Illness representations of people with later-onset functional seizures.

PURPOSE: Although functional seizures can start at any age, little is known about the individuals for whom onset occurs after the age of 40. It has been proposed that health-related traumatic events are more relevant causal factors for people with 'later-onset functional seizures' than for those whose functional seizures begin earlier in life, however, the illness representations of people with later-onset functional seizures have not yet been investigated. This study aimed to understand the experiences and illness representations of people with later-onset functional seizures. METHODS: This was a mixed-methods study. People with later-onset functional seizures were recruited via a neurologist's caseload and online membership-led organisations. Semi-structured interview transcripts were analysed using Template Analysis according to the Common-Sense Model (CSM). Self-report measures of demographic and clinical details were collected to characterise the sample and verify themes. RESULTS: Eight people with later-onset functional seizures participated in the study. Illness representations relating to all domains of the CSM as well as an additional theme of 'Triggers' were identified. Functional seizures were characterised as a mysterious brain disorder analogous to a computer malfunction and involving involuntary movements associated with alterations in consciousness. Perceptions of duration were indefinite, and triggers were unknown or at the extremes of autonomic arousal. Half of the sample identified health-related events/trauma as causal. Opinions were divided on 'cumulative life stress' as a causal factor. Most perceived themselves to have limited or no control but having 'control' over seizures was conceptualised as different to reducing their likelihood, frequency, or impact. Later-onset functional seizures were viewed as being more detrimental for caring and financial responsibilities but to have advantages for acceptance. CONCLUSIONS: This is the first study to assess the illness representations of people with later-onset functional seizures. Many themes were similar to those identified in samples including people with earlier-onset functional seizures. Health-related trauma or events were the most strongly endorsed perceived causal factor, but with the exception of 'consequences', all representations were characterised by uncertainty. Clinicians should hold in mind the interaction between life stage and the consequences of later-onset functional seizures.

Uncertainties and opportunities in delivering environmentally sustainable surgery: the surgeons' view.

Surgery is a carbon-heavy activity and creates a high volume of waste. Surgical teams around the world want to deliver more environmentally sustainable surgery but are unsure what to do and how to create change. There are many interventions available, but resources and time are limited. Capital investment into healthcare and engagement of senior management are challenging. However, frontline teams can change behaviours and drive wider change. Patients have a voice here too, as they would like to ensure their surgery does not harm their local community but are concerned about the effects on them when changes are made. Environmentally sustainable surgery is at the start of its journey. Surgeons need to rapidly upskill their generic knowledge base, identify which measures they can implement locally and take part in national research programmes. Surgical teams in the NHS have the chance to create a world-leading programme that can bring change to hospitals around the world. This article provides an overview of how surgeons see the surgical team being involved in environmentally sustainable surgery.

Respiratory symptoms and chronic bronchitis in people with and without HIV infection.

OBJECTIVES: High rates of respiratory symptoms and chronic bronchitis (CB) are reported in people with HIV infection (PWH). We investigated the prevalence of respiratory symptoms and CB in PWH and HIV-negative people in the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. METHODS: Assessment of respiratory symptoms and CB was undertaken using the modified form of the St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (COPD). Univariate (χ2 tests, Mann-Whitney U tests and Spearman's rank correlation) and multivariable (linear and logistic regression) analyses were performed to consider associations of respiratory symptoms with demographic, lifestyle and HIV-related parameters, and with depressive symptoms and quality of life. RESULTS: Among the 619 participants, respiratory Symptom scores were higher in older and younger PWH compared to older HIV-negative people, with median (interquartile range) scores of 17.7 (6.2, 39.5), 17.5 (0.9, 30.0) and 9.0 (0.9, 17.5), respectively (P = 0.0001); these differences remained significant after confounder adjustment. Sixty-three participants (10.2%) met the criteria for CB [44 (14.0%) older PWH, 14 (9.2%) younger PWH, and five (3.3%) older HIV-negative people; P = 0.002], with these differences also remaining after adjustment for confounding variables, particularly smoking status [older vs. younger PWH: odds ratio (OR) 4.48 (95% confidence interval (CI) 1.64, 12.30); P = 0.004; older PWH vs. HIV-negative people: OR 4.53 (95% CI 1.12, 18.28); P = 0.03]. Respiratory symptoms and CB were both associated with greater depressive symptom scores and poorer quality of life. No strong associations were reported between CB and immune function, HIV RNA or previous diagnosis of any AIDS event. CONCLUSIONS: Respiratory symptoms and CB are more common in PWH than in demographically and lifestyle-similar HIV-negative people and are associated with poorer mental health and quality of life.

Takayasu's arteritis and acute type B aortic dissection treated with a stent graft.

OBJECTIVES: Takayasu's arteritis is a large vessel vasculitis which usually involves the aorta and its first generation branches. Aortic dissection, however, is a rare manifestation of Takayasu's arteritis and for this reason optimum management in both short and long term is unknown. METHODS: This is a case of a 31-year-old female presenting with acute type B AD in association with underlying TA which failed to respond to conservative management and underwent thoracic stent grafting (TEVAR). RESULTS: Despite successful coverage of the intimal breach in the thoracic aorta by TEVAR there were complications with delivery of the stent which required a conduit sutured to the right common iliac artery. Also post-TEVAR computed tomography showed a localised dissection of the origin of the left common carotid artery which may have been iatrogenic possibly due to the stiff guidewire used during delivery of the stent graft to the thoracic aorta. CONCLUSIONS: The use of TEVAR for an acute type B AD in those with TA may be problematic. The fragility of the major arteries increases the likelihood of iatrogenic periprocedural complications and long-term surveillance is essential due to significant chance of further arterial complications in type B AD occurring in TA.

Factors associated with obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort: an observational cross-sectional analysis.

OBJECTIVES: The aims of the study were to describe the prevalence of obesity in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) cohort, to identify demographic, clinical and HIV-specific factors associated with obesity, and to characterize the association between obesity and sociodemographic, clinical and HIV-specific factors and quality of life (QoL). METHODS: A cross-sectional analysis was carried out of baseline data from the three groups ["older" people with HIV infection (PWH) aged ≥ 50 years, "younger" PWH aged < 50 years and HIV-negative controls aged ≥ 50 years] within the POPPY cohort. Obesity was defined as a body mass index (BMI) > 30 kg/m2 . RESULTS: A total of 1361 subjects were included in the study, of whom 335 (24.6%) were obese. The prevalence of obesity was higher in controls (22.3%) than in older (16.8%) and younger (14.2%) PWH, with no differences between the two groups of PWH. Factors associated with obesity were older age, female gender, black African ethnicity and alcohol consumption. Recreational drug use and a higher current CD4 T-cell count (in PWH) were associated with lower and higher odds of being obese, respectively. The presence of obesity was associated with worse physical health QoL scores, higher odds of having cardiovascular disease, type 2 diabetes and hypertension, but lower odds of having osteopenia/osteoporosis, irrespective of HIV status. CONCLUSIONS: Despite a lower prevalence of obesity in PWH, specific subgroups (women, people of black African origin and older people) were more likely to be obese, and negative health consequences of obesity were evident, regardless of HIV status. Whether targeted preventive strategies can reduce the burden of obesity and its complications in PWH remains to be determined.

Detecting national human enteric disease outbreaks linked to animal contact in the United States of America.

Enteric pathogens, such as non-typhoidal Salmonella, Campylobacter and Escherichia coli, can reside in the intestinal tract of many animals, including livestock, companion animals, small mammals and reptiles. Often, these animals can appear healthy; nonetheless, humans can become infected after direct or indirect contact, resulting in a substantial illness burden. An estimated 14% of the 3.2 million illnesses that occur in the United States of America (USA) each year from such enteric pathogens are attributable to animal contact. Surveillance for enteric pathogens in the USA includes the compilation and interpretation of both laboratory and epidemiologic data. However, the authors feel that a collaborative, multisectoral and transdisciplinary - or One Health - approach is needed for data collection and analysis, at every level. In addition, they suggest that the future of enteric illness surveillance lies in the development of improved technologies for pathogen detection and characterisation, such as genomic sequencing and metagenomics. In particular, using whole-genome sequencing to compare genetic sequences of enteric pathogens from humans, food, animals and the environment, can help to predict antimicrobial resistance among these pathogens, determine their genetic relatedness and identify outbreaks linked to a common source. In this paper, the authors describe three recent, multi-state human enteric illness outbreaks linked to animal contact in the USA and discuss how integrated disease surveillance was essential to outbreak detection and response. Additional datasharing between public health and animal health laboratories and epidemiologists at the local, national, regional and international level may help to improve surveillance for emerging animal and human health threats and lead to new opportunities for prevention.

Les agents pathogènes entériques tels que les Salmonella non typhiques, Campylobacter et Escherichia coli peuvent coloniser le tractus intestinal d'un grand nombre d'animaux y compris les espèces d'élevage, les animaux de compagnie, les petits mammifères et les reptiles. Les animaux porteurs sont souvent sains en apparence ; néanmoins, les humains peuvent contracter l'infection après un contact direct ou indirect avec un animal atteint, ce qui induit un fardeau significatif associé à ces maladies. D'après les estimations, environ 14 % des 3,2 millions de cas annuels d'infections par des agents pathogènes entériques aux États-Unis d'Amérique ont pour origine un contact avec des animaux. Aux États-Unis, la surveillance des agents pathogènes entériques est basée sur la collecte et l'interprétation des résultats de laboratoire et des données épidémiologiques. Les auteurs sont néanmoins convaincus de la nécessité de recourir à une approche collaborative, multisectorielle et transdisciplinaire (en d'autres termes, une approche Une seule santé) pour la collecte et l'analyse des données, à tous les niveaux. Ils considèrent également que la surveillance des infections entériques reposera à l'avenir sur le développement de technologies avancées dans le domaine de la détection et de la caractérisation des agents pathogènes, notamment le séquençage génomique et la métagénomique. En particulier, le recours au séquençage du génome entier afin de comparer les séquences d'agents pathogènes d'origine humaine, alimentaire, animale et environnementale permettra d'anticiper l'apparition d'antibiorésistances, de déterminer le degré de parenté génétique de ces agents et d'identifier les foyers provenant d'une même source. Les auteurs décrivent trois foyers récents d'infections entériques humaines survenus dans plusieurs états des États-Unis et soulignent à quel point l'exercice d'une surveillance sanitaire intégrée a été déterminant pour la détection de ces foyers et la mise en œuvre d'une réponse appropriée. Un partage accru d'informations entre les laboratoires et les épidémiologistes de santé publique et animale aux niveaux local, national, régional et international pourrait contribuer à améliorer la surveillance des menaces émergentes pesant sur la santé animale et humaine et à mettre en œuvre de nouvelles modalités de prévention.

En el tracto intestinal de muchos animales, entre ellos ganado, mascotas, pequeños mamíferos o reptiles, puede haber patógenos intestinales como salmonelas no tifoideas, Campylobacter o Escherichia coli. A menudo los animales parecen sanos, pese a lo cual las personas pueden infectarse por contacto directo o indirecto con ellos, lo que da lugar a una considerable carga de morbilidad. Se calcula que, de los 3,2 millones de casos de enfermedad que estos patógenos intestinales causan al año en los EE. UU., un 14% es atribuible al contacto con animales. La vigilancia de patógenos intestinales que se practica en los EE. UU. incluye la compilación e interpretación de datos tanto epidemiológicos como de laboratorio. En opinión de los autores, sin embargo, es preciso que la obtención y el análisis de datos respondan a un planteamiento de colaboración multisectorial y transdisciplinar ­ esto es, a la lógica de Una sola salud ­ que abarque todos los niveles. Los autores apuntan además que el futuro de la vigilancia de las enfermedades intestinales pasa por el desarrollo de tecnologías más eficaces de detección y caracterización de patógenos, como la secuenciación genómica o la metagenómica. En particular, el uso de la secuenciación de genomas completos para comparar entre sí las secuencias genéticas de patógenos intestinales presentes en personas, alimentos, animales y el medio ambiente puede ayudar a predecir la aparición de resistencias a los antimicrobianos en estos patógenos, determinar su parentesco genético e identificar brotes vinculados con un origen común. Los autores, tras describir tres recientes brotes de enfermedad intestinal humana ligados al contacto con animales que afectaron a varios estados de los EE. UU., explican la función esencial que cumplió la vigilancia integrada de enfermedades para detectar esos brotes y responder a ellos. El intercambio de más datos entre los laboratorios de salud pública y sanidad animal y los epidemiólogos a escala local, nacional, regional e internacional puede ser de ayuda para mejorar la vigilancia de amenazas sanitarias y zoosanitarias emergentes y abrir nuevas posibilidades de prevención.

Depression, lifestyle factors and cognitive function in people living with HIV and comparable HIV-negative controls.

OBJECTIVES: We investigated whether differences in cognitive performance between people living with HIV (PLWH) and comparable HIV-negative people were mediated or moderated by depressive symptoms and lifestyle factors. METHODS: A cross-sectional study of 637 'older' PLWH aged ≥ 50 years, 340 'younger' PLWH aged < 50 years and 276 demographically matched HIV-negative controls aged ≥ 50 years enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study was performed. Cognitive function was assessed using a computerized battery (CogState). Scores were standardized into Z-scores [mean = 0; standard deviation (SD) = 1] and averaged to obtain a global Z-score. Depressive symptoms were evaluated via the Patient Health Questionnaire (PHQ-9). Differences between the three groups and the effects of depression, sociodemographic factors and lifestyle factors on cognitive performance were evaluated using median regression. All analyses accounted for age, gender, ethnicity and level of education. RESULTS: After adjustment for sociodemographic factors, older and younger PLWH had poorer overall cognitive scores than older HIV-negative controls (P < 0.001 and P = 0.006, respectively). Moderate or severe depressive symptoms were more prevalent in both older (27%; P < 0.001) and younger (21%; P < 0.001) PLWH compared with controls (8%). Depressive symptoms (P < 0.001) and use of hashish (P = 0.01) were associated with lower cognitive function; alcohol consumption (P = 0.02) was associated with better cognitive scores. After further adjustment for these factors, the difference between older PLWH and HIV-negative controls was no longer significant (P = 0.08), while that between younger PLWH and older HIV-negative controls remained significant (P = 0.01). CONCLUSIONS: Poorer cognitive performances in PLWH compared with HIV-negative individuals were, in part, mediated by the greater prevalence of depressive symptoms and recreational drug use reported by PLWH.

Level of agreement between frequently used cardiovascular risk calculators in people living with HIV.

OBJECTIVES: The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). METHODS: PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into 'low' (< 10%), 'intermediate' (10-20%) and 'high' (> 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland-Altman plots. RESULTS: The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49-59] years. The median calculated 10-year CVD risk was 11.9% (IQR 6.8-18.4%), 8.9% (IQR 4.6-15.0%), 8.5% (IQR 4.8-14.6%) and 6.9% (IQR 4.1-11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50-0.60 range. CONCLUSIONS: Estimates of predicted 10-year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone.

High-risk behaviours, and their associations with mental health, adherence to antiretroviral therapy and HIV parameters, in HIV-positive men who have sex with men.

OBJECTIVES: To investigate the patterns and frequency of multiple risk behaviours (alcohol, drugs, smoking, higher risk sexual activity) among men who have sex with men (MSM) living with HIV. METHODS: Cross sectional study. RESULTS: 147 out of 819 HIV-positive MSM exhibited a high-risk phenotype (defined as >3 of smoking, excess alcohol, sexually transmitted infection and recent recreational drug use). This phenotype was associated with younger age, depressive symptoms and <90% adherence in multivariable logistic regression. CONCLUSION: In a cohort of MSM, a small, but significant proportion exhibited multiple concurrent risk behaviours.

Cardiorespiratory fitness is impaired and predicts mid-term postoperative survival in patients with abdominal aortic aneurysm disease.

NEW FINDINGS: What is the central question of this study? To what extent cardiorespiratory fitness is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake of <13.1 ml O2  kg-1  min-1 and ventilatory equivalent for carbon dioxide at anaerobic threshold ≥34 are associated with increased risk of postoperative mortality at 2 years. These findings demonstrate that cardiorespiratory fitness can predict mid-term postoperative survival in AAA patients, which may help to direct care provision. ABSTRACT: Preoperative cardiopulmonary exercise testing is a standard assessment of cardiorespiratory fitness (CRF) and risk stratification. However, to what extent CRF is impaired in patients undergoing surgical repair of abdominal aortic aneurysm (AAA) disease and the corresponding implications for postoperative outcome requires further investigation. We measured CRF during an incremental exercise test to exhaustion using online respiratory gas analysis in patients with AAA disease (n = 124, aged 72 ± 7 years) and healthy sedentary control subjects (n = 104, aged 70 ± 7 years). Postoperative survival was examined for association with CRF, and threshold values were calculated for independent predictors of mortality. Patients who underwent preoperative cardiopulmonary exercise testing before surgical repair had lower CRF [age-adjusted mean difference of 12.5 ml O2  kg-1  min-1 for peak oxygen uptake ( V ̇ O 2 peak ), P < 0.001 versus control subjects]. After multivariable analysis, both V ̇ O 2 peak and the ventilatory equivalent for carbon dioxide at anaerobic threshold ( V ̇ E / V ̇ C O 2 - AT ) were independent predictors of mid-term postoperative survival (2 years). Hazard ratios of 5.27 (95% confidence interval 1.62-17.14, P = 0.006) and 3.26 (95% confidence interval 1.00-10.59, P = 0.049) were observed for V ̇ O 2 peak  < 13.1 ml O2  kg-1  min-1 and V ̇ E / V ̇ C O 2 - AT ≥ 34, respectively. Thus, CRF is lower in patients with AAA, and those with a V ̇ O 2 peak  < 13.1 ml O2  kg-1  min-1 and V ̇ E / V ̇ C O 2 - AT ≥ 34 are associated with a markedly increased risk of postoperative mortality. Collectively, our findings demonstrate that CRF can predict mid-term postoperative survival in AAA patients, which may help to direct care provision.

An outbreak of Escherichia coli O157:H7 infections following a dairy education school field trip in Washington state, 2015.

On 27 April 2015, Washington health authorities identified Escherichia coli O157:H7 infections associated with dairy education school field trips held in a barn 20-24 April. Investigation objectives were to determine the magnitude of the outbreak, identify the source of infection, prevent secondary illness transmission and develop recommendations to prevent future outbreaks. Case-finding, hypothesis generating interviews, environmental site visits and a case-control study were conducted. Parents and children were interviewed regarding event activities. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Environmental testing was conducted in the barn; isolates were compared to patient isolates using pulsed-field gel electrophoresis (PFGE). Sixty people were ill, 11 (18%) were hospitalised and six (10%) developed haemolytic uremic syndrome. Ill people ranged in age from <1 year to 47 years (median: 7), and 20 (33%) were female. Twenty-seven case-patients and 88 controls were enrolled in the case-control study. Among first-grade students, handwashing (i.e. soap and water, or hand sanitiser) before lunch was protective (adjusted OR 0.13; 95% CI 0.02-0.88, P = 0.04). Barn samples yielded E. coli O157:H7 with PFGE patterns indistinguishable from patient isolates. This investigation provided epidemiological, laboratory and environmental evidence for a large outbreak of E. coli O157:H7 infections from exposure to a contaminated barn. The investigation highlights the often overlooked risk of infection through exposure to animal environments as well as the importance of handwashing for disease prevention. Increased education and encouragement of infection prevention measures, such as handwashing, can prevent illness.

The cardiopulmonary exercise test grey zone; optimising fitness stratification by application of critical difference.

BACKGROUND: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification. METHODS: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (V˙O2-AT): 11 ml O2 kg-1 min-1, peak oxygen uptake (V˙O2 peak): 16 ml O2 kg-1 min-1, and ventilatory equivalent for carbon dioxide at AT (V̇E/V̇CO2-AT): 36]. RESULTS: The critical difference for V˙O2-AT, V˙O2 peak, and V˙E/V˙CO2-AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and ≥13.6 ml O2 kg-1 min-1, V˙O2 peak <14.2 and ≥18.3 ml kg-1 min-1, V˙E/V˙CO2-AT ≥40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness. CONCLUSIONS: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for.

Associations between cognitive impairment and patient-reported measures of physical/mental functioning in older people living with HIV.

OBJECTIVES: While cognitive impairment is frequently reported in HIV-positive individuals and has historically been associated with poorer functional outcomes, the associations between cognitive impairment and patient-reported outcome measures (PROMs) in contemporary cohorts are unclear. METHODS: We tested cognitive function using a computerized battery (CogState™ ) in 290 HIV-positive and 97 HIV-negative individuals aged ≥ 50 years participating in the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study. Participants completed questionnaires detailing physical and mental health [Short Form Health Survey (SF-36)], cognitive function [European AIDS Clinical Society (EACS) questions], activities of daily living [Lawton Instrumental Activities of Daily Living (IADL)], depression [Patient Depression Questionnaire (PHQ-9) and Centres for Epidemiologic Studies Depression scale (CES-D)], falls and sexual desire. Cognitive impairment was defined using the Frascati criteria, global deficit score (GDS) and multivariate normative comparison (MNC). In the HIV-positive group, the classification performances of the different definitions of cognitive impairment and dichotomized questionnaire results were calculated. RESULTS: The prevalence of cognitive impairment in the HIV-positive group was 34.5% (GDS), 30.0% (Frascati) and 22.1% (MNC), with only 2% diagnosed with HIV-associated dementia. In general, the associations between cognitive impairment and PROMs were weak regardless of the definition used: mean c-statistics were 0.543 (GDS), 0.530 (MNC) and 0.519 (Frascati). Associations were similar using the global T-score to define cognitive impairment. Summary health scores (SF-36) were lower, but only significantly so for those with cognitive impairment identified using MNC, for both mental health (61.4 vs. 75.8; P = 0.03) and physical health (60.9 vs. 75.0; P = 0.03). CONCLUSIONS: The associations between cognitive impairment and PROMs were weak, possibly because impairment was mild and therefore largely asymptomatic. Further work is needed to elucidate the clinical implications of cognitive impairment in HIV-disease.

Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom.

OBJECTIVES: Transmission of drug-resistant HIV-1 has decreased in the UK since the early 2000s. This analysis reports recent trends and characteristics of transmitted drug resistance (TDR) in the UK from 2010 to 2013. METHODS: Resistance tests conducted in antiretroviral treatment (ART)-naïve individuals between 2010 and 2013 were analysed for the presence of transmitted drug resistance mutations (TDRMs), defined as any mutations from a modified 2009 World Health Organization surveillance list, or a modified 2013 International Antiviral Society-USA list for integrase tests. Logistic regression was used to examine associations between demographics and the prevalence of TDRMs. RESULTS: TDRMs were observed in 1223 (7.5%) of 16 425 individuals; prevalence declined from 8.1% in 2010 to 6.6% in 2013 (P = 0.02). The prevalence of TDRMs was higher among men who have sex with men (MSM) compared with heterosexual men and women (8.7% versus 6.4%, respectively) with a trend for decreasing TDRMs among MSM (P = 0.008) driven by a reduction in nucleoside reverse transcriptase inhibitor (NRTI)-related mutations. The most frequently detected TDRMs were K103N (2.2%), T215 revertants (1.6%), M41L (0.9%) and L90M (0.7%). Predicted phenotypic resistance to first-line ART was highest to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine and efavirenz (6.2% and 3.4%, respectively) but minimal to NRTIs, including tenofovir, and protease inhibitors (PIs). No major integrase TDRMs were detected among 101 individuals tested while ART-naïve. CONCLUSIONS: We observed a decrease in TDRMs in recent years. However, this was confined to the MSM population and rates remained stable in those with heterosexually acquired HIV infection. Resistance to currently recommended first-line ART, including integrase inhibitors, remained reassuringly low.

Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling.

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5-9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques (Macaca mulatta, n = 7-8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-ß1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.

Systematic Review and Meta-analysis of the Effect of Internal Iliac Artery Exclusion for Patients Undergoing EVAR.

OBJECTIVE: Endovascular abdominal aortic aneurysm repair (EVAR) sometimes requires internal iliac artery (IIA) coverage to achieve a landing zone in the external iliac artery. The aim of this study was to determine complication rates following IIA exclusion. MATERIALS AND METHODS: A systematic review of key journals was undertaken from January 1980 to April 2016. Studies detailing occlusion (using coils or plugs) or coverage of the IIA with outcome data were included. Weighted means were calculated for continuous variables. Meta-analysis was performed when comparative data were available. Quality was assessed using the GRADE system. RESULTS: Sixty-one non-randomised studies (2671 patients; 2748 IIAs) were analysed. Fifteen per cent of EVARs require IIA sacrifice. Buttock claudication (BC) occurred in 27.9% of patients, although 48.0% resolved after 21.8 months. BC rates were 32.6% with coils, 23.8% with plugs, and 12.9% with coverage alone, and less with unilateral (vs. bilateral) IIA treatment (OR 0.57, 95% CI 0.36-0.91). More proximal coil placement resulted in lower rates of BC (OR 0.12, 95% CI 0.03-0.48). Erectile dysfunction occurred in 10.2% of males, with higher rates after coiling. Type II endoleaks were more frequent after covering alone; however re-interventions were rare. Significant ischaemic events (bowel/gluteal/spinal ischaemia) were very rare. Plugs were quicker to place and required less radiation (p < .001) than coils. GRADE scoring was very low for all outcomes. CONCLUSION: Overall the quality of reported data on IIA sacrifice is poor. Buttock claudication and erectile dysfunction occurred frequently after IIA sacrifice. Where both options are technically possible, plugs could be considered preferential to coils, and placed as proximally in the IIA as possible.

International outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder - USA and Canada, 2013-2014.

Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013-2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy.

OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/µL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. CONCLUSIONS: In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.

Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses.

OBJECTIVE: To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject. METHODS: We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression. RESULTS: The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (ß = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (ß = 10.6, P = 0.04 and ß = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (ß = -14.7, P = 0.03). CONCLUSION: In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.