Iris Delgado

Exclusion Criteria for Intravenous Thrombolysis in Stroke Mimics: An Observational Study

BACKGROUND Stroke mimics (SMs) are frequent in emergency departments (EDs), but are treated infrequently with intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis. We aimed at identifying the factors that lead to the exclusion of SMs from thrombolytic therapy. METHODS Consecutive patients presenting to the ED between December 2004 and March 2011 with symptoms that suggested acute ischemic stroke were included. RESULTS Eight hundred forty-two patients were included in this study; 113 (13.4%) were considered SMs; these patients were younger (P = .01), more frequently diabetic (P = .001), arrived later to the ED (P = .03), had lower National Institutes of Health Stroke Scale scores (P < .001), and higher frequencies of negative diffusion-weighted imaging studies (P = .002). The most common causes of cases of SM were toxic metabolic disorders (n = 34 [30.1%]) and seizures (n = 22 [19.5%]). The most frequent cause of consultation was aphasia (n = 43 [37.6%]). SM patients had a total of 152 contraindications for rt-PA, with 34 (30%) patients having >1 contraindication. The most frequent of these were being beyond the therapeutic window for thrombolysis (n = 96) and having deficits not measurable by the National Institutes of Health Stroke Scale or very mild symptoms before the start of rt-PA (n = 37). Twenty-four (21.2%) patients had both contraindications simultaneously. Two patients (1.76%) in the SM group were candidates for rt-PA but did not receive this treatment because they or their family rejected it. Of 729 stroke patients, 87 (11.9%) did receive rt-PA. CONCLUSIONS SM patients frequently had exclusion criteria for systemic thrombolysis, the most frequent being presenting beyond the established thrombolytic window.

Ventilatory inefficiency as a limiting factor for exercise in patients with COPD.

BACKGROUND: Ventilatory inefficiency increases ventilatory demand; corresponds to an abnormal increase in the ratio of minute ventilation (V̇E) to CO2 production (V̇CO2); represents increased dead space, deregulation of respiratory control, and early lactic threshold; and is associated with expiratory flow limitation that enhances dynamic hyperinflation and may limit exercise capacity. OBJECTIVE: To evaluate the influence of ventilatory inefficiency over exercise capacity in COPD patients. METHODS: Prospective study of 35 COPD subjects with different levels of severity, in whom cardiopulmonary stress test was performed. Ventilatory inefficiency was represented by the V̇E/V̇CO2 relation. Its influence over maximal oxygen consumption (V̇O2max), power (W), and ventilatory threshold was evaluated. Surrogate parameters of cardiac function, like oxygen pulse (V̇O2/heart rate) and circulatory power (%V̇O2max × peak systolic pressure), were also evaluated. RESULTS: Cardiopulmonary stress test was stopped due to dyspnea with elevated V̇E and marked reduction of breathing reserve. A severe increase in V̇E/V̇CO2 (mean ± SD 35.9 ± 5.6), a decrease of V̇O2max (mean ± SD 75.2 ± 20%), and a decrease of W (mean ± SD 68.6 ± 23.3%) were demonstrated. Twenty-eight patients presented dynamic hyperinflation. Linear regression showed a reduction of 2.04% on V̇O2max (P < .001), 2.6% on W (P < .001), 1% on V̇O2/heart rate (P = .049), and 322.7 units on circulatory power (P = .02) per each unit of increment in V̇E/V̇CO2, respectively. CONCLUSIONS: Ventilatory inefficiency correlates with a reduction in exercise capacity in COPD patients. Including this parameter in the evaluation of exercise limitation in this patient population may mean a contribution toward the understanding of its pathophysiology.

Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis

Background Fibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes of FGF23 and Klotho levels and their regulatory factors in children on chronic peritoneal dialysis (PD). Methods FGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) plasma concentrations were measured during 1 year of follow-up in PD children. Anthropometric and dialytical parameters were evaluated in addition to mineral metabolism variables. Results Thirty-one patients under chronic PD were followed for 12 months. FGF23 mean plasma levels at Month 1 were significantly increased compared with controls, 215.1 ± 303.6 versus 9.4 ± 5.7 pg/mL, respectively (P < 0.001). Baseline Klotho levels were 41% lower in patients compared with controls, 132.1 ± 58 versus 320 ± 119.4 pg/mL, respectively (P < 0.001), and did not correlate with FGF23 and phosphorus levels. At Month 12, FGF23 (195 ± 300 pg/mL) and Klotho levels (130 ± 34 pg/mL) remained similar to baseline values. Log-FGF23 correlated significantly with height/age Z score (r= −0.38) and residual renal function (r = −0.44), but no correlation was found with serum phosphorus, phosphate intake, PTH and vitamin D levels. The log-FGF23 strongly correlated with calcium levels at Months 1, 6 and 12, however, this relationship was blunted if serum phosphorus was >6 mg/dL. By multiple regression analysis, calcium was the strongest variable determining FGF23 levels. Conclusions In this longitudinal study, FGF23 levels are markedly increased, and Klotho levels are reduced in PD children compared with controls. FGF23 levels appeared to be regulated primarily by serum calcium, showing a significant correlation at each time of measurement. This relationship was lost in patients with phosphorus >6 mg/dL. These observations may have important consequences to the therapeutic management of phosphate homeostasis in CKD patients.

Steroid Withdrawal in Pediatric Kidney Transplant Allows Better Growth, Lipids and Body Composition: A Randomized Controlled Trial

Background: Glucocorticoid immunosuppressant therapy in pediatric kidney transplant (Tx) recipients does not allow the improvement of growth after Tx. Objective: To determine the effect of early steroid withdrawal (SW) on longitudinal growth, insulin sensitivity (IS), and body composition (BC). Methods: This was a prospective, randomized, multicenter study in Tx. Insulin-like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP3), IS, and BC (DEXA/pQCT) were determined at baseline and up to 12 months after Tx. Results: A total of 30 patients were examined; 14 patients were assigned to the SW group (7 male, 7 female; 12 in Tanner stage I) and 16 patients were assigned to the steroid control (SC) group (10 male, 6 female;12 in Tanner stage I). Their chronological age was 7.8 ± 4.3 years, height was -2.3 ± 0.99 SD scores (SDS), and body mass index -0.3 ± 1.2 SDS. After 1 year, the SW group showed an increase in height SDS (+1.2 ± 0.22 vs. +0.60 ± 0.13 SDS in the SC group, p < 0.02), lower IGFBP3 (p < 0.05), cholesterol (p < 0.05), and higher high-density lipoprotein cholesterol (p < 0.05). SW patients had lower trunk fat with no differences in IS. Only in prepubertal patients, the SW group had lower glycemia (p < 0.05), very low-density lipoprotein cholesterol (p < 0.01), triglycerides (p < 0.05), triglycerides/glycemia index (TyG; p < 0.02), and better lean mass. Both groups showed an improvement in lean mass after kidney Tx. Conclusions: SW improved longitudinal growth, lipid profile, and trunk and lean fat in Tx patients. In prepubertal recipients, the decrease in TyG suggests better IS.

Socioeconomic and Cardiovascular Variables Explaining Regional Variations in Stroke Mortality in Chile: An Ecological Study

Background: Regional differences in stroke mortality rates have been described in Chile. These could be related to the distribution of cardiovascular risk factors, the quality of medical care or socioeconomic status influencing incidence or case fatality rates. Our objective was to investigate variables explaining the variability in stroke mortality rates in the different regions of Chile. Methods: Adjusted stroke mortality rates in different regions were calculated for the year 2003. Variables were added from three sources: the National Death Certificate Database, the National Socioeconomic Characterization Survey and the National Health Survey. A logistic regression model was used to investigate regions, demographic variables and socioeconomic variables associated with the risk of death from stroke. A linear regression model was used to study the association of socioeconomic variables and cardiovascular risk factors with the standardized mortality rate by region and the contribution of these to the variability. Results: A twofold increase was found in adjusted stroke mortality rates among regions. Greater risk was associated with older age, female gender and residence in regions V, VII, VIII and IX. Sixty-two percent of the regional variability rate was explained by the combined prevalence of poverty (34%), diabetes (17%), sedentarism (8%) and overweight (3%). Conclusion: The risk of death from stroke in Chile is associated with age, sex and living in four specific regions of the country. The majority of the increased risk in these regions is explained by the prevalence of poverty, diabetes, a sedentary lifestyle and overweight.

Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study

Objective Chromosome 22q11.2 deletion is the most commonly occurring known microdeletion syndrome. Deaths related to the syndrome have been reported, but the magnitude of death has not been quantified. This study evaluated the deletions impact on survival and its clinical manifestations in a large cohort of Chilean patients. Design Demographic and clinical data of individuals with 22q11 deletions diagnosed between 1998 and 2013 were collected from medical records and death certificates. Case fatality rate was calculated and compared with national vital statistics. OR with 95% CI analysis was used to assess the association between clinical manifestations and death. Setting Genetic services in tertiary care centres in Chile, following patients with 22q11.2 deletion. Outcomes Fatality rate and associated factors. Results 59 of 419 patients (14.1%) died during the study period at a median of 3.4 months (range 0 to 32 years of age). Factors associated with death included congenital heart disease (OR 5.27; 95% CI 2.06 to 13.99; p<0.0001), hypocalcaemia (OR 4.27; 95% CI 1.67 to 11.15; p<0.002) and airway malacia (OR 13.37; 95% CI 1.19 to 110.51; p<0.002). Patients with deletions and defects such as tetralogy of Fallot with or without pulmonary atraesia, truncus arteriosus or ventricular septal defect, had a 2.6-fold to 4.6-fold higher death rate compared with nationwide reports for the same types of defects. Conclusions In this cohort, we observed a death rate of 14.1%, implying that one in seven patients with 22q11 deletion died during the study period. Significant associations with cardiac defects, hypocalcaemia and airway malacia were observed. Furthermore, the death risk in patients with 22q11 deletion and cardiac defects exceeded the global figures observed in Chile for infants with structurally similar but apparently isolated anomalies. These observations indicate a need to identify patients who may require specific perioperative management to improve survival.

A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus.

BACKGROUND In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.

Growth in Chilean infants with chromosome 22q11 microdeletion syndrome.

Chromosome 22q11 microdeletion syndrome has a wide range of clinical manifestations including congenital heart malformations, palatal defects, endocrine abnormalities, immunologic deficits, learning difficulties, and an increased predisposition to psychiatric disease. Short stature and poor weight gain in infancy are common findings and are usually seen in the absence of hormone deficiencies. An increased frequency of obesity has been observed in adolescents and adults. We generated gender‐specific growth curves from 0 to 24 months of age, based on 479 length and 475 weight measurements from 138 Chilean patients with 22q11 deletion. Final adult height and weight on 25 individuals were analyzed. The 10th, 50th, and 90th centile‐smoothed curves for infants were built using the LMS method and compared with World Health Organization Child Growth Standards. The 50th centile for length in the deleted patients was slightly lower than the 10th centile of WHO standards in boys and girls. The same was observed for weight, although a trend toward a gradual increase near 2 years of age was observed, particularly in boys. Average adult height was 152 cm (ranging from 143 to 162 cm) in females, corresponding to the 10th centiles of WHO standards, and 166 cm for males (160–172 cm), at the 20th centile of WHO standards. A third of the adult females and none of the males had body mass index (BMI) greater than 25. The curves should be useful to monitor growth in infants with 22q11 microdeletion syndrome.

Did Socioeconomic Inequality in Self-Reported Health in Chile Fall after the Equity-Based Healthcare Reform of 2005? A Concentration Index Decomposition Analysis.

Objective Chile, a South American country recently defined as a high-income nation, carried out a major healthcare system reform from 2005 onwards that aimed at reducing socioeconomic inequality in health. This study aimed to estimate income-related inequality in self-reported health status (SRHS) in 2000 and 2013, before and after the reform, for the entire adult Chilean population. Methods Using data on equivalized household income and adult SRHS from the 2000 and 2013 CASEN surveys (independent samples of 101 046 and 172 330 adult participants, respectively) we estimated Erreygers concentration indices (CIs) for above average SRHS for both years. We also decomposed the contribution of both “legitimate” standardizing variables (age and sex) and “illegitimate” variables (income, education, occupation, ethnicity, urban/rural, marital status, number of people living in the household, and healthcare entitlement). Results There was a significant concentration of above average SRHS favoring richer people in Chile in both years, which was less pronounced in 2013 than 2000 (Erreygers corrected CI 0.165 [Standard Error, SE 0.007] in 2000 and 0.047 [SE 0.008] in 2013). To help interpret the magnitude of this decline, adults in the richest fifth of households were 33% more likely than those in the poorest fifth to report above-average health in 2000, falling to 11% in 2013. In 2013, the contribution of illegitimate factors to income-related inequality in SRHS remained higher than the contribution of legitimate factors. Conclusions Income-related inequality in SRHS in Chile has fallen after the equity-based healthcare reform. Further research is needed to ascertain how far this fall in health inequality can be attributed to the 2005 healthcare reform as opposed to economic growth and other determinants of health that changed during the period.

Tuberculosis in prisoners and their contacts in Chile: estimating incidence and latent infection.

SETTING Contact investigation of tuberculosis (TB) patients in Chilean prisons. OBJECTIVE 1) To estimate TB incidence and the prevalence of latent tuberculous infection (LTBI) among prisoners and their contacts; and 2) to determine factors associated with disease transmission. DESIGN Cross-sectional study conducted in 46 prisons (51% of the total prison population) to assess the prevalence of and risk factors for LTBI among contacts of prisoners newly diagnosed with pulmonary TB. We used in vitro interferon-gamma release assays to establish LTBI and a questionnaire to address risk factors. RESULTS During the 1-year follow-up, we studied 418 contacts of 33 active TB cases. We found high TB incidence (123.9 per 100,000 prisoners) and high LTBI prevalence (29.4%) among contacts. LTBI rates are significantly higher in prison inmates than in non-prisoners (33.2% vs. 15.6%). Male sex, illicit drugs, malnutrition, corticosteroid use, low educational level and sharing a cell with a case increase the risk of LTBI. Multivariate analyses showed that corticosteroid use, duration of incarceration and overcrowding are the most relevant determinants for LTBI among all contacts. CONCLUSIONS Our results confirm that incarceration increases the risk of tuberculous infection and TB disease, and that it was associated not only with origin from vulnerable groups, but also with the prison environment. Reinforcing TB control is essential to prevent TB transmission in prisons.