Electronic health record reveals community-level cardiometabolic health benefits associated with 10 years of community-based participatory research.

BACKGROUND: While a major goal of community-based participatory research (CBPR) is to improve community health; it is unclear how to measure longstanding success of CBPR. OBJECTIVE: We sought to determine the impact of ongoing CBPR on cardiometabolic health of participating communities, including in people not directly participating in research. METHODS: We used linear mixed-effects modelling with electronic medical records from 2002 to 2012 from the Yukon-Kuskokwim Health Corporation, which provides health care to all Alaska Native people in southwestern Alaska, to compare rates of change in cardiometabolic risk factors between communities that did and did not participate in ongoing CBPR beginning in 2003. RESULTS: We analysed 1,262,035 medical records from 12,402 individuals from 10 study and 38 control communities. Blood pressure declined faster in study than in control communities: systolic blood pressure (0.04 mmHg/year; 95% confidence interval [CI]: 0.01, 0.08); diastolic blood pressure (DBP) (0.07 mmHg/year; 95% CI: 0.04, 0.09). Body mass index increased 0.04 units/year faster in study communities than in control communities (95% CI: 0.03, 0.05). More study visits were associated with faster reduction of DBP and triglyceride levels in study communities. CONCLUSIONS: Ongoing CBPR may improve overall cardiometabolic health in communities, perhaps by increasing engagement in health and advocacy.

An evaluation of a pilot of daily testing of SARS-CoV-2 contacts in acute hospital and ambulance trusts in England.

OBJECTIVES: Healthcare worker (HCW) SARS-CoV-2 contacts in England have been required to quarantine, creating staff shortages. We piloted daily contact testing (DCT) to assess its feasibility as an alternative. STUDY DESIGN: Observational service evaluation. METHODS: We conducted an observational service evaluation of 7-day DCT using antigen lateral flow devices (LFDs) at four acute hospital trusts and one ambulance trust in England. Mixed methods were used, using aggregate and individual-level test monitoring data, semi-structured interviews, and a survey of eligible contacts. RESULTS: In total, 138 HCWs were identified as contacts of a confirmed SARS-CoV-2 case. Of these, 111 (80%) consented to daily LFD testing, of whom 82 (74%) completed the required programme without interruption and 12 (11%) completed with interruption. Fifty-eight participants (52%) and two non-participants (7.4%) completed the survey. In total, 28 interviews were conducted with participants, site and infection control leads, and union representatives. One participant tested positive on LFD and polymerase chain reaction (PCR) test. Three participants tested positive on PCR but not LFD. DCT was well-accepted by trusts and staff. Participants reported no relaxation of their infection prevention and control behaviours. No incidents of transmission were detected. An estimated 729 potential days of work absence were averted. CONCLUSIONS: DCT can be acceptably operated in a healthcare setting, averting quarantine-related work absences in HCW SARS-CoV-2 contacts.

Supply of care by dental therapists and emergency dental consultations in Alaska native communities in the Yukon-Kuskokwim delta: a mixed methods evaluation.

OBJECTIVES: Examine the relationship between supply of care provided by dental therapists and emergency dental consultations in Alaska Native communities. METHODS: Explanatory sequential mixed-methods study using Alaska Medicaid and electronic health record (EHR) data from the Yukon-Kuskokwim Health Corporation (YKHC), and interview data from six Alaska Native communities. From the Medicaid data, we estimated community-level dental therapy treatment days and from the EHR data we identified emergency dental consultations. We calculated Spearman partial correlation coefficients and ran confounder-adjusted models for children and adults. Interview data collected from YKHC providers (N=16) and community members (N=125) were content analysed. The quantitative and qualitative data were integrated through connecting. Results were visualized with a joint display. RESULTS: There were significant negative correlations between dental therapy treatment days and emergency dental consultations for children (partial rank correlation = -0.48; p⟨0.001) and for adults (partial rank correlation = -0.18; p=0.03). Six pediatric themes emerged: child-focused health priorities; school-based dental programs; oral health education and preventive behaviors; dental care availability; healthier teeth; and satisfaction with care. There were four adult themes: satisfaction with care; adults as a lower priority; difficulties getting appointments; and limited scope of practice of dental therapy. CONCLUSIONS: Alaska Native children, and to a lesser extent adults, in communities served more intensively by dental therapists have benefitted. There are high levels of unmet dental need as evidenced by high emergency dental consultation rates. Future research should identify ways to address unmet dental needs, especially for adults.

Discordance in latent tuberculosis (TB) test results in patients with end-stage renal disease.

OBJECTIVES: This natural experiment was designed to assess the impact of exposure to an active case of tuberculosis (TB) on a group of immunosuppressed individuals, with end-stage renal disease over an extended follow-up. STUDY DESIGN: Close contacts of people with sputum smear-positive Mycobacterium tuberculosis are at high risk of infection, particularly immunosuppressed individuals. An infectious TB healthcare worker worked in a renal dialysis unit for a month before diagnosis, with 104 renal dialysis patients, was exposed for ≥8 h. METHODS: Patients were informed and invited for screening 8-10 weeks postexposure. They either underwent standard two-step assessment with tuberculin skin test (TST) and QuantiFERON®-TB Gold (Cellestis GmbH; QFN) interferon-gamma release assay (IGRA) or after consent, enrolled in a study where these two tests were performed simultaneously with T-SPOT®-TB (Oxford Immunotec Ltd; TSPOT). Patients within the study were followed up for 2 years from exposure, with QFN and TSPOT repeated at months 3 and 6 from the first testing. RESULTS: Of 104 exposed individuals, 75 enrolled in the study. There was a high degree of discordance among QFN, TSPOT and TST. This was seen at both the first time point and also over time in subjects who were retested. No patients had active TB at the baseline testing. None received treatment for latent TB infection. Over the following 2 years, no one developed TB disease. CONCLUSION: This study suggests that there is a low risk of progression to active TB in low-incidence countries even in high-risk groups. This plus the degree of the test result discordance emphasises the complexities of managing TB in such settings as it is unclear which of these tests, if any, provides the best diagnostic accuracy.

A national quality incentive scheme to reduce antibiotic overuse in hospitals: evaluation of perceptions and impact.

Background: In 2016/2017, a financially linked antibiotic prescribing quality improvement initiative Commissioning for Quality and Innovation (AMR-CQUIN) was introduced across acute hospitals in England. This aimed for >1% reductions in DDDs/1000 admissions of total antibiotics, piperacillin/tazobactam and carbapenems compared with 2013/2014 and improved review of empirical antibiotic prescriptions. Objectives: To assess perceptions of staff leading antimicrobial stewardship activity regarding the AMR-CQUIN, the investments made by hospitals to achieve it and how these related to achieving reductions in antibiotic use. Methods: We invited antimicrobial stewardship leads at acute hospitals across England to complete a web-based survey. Antibiotic prescribing data were downloaded from the PHE Antimicrobial Resistance Local Indicators resource. Results: Responses were received from 116/155 (75%) acute hospitals. Owing to yearly increases in antibiotic use, most trusts needed to make >5% reductions in antibiotic consumption to achieve the AMR-CQUIN goal of 1% reduction. Additional funding was made available at 23/113 (20%) trusts and, in 18 (78%), this was <10% of the AMR-CQUIN value. Nationally, the annual trend for increased antibiotic use reversed in 2016/2017. In 2014/2015, year-on-year changes were +3.7% (IQR -0.8%, +8.4%), +9.4% (+0.2%, +19.5%) and +5.8% (-6.2%, +18.2%) for total antibiotics, piperacillin/tazobactam and carbapenems, respectively, and +0.1% (-5.4%, +4.0%), -4.8% (-16.9%, +3.2%) and -8.0% (-20.2%, +4.0%) in 2016/2017. Hospitals where staff believed they could reduce antibiotic use were more likely to do so (P < 0.001). Conclusions: Introducing the AMR-CQUIN was associated with a reduction in antibiotic use. For individual hospitals, achieving the AMR-CQUIN was associated with favourable perceptions of staff and not availability of funding.

Seasonality of urinary tract infections in the United Kingdom in different age groups: longitudinal analysis of The Health Improvement Network (THIN).

Evidence regarding the seasonality of urinary tract infection (UTI) consultations in primary care is conflicting and methodologically poor. To our knowledge, this is the first study to determine whether this seasonality exists in the UK, identify the peak months and describe seasonality by age. The monthly number of UTI consultations (N = 992 803) and nitrofurantoin and trimethoprim prescriptions (N = 1 719 416) during 2008-2015 was extracted from The Health Improvement Network (THIN), a large nationally representative UK dataset of electronic patient records. Negative binomial regression models were fitted to these data to investigate seasonal fluctuations by age group (14-17, 18-24, 25-45, 46-69, 70-84, 85+) and by sex, accounting for a change in the rate of UTI over the study period. A September to November peak in UTI consultation incidence was observed for ages 14-69. This seasonality progressively faded in older age groups and no seasonality was found in individuals aged 85+, in whom UTIs were most common. UTIs were rare in males but followed a similar seasonal pattern than in females. We show strong evidence of an autumnal seasonality for UTIs in individuals under 70 years of age and a lack of seasonality in the very old. These findings should provide helpful information when interpreting surveillance reports and the results of interventions against UTI.

Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.

Graphical abstract key: ADHD, attention deficit hyperactivity disorder; ASD, atrial septal defect; DD, developmental delay; EEG, electroencephalogram; Ht, height; ID, intellectual disability; OCD, obsessive-compulsive disorder; OFC, open fontanelle; PDA, patent ductus arteriosis; PFO, patent foramen ovale; VSD, ventricular septal defect; Wt, weight.

A Review on Bone Mineral Density Loss in Total Knee Replacements Leading to Increased Fracture Risk.

The link between low bone mineral density (BMD) scores leading to greater fracture risk is well established in the literature; what is not fully understood is the impact of total knee replacements/revisions or arthroplasties on BMD levels. This literature review attempts to answer this question. Several different databases using specific key terms were searched, with additional papers retrieved via bibliographic review. Based on the available evidence, total knee replacements/revisions and arthroplasties lower BMD and thus increase fracture risk. This review also addresses the possible implications of this research and possible options to reduce this risk.

Implementation of antimicrobial stewardship interventions recommended by national toolkits in primary and secondary healthcare sectors in England: TARGET and Start Smart Then Focus.

OBJECTIVES: To assess and compare the implementation of antimicrobial stewardship (AMS) interventions recommended within the national AMS toolkits, TARGET and Start Smart Then Focus, in English primary and secondary healthcare settings in 2014, to determine the prevalence of cross-sector engagement to drive AMS interventions and to propose next steps to improve implementation of AMS. METHODS: Electronic surveys were circulated to all 211 clinical commissioning groups (CCGs; primary sector) and to 146 (out of the 159) acute trusts (secondary sector) in England. Response rates were 39% and 63% for the primary and secondary sectors, respectively. RESULTS: The majority of CCGs and acute trusts reported reviewing national AMS toolkits formally or informally (60% and 87%, respectively). However, only 13% of CCGs and 46% of acute trusts had developed an action plan for the implementation of these toolkits. Only 5% of CCGs had antimicrobial pharmacists in post; however, the role of specialist antimicrobial pharmacists continued to remain embedded within acute trusts, with 83% of responding trusts having an antimicrobial pharmacist at a senior grade. CONCLUSIONS: The majority of healthcare organizations review national AMS toolkits; however, implementation of the toolkits, through the development of action plans to deliver AMS interventions, requires improvement. For the first time, we report the extent of cross-sector and multidisciplinary collaboration to deliver AMS interventions in both primary and secondary care sectors in England. Results highlight that further qualitative and quantitative work is required to explore mutual benefits and promote best practice. Antimicrobial pharmacists remain leaders for implementing AMS interventions across both primary and secondary healthcare sectors.

A study investigating short- and medium-term effects on function, bone mineral density and lean tissue mass post-total knee replacement in a Caucasian female post-menopausal population: implications for hip fracture risk.

UNLABELLED: Significant increased hip fracture incidence has been reported in the year following total knee replacement. This study demonstrates that bone and muscle loss is a post-surgical consequence of total knee replacement, alongside poor outcomes in function and activity potentially contributing to reduced quality of life and increased hip fracture risk. INTRODUCTION: A significant increase in hip fracture incidence in the year following total knee replacement (TKR) surgery has been reported. This study investigated function and activity following TKR and the effects of limited mobility on bone and muscle loss and their potential contribution to hip fracture risk. METHODS: Changes in dual-energy X-ray absorptiometry (DXA) (GE Lunar Prodigy, Bedford MA), bone mineral density (BMD) at the neck of femur (NOF), total hip region (TH) and lumbar spine were measured alongside leg lean tissue mass (LLTM) in post-menopausal Caucasian females following TKR (N = 19) compared to controls (N = 43). Lumbar spine trabecular bone scores (TBSs) were calculated. Ipsilateral/contralateral weight bearing, lower limb function, 3-day pedometer readings, pain levels and falls were also recorded. Measurements were obtained at pre-surgery baseline and at 6 weeks, 6 months and 12 months post-surgery. RESULTS: No statistically significant differences were demonstrated between groups at baseline bilaterally in LLTM or BMD at the NOF and TH. Losses in ipsilateral NOF and TH BMD and contralateral LLTM were significantly higher in the TKR group at 6 months. Impairment in function and weight bearing persisted in the TKR group 12 months post-operatively alongside deficits in bilateral muscle mass and ipsilateral NOF and TH BMD. Falls incidence was not significantly higher in the TKR group. CONCLUSIONS: Bone loss at the hip with associated muscle loss is a consequence of TKR that, in addition to poor patient outcomes in function and activity, potentially contributes to increased hip fracture risk in the year following surgery.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

OBJECTIVE/BACKGROUND: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI. METHODS: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition. RESULTS: Diagnostic criteria from three categories were classified as major or minor. It is proposed that AGI should be suspected if a single major criterion or two or more minor criteria from different categories are present. AGI is diagnosed if there is one major plus any criterion (major or minor) from another category. (i) Clinical/surgical major criteria comprise intraoperative identification of pus around a graft and situations where direct communication between the prosthesis and a nonsterile site exists, including fistulae, exposed grafts in open wounds, and deployment of an endovascular stent-graft into an infected field (e.g., mycotic aneurysm); minor criteria are localized AGI features or fever ≥38°C, where AGI is the most likely cause. (ii) Radiological major criteria comprise increasing perigraft gas volume on serial computed tomography (CT) imaging or perigraft gas or fluid (≥7 weeks and ≥3 months, respectively) postimplantation; minor criteria include other CT features or evidence from alternative imaging techniques. (iii) Laboratory major criteria comprise isolation of microorganisms from percutaneous aspirates of perigraft fluid, explanted grafts, and other intraoperative specimens; minor criteria are positive blood cultures or elevated inflammatory indices with no alternative source. CONCLUSION: This AGI definition potentially offers a practical and consistent diagnostic standard, essential for comparing clinical management strategies, trial design, and developing evidence-based guidelines. It requires validation that is planned in a multicenter, clinical service database supported by the Vascular Society of Great Britain & Ireland.

An in vitro cell irradiation protocol for testing photopharmaceuticals and the effect of blue, green, and red light on human cancer cell lines.

Traditionally, ultraviolet light (100-400 nm) is considered an exogenous carcinogen while visible light (400-780 nm) is deemed harmless. In this work, a LED irradiation system for in vitro photocytotoxicity testing is described. The LED irradiation system was developed for testing photopharmaceutical drugs, but was used here to determine the basal level response of human cancer cell lines to visible light of different wavelengths, without any photo(chemo)therapeutic. The effects of blue (455 nm, 10.5 mW cm(-2)), green (520 nm, 20.9 mW cm(-2)), and red light (630 nm, 34.4 mW cm(-2)) irradiation was measured for A375 (human malignant melanoma), A431 (human epidermoid carcinoma), A549 (human lung carcinoma), MCF7 (human mammary gland adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), and U-87 MG (human glioblastoma-grade IV) cell lines. In response to a blue light dose of 19 J cm(-2), three cell lines exhibited a minimal (20%, MDA-MB-231) to moderate (30%, A549 and 60%, A375) reduction in cell viability, compared to dark controls. The other cell lines were not affected. Effective blue light doses that produce a therapeutic response in 50% of the cell population (ED50) compared to dark conditions were found to be 10.9 and 30.5 J cm(-2) for A375 and A549 cells, respectively. No adverse effects were observed in any of the six cell lines irradiated with a 19 J cm(-2) dose of 520 nm (green) or 630 nm (red) light. The results demonstrate that blue light irradiation can have an effect on the viability of certain human cancer cell types and controls should be used in photopharmaceutical testing, which uses high-energy (blue or violet) visible light activation.

Ebola virus disease: the UK critical care perspective.

The recent outbreak of Ebola virus disease (EVD) has required the treatment of affected patients in the NHS system within the UK. Managing patients with a confirmed viral haemorrhagic fever requires a thorough understanding of treatment options within the confines of an effective biocontainment setting. The Royal Free Hospital High Level Isolation Unit (HLIU) in London, is a purpose built facility that allows healthcare workers to safely treat patients with highly contagious diseases. This HLIU uses Trexler isolator tents to prevent the spread of infection from patients to healthcare workers. Provision of invasive organ support can be provided in this environment, if considered appropriate, and is achievable without posing additional risk to staff. We report our recent experiences of managing patients with EVD, with particular focus on those aspects of care pertinent to anaesthesia and critical care medicine.

Antimicrobial resistance: moving from professional engagement to public action.

Antimicrobial-resistant infections claim ≥700 000 lives each year globally. It is therefore important that both healthcare professionals and the public know the threat antimicrobial resistance poses and the individual actions they can take to combat antimicrobial resistance. Antibiotic awareness campaigns in England using posters or leaflets have had little or no impact on knowledge, behaviour or prescription rates. Centrally coordinated, multimodal campaigns in two European countries (ongoing for several years and including print and mass media, web site and guidelines, as well as academic detailing and individual feedback to prescribers) have led to reductions in antibiotic use. To change behaviour and reduce antibiotic use in England, a coordinated and comprehensive interdisciplinary and multifaceted (multimodal) approach using behavioural science and targeted at specific groups (both professional and public) is required. Such campaigns should have an integrated evaluation plan using a combination of formative, process and summative measures from the outset to completion of a campaign.

Sex differences in obesity prevalence and cardiometabolic factors among Western Alaska Native people.

BACKGROUND AND AIMS: Obesity is associated with increased risks of cardiovascular disease, type 2 diabetes, and other chronic diseases. Prevalence estimates for metabolic disorders are well documented in many populations, but Alaska Native groups are understudied. The Western Alaska Tribal Collaborative for Health Study combines data from three Alaska Native study cohorts to assess differences in obesity prevalence and associations with cardiometabolic risk factors by sex. METHODS AND RESULTS: Analyses were based upon a sample of 3985 adult Yup'ik and Inupiat participants with a mean age of 40 years. Prevalence of obesity and metabolic risk factors was assessed according to nationally recognized guidelines. Regression analysis was used to evaluate the association between obesity and cardiometabolic risk factors, including lipids, blood pressure and glucose. The prevalence of obesity (BMI ≥ 30) was significantly higher in women (40%) than men (20%). Only 18.6% of men had a waist circumference (WC) > 102 cm, while 58% of women had a WC > 88 cm (p < 0.001). Women had higher mean HDL-C and triglyceride levels compared to men, while systolic and diastolic blood pressure, LDL-C, and glucose means were higher in men than in women. In multivariate analyses, BMI and WC were significantly associated with all of the cardiometabolic risk factors, although these associations were more pronounced in men than women. CONCLUSION: The high prevalence of obesity and central adiposity among AN women is an important public health concern. Differences in associations between obesity and cardiometabolic risk factors by sex warrants further investigation to develop effective intervention programs.

Associations between diet and cardiometabolic risk among Yup'ik Alaska Native people using food frequency questionnaire dietary patterns.

BACKGROUND AND AIMS: In previous analyses, we identified three dietary patterns from food frequency questionnaire data among a sample of Yup'ik Alaska Native people living in Southwest Alaska: a "subsistence foods" dietary pattern and two market-based dietary patterns "processed foods" and "fruits and vegetables". In this analysis, we aimed to characterize the association between the dietary patterns and cardiometabolic (CM) risk factors (lipids, blood pressure, glucose, adiposity). METHODS AND RESULTS: We used multilevel linear regression to estimate the mean of each CM risk factor, comparing participants in the 4th to the 1st quartile of each dietary pattern (n = 637). Models were adjusted for age, sex, past smoking, current smoking, and physical activity. Mean log triglyceride levels were significantly higher among participants in the 4th compared to the 1st quartile of the processed foods dietary pattern (ß = 0.11). Mean HbA1c percent was significantly lower (ß = -0.08) and mean diastolic blood pressure (DBP) mm Hg was significantly higher (ß = 2.87) among participants in the 4th compared to the 1st quartile of the fruits and vegetables dietary pattern. Finally, mean log triglyceride levels and mean DBP mm Hg were significantly lower among participants in the 4th compared to the 1st quartile of the subsistence foods dietary pattern (ß = -0.10 and ß = -3.99 respectively). CONCLUSIONS: We found increased CM risk, as reflected by increased triglycerides, associated with eating a greater frequency of processed foods, and reduced CM risk, as reflected by lower triglycerides and DBP, associated with eating a greater frequency of subsistence foods.

Characteristics associated with the consumption of malted drinks among Malaysian primary school children: findings from the MyBreakfast study.

BACKGROUND: The consumption of beverages contributes to diet quality and overall nutrition. Studies on malted drinks, one of the widely consumed beverage choices among children in Asia, however, have received limited attention. This study aimed to examine the prevalence of malted drink consumption and explored associations of sociodemographic characteristics, nutrient intakes, weight status and physical activity levels with malted drink consumption among primary school children in Malaysia. METHODS: Data for this analysis were from the MyBreakfast Study, a national cross-sectional study conducted from April to October 2013 throughout all regions in Malaysia. A total of 2065 primary school children aged 6 to 12 years were included in the present analysis. Data on two days 24-h dietary recall or record, anthropometry, physical activity and screen time were recorded. Associations between malted drink consumption and related factors were examined using binary logistic regression, adjusting for region, area, gender, ethnicity and household income. RESULTS: Among children aged 6 to 12 years, 73.5% reported consuming malted drinks for at least once per week. Consumption of malted drinks was significantly associated with region (χ(2) = 45.64, p < 0.001), gender (χ(2) = 4.41, p = 0.036) and ethnicity (χ(2) = 13.74, p = 0.008). Malted drink consumers had similar total energy intake but higher micronutrient intakes compared to non-consumers. High physical activity level (OR = 1.77, 95% CI = 1.06, 2.99) and lower screen time during weekends (OR = 0.93, 95% CI = 0.86, 0.99) were independently associated with malted drink consumption among 6 to 9 year-old children, but not among 10 to 12 year-old children. No association was observed between malted drink consumption and weight status. CONCLUSIONS: Malted drink consumption is prevalent among Malaysian primary school children, particularly higher among boys, indigenous children and those who lived in the East Coast region of Malaysia. Consuming malted drinks is associated with higher micronutrient intakes and higher levels of physical activity, but not with body weight status.

A pilot validation in 10 European Union Member States of a point prevalence survey of healthcare-associated infections and antimicrobial use in acute hospitals in Europe, 2011.

We present a pilot validation study performed on 10 European Union (EU) Member States, of a point prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in Europe in 2011 involving 29 EU/European Economic Area (EEA) countries and Croatia. A total of 20 acute hospitals and 1,950 patient records were included in the pilot study, which consisted of validation and inter-rater reliability (IRR) testing using an in-hospital observation approach. In the validation, a sensitivity of 83% (95% confidence interval (CI): 79­87%) and a specificity of 98% (95% CI: 98­99%) were found for HAIs. The level of agreement between the primary PPS and validation results were very good for HAIs overall (Cohen's κappa (κ):0.81) and across all the types of HAIs (range: 0.83 for bloodstream infections to 1.00 for lower respiratory tract infections). Antimicrobial use had a sensitivity of 94% (95% CI: 93­95%) and specificity of 97% (95% CI: 96­98%) with a very good level of agreement (κ:0.91). Agreement on other demographic items ranged from moderate to very good (κ: 0.57­0.95): age (κ:0.95), sex (κ: 0.93), specialty of physician (κ: 0.87) and McCabe score (κ: 0.57). IRR showed a very good level of agreement (κ: 0.92) for both the presence of HAIs and antimicrobial use. This pilot study suggested valid and reliable reporting of HAIs and antimicrobial use in the PPS dataset. The lower level of sensitivity with respect to reporting of HAIs reinforces the importance of training data collectors and including validation studies as part of a PPS in order for the burden of HAIs to be better estimated.

Novel agents and associated toxicities of inhibitors of the pi3k/Akt/mtor pathway for the treatment of breast cancer.

UNLABELLED: The pi3k/Akt/mtor (phosphatidylinositol 3 kinase/ Akt/mammalian target of rapamycin) signalling pathway is an established driver of oncogenic activity in human malignancies. Therapeutic targeting of this pathway holds significant promise as a treatment strategy. Everolimus, an mtor inhibitor, is the first of this class of agents approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Everolimus has been associated with significant improvements in progression-free survival; however, it is also associated with increased toxicity related to its specific mechanism of action. METHODS: A comprehensive review of the literature conducted using a focused medline search was combined with a search of current trials at http://ClinicalTrials.gov/. Summary tables of the toxicities of the various classes of pi3k/Akt/mtor inhibitors were created. A broad group of Canadian health care professionals was assembled to review the data and to produce expert opinion and summary recommendations for possible best practices in managing the adverse events associated with these pathway inhibitors. RESULTS: Differing toxicities are associated with the various classes of pi3k/Akt/mtor pathway inhibitors. The most common unique adverse events observed in everolimus clinical trials in breast cancer include stomatitis (all grades: approximately 60%), noninfectious pneumonitis (15%), rash (40%), hyperglycemia (15%), and immunosuppression (40%). To minimize grades 3 and 4 toxicities and to attempt to attain optimal outcomes, effective management of those adverse events is critical. Management should be interdisciplinary and should use approaches that include education, early recognition, active intervention, and potentially prophylactic strategies. DISCUSSION: Everolimus likely represents the first of many complex oral targeted therapies for the treatment of breast cancer. Using this agent as a template, it is essential to establish best practices involving and integrating multiple disciplines for the management of future pi3k/Akt/mtor signalling pathway inhibitors.

Managing latent tuberculosis in UK renal transplant units: how does practice compare with published guidance?

Renal transplantation significantly increases the risk of active tuberculosis (TB) in individuals with latent TB infection (LTBI). UK transplant recipients are often born in TB endemic areas. Using a self-completed questionnaire, we evaluated how the 23 UK renal transplant units' LTBI management compared with recently published national guidance. Three-quarters had a management protocol, but only one-third of these were in line with the guidance. Interferon-gamma release assays were rarely used to confirm LTBI. Almost half of the units prescribed LTBI treatment at the wrong dose or duration. We conclude that units should develop local protocols in line with evidence-based guidance. This must be in a format that enables national audit programmes and quality improvement to be routinely performed.