Risk of hospitalization and death for healthcare workers with COVID-19 in nine European countries, January 2020-January 2021.

This article presents and compares coronavirus disease 2019 attack rates for infection, hospitalization, intensive care unit (ICU) admission and death in healthcare workers (HCWs) and non-HCWs in nine European countries from 31st January 2020 to 13th January 2021. Adjusted attack rate ratios in HCWs (compared with non-HCWs) were 3.0 [95% confidence interval (CI) 2.2-4.0] for infection, 1.8 (95% CI 1.2-2.7) for hospitalization, 1.9 (95% CI 1.1-3.2) for ICU admission and 0.9 (95% CI 0.4-2.0) for death. Among hospitalized cases, the case-fatality ratio was 1.8% in HCWs and 8.2% in non-HCWs. Differences may be due to better/earlier access to treatment, differential underascertainment and the healthy worker effect.

Retrospective assessment of rapid outbreak investigation for gastrointestinal diseases using only cases and background exposure data.

For outbreaks of gastrointestinal disease, rapid identification of the source is crucial to enable public health intervention and prevent further cases. Outbreak investigation comprises analyses of exposure information from cases and, if required, undertaking analytical epidemiological studies. Hypothesis generation has been reliant on empirical knowledge of exposures historically associated with a given pathogen. Epidemiology studies are resource-intensive and prone to bias, one of the reasons being the difficulties in recruiting appropriate controls. For this paper, the information from cases was compared against pre-defined background exposure information. As exemplars, three past outbreaks were used, one of common and two of rare exposures. Information from historical case trawling questionnaires was used to define background exposure having removed any exposures implicated with the outbreak. The case-background approach showed good sensitivity and specificity, identifying correctly all outbreak-related exposures. One additional exposure related to a retailer was identified and four food items where all cases had been exposed. In conclusion, the case-background method, a development of the case-case design, can be used to assist with hypothesis generation or when a case-control study may not be possible to carry out.

Are food exposures obtained through commercial market panels representative of the general population? Implications for outbreak investigations.

Current methods of control recruitment for case-control studies can be slow (a particular issue for outbreak investigations), resource-intensive and subject to a range of biases. Commercial market panels are a potential source of rapidly recruited controls. Our study evaluated food exposure data from these panel controls, compared with an established reference dataset. Market panel data were collected from two companies using retrospective internet-based surveys; these were compared with reference data from the National Diet and Nutrition Survey (NDNS). We used logistic regression to calculate adjusted odds ratios to compare exposure to each of the 71 food items between the market panel and NDNS participants. We compared 2103 panel controls with 2696 reference participants. Adjusted for socio-demographic factors, exposure to 90% of foods was statistically different between both panels and the reference data. However, these differences were likely to be of limited practical importance for 89% of Panel A foods and 79% of Panel B foods. Market panel food exposures were comparable with reference data for common food exposures but more likely to be different for uncommon exposures. This approach should be considered for outbreak investigation, in conjunction with other considerations such as population at risk, timeliness of response and study resources.

Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25-49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8-76.1% male), Giardia (53.1-57.6%) and Campylobacter (52.1-53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.

Online market research panel members as controls in case-control studies to investigate gastrointestinal disease outbreaks: early experiences and lessons learnt from the UK.

Established methods of recruiting population controls for case-control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case-control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.

Selection of population controls for a Salmonella case-control study in the UK using a market research panel and web-survey provides time and resource savings.

Timely recruitment of population controls in infectious disease outbreak investigations is challenging. We evaluated the timeliness and cost of using a market research panel as a sampling frame for recruiting controls in a case-control study during an outbreak of Salmonella Mikawasima in the UK in 2013. We deployed a web-survey by email to targeted members of a market research panel (panel controls) in parallel to the outbreak control team interviewing randomly selected public health staff by telephone and completing paper-based questionnaires (staff controls). Recruitment and completion of exposure history web-surveys for panel controls (n = 123) took 14 h compared to 15 days for staff controls (n = 82). The average staff-time cost per questionnaire for staff controls was £13·13 compared to an invoiced cost of £3·60 per panel control. Differences in the distribution of some exposures existed between these control groups but case-control studies using each group found that illness was associated with consumption of chicken outside of the home and chicken from local butchers. Recruiting market research panel controls offers time and resource savings. More rapid investigations would enable more prompt implementation of control measures. We recommend that this method of recruiting controls is considered in future investigations and assessed further to better understand strengths and limitations.

Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men--Shigella flexneri and S. sonnei in England, 2004 to end of February 2015.

Surveillance data suggest an intensification of the shigellosis epidemic associated with sexual transmissionin men who have sex with men (MSM) in England with separate introductions into the population. In 2014, sexual transmission between MSM might have accounted for 97%, 89%, and 43% of non-travel associated Shigella flexneri 3a and S. flexneri 2a, andS. sonnei diagnoses. Clinicians should sensitively ascertain sexual history for men with enteric infections to facilitate prompt diagnosis and appropriate management.

Pregnancy-associated listeriosis in England and Wales.

Listeriosis is a rare but severe foodborne disease with low morbidity and high case-fatality rates. Pregnant women, unborn and newborn babies are among the high-risk groups for listeriosis. We examined listeriosis cases reported to the enhanced surveillance system in England and Wales from 1990 to 2010 to identify risk factors influencing outcome. Cases were defined as pregnancy-associated if Listeria monocytogenes was isolated from a pregnant woman or newborn infants aged <28 days. Of the 3088 cases reported, pregnancy-associated listeriosis accounted for 462 (15%) cases and 315 cases resulted in a live birth. Several factors were identified as affecting the severity and outcome of listeriosis in pregnancy in both mother and child including: presence or absence of maternal symptoms, gestational age at onset of symptoms, and clinical presentation in the infant (meningitis or septicaemia). Deprivation, ethnicity and molecular serotype had no effect on outcome.

Existing medications among non-pregnancy-related listeriosis patients in England, 2007-2009.

To identify which medications were most commonly taken by non-pregnancy-related listeriosis patients prior to illness, we compared the medications reported by 512 cases identified via national surveillance in England between 2007 and 2009 with national prescription data, using British National Formulary (BNF) coding. Relative risks and corresponding confidence intervals were calculated, as appropriate, for BNF chapters and sections. Among listeriosis cases, the rates for cytotoxic drugs, drugs affecting the immune response and corticosteroids were significantly higher than for other medications. However, interactions between medications and how medications might confound or be confounded by concurrent medical conditions need to be investigated further. Nevertheless our findings suggest that targeting food-safety advice to prevent this foodborne disease in certain treatment groups is warranted.

Risk factors for mortality in non-pregnancy-related listeriosis.

We examined non-pregnancy-related listeriosis cases in England and Wales reported to the Health Protection Agency between 1990 and 2009 (n=1864) using unconditional multivariate logistic regression analysis to identify factors independently associated with mortality. A subset analysis of cases between 2005 and 2009 (n=694) investigated the additional effect of antibiotic therapy on survival. In these cases particular malignancies, alcoholism, cardiovascular disease, increasing age, and treatment to reduce gastric acid secretion were positively associated with mortality. The absence of a concurrent condition and presence of autoimmune disease had a protective effect. The subset analysis identified illness in winter or spring as a risk factor and antibiotic therapy as a protective factor for mortality. The impact of antibiotic therapy, seasonality and reduced gastric acid status on survival should be further investigated. Policy-makers and clinicians need to more broadly advise those at risk of contracting this disease and dying as a consequence.

Emergence of pregnancy-related listeriosis amongst ethnic minorities in England and Wales.

Listeriosis is a rare but severe food-borne disease that predominantly affects pregnant women, the unborn, newborns, the elderly and immunocompromised people. Following a large outbreak in the 1980s, specific food safety advice was provided to pregnant women and the immunocompromised in the United Kingdom. Following two coincident yet unconnected cases of pregnancy-related listeriosis in eastern European women in 2008, a review of the role of ethnicity in pregnancy-related listeriosis in England and Wales was undertaken in 2009. Cases reported to the national listeriosis surveillance scheme were classified as 'ethnic', belonging to an ethnic minority, or 'non-ethnic' based on their name, and trends were examined. Between 2001 and 2008, 1,510 cases of listeriosis were reported in England and Wales and, of these, 12% were pregnancy-related cases. The proportion of pregnancy-related cases classified as ethnic increased significantly from 16.7% to 57.9% (chi-square test for trend p=0.002). The reported incidence among the ethnic population was higher than that among the non-ethnic population in 2006, 2007 and 2008 (Relative Risk: 2.38, 95% confidence interval: 1.07 to 5.29; 3.82, 1.82 to 8.03; 4.33, 1.74 to 10.77, respectively). This effect was also shown when analysing data from January to September 2009, using extrapolated live births as denominator. Increased immigration and/or economic migration in recent years appear to have altered the population at risk of pregnancy-related listeriosis in England and Wales. These changes need to be taken into account in order to target risk communication strategies appropriately.

Human listeriosis in England, 2001-2007: association with neighbourhood deprivation.

Listeriosis is a rare but severe food-borne disease that predominantly affects pregnant women, the unborn, newborns, the elderly and immunocompromised people. Despite the high mortality rate of the disease, its socio-economic determinants have not been studied in detail, meaning that health inequalities that might exist in relation to this disease are not apparent. Laboratory surveillance data on listeriosis cases reported in England between 2001 and 2007 were linked to indices of deprivation and denominator data using patients' postcodes. Incidence relative to increasing quintiles of deprivation was calculated by fitting generalised linear models while controlling for population size. Patient food purchasing and consumption data were scrutinised and compared with commercial food purchasing denominator data to further quantify the observed differences in disease incidence. For all patient groups, listeriosis incidence was highest in the most deprived areas of England when compared with the most affluent, and cases were more likely to purchase foods from convenience stores or from local services (bakers, butchers, fishmongers and greengrocers) than the general population were. Patients' risk profile also changed with increasing neighbourhood deprivation. With increased life expectancy and rising food prices, food poverty could become an increasingly important driver for foodborne disease in the future. While United Kingdom Government policy should continue to focus on small food businesses to ensure sufficient levels of food hygiene expertise, tailored and targeted food safety advice on the avoidance of listeriosis is required for all vulnerable groups. Failure to do so may enhance health inequality across socio-economic groups.

Why i.p. therapy cannot yet be considered as a standard of care for the first-line treatment of ovarian cancer: a systematic review.

A National Cancer Institute (NCI) clinical announcement recommended i.p. therapy for women with optimally debulked ovarian cancer. Its basis was a summary of eight randomised controlled trials and two systematic reviews, which appear to indicate benefit of i.p. therapy. However, the systematic reviews that inform the recommendations have been inappropriately presented and interpreted. The systematic reviews inappropriately pooled results from 'confounded' trials in which different drugs and different doses of drugs were given in the control and i.p. treatment arms. Therefore, it is not possible to assess which component of treatment is responsible for improving outcome. In addition, none of the trials use a control arm of the internationally accepted standard of care. Using just the unconfounded trials, indirect comparisons show that the magnitude of benefit observed when i.p. regimens are compared with older i.v. regimens [hazard ratio (HR) for overall survival (OS) 0.75; 95% confidence interval (CI) 0.60-0.92, P = 0.006] is smaller than the magnitude of benefit achieved with modern day standard of i.v. treatment compared with the same i.v. regimen used as control in the unconfounded i.p. trials (HR for OS 0.68; 95% CI 0.58-0.80, P < 0.001). A further difficulty is that the reviews cannot recommend an i.p. regimen for standard use. Drug-related toxicity and catheter complications that occur with i.p. therapy are considerable. The NCI recommendations have major implications for the treatment of women with ovarian cancer and for the next generation of clinical trials. We do not believe that the body of evidence currently available supports the recommendation that i.p. therapy should form part of routine care. The choice of treatment of women with newly diagnosed, optimally debulked, ovarian cancer, where therapy has the best chance of influencing OS, is too important to be left with this uncertainty. A clinical trial that investigates a practical and acceptable regimen which gives some or all chemotherapy by the i.p. route and compares this with standard i.v. chemotherapy should be a priority for those who wish to promote its use.

Pilot scheme for monitoring sickness absence in schools during the 2006/07 winter in England: can these data be used as a proxy for influenza activity?

During influenza epidemics, school-aged children are amongst the first affected patients. They frequently then spread the virus within their families. Recognising influenza activity in schools may therefore be an important indicator of early activity in the wider community. During 2005/06, influenza B was associated with high levels of morbidity in school-children and over 600 schools outbreaks were reported to the Health Protection Agency by local Health Protection Units. While it is not possible to directly monitor influenza in schools, the feasibility and validity of using sentinel school absenteeism data, as a proxy for influenza in the community can be investigated. From week 02/07 to 20/07, eight primary and three secondary schools from five HPA regions were able, via the Department of Health-funded Health Protection Informatics website, to report daily electronic registration data, relating to absenteeism due to illness. Aggregated absenteeism data due to illness peaked the same week as indices for the age group comparable to that used by the Royal College for General Practitioners and NHS Direct schemes. When illness-defined absenteeism data was stratified into primary and secondary schools, absence in primary schools peaked one week before that in secondary schools and the established schemes for all ages. The start time of the study meant that initial increases in activity could not be measured. These encouraging results justify expanding this sentinel scheme to collect more rigorous evidence of the usefulness of absenteeism as a proxy for influenza activity and a tool to inform policy and trigger local responses.

Control of urinary schistosomiasis on Zanzibar (Unguja Island): a pilot evaluation of the educational impact of the Juma na Kichocho health booklet within primary schools

To improve health education within primary schools, the health education booklet Juma na kichocho was evaluated during a study within 5 schools using key-informant questionnaires that recorded children's knowledge and attitude (KA) towards schistosomiasis before and after daily structured-use of booklets. A total of 229 schoolchildren (114 boys : 115 girls) of between 11 and 15 years of age were interviewed and re-assessed after a working school week. Existing and putative booklet-induced changes in KA scores for schistosomiasis were compared directly against equivalent KA scores for malaria. In total 47.4 percent of children were already aware that schistosomiasis was a water-borne disease while only 10.5 percent knew of its exact aetiology; after booklet intervention these levels increased to 54.6 and 15.7 percent, respectively. The majority of children still failed, however, to realise that re-infection could take place soon after treatment. While a positive increase was observed for children's total KA questionnaire scores for both malaria and schistosomiasis after booklet intervention, these were not statistically significant. In the context of control, further educational efforts are needed to promote and guide behavioural change, especially in relation to reduction of environmental water contact.

Control of urinary schistosomiasis on Zanzibar (Unguja Island): a pilot evaluation of the educational impact of the Juma na Kichocho health booklet within primary schools.

To improve health education within primary schools, the health education booklet "Juma na kichocho" was evaluated during a study within 5 schools using key-informant questionnaires that recorded children's knowledge and attitude (KA) towards schistosomiasis before and after daily structured-use of booklets. A total of 229 schoolchildren (114 boys : 115 girls) of between 11 and 15 years of age were interviewed and re-assessed after a working school week. Existing and putative booklet-induced changes in KA scores for schistosomiasis were compared directly against equivalent KA scores for malaria. In total 47.4% of children were already aware that schistosomiasis was a water-borne disease while only 10.5% knew of its exact aetiology; after booklet intervention these levels increased to 54.6 and 15.7%, respectively. The majority of children still failed, however, to realise that re-infection could take place soon after treatment. While a positive increase was observed for children's total KA questionnaire scores for both malaria and schistosomiasis after booklet intervention, these were not statistically significant. In the context of control, further educational efforts are needed to promote and guide behavioural change, especially in relation to reduction of environmental water contact.

Reduction in adverse effects of mechanical ventilation in rabbits with acute respiratory failure by treatment with extracorporeal CO2 removal and a large fluid volume of diluted surfactant.

The long-term outcome of infants with severe respiratory distress syndrome can be improved by optimizing surfactant therapy and minimizing the risk for pulmonary barovolutrauma and oxygen toxicity. The authors hypothesized that this may be achieved with low frequency ventilation and extracorporeal CO2 removal (LFV-ECCO2R), in combination with intratracheal instillation of a large fluid volume with diluted surfactant. Lung lavaged rabbits were initially ventilated with continuous positive pressure ventilation. The rabbits were randomized to treatment with LFV-ECCO2R and surfactant (experimental group), or surfactant only (control group). In the experimental group, the rabbits were treated with a large volume (16 ml/kg) of diluted surfactant (6.25 mg/ml) at a dose of 100 mg/kg body weight. After surfactant therapy, the FiO2 100% was gradually decreased. During 4 hours, the extracorporeal bloodflow was adjusted to maintain the PaCO2 between 4.0-6.0 kPa. Thereafter, the rabbits were allowed to breathe spontaneously with 2.5 cm H2O continuous positive airway pressure ventilation (CPAP) and 40% oxygen. In the control group, the rabbits received the same surfactant therapy. During the study period, the rabbits remained ventilated with an inspiratory oxygen concentration (FiO2) of 100% for 4 hours. The ventilator flow was adjusted to maintain the PaCO2 between 4.0 and 6.0 kPa. Thereafter, positive-end expiratory pressure was decreased to 2.5 cm H2O and FiO2 was gradually decreased to 40%. In the experimental group, FiO2 was decreased to 40% in a stepwise fashion whereby the PaO2 could be maintained easily within the normal range. Extracorporeal flow rates during perfusion ranged from 20-35 ml/kg/min and were sufficient to keep the PaCO2 and pH within normal limits. After 4 hours, the rabbits could breathe spontaneously with CPAP and 40% oxygen, while normal blood gas values were maintained. All rabbits survived the experiment. In the control group, all rabbits experienced severe hypoxemia, despite FiO2 of 100% oxygen and, during the course of weaning, all rabbits died because of hypoxia. In conclusion, the present study demonstrated that barovolutrauma due to mechanical ventilation, and oxygen toxicity due to high FiO2, can be minimized in an animal model of acute respiratory failure by the combination of LFV-ECCO2R and surfactant therapy.

Electrophysiological, rate dependent, and autonomic effects of the class III antiarrhythmic almokalant after myocardial infarction in the pig.

Ventricular arrhythmias remain a major problem, in particular in patients with left ventricular dysfunction or heart failure. In this group of patients, Class I drugs were shown to be ineffective, and they even increased mortality during chronic treatment. New antiarrhythmic agents should preferably not only have pure antiarrhythmic effects, but should also be free from adverse autonomic properties. In the present study, the electrophysiological, rate dependent and autonomic effects of intravenously administered almokalant, a new Class III antiarrhythmic drug, were investigated in nine pigs surviving a myocardial infarction. The ventricular effective refractory period (VERP) increased after almokalant (loading dose: 0.05 mumol.kg-1.min-1, continuous infusion: 0.0025 mumol.kg-1.min-1) from 292 +/- 25 to 308 +/- 13 ms (pacing cycle length [PCL] 500 ms + 1 extrasystole [ES]), from 249 +/- 19 to 261 +/- 16 ms (PCL 400 ms +1ES), and from 209 +/- 18 to 219 +/- 18 ms (PCL 300 ms +1ES). The VERPs increased most after three ES at PCL 400 ms: from 167 +/- 27 to 186 +/- 29 ms (P < 0.05) and at PCL 300 ms: from 150 +/- 29 to 174 +/- 27 ms (P < 0.05). The ventricular monophasic action potential durations (MAPD) were similarly prolonged and the ratio VERP/MAPD did not change. Prolongation of MAPD after almokalant remained present at short pacing cycle lengths. Before almokalant infusion, sustained monomorphic ventricular tachycardia (VT) was inducible in two pigs, and nonsustained VT in a third animal. After almokalant, only one pig remained inducible. Two weeks after myocardial infarction, heart rate variability and baroreflex sensitivity were reduced. Furthermore, subsequent electrophysiological testing transiently reduced these parameters of autonomic activity. During almokalant however, no changes in autonomic functions were observed after programmed stimulation. Heart rate variability decreased after myocardial infarction from 6.3 +/- 2.5 ms to 5.4 +/- 4.2 ms (P = NS). After programmed stimulation, it further decreased to 2.8 +/- 2.0 ms (P = 0.028). Almokalant infusion prevented autonomic deterioration: 3.3 +/- 2.2 ms before stimulation and 3.3 +/- 1.3 after stimulation (P = NS). In postinfarct pigs, almokalant prolongs VERP and MAPD at shorter pacing cycle lengths. The results indicate absence of reverse rate dependence and of adverse autonomic changes.

Large volume instillation of surfactant during extracorporeal life support improves lung function in lung lavaged rabbits.

The sometimes limited effect of surfactant therapy in neonates might be explained in part by an non homogeneous distribution of the surfactant after endotracheal instillation. This distribution can be improved significantly by increasing the fluid volume. The aim of this study was to evaluate the effect of two methods for gas exchange during a large volume instillation of surfactant on the outcome of this treatment in lung lavaged rabbits. In the control group (n = 6) gas exchange was maintained with continuous positive pressure ventilation (CV), whereas in the other group gas exchange was established with extracorporeal life support (ECLS) (n = 6) and intermittent sighs. Five hours after surfactant administration, an identical weaning procedure was started in both groups. The authors found significantly higher PaO2 values in the ECLS group than in the control group in the normocarbia state. All animals in the ECLS group could be weaned to room air maintaining normal blood gases, whereas all the animals in the control group died in the course of weaning. The ventilator efficiency index was significantly higher during the weaning period in the ECLS group, indicating better lung function, than in the control group. The authors conclude that a large volume instillation of surfactant is feasible by applying ECLS and intermittent sighs. Additional studies are needed to elucidate if this combined treatment will be an improvement over current surfactant therapy.