Cardiogenetics is an international, peer-reviewed, open access journal that provides an advanced forum for studies related to all aspects of cardiogenetics (clinical, molecular, cellular, pharmacological). Cardiogenetics publishes reviews, regular research papers, and short communications.
A search strategy that follows the PICO format was established. This question was made visible in the descriptors in health science (DeCS, for its Spanish acronym) and the medical subject headings (MeSH). A search of articles was conducted in the following databases: Biblioteca Virtual de Salud (BVS), Base de Datos de la Fundación Index sobre Cuidados de Salud en Iberoamérica (CUIDEN), National Library of Medicine (MEDLINE), Joanna Briggs Institute (JBI), collection of databases of controlled clinical trials in health sciences (COCHRANE), and more. The following keywords were used for the search strategy: primary health care, nursing, workload, burnout, occupational health, patient safety, quality of care. They were combined using the booleans operators AND and OR for electronic searches conducted in the mentioned databases, as is shown in Tables S1 and S2.
Epidemiologia Clinica Alvaro Rui
Critical illness in COVID-19 is both an extreme disease phenotype and a relatively homogeneous clinical definition; it includes patients with hypoxaemic respiratory failure5 with acute lung injury6, and excludes many patients with non-pulmonary clinical presentations7, who are known to have divergent responses to therapy8. In the UK, individuals in the critically ill group are younger, less likely to have significant comorbidity and more severely affected than a general hospitalized cohort5, characteristics which may amplify observed genetic effects. In addition, as development of critical illness is in itself a key clinical end-point for therapeutic trials8, using critical illness as a phenotype in genetic studies enables the detection of directly therapeutically relevant genetic effects1.
Although our genome-wide gene-based association tests did not replicate any findings from a previous pathway-specific study of rare deleterious variants4, our results provide robust evidence implicating reduced interferon signalling in susceptibility to critical COVID-19. Notably, systemic administration of interferon in two large clinical trials, albeit late in disease, did not reduce mortality29,30.
Patients were recruited to the GenOMICC study in 224 UK intensive care units ( ). All individuals had confirmed COVID-19 according to local clinical testing and were deemed, in the view of the treating clinician, to require continuous cardiorespiratory monitoring. In UK practice this kind of monitoring is undertaken in high-dependency or intensive care units.
For those reasons, after considering other factors known to improve adaptation of the patient to NPPV, the use of sedation during NPPV can be part of a strategy designed to optimize its use. An international survey regarding current sedation practices during NPPV in patients with acute respiratory failure showed that among physicians, 41 % used sedation and 48 % analgesic therapy for NPPV in the USA, whilst 24 % used sedation and 35 % used analgesic therapy in Europe [6]. Pilot studies suggest that continuous infusion of a single sedative agent may decrease patient discomfort, with no significant effects on respiratory drive, respiratory pattern, or hemodynamics [7]. While the current limited data available suggests that sedation during NPPV is safe and feasible, more widespread application should await the results of larger observational studies or randomized clinical trials.
Our study represents the largest observational study in patients in NPPV receiving analgesic and/or sedative drugs. We observed a rate of unsuccessful NPPV in patients who received analgesic or sedative drugs in the range of previous reports (39 %). Using a marginal structural model, we showed an independent association between the use of combined sedation or analgesia during NPPV and NPPV failure. This potentially deleterious effect of simultaneous use of analgesic and sedative drugs on outcome of critically ill patients receiving NPPV has not previously been reported [20]. Nevertheless, randomized clinical trials are encouraged to further address this question.
To investigate the prevalence of Campylobacter spp. and C. jejuni in dog faecal material collected from dog walkways in the city of Palmerston North, New Zealand, and to characterise the C. jejuni isolates by multilocus sequence typing (MLST) and porA and flaA antigen gene typing. A total of 355 fresh samples of dogs faeces were collected from bins provided for the disposal of dog faeces in 10 walkways in Palmerston North, New Zealand, between August 2008-July 2009. Presumptive Campylobacter colonies, cultured on modified charcoal cefoperazone deoxycholate plates, were screened for genus Campylobacter and C. jejuni by PCR. The C. jejuni isolates were subsequently characterised by MLST and porA and flaA typing, and C. jejuni sequence types (ST) were assigned. Of the 355 samples collected, 72 (20 (95% CI=16-25)%) were positive for Campylobacter spp. and 22 (6 (95% CI=4-9)%) were positive for C. jejuni. Of the 22 C. jejuni isolates, 19 were fully typed by MLST. Ten isolates were assigned to the clonal complex ST-45 and three to ST-52. The allelic combinations of ST-45/flaA 21/porA 44 (n=3), ST-45/flaA 22/porA 53 (n=3) and ST-52/ flaA 57/porA 905 (n=3) were most frequent. The successful isolation of C. jejuni from canine faecal samples collected from faecal bins provides evidence that Campylobacter spp. may survive outside the host for at least several hours despite requiring fastidious growth conditions in culture. The results show that dogs carry C. jejuni genotypes (ST-45, ST-50, ST-52 and ST-696) that have been reported in human clinical cases. Although these results do not provide any evidence either for the direction of infection or for dogs being a potential risk factor for human campylobacteriosis, dog owners are advised to practice good hygiene with respect to their pets to reduce potential exposure to infection.
Research highlights: yields Cytochrome P450 3A4 (CYP3A4), metabolizes 50% of drugs in clinical use and requires NADPH-P450 reductase (POR). yields Mutations in human POR cause congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. yields We are reporting that mutations in POR may reduce CYP3A4 activity. yields POR mutants Y181D, A457H, Y459H, V492E and R616X lost 99%, while A287P, C569Y and V608F lost 60-85% CYP3A4 activity. yields Reduction of CYP3A4 activity may cause increased risk of drug toxicities/adverse drug reactions in patients with POR mutations. -- Abstract: Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizesmore approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations. less
Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines
Cytochrome P450 enzymes catalyze the biosynthesis of steroid hormones and metabolize drugs. There are seven human type I P450 enzymes in mitochondria and 50 type II enzymes in endoplasmic reticulum. Type II enzymes, including both drug-metabolizing and some steroidogenic enzymes, require electron donation from a two-flavin protein, P450 oxidoreductase (POR). Although knockout of the POR gene causes embryonic lethality in mice, we discovered human POR deficiency as a disorder of steroidogenesis associated with the Antley-Bixler skeletal malformation syndrome and found mild POR mutations in phenotypically normal adults with infertility. Assay results of mutant forms of POR using the traditional but nonphysiologic assay (reduction of cytochrome c) did not correlate with patient phenotypes; assays based on the 17,20 lyase activity of P450c17 (CYP17) correlated with clinical phenotypes. The POR sequence in 842 normal individuals revealed many polymorphisms; amino acid sequence variant A503V is encoded by 28% of human alleles. POR A503V has about 60% of wild-type activity in assays with CYP17, CYP2D6, and CYP3A4, but nearly wild-type activity with P450c21, CYP1A2, and CYP2C19. Activity of a particular POR variant with one P450 enzyme will not predict its activity with another P450 enzyme: Each POR-P450 combination must be studied individually. Human POR transcription, initiated from an untranslated exon, is regulated by Smad3/4, thyroid receptors, and the transcription factor AP-2. A promoter polymorphism reduces transcription to 60% in liver cells and to 35% in adrenal cells. POR deficiency is a newly described disorder of steroidogenesis, and POR variants may account for some genetic variation in drug metabolism.
Fecal calprotectin (FC) is the best noninvasive biomarker of disease activity in inflammatory bowel disease. Its correlation with endoscopic mucosal lesions could save inconvenient, expensive, and repeated endoscopic examinations in particular clinical settings. To assess the correlation between FC and the existence and severity of endoscopic postoperative recurrence (POR), a group of clinically stable outpatients with Crohn's disease for whom an ileocolonoscopy was routinely planned to assess POR were invited to collect a stool sample before starting bowel cleansing to measure FC. POR was graded by means of Rutgeerts endoscopic score. One hundred nineteen ileocolonoscopies were included, 42% with endoscopic POR. FC was significantly lower in the absence of endoscopic POR and in the absence of any endoscopic lesion. The area under the receiver operating characteristic curve was 0.76 (95% confidence interval, 0.68-0.85) for the diagnosis of the absence of lesions and 0.75 (95% confidence interval, 0.66-0.84) for endoscopic POR. Better sensitivity and negative predictive value were observed when combining FC and serum C-reactive protein (CRP), leading to a sensitivity of 82%, a specificity of 53%, and negative and positive predictive values of 81% and 54%, respectively, for the prediction of endoscopic POR with a combination of FC 100 μg/g and CRP 5 mg/L cutoff values. FC correlates closely with endoscopic POR in clinically stable postoperative patients with Crohn's disease and, when used in combination with CRP, might save endoscopic examinations and allow for a high-grade suspicion of endoscopic POR in the long-term monitoring of these patients. 2ff7e9595c
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