Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness

Objectives: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality

Narrowing the Genetic Causes of Language Dysfunction in the 1q21.1 Microduplication Syndrome

The chromosome 1q21.1 duplication syndrome (OMIM# 612475) is characterized by head anomalies, mild facial dysmorphisms, and cognitive problems, including autistic features, mental retardation, developmental delay, and learning disabilities. Speech and language development are sometimes impaired, but no detailed characterization of language problems in this condition has been provided to date. We report in detail on the cognitive and language phenotype of a child who presents with a duplication in 1q21.1 (arr[hg19] 1q21.1q21.2(145,764,455-147,824,207) × 3), and who exhibits cognitive delay and behavioral disturbances. Language is significantly perturbed, being the expressive domain the most impaired area (with significant dysphemic features in absence of pure motor speech deficits), although language comprehension and use (pragmatics) are also affected. Among the genes found duplicated in the child, CDH1L is upregulated in the blood of the proband. ROBO1, a candidate for dyslexia, is also highly upregulated, whereas, TLE3, a target of FOXP2, is significantly downregulated. These changes might explain language, and particularly speech dysfunction in the proband

Absence of disparities in anthropometric measures among Chilean indigenous and non-indigenous newborns

<p>Abstract</p> <p>Background</p> <p>Studies throughout North America and Europe have documented adverse perinatal outcomes for racial/ethnic minorities. Nonetheless, the contrast in newborn characteristics between indigenous and non-indigenous populations in Latin America has been poorly characterized. This is due to many challenges, including a lack of vital registration information on ethnicity. The objective of this study was to analyze trends in anthropometric measures at birth in Chilean indigenous (Mapuche) and non-indigenous children over a 5-year period.</p> <p>Methods</p> <p>We examined weight and length at birth using information available through a national data base of all birth records for the years 2000 through 2004 (n = 1,166.513). Newborns were classified ethnically according to the origins of the parents' last names.</p> <p>Result</p> <p>The average birthweight was stable over the 5 year period with variations of less than 20 g in each group, and with mean values trivially higher in indigenous newborns. The proportion weighing less than 2500 g at birth increased modestly from 5.2% to 5.6% in non-indigenous newborns whereas the indigenous births remained constant at 5.2%. In multiple regression analyses, adjusting flexibly for gestational age and maternal characteristics, the occurrence of an indigenous surname added only 14 g to an average infant's birthweight while holding other factors constant. Results for length at birth were similar, and adjusted time trend variation in both outcomes was trivially small after adjustment. Anthropometric indexes at birth in Chile are quite favorable by international standards.</p> <p>Conclusion</p> <p>There is only a trivial degree of ethnic disparity in these values, in contrast to conditions for ethnic minorities in other countries. Moreover, these values remained roughly constant over the 5 years of observation in this study.</p

Rationale and design of a randomised controlled trial evaluating the effectiveness of an exercise program to improve the quality of life of patients with heart failure in primary care : the EFICAR study protocol

Background: Quality of life (QoL) decreases as heart failure worsens, which is one of the greatest worries of these patients. Physical exercise has been shown to be safe for people with heart failure. Previous studies have tested heterogeneous exercise programs using different QoL instruments and reported inconsistent effects on QoL. The aim of this study is to evaluate the effectiveness of a new exercise program for people with heart failure (EFICAR), additional to the recommended optimal treatment in primary care, to improve QoL, functional capacity and control of cardiovascular risk factors. Methods/Design: Multicenter clinical trial in which 600 patients with heart failure in NYHA class II-IV will be randomized to two parallel groups: EFICAR and control. After being recruited, through the reference cardiology services, in six health centres from the Spanish Primary Care Prevention and Health Promotion Research Network (redIAPP), patients are followed for 1 year after the beginning of the intervention. Both groups receive the optimized treatment according to the European Society of Cardiology guidelines. In addition, the EFICAR group performs a 3 month supervised progressive exercise program with an aerobic (high-intensity intervals) and a strength component; and the programme continues linked with community resources for 9 months. The main outcome measure is the change in health-related QoL measured by the SF-36 and the Minnesota Living with Heart Failure Questionnaires at baseline, 3, 6 and 12 months. Secondary outcomes considered are changes in functional capacity measured by the 6-Minute Walking Test, cardiac structure (B-type natriuretic peptides), muscle strength and body composition. Both groups will be compared on an intention to treat basis, using multi-level longitudinal mixed models. Sex, age, social class, co-morbidity and cardiovascular risk factors will be considered as potential confounding and predictor variables. Discussion: A key challenges of this study is to guarantee the safety of the patients; however, the current scientific evidence supports the notion of there being no increase in the risk of decompensation, cardiac events, hospitalizations and deaths associated with exercise, but rather the opposite. Safety assurance will be based on an optimized standardised pharmacological therapy and health education for all the participants

Smoking among pregnant women in Cantabria (Spain): trend and determinants of smoking cessation

<p>Abstract</p> <p>Background</p> <p>Cantabria (Spain) has one of the highest prevalence of smoking among women of the European Union. The objectives are to assess the trend of smoking during pregnancy in a five-year period and the determinants of smoking cessation during pregnancy in Cantabria.</p> <p>Methods</p> <p>A 1/6 random sample of all women delivering at the reference hospital of the region for the period 1998–2002 was drawn, 1559 women. Information was obtained from personal interview, clinical chart, and prenatal care records. In the analysis relative risks and 95% confidence intervals were estimated. Multivariable analysis was carried out using stepwise logistic regression.</p> <p>Results</p> <p>Smoking prior to pregnancy decreased from 53.6% in 1998 to 39.4% in 2002. A decrease in smoking cessation among women smoking at the beginning of pregnancy was observed, from 37.3% in 1998 to 20.6% in 2002. The mean number of cigarettes/day (cig/d) before pregnancy remained constant, around 16 cig/d, whereas a slight trend to increase over time was seen, from 7.7 to 8.9 cig/d. In univariate analysis two variables favoured significantly smoking cessation, although they were not included in the stepwise logistic regression analysis, a higher education level and to be married. The logistic regression model included five significant predictors (also significant in univariate analysis): intensity of smoking, number of previous pregnancies, partner's smoking status, calendar year of study period (these four variables favoured smoking continuation), and adequate prenatal care (which increased smoking cessation).</p> <p>Conclusion</p> <p>The frequency of smoking among pregnant women is very high in Cantabria. As smoking cessation rate has decreased over time, a change in prenatal care programme on smoking counseling is needed. Several determinants of smoking cessation, such as smoking before pregnancy and partner's smoking, should be also addressed by community programmes.</p

Health-related quality of life and mental health in the medium-term aftermath of the Prestige oil spill in Galiza (Spain): a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>In 2002 the oil-tanker <it>Prestige </it>sank off the Galician coast. This study analyzes the effect of this accident on health-related quality of life (HRQoL) and mental health in the affected population.</p> <p>Methods</p> <p>Using random sampling stratified by age and sex, 2700 residents were selected from 7 coastal and 7 inland Galician towns. Two exposure criteria were considered: a) residential exposure, i.e., coast versus interior; and b) individual exposure-unaffected, slightly affected, or seriously affected-according to degree of personal affectation. SF-36, GHQ-28, HADS and GADS questionnaires were used to assess HRQoL and mental health. Association of exposure with suboptimal scores was summarized using adjusted odds ratios (OR) obtained from logistic regression.</p> <p>Results</p> <p>For residential exposure, the SF-36 showed coastal residents as having a lower likelihood of registering suboptimal HRQoL values in physical functioning (OR:0.69; 95%CI:0.54–0.89) and bodily pain (OR:0.74; 95%CI:0.62–0.91), and a higher frequency of suboptimal scores in mental health (OR:1.28; 95%CI:1.02–1.58). None of the dimensions of the other questionnaires displayed statistically significant differences.</p> <p>For individual exposure, no substantial differences were observed, though the SF-36 physical functioning dimension rose (showed better scores) with level of exposure (91.51 unaffected, 93.86 slightly affected, 95.28 seriously affected, p < 0.001).</p> <p>Conclusion</p> <p>Almost one and a half years after the accident, worse HRQoL and mental health levels were not in evidence among subjects exposed to the oil-spill. Nevertheless, some of the scales suggest the possibility of slight impact on the mental health of residents in the affected areas.</p

Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region

<p>Abstract</p> <p>Background</p> <p>Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes.</p> <p>Methods</p> <p>A combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region.</p> <p>Results</p> <p>In this study we present a new clinical association of severe neonatal encephalopathy (Lubs syndrome) and HSCR, in a male patient carrying a duplication at the Xq28 region which encompasses the <it>MECP2 </it>and <it>L1CAM </it>genes.</p> <p>Conclusions</p> <p>While the encephalopathy has been traditionally attributed to the <it>MECP2 </it>gene duplication in patients with Lubs syndrome, here we propose that the enteric phenotype in our patient might be due to the dosage variation of the L1CAM protein, together with additional molecular events not identified yet. This would be in agreement with the hypothesis previously forwarded that mutations in <it>L1CAM </it>may be involved in HSCR development in association with a predisposing genetic background.</p

The functioning of the Cuban home hospitalization programme: a descriptive analysis

BACKGROUND: Over the last decades hospital at home (HaH) programmes have been set up in many, mainly European, countries. The Cuban HaH programme is not hospital driven, but the responsibility of the first line health services, and family doctors play a pivotal role. METHODS: We analyse the structure and functioning of the Cuban programme. In this descriptive study, information was prospectively collected on HaH patients admitted between July 1st 2001 and June 30th 2002. RESULTS: Admission rates varied between areas from 0.014 to 0.035 per person per year (ppy). The < 1 y and 1-4 y age groups had the highest admission rates. In one area the follow-up of pregnancy problems led to high 15-24 y and 25-49 y female admission rates (0,070 and 0,058 respectively). Respiratory affections were the most frequent reason for admission (32,6%), followed by early hospital discharge (16,0%) and gynaeco-obstetrical problems (10.8%). The median length of stay varied from 5 to 7 days between regions and from 5 days (early discharge) to 7 days (gynaeco-obstetrical problems) in function of the reason for admission. On average an HaH episode entailed 1.4 and 1.6 contacts per patient-day with the family doctor and nurse respectively. CONCLUSION: Difference in admission criteria in function of geography, distance to the hospital, transport facilities, and staff factors, as well as differences in hospital policy on early discharge explain the observed variability. The programme plays an important role in the integrated approach to quality care in the Cuban health system, but could benefit from more uniform admission criteria

Breast-Milk Substitutes: A New Old-Threat for Breastfeeding Policy in Developing Countries. A Case Study in a Traditionally High Breastfeeding Country

Background: Developing countries with traditionally breastfeeding are now experiencing the increasing pressure of formula milk marketing. This may endanger lives and undermine the efforts of national policies in achieving the objectives of the Millennium Development Goals. We examined the use of, and factors for use, of all available breast-milk substitutes (BMS) in a country with a traditionally high rate of breastfeeding. Methods: Randomised multi-stage sampling surveys in 90 villages in 12/17 provinces in Laos. Participants: 1057 mothers with infants under 24 months of age. Tools: 50-query questionnaire and a poster of 22 BMS (8 canned or powdered milk; 6 non-dairy; 6 formulas; 2 non-formulas). Outcome measures included: prevalence of use and age of starting BMS in relation to socio-demographic characteristics and information sources, by univariate and multivariate analyses