Factors associated with SARS-CoV-2-related hospital outcomes among and between persons living with and without diagnosed HIV infection in New York State.

BACKGROUND: Persons living with diagnosed HIV (PLWDH) are at increased risk for severe illness due to COVID-19. The degree to which this due to HIV infection, comorbidities, or other factors remains unclear. METHODS: We conducted a retrospective matched cohort study of individuals hospitalized with COVID-19 in New York State between March and June 2020, during the first wave of the pandemic, to compare outcomes among 853 PLWDH and 1,621 persons without diagnosed HIV (controls). We reviewed medical records to compare sociodemographic and clinical characteristics at admission, comorbidities, and clinical outcomes between PLWDH and controls. HIV-related characteristics were evaluated among PLWDH. RESULTS: PLWDH were significantly more likely to have cardiovascular (matched prevalence-ratio [mPR], 1.22 [95% CI, 1.07-1.40]), chronic liver (mPR, 6.71 [95% CI, 4.75-9.48]), chronic lung (mPR, 1.76 [95% CI, 1.40-2.21]), and renal diseases (mPR, 1.77 [95% CI, 1.50-2.09]). PLWDH were less likely to have elevated inflammatory markers upon hospitalization. Relative to controls, PLWDH were 15% less likely to require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) and 15% less likely to require admission to the intensive care unit. No significant differences were found in in-hospital mortality. PLWDH on tenofovir-containing regimens were significantly less likely to require mechanical ventilation or ECMO (risk-ratio [RR], 0.73 [95% CI, 0.55-0.96]) and to die (RR, 0.74 [95% CI, 0.57-0.96]) than PLWDH on non-tenofovir-containing regimens. CONCLUSIONS: While hospitalized PLWDH and controls had similar likelihood of in-hospital death, chronic disease profiles and degree of inflammation upon hospitalization differed. This may signal different mechanisms leading to severe COVID-19.

Emergence of Congenital Chagas Disease in Ireland.

Chagas disease (CD) is an under-diagnosed tropical disease that is increasingly being observed outside of Latin America. We describe the first 2 infants with congenital Chagas Disease (cCD) in Ireland. Clinicians in nonendemic countries need to be aware of the potential for cCD due to the migration of women from countries of high prevalence.

Assessing standards for prevention of early onset group B streptococcal (GBS) disease in Ireland.

BACKGROUND: Early onset group B streptococcal (GBS) disease can cause significant neonatal morbidity and mortality. There is currently no Irish national guideline for GBS screening, and protocols vary across maternity units. Polymerase chain reaction (PCR) testing at induction or labour onset informs triage for antibiotic prophylaxis; however, there are human and infrastructural resource requirements to enable widespread implementation. AIM: Our aim was to identify current standard practices for GBS prevention in Irish obstetric and neonatal services and to utilise this data to inform the need for, and potential impact of implementation of, a national guideline. METHODS: A questionnaire on GBS screening, management and existing resources was completed by an informed staff member from each of the 19 Irish maternity units, including questions regarding timing and method of screening, antibiotic usage, and neonatal management. RESULTS: One unit (5.2%) performs routine GBS screening at 35-37 weeks of gestation. Twelve units (63%) screen for GBS following spontaneous rupture of membranes (SROM) after 37 weeks, of which two (17%) perform PCR and ten (83%) culture testing. Seventeen units (89.3%) have access to a GeneXpert PCR machine, and of these, two (11.7%) use the machine for rapid GBS testing. Two units screen patients for GBS at either the start of labour or induction of labour. Four units (21%) use the neonatal early onset sepsis (EOS) calculator. Sixteen units (84%) do not treat asymptomatic infants born to GBS-positive mothers.  CONCLUSION: There is a lack of consistency in the methods for GBS screening and disease prevention across the country, highlighting the need for a national guideline accompanied by an implementation plan and budget to standardise care.

Haematological parameters and coagulation in umbilical cord blood following COVID-19 infection in pregnancy.

OBJECTIVE: The aim of this study was to evaluate infants, born to women with SARS-CoV-2 detected during pregnancy, for evidence of haematological abnormalities or hypercoagulability in umbilical cord blood. STUDY DESIGN: This was a prospective observational case-control study of infants born to women who had SARS-CoV-2 RNA detected by PCR at any time during their pregnancy (n = 15). The study was carried out in a Tertiary University Maternity Hospital (8,500 deliveries/year) in Ireland. This study was approved by the Hospital Research Ethics Committee and written consent was obtained. Umbilical cord blood samples were collected at delivery, full blood count and Calibrated Automated Thrombography were performed. Demographics and clinical outcomes were recorded. Healthy term infants, previously recruited as controls to a larger study prior to the outbreak of COVID-19, were the historical control population (n = 10). RESULTS: Infants born to women with SARS-CoV-2 had similar growth parameters (birth weight 3600 g v 3680 g, p = 0.83) and clinical outcomes to healthy controls, such as need for resuscitation at birth (2 (13.3%) v 1 (10%), p = 1.0) and NICU admission (1 (6.7%) v 2 (20%), p = 0.54). Haematological parameters (Haemoglobin, platelet, white cell and lymphocyte counts) in the COVID-19 group were all within normal neonatal reference ranges. Calibrated Automated Thrombography revealed no differences in any thrombin generation parameters (lag time (p = 0.92), endogenous thrombin potential (p = 0.24), peak thrombin (p = 0.44), time to peak thrombin (p = 0.94)) between the two groups. CONCLUSION: In this prospective study including eligible cases in a very large population of approximately 1500 women, there was no evidence of derangement of the haematological parameters or hypercoagulability in umbilical cord blood due to COVID-19. Further research is required to investigate the pathological placental changes, particularly COVID-19 placentitis and the impact of different strains of SARS-CoV-2 (particularly the B.1.1.7 and the emerging Delta variant) and the severity and timing of infection on the developing fetus.

The Effect of COVID-19 Infection During Pregnancy; Evaluating Neonatal Outcomes and the Impact of the B.1.1.7. Variant.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection during pregnancy has been associated with adverse perinatal outcomes. We aim to evaluate the neonatal outcomes including the incidence of preterm birth, admission to the neonatal unit and incidence of congenital anomalies in this cohort. We will also describe these outcomes in the context of the B.1.1.7. variant outbreak, the dominant variant in Ireland since January 2021, which has had a greater impact on pregnant patients. METHODS: This was a retrospective study of liveborn infants, delivered between 1st March 2020 and 1st March 2021, to women with a severe acute respiratory syndrome coronavirus 2 diagnosis during pregnancy, in a tertiary maternity hospital (8,500 deliveries/year). Clinical data were collected, and analyses were performed to evaluate the impact of maternal symptom status, time from diagnosis to delivery and the B.1.1.7. variant on neonatal outcome. RESULTS: In total 133 infants (1.6%) were born to women with severe acute respiratory syndrome coronavirus 2 identified during pregnancy. The median birth weight was 3.45 kg and gestational age at birth was 39.3 weeks. 14 infants (10.5%) were preterm. 22 infants (16.5%) required admission to the neonatal unit and 7 (5.3%) were small for gestational age. There was no difference in growth, preterm birth or neonatal unit admission based on maternal symptom status or infection after the outbreak of B.1.1.7. as the dominant strain. CONCLUSIONS: Following a COVID-19 infection in pregnancy, there was no increase in the incidence of preterm birth or neonatal intensive care unit admission compared with 5-year hospital data. Maternal symptom status did not influence neonatal outcomes. Further studies to evaluate the impact of COVID-19 in early pregnancy, the variants of concern, particularly the emerging Delta variant and COVID-19 placentitis are required.

Vertical Transmission of Trypanosoma Cruzi in a Non-Endemic Country: Histology of the Infected Placenta.

Chagas disease, once confined to rural Latin America is an increasing public health concern in non-endemic countries due to population movements. Here we present an unexpected finding of a placenta infected with T. cruzi from a Brazilian woman residing in Ireland. Histology of the placenta showed a lymphocytic chorioamnionitis with multinucleated giant cells (MNGCs) as well as cord vasculitis and funisitis. Amastigotes of trypanosomiasis were found in both cord and membranes. The placenta parenchyma, however, had no villitis or amastigotes and maturation was appropriate for gestation. To date, there have been few reported cases of vertical transmission in non-endemic countries. We discuss the histological findings and review the literature on potential modes of transmission from mother to fetus.

Local Anesthetic Systemic Toxicity (LAST): Designing an Educational Effort for Nurses That Will Last.

PURPOSE: To improve knowledge and raise awareness of nurses who assist certified registered nurse anesthetists or anesthesiologists with peripheral nerve block or spinal block procedures about a potential life-threatening local anesthetic systemic toxicity (LAST) event. DESIGN: An evidence-based practice project design. METHODS: Nurses in units where nerve block procedures were performed (ie, postanesthesia care unit, preoperative, operating room, outpatient services, labor and delivery unit) received a pretest about their knowledge of LAST events, participated in a 30-minute educational session, and then completed a post-test. The data were analyzed for differences and statistical significance. Included in the test was a question about the nurse's comfort level with managing a LAST event. FINDINGS: The findings demonstrated a knowledge deficit related to LAST events. The average of all three units combined pretest scores was 60% and post-test scores increased to 95%. The average comfort level of all three units was 3.5/10 (35%) before the educational in-service program and increased to 7.9/10 (79%) after education. CONCLUSIONS: Nurses working in units where nerve blocks are performed are lacking in knowledge of the signs and symptoms and the correct course of treatment for a LAST event. This could lead to poor outcomes of a very high-risk low-volume event.

Screening for group B Streptococcus (GBS) at labour onset using PCR: accuracy and potential impact - a pilot study.

This pilot study assessed the diagnostic accuracy and potential impact of a rapid PCR-based screening test for the detection of group B Streptococcus (GBS) at the onset of labour for the purpose of optimising intrapartum antibiotic prophylaxis (IAP). Vaginal and rectal swabs from a convenience sample of 158 women were analysed by conventional broth-enriched culture and a rapid PCR test. Overall, GBS carriage was 18.98% by culture and 19.62% by PCR. PCR for the detection of GBS had a sensitivity of 93.1%, specificity of 96.67% and area under the curve (AUC) of 0.95. Only 19.3% GBS-positive women received IAP. Three-fourths of babies born to GBS-positive mothers did not receive surveillance for early-onset GBS disease. Of the women who received IAP, only 32.5% were GBS carriers. Seventy-four percent of the GBS-positive mothers delivered more than 5 h after recruitment, which gives adequate swab to delivery interval for appropriate antibiotic prophylaxis in labour. Impact statement What is already known about this subject: Appropriate intra-partum treatment of colonized mothers reduces the risk of GBS transmission to neonates. Universal ante partum screening of pregnant women or IAP based on risk factors in labour for GBS prevention fail to accurately identify and treat the woman who actually harbors GBS in the birth canal in labour. A PCR based rapid test, allows for real-time assessment of GBS carriage in labour. WHAT THIS STUDY ADDS: This study highlights the fact that a large number of GBS carriers in labour, who could potentially infect their babies, do not receive IAP, and most of their babies do not receive added surveillance in the neonatal period for EOGBS disease. It also confirms that PCR testing at onset of labour is a highly sensitive and reliable test that identifies the women who are GBS carriers in labour and hence need IAP. What the implications are of these findings for clinical practice and/or further research: Timely provision of IAP for the appropriate woman is possible by adopting universal GBS screening at the onset of labor using GBS-PCR. This would involve additional costs to health care facilities and added work to laboratory personnel.

Assessing children's speech using picture-naming: The influence of differing phonological variables on some speech outcomes.

PURPOSE: Sometimes, children's speech is judged as typical on picture-naming tests and not on other speech tests, even other picture-naming tests. This study attempts to explain this observation by examining the impact of increasing the numbers of polysyllabic words in a picture-naming test on the outcomes of percentages of consonants and vowels correct and phonological processes. METHOD: The participants were 283 randomly sampled, typically-developing children, aged 3-7-years. These Australian English speakers named pictures, yielding ∼166 selected words, varied for syllable number, stress and shape, which repeatedly sampled all consonants and vowels of Australian English. RESULT: Most mismatches occurred in di- and polysyllabic words, with few in monosyllabic words: the usual words in picture-naming speech tests. Significant age effects existed for percentages of consonants and vowels correct and for 12 of the 16 phonological processes investigated. Many age effects were present at 7 years; later than often reported. CONCLUSION: These findings imply that additional di- and polysyllabic words add value to routine speech testing. Further, children, especially school children, who "pass" speech tests dominated by monosyllabic words may benefit from further examination of their productions of di- and polysyllabic words before finalizing clinical judgements about their speech status.

Syphilis serology in pregnancy: an eight-year study (2005-2012) in a large teaching maternity hospital in Dublin, Ireland.

All cases of positive syphilis serology detected in antenatal and peripartum screening in a large teaching maternity hospital in inner city Dublin, Ireland over an eight-year period (2005-2012 inclusive) were reviewed and included in our study. Demographic, antenatal registration, laboratory (including co-infections), partner serology, treatment and delivery data were recorded in our database. Infant follow-up, treatment and outcome data were also collected. During this period, 194 women had positive syphilis serology, of which 182 completed their pregnancies at the institution. This accounts for 0.28% of the total number of women completing their pregnancies during this time (N = 66038); 79 had no previous diagnosis of infection. There was one case of re-infection during pregnancy. Thirty-two women were co-infected with human immunodeficiency virus, hepatitis B or hepatitis C. There was one case suggestive of congenital syphilis infection. Our study is a comprehensive analysis of the diagnosis, management and clinical outcomes of women testing positive for syphilis infection in pregnancy. It reveals the relatively high prevalence of syphilis infection in the population utilising the maternity services in north inner-city Dublin. It re-enforces the importance of continued active surveillance to prevent morbidity and mortality associated with maternal syphilis infection. It also highlights the importance of strategies such as re-testing high-risk groups and definitive screening of spouse serology.

Pregnancy Outcomes of Mothers with Detectable CMV-Specific IgM Antibodies: A Three-Year Review in a Large Irish Tertiary Referral Maternity Hospital.

A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan.

Recovery of drugs of abuse from Dräger DCD5000 oral fluid collection device in Australia.

In Australia, it is a requirement of workplace oral fluid (OF) drugs of abuse testing that drug recovery from collection devices be verified by an accredited laboratory. Recovery data are used in conjunction with collection volume imprecision data and uncertainty of measurement to provide an estimation of drug concentration in neat OF. The manufacturer's product information for the DCD5000 collection device indicates that the collection volume of the swab is 380 µL. Recovery data for the swab when used with the isopropanol provided by the manufacturer are not available. A series of experiments using fortified drug-free OF were performed to assess the collection volume imprecision of the Dräger DCD5000 swab and the recovery of drugs from the swab using isopropanol. The fortified OF was collected with the swabs (n = 16), and swabs were discharged into vials of isopropanol as per the manufacturer's instructions. The mean collection volume of the DCD5000 swab was 487 µL with an imprecision of 1.3%. Recovery of drug from the device ranged from 86 to 98% for drugs listed in the Australian OF workplace testing standard. Recovery of methadone, buprenorphine and norbuprenorphine ranged from 93 to 102%. Recovery of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene was 45%, suggesting that urine is more suitable sample if methadone therapy is being monitored. Overall, drug recovery from the device using isopropanol was acceptable when the increased collection volume of the swab was taken into account.

Symptomatic primary Cytomegalovirus infection in a HIV-positive pregnant woman.

We describe a case of symptomatic primary Cytomegalovirus infection in a HIV-positive pregnant woman on antiretroviral treatment with a CD4 count >200 × 10(6)/l requiring intravenous ganciclovir. No adverse consequences from ganciclovir or evidence of congenital Cytomegalovirus infection were found.

LC-MS/MS method for the quantitation of metabolites of eight commonly-used synthetic cannabinoids in human urine--an Australian perspective.

An LC-MS/MS method for the quantitation of urinary metabolites of eight JWH-type synthetic cannabinoids (SCs) has been developed and validated. Urine samples are subjected to deconjugation using ß-glucuronidase, followed by a solvent extraction procedure. Compounds are separated on a reverse-phase HPLC column within a 14 min cycle. Low assay limits are required in order to demonstrate prior exposure to SCs. Matrix effects were studied and proved to be significant for selected analytes, and were challenging to circumvent as isotope-labeled internal standards are not available. An elimination profile from a naïve user following a single smoke of "Kronic" was constructed, showing urinary excretion over 2-3 days with peak concentrations of different metabolites 3-16.5 h after smoking. This method has been developed to process several hundred samples within a high-throughput drugs of abuse laboratory, with growing evidence that the use of synthetic cannabinoid blends is common within the Australian workforce.

Evaluation of 4 weeks' neonatal antiretroviral prophylaxis as a component of a prevention of mother-to-child transmission program in a resource-rich setting.

BACKGROUND: In resource-rich settings, universal adoption of a 4- rather than 6-week neonatal antiretroviral (ARV) prophylaxis regimen could reduce toxicity and results in cost savings, provided prevention of mother-to-child transmission program effectiveness is not compromised. METHODS: Between January 1999 and December 2008, a 10-year study of the observational database of the Irish prevention of mother-to-child transmission program that uses a 4- rather than 6-week neonatal ARV prophylaxis regimen was undertaken. Maternal and infant data were analyzed to determine the vertical transmission rate (VTR) and infant outcome. Infants were categorized as uninfected if, off ARVs, they had 2 negative human immunodeficiency virus (HIV) polymerase chain reaction (PCR) tests, the second at 3 months of age or older. RESULTS: Between January 1999 and December 2008, there were 964 HIV-exposed live births. Excluding 7 early neonatal deaths, 4 weeks of ARV prophylaxis was prescribed for 957 infants: 61% received mono, 32% triple, and 7% dual therapy. Of 957 infants, 906 were uninfected, 10 infected, and 41 of indeterminate status. Twenty-four of the indeterminate status infants had at least one negative HIV PCR test at ≥ 6 weeks and 17 were lost to follow-up before 6 weeks of age. On the basis of 916 infants of known outcome, the VTR was 1.09% (95% confidence interval, 1.07-1.11). If restricted to 910 infants whose mothers received at least 4 weeks of antiretroviral therapy (ART), the VTR was 0.4%. CONCLUSIONS: This study provides evidence to support the current clinical practice toward use of a 4-week neonatal ARV prophylaxis regimen.

Targeting points for further intervention: a review of HIV-infected infants born in ireland in the 7 years following introduction of antenatal screening.

Even in countries with well-developed programs for prevention of mother-to-child transmission (MTCT) of HIV, there remains a low level of ongoing transmission. Pregnant, HIV-infected women may not always access screening and available interventions because of circumstances, beliefs, and other influences. Missed opportunities for the prevention of MTCT remains an issue to be addressed. Through a review of HIV-infected children born during the years of antenatal screening in Ireland, we sought to identify further targets for intervention to further reduce MTCT.

The determination of the 99th centile level for troponin assays in an Australian reference population.

BACKGROUND: Current guidelines for the diagnosis and risk assessment of patients presenting with myocardial infarction recommend a single decision cut-off point for cardiac troponin (cTn) based on the 99th centile of a reference population. The 99th centile level for eight troponin assays was determined in an apparently cardio-healthy Australian reference population. METHODS: Nine laboratories measured troponin in serum and plasma collected from 111 reference individuals. An imprecision profile was determined using up to 10 serum samples analysed on 10 separate days. Method comparison using 100 routinely tested plasma samples was performed to estimate method concordance. RESULTS: Generally 99th centile values determined in this study were lower than, or the same as manufacturers' levels, except for cTnI by Architect (0.020 vs. 0.012 microg/L), and imprecision at the 99th centile was 20% coefficient of variation (CV) or higher. Troponin concentrations at 10% CV were greater than those quoted in the manufacturer's package insert except by AxSYM, 0.06 vs. 0.16 microg/L cTnI, and by E-170, 0.02 vs. 0.03 microg/L cTnT. In the method comparison 74, 70, 65, 75, 58, 66, 58 and 77 samples measured by Access, Architect, AxSYM, Centaur, Dimension RxL, E-170, i-STAT and Vitros ECi assays, respectively, had troponin concentrations above the study 99th centile. CONCLUSIONS: Depending on the selected reference population for troponin, there is likely to be variability in the 99th centile as shown in this study. Some differences in sample concordance at the 99th centile cut-off were observed between cTn methods and may result in different clinical classification.

HIV type 1 persistence in CD4- /CD8- double negative T cells from patients on antiretroviral therapy.

The establishment of reservoirs of latently infected cells is thought to contribute to the persistence of HIV-1 infection in the host. Studies so far have mainly focused on the long-lived reservoir of HIV-infected resting CD4+ T cells. A discrete population of HIV-infected CD4-/CD8- double negative (DN) T cells has recently been shown to exist and may also play a role in HIV-1 persistence. DN T cells are CD3 positive, either TCRalphabeta or TCRgammadelta positive, but lack both CD4 and CD8 surface markers. We developed a novel, magnetic bead column-based cell fractionation procedure for isolating >99% pure DN T cells. CD4+, CD8+, and DN T cells were purified from 23 samples of a cohort of 18 HIV-1-infected patients. Each cell fraction was analyzed for levels of total and integrated HIV-1 DNA. A correlation was observed between the presence of HIV-1 DNA in the DN T cell fraction and plasma viral load (VL). Using a micrococulture technique, we saw an initial release of virus from DN T cells of a patient with high VL. Analysis of env and nef sequence data suggested that the HIV-1 present in CD4+ and DN T cells originated from a common infecting strain. Different from the published literature, we have demonstrated the presence of HIV-1 DNA in DN T cells only in patients who are experiencing HAART failure. While these cells may have a limited role in viral persistence in high VL patients, our results suggest DN T cells are unlikely to be a major reservoir in patients on HAART with clinically undetectable plasma viral RNA.