Investigation of 89 candidate gene variants for effects on all-cause mortality following acute coronary syndrome

Background  

Many candidate genes have been reported to be risk factors for acute coronary syndrome (ACS), but their impact on clinical prognosis following ACS is unknown.     

COMPRI--an instrument to detect patients with complex care needs: results from a European study

The authors developed a screening instrument to detect patients in need of complex care coordination at admission to a general hospital. On the basis of a series of risk factors for care complexity, the authors constructed a short, care complexity prediction instrument (COMPRI) and assessed its qualities. The COMPRI is an easily administered screening instrument that detects patients at risk for complex care needs for whom care coordination is indicated. COMPRI's predictive power exceeds all currently available case-mix instruments.     

Murine model of pulmonary anthrax: kinetics of dissemination, histopathology, and mouse strain susceptibility

Bioweapons are most often designed for delivery to the lung, although this route is not the usual portal of entry for many of the pathogens in the natural environment. Vaccines and therapeutics that are efficacious for natural routes of infection may not be effective against the pulmonary route. Pulmonary models are needed to investigate the importance of specific bacterial genes in virulence, to identify components of the host immune system that are important in providing innate and acquired protection, and for testing diagnostic and therapeutic strategies. This report describes the characteristics of host and Bacillus anthracis interactions in a murine pulmonary-infection model. The infective dose varied depending on the route and method of inoculation. The germination process in the lung began within 1 h of inoculation into the lung, although growth within the lung was limited. B. anthracis was found in the lung-associated lymph nodes approximately 5 h after infection. Minimal pneumonitis was associated with the lung infection, but significant systemic pathology was noted after dissemination. Infected mice typically succumbed to infection approximately 3 to 4 days after inoculation. The 50% lethal doses differed among inbred strains of mice, but within a given mouse strain, neither the age nor the sex of the mice influenced susceptibility to B. anthracis.     

Asthma medication use in pregnancy and fetal growth

BACKGROUND: Given the high prevalence of asthma in pregnancy, it is important to understand the relationship between asthma medications and fetal growth in the context of appropriate treatment. OBJECTIVE: This study examines the effect of inhaled corticosteroids, systemic corticosteroids, and beta(2)-agonists on fetal growth in 654 infants born to women with asthma compared with 303 infants born to controls without asthma. METHODS: Subjects for this prospective study were enrolled throughout North America between 1998 and 2003 and followed up by the Organization of Teratology Information Services. Incidence of small for gestational age (SGA) infants and mean birth size measures were compared among groups. RESULTS: Mean birth weight of full-term infants born to mothers who used systemic corticosteroids (3373 g) was lower than in the beta(2)-agonist group (3552 g) and controls without asthma (3540 g; P < .05) after adjustment for other risk factors. However, no differences in the incidence of SGA for weight were observed among groups. Adjusted mean birth length was slightly shorter in the systemic steroid group compared with controls (P=.02). Incidence of SGA for length and head circumference and mean head circumference did not vary among groups (P>.05). CONCLUSION: The treatment of asthma with systemic corticosteroids resulted in a deficit of about 200 g in birth weight compared with controls and exclusive beta(2)-agonist users and no increased incidence of SGA. These results suggest that asthma management with beta(2)-agonists and/or inhaled corticosteroids during pregnancy does not impair fetal growth, whereas systemic corticosteroids have a minimal effect which should be weighed against the necessity to control severe asthma.     

The relationship of residents' autonomy and use of a teaching hospital's resources

This 1990 study examines the relationship between the degree of use of patient care resources and the degree of supervision of residents by attending physicians (as perceived by residents) at a large midwestern teaching hospital. Ratings of the degree of clinical autonomy allowed residents by 65 attending physicians--each of whom had a general internal medicine practice with a significant hospital component--were provided by 23 former internal medicine chief residents and 17 internal medicine residents who were in their third year at the time of the study. A regression model was used to test the association between hospital resource use (as shown by total hospital charges to patients and their lengths of stay) and the residents' mean ratings of the degrees of autonomy the attending physicians permitted residents, for 7,169 of these physicians' patients discharged between 1986 and 1989 in 28 diagnosis-related groups. The analysis was controlled for patients' insurance status and chronic disease comorbidities. The patients whose attending physicians were rated as allowing substantial clinical autonomy had significantly lower total charges and lengths of stay (p less than .0001). These results suggest that internal medicine residents have an inherently conservative practice style that values low-intensity workups and rapid discharge of patients.     

Complete genomic screen in Parkinson disease: evidence for multiple genes.

CONTEXT: The relative contribution of genes vs environment in idiopathic Parkinson disease (PD) is controversial. Although genetic studies have identified 2 genes in which mutations cause rare single-gene variants of PD and observational studies have suggested a genetic component, twin studies have suggested that little genetic contribution exists in the common forms of PD. OBJECTIVE: To identify genetic risk factors for idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Genetic linkage study conducted 1995-2000 in which a complete genomic screen (n = 344 markers) was performed in 174 families with multiple individuals diagnosed as having idiopathic PD, identified through probands in 13 clinic populations in the continental United States and Australia. A total of 870 family members were studied: 378 diagnosed as having PD, 379 unaffected by PD, and 113 with unclear status. MAIN OUTCOME MEASURES: Logarithm of odds (lod) scores generated from parametric and nonparametric genetic linkage analysis. RESULTS: Two-point parametric maximum parametric lod score (MLOD) and multipoint nonparametric lod score (LOD) linkage analysis detected significant evidence for linkage to 5 distinct chromosomal regions: chromosome 6 in the parkin gene (MLOD = 5.07; LOD = 5.47) in families with at least 1 individual with PD onset at younger than 40 years, chromosomes 17q (MLOD = 2.28; LOD = 2.62), 8p (MLOD = 2.01; LOD = 2.22), and 5q (MLOD = 2.39; LOD = 1.50) overall and in families with late-onset PD, and chromosome 9q (MLOD = 1.52; LOD = 2.59) in families with both levodopa-responsive and levodopa-nonresponsive patients. CONCLUSIONS: Our data suggest that the parkin gene is important in early-onset PD and that multiple genetic factors may be important in the development of idiopathic late-onset PD.     

Association of single-nucleotide polymorphisms of the tau gene with late-onset Parkinson disease.

CONTEXT: The human tau gene, which promotes assembly of neuronal microtubules, has been associated with several rare neurologic diseases that clinically include parkinsonian features. We recently observed linkage in idiopathic Parkinson disease (PD) to a region on chromosome 17q21 that contains the tau gene. These factors make tau a good candidate for investigation as a susceptibility gene for idiopathic PD, the most common form of the disease. OBJECTIVE: To investigate whether the tau gene is involved in idiopathic PD. DESIGN, SETTING, AND PARTICIPANTS: Among a sample of 1056 individuals from 235 families selected from 13 clinical centers in the United States and Australia and from a family ascertainment core center, we tested 5 single-nucleotide polymorphisms (SNPs) within the tau gene for association with PD, using family-based tests of association. Both affected (n = 426) and unaffected (n = 579) family members were included; 51 individuals had unclear PD status. Analyses were conducted to test individual SNPs and SNP haplotypes within the tau gene. MAIN OUTCOME MEASURE: Family-based tests of association, calculated using asymptotic distributions. RESULTS: Analysis of association between the SNPs and PD yielded significant evidence of association for 3 of the 5 SNPs tested: SNP 3, P =.03; SNP 9i, P =.04; and SNP 11, P =.04. The 2 other SNPs did not show evidence of significant association (SNP 9ii, P =.11, and SNP 9iii, P =.87). Strong evidence of association was found with haplotype analysis, with a positive association with one haplotype (P =.009) and a negative association with another haplotype (P =.007). Substantial linkage disequilibrium (P<.001) was detected between 4 of the 5 SNPs (SNPs 3, 9i, 9ii, and 11). CONCLUSIONS: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.     

Apnoeic oxygenation in paediatric anaesthesia: a narrative review

Apnoeic oxygenation refers to oxygenation in the absence of any patient or ventilator effort to move the lungs. This phenomenon was first described in humans in the mid-20th century but has seen renewed interest in the last decade following the demonstration of apnoeic oxygenation with low-flow, and subsequently high-flow, nasal oxygen. This narrative review summarises our understanding of apnoeic oxygenation in the paediatric population. We examine the evidence supporting oxygenation via tracheal tube, modified laryngoscopes and nasal cannulae. The evidence for prolongation of safe apnoea time at induction of anaesthesia is also appraised. We explore the capacity for carbon dioxide clearance, flow rate selection with high-flow nasal oxygen and complications associated with the technique. It remains uncertain whether apnoeic oxygenation in paediatric patients results in a meaningful clinical benefit compared with standard care for outcomes such as the number of tracheal intubation attempts or the incidence of hypoxaemia. In particular, the role of apnoeic oxygenation in paediatric difficult airway management is unclear as this has not been the targeted focus of any published research to date.     

Comparison of local influenza vaccine effectiveness using two methods

BackgroundIn some settings, research methods to determine influenza vaccine effectiveness (VE) may not be appropriate because of cost, time constraints, or other factors. Administrative database analysis of viral testing results and vaccination history may be a viable alternative. This study compared VE estimates from outpatient research and administrative databases.MethodsUsing the test-negative, case-control design, data for 2017–2018 and 2018–2019 influenza seasons were collected using: 1) consent, specimen collection, RT-PCR testing and vaccine verification using multiple methods; and 2) an administrative database of outpatients with a clinical respiratory viral panel combined with electronic immunization records. Odds ratios for likelihood of influenza infection by vaccination status were calculated using multivariable logistic regression. VE = (1 ? aOR) × 100.ResultsResearch participants were significantly younger (P < 0.001), more often white (69% vs. 59%; P < 0.001) than non-white and less frequently enrolled through the emergency department (35% vs. 72%; P < 0.001) than administrative database participants. VE was significant against all influenza and influenza A in each season and both seasons combined (37–49%). Point estimate differences between methods were evident, with higher VE in the research database, but insignificant due to low sample sizes. When enrollment sites were separately analyzed, there were significant differences in VE estimates for all influenza (66% research vs. 46% administrative P < 0.001) and influenza A (67% research vs. 49% administrative; P < 0.001) in the emergency department.Conclusions:The selection of the appropriate method for determining influenza vaccine effectiveness depends on many factors, including sample size, subgroups of interest, etc., suggesting that research estimates may be more generalizable. Other advantages of research databases for VE estimates include lack of clinician-related selection bias for testing and less misclassification of vaccination status. The advantages of the administrative databases are potentially shorter time to VE results and lower cost.