Autoimmune hepatitis: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunisation safety data

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management

Speech produced in noise: Relationship between listening difficulty and acoustic and durational parameters.

Conversational speech produced in noise can be characterised by increases in intelligibility relative to such speech produced in quiet. Listening difficulty (LD) is a metric that can be used to evaluate speech transmission performance more sensitively than intelligibility scores in situations in which performance is likely to be high. The objectives of the present study were to evaluate the LD of speech produced in different noise and style conditions, to evaluate the spectral and durational speech modifications associated with these conditions, and to determine whether any of the spectral and durational parameters predicted LD. Nineteen subjects were instructed to speak at normal and loud volumes in the presence of background noise at 40.5 dB(A) and babble noise at 61 dB(A). The speech signals were amplitude-normalised, combined with pink noise to obtain a signal-to-noise ratio of -6 dB, and presented to twenty raters who judged their LD. Vowel duration, fundamental frequency and the proportion of the spectral energy in high vs low frequencies increased with the noise level within both styles. LD was lowest when the speech was produced in the presence of high level noise and at a loud volume, indicating improved intelligibility. Spectrum balance was observed to predict LD

Cancer risk among users of neuroleptic medication: a population-based cohort study

It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25 264 users (⩾2 prescriptions) of neuroleptic medications in the county of North Jutland, Denmark, during 1989–2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41–0.91) and 0.82 (0.56–1.19), respectively) and for colon cancer in female users (0.78; 0.62–0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69–1.08), but breast cancer risk was close to unity (0.93; 0.74–1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk

SARS Surveillance during Emergency Public Health Response, United States, March–July 2003

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology

Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

Cigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers