COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.

BACKGROUND: Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection. OBJECTIVES: To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023. METHODS: We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test. RESULTS: A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%. CONCLUSIONS: Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.

Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care.

BACKGROUND: Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town. METHODS: YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability. RESULTS: Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%). Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire. CONCLUSION: Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.

Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Factors affecting turnaround time of SARS-CoV-2 sequencing for inpatient infection prevention and control decision making: analysis of data from the COG-UK HOCI study.

BACKGROUND: Barriers to rapid return of sequencing results can affect the utility of sequence data for infection prevention and control decisions. AIM: To undertake a mixed-methods analysis to identify challenges that sites faced in achieving a rapid turnaround time (TAT) in the COVID-19 Genomics UK Hospital-Onset COVID-19 Infection (COG-UK HOCI) study. METHODS: For the quantitative analysis, timepoints relating to different stages of the sequencing process were extracted from both the COG-UK HOCI study dataset and surveys of study sites. Qualitative data relating to the barriers and facilitators to achieving rapid TATs were included from thematic analysis. FINDINGS: The overall TAT, from sample collection to receipt of sequence report by infection control teams, varied between sites (median 5.1 days, range 3.0-29.0 days). Most variation was seen between reporting of a positive COVID-19 polymerase chain reaction (PCR) result to sequence report generation (median 4.0 days, range 2.3-27.0 days). On deeper analysis, most of this variability was accounted for by differences in the delay between the COVID-19 PCR result and arrival of the sample at the sequencing laboratory (median 20.8 h, range 16.0-88.7 h). Qualitative analyses suggest that closer proximity of sequencing laboratories to diagnostic laboratories, increased staff flexibility and regular transport times facilitated a shorter TAT. CONCLUSION: Integration of pathogen sequencing into diagnostic laboratories may help to improve sequencing TAT to allow sequence data to be of tangible value to infection control practice. Adding a quality control step upstream to increase capacity further down the workflow may also optimize TAT if lower quality samples are removed at an earlier stage.

Twin chorionicity-specific population birth-weight charts adjusted for estimated fetal weight.

OBJECTIVES: To construct chorionicity-specific birth-weight reference charts for dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies, incorporating estimated-fetal-weight (EFW) data in order to adjust for the relationship between suboptimal growth and preterm delivery. An additional aim was to determine if the inclusion of complicated twin pregnancies impacts on the reference charts produced. METHODS: The inclusion criteria for this retrospective cohort study were twin pregnancy of known DCDA or MCDA chorionicity, known pregnancy outcome, last ultrasound scan within 14 days before birth and delivery between 25 and 38 weeks' gestation (Analysis A). An analysis was also conducted excluding pregnancies with complications recorded (Analysis B). Previously published twin EFW reference ranges were used in the analysis. A joint statistical model for EFW and observed birth weight for each pregnancy was created in order to estimate population birth-weight reference ranges corresponding to the distribution expected if all pregnancies delivered at any given gestational age. It was not assumed that the median EFW was equal to birth weight for any given gestational age. The models were fitted using a Bayesian approach. RESULTS: We retrieved data on 1664 twin pregnancies, of which 707 DCDA and 241 MCDA pregnancies met the inclusion criteria. In Analysis A, the estimated population median birth weight was similar to the median EFW at around 27 weeks' gestation but fell below the EFW values with increasing gestation, being 156 g lower in both DCDA and MCDA pregnancies at 35 weeks; this finding was confirmed by direct comparison of the last EFW and birth-weight values in each pregnancy. When the analysis was repeated after excluding complicated twin pregnancies (Analysis B), compared with Analysis A, there was very little difference in the median birth-weight results obtained across gestation. The largest absolute difference between Analyses A and B for DCDA twins was at 31, 32 and 33 weeks, with a 9-g lower median birth weight in Analysis A compared with Analysis B. The largest absolute difference for MCDA twins was greater than that for DCDA twins, with a 21-g lower median birth weight at 25 weeks in Analysis A compared with Analysis B. CONCLUSIONS: We have established population chorionicity-specific birth-weight reference charts for DCDA and MCDA twin pregnancies, corresponding to the range expected were all pregnancies to deliver at any given gestational age. In this population of twins, the median birth weight was consistently lower than that reported for singletons, and there was variation in the median birth weight at different gestational ages according to chorionicity. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation.

OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

Influence of maternal characteristics and gestational age on hemodynamic indices: NICOM device-specific reference ranges.

OBJECTIVES: To construct reference ranges for stroke volume, cardiac output and systemic vascular resistance (SVR) in normal pregnancy for the NICOM® device, and to explore associations between maternal characteristics and these hemodynamic variables. METHODS: This was a prospective cohort study of healthy singleton pregnancies between 10 and 40 weeks' gestation attending a tertiary referral hospital between September 2012 and May 2018. Measurements of stroke volume, cardiac output and SVR were obtained throughout pregnancy using NICOM, a non-invasive device based on bioreactance technology. NICOM device-specific reference ranges were created with respect to gestational age and maternal characteristics. Once the distribution of the data had been determined with respect to the gestational age, patient characteristics were added to the model to test whether they provided a significant improvement in prediction of the median value. The effect was assessed of maternal weight, height, smoking status, conception using assisted reproductive technology, nulliparity and ethnicity. RESULTS: We included 411 women in this study. The relationships between cardiac variables and gestational age observed in the NICOM-specific reference ranges are consistent with previous findings, with increasing cardiac output values until around 35 weeks and a decrease thereafter until term, and decreasing SVR until around 36 weeks, followed by an increase towards 40 weeks. Stroke volume showed a small linear increase across gestation with lower variability in observations close to term. Maternal weight, height and age were associated with cardiac output (all P < 0.05) and SVR (all P < 0.01), whilst maternal weight and height were associated with stroke volume (both P < 0.001). Ethnicity was significantly associated with stroke volume (P = 0.001) but not with cardiac output or SVR. CONCLUSIONS: This study presents device-specific reference ranges for stroke volume, cardiac output and SVR for the NICOM device in healthy pregnancy and describes the maternal characteristics that are associated with the values of these hemodynamic measurements. Studies using NICOM in pregnancy can use these ranges in order to evaluate observations relative to those expected in uncomplicated pregnancy conditional on maternal characteristics. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Maternal hemodynamics in normal pregnancy: reference ranges and role of maternal characteristics.

OBJECTIVES: The main aim of this study was to construct reference ranges of maternal central hemodynamic parameters during pregnancy. The second aim was to determine the maternal and pregnancy characteristics that influence these hemodynamic parameters. METHODS: This was a prospective cohort study of low-risk pregnant women attending for routine antenatal care at St George's Hospital, London, UK. Exclusion criteria included any medical disorder present at the time of study recruitment, or development of hypertension or intrauterine fetal growth restriction following study recruitment. Stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) were obtained using non-invasive cardiac output monitoring (USCOM-1A®). USCOM-1A utilizes a non-imaging probe in the suprasternal notch to obtain velocity-time integrals of transaortic blood flow at the left ventricular outflow tract. Once the distribution of the data with respect to gestational age had been determined, maternal characteristics were added to the model to test whether they provided a significant improvement in the prediction of the median value. RESULTS: The study included 627 women with a singleton pregnancy. The estimated median CO was constant for a maternal age above 32 years, but was around 0.5 L/min higher for women aged ≤ 25 years (P < 0.001). Maternal weight (P < 0.001) and height (P < 0.001) significantly affected CO values and there was a significant interaction (P = 0.002) between them. In women with a height of less than 1.60 m, there was no association between median CO and weight; however, in those with a height exceeding 1.60 m, an increase in weight was associated with an increase in CO. SV was primarily associated with height (P < 0.001), although some positive association with weight (P < 0.001) could also be observed within the normal body-mass-index range. Greater height (P < 0.001) was associated with lower median values of SVR, with an estimated difference of around 120 dynes × s/cm5 between 1.60 m and 1.80 m. Advancing maternal age was associated with higher median SVR, with an estimated difference of around 50 dynes × s/cm5 between 25 and 35 years. Smokers had a lower SVR by 73.5 (95% CI, 8.6-138.4) dynes × s/cm5 . CONCLUSION: Maternal hemodynamics are influenced significantly by maternal age, height and weight. We provide USCOM-1A-specific reference ranges and a calculator for SV, CO and SVR in uncomplicated pregnancies that correct for maternal age, height and weight. This should enable clinical application and comparison in both uncomplicated and pathological pregnancies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.

OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.

Fetal growth reference ranges in twin pregnancy: analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort.

OBJECTIVE: To generate reference charts for expected fetal growth in dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies and to compare these with those from singleton pregnancies. METHODS: This was a retrospective study of biometric measurements from serial ultrasound examinations of twin pregnancies in the second and third trimesters, from 14 weeks' gestation to term, collected by nine hospitals over a 10-year period. The measurements obtained in each fetus at each examination included head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL). Multilevel mixed effects statistical models were used to evaluate growth in each biometric variable in relation to gestational age, taking account of the serial examinations and the association between the two fetuses in each pregnancy, with separate models constructed for DCDA and MCDA pregnancies. RESULTS: The final dataset for analysis included a total of 9866 second- and third-trimester ultrasound examinations in 1802 DCDA and 323 MCDA twin pregnancies, with a median of five (range, 1-14) scans per pregnancy. For each variable, the mean value for DCDA twins was close to the reported value in singletons at 20-30 weeks and showed a decrease relative to singletons beyond 30 weeks. The differences were greater for AC and HC, for which the mean in twins was approximately equivalent to the 30th percentile in singletons at 18 weeks, the 35th percentile at 25 weeks and the 30th percentile at 35 weeks. Fetuses in MCDA twin pregnancies displayed lower mean measurements than did those in DCDA pregnancies throughout the gestational age range considered. CONCLUSIONS: Ultrasound biometry shows a small but statistically significant reduction in fetal growth in twin pregnancies relative to that in singletons, particularly in the third trimester, with a more marked difference for MCDA than for DCDA pregnancies.