Skin and respiratory ill-health attributed to occupational face mask use.

BACKGROUND: Face mask use in the workplace has become widespread since the onset of the Covid-19 pandemic and has been anecdotally linked to adverse health consequences. AIMS: To examine reports of adverse health consequences of occupational face mask use received by The Health and Occupation Research (THOR) network before and after the pandemic onset. METHODS: THOR databases were searched to identify all cases of ill-health attributed to 'face mask' or similar suspected causative agent between 1 January 2010 and 30 June 2021. RESULTS: Thirty two cases were identified in total, 18 reported by occupational physicians and 14 by dermatologists. Seventy-five per cent of cases were reported after the pandemic onset and 91% cases were in the health and social care sector. 25 of the 35 (71%) diagnoses were dermatological, the most frequent diagnoses being contact dermatitis (14 cases) and folliculitis/acne (6 cases). Of the seven respiratory diagnoses, four were exacerbation of pre-existing asthma. CONCLUSIONS: There is evidence of an abrupt increase in reports of predominantly dermatological ill-health attributed to occupational face mask use since the start of the pandemic. Respiratory presentations have also occurred.

Persisting Symptomatic Severe Secondary Mitral Regurgitation in Heart Failure Patients.

Aims We aimed to assess the rate of persisting severe symptomatic secondary mitral regurgitation (MR) in a newly diagnosed heart failure (HF) population following optimisation of guideline directed medical therapy (GDMT), cardiac resynchronisation therapy (CRT) and revascularisation. Methods We assessed all new patients referred to our hospital group's HF clinics. We retrospectively reviewed these patients at HF clinic enrolment, HF programme completion, as well as most recent follow up. Results Of the 242 new patients referred to our HF clinics, there were 10 patients (4.1%) who had either persisting symptomatic severe secondary MR at HF programme completion, or had undergone mitral valve surgery. There were no percutaneous mitral valve repairs at the time of these patients' referrals. The rates of ACE/ARB/ARNI, BB and MRA use were 87.8%, 94.1%, and 49.8% in those with mid ranged, or reduced ejection fraction. The rates of ICD and CRT therapy were 15.1% and 4.4% at follow up. Patients with severe MR had higher time adjusted rates of death or hospitalization for heart failure. Conclusion In a well-treated newly diagnosed HF population, repeat assessment at HF programme completion suggests 4.1% of patients have a persisting indication for percutaneous mitral valve repair based on persisting severe symptomatic secondary MR.

Epidemiological investigation of recurrent outbreaks of haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli serotype O55:H7 in England, 2014-2018.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

A Review of a Tertiary Referral Centre's CT Coronary Angiography Programme.

Aims To investigate the implication of outpatient CT coronary angiogram (CTCA) waiting times on patient outcomes and service provision. Methods All outpatient CTCAs requested for stable chest pain during 2017 in our catchment area were included. Rate of major adverse cardiovascular events (MACE), presentations with chest pain to the emergency department (ED), cardiology outpatient attendance, time interval in alteration of Coronary artery disease (CAD) prognostic treatment, rate of angiography and percutaneous coronary intervention (PCI) were noted. Results 172 CTCAs were included. 11 (6.4%) presented to ED with chest pain. 38 (22.1%) attended outpatients prior to scan completion. 17 (9.9%) required alteration of prognostic treatment, taking on average 10.4 (+/-4.5) months to occur. 21 (12.2%) underwent coronary angiography and 7 (4.1%) had PCI, which took on average 9.9 (+/-6.6) months. One non-fatal MI requiring CABG was noted. Conclusion The low rate of MACE and revascularisation likely represents appropriately low risk patient selection for CTCA. Presentation to clinic prior to scan completion highlights a need for better administration support.

Impact and Mechanism of Covid-19 on Mental Health and Wellbeing.

The Covid-19 pandemic has brought unprecedented pressure to healthcare systems worldwide, resulting in significant and precipitous changes in demand, burden and method of delivery. The psychosocial impact of this crisis is likely to increase over the course of the pandemic, peak later than medical cases and endure for longer thereby significantly exceeding medical morbidity. It will have far reaching impact on the individual, their family and their care providers. Frontline healthcare workers and those with pre-existing mental health difficulties are recognised at increased risk. Now that the initial surge has been expertly curtailed, it is essential that urgent consideration is now directed towards the mental health implications of the current outbreak and ensure that we are as ready for the increased MH needs of the community as we were for the intensive medical care.

Irish Inquiry Reports Relating to Perinatal Deaths and Pregnancy Loss Services.

Aims External inquiries are carried out following specific adverse events in healthcare, many in maternity care; to identify issues and make recommendations to improve standards of care. Methods Ten publically-available national inquiry reports published between 2005-2018 relating to pregnancy loss services, were reviewed by 2 clinicians, separately, examining the content and recommendations from each report. Results A total of 258 recommendations were made in 9 reports (90%). Five inquiries (50%) clearly stated that affected families were involved and four (40%) involved affected clinical staff. In 9 reports (90%) recommendations included: increase workforce staffing and/or training, strengthen clinical governance, enhance adverse incident management and comprehensive data collection e.g. maternity outcomes. Only two inquiry reports (20%) stated that feedback was sought from key stakeholders prior to publication. Conclusion A collaborative and standardised inquiry process involving and supporting all persons affected as well as key stakeholders would ensure that all relevant issues are identified, recommendations are implemented and essential lessons are learned.

Effect of neoadjuvant chemoradiation on preoperative pulmonary physiology, postoperative respiratory complications and quality of life in patients with oesophageal cancer.

BACKGROUND: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer. METHODS: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose-volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41·4 Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were assessed at baseline and 1 month after nCRT. Radiation-induced lung injury (grade 2 or greater), comprehensive complications index (CCI) and pulmonary complications were monitored prospectively. Health-related quality of life was assessed among disease-free patients in survivorship. RESULTS: Some 228 patients were studied. Comparing pulmonary physiology values before with those after nCRT, FEV1 decreased from mean(s.d.) 96·8(17·7) to 91·5(20·4) per cent (-3·6(10·6) per cent; P < 0·001), FVC from 104·9(15·6) to 98·1(19·8) per cent (-3·2(11·9) per cent; P = 0·005) and DLCO from 97·6(20·7) to 82·2(20·4) per cent (-14·8(14·0) per cent; P < 0·001). Five patients (2·2 per cent) developed radiation-induced lung injury precluding surgical resection. Smoking (P = 0·005) and increased age (P < 0·001) independently predicted percentage change in DLCO. Carboplatin and paclitaxel with 41·4 Gy resulted in a greater DLCO decline than cisplatin and 5-fluorouracil with 40 Gy (P = 0·001). On multivariable analysis, post-treatment DLCO predicted CCI (P = 0·006), respiratory failure (P = 0·020) and reduced physical function in survivorship (P = 0·047). CONCLUSION: These data indicate that modern nCRT alters pulmonary physiology, in particular diffusion capacity, which is linked to short- and longer-term clinical consequences, highlighting a potentially modifiable index of risk.

ANTECEDENTES: El tema de si en el cáncer de esófago la quimiorradioterapia neoadyuvante (neoadjuvant chemoradiation, nCRT) repercute sobre la morbilidad postoperatoria, especialmente sobre la morbilidad pulmonar y la calidad de vida de los pacientes que sobreviven sigue siendo controvertido. Este estudio combina datos sobre resultados clínicos con una evaluación sistemática de la fisiología pulmonar para determinar el impacto de la nCRT sobre la fisiología pulmonar y los resultados clínicos en el cáncer de esófago localmente avanzado. MÉTODOS: Se incluyeron pacientes consecutivos tratados entre 2010-2016. La radioterapia conformal 3D fue la estándar, con un histograma dosis-volumen del pulmón V20 < 25% y radiación entre 40-41,4 Gy. Se evaluaron el volumen espiratorio forzado (forced expiratory volume, FEV1), la capacidad vital forzada (forced vital capacity, FVC) y la capacidad de difusión del monóxido de carbono (diffusion capacity for carbon monoxide, DLCO) al inicio y un mes tras la nCRT. La lesión pulmonar inducida por la radioterapia (EORTC grado ≥ 2), el índice de complicaciones integral (comprehensive complications index, CCI), grado de Clavien-Dindo, y complicaciones pulmonares fueron analizadas de manera prospectiva. Se evaluó la calidad de vida relacionada con la salud entre los pacientes supervivientes libres de enfermedad (EORTC QLQ-C30, OG25, OES18). RESULTADOS: Se estudiaron un total de 228 pacientes. Al comparar los valores de la fisiología pulmonar antes y después de la nCRT respectivamente, la FEV1 disminuyó de 96,8 ± 17,7% a 91,5 ± 20,4% (-3,6 ± 10,6%, P = 0,0002), la FVC de 104,9 ± 15,6 a 98,1 ± 19,8% (-3,2 ± 11,9%, P = 0,005) y la DLCO de 97,6 ± 20,7 a 82,2 ± 20,4% (-14,8 ± 14,0%, P < 0,0001). Cinco pacientes (2,2%) desarrollaron lesión pulmonar relacionada con la radioterapia impidiendo la resección quirúrgica. Los factores predictores independientes de %ΔDLCO fueron el hábito tabáquico (P = 0,005) y la edad avanzada (P < 0,001). El tratamiento con carboplatino/paclitaxel/41,4Gy determinó un mayor descenso de la DLCO en comparación con cisplatino/5-fluorouracilo/40Gy (P = 0,001). En el análisis multivariable, la DLCO tras el tratamiento fue una variable predictora de CCI (P = 0,006), fracaso respiratorio/intubación prolongada (P = 0,020) y reducción de la función física en los supervivientes (P = 0,047). CONCLUSIÓN: Estos datos indican que la moderna nCRT altera la fisiología pulmonar, especialmente la difusión pulmonar, con consecuencias clínicas a corto y largo plazo. La DLCO podría constituir un factor de riesgo potencialmente modificable.

Analysis of individual patient data to describe the incubation period distribution of Shiga-toxin producing Escherichia coli.

Shiga-toxin producing Escherichia coli (STEC) is a pathogen that can cause bloody diarrhoea and severe complications. Cases occur sporadically but outbreaks are also common. Understanding the incubation period distribution and factors influencing it will help in the investigation of exposures and consequent disease control. We extracted individual patient data for STEC cases associated with outbreaks with a known source of exposure in England and Wales. The incubation period was derived and cases were described according to patient and outbreak characteristics. We tested for heterogeneity in reported incubation period between outbreaks and described the pattern of heterogeneity. We employed a multi-level regression model to examine the relationship between patient characteristics such as age, gender and reported symptoms; and outbreak characteristics such as mode of transmission with the incubation period. A total of 205 cases from 41 outbreaks were included in the study, of which 64 cases (31%) were from a single outbreak. The median incubation period was 4 days. Cases reporting bloody diarrhoea reported shorter incubation periods compared with cases without bloody diarrhoea, and likewise, cases aged between 40 and 59 years reported shorter incubation period compared with other age groups. It is recommended that public health officials consider the characteristics of cases involved in an outbreak in order to inform the outbreak investigation and the period of exposure to be investigated.

Gastrointestinal infections caused by consumption of raw drinking milk in England & Wales, 1992-2017.

Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003-2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.

Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010-2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19-2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10-1.75) and hospitalisation (OR 1.71, 95% CI 1.36-2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16-2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40-2.27; OR 1.85, 95% CI 1.35-2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22-2.70; soil contact, OR 1.52, 95% CI 2.13-1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

A practical guide to active stand testing and analysis using continuous beat-to-beat non-invasive blood pressure monitoring.

PURPOSE: The average adult stands approximately 50-60 times per day. Cardiovascular responses evoked during the first 3 min of active standing provide a simple means to clinically assess short-term neural and cardiovascular function across the lifespan. Clinically, this response is used to identify the haemodynamic correlates of patient symptoms and attributable causes of (pre-)syncope, and to detect autonomic dysfunction, variants of orthostatic hypotension, postural orthostatic tachycardia syndrome and orthostatic hypertension. METHODS: This paper provides a set of experience/expertise-based recommendations detailing current state-of-the-art measurement and analysis approaches for the active stand test, focusing on beat-to-beat BP technologies. This information is targeted at those interested in performing and interpreting the active stand test to current international standards. RESULTS: This paper presents a practical step-by-step guide on (1) how to perform active stand measurements using beat-to-beat continuous blood pressure measurement technologies, (2) how to conduct an analysis of the active stand response and (3) how to identify the spectrum of abnormal blood pressure and heart rate responses which are of clinical interest. CONCLUSION: Impairments in neurocardiovascular control are an attributable cause of falls and syncope across the lifespan. The simple active stand test provides the clinician with a powerful tool for assessing individuals at risk of such common disorders. However, its simplicity belies the complexity of its interpretation. Care must therefore be taken in administering and interpreting the test in order to maximise its clinical benefit and minimise its misinterpretation.

National audit of perinatal HIV infections in the UK, 2006-2013: what lessons can be learnt?

OBJECTIVES: The aim of the study was to investigate circumstances surrounding perinatal transmissions of HIV (PHIVs) in the UK. METHODS: The National Study of HIV in Pregnancy and Childhood conducts comprehensive surveillance of all pregnancies in women diagnosed with HIV infection and their infants in the UK; reports of all HIV-diagnosed children are also sought, regardless of country of birth. Children with PHIV born in 2006-2013 and reported by 2014 were included in an audit, with additional data collection via telephone interviews with clinicians involved in each case. Contributing factors for each transmission were identified, and cases described according to main likely contributing factor, by maternal diagnosis timing. RESULTS: A total of 108 PHIVs were identified. Of the 41 (38%) infants whose mothers were diagnosed before delivery, it is probable that most were infected in utero, around 20% intrapartum and 20% through breastfeeding. Timing of transmission was unknown for most children of undiagnosed mothers. For infants born to diagnosed women, the most common contributing factors for transmission were difficulties with engagement and/or antiretroviral therapy (ART) adherence in pregnancy (14 of 41) and late antenatal booking (nine of 41); for the 67 children with undiagnosed mothers, these were decline of HIV testing (28 of 67) and seroconversion (23 of 67). Adverse social circumstances around the time of pregnancy were reported for 53% of women, including uncertain immigration status, housing problems and intimate partner violence. Eight children died, all born to undiagnosed mothers. CONCLUSIONS: Priority areas requiring improvement include reducing incident infections, improving ART adherence and facilitating better engagement in care, with attention to addressing the health inequalities and adverse social situations faced by these women.

Predictors of coverage of the national maternal pertussis and infant rotavirus vaccination programmes in England.

This study assessed variation in coverage of maternal pertussis vaccination, introduced in England in October 2012 in response to a national outbreak, and a new infant rotavirus vaccination programme, implemented in July 2013. Vaccine eligible patients were included from national vaccine coverage datasets and covered April 2014 to March 2015 for pertussis and January 2014 to June 2016 for rotavirus. Vaccine coverage (%) was calculated overall and by NHS England Local Team (LT), ethnicity and Index of Multiple Deprivation (IMD) quintile, and compared using binomial regression. Compared with white-British infants, the largest differences in rotavirus coverage were in 'other', white-Irish and black-Caribbean infants (-13·9%, -12·1% and -10·7%, respectively), after adjusting for IMD and LT. The largest differences in maternal pertussis coverage were in black-other and black-Caribbean women (-16·3% and -15·4%, respectively). Coverage was lowest in London LT for both programmes. Coverage decreased with increasing deprivation and was 14·0% lower in the most deprived quintile compared with the least deprived for the pertussis programme and 4·4% lower for rotavirus. Patients' ethnicity and deprivation were therefore predictors of coverage which contributed to, but did not wholly account for, geographical variation in coverage in England.

Presentation for care and antenatal management of HIV in the UK, 2009-2014.

OBJECTIVES: Despite very low rates of vertical transmission of HIV in the UK overall, rates are higher among women starting antenatal antiretroviral therapy (ART) late. We investigated the timing of key elements of the care of HIV-positive pregnant women [antenatal care booking, HIV laboratory assessment (CD4 count and HIV viral load) and antenatal ART initiation], to assess whether clinical practice is changing in line with recommendations, and to investigate factors associated with delayed care. METHODS: We used the UK's National Study of HIV in Pregnancy and Childhood for 2009-2014. Data were analysed by fitting logistic regression and Cox proportional hazards models. RESULTS: A total of 5693 births were reported; 79.5% were in women diagnosed with HIV prior to that pregnancy. Median gestation at antenatal booking was 12.1 weeks [interquartile range (IQR) 10.0-15.6 weeks] and booking was significantly earlier during 2012-2014 vs. 2009-2011 (P < 0.001), although only in previously diagnosed women. Overall, 42.2% of pregnancies were booked late (≥ 13 gestational weeks). Among women not already on treatment, antenatal ART commenced at a median of 21.4 (IQR18.1-24.5) weeks and started significantly earlier in the most recent time period (P < 0.001). Compared with previously diagnosed women, those newly diagnosed during the current pregnancy booked later for antenatal care and started antenatal ART later (both P < 0.001). Multivariable analyses revealed demographic variations in access to or uptake of care, with groups including migrants and parous women initiating care later. CONCLUSIONS: Although women are accessing antenatal and HIV care earlier in pregnancy, some continue to face barriers to timely initiation of antenatal care and ART.

Duration of ruptured membranes and mother-to-child HIV transmission: a prospective population-based surveillance study.

OBJECTIVE: To investigate the association between duration of rupture of membranes (ROM) and mother-to-child HIV transmission (MTCT) rates in the era of combination antiretroviral therapy (cART). DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) undertakes comprehensive population-based surveillance of HIV in pregnant women and children. SETTING: UK and Ireland. POPULATION: A cohort of 2398 singleton pregnancies delivered vaginally, or by emergency caesarean section, in women on cART in pregnancy during the period 2007-2012 with information on duration of ROM; HIV infection status was available for 1898 infants. METHODS: Descriptive analysis of NSHPC data. MAIN OUTCOME MEASURES: Rates of MTCT. RESULTS: In 2116 pregnancies delivered at term, the median duration of ROM was 3 hours 30 minutes (interquartile range, IQR 1-8 hours). The overall MTCT rate for women delivering at term with duration of ROM ≥4 hours was 0.64% compared with 0.34% for ROM <4 hours, with no significant difference between the groups (OR 1.90, 95% CI 0.45-7.97). In women delivering at term with a viral load of <50 copies/ml, there was no evidence of a difference in MTCT rates with duration of ROM ≥4 hours, compared with <4 hours (0.14% for ≥4 hours versus 0.12% for <4 hour; OR 1.14, 95% CI 0.07-18.27). Among infants born preterm with infection status available, there were no transmissions in 163 deliveries where the maternal viral load was <50 copies/ml. CONCLUSIONS: No association was found between duration of ROM and MTCT in women taking cART. TWEETABLE ABSTRACT: Rupture of membranes of more than 4 hours is not associated with MTCT of HIV in women on effective ART delivering at term.

The epidemiology, microbiology and clinical impact of Shiga toxin-producing Escherichia coli in England, 2009-2012.

Between 1 January 2009 and 31 December 2012 in England, a total of 3717 cases were reported with evidence of Shiga toxin-producing E. coli (STEC) infection, and the crude incidence of STEC infection was 1·80/100 000 person-years. Incidence was highest in children aged 1-4 years (7·63/100 000 person-years). Females had a higher incidence of STEC than males [rate ratio (RR) 1·24, P < 0·001], and white ethnic groups had a higher incidence than non-white ethnic groups (RR 1·43, P < 0·001). Progression to haemolytic uraemic syndrome (HUS) was more frequent in females and children. Non-O157 STEC strains were associated with higher hospitalization and HUS rates than O157 STEC strains. In STEC O157 cases, phage type (PT) 21/28, predominantly indigenously acquired, was also associated with more severe disease than other PTs, as were strains encoding stx2 genes. Incidence of STEC was over four times higher in people residing in rural areas than urban areas (RR 4·39, P < 0·001). Exposure to livestock and/or their faeces was reported twice as often in cases living in rural areas than urban areas (P < 0·001). Environmental/animal contact remains an important risk factor for STEC transmission and is a significant driver in the burden of sporadic STEC infection. The most commonly detected STEC serogroup in England was O157. However, a bias in testing methods results in an unquantifiable under-ascertainment of non-O157 STEC infections. Implementation of PCR-based diagnostic methods designed to detect all STEC, to address this diagnostic deficit, is therefore important.

The utility and public health implications of PCR and whole genome sequencing for the detection and investigation of an outbreak of Shiga toxin-producing Escherichia coli serogroup O26:H11.

Many serogroups of Shiga toxin-producing Escherichia coli (STEC) other than serogroup O157 (non-O157 STEC), for example STEC O26:H11, are highly pathogenic and capable of causing haemolytic uraemic syndrome. A recent increase in non-O157 STEC cases identified in England, resulting from a change in the testing paradigm, prompted a review of the current methods available for detection and typing of non-O157 STEC for surveillance and outbreak investigations. Nineteen STEC O26:H11 strains, including four from a nursery outbreak were selected to assess typing methods. Serotyping and multilocus sequence typing were not able to discriminate between the stx-producing strains in the dataset. However, genome sequencing provided rapid and robust confirmation that isolates of STEC O26:H11 associated with a nursery outbreak were linked at the molecular level, had a common source and were distinct from the other strains analysed. Virulence gene profiling of DNA extracted from a polymerase chain reaction (PCR)-positive/culture-negative faecal specimen from a case that was epidemiologically linked to the STEC O26:H11 nursery outbreak, provided evidence at the molecular level to support that link. During this study, we describe the utility of PCR and the genome sequencing approach in facilitating surveillance and enhancing the response to outbreaks of non-O157 STEC.

Retinoschisin gene therapy in photoreceptors, Müller glia or all retinal cells in the Rs1h-/- mouse.

X-linked retinoschisis, a disease characterized by splitting of the retina, is caused by mutations in the retinoschisin gene, which encodes a putative secreted cell adhesion protein. Currently, there is no effective treatment for retinoschisis, though viral vector-mediated gene replacement therapies offer promise. We used intravitreal delivery of three different AAV vectors to target delivery of the RS1 gene to Müller glia, photoreceptors or multiple cell types throughout the retina. Müller glia radially span the entire retina, are accessible from the vitreous, and remain intact throughout progression of the disease. However, photoreceptors, not glia, normally secrete retinoschisin. We compared the efficacy of rescue mediated by retinoschisin secretion from these specific subtypes of retinal cells in the Rs1h-/- mouse model of retinoschisis. Our results indicate that all three vectors deliver the RS1 gene, and that several cell types can secrete retinoschisin, leading to transport of the protein across the retina. The greatest long-term rescue was observed when photoreceptors produce retinoschisin. Similar rescue was observed with photoreceptor-specific or generalized expression, although photoreceptor secretion may contribute to rescue in the latter case. These results collectively point to the importance of cell targeting and appropriate vector choice in the success of retinal gene therapies.

Predicting carotid artery disease and plaque instability from cell-derived microparticles.

OBJECTIVES: Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease. METHODS: This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase. RESULTS: Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model. CONCLUSIONS: EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers.

Identification of verocytotoxin-producing Escherichia coli O117:H7 in men who have sex with men, England, November 2013 to August 2014.

Between November 2013 and August 2014, nine cases of verocytotoxin-producing Escherichia coli O117:H7 VT1 were confirmed in adult men. Further investigation using semi-structured interviews revealed that eight cases were United Kingdom (UK)-born men who have sex with men (MSM) who had sexually acquired infection in the UK. Most were HIV-positive with high numbers of sexual partners. This behavioural profile resembles that associated with the recent rapid increase in other sexually acquired infections in MSM.