Exposure risk and COVID-19 infection among frontline health-care workers: A single tertiary care centre experience.

BACKGROUND: There is limited data on frontline health-care workers and risk of COVID-19 from the developing nations. It is imperative to identify those at higher risk to prevent further transmission. We assessed the relationship between exposure risk and COVID-19 among front-line health-care workers who were primary contacts of a COVID-19 patient. METHODS: A retrospective cohort study was conducted among front-line health-care workers in a tertiary care hospital who were exposed to a COVID-19 patient. Information on demographic factors, medical history, exposure related factors and subsequently COVID-19 lab reports were collected. An exposure risk assessment designed collating various exposure related factors categorized the participants into those with high and low risk. We used logistic regression to estimate the odds ratio of our primary outcome, a positive COVID-19 test when the independent variables were exposure risk, age, gender and occupation. RESULTS: Among1858 frontline workers who were primary contacts of a COVID-19 patient at the hospital, 106 (5.7%) incident reports of a positive COVID-19 test were recorded. None of the exposure related factors had any significant association with a positive COVID-19 test. However, high exposure risk category was significantly associated with COVID-19 positive test at the end of quarantine. CONCLUSION: COVID-19 was more frequent among front-line health-care workers who belonged to high exposure category. Education at different levels of service delivery at hospitals is required for best practice in order to prevent COVID-19 among health care providers. There is need to develop additional strategies to ensure that the information is translated in to practice.

An invasive management strategy is associated with improved outcomes in high-risk acute coronary syndromes in patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is associated with poor outcomes after acute coronary syndromes, yet selection for invasive investigation and management is low. METHODS: Patients presenting with ST segment elevation myocardial infarction (STEMI) or intermediate- to high-risk non-ST segment elevation acute coronary syndrome (NSTEACS) (n=2597) were stratified into groups based on kidney function, defined as normal (glomerular filtration rate (GFR)≥60mL/min/1.73m(2) ), moderate CKD (GFR 30-59mL/min/1.73m(2) ) and severe CKD (GFR <30mL/min/1.73m(2)). Based on these stratums of kidney function, incidence and outcome measures were obtained for: rates of angiography and revascularization; 6-month mortality; and the incidence and outcome of in-hospital acute kidney impairment (AKI). RESULTS: Patients with CKD were less likely to be offered coronary angiography after STEMI/NSTEACS (P<0.001); however, after selection, revascularization rates were similar (percutaneous coronary intervention (P=0.8); surgery (P=0.4)). Six-month mortality rates increased with CKD (GFR≥60, 2.8%; GFR 30-59, 9.9%; GFR<30, 16.5%, P≤0.001), as well as the combined efficacy/safety end-point (GFR≥60, 9.4%; GFR 30-59, 20.2%; GFR<30, 27.1%, P≤0.001). Six-month mortality was lower in patients who had received prior angiography (GFR≥60, 1.5% vs 3.6%, P=0.001; GFR 30-59, 5.1% vs 12.7%, P<0.001; GFR<30, 7.3% vs 18.5%, P=0.094). Risk of AKI increased with CKD (GFR≥60, 0.7%; GFR 30-59, 3.4%; GFR<30, 6.8%, P≤0.001), and was associated with high 6-month mortality (35.6% vs 4.1%, P<0.001). CONCLUSIONS: In patients with CKD after STEMI/NSTEACS, 6-month mortality and morbidity is high, selection for angiography is lower, yet angiography is associated with a reduced long-term mortality, and with comparable revascularization rates to those without CKD. In-hospital AKI is more common in CKD and predicts a high 6-month mortality.

Low level determination of 4-amino-2-ethoxy-cinnamic acid and its ethyl ester in a drug substance and its formulation prototypes by HPLC-UV-DAD.

A reversed-phase high-performance liquid chromatographic method (HPLC) with diode-array detection (DAD) has been evaluated for monitoring trace levels of impurities, such as 4-amino-2-ethoxy-cinnamic acid (impurity A), hydrochloride salt of 4-amino-2-ethoxy-ethyl cinnamate (impurity B), and 4-bromo-3-ethoxy-nitrobenzene (impurity C), in drug substance and 3 different formulation prototypes. These compounds have been highlighted as potential genotoxins and 2-ethoxy-4-amino-cinnamic acid (impurity A) as possible degradant isolated during the synthesis of BI drug substance. HPLC-UV-DAD was found to be more promising, and limits of quantification were between 0.09 and 0.6 microg/mL, which enabled detection limits in drug substance at 2-15 ppm for a 15 mg/mL solution. All three genotoxic impurities are completely resolved from each other as well as from diluent peaks, drug substance, and other related impurities within 40 min. The retention times of impurities A, B, and C were 3.4, 13.1, and 21.3 min. The results demonstrating the specificity, assay precision, recovery, linearity, and range achieved during the method validation experiments are presented in this paper.

HPLC-UV method development and validation for the determination of low level formaldehyde in a drug substance.

A reversed-phase high-performance liquid chromatographic method (HPLC) with diode-array detection is developed and validated for the quantitative determination of formaldehyde in a drug substance. Formaldehyde (HCHO) is reacted with 2,4-dinitrophenylhydrazine (DNPH) to form a Schiff base (HCHO-DNPH derivatization product), which has an absorbing maximum (lambda max) at 360 nm. The HPLC method employs a C8, 3-microm particle size analytical column (150 mm x 4.6 mm), 15-microL injection volume, column temperature controlled at 30 degrees C, detection at 360 nm, and a water-acetonitrile (55:45, v/v) mobile phase at a flow rate of 1 mL/min. These conditions resolve the HCHO-DNPH product from unreacted DNPH, the drug substance and related impurities, as well as diluent peaks within 20 min. The retention time of the HCHO-DNPH product is approximately 6.4 min. The method is linear, accurate in the specified range (0.33-333 ppm), and robust based on analyte (HCHO-DNPH derivatization product) stability in standard and sample. Detection limit is 0.03 ng (0.1 ppm).

Disparate surgical margin lengths of colorectal resection specimens between in vivo and in vitro measurements. The effects of surgical resection and formalin fixation on organ shrinkage.

We noticed almost routine disparate results in margin lengths when colorectal specimens are measured in vivo by the surgeon and in vitro by the pathologist. We studied 26 sigmoid and rectum specimens to document the amount of organ shrinkage after surgical removal and fixation. Each specimen had a 5.0-cm segment at each end of the specimen marked by serosal sutures before vascular devitalization. The segments were measured after the specimen sat unfixed for 10 to 20 minutes and after 12 to 18 hours of formalin fixation. The segments shrank to a median length of 3.0 cm (40% of the in vivo length) after 10 to 20 minutes and an additional 0.85 cm, to a median length of 2.15 cm, after fixation. Overall after fixation, the segments shrank 57% of the in vivo length. Approximately 70% of the shrinkage occurred during the first 10 to 20 minutes after removal, and the remaining 30% occurred after fixation. For optimal accuracy, margin distance must be obtained immediately after surgical removal. Once the specimen has been removed for several minutes, the difference between unfixed and fixed margin lengths is 30%. A correction factor of approximately 2x should be applied when interpreting the margin length.

Portal tract eosinophils and hepatocyte cytokeratin 7 immunoreactivity helps distinguish early-stage, mildly active primary biliary cirrhosis and autoimmune hepatitis.

We studied nondiagnostic liver biopsy specimens from 20 patients with definite primary biliary cirrhosis (PBC) and 18 with definite autoimmune hepatitis (AIH) to identify distinguishing features. All patients had early-stage disease; biopsy specimens were devoid of granulomas or diagnostic features of PBC or AIH. Diagnoses were based on serologic and clinical variables. Sixteen specimens from each group were immunostained with cytokeratin 7. The density of portal tract eosinophils and number with cytokeratin 7-reactive periportal hepatocytes were quantified. Sixteen of 18 patients with AIH and 13 of 20 with PBC had no or minimal bile duct injury. Histologic activity index scores were 5.8 in AIH and 5.7 in PBC. The mean portal eosinophil score was greater in PBC than in AIH. Cytokeratin 7 identified many central bile ducts that were obscured by portal inflammation. The mean periportal cytokeratin 7-reactive hepatocyte score was greater in PBC than in AIH. Portal eosinophils and cytokeratin 7 reactivity in periportal hepatocytes are supportive of PBC rather than AIH. No morphologic features were supportive of AIH. Cytokeratin 7 reactivity in periportal hepatocytes may be an early response to PBC-induced biliary obstruction in other regions of the liver.

Potential survival gains in the treatment of myocardial infarction.

OBJECTIVES: To evaluate the potential impact of complete implementation of guideline recommendations in myocardial infarction (MI) care, and contrast this with new innovations. DESIGN: Modelling of potential events prevented from literature-based treatment effects and observed guideline recommendation utilisation rates. SETTING: Hospital-based care. PARTICIPANTS: Nationwide registry of 1630 patients with MI adjusted for age, gender and GRACE score extrapolated to a population of 10 000 patients. INTERVENTIONS: Literature-based efficacy estimates associated with guideline-recommended treatments and a putative treatment providing a 10-30% 12-month event reduction. MAIN OUTCOME MEASURES: Mortality and recurrent MI or stroke by 30 days and 30 days to 12 months. RESULTS: Adjusted-mortality rates for optimally managed patients with ST-segment MI (STEMI) and non-ST-segment MI (NSTEMI) to 30 days were 0.6% and 2.5%, respectively. Adjusted mortality from 30 days to 12 months was 1.8% among optimally managed patients. No reperfusion occurred in 31% of patients with STEMI. Fewer than four guideline treatments were prescribed in 26% of patients at discharge. Compared with in-hospital care, better application of secondary prevention treatments provided the greater absolute gains (STEMI 23 lives/10 000 patients by 30 days, NSTEMI 43 lives/10 000 by 30 days and secondary prevention 104 lives/10 000 by 12 months). A putative novel treatment reducing mortality by 30% among optimally managed patients would save a further 4 lives/10 000 by 12 months. CONCLUSIONS: Potential gains from improved clinical effectiveness in MI care are likely to compare favourably with benefits achieved though innovations, and should inform priorities in research and implementation strategies for improving MI outcomes.

Impact of acute and chronic risk factors on use of evidence-based treatments in patients in Australia with acute coronary syndromes.

OBJECTIVE: To determine whether acute risk factors (ARF) and chronic risk factors (CRF) contribute differently to the use of evidence-based treatments (EBT) for patients with acute coronary syndromes (ACS). DESIGN: Data were collected through a prospective audit of patients with ACS. Management was analysed by the presence of acute myocardial risk factors and chronic comorbid risk factors at presentation. SETTING: 39 hospitals across Australia. PATIENTS: 2599 adults presenting with ACS. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Use of EBT, in-hospital and 12-month death, recurrent myocardial infarction and bleeding. RESULTS: The number of ARF and CRF at presentation predicted in-hospital and 12-month death, recurrent myocardial infarction and bleeding. Patients with higher numbers of ARF were more likely to receive EBT (aspirin at presentation, 81.1% for zero ARF to 85.7% for > or =3 ARF, p<0.001; angiography 45.9% to 67.5%, p<0.001; reperfusion for ST elevation 50% to 70%, p = 0.392; beta blocker at discharge 66.5% to 74.4%, p<0.001). Patients with higher numbers of CRF were less likely to receive EBT (aspirin at presentation 90.4% for zero CRF to 68.8% for > or =4 CRF, p<0.001; angiography 78.8% to 24.7%, p<0.001; reperfusion for ST elevation 73.4% to 30%; p<0.001, beta blocker at discharge 75.2% to 55.6%; p<0.001). In multivariate regression analysis, ARF and CRF were the strongest predictors of receiving or failing to receive EBT, respectively. CONCLUSIONS: Patients presenting with many ARF are more likely to receive EBT, while patients presenting with many CRF are less likely to receive them. This has important implications for future quality-improvement efforts.

Antifungal and antibacterial metabolites from a sclerotium-colonizing isolate of Mortierella vinacea.

The known compound methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (1) and three new related metabolites, which we have named mortivinacins A (2), B (3), and C (4), were identified as metabolites of the fungus Mortierella vinacea. Nicotinic acid (5) was also encountered. This isolate of M. vinacea was obtained from an Aspergillus flavus sclerotium during field studies of sclerotium longevity in soil. Compounds 1-5 were isolated by chromatographic fractionation of organic extracts from M. vinacea solid-substrate fermentation cultures, and the structures were assigned by analysis of NMR and MS data. Compounds 1, 2, and 5 were responsible for the antibacterial and antifungal activities of the extract.

Sporovexins A-C and a new preussomerin analog: antibacterial and antifungal metabolites from the coprophilous fungus Sporormiella vexans.

Sporovexins A-C (1-3) and 3'-O-desmethyl-1-epipreussomerin C (4) have been isolated from liquid cultures of the coprophilous fungus Sporormiella vexans (JS 306). The structures of these new metabolites were elucidated on the basis of MS and NMR analysis. Compounds 1 and 4 show antifungal activity against competitor fungi, as well as antibacterial effects.

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

Vertilecanins: new phenopicolinic acid analogues from Verticillium lecanii.

Five new phenopicolinic acid analogues (1-5) have been isolated from solid-substrate fermentation cultures of Verticillium lecanii. The most abundant component (vertilecanin A; 1) displays antiinsectan activity against Helicoverpa zea. These compounds were obtained by chromatographic fractionation of the EtOAc culture extract and identified by analysis of NMR and MS data. The known fungal metabolites 2-decenedioic acid and 10-hydroxy-8-decenoic acid were also isolated from these cultures.