Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.

OBJECTIVES: At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). STUDY DESIGN: We undertook an ecological study using routinely available national data. METHODS: We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. RESULTS: Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. CONCLUSIONS: These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

Antimicrobial stewardship in care homes: outcomes of importance to stakeholders.

BACKGROUND: Heterogeneity of outcomes measured in trials to improve antimicrobial stewardship (AMS) in care homes has compromised quality of evidence. A core outcome set (COS) is needed to facilitate interpretation and synthesis of evidence in this area. AIM: To determine outcomes deemed important by relevant stakeholders for interventions aimed at improving AMS in care homes, and to produce a refined list of outcomes that could be considered for use in future research. METHODS: Semi-structured face-to-face or telephone interviews were conducted with key stakeholders. Outcomes reported in previous randomized controlled trials (RCTs) of AMS in care homes were included in a topic guide for interviews. Content analysis was undertaken to identify potential outcomes suggested by participants, followed by further review. FINDINGS: Twenty-seven outcomes reported in RCTs were refined into a list of 12 overarching outcomes. Interviews with participants (six researchers, 31 healthcare professionals, and four family members of care home residents) identified 40 additional outcomes that were important to them. From these 52 outcomes, the total number of antimicrobials, the appropriateness of antimicrobial prescribing and adherence to guidelines were highlighted by most participants. After reviewing all 52 outcomes, a refined list of 14 outcomes potentially feasible for use in AMS trials in care homes was generated. CONCLUSION: s: A number of potential outcomes for AMS in care homes, some of which had not been reported in previous studies, were identified. The refined list of 14 outcomes will be used in a future study to agree a COS for care home AMS trials.

Comparing the epidemiology of community- and hospital-associated Clostridium difficile infections in Northern Ireland, 2012-2016: a population data linkage and case-case study.

The burden of community-associated Clostridium difficile infection (CA-CDI) has increased. We aimed to describe the epidemiology of CA-CDI to inform future interventions. We used population-based linked surveillance data from 2012 to 2016 to describe socio-demographic factors, ribotype and mortality for all CA (n = 1303) and hospital-associated (HA, n = 1356) CDI. For 483 community-onset (CO) CA-CDI and 287 COHA-CDI cases, a questionnaire on risk factors was completed and we conducted a case-case study using logistic regression models for univariate and multivariable analysis. CA-CDI cases had lower odds of being male (adjusted odds ratio (AOR) 0.71, 95% confidence interval (CI) 0.58-0.87; P < 0.001), and higher odds of living in rural rather than urban settlement (AOR 1.5, 95% CI 1.1-2.1; P = 0.05) compared with HA-CDI cases. The distribution of ribotypes was similar in both groups with RT078 being most prevalent. CDI-specific death was lower in CA-CDI than HA-CDI (7% vs. 11%, P < 0.001). COCA-CDI had lower odds of having had an outpatient appointment in the previous 4 weeks compared with COHA-CDI (AOR 0.61; 95% CI 0.41-0.9, P = 0.01) and lower odds of being in a care home or hospice when compared with their own home, than COHA-CDI (AOR 0.66; 95% CI 0.45-0.98 and AOR 0.35; 95% CI 0.13-0.92, P = 0.02). Exposure to gastric acid suppressants (50% in COCA-CDI and 55% in COHA-CDI) and antimicrobial therapy (18% in COCA-CDI and 20% in COHA-CDI) prior to CDI was similar. Our analysis of community-onset cases suggests that other risk factors for COHA-CDI may be equally important for COCA-CDI. Opportunities to safely reduce antibiotic and gastric acid suppressants use should be investigated in all healthcare settings.

The £ for lb. Challenge. Evaluation of a novel, workplace-based peer-led weight management programme, 2014-2016.

OBJECTIVES: To evaluate the £ for lb. Challenge, a novel country-wide, workplace-based, peer-led weight management programme with participants from a range of private and public organisations in Northern Ireland. STUDY DESIGN: Pre- and post-intervention studies. METHODS: The intervention was workplace-based, led by volunteer co-worker champions and based on the NHS Choices 12-week weight loss guide which incorporates dietary advice, physical activity, behaviour change methods and weekly weight monitoring. It operated from January to April in three consecutive years (2014-16). Overweight and obese adult workers were eligible. Training of peer champions involved two half-day workshops delivered by dieticians and physical activity professionals. Employers and/or participants pledged £1 to charity for every pound of weight lost. Weight was reported at enrolment and at either 12 weeks (2014) or at 12 weekly intervals (2015-16). Changes in weight and % weight, and body mass index were determined for all the participants and for gender and deprivation subgroups. RESULTS: There were 734, 1559 and 1513 eligible participants, and 21, 31 and 35 participating companies in 2014, 2015 and 2016, respectively. Engagement rates were 94% and 96% and completion rates were 70% and 71% in 2015 and 2016, respectively. Mean weight loss was 1.9 kg (2.2%; 2014), 2.5 kg (2.8%; 2015) and 2.4 kg (2.7%; 2016). The proportions losing ≥5% initial bodyweight were 21% (2014), 24% (2015) and 26% (2016). Male participants were more than twice as likely as women to complete the programme (odds ratio: 2.5 [2015]; 2.2 [2016]) and to lose ≥5% bodyweight (odds ratio: 2.5 [2015]; 3.7 [2016]). CONCLUSIONS: The £ for lb. Challenge was an effective, low-cost health improvement intervention with meaningful weight loss for many participants, particularly male workers. With high levels of engagement and ownership, and successful collaboration between public health, voluntary bodies, private companies and public organisations, it is a novel workplace-based model with potential to expand.

Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis.

OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations. METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline. RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses. CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.

Genetic susceptibility to invasive meningococcal disease: MBL2 structural polymorphisms revisited in a large case-control study and a systematic review.

Invasive infection caused by Neisseria meningitidis is a worldwide public health problem. Previous reports have indicated that carriage of common 'defective' structural polymorphisms of the host mannose-binding lectin gene (MBL2) greatly increases an individual's risk of developing the disease. We report the largest case-control study so far to investigate the effect of these polymorphisms in meningococcal disease (296 PCR-positive cases and 5196 population controls, all of European ancestry) and demonstrate that no change in risk is associated with the polymorphisms overall or in any age-defined subgroup. This finding contrasts with two smaller studies that reported an increase in risk. A systematic review of all studies of MBL2 polymorphisms in people of European ancestry published since 1999, including 24,693 individuals, revealed a population frequency of the combined 'defective'MBL2 allele of 0.230 (95% confidence limits: 0.226-0.234). The past reported associations of increased risk of meningococcal disease were because of low 'defective' allele frequencies in their study control populations (0.13 and 0.04) that indicate systematic problems with the studies. The data from our study and all other available evidence indicate that MBL2 structural polymorphisms do not predispose children or adults to invasive meningococcal disease.

Complement in age-related macular degeneration: a focus on function.

Age-related macular degeneration (AMD) is an inflammatory disease, which causes visual impairment and blindness in older people. The proteins of the complement system are central to the development of this disease. Local and systemic inflammation in AMD are mediated by the deregulated action of the alternative pathway of the complement system. Variants in complement system genes alter an individual's risk of developing AMD. Recent studies have shown how some risk-associated genetic variants alter the function of the complement system. In this review, we describe the evolution of the complement system and bring together recent research to form a picture of how changes in complement system genes and proteins affect the function of the complement cascade, and how this affects the development of AMD. We discuss the application of this knowledge to prevention and possible future treatments of AMD.

Coding polymorphisms in the genes of the alternative complement pathway and abdominal aortic aneurysm.

Variants in the genes of the alternative complement pathway are associated with risk of numerous inflammatory diseases. Abdominal aortic aneurysm is associated with inflammation and is a common cause of illness and death among European populations. This study tested 49 single nucleotide polymorphisms, including common putatively functional polymorphisms, in the genes of the alternative complement cascade (CFH, CFB, CFD, CFI, properdin, CR1, CR1L, CR2, CD46, vitronectin, C3, C5, C6, C7, C8A, C8B, C8G and C9). The study group were 434 cases with infra-renal aortic diameter ≥30 mm and 378 disease-free controls from two UK centres, all with self-reported European ancestry. There was no evidence for significant association with presence or size of aneurysm following correction for multiple testing. This study suggests that variation in the genes of the alternative pathway is not an important cause of abdominal aortic aneurysm development.

Scar revision via resurfacing.

Numerous techniques exist to treat noticeable facial scars. Techniques range from surgical excision to resurfacing. In this review of dermabrasion and laser resurfacing, we address the clinical considerations, techniques, adjuncts, and peri-operative management of scar resurfacing. Dermabrasion offers the advantage of being a tried-and-true technique familiar to surgeons. Recent advances in laser technology have resulted in the increased use of pulsed-dye lasers (PDLs), erbium:yttrium-aluminum-garnet (YAG) lasers, and CO(2) lasers. PDLs are effective for hypertrophic scars and show lower rates of recurrence compared with erbium:YAG and CO2 lasers. In contrast, erbium:YAG and CO(2) lasers are well suited to treating atrophic and acne scars. Chemical peels play a minor role in scar resurfacing and function primarily as an adjunct. Scar resurfacing is an integral part of scar camouflage and is often used in conjunction with excision and irregularization techniques.

Correlates of arterial oxygenation during exercise in severe chronic obstructive pulmonary disease.

In the present study, we have undertaken a detailed analysis of the respiratory physiologic correlates of SaO2 during mild constant-load exercise in 38 patients with severe but stable COPD. Several respiratory physiologic variables that would be expected to influence exercise SaO2 were entered into a stepwise multiple linear regression analysis with mean exercise SaO2 as the dependent variable. Two variables (Dco and resting SaO2) were found to correlate strongly with mean exercise SaO2 (multiple r = 0.80; p less than 0.00001) and accounted for 65 percent of the variability among patients. The PaCO2 influenced resting SaO2 but had no independent influence on exercise SaO2. Subsequently, the model of mean exercise SaO2 derived in the present analysis was found to accurately predict mean exercise SaO2 in a group of 19 similar patients (r = 0.85; p less than 0.0001). While these findings do not establish a cause-and-effect relationship, they may provide clinicians with further insight as to which patients are likely to desaturate during exercise.