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In 2013, shingles vaccination was introduced in Wales as a routine immunisation programme for older adults. Invitation for this vaccination has historically been recommended but not mandated by vaccination policy. We surveyed general practices to investigate if invitations and reminders are associated with higher uptake of shingles vaccine. Using data from general practices, we calculated practice-level shingles vaccine uptake between 01/07/2021 and 31/06/2022 for registered patients aged 70–84 years. We distributed an online survey via email to all general practices in Wales on their use of vaccination invitations and reminders, method of invitations, and characteristics of their vaccination delivery. We used linear regression to calculate coefficients and 95 %CI to measure associations between invitations and vaccine uptake, adjusting for key demographics, with a multi-level component to account for similarities between general practices within the same health board. Survey response rate was 37 % (143/384). Median vaccine uptake for responding general practices was 57 % (IQR 50–68 %) compared to 58 % (IQR 48–68 %) nationally. General practices inviting all eligible patients (n = 95) had a 9 % (95 %CI 6–13 %) higher vaccination uptake compared to those inviting none or some (n = 48, p < 0.001). Of practices sending invitations, those who reminded all patients (n = 42) had a 6 % (95 %CI 1–11 %, p = 0.02) higher uptake compared to those that reminded none (n = 30). Practice size was associated with higher uptake, with small practices (n = 11, p = 0.02) having coverage 9 % (95 %CI 2–16 %) higher compared to the reference population (medium-sized practices, n = 78). General practices inviting and reminding all eligible patients for shingles vaccination have a higher uptake compared to those inviting and reminding only some or none. From September 2023, shingles vaccination policy in Wales has been updated to explicitly mandate effective universal call and recall mechanisms in general practices.

Between 21 November and 22 December 2020, a SARS-CoV-2 community testing pilot took place in the South Wales Valleys. We conducted a case-control study in adults taking part in the pilot using an anonymous online questionnaire. Social, demographic and behavioural factors were compared in people with a positive lateral flow test (cases) and a sample of negatives (controls). A total of 199 cases and 2621 controls completed a questionnaire (response rates: 27.1 and 37.6% respectively). Following adjustment, cases were more likely to work in the hospitality sector (aOR 3.39, 95% CI 1.43–8.03), social care (aOR 2.63, 1.22–5.67) or healthcare (aOR 2.31, 1.29–4.13), live with someone self-isolating due to contact with a case (aOR 3.07, 2.03–4.62), visit a pub (aOR 2.87, 1.11–7.37) and smoke or vape (aOR 1.54, 1.02–2.32). In this community, and at this point in the epidemic, reducing transmission from a household contact who is self-isolating would have the biggest public health impact (population-attributable fraction: 0.2). As restrictions on social mixing are relaxed, hospitality venues will become of greater public health importance, and those working in this sector should be adequately protected. Smoking or vaping may be an important modifiable risk factor.

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures. We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission. Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%). Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.

ObjectivesMSM Internet Survey Ireland (MISI) 2015 was an anonymous, self-completed, cross-sectional internet survey assessing sexual behaviours and health needs among men who have sex with men (MSM) in Ireland. We explored factors associated with self-reported STI diagnosis among MSM who were sexually active and had an STI test in the previous year.MethodsWe compared the study population (n=1158; 37% of total population), with the sexually active MISI population not testing for STIs (n=1620; 52% of total population). Within the study population, we identified sociodemographics and sexual behaviours associated with self-reporting STI diagnosis. We used multivariable logistic regression to estimate adjusted odds ratios (aORs).ResultsThe sociodemographics, lifestyle and sexual behaviours of the study population differed significantly from the sexually active MISI population who did not test for STIs. Within the study population, 65% met a sexual partner via geosocial networking smartphone application (GSNa) and 21% self-reported an STI diagnosis in the previous year. On univariable analysis, factors associated with STI diagnosis included: older age, identifying as gay, HIV-positive status, increasing number of sexual partners in the previous year, condomless anal intercourse (CAI) with ≥2 non-steady partners and using GSNa to meet a new sexual partner in the previous year or most recent sexual partner. On multivariable analysis, STI diagnosis was associated with: being aged 25–39 years (aOR 1.8, 95% CI 1.04 to 3.15), CAI with ≥2 non-steady partners (aOR 2.8, 95% CI 1.84 to 4.34), total number of sexual partners (aOR 1.02, 95% CI 1.00 to 1.03) and using GSNa to meet a new sexual partner (aOR 1.95, 95% CI 1.12 to 3.39).ConclusionsSTI diagnosis among MSM testing for STIs is associated with GSNa use, as well as sexual behaviours. GSNas are key settings for STI prevention interventions, which should prioritise men with high numbers of sexual partners and those with multiple CAI partners.

Plasma stromal cell–derived factor (SDF)-1 levels, SDF1-3′A polymorphism, and CXCR4+ T lymphocytes in relation to resistance to human immunodeficiency virus (HIV)-1 infection and its progression were investigated in a study of HIV-positive patients, exposed but uninfected (EU) subjects, and healthy control subjects, all lacking CCR5Δ32 homozygosity. SDF1-3′A homozygosity was associated with low plasma SDF-1 levels in uninfected persons and was not related to long-term nonprogression. HIV-1 infection involved increased plasma SDF-1 levels, which were not attributable to any kind of chronic viral infection, because all EU hemophiliacs were hepatitis C virus–positive but had normal SDF-1 levels. High plasma SDF-1 levels and low CXCR4 expression on T lymphocytes was associated with long-term nonprogression, whereas in advancing disease expression of CXCR4 increased, accompanied by a decrease in plasma SDF-1 during the more advanced stages of HIV-1 infection. EU subjects with sexual exposure to HIV-1, but not EU hemophiliacs, showed an underpresentation of SDF1-3′A allele frequency, which was coupled with high plasma SDF-1 levels and low CXCR4 expression

Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor α chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV⁺ long-term nonprogressors (LTNP), 36 HIV⁺ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus⁺), and 97 healthy controls (HC), all Caucasians and lacking CCR5Δ32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p=0.005; relative risk ratio=3.4, 95% confidence interval (CI)=1.12-10.6, p=0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV⁺ individuals (n=64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p=0.01; odds ratio (OR)=2.14, 95% CI=1.25-3.67, p=0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR=2.10, 95% CI=1.03-4.21, p=0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p=0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.

Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor α chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV^sup +^ long-term nonprogressors (LTNP), 36 HIV^sup +^ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus^sup +^), and 97 healthy controls (HC), all Caucasians and lacking CCR5Δ32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p=0.005; relative risk ratio=3.4, 95% confidence interval (CI)=1.12-10.6, p=0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV^sup +^ individuals (n=64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p=0.01; odds ratio (OR)=2.14, 95% CI=1.25-3.67, p=0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR=2.10, 95% CI=1.03-4.21, p=0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p=0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.[PUBLICATION ABSTRACT]

Plasma stromal cell-derived factor (SDF)-1 levels, SDF1-3'A polymorphism, and CXCR4(+) T lymphocytes in relation to resistance to human immunodeficiency virus (HIV)-1 infection and its progression were investigated in a study of HIV-positive patients, exposed but uninfected (EU) subjects, and healthy control subjects, all lacking CCR5 Delta 32 homozygosity. SDF1-3'A homozygosity was associated with low plasma SDF-1 levels in uninfected persons and was not related to long-term nonprogression. HIV-1 infection involved increased plasma SDF-1 levels, which were not attributable to any kind of chronic viral infection, because all EU hemophiliacs were hepatitis C virus-positive but had normal SDF-1 levels. High plasma SDF-1 levels and low CXCR4 expression on T lymphocytes was associated with long-term nonprogression, whereas in advancing disease expression of CXCR4 increased, accompanied by a decrease in plasma SDF-1 during the more advanced stages of HIV-1 infection. EU subjects with sexual exposure to HIV-1, but not EU hemophiliacs, showed an underpresentation of SDF1-3'A allele frequency, which was coupled with high plasma SDF-1 levels and low CXCR4 expression.

Background Traditionally, renal function in critically ill patients has been assessed to identify renal dysfunction, and dose adjustment is generally accepted in such a context. Nevertheless, augmented renal clearance (ARC) is a less well-studied phenomenon that could lead to faster elimination of drugs, resulting in subtherapeutic concentrations and poorer clinical outcomes when standard dosage guidelines are followed. Objective The aim of this systematic review was to gather and summarise all the available evidence on ARC in critically ill patients, including its definition, underlying mechanisms, epidemiology, diagnosis and impact on both drug pharmacokinetics and clinical outcomes. Method A systematic review was conducted to include all the original studies that provided information on ARC in critically ill patients, and is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Augmented renal clearance, defined as a creatinine clearance (CrCl) > 130 mL/min/1.73 m 2 , preferably measured in urine, is present in 20–65% of critically ill patients. Younger age, polytrauma and lower severity illness have been identified as risk factors. An influence of ARC on antimicrobial pharmacokinetics has been observed, with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations. Conclusion ARC is a prevalent condition in critically ill patients, especially in young people, with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl. ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels, but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs. Research on the need to stage ARC and establish specific dosing guidelines is warranted.

To assess the pharmacokinetics of linezolid in septic patients undergoing continuous renal replacement therapy (CRRT) and investigate whether residual renal function affects the probability of attaining the pharmacokinetic/pharmacodynamic (PK/PD) target. Prospective study conducted in three Spanish hospitals. Linezolid concentrations were measured in plasma and effluent samples and pharmacokinetic parameters were calculated. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) were calculated considering AUC24/MIC>80 and %T>MIC > 85% as the PK/PD indexes related to efficacy. In anuric patients (CrCl<10 mL/min), the contribution of extracorporeal Cl to total Cl was higher (47% vs 16%) than in patients with residual renal function (CrCl≥10 mL/min). For an MIC of 2 mg/L, AUC24/MIC>80 was achieved in >85% of the anuric patients, but in <15% of the patients with residual renal function. The standard dose (600 mg q12h) ensures a moderately high probability of treatment success in anuric patients when the infection is due to microorganisms with MIC≤2 mg/L; although higher doses increase the probability of treatment success, the safety is compromised. In patients with residual renal function, the standard dose is insufficient, but 900 mg q8h provide higher probability of treatment success without compromising the safety. •In acute renal failure, CRRT conditions the total clearance of linezolid.•The contribution of extracorporeal to total clearance is 3 times higher in anurics.•For MIC≤2 mg/L, 600 mg q12h provide high probability of success in anuric patients.•600 mg q12h is deficient for patients with residual renal function receiving CRRT.•900 mg q8h improve the probability of success in nonanuric patients receiving CRRT.