The aim of this paper was to estimate respiratory morbidity and its determinants for premature infants aged 12 to 36 months. The population comprised 84 infants from a cohort of very low birth weight premature infants. The outcome was the respiratory morbidity incidence rate. The relationship between the independent variables and respiratory morbidity was estimated using a Poisson regression model. From 12 to 24 months of age, 56.3 percent of children had experienced at least one episode of respiratory disease. >From 24 to 36 months, 38.1 percent of children were affected. Variables significantly associated with respiratory morbidity were bronchopulmonary dysplasia (RR = 1.9; 95 percentCI: 1.2-2.9), abnormal lung compliance (RR = 1.6; 95 percentCI: 1.1-2.3), neonatal pneumonia (RR = 2.8; 95 percentCI: 1.9-4.0), patent ductus arteriosus (RR = 1.6; 95 percentCI: 1.1-2.5), and respiratory morbidity in the first year of life (RR = 1.7; 95 percentCI: 1.2-2.5). The incidence of respiratory morbidity remains high in this group of high-risk infants, which calls for regular follow-up and effective interventions to prevent respiratory disease and to improve the quality of life of these children and their families.

Results of primary angioplasty in a reference center: in-hospital outcomes.

INTRODUCTION: Primary angioplasty is accepted as the preferred treatment for acute myocardial infarction in the first 12 hours. However, outcomes depend to a large extent on the volume of activity and experience of the center. Continuous monitoring of methods and results obtained is therefore crucial to quality control. OBJECTIVE: To describe the demographic, clinical and angiographic characteristics as well as in-hospital outcomes of patients undergoing primary PCI in a high-volume Portuguese center. We also aimed to identify variables associated with in-hospital mortality in this population. METHODS: This was a retrospective registry of consecutive primary PCIs performed at Santa Marta Hospital between January 2001 and August 2007. Demographic, clinical, and angiographic characteristics and in-hospital outcomes were analyzed. Independent predictors of in-hospital mortality were identified by multivariate logistic regression analysis. RESULTS: A total of 1157 patients were identified, mean age 61+/-12 years, 76% male. Mean pain-to-balloon time was 7.6 hours and primary angiographic success was 88%. Overall in-hospital mortality was 6.9%, or 5.5% if patients presenting in cardiogenic shock were excluded from the analysis. Previous history of heart failure, cardiogenic shock on admission, invasive ventilatory support, major hemorrhage, and age over 75 years were found to be associated with increased risk of in-hospital death. CONCLUSIONS: In this center primary PCI is effective and safe. Angiographic success rates and in-hospital mortality and morbidity are similar to other international registries. Patients at increased risk for adverse outcome can be identified by simple clinical characteristics such as advanced age, cardiogenic shock on admission, mechanical ventilation and major hemorrhage during hospitalization.

Alternatives in modeling of body mass index as a continuous response variable and relevance of residual analysis.

This article presents alternatives for modeling body mass index (BMI) as a continuous variable and the role of residual analysis. We sought strategies for the application of generalized linear models with appropriate statistical adjustment and easy interpretation of results. The analysis included 2,060 participants in Phase 1 of a longitudinal study (Pró-Saúde Study) with complete data on weight, height, age, race, family income, and schooling. In our study, the residual analysis of models estimated by maximum likelihood methods yielded inadequate adjustment. The transformed response variable resulted in a good fit but did not lead to estimates with straightforward interpretation. The best alternative was to apply quasi-likelihood as the estimation method, presenting a better adjustment and constant variance. In epidemiological data modeling, researchers should always take trade-offs into account between adequate statistical techniques and interpretability of results.