The incubation period of hepatitis E genotype 1: insights from pooled analyses of travellers.

Hepatitis E virus genotype 1 (HEV G1) is an important cause of morbidity and mortality in Africa and Asia. HEV G1's natural history, including the incubation period, remains poorly understood, hindering surveillance efforts and effective control. Using individual-level data from 85 travel-related HEV G1 cases in England and Wales, we estimate the incubation period distribution using survival analysis methods, which allow for appropriate inference when only time ranges, rather than exact times are known for the exposure to HEV and symptom onset. We estimated a 29.8-day (95% confidence interval (CI) 24.1-36.0) median incubation period with 5% of people expected to develop symptoms within 14.3 days (95% CI 10.1-21.7) and 95% within 61.9 days (95% CI 47.4-74.4) of exposure. These estimates can help refine clinical case definitions and inform the design of disease burden and intervention studies.

Pork products associated with human infection caused by an emerging phylotype of hepatitis E virus in England and Wales.

Since 2010, human hepatitis E infections have increased in England and Wales. Most cases are locally acquired and caused by hepatitis E virus genotype 3 (HEV G3). HEV G3 is linked to the consumption of pork products. The increase is associated with the emergence of a new phylotype, HEV G3-group 2 (G3-2, also known as G3abcdhij). Sixty individuals with confirmed hepatitis E infection and no history of travel outside the UK were recruited: 19 were infected with HEV G3-group 1 (G3-1 or G3efg) and 41 with G3-2. Epidemiological data relating to usual shopping habits and consumption of ham and sausages were analysed together with typing data to identify any associations with HEV phylotype. Study participants who purchased ham and/or sausage from a major supermarket were more likely to have HEV G3-2 infection (Relative risks 1·85, P = 0·06, CI 0·97-3·53). The HEV G3-2 phylotype has not been detected in indigenous UK pigs and it is suggested that human infections could be the result of consumption of products made from pork originating outside the UK. This does not infer blame on the supermarket but the epidemiology of HEV is dynamic and reflects complex animal husbandry practices which need to be explored further.

Using data linkage to improve surveillance methods for acute hepatitis E infections in England and Wales 2010-2016.

Indigenous, foodborne transmission of hepatitis E has been increasing across industrialised countries. Public Health England has conducted enhanced surveillance in England and Wales since 2003.This report gives an account of acute infections from 2010 to 2016 and describes modification made to the methods of surveillance to account for changes in reporting behaviours and improve ascertainment.

Risk factors for acute toxoplasmosis in England and Wales.

Over 300 cases of acute toxoplasmosis are confirmed by reference testing in England and Wales annually. We conducted a case-control study to identify risk factors for Toxoplasma gondii infection to inform prevention strategies. Twenty-eight cases and 27 seronegative controls participated. We compared their food history and environmental exposures using logistic regression to calculate odds ratios (OR) and 95% confidence intervals in a model controlling for age and sex. Univariable analysis showed that the odds of eating beef (OR 10·7, P < 0·001), poultry (OR 6·4, P = 0·01) or lamb/mutton (OR 4·9, P = 0·01) was higher for cases than controls. After adjustment for potential confounders a strong association between beef and infection remained (OR 5·6, P = 0·01). The small sample size was a significant limitation and larger studies are needed to fully investigate potential risk factors. The study findings emphasize the need to ensure food is thoroughly cooked and handled hygienically, especially for those in vulnerable groups.

[Fixed drug eruption to clarithromycin: The importance of challenge tests in diagnosis]. / Érythème pigmenté fixe à la clarithromycine : importance des tests de provocation pour le diagnostic.

BACKGROUND: Determining the substance responsible for recurrent fixed drug eruption (FDE) may be difficult in the case of patients on multiple medication. Allergy testing may prove invaluable in such situations, as we demonstrate herein with an original case. PATIENTS AND METHODS: A 49-year-old man presented a rash on the seventh day of treatment with esomeprazole, clarithromycin and amoxicillin prescribed for gastritis involving Helicobacter pylori. The condition regressed spontaneously within a few days, but left three areas of hyperpigmentation. The patient subsequently reported four further episodes consisting of stereotypical reactivation in the areas of the three initial lesions and occurring 24hours after use of clarithromycin (2 episodes) and amoxicillin (2 episodes). The patient resumed proton pump inhibitor therapy (esomeprazole) without incident. Based on history taking, an initial diagnosis was made of multiple fixed drug eruption involving amoxicillin and clarithromycin. The initial skin allergy investigations were negative (patch-tests for amoxicillin and clarithromycin on healthy skin on the patient's back and on the affected area). After discussion, we decided to reintroduce the suspected drugs in succession. Beginning with clarithromycin, 12h after a single dose of 250mg, we noted an erythematous reaction on the pigmented areas, together with a burning sensation. In an identical challenge test with amoxicillin (500mg), the latter drug was perfectly well tolerated, ruling out the diagnosis of FDE to amoxicillin and thus the diagnosis of multiple FDE suggested by the patient history. DISCUSSION: FDEs to macrolides are rare, and herein we report a new case. Our observation confirms the diagnostic value of challenge tests in FDE. These tests should only be performed in the event of non-severe FDE, in other words not in bullous or systemic reactions, and they often constitute the only diagnostic approach possible, since skin tests are rarely positive during investigation for FDE.

Hepatitis E virus in England and Wales: indigenous infection is associated with the consumption of processed pork products.

Indigenously acquired hepatitis E infections have increased substantially in England and Wales since 2010. Epidemiological investigations were undertaken to determine risk factors for the acquisition of infection. A case-control study (25 cases, 75 controls) was used to test the hypothesis that hepatitis E infection was related to consumption of pork products. In a multivariable model, consumption of pork pie [odds ratio (OR) 6·33, 95% confidence interval (CI) 1·41-28·48, P = 0·009] and consumption of ham and sausages purchased from a major UK supermarket chain (OR 10·12, 95% CI 1·68-60·81, P = 0·023) were significantly associated with indigenous infection. The consumption of sausages and ham purchased from the supermarket was highly correlated; however. separate models showed that each variable was significantly associated with infection (OR 7·59, 95% CI 1·81-31·84, P = 0·004 and OR 10·98, 95% CI 1·84-65·35, P = 0·003, respectively). Although contamination of sausages with HEV has previously been shown this study also raises concerns about other processed pork products and whether current practice in preparing these products is sufficient to prevent transmission of HEV.

Enhanced surveillance for toxoplasmosis in England and Wales, 2008-2012.

A report on Toxoplasma gondii by the UK Advisory Committee on the Microbiological Safety of Food recommended that more accurate figures on the burden of disease in the UK are needed. We present the first 5 years of data from an enhanced surveillance scheme for toxoplasmosis in England and Wales. Between 2008 and 2012, 1824 cases were reported, with an average of 365 each year. There were 1109 immunocompetent cases, the majority presenting with lymphadenopathy, and 364 immunosuppressed cases, with central nervous system and systemic symptoms most frequently reported. There were also 190 pregnant and 33 congenital cases. Of the pregnant cases, 148 were asymptomatic (probably detected during screening), while 28 suffered a fetal loss or stillbirth. The enhanced surveillance system has led to an improvement in the detection of toxoplasmosis in England and Wales. However, numbers are still likely to be an underestimate, biasing towards the more severe infections.

Using public health scenarios to predict the utility of a national syndromic surveillance programme during the 2012 London Olympic and Paralympic Games.

During 2012 real-time syndromic surveillance formed a key part of the daily public health surveillance for the London Olympic and Paralympic Games. It was vital that these systems were evaluated prior to the Games; in particular what types and scales of incidents could and could not be detected. Different public health scenarios were created covering a range of potential incidents that the Health Protection Agency would require syndromic surveillance to rapidly detect and monitor. For the scenarios considered it is now possible to determine what is likely to be detectable and how incidents are likely to present using the different syndromic systems. Small localized incidents involving food poisoning are most likely to be detected the next day via emergency department surveillance, while a new strain of influenza is more likely to be detected via GP or telephone helpline surveillance, several weeks after the first seed case is introduced.

Evaluation of the surveillance system for undiagnosed serious infectious illness (USII) in intensive care units, England, 2011 to 2013.

Emerging infections are a potential risk during mass gathering events due to the congregation of large numbers of international travellers. To mitigate this risk for the London 2012 Olympic and Paralympic Games, a sentinel surveillance system was developed to identify clusters of emerging infections presenting as undiagnosed serious infectious illness (USII) in intensive care units (ICUs). Following a six month pilot period, which had begun in January 2011, the surveillance was operational for a further 18 months spanning the Games. The surveillance system and reported USII cases were reviewed and evaluated after this 18 month operational period including assessment of positive predictive value (PPV), timeliness, acceptability and sensitivity of the system. Surveillance records were used to review reported cases and calculate the PPV and median reporting times of USII surveillance. Sensitivity was assessed through comparison with the pilot period. Participating clinicians completed a five-point Likert scale questionnaire about the acceptability of surveillance. Between 11 July 2011 and 10 January 2013, 34 cases were reported. Of these, 22 remained classified as USII at the time of the evaluation, none of which were still hospitalised. No clusters were identified. The 22 USII cases had no association with the Games, suggesting that they represented the background level of USII in the area covered by the surveillance. This corresponded to an annualised rate of 0.39 cases/100,000 population and a PPV of 65%. Clinicians involved in the surveillance reported high acceptability levels. The USII surveillance model could be a useful public health tool in other countries and during mass gathering events for identifying potential clusters of emerging infections.

[Recurrent pyoderma gangrenosum-like ulcers induced by oral anticoagulants]. / Ulcérations récidivantes à type de pyoderma grangrenosum induites par les antivitamines K.

BACKGROUND: Other than the classic skin necrosis induced by oral anticoagulants (OAC) in patients with protein C and S deficiencies, other types of OAC induced-skin ulcers are little known. Herein, we describe an original case of recurrent pyoderma gangrenosum (PG)-like ulcers induced by OAC. PATIENTS AND METHODS: A 70-year-old female heart-transplant recipient presented deep, hyperalgesic and quickly-spreading necrotic ulceration of the right leg 6 weeks after starting oral anticoagulant therapy with fluindione. Histological analysis revealed dermal infiltrate containing polynuclear neutrophils, which accords with the histopathological diagnosis of leukocytoclastic vasculitis or PG. Infectious, autoimmune and thrombophilic causes were ruled out. Fluindione was withdrawn and the ulcer healed completely within a month. Six months later, right leg ulceration recurred two weeks after the patient resumed fluindione but healed within 1 month of discontinuation of the drug. An OAC from another chemical family (warfarin) was then introduced, with further recurrence of ulceration after 2 weeks of treatment. DISCUSSION: The chronology of events and the negativity of aetiological explorations allowed a diagnosis to be made of OAC-induced skin ulcer, a rare complication of which the pathophysiology is unclear. This is the first case of PG-like ulcers induced by OAC.

[Sexuality and prostate cancer]. / Sexualité et cancer de la prostate.

INTRODUCTION: All treatments for prostate cancer have a negative impact on sexuality. The objective of this review is to highlight recent developments in the management of sexual dysfunction associated with prostate cancer. MATERIAL AND METHODS: We performed a literature search in the Pubmed database to select relevant articles. RESULTS: There is a specific profile of changes in the fields of sexual, urinary, bowel and general quality of life, according to the treatment modalities chosen. Maintenance of a satisfying sex life is a major concern of a majority of men facing prostate cancer and its treatments. It is essential to assess the couple's sexuality before treating prostate cancer in order to deliver comprehensive information and consider early therapeutic solutions adapted to the couple's expectations. The results of randomized studies show that robotic radical prostatectomy allows a faster recovery of natural erections compared to classic laparoscopy. Active pharmacological erectile rehabilitation (intracavernous injections or phosphodiesterase type 5 inhibitors [PDE5i] on demand, during the month following surgery) or passive (daily PDE5i after surgery) might improve the quality of erections especially in response to PDE5i. Unimpaired aspects of sexual response (orgasm) may, when the erection is not yet recovered, represent an alternative allowing the couple to preserve intimacy and complicity. Androgen blockade is a major barrier to maintain or return to a satisfying sex. CONCLUSION: After the treatment of prostate cancer, one specific support sometimes assisted by networking will optimize satisfying sex life recovery.

Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

A new surveillance system for undiagnosed serious infectious illness for the London 2012 Olympic and Paralympic Games.

A new surveillance system was developed to detect possible new or emerging infections presenting as undiagnosed serious infectious illness (USII) for use during the London 2012 Olympic and Paralympic Games. Designated clinicians in sentinel adult and paediatric intensive care units (ICU/ PICUs) reported USII using an online reporting tool or provided a weekly nil notification. Reported cases were investigated for epidemiological links. A pilot study was undertaken for six months between January and July 2011 to evaluate the feasibility and acceptability of the system. In this six-month period, 5 adults and 13 children were reported by six participating units (3 ICUs, 3 PICUs). Of these 18 patients, 12 were reported within four days after admission to an ICU/PICU. Nine patients were subsequently diagnosed and were thus excluded from the surveillance. Therefore, only nine cases of USII were reported. No clustering was identified.On the basis of the pilot study, we conclude that the system is able to detect cases of USII and is feasible and acceptable to users. USII surveillance has been extended to a total of 19 sentinel units in London and the south-east of England during the London 2012 Olympic and Paralympic Games.

Cryptococcemia in a patient with COVID-19: A case report.

The authors urge clinicians to balance the use of Immunosuppressant drugs and tocilizumab for COVID-19 patients to avoid the development of infections like Cryptococcemia, leading to death within 30 days.

[Management of drug reaction with eosinophilia and systemic symptoms (DRESS)]. / Prise en charge du drug reaction with eosinophilia and systemic symptoms (DRESS).

OBJECTIVE: The management of drug-induced hypersensitivity syndrome or drug reaction with eosinophilia and systemic symptoms (DRESS) is not codified. Demonstration of the reactivation of Herpesviruses illustrates the specific pathophysiology of this syndrome. Proposals for the management of DRESS were elaborated by the cutaneous adverse drug reaction working group of the French Society of Dermatology to help with its management. METHODS: From a review of literature and the experience of the members of this group, consensual proposals were written about diagnostic criteria, tests, treatment options, and follow-up. These proposals will need to be validated in prospective studies. RESULTS: A decisional tree of treatment options is proposed, based on the severity of visceral manifestations. The importance of a rapid withdrawal of the culprit drug and of a long-term follow-up is underlined. Treatment will be adapted to the clinicobiological status (topical corticosteroid, systemic corticosteroid, intravenous gammaglobulins, antivirals).

Longitudinal health utilities, symptoms and toxicities in patients with ALK-rearranged lung cancer treated with tyrosine kinase inhibitors: a prospective real-world assessment.

Background: Tyrosine kinase inhibitors (tkis) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (nsclc). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple tki therapies in the population with ALK+ nsclc. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of tkis, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (hus). Results: In 499 longitudinal encounters of 76 patients with ALK+ nsclc, each tki had stable longitudinal hus when disease was controlled, even after months to years: the mean overall hus for each tki ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation tkis of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean hus decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from -0.094 to -0.557. Fewer symptoms and toxicities were associated with the second- and third-generation tkis compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved hus. Conclusions: There was no significant decrease in hus when patients with ALK+ disease were treated longitudinally with each tki, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean hus longitudinally in the real-world setting.

Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: french national audit of practices, literature review, and consensus agreement.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.

First experience of combined cardiac PET/64-detector CT angiography with invasive angiographic validation.

PURPOSE: Despite modern CT systems and expert evaluators, the diagnostic performance of coronary CT angiography is limited by overestimation of vessel stenosis which reduces the positive predictive value (PPV) of the test. The aim of this study was to evaluate the performance of combined cardiac PET/64-detector CT angiography. METHODS: Included in this retrospective study were 33 consecutive patients (5 women, 28 men; mean age 61.6 years, range 47-87 years, mean BMI 27.3+/-5.2 kg/m(2)) with clinically suspected flow-limiting coronary artery disease who underwent combined cardiac PET/64-detector CT angiography and invasive angiography. Combined PET/CT images were reported by an experienced dual-accredited radiologist/nuclear physician. An experienced cardiac CT radiologist re-read the CT images without PET. Stenotic disease was defined as >50% vessel narrowing. Invasive coronary angiography was used as a reference standard. Local ethics committee approval and patient consent were obtained. RESULTS: CT angiography (without PET data) was concordant with invasive angiography in 31/33 patients and at a patient level, the sensitivity in detecting significant coronary artery lesions was 100%, the specificity was 82%, the PPV was 92% and the negative predictive value (NPV) was 100%. Using combined PET/CT angiography the findings were concordant with invasive angiography in 32/33 patients and at a patient level, the sensitivity was 96%, the specificity was 100%, the PPV was 100% and the NPV was 91%. CONCLUSION: The use of integrated cardiac PET/64-detector CT angiography is feasible and appears to improve some aspects of the diagnostic performance of 64-detector coronary artery angiography in detecting coronary artery disease.