Prevalência de infecção relacionada à assistência à saúde em pacientes internados em unidade de terapia intensiva

Objective: To determine the prevalence of Infection Related to Health Care (IRHC) in patients admitted to the Intensive Care Unit (ICU).Method: Descriptive, retrospective study, with a quantitative approach. Data were collected through a form completed from infection notifications, followed by analysis of the results of microbiological tests available on the MV 2000i system.Results: The patients admitted to the ICU were female, elder and came from other inpatient units of the institution. The prevalence rate of infection was 5.3% confirmed by positive culture, and the respiratory system was the most frequent site of infection (42.5%). Most isolates were gram-negative pathogens (71.05%), highlighting the Acinetobacter sp. The antibiogram showed that Klebsiella sp. was resistant to ampicillin and amoxicillin plus clavulanic acid. Regarding Pseudomonas sp., 50% were resistant to imipenem, cefepime and ciprofloxacin. All Acinetobacteres were resistant to ceftazidime, followed by ceftriaxone and cefepime.Conclusion: The prevalence of IRHCs in critically ill patients represents a huge challenge, not only for professionals, but also for health managers and the whole society, justifying the need and relevance of actions aimed at prevention and control.Objetivo: Determinar la prevalencia de infección relacionada con la atención sanitaria (IRAS) en los pacientes ingresados en la Unidad de Cuidados Intensivos (UCI).Método: Estudio descriptivo, retrospectivo, con un enfoque cuantitativo. Los datos fueron recolectados a través de un formulario lleno de notificaciones de infección, seguido por el análisis de los resultados de las pruebas microbiológicas disponibles en el sistema 2000i MV.Resultados: Los pacientes ingresados en la UCI fueron las mujeres, los ancianos y los procedentes de otras unidades de hospitalización de la institución. La tasa de prevalencia de la infección fue del 5,3% confirmada por cultivo positivo, y el sistema respiratorio el lugar más frecuente de infección (42,5%). La mayoría de los patógenos aislados fueron gramnegativos (71,05%), destacando el Acinetobacter sp. El antibiograma mostró que Klebsiella sp. era resistente a la ampicilina y amoxicilina más ácido clavulánico. La Pseudomonas sp. 50% mostró resistencia a imipenem, cefepima y ciprofloxacina. Todos los Acinetobacteres eran resistentes a la ceftazidima, ceftriaxona y seguido de cefepima.Conclusión: La prevalencia de infecciones hospitalarias en pacientes críticamente enfermos se configura en un reto, no sólo para los profesionales, sino para los gerentes de salud y toda la sociedad, lo que justifica la necesidad y pertinencia de las acciones dirigidas a la prevención y control.Objetivo: Determinar a prevalência de Infecção Relacionada à Assistência à Saúde (IRAS) em pacientes internados em Unidade de Terapia Intensiva (UTI).Método: Estudo descritivo, retrospectivo, com abordagem quantitativa. Os dados foram coletados por meio de um formulário preenchido a partir das notificações de infecção, seguido de análise dos resultados de exames microbiológicos disponíveis no sistema MV 2000i.Resultados: Os pacientes admitidos na UTI eram do sexo feminino, idosos e procedentes de outras unidades de internamento da instituição. A taxa de prevalência de infecção foi de 5,3% confirmada por cultura positiva, sendo o sistema respiratório o sítio de infecção mais frequente (42,5%). A maioria dos patógenos isolados eram gram-negativos (71,05%), com destaque para o Acinetobacter sp. O antibiograma evidenciou que a Klebsiella sp. era resistente a ampicilina e amoxicilina mais ácido clavulânico. Quanto a Pseudomonas sp. 50% apresentou resistência a imipenem, cefepime e ciprofloxacino. Todos os Acinetobacteres foram resistentes a ceftazidima, seguido por ceftriaxona e cefepime.Conclusão: A prevalência das IRAS em pacientes críticos se configura em um desafio, não apenas aos profissionais, mas, aos gestores de saúde e a toda sociedade, justificando a necessidade e a relevância de ações voltadas à prevenção e controle

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P <.001). Overall motor and cognitive performance (P <.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P <.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P <.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P <.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used