Six-year experience of detection and investigation of possible Middle East Respiratory Syndrome coronavirus cases, England, 2012-2018.

OBJECTIVES: Surveillance for Middle East Respiratory Syndrome (MERS) has been undertaken in the UK since September 2012. This study describes the surveillance outcomes in England from 2012 to 2018. STUDY DESIGN: This was a descriptive study using surveillance data. METHODS: Local health protection teams in England report possible MERS cases to the National Infection Service with clinical and laboratory data. RESULTS: A total of 1301 possible MERS cases were identified in the study period. Five cases were laboratory-confirmed MERS. The majority of cases had travelled to Saudi Arabia (56.7%) and United Arab Emirates (25.9%). Fifty-four percent of cases were men and 43.7% were women. The majority of cases (65.1%) were aged 45 years or older. The number of tests increased in the period after Hajj each year. Laboratory-confirmed alternative diagnoses were available for 513 (39.4%) cases; influenza was the most common virus detected (n = 255, 52.4%). CONCLUSIONS: Our study highlights the importance of differential diagnosis of influenza and other respiratory pathogens and early influenza antiviral treatment.

Von Willebrand factor for menorrhagia: a survey and literature review.

BACKGROUND: von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. METHODS: We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. RESULTS: Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg(-1) on day 1-6 of menstrual cycle. CONCLUSIONS: This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings.

Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Microtubule stability in budding yeast: characterization and dosage suppression of a benomyl-dependent tubulin mutant.

To better understand the dynamic regulation of microtubule structures in yeast, we studied a conditional-lethal beta-tubulin mutation tub2-150. This mutation is unique among the hundreds of tubulin mutations isolated in Saccharomyces cerevisiae in that it appears to cause an increase in the stability of microtubules. We report here that this allele is a mutation of threonine 238 to alanine, and that tub2-150 prevents the spindle from elongating during anaphase, suggesting a nuclear microtubule defect. To identify regulators of microtubule stability and/or anaphase, yeast genes were selected that, when overexpressed, could suppress the tub2-150 temperature-sensitive phenotype. One of these genes, JSN1, encodes a protein of 125 kDa that has limited similarity to a number of proteins of unknown function. Overexpression of the JSN1 gene in a TUB2 strain causes that strain to become more sensitive to benomyl, a microtubule-destabilizing drug. Of a representative group of microtubule mutants, only one other mutation, tub2-404, could be suppressed by JSN1 overexpression, showing that JSN1 is an allele-specific suppressor. As tub2-404 mutants are also defective for spindle elongation, this provides additional support for a role for JSN1 during anaphase.

Dosage suppressors of a benomyl-dependent tubulin mutant: evidence for a link between microtubule stability and cellular metabolism.

To identify factors important for the regulation of microtubule stability in yeast, dosage suppressors of the hyperstable microtubule phenotype of the budding yeast tub2-150 beta-tubulin mutation were isolated. Of the two suppressors reported here, one (JSN2) encodes a tRNAVal, and the other (JSN3) is an antimorphic allele of the methionine biosynthesis transcription factor Met4p. Furthermore, growth of tub2-150 mutants and suppression of tub2-150 mutants by JSN3 are sensitive to levels of methionine in the growth medium. We explore several possible explanations for these findings, including the potential involvement of the general amino acid control and the involvement of Cbflp, a component of yeast kinetochores that is also necessary for Met4p-mediated transcription.

The use of a European telemedicine system to examine the effects of pollutants and allergens on asthmatic respiratory health.

The experience of using a telemedicine feasibility study to integrate respiratory health response and environmental stimuli information is presented. The effects of ambient air quality, pollen and local environment conditions on asthmatic patients' lung function were investigated through the use of a novel European health telematic system. The Medical Diagnosis, Communication and Analysis Throughout Europe (MEDICATE) project developed and tested the feasibility of using a telemedicine system for chronic asthmatics in London, UK, and Barcelona, Spain. The key to this was the determination of the real time health (lung function) response to the ambient environment and allergens. Air quality, pollen and environmental lifestyle information were related to respiratory measurements for recruited asthmatic patients in the study through the design of a dedicated environmental management system (EMS) database. In total, 28 patients completed the study trial, subject to ambulatory monitoring of spirometric lung function (PEF, FEV(1) and FVC) up to four times a day over a 2-week period recorded during the year 2000. Alongside this, ambient air quality and pollen counts were used to represent local exposure to potential environmental stimuli. Personal questionnaire interviewing collected additional data about patient lifestyles, social-economic conditions and quality of life perceptions. The methods and indicative results of integrating environmental and health data in this respect are examined. Assessment tools such as GIS and object-orientated databases were designed to locate and compile environmental information about the patients' locations and lifestyles in the study areas (London and Barcelona). Socioeconomic and lifestyle factors, such as exposure to smoking, pets, personal journey lengths and modes, income, household occupancy and domestic fuel use, were found to have limited detectable effects on the patients' basic lung function levels. Patients' gender, age and predicted PEFR were significantly associated with the 2-week mean and minimum respiratory measurements. Lung function data were compared with air quality and pollen indicators to examine relationships on a daily or lagged-day basis controlling for confounding factors. The paper discusses the new methodology and the practicalities of using the telemedical system as a tool for assessing the impacts of environmental stimuli on respiratory health.

Social awareness of air quality information.

In the UK, air quality information is made available through a range of media. However, limited attention has been paid to ensuring that the information is provided to the public in a format that is understandable and relevant to their needs. This research has begun the task of determining the nature and extent of public air quality requirements by performing a social survey (using a postal questionnaire) to provide a basic snapshot of the public's views and by determining the views of information providers and interested professionals. The paper identifies the main shortcomings in current public air quality information provision. The social survey and workshop results demonstrate that current information provision and dissemination does not match public requirements; the depth and breadth of local information needs to be enhanced. Local authorities need to improve their co-ordination and collaboration, the role of the mass-media needs to be considered carefully, air quality needs to be better described and its implications for individuals spelled out and certain public groups need special consideration. In addition, local authorities need more guidance on communicating air quality, possibly through a best practice guide. Further research is required to identify the best descriptors for air quality, to improve the effectiveness of public advice during episodes of poor air quality and to use public air quality information to effect behavioral changes.

Calidad del tratamiento aplicado a gestantes con hipertensión arterial en el Distrito de Salud 4 Abel Santamaria Cuadrado / Quality of treatment applied to pregnant women with hypertension at Abel Santamaría Cuadrado Health District 4

Se evaluó la calidad del tratamiento aplicado a 32 embarazadas con hipertensión arterial, pertenecientes al Distrito de Salud 4 Abel Santamaría Cuadrado de Santiago de Cuba. El estudio, efectuado desde octubre de 2009 hasta mayo de 2010, incluyó a dichas gestantes y 93 médicos de familia de la localidad. La evaluación, que contempló proceso (calidad cientificotécnica) y resultado (satisfacción), se basó en el análisis retrospectivo de las historias obstétricas, el examen de conocimiento y la información obtenida a través de las encuestas. Se concluyó, entre otros aspectos, que tanto los profesionales en cuestión como las gestantes se mostraron insatisfechos en sentido general, de donde se derivó que tampoco la terapéutica fue adecuada al comparar los indicadores de cada criterio con los estándares prefijados.

The quality of the treatment applied to 32 pregnant women with hypertension, belonging to Abel Santamaría Cuadrado Health District 4 in Santiago de Cuba was evaluated. The study carried out from October 2009 to May 2010 included these pregnant women and 93 family physicians of the locality. The evaluation, which looked at process (scientific and technical quality) and result (satisfaction), was based on retrospective analysis of the obstetric records, examination of knowledge and information obtained through surveys. It was concluded, among other issues, that both the professionals and pregnant women were generally dissatisfied, therefore the therapy was inappropriate when comparing the indicators of each criterion with the preset standards.

A DNA double chain break stimulates triparental recombination in Saccharomyces cerevisiae.

Mitotic recombination between his3 heteroalleles on heterologous chromosomes is stimulated by a DNA double chain break delivered in vivo at a site 8.6 kilobase pairs distant from one his3 allele and unlinked to the other. The induced recombination at his3 is accompanied by gap repair at the break site using the uncut homolog as a template. The DNA between the break site and his3 is not deleted in most of the His+ recombinants.

Serum angiotensin converting enzyme in Sjogren's syndrome--a case report and study of 21 further cases.

We report the case of an elderly woman with primary Sjogren's syndrome and abnormal liver function tests indicative of primary biliary cirrhosis. She was found to have a raised serum angiotensin converting enzyme activity. We proceeded to study 21 further cases of Sjogren's syndrome to discover whether raised levels of this enzyme were a feature of Sjogren's syndrome. None of them had any features to suggested associated primary biliary cirrhosis. The cases included 12 with associated rheumatoid arthritis, two with systemic sclerosis, three with systemic lupus erythematosus and four with primary Sjogren's syndrome. In only two of these 21 patients was a raised serum angiotensin converting enzyme obtained, the elevation being modest. We conclude that a raised activity of the enzyme is not usually associated with primary or secondary Sjogren's syndrome, and that discovery of such an abnormality should prompt a search for an associated condition.