bluuebunny/crossref_metadata_2025 huggingface dataset:
Juvenile systemic lupus erythematosus with primary neuropsychiatric presentation
Authors: Ferraria Nélia , Rocha Susana , Fernandes Vera Silva , Correia Teresa , Gonçalves Elisabete
Published: January 2013

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple manifestations in several organs and systems. Neuropsychiatric manifestations can occur in 22–95% of paediatric cases, being much less frequent as an initial clinical event. We report a case of SLE, presenting primarily with neuropsychiatric symptoms. An African-descendant 7-year-old girl was admitted with a 4-day history of ataxia, diplopia and morning vomiting, as well as severe headache, psychiatric symptoms and cognitive dysfunction beginning 1 year prior to admission. Brain MRI was suggestive of encephalitis. Investigation excluded infectious aetiology. Immunological markers revealed high titre of antinuclear and anti-double-stranded DNA antibodies. Neuropsychiatric lupus (NPL) was considered, and cyclophosphamide and methylprednisolone pulses were started, with good initial response. Clinical deterioration motivated therapy with azathioprine with subsequent clinical stabilisation and a latent cognitive dysfunction. In unusual encephalitis presentation, a wide range of differential diagnosis has to be considered. Primary NPL presents difficult diagnostic and therapeutic challenges.
The use of individual patient-level data (IPD) to quantify the impact of pretreatment predictors of response to treatment in chronic hepatitis B patients
Authors: Ali Shehzad , Mealing Stuart , Hawkins Neil , Lescrauwaet Benedicte , Bjork Stefan , Mantovani Lorenzo , Lampertico Pietro
Published: January 2013

Objectives

Evidence synthesis is an integral part decision-making by reimbursement agencies. When direct evidence is not available, network-meta-analysis (NMA) techniques are commonly used. This approach assumes that the trials are sufficiently similar in terms of treatment-effect modifiers. When imbalances in potential treatment-effect modifiers exist, the NMA approach may not produce fair comparisons. The objective of this study was to identify and quantify the interaction between treatment-effect and potential treatment-effect modifiers, including time-of-response measurement and baseline viral load in chronic hepatitis B (CHB) patients.

Design

Retrospective patient-level data econometric analysis.

Participants

1353 individuals from two randomised controlled trials of nucleoside-naïve CHB taking 0.5 mg entecavir (n=679) or 100 mg lamivudine (n=668) daily for 48 weeks.

Interventions

Hepatitis B virus (HBV) DNA levels for both drugs were measured at baseline and weeks 24, 36 and 48. Generalised estimating equation for repeated binary responses was used to identify treatment-effect modifiers for response defined at ≤400 or ≤300 copies/ml.

Primary outcome measures

OR at 48 weeks.

Results

The OR for the time-of-response measurement and treatment-effect interaction term was 1.039 (p=0.00) and 1.035 (p=0.00) when response was defined at ≤400 or ≤300 copies/ml, respectively. The baseline HBV DNA and treatment-effect interaction OR was 0.94 (p=0.047) and 0.95 (p=0.096), respectively, for the two response definitions suggesting evidence of interaction between baseline disease activity and treatment effect. The interaction between HBeAg status and treatment effect was not statistically significant.

Conclusions

The measurement time point seems to modify the relative treatment effect of entacavir compared to lamivudine, measured on the OR scale. Evidence also suggested that differences in baseline viral load may also alter relative treatment effect. Meta-analyses should account for such modifiers when generating relative efficacy estimates.
Emergency department visits for fall-related fractures among older adults in the USA: a retrospective cross-sectional analysis of the National Electronic Injury Surveillance System All Injury Program, 2001–2008
Authors: Orces Carlos H
Published: January 2013

Objectives

To describe the demographic characteristics and incidence of unintentional fall-related fractures among older adults treated in the US hospital emergency departments (EDs).

Design

Retrospective observational study.

Settings

Hospitals’ ED participants in the National Electronic Injury Surveillance System All Injury Program (NEISS-AIP).

Participants

The NEISS-AIP was used to generate national estimates of hospital ED visits for unintentional fall-related fracture among adults aged 65 years or older between 2001 and 2008. Census population estimates were used as the denominator to calculate age-specific and age-adjusted fracture rates per 100 000 persons.

Main outcome measures

Fall-related fracture rates and ED disposition.

Results

On the basis of 70 199 cases, an estimated 4.05 million older adults were treated in US hospital EDs for fall-related fracture during the 8-year period. Two-thirds of the injuries occurred at home and 69.5% (95% CI 59.7% to 77.8%) of the affected individuals were white. Fall-related fracture rates increased gradually with age and were on average twofold higher among women. Of those hospitalised, women and fractures of the lower trunk represented 75.2% and 65.1% of the admissions, respectively. The estimated number of fall-related fractures treated in EDs increased from 574 500 in 2001 to 714 800 in 2008, a 24.4% increase. By gender, a non-significant upward trend in age-adjusted fall-related fracture rates was predominantly seen among men at an annual rate of 1.9% (95% CI −0.1% to 4.0%), whereas fracture rates among women remained stable at 0.9% (95% CI −0.7% to 2.5%) per year.

Conclusions

The oldest old, women and lower trunk fractures account for the majority of fall-related fractures among persons aged 65 years or older treated in US hospital EDs. Increasing ED visits and hospitalisations for fall-related fracture among older adults deserve further research.
Heat-related respiratory hospital admissions in Europe in a changing climate: a health impact assessment
Authors: Åström Christofer , Orru Hans , Rocklöv Joacim , Strandberg Gustav , Ebi Kristie L , Forsberg Bertil
Published: January 2013

Objectives

Respiratory diseases are ranked second in Europe in terms of mortality, prevalence and costs. Studies have shown that extreme heat has a large impact on mortality and morbidity, with a large relative increase for respiratory diseases. Expected increases in mean temperature and the number of extreme heat events over the coming decades due to climate change raise questions about the possible health impacts. We assess the number of heat-related respiratory hospital admissions in a future with a different climate.

Design

A Europe-wide health impact assessment.

Setting

An assessment for each of the EU27 countries.

Methods

Heat-related hospital admissions under a changing climate are projected using multicity epidemiological exposure–response relationships applied to gridded population data and country-specific baseline respiratory hospital admission rates. Times-series of temperatures are simulated with a regional climate model based on four global climate models, under two greenhouse gas emission scenarios.

Results

Between a reference period (1981–2010) and a future period (2021–2050), the total number of respiratory hospital admissions attributed to heat is projected to be larger in southern Europe, with three times more heat attributed respiratory hospital admissions in the future period. The smallest change was estimated in Eastern Europe with about a twofold increase. For all of Europe, the number of heat-related respiratory hospital admissions is projected to be 26 000 annually in the future period compared with 11 000 in the reference period.

Conclusions

The results suggest that the projected effects of climate change on temperature and the number of extreme heat events could substantially influence respiratory morbidity across Europe.
Spatial analysis of health effects of large industrial incinerators in England, 1998–2008: a study using matched case–control areas
Authors: Reeve Nicola F , Fanshawe Thomas R , Keegan Thomas J , Stewart Alex G , Diggle Peter J
Published: January 2013

Objectives

To assess whether residential proximity to industrial incinerators in England is associated with increased risk of cancer incidence and mortality.

Design

Retrospective study using matched case–control areas.

Setting

Five circular regions of radius 10 km near industrial incinerators in England (case regions) and five matched control regions, 1998–2008.

Participants

All cases of diseases of interest within the circular areas.

Primary and secondary outcome measures

Counts of childhood cancer incidence (<15 years); childhood leukaemia incidence (<15 years); leukaemia incidence; liver cancer incidence; lung cancer incidence; non-Hodgkin's lymphoma incidence; all-cause mortality; infant mortality (<1 year) and liver cancer mortality.

Results

The estimated relative risks for case circles versus control circles for the nine outcomes considered  range from 0.94 to 1.14, and show neither elevated risk in case circles compared to control areas nor elevated risk with proximity to incinerators within case circles.

Conclusions

This study applies statistical methods for analysing spatially referenced health outcome data in regions with a hypothesised exposure relative to matched regions with no such exposure. There is no evidence of elevated risk of cancer incidence or mortality in the vicinity of large industrial incinerators in England.
Does implementation of the IMCI strategy have an impact on child mortality? A retrospective analysis of routine data from Egypt
Authors: Rakha Mona Ali , Abdelmoneim Ahmed-Nagaty Mohamed , Farhoud Suzanne , Pièche Sergio , Cousens Simon , Daelmans Bernadette , Bahl Rajiv
Published: January 2013

Background

Between 1999 and 2007, the Ministry of Health and Population in Egypt scaled up the Integrated Management of Childhood Illness (IMCI) strategy in 84% of public health facilities.

Objectives

This retrospective analysis, using routinely available data from vital registration, aimed to assess the impact of IMCI implementation between 2000 and 2006 on child mortality. It also presents a systematic and comprehensive approach to scaling-up IMCI interventions and information on quality of child health services, using programme data from supervision and surveys.

Methods

We compared annual levels of under-five mortality in districts before and after they had started implementing IMCI. Mortality data were obtained from the National Bureau for Statistics for 254 districts for the years 2000–2006, 41 districts of which were excluded. For assessment of programme activities, we used information from the central IMCI data base, annual progress reports, follow-up after training visits and four studies on quality of child care in public health facilities.

Results

Across 213 districts retained in the analysis, the estimated average annual rate of decline in under-five mortality was 3.3% before compared with 6.3% after IMCI implementation (p=0.0001). In 127 districts which started implementing IMCI between 2002 and 2005, the average annual rate of decline of under-five mortality was 2.6% (95% CI 1.1% to 4.1%) before compared with 7.3% (95% CI 5.8% to 8.7%) after IMCI implementation (p<0.0001). IMCI implementation also led to marked improvements in the quality of child health services.

Interpretation

IMCI implementation was associated with a doubling in the annual rate of under-five mortality reduction (3.3% vs 6.3%). This mortality impact is plausible, since substantial improvements occurred in quality of care provided to sick children in health facilities implementing IMCI.
Framework of policy recommendations for implementation of evidence-based practice: a systematic scoping review
Authors: Ubbink Dirk T , Guyatt Gordon H , Vermeulen Hester
Published: January 2013

Objectives

Evidence-based practice (EBP) may help improve healthcare quality. However, not all healthcare professionals and managers use EBP in their daily practice. We systematically reviewed the literature to summarise self-reported appreciation of EBP and organisational infrastructure solutions proposed to promote EBP.

Design

Systematic review. Two investigators independently performed the systematic reviewing process.

Information sources

MEDLINE, EMBASE and Cochrane Library were searched for publications between 2000 and 2011.

Eligibility criteria for included studies

Reviews and surveys of EBP attitude, knowledge, awareness, skills, barriers and facilitators among managers, doctors and nurses in clinical settings.

Results

We found 31 surveys of fairly good quality. General attitude towards EBP was welcoming. Respondents perceived several barriers, but also many facilitators for EBP implementation. Solutions were proposed at various organisational levels, including (inter)national associations and hospital management promoting EBP, pregraduate and postgraduate education, as well as individual support by EBP mentors on the wards to move EBP from the classroom to the bedside.

Conclusions

More than 20 years after its introduction, the EBP paradigm has been embraced by healthcare professionals as an important means to improve quality of patient care, but its implementation is still deficient. Policy exerted at microlevel , middlelevel and macrolevel, and supported by professional, educational and managerial role models, may further facilitate EBP.
Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study
Authors: Raschpichler Matthias , Straatman Kees , Schroeter Matthias Leopold , Arelin Katrin , Schlögl Haiko , Fritzsch Dominik , Mende Meinhard , Pampel André , Böttcher Yvonne , Stumvoll Michael , Villringer Arno , Mueller Karsten
Published: January 2013

Objectives

To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age.

Design

Cross-sectional, exploratory.

Setting

University Clinic, Integrative Research and Treatment Centre.

Participants

We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups:young-to-mid-age(n=51, 20–45 years of age, mean BMI=24.9, 24 women) versusold(n=49, 65–70 years of age, mean BMI=27.0, 18 women).

Main outcome measures

VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC).

Results

We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT.

Conclusions

Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected.
Effects of exenatide and liraglutide on heart rate, blood pressure and body weight: systematic review and meta-analysis
Authors: Robinson Louise E , Holt Tim A , Rees Karen , Randeva Harpal S , O'Hare Joseph P
Published: January 2013

Objectives

To synthesise current evidence for the effects of exenatide and liraglutide on heart rate, blood pressure and body weight.

Design

Meta-analysis of available data from randomised controlled trials comparing Glucagon-like peptide-1 (GLP-1) analogues with placebo, active antidiabetic drug therapy or lifestyle intervention.

Participants

Patients with type 2 diabetes.

Outcome measures

Weighted mean differences between trial arms for changes in heart rate, blood pressure and body weight, after a minimum of 12-week follow-up.

Results

32 trials were included. Overall, GLP-1 agonists increased the heart rate by 1.86 beats/min (bpm) (95% CI 0.85 to 2.87) versus placebo and 1.90 bpm (1.30 to 2.50) versus active control. This effect was more evident for liraglutide and exenatide long-acting release than for exenatide twice daily. GLP-1 agonists decreased systolic blood pressure by −1.79 mm Hg (−2.94 to −0.64) and −2.39 mm Hg (−3.35 to −1.42) compared to placebo and active control, respectively. Reduction in diastolic blood pressure failed to reach statistical significance (−0.54 mm Hg (−1.15 to 0.07) vs placebo and −0.50 mm Hg (−1.24 to 0.24) vs active control). Body weight decreased by −3.31 kg (−4.05 to −2.57) compared to active control, but by only −1.22 kg (−1.51 to −0.93) compared to placebo.

Conclusions

GLP-1 analogues are associated with a small increase in heart rate and modest reductions in body weight and blood pressure. Mechanisms underlying the rise in heart rate require further investigation.
Optimising drug prescribing and dispensing in subjects at risk for drug errors due to renal impairment: improving drug safety in primary healthcare by low eGFR alerts
Authors: Joosten Hanneke , Drion Iefke , Boogerd Kees J , van der Pijl Emiel V , Slingerland Robbert J , Slaets Joris P J , Jansen Tiele J , Schwantje Olof , Gans Reinold O B , Bilo Henk J G
Published: January 2013

Objectives

To assess the risk of medication errors in subjects with renal impairment (defined as an estimated glomerular filtration rate (eGFR) ≤40 ml/min/1.73 m2) and the effectiveness of automatic eGFR ≤40-alerts relayed to community pharmacists.

Design

Clinical survey.

Setting

The city of Zwolle, The Netherlands, in a primary care setting including 22 community pharmacists and 65 general practitioners.

Participants

All adults who underwent ambulatory creatine measurements which triggered an eGFR ≤40-alert.

Primary and secondary outcome measures

The total number of ambulatory subjects with an eGFR ≤40-alert during the study period of 1 year and the number of medication errors related to renal impairment. The type and number of proposed drug adjustments recommended by the community pharmacist and acceptance rate by the prescribing physicians. Classification of all medication errors on their potential to cause an adverse drug event (ADE) and the actual occurrence of ADEs (limited to those identified through hospital record reviews) 1 year after the introduction of the alerts.

Results

Creatine measurements were performed in 25 929 adults. An eGFR ≤40-alert was indicated for 5.3% (n=1369). This group had a median (IQR) age of 78 (69, 84) years, and in 73% polypharmacy (≥5 drugs) was present. In 15% (n=211) of these subjects, a medication error was detected. The proportion of errors increased with age. Pharmacists recommended 342 medication adjustments, mainly concerning diuretics (22%) and antibiotics (21%). The physicians’ acceptance rate was 66%. Of all the medication errors, 88% were regarded as potential ADEs, with most classified as significant or serious. At follow-up, the ADE risk (n=40) appeared highest when the proposed medication adjustments were not implemented (38% vs 6%).

Conclusions

The introduction of automatic eGFR-alerts identified a considerable number of subjects who are at risk for ADEs due to renal impairment in an ambulatory setting. The nationwide implementation of this simple protocol could identify many potential ADEs, thereby substantially reducing iatrogenic complications in subjects with impaired renal function.
The daily 10 kcal expenditure deficit: a before-and-after study on low-cost interventions in the work environment
Authors: Dorresteijn Johannes A N , van der Graaf Yolanda , Zheng Kailiang , Spiering Wilko , Visseren Frank L J
Published: January 2013

Objectives

To evaluate whether four types of low-cost interventions in the working environment can promote the small everyday lifestyle adaptations that can halt the epidemics of obesity and hypertension when maintained long term.

Design

A single-blind uninterrupted time-series intervention study consisting of four study periods: run-in (2 weeks), baseline (2 weeks), intervention (2 weeks), and after intervention 2 weeks).

Setting

University Medical Centre with over 11 000 employees, over 1000 hospital beds and over 2000 customers visiting the hospital restaurant each day.

Participants

Hospital staff and visitors.

Interventions

(1) Point-of-decision prompts on hospital elevator doors promoting stair use. (2) Point-of-purchase prompts in the hospital restaurant promoting reduced-salt soup. (3) Point-of-purchase prompts in the hospital restaurant promoting lean croissants. (4) Reversal of the accessibility and availability of diet margarine and butter in the hospital restaurant.

Main outcome measures

(1) Number of passages through 15 different parts of the hospital staircases. (2) Number and ratio of normal-salt and reduced-salt soup purchased. (3) Number and ratio of butter croissants and lean croissants purchased. (4) Number and ratio of diet margarine and butter purchased.

Results

Elevator signs increased the mean 24-h number of stair passages per measurement site (baseline: 992 ± 479 on week days and 208 ± 116 on weekend days) by 11.2% (95% CI 8.7% to 13.7%). This effect was maintained at least 2 weeks after the point-of-decision prompts were removed. Point-of-purchase prompts promoting low-salt soup and lean croissants did not result in altered purchase behaviour. The ratio between the purchase of margarine and butter was changed sevenfold (p<0.01) by reversing the positions of these products in the hospital restaurant.

Conclusions

Healthy lifestyle adaptations in the working environment can be effectively promoted by making healthy choices easier than unhealthy ones. Educational prompts at points-of-decision moderately increase stair climbing, but do not affect healthy food choices.

Protocol registration

Clinicaltrials.gov identifier number:NCT01574040.
The beliefs and expectations of patients and caregivers about home haemodialysis: an interview study
Authors: Tong Allison , Palmer Suetonia , Manns Braden , Craig Jonathan C , Ruospo Marinella , Gargano Letizia , Johnson David W , Hegbrant Jörgen , Olsson Måns , Fishbane Steven , Strippoli Giovanni F M
Published: January 2013

Objectives

To explore the beliefs and expectations of patients and their caregivers about home haemodialysis in Italy where the prevalence of home haemodialysis is low.

Design

Semistructured, qualitative interview study with purposive sampling and thematic analysis.

Setting

Four dialysis centres in Italy without home haemodialysis services (Bari, Marsala, Nissoria and Taranto).

Participants

22 patients receiving in-centre haemodialysis and 20 of their identified caregivers.

Results

We identified seven major themes that were central to patient and caregiver perceptions of home haemodialysis in regions without established services. Three positive themes were: flexibility and freedom (increased autonomy, minimised wasted time, liberation from strict dialysis schedules and gaining self-worth); comfort in familiar surroundings (family presence and support, avoiding the need for dialysis in hospital) and altruistic motivation to do home haemodialysis as an exemplar for other patients and families. Four negative themes were: disrupting sense of normality; family burden (an onerous responsibility, caregiver uncertainty and panic and visually confronting); housing constraints; healthcare by ‘professionals’ not ‘amateurs’ (relinquishing security and satisfaction with in-centre services) and isolation from peer support.

Conclusions

Patients without direct experience or previous education about home haemodialysis and their caregivers recognise the autonomy of home haemodialysis but are very concerned about the potential burden and personal sacrifice home haemodialysis will impose on caregivers and feel apprehensive about accepting the medical responsibilities of dialysis. To promote acceptance and uptake of home haemodialysis among patients and caregivers who have no experience of home dialysis, effective strategies are needed that provide information about home haemodialysis to patients and their caregivers, assure access to caregiver respite, provide continuous availability of medical and technical advice and facilitate peer patient support.
The TrueBlue model of collaborative care using practice nurses as case managers for depression alongside diabetes or heart disease: a randomised trial
Authors: Morgan Mark A J , Coates Michael J , Dunbar James A , Reddy Prasuna , Schlicht Kate , Fuller Jeff
Published: January 2013

Objectives

To determine the effectiveness of collaborative care in reducing depression in primary care patients with diabetes or heart disease using practice nurses as case managers.

Design

A two-arm open randomised cluster trial with wait-list control for 6 months. The intervention was followed over 12 months.

Setting

Eleven Australian general practices, five randomly allocated to the intervention and six to the control.

Participants

400 primary care patients (206 intervention, 194 control) with depression and type 2 diabetes, coronary heart disease or both.

Intervention

The practice nurse acted as a case manager identifying depression, reviewing pathology results, lifestyle risk factors and patient goals and priorities. Usual care continued in the controls.

Main outcome measure

A five-point reduction in depression scores for patients with moderate-to-severe depression. Secondary outcome was improvements in physiological measures.

Results

Mean depression scores after 6 months of intervention for patients with moderate-to-severe depression decreased by 5.7±1.3 compared with 4.3±1.2 in control, a significant (p=0.012) difference. (The plus–minus is the 95% confidence range.) Intervention practices demonstrated adherence to treatment guidelines and intensification of treatment for depression, where exercise increased by 19%, referrals to exercise programmes by 16%, referrals to mental health workers (MHWs) by 7% and visits to MHWs by 17%. Control-practice exercise did not change, whereas referrals to exercise programmes dropped by 5% and visits to MHWs by 3%. Only referrals to MHW increased by 12%. Intervention improvements were sustained over 12 months, with a significant (p=0.015) decrease in 10-year cardiovascular disease risk from 27.4±3.4% to 24.8±3.8%. A review of patients indicated that the study's safety protocols were followed.

Conclusions

TrueBlue participants showed significantly improved depression and treatment intensification, sustained over 12 months of intervention and reduced 10-year cardiovascular disease risk. Collaborative care using practice nurses appears to be an effective primary care intervention.

Trial registration

ACTRN12609000333213 (Australia and New Zealand Clinical Trials Registry).
A clustered randomised trial examining the effect of social marketing and community mobilisation on the age of uptake and levels of alcohol consumption by Australian adolescents
Authors: Rowland Bosco , Toumbourou John Winston , Osborn Amber , Smith Rachel , Hall Jessica Kate , Kremer Peter , Kelly Adrian B , Williams Joanne , Leslie Eva
Published: January 2013

Introduction

Throughout the world, alcohol consumption is common among adolescents. Adolescent alcohol use and misuse have prognostic significance for several adverse long-term outcomes, including alcohol problems, alcohol dependence, school disengagement and illicit drug use. The aim of this study was to evaluate whether randomisation to a community mobilisation and social marketing intervention reduces the proportion of adolescents who initiate alcohol use before the Australian legal age of 18, and the frequency and amount of underage adolescent alcohol consumption.

Method and analysis

The study comprises 14 communities matched with 14 non-contiguous communities on socioeconomic status (SES), location and size. One of each pair was randomly allocated to the intervention. Baseline levels of adolescent alcohol use were estimated through school surveys initiated in 2006 (N=8500). Community mobilisation and social marketing interventions were initiated in 2011 to reduce underage alcohol supply and demand. The setting is communities in three Australian states (Victoria, Queensland and Western Australia). Students (N=2576) will complete school surveys in year 8 in 2013 (average age 12). Primary outcomes: (1) lifetime initiation and (2) monthly frequency of alcohol use. Reports of social marketing and family and community alcohol supply sources will also be assessed. Point estimates with 95% CIs will be compared for student alcohol use in intervention and control communities. Changes from 2006 to 2013 will be examined; multilevel modelling will assess whether random assignment of communities to the intervention reduced 2013 alcohol use, after accounting for community level differences. Analyses will also assess whether exposure to social marketing activities increased the intervention target of reducing alcohol supply by parents and community members.

Trial registration

ACTRN12612000384853.
Does an intensive self-management structured education course improve outcomes for children and young people with type 1 diabetes? The Kids In Control OF Food (KICk-OFF) cluster-randomised controlled trial protocol
Authors: Price Katherine J , Wales Jerry , Eiser Christine , Knowles Julie , Heller Simon , Freeman Jenny , Brennan Alan , McPherson Amy , Wellington Jerry
Published: January 2013

Introduction

The Kids In Control OF Food (KICk-OFF) is a cluster-randomised controlled trial, which aims to determine the efficacy of a 5 day structured education course for 11-year-olds to 16-year-olds with type 1 diabetes (T1DM) when compared with standard care, and its cost effectiveness. Less than 15% of children and young people with T1DM in the UK meet the recommended glycaemic target. Self-management education programmes for adults with T1DM improve clinical and psychological outcomes, but none have been evaluated in the paediatric population. KICk-OFF is a 5-day structured education course for 11-year-olds to 16- year-olds with T1DM. It was developed with input from young people, parents, teachers and educationalists.

Methods and analysis

36 paediatric diabetes centres across the UK randomised into intervention and control arms. Up to 560 participants were recruited prior to centre randomisation. KICk-OFF courses are delivered in the intervention centres, with standard care continued in the control arm. Primary outcomes are change in glycaemic control (HbA1c) and quality of life between baseline and 6 months postintervention, and the incidence of severe hypoglycaemia. Sustained change in self-management behaviour is assessed by follow-up at 12 and 24 months. Health economic analysis will be undertaken. Data will be reported according to the CONSORT statement for cluster-randomised clinical trials. All analyses will be by intention-to-treat with a two-sided p value of <0.05 being regarded as statistically significant. The study commenced in 2008. Data collection from participants is ongoing and the study will be completed in 2013.

Ethics

The study has been approved by the Sheffield Research Ethics Committee.

Dissemination

Results will be reported in peer reviewed journals and conferences.

Trial registration

Current Controlled TrialsISRCTN37042683.
Going DEEP: guidelines for building simulation-based team assessments
Authors: Grand James A , Pearce Marina , Rench Tara A , Chao Georgia T , Fernandez Rosemarie , Kozlowski Steve W J
Published: January 2013

Background

Whether for team training, research or evaluation, making effective use of simulation-based technologies requires robust, reliable and accurate assessment tools. Extant literature on simulation-based assessment practices has primarily focused on scenario and instructional design; however, relatively little direct guidance has been provided regarding the challenging decisions and fundamental principles related to assessment development and implementation.

Objective

The objective of this manuscript is to introduce a generalisable assessment framework supplemented by specific guidance on how to construct and ensure valid and reliable simulation-based team assessment tools. The recommendations reflect best practices in assessment and are designed to empower healthcare educators, professionals and researchers with the knowledge to design and employ valid and reliable simulation-based team assessments.

Overview

Information and actionable recommendations associated with creating assessments of team processes (non-technical ‘teamwork’ activities) and performance (demonstration of technical proficiency) are presented which provide direct guidance on how to Distinguish the underlying competencies one aims to assess, Elaborate the measures used to capture team member behaviours during simulation activities, Establish the content validity of these measures and Proceduralise the measurement tools in a way that is systematically aligned with the goals of the simulation activity while maintaining methodological rigour (DEEP).

The DEEP framework targets fundamental principles and critical activities that are important for effective assessment, and should benefit healthcare educators, professionals and researchers seeking to design or enhance any simulation-based assessment effort.
Diagnosis and management of giant cell arteritis and polymyalgia rheumatica: challenges, controversies and practical tips
Authors: Mackie Sarah Louise , Pease Colin Thomas
Published: January 2013

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are inflammatory rheumatic diseases that may present to a variety of disciplines and specialities. The mainstay of treatment is glucocorticoids (steroids); together PMR and GCA now represent one of the most common reasons for medium-to-high dose, long-term glucocorticoid treatment in primary care. However, adverse effects of glucocorticoids are common in these patients. Management of both diseases involves balancing the symptoms and risks of the disease against the adverse effects and risks of glucocorticoids. The crucial first step in management is to make a firm, well-documented diagnosis, since once glucocorticoids are started they can mask the symptoms of a number of other diseases. Diagnosis however can be challenging and there are still substantial gaps in the evidence for treatment.
Intraventricular and interventricular cellular heterogeneity of inotropic responses to α1-adrenergic stimulation
Authors: Chu Charles , Thai Kevin , Park Ki Wan , Wang Paul , Makwana Om , Lovett David H. , Simpson Paul C. , Baker Anthony J.
Published: January 2013

α1-Adrenergic receptors (α1-ARs) elicit a negative inotropic effect (NIE) in the mouse right ventricular (RV) myocardium but a positive inotropic effect (PIE) in the left ventricular (LV) myocardium. Effects on myofilament Ca2+sensitivity play a role, but effects on Ca2+handling could also contribute. We monitored the effects of α1-AR stimulation on contraction and Ca2+transients using single myocytes isolated from the RV or LV. Interestingly, for both the RV and LV, we found heterogeneous myocyte inotropic responses. α1-ARs mediated either a PIE or NIE, although RV myocytes had a greater proportion of cells manifesting a NIE (68%) compared with LV myocytes (36%). Stimulation of a single α1-AR subtype (α1A-ARs) with a subtype-selective agonist also elicited heterogeneous inotropic responses, suggesting that the heterogeneity arose from events downstream of the α1A-AR subtype. For RV and LV myocytes, an α1-AR-mediated PIE was associated with an increased Ca2+transient and a NIE was associated with a decreased Ca2+transient, suggesting a key role for Ca2+handling. For RV and LV myocytes, α1-AR-mediated decreases in the Ca2+transient were associated with increased Ca2+export from the cell and decreased Ca2+content of the sarcoplasmic reticulum. In contrast, for myocytes with α1-AR-induced increased Ca2+transients, sarcoplasmic reticulum Ca2+content was not increased, suggesting that other mechanisms contributed to the increased Ca2+transients. This study demonstrates the marked heterogeneity of LV and RV cellular inotropic responses to stimulation of α1-ARs and reveals a new aspect of biological heterogeneity among myocytes in the regulation of contraction.
Time delay of baroreflex control and oscillatory pattern of sympathetic activity in patients with metabolic syndrome and obstructive sleep apnea
Authors: Toschi-Dias Edgar , Trombetta Ivani C. , Dias da Silva Valdo J. , Maki-Nunes Cristiane , Cepeda Felipe X. , Alves Maria-Janieire N. N. , Drager Luciano F. , Lorenzi-Filho Geraldo , Negrao Carlos E. , Rondon Maria Urbana P. B.
Published: January 2013

The incidence and strength of muscle sympathetic nerve activity (MSNA) depend on the magnitude (gain) and latency (time delay) of the arterial baroreflex control (ABR). However, the impact of metabolic syndrome (MetS) and obstructive sleep apnea (OSA) on oscillatory pattern of MSNA and time delay of the ABR of sympathetic activity is unknown. We tested the hypothesis that MetS and OSA would impair the oscillatory pattern of MSNA and the time delay of the ABR of sympathetic activity. Forty-three patients with MetS were allocated into two groups according to the presence of OSA (MetS + OSA, n = 21; and MetS − OSA, n = 22). Twelve aged-paired healthy controls (C) were also studied. OSA (apnea-hypopnea index > 15 events/h) was diagnosed by polysomnography. We recorded MSNA (microneurography), blood pressure (beat-to-beat basis), and heart rate (EKG). Oscillatory pattern of MSNA was evaluated by autoregressive spectral analysis and the ABR of MSNA (ABRMSNA, sensitivity and time delay) by bivariate autoregressive analysis. Patients with MetS + OSA had decreased oscillatory pattern of MSNA compared with MetS − OSA ( P < 0.01) and C ( P < 0.001). The sensitivity of the ABRMSNAwas lower and the time delay was greater in MetS + OSA compared with MetS − OSA ( P < 0.001 and P < 0.01, respectively) and C ( P < 0.001 and P < 0.001, respectively). Patients with MetS − OSA showed decreased oscillatory pattern of MSNA compared with C ( P < 0.01). The sensitivity of the ABRMSNAwas lower in MetS − OSA than in C group ( P < 0.001). In conclusion, MetS decreases the oscillatory pattern of MSNA and the magnitude of the ABRMSNA. OSA exacerbates these autonomic dysfunctions and further increases the time delay of the baroreflex response of MSNA.
Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury
Authors: Masuzawa Akihiro , Black Kendra M. , Pacak Christina A. , Ericsson Maria , Barnett Reanne J. , Drumm Ciara , Seth Pankaj , Bloch Donald B. , Levitsky Sidney , Cowan Douglas B. , McCully James D.
Published: January 2013

Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased ( P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury.
Automated open flow respirometry in continuous and long-term measurements: design and principles
Authors: Tøien Øivind
Published: January 2013

Sustaining high-quality respirometry measurements on animals for estimating metabolic rate and fuel use is challenging. I present a general discussion and selected methods for automated measurements spanning over >4 mo with little need for adjustments or maintenance. 1) Lack of compensation for respiratory volume change may cause 6% error in the results on a fasting animal. The Haldane transformation provides the simplest calculation method for both O2and CO2measurements. 2) Use of Nafion tube dryers configured as countercurrent moisture exchangers provides maintenance-free drying of gases, with typical outlet dew points at −25 to −38°C and no CO2adsorption. The accuracy is improved by low dead space, making it feasible to pass gases though the same dryer. 3) A software algorithm employing a triple interpolation technique allows corrections for automated calibrations of O2and CO2with both zero-reference and span gas. 4) Burning known amounts of 100% ethanol provides total system verification of both O2consumption and respiratory quotient. A calculation method to supply instant CO2calibration gas from an alcohol burn is presented. 5) Automatic flow switching triggered by low/high O2thresholds improves accuracy of measurements and safety for the animals experiencing large ranges of O2consumption; this is a special requirement for recording metabolism in small hibernating mammals.
Drinking Water Arsenic in Northern Chile: High Cancer Risks 40 Years after Exposure Cessation
Authors: Steinmaus Craig M. , Ferreccio Catterina , Romo Johanna Acevedo , Yuan Yan , Cortes Sandra , Marshall Guillermo , Moore Lee E. , Balmes John R. , Liaw Jane , Golden Todd , Smith Allan H.
Published: January 2013

Background: Millions of people worldwide are exposed to arsenic-contaminated water. In the largest city in northern Chile (Antofagasta), more than 250,000 people were exposed to high arsenic drinking water concentrations from 1958 until 1970 when a water treatment plant was installed. Because of its unique geology, limited water sources, and good historical records, lifetime exposure and long-term latency patterns can be assessed in this area with better accuracy than in other arsenic-exposed areas worldwide.

Methods: We conducted a population-based case–control study in northern Chile from October 2007 to December 2010 involving 232 bladder and 306 lung cancer cases and 640 age- and gender-matched controls, with detailed information on past exposure and potential confounders, including smoking and occupation.

Results: Bladder cancer ORs for quartiles of average arsenic concentrations in water before 1971 (<11, 11–90, 91–335, and >335 μg/L) were 1.00, 1.36 [95% confidence interval (CI), 0.78–2.37], 3.87 (2.25–6.64), and 6.50 (3.69–11.43), respectively. Corresponding lung cancer ORs were 1.00, 1.27 (0.81–1.98), 2.00 (1.24–3.24), and 4.32 (2.60–7.17). Bladder and lung cancer ORs in those highly exposed in Antofagasta during 1958 to 1970 but not thereafter were 6.88 (3.84–12.32) and 4.35 (2.57–7.36), respectively.

Conclusions: The lung and bladder cancer risks that we found up to 40 years after high exposures have ended are very high.

Impact: Our findings suggest that prevention, treatment, and other mortality reduction efforts in arsenic-exposed countries will be needed for decades after exposure cessation. Cancer Epidemiol Biomarkers Prev; 22(4); 623–30. ©2013 AACR.
Cervical Cancer Screening Among Young Adult Women in the United States
Authors: Roland Katherine B. , Benard Vicki B. , Soman Ashwini , Breen Nancy , Kepka Deanna , Saraiya Mona
Published: January 2013

Background: Cervical cancer screening guidelines have evolved significantly in the last decade for young adult women, with current recommendations promoting later initiation and longer intervals.

Methods: Using self-reported cross-sectional National Health Interview Survey (NHIS) 2000–2010 data, trends in Papanicolaou (Pap) testing among women ages 18–29 years were examined. NHIS 2010 data were used to investigate age at first Pap test (N = 2,198), time since most recent Pap test (n = 1,622), and predictors of Pap testing within the last 12 months (n = 1,622).

Results: The percentage of 18-year-olds who reported ever having a Pap test significantly decreased from 49.9% in 2000 to 37.9% in 2010. Mean age at first Pap test in 2010 was significantly younger for non-Hispanic black women (16.9 years), women < high school education (16.9 years), women who received the HPV vaccine (17.1 years), and women who have ever given birth (17.3 years). The majority reported their last Pap test within the previous 12 months (73.1%). Usual source of healthcare (OR, 2.31) and current birth control use (OR, 1.64) significantly increased chances of having a Pap test within the previous 12 months.

Conclusions: From 2000 to 2010, there was a gradual decline in Pap test initiation among 18-year-olds; however, in 2010, many women reported ≤12 months since last screening. Evidence-based guidelines should be promoted, as screening young adult women for cervical cancer more frequently than recommended can cause considerable harms.

Impact: A baseline of cervical cancer screening among young adult women in the United States to assess adherence to evidence-based screening guidelines. Cancer Epidemiol Biomarkers Prev; 22(4); 580–8. ©2013 AACR.
Molecular Pathways: Adiponectin and Leptin Signaling in Cancer
Authors: VanSaun Michael N.
Published: January 2013

The increasing percentage of obese individuals in the population and its independent association of increased risk for the development of cancer have heightened the necessity to understand the molecular mechanisms that underlie this connection. The deregulation of adipokines in the setting of obesity and their impact on cancer progression and metastasis is one such area of research. Adipokines are bioactive proteins that mediate metabolism, inflammation, angiogenesis, and proliferation. Altered levels of adipokines or their cognate receptors in cancers can ultimately lead to an imbalance in downstream molecular pathways. Discovery of adipokine receptors in various cancers has highlighted the potential for novel therapeutic targets. Leptin and adiponectin represent two adipokines that elicit generally opposing molecular effects. Epidemiologic studies have highlighted associations between increased serum leptin levels and increased tumor growth, whereas adiponectin exhibits an inverse correlation with cancer development. This review addresses the current level of understanding of molecular pathways activated by adiponectin and leptin to identify the areas of intervention and facilitate advancement in the field. Clin Cancer Res; 19(8); 1926–32. ©2013 AACR.