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.

Feasibility study of hospital antimicrobial stewardship analytics using electronic health records.

BACKGROUND: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimize antimicrobial use. Most hospitals depend on time-consuming manual audits to monitor clinicians' prescribing. But much of the information needed could be sourced from electronic health records (EHRs). OBJECTIVES: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records. METHODS: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialities at Queen Elizabeth Hospital, Birmingham, UK (September 2017-August 2018). The study involved: (i) a review of AMS standards of care; (ii) their translation into concepts measurable from commonly available EHRs; and (iii) a pilot application in an EHR cohort study (n = 61679 admissions). RESULTS: We developed data modelling methods to characterize antimicrobial use (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy 5.8 days), enabling several actionable findings. For example, 22% of therapy episodes for low-severity community-acquired pneumonia were congruent with prescribing guidelines, with a tendency to use broader-spectrum antibiotics. Analysis of therapy changes revealed IV to oral therapy switching was delayed by an average 3.6 days (95% CI: 3.4-3.7). Microbial cultures were performed prior to treatment initiation in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice down to specialities, wards and individual clinical teams by case mix, enabling more meaningful peer comparison. CONCLUSIONS: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimizing prescribing, and AMS impact evaluation studies.

The relationship between clinical outcomes and empirical antibiotic therapy in patients with community-onset Gram-negative bloodstream infections: a cohort study from a large teaching hospital.

Antibiotic-resistant Gram-negative bacteraemias (GNB) are increasing in incidence. We aimed to investigate the impact of empirical antibiotic therapy on clinical outcomes by carrying out an observational 6-year cohort study of patients at a teaching hospital with community-onset Escherichia coli bacteraemia (ECB), Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB). Antibiotic therapy was considered concordant if the organism was sensitive in vitro and discordant if resistant. We estimated the association between concordant vs. discordant empirical antibiotic therapy on odds of in-hospital death and ICU admission for KPB and ECB. Of 1380 patients, 1103 (79.9%) had ECB, 189 (13.7%) KPB and 88 (6.4%) PsAB. Discordant therapy was not associated with increased odds of either outcome. For ECB, severe illness and non-urinary source were associated with increased odds of both outcomes (OR of in-hospital death for non-urinary source 3.21, 95% CI 1.73-5.97). For KPB, discordant therapy was associated with in-hospital death on univariable but not multivariable analysis. Illness severity was associated with increased odds of both outcomes. These findings suggest broadening of therapy for low-risk patients with community-onset GNB is not warranted. Future research should focus on the relationship between patient outcomes, clinical factors, infection focus and causative organism and resistance profile.

Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London.

Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in the homeless and prisoners. Capturing accurate data on disease prevalence within these groups is challenging but is essential to inform strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these populations. We conducted a cross-sectional study between May 2011 and June 2013 in London and, using convenience sampling, recruited participants from hostels for the homeless, drug treatment services and a prison. A questionnaire was administered and blood samples were tested for hepatitis C. We recruited 491 individuals who were homeless (40.7%), 205 drug users (17%) and 511 prisoners (42.3%). Eight per cent of patients (98/1207, 95% CI: 6.7%-9.8%) had active HCV infection and 3% (38/1207, 95% CI: 2.3%-4.3%) past HCV infection. Overall, one quarter (51/205) of people recruited in drug treatment services, 13% (65/491) of people from homeless residential sites and 4% (20/511) prisoners in this study were anti-HCV positive. Seventy-seven of the 136 (56.6%, 95% CI: 47.9%-65%) of HCV infected participants identified had a history of all three risk factors (homelessness, imprisonment and drug use), 27.3% (95% CI: 20.1%-35.6%) had 2 overlapping risk factors, and 15.4% (95% CI: 10.6%-23.7%) one risk factor. Drug treatment services, prisons and homelessness services provide good opportunities for identifying hepatitis C-infected individuals. Effective models need to be developed to ensure case identification in these settings that can lead to an effective treatment and an efficient HCV prevention.

Assessing hepatitis C spontaneous clearance and understanding associated factors-A systematic review and meta-analysis.

New advances in the treatment of hepatitis C provide high levels of sustained viral response but their expense limits availability in publicly funded health systems. The aim of this review was to estimate the proportion of patients who will spontaneously clear HCV, to identify factors that are associated with clearance and to support better targeting of directly acting antivirals. We searched Ovid EMBASE, Ovid MEDLINE and PubMed from 1 January 1994 to 30 June 2015 for studies reporting hepatitis C spontaneous clearance and/or demographic, clinical and behavioural factors associated with clearance. We undertook meta-analyses to estimate the odds of clearance for each predictor. Forty-three studies met the inclusion criteria, representing 20 110 individuals, and 6 of these studies included sufficient data to estimate spontaneous clearance. The proportion achieving clearance within 3, 6, 12 and 24 months following infection were, respectively, 19.8% (95% CI: 2.6%-47.5%), 27.9% (95% CI: 17.2%-41.8%), 36.1% (95% CI: 23.5%-50.9%) and 37.1% (95% CI: 23.7%-52.8%). Individuals who had not spontaneously cleared by 12 months were unlikely to do so. The likelihood of spontaneous clearance was lower in males and individuals with HIV co-infection, the absence of HBV co-infection, asymptomatic infection, black or nonindigenous race, nongenotype 1 infection, older age and alcohol or drug problems. This study suggests that patients continue to spontaneously clear HCV for at least 12 months following initial infection. However, injecting drug users are comparatively less likely to achieve clearance; thus, they should be considered a priority for early treatment given the continuing risks that these individuals pose for onwards transmission.

Mismatch between suspected pyelonephritis and microbiological diagnosis: a cohort study from a UK teaching hospital.

Urinary tract infections are a common reason for prescribing empirical antibiotics in the emergency department. This study investigated the role of microbiological culture and urinalysis in the diagnosis of pyelonephritis by extracting data on 105 patients with a clinical diagnosis of pyelonephritis at a London teaching hospital. In total, 99 of 102 patients were treated empirically with intravenous antibiotics, but only 55 of 100 patients who were sampled had microbiological evidence of infection in urine and/or blood. Almost half (10/21) of the patients with a negative urine dipstick test had a positive urine culture. Diagnostic uncertainty in this context undoubtedly drives inappropriate antibiotic use.

Evidence for increasing severity of community-onset boils and abscesses in UK General Practice.

In England, hospital admissions for severe staphylococcal boils and abscesses trebled between 1989 and 2004. We investigated this trend using routine data from primary and secondary care. We used The Health Improvement Network (THIN), a large primary-care database and national data on hospital admissions from Hospital Episode Statistics (HES). Time trends in the incidence of primary-care consultations for boils and abscesses were estimated for 1995-2010. HES data were used to calculate age-standardized hospital admission rates for boils, abscesses and cellulitis. The incidence of boil or abscess was 450 [95% confidence interval (CI) 447-452] per 100 000 person-years and increased slightly over the study period (incidence rate ratio 1·005, 95% CI 1·004-1·007). The rate of repeat consultation for a boil or abscess increased from 66 (95% CI 59-73) per 100 000 person-years in 1995 to peak at 97 (95% CI 94-101) per 100 000 person-years in 2006, remaining stable thereafter. Hospital admissions for abscesses, carbuncles, furuncles and cellulitis almost doubled, from 123 admissions per 100 000 in 1998/1999 to 236 admissions per 100 000 in 2010/2011. Rising hospitalization and recurrence rates set against a background of stable community incidence suggests increased disease severity. Patients may be experiencing more severe and recurrent staphylococcal skin disease with limited treatment options.

Panton-Valentine leukocidin associated staphylococcal disease: a cross-sectional study at a London hospital, England.

Recently, there has been international concern at the rapid emergence of highly pathogenic strains of Staphylococcus aureus associated with a toxin called Panton-Valentine leukocidin (PVL). In the UK, these strains are considered to be rare and mainly severe. We estimate the proportion of staphylococcal infections that are caused by strains containing the PVL genes, and describe risk factors for these infections. Three hundred and ninety consecutive S. aureus clinical isolates, submitted for routine diagnostic purposes were screened for PVL genes. Risk factors for infection were identified from the patient medical record. 9.7% (95% CI 7.0-13.1%) of clinical isolates and 20.8% of skin and soft tissue specimens contained the genes for PVL. Methicillin-resistant S. aureus with PVL was rare (0.8% of all isolates) but PVL with methicillin-sensitive S. aureus was common (9.0% of all specimens). PVL infection was more frequent in males (OR 3.0, 95% CI 1.3-7.0), and in young adults aged 20-39 years (OR 3.7, 95% CI 1.3-10.4). Over half of PVL positive S. aureus infections originated in patients based in the community. Community-onset PVL-associated disease is common in the UK and mainly causes skin and soft tissue infections that do not require admission to hospital. Consideration should be given to current infection control strategy, which advocates household contact screening and decolonization on the assumption that PVL-associated disease is rare.

Clinical and molecular epidemiology of ciprofloxacin-susceptible MRSA encoding PVL in England and Wales.

We aimed to enhance our case ascertainment of meticillin-resistant Staphylococcus aureus encoding Panton-Valentine leucocidin (PVL-MRSA), determine the patient demographic, risk factor and disease associations, and define the clonal diversity amongst isolates referred to the UK Health Protection Agency's Staphylococcus Reference Unit. PVL-MRSA collected during 2005-6 from community-based and hospitalised patients located across England and Wales were identified by polymerase chain reaction (PCR). Representative geographically and temporally unrelated isolates were characterised via toxin gene profiling, SCCmec, spa and agr typing, multilocus sequence typing (MLST) and minimum inhibitory concentration (MIC) determinations. PVL-MRSA were identified from 275 patients. Affected individuals were <1 to 95 years of age (mean 30, median 27 years). Forty-five isolates were from 18 household or community-based clusters and 23 isolates were from outbreaks in healthcare settings. Overall, 58% (n = 161) had skin and soft tissue infections and 9% (n = 25) presented with or developed more serious disease, including eight patients (3%) with necrotising pneumonia, five of whom subsequently died. PVL-MRSA were genetically diverse and harboured SCCmecIV or V(T)/VII. Representatives of MLST clonal complexes (CCs) 8, 30 and 80 were identified the most often. The 275 PVL-MRSA included internationally disseminated community-associated MRSA (CA-MRSA) strains, as well as other minor lineages, and were associated with typical risk factors and disease presentations.

A dietary education program for hypercholesterolemic children and their parents.

A parent-child autotutorial dietary education program for 4- to 10-year-old, hypercholesterolemic children and their families was developed and pilot tested. The 10-lesson program, designed for weekly use at home, uses a "talking-book" approach (audiotapes with accompanying picture booklet) for the child. Parents are provided with information on ways to make recommended dietary changes, along with hands-on activities to do with the children. To help match the instructional approach to the wide developmental range within the children's age span, materials are divided into three program levels that use different story characters and concept presentations. During program development, evaluation by two children (and their parents) for each of the program levels guided the design and refinement of the lessons. A pilot test among 22 hypercholesterolemic children (whose treatment was limited to diet modification) revealed that children within the 4- to 10-year age range liked the "talking-book" approach and identified positively with the story characters. Parents indicated that their materials were clear and helpful. Between the baseline and 3-month follow-up visits, the children exhibited a significant increase in knowledge of heart healthy foods, a decrease in total fat consumption that approached significance, and a significant decrease in plasma low-density-lipoprotein cholesterol values.