bluuebunny/crossref_metadata_2025 huggingface dataset:
CapeOX perioperative chemotherapy versus postoperative chemotherapy for locally advanced resectable colon cancer: protocol for a two-period randomised controlled phase III trial
Authors: Liu Fangqi , Tong Tong , Huang Dan , Yuan Weitang , Li Dechuan , Lin Jianjiang , Cai Sanjun , Xu Ye , Chen Wenbin , Sun Yueming , Zhuang Jing
Published: January 2019

Introduction

Adjuvant chemotherapy with the CapeOX regimen is now widely used for treating colorectal cancer. However, prior studies have demonstrated better efficacy of pre-operative/neoadjuvant chemotherapy without increase of safety risks.

Methods and Analysis

This multicentre, open-label, parallel-group, randomised, controlled, phase III study aims to compare the efficacy and safety of perioperative CapeOX chemotherapy with the postoperative one for treating patients with locally advanced R0 resectable colon cancers in China. In total 1370 eligible patients will be randomised to: the test group, up to four cycles (every 3 weeks is a cycle, Q3W) of chemotherapy plus radical surgery plus up to four cycles of post-operative chemotherapy; or the control group, radical surgery first, then up to eight cycles of chemotherapy. In each cycle, oxaliplatin will be given at a dose of 130 mg/m2through continuous IV infusion for 2 hours on the first day. From day 1 to day 14, capecitabine will be taken orally every morning and evening at a dose of 1000mg/m2/d. The primary outcome measure is the 3-year disease free survival. The objective response rate, R0 resection rate, overall survival, as well as the adverse events will also be measured as second endpoints. The study may include two periods. If results of period 1 are not favourable, period 2 will be initiated, recruiting genetically sensitive patients and repeating the same process with period 1.

Ethics and dissemination

Informed consent will be required from, and provided, by all subjects. The study protocol has been approved by the independent ethics committee of Shanghai Fudan University Cancer Centre. This study will clearly demonstrate the potential benefit of perioperative chemotherapy with the CapeOX regimen. Results will be shared among all the participating centres, and with policymakers and the academic community to promote the clinical management of colon cancer.

Trial registration number

NCT03125980.
Economic impact of potentially inappropriate prescribing and related adverse events in older people: a cost-utility analysis using Markov models
Authors: Moriarty Frank , Cahir Caitriona , Bennett Kathleen , Fahey Tom
Published: January 2019

Objectives

To determine the economic impact of three drugs commonly involved in potentially inappropriate prescribing (PIP) in adults aged ≥65 years, including their adverse effects (AEs): long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines and proton pump inhibitors (PPIs) at maximal dose; to assess cost-effectiveness of potential interventions to reduce PIP of each drug.

Design

Cost-utility analysis. We developed Markov models incorporating the AEs of each PIP, populated with published estimates of probabilities, health system costs (in 2014 euro) and utilities.

Participants

A hypothetical cohort of 65 year olds analysed over 35 1-year cycles with discounting at 5% per year.

Outcome measures

Incremental cost, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios with 95% credible intervals (CIs, generated in probabilistic sensitivity analysis) between each PIP and an appropriate alternative strategy. Models were then used to evaluate the cost-effectiveness of potential interventions to reduce PIP for each of the three drug classes.

Results

All three PIP drugs and their AEs are associated with greater cost and fewer QALYs compared with alternatives. The largest reduction in QALYs and incremental cost was for benzodiazepines compared with no sedative medication (€3470, 95% CI €2434 to €5001; −0.07 QALYs, 95% CI −0.089 to –0.047), followed by NSAIDs relative to paracetamol (€806, 95% CI €415 and €1346; −0.07 QALYs, 95% CI −0.131 to –0.026), and maximal dose PPIs compared with maintenance dose PPIs (€989, 95% CI -€69 and €2127; −0.01 QALYs, 95% CI −0.029 to 0.003). For interventions to reduce PIP, at a willingness-to-pay of €45 000 per QALY, targeting NSAIDs would be cost-effective up to the highest intervention cost per person of €1971. For benzodiazepine and PPI interventions, the equivalent cost was €1480 and €831, respectively.

Conclusions

Long-term benzodiazepine and NSAID prescribing are associated with significantly increased costs and reduced QALYs. Targeting inappropriate NSAID prescribing appears to be the most cost-effective PIP intervention.
Inequalities in healthcare resources and outcomes threatening sustainable health development in Ethiopia: panel data analysis
Authors: Woldemichael Abraha , Takian Amirhossein , Akbari Sari Ali , Olyaeemanesh Alireza
Published: January 2019

Objective

To measure inequalities in the distributions of selected healthcare resources and outcomes in Ethiopia from 2000 to 2015.

Design

A panel data analysis was performed to measure inequalities in distribution of healthcare workforce, infrastructure, outcomes and finance, using secondary data.

Setting

The study was conducted across 11 regions in Ethiopia.

Participants

Regional population and selected healthcare workforce.

Outcomes measured

Aggregate Theil and Gini indices, changes in inequalities and elasticity of healthcare resources.

Results

Despite marked inequality reductions over a 16 year period, the Theil and Gini indices for the healthcare resources distributions remained high. Among the healthcare workforce distributions, the Gini index (GI) was lowest for nurses plus midwives (GI=0.428, 95% CI 0.393 to 0.463) and highest for specialist doctors (SPDs) (GI=0.704, 95% CI 0.652 to 0.756). Inter-region inequality was the highest for SPDs (95.0%) and the lowest for health officers (53.8%). The GIs for hospital beds, hospitals and health centres (HCs) were 0.592(95% CI 0.563 to 0.621), 0.460(95% CI 0.404 to 0.517) and 0.409(95% CI 0.380 to 0.439), respectively. The interaction term was highest for HC distributions (47.7%). Outpatient department visit per capita (GI=0.349, 95% CI 0.321 to 0.377) and fully immunised children (GI=0.307, 95% CI 0.269 to 0.345) showed inequalities; inequality in the under 5 years of age mortality rate increased overtime (P=0.048). Overall, GI for government health expenditure (GHE) was 0.596(95% CI 0.544 to 0.648), and the estimated relative GHE share of the healthcare workforce and infrastructure distributions were 46.5% and 53.5%, respectively. The marginal changes in the healthcare resources distributions were towards the advantaged populations.

Conclusion

This study revealed high inequalities in healthcare resources in favour of the advantaged populations which can hinder equal access to healthcare and the achievements of healthcare outcomes. The government should strengthen monitoring mechanisms to address inequalities based on the national healthcare standards.
Determinants of imbalanced sex ratio at birth in Nepal: evidence from secondary analysis of a large hospital-based study and nationally-representative survey data
Authors: Pradhan Elina , Pearson Erin , Puri Mahesh , Maharjan Manju , Maharjan Dev Chandra , Shah Iqbal
Published: January 2019

Objectives

To quantify sex ratios at births (SRBs) in hospital deliveries in Nepal, and understand the socio-demographic correlates of skewed SRB. Skewed SRBs in hospitals could be explained by sex selective abortion, and/or by decision to have a son delivered in a hospital—increased in -utero investments for male fetus. We use data on ultrasound use to quantify links between prenatal knowledge of sex, parity and skewed SRBs.

Design

Secondary analysis of: (1) de-identified data from a randomised controlled trial, and (2) 2011 Nepal Demographic and Health Survey (NDHS).

Setting

Nepal.

Participants

(1) 75 428 women who gave birth in study hospitals, (2) NDHS: 12 674 women aged 15–49 years.

Outcome measures

SRB, and conditional SRB of a second child given first born male or female were calculated.

Results

Using data from 75 428 women who gave birth in six tertiary hospitals in Nepal between September 2015 and March 2017, we report skewed SRBs in these hospitals, with some hospitals registering deliveries of 121 male births per 100 female births. We find that a nationally representative survey (2011 NDHS) reveals no difference in the number of hospital delivery of male and female babies. Additionally, we find that: (1) estimated SRB of second-order births conditional on the first being a girl is significantly higher than the biological SRB in our study and (2) multiparous women are more likely to have prenatal knowledge of the sex of their fetus and to have male births than primiparous women with the differences increasing with increasing levels of education.

Conclusions

Our analysis supports sex-selective abortion as the dominant cause of skewed SRBs in study hospitals. Comprehensive national policies that not only plan and enforce regulations against gender-biased abortions and, but also ameliorate the marginalised status of women in Nepal are urgently required to change this alarming manifestation of son preference.

Trial registration number

NCT02718222.
Young people’s preferences for the use of emerging technologies for asymptomatic regular chlamydia testing and management: a discrete choice experiment in England
Authors: Eaton Sue , Biggerstaff Deborah , Petrou Stavros , Osipenko Leeza , Gibbs Jo , Estcourt Claudia S , Sadiq Tariq , Szczepura Ala
Published: January 2019

Objective

To undertake a comprehensive assessment of the strength of preferences among young people for attributes of emerging technologies for testing and treatment of asymptomatic chlamydia.

Design

Discrete choice experiment (DCE) with sequential mixed methods design. A staged approach to selection of attributes/levels included two literature reviews, focus groups with young people aged 16–24 years (n=21), experts’ review (n=13) and narrative synthesis. Cognitive testing was undertaken to pilot and adapt the initial questionnaire. Online national panel was used for final DCE survey to maximise generalisability. Analysis of questionnaire responses used multinomial logit models and included validity checks.

Setting

England.

Participants

1230 young people aged 16–24 from a national online panel (completion rate 73%).

Outcome measures

ORs for service attributes in relation to reference levels.

Results

The strongest attribute influencing preferences was chlamydia test accuracy (OR 3.24, 95% CI 3.13 to 3.36), followed by time to result (OR 1.81, 95% CI 1.71 to 1.91). Respondents showed a preference for remote chlamydia testing options (self-testing, self-sampling and postal testing) over attendance at a testing location. For accessing treatment following a positive test result, there was a general preference for online (OR 1.21, 95% CI 1.15 to 1.28) versus traditional general practitioner (OR 1.18, 95% CI 1.12 to 1.24) or pharmacy (OR 1.15, 95% CI 1.10 to 1.22) over clinic services. For accessing a healthcare professional and receipt of antibiotics, there was little difference in preferences between options.

Conclusions

Both test accuracy and very short intervals between testing and results were important factors for young people when deciding whether to undergo a routine test for asymptomatic chlamydia, with test accuracy being more important. These findings should assist technology developers, policymakers, commissioners and service providers to optimise technology adoption in service redesign, although use of an online panel may limit generalisability of findings to other populations.
Accelerometer compared with questionnaire measures of physical activity in relation to body size and composition: a large cross-sectional analysis of UK Biobank
Authors: Guo Wenji , Key Timothy J , Reeves Gillian K
Published: January 2019

Objectives

Previous studies of the association between physical activity and adiposity are largely based on physical activity and body mass index (BMI) from questionnaires, which are prone to inaccurate and biased reporting. We assessed the associations of accelerometer-measured and questionnaire-measured physical activity with BMI, waist circumference and body fat per cent measured by bioelectrical impedance and dual-energy X-ray absorptiometry (DXA).

Design

Cross-sectional analysis of UK Biobank participants.

Setting

UK Biobank assessment centres.

Participants

78 947 UK Biobank participants (35 955 men and 42 992 women) aged 40–70 at recruitment, who had physical activity measured by both questionnaire and accelerometer.

Main outcome measures

BMI, waist circumference and body fat per cent measured by bioelectrical impedance.

Results

Greater physical activity was associated with lower adiposity. Women in the top 10th of accelerometer-measured physical activity had a 4.8 (95% CI 4.6 to 5.0) kg/m2lower BMI, 8.1% (95% CI 7.8% to 8.3%) lower body fat per cent and 11.9 (95% CI 11.4 to 12.4) cm lower waist circumference. Women in the top 10th of questionnaire-measured physical activity had a 2.5 (95% CI 2.3 to 2.7) kg/m2lower BMI, 4.3% (95% CI 4.0% to 4.5%) lower body fat per cent and 6.4 (95% CI 5.9 to 6.9) cm lower waist circumference, compared with women in the bottom 10th. The patterns were similar in men and also similar to body fat per cent measured by DXA compared with impedance.

Conclusion

Our findings of approximately twofold stronger associations between physical activity and adiposity with objectively measured than with self-reported physical activity emphasise the need to incorporate objective measures in future studies.
Internet delivery of intensive speech and language therapy for children with cerebral palsy: a pilot randomised controlled trial
Authors: Pennington Lindsay , Stamp Elaine , Smith Johanna , Kelly Helen , Parker Naomi , Stockwell Katy , Aluko Patricia , Othman Mohammad , Brittain Katie , Vale Luke
Published: January 2019

Objectives

To test the feasibility of recruitment, retention, outcome measures and internet delivery of dysarthria therapy for young people with cerebral palsy in a randomised controlled trial.

Design

Mixed methods. Single blind pilot randomised controlled trial, with control offered Skype therapy at end of study. Qualitative study of the acceptability of therapy delivery via Skype.

Setting

Nine speech and language therapy departments in northern England recruited participants to the study. Skype therapy was provided in a university setting.

Participants

Twenty-two children (14 M, 8 F) with dysarthria and cerebral palsy (mean age 8.8 years (SD 3.2)) agreed to take part. Participants were randomised to dysarthria therapy via Skype (n=11) or treatment as usual (n=11).

Interventions

Children received either usual speech therapy from their local therapist for 6 weeks or dysarthria therapy via Skype from a research therapist. Usual therapy sessions varied in frequency, duration and content. Skype dysarthria therapy focused on breath control and phonation to produce clear speech at a steady rate, and comprised three 40 min sessions per week for 6 weeks.

Primary and secondary outcome measures

Feasibility and acceptability of the trial design, intervention and outcome measures.

Results

Departments recruited two to three participants. All participants agreed to random allocation. None withdrew from the study. Recordings of children’s speech were made at all time points and rated by listeners. Families allocated to Skype dysarthria therapy judged internet delivery of the therapy to be acceptable. All families reported that the study design was acceptable. Treatment integrity checks suggested that the phrases practised in one therapy exercise should be reduced in length.

Conclusions

A delayed treatment design, in which dysarthria therapy is offered at the end of the study to families allocated to treatment as usual, is acceptable. A randomised controlled trial of internet delivered dysarthria therapy is feasible.
Alternative service models for delivery of healthcare services in high-income countries: a scoping review of systematic reviews
Authors: Jessup Rebecca L , O’Connor Denise A , Putrik Polina , Rischin Kobi , Nezon Janet , Cyril Sheila , Shepperd Sasha , Buchbinder Rachelle
Published: January 2019

Introduction

Costs associated with the delivery of healthcare services are growing at an unsustainable rate. There is a need for health systems and healthcare providers to consider the economic impacts of the service models they deliver and to determine if alternative models may lead to improved efficiencies without compromising quality of care. The aim of this protocol is to describe a scoping review of the extent, range and nature of available synthesised research on alternative delivery arrangements for health systems relevant to high-income countries published in the last 5 years.

Design

We will perform a scoping review of systematic reviews of trials and economic studies of alternative delivery arrangements for health systems relevant to high-income countries published on ‘Pretty Darn Quick’ (PDQ)-Evidence between 1 January 2012 and 20 September 2017. All English language systematic reviews will be included. The Cochrane Effective Practice and Organisation of Care taxonomy of health system interventions will be used to categorise delivery arrangements according to: how and when care is delivered, where care is provided and changes to the healthcare environment, who provides care and how the healthcare workforce is managed, co-ordination of care and management of care processes and information and communication technology systems. This work is part of a 5-year Partnership Centre for Health System Sustainability aiming to investigate and create interventions to improve health-system-performance sustainability.

Ethics and dissemination

No primary data will be collected, so ethical approval is not required. The study findings will be published and presented at relevant conferences.
Nordic Innovative Trials to Evaluate osteoPorotic Fractures (NITEP) Collaboration: The Nordic DeltaCon Trial protocol—non-operative treatment versus reversed total shoulder arthroplasty in patients 65 years of age and older with a displaced proximal humerus fracture: a prospective, randomised controlled trial
Authors: Launonen Antti P , Fjalestad Tore , Laitinen Minna K , Lähdeoja Tuomas , Ekholm Carl , Wagle Tone , Mattila Ville M
Published: January 2019

Introduction

The proximal humerus fracture (PHF) is one of the most common fractures in the elderly. The majority of PHFs are treated non-operatively, while 15%–33% of patients undergo surgical treatment. Recent randomised controlled trial (RCT) and meta-analyses have shown that there is no difference in outcome between non-operative treatment and locking plate or hemi-arthroplasty. During the past decade, reverse total shoulder arthroplasty (RTSA) has gained popularity in the treatment of PHF, although there is a lack of RCTs comparing RTSA to non-operative treatment.

Methods

This is a prospective, single-blinded, randomised, controlled, multicentre and multinational trial comparing RTSA with non-operative treatment in displaced proximal humeral fractures in patients 65–85 years. The primary outcome in this study is QuickDASH-score measured at 2 years. Secondary outcomes include visual analogue scale for pain, grip strength, Oxford shoulder score, Constant score and the number of reoperations and complications.

The hypothesis of the trial is that operative treatment with RTSA produces better outcome after 2 and 5 years measured with QuickDASH.

Ethics and dissemination

In this protocol, we describe the design, method and management of the Nordic DeltaCon trial. The ethical approval for the trial has been given by the Regional Committee for Medical and Health Research Ethics, Norway. There have been several examples in orthopaedics of innovations that result in failure after medium-term follow-ups . In order to prevent such failures and to increase our knowledge of RSTA, we feel a large-scale study of the effects of the surgery on the outcome that focuses on the complications and reoperations is warranted. After the trial 2-year follow-up, the results will be disseminated in a major orthopaedic publication.

Trial registration number

NCT03531463; Pre-Results.
Protocol for a multicentre randomised controlled parallel-group trial to compare the effectiveness of remotely delivered cognitive-behavioural and graded exercise interventions with usual care alone to lessen the impact of fatigue in inflammatory rheumatic diseases (LIFT)
Authors: Martin Kathryn R , Bachmair Eva-Maria , Aucott Lorna , Dures Emma , Emsley Richard , Gray Stuart R , Hewlett Sarah , Kumar Vinod , Lovell Karina , Macfarlane Gary J , MacLennan Graeme , McNamee Paul , Norrie John , Paul Lorna , Ralston Stuart , Siebert Stefan , Wearden Alison , White Peter D , Basu Neil
Published: January 2019

Introduction

Fatigue remains pervasive, disabling and challenging to manage across all inflammatory rheumatic diseases (IRDs). Non-pharmacological interventions, specifically cognitive-behavioural approaches (CBAs) and graded exercise programmes designed to support and increase exercise, are valuable treatments which help patients with IRD to manage their fatigue. Yet, healthcare systems have encountered substantial barriers to the implementation of these therapeutic options. Lessening the Impact of Fatigue in Inflammatory Rheumatic Diseases: a Randomised Trial (LIFT) is designed to give insights into the effectiveness of a remotely delivered standardised intervention for a range of patients with IRD. It will also enable the exploration of putative moderating factors which may allow for the future triage of patients and to investigate the precise mediators of treatment effect in IRD-related fatigue.

Methods and analysis

LIFT is a pragmatic, multicentre, three-arm randomised, controlled trial, which will test whether adapted CBA and personalised exercise programme interventions can individually reduce the impact and severity of fatigue. This will be conducted with up to 375 eligible patients diagnosed with IRD and interventions will be delivered by rheumatology healthcare professionals, using the telephone or internet-based audio/video calls.

Ethics approval and dissemination

Ethical approval has been granted by Wales REC 7 (17/WA/0065). Results of this study will be disseminated through presentation at scientific conferences and in scientific journal. A lay summary of the results will be sent to participants.

Trial registration number

NCT03248518; Pre-results.
STING signalling protects against chronic pancreatitis by modulating Th17 response
Authors: Zhao Qinglan , Manohar Murli , Wei Yi , Pandol Stephen J , Habtezion Aida
Published: January 2019

Objective

Chronic pancreatitis (CP) is an inflammatory disease with progressive fibrosis leading to exocrine and endocrine dysfunction. Currently, there are no approved effective therapies for CP. Stimulator of interferon genes (STING) signalling is a key innate immune sensor of DNA. In this study, we evaluated the role of STING signalling in CP.

Design

We used an experimental model of CP to test the effect of STING signalling in STING wild-type and knockout mice as well as bone marrow chimaeras (BMCs). STING was activated using a pharmacological agent. Since we found changes in Th17 cells, we used neutralising and control antibodies to determine the role of IL-17A. The effect of STING signalling was further explored in IL-17A generation and we examined the effect of IL-17A on pancreatic stellate cells (PSCs). Human pancreas from patients with CP and without CP were also stained for IL-17A.

Results

STING activation decreased CP-associated pancreatic inflammation and fibrosis, whereas absence of STING led to worsening of the disease. BMCs showed that leucocytes play an important role in STING signalling–mediated amelioration of experimental CP. STING deletion was associated with increased Th17 cell infiltration in the pancreas, whereas STING agonist limited this Th17 response. Importantly, anti-IL-17A antibody treatment mitigated the severity of CP in the absence of STING signalling. STING deficiency promoted Th17 polarisation and PSCs express functional IL-17 receptor by upregulating fibrosis genes. Compared with tumour margins, pancreas from patients with CP had significant increase in IL-17A+cells.

Conclusion

Unlike acute pancreatitis, STING activation is protective in CP. STING signalling is important in regulating adaptive immune responses by diminishing generation of IL-17A during CP and presents a novel therapeutic target for CP.
Hospital-based quality improvement interventions for patients with heart failure: a systematic review
Authors: Agarwal Anubha , Bahiru Ehete , Yoo Sang Gune Kyle , Berendsen Mark A , Harikrishnan Sivadasanpillai , Hernandez Adrian F , Prabhakaran Dorairaj , Huffman Mark D
Published: January 2019

Objective

To estimate the direction and magnitude of effect and quality of evidence for hospital-based heart failure (HF) quality improvement interventions on process of care measures and clinical outcomes among patients with acute HF.

Review methods

We performed a structured search to identify relevant randomised trials evaluating the effect of in-hospital quality improvement interventions for patients hospitalised with HF through February 2017. Studies were independently reviewed in duplicate for key characteristics, outcomes were summarised and a qualitative synthesis was performed due to substantial heterogeneity.

Results

From 3615 records, 14 randomised controlled trials were identified for inclusion with multifaceted interventions. There was a trend towards higher in-hospital use of ACE inhibitors (ACE-I; 57.9%vs40.0%) and beta-blockers (BBs; 46.7%vs10.2%) in the intervention than the comparator in one trial (n=429 participants). Five trials (n=78 727 participants) demonstrated no effect of the intervention on use of ACE-I or angiotensin receptor blocker at discharge. Three trials (n=89 660 participants) reported no effect on use of BB at discharge. Two trials (n=419 participants) demonstrated a trend towards lower hospital readmission up to 90 days after discharge. There was no consistent effect of the quality improvement intervention on 30-day all-cause mortality, hospital length of stay and patient-level health-related quality of life.

Conclusions

Randomised trials of hospital-based HF quality improvement interventions do not show a consistent effect on most process of care measures and clinical outcomes. The overall quality of evidence for the prespecified primary and key secondary outcomes was very low to moderate, suggesting that future research will likely influence these estimates.

Trial registration number

CRD42016049545.
International comparison of acute myocardial infarction care and outcomes using quality indicators
Authors: Zusman Oren , Bebb Owen , Hall Marlous , Dondo Tatendashe Bernadette , Timmis Adam , Schiele Francois , Fox Keith AA , Kornowski Ran , Gale Chris P , Iakobishvili Zaza
Published: January 2019

Objective

To compare temporal changes in European Society of Cardiology (ESC) acute myocardial infarction (AMI) quality indicator (QI) attainment in the UK and Israel.

Methods

Data cross-walking using information from the Myocardial Ischaemia National Audit Project and the Acute Coronary Syndrome in Israel Survey for matching 2-month periods in 2006, 2010 and 2013 was used to compare country-specific attainment of 14 ESC AMI QIs.

Results

Patients in the UK (n=17 068) compared with Israel (n=5647) were older, more likely to be women, and had less diabetes, dyslipidaemia and heart failure. Baseline ischaemic risk was lower in Israel than the UK (Global Registry of Acute Coronary Events (GRACE) risk, 110.5 vs 121.0). Overall, rates of coronary angiography (87.6% vs 64.8%) and percutaneous coronary intervention (70.3% vs 41.0%) were higher in Israel compared with the UK. Composite QI performance increased more in the UK (1.0%–86.0%) than Israel (70.2%–78.0%). Mortality rates at 30 days declined in each country, with lower rates in Israel in 2013 (4.2% vs 7.6%). Composite QI adherence adjusted for GRACE risk score was inversely associated with 30-day mortality (OR 0.95; CI 0.95 to 0.97, p<0.001).

Conclusions

International comparisons of guideline recommended AMI care and outcomes can be quantified using the ESC AMI QIs. International implementation of the ESC AMI QIs may reveal country-specific opportunities for improved healthcare delivery.
Atrial septal defect closure in adulthood is associated with normal survival in the mid to longer term
Authors: Brida Margarita , Diller Gerhard-Paul , Kempny Aleksander , Drakopoulou Maria , Shore Darryl , A Gatzoulis Michael , Uebing Anselm
Published: January 2019

Objective

The prognostic benefit of atrial septal defect (ASD) closure in adulthood, particularly in advanced age, remains uncertain. The aim of our study was to examine the impact of ASD closure in a contemporary adult cohort on mid to longer term survival as compared with expected survival in the general population.

Methods

We study herewith all consecutive patients (≥16 years of age) who underwent ASD closure, catheter or surgical, at our tertiary centre between 2001 and 2012. Furthermore, we compare survival of our ASD closure cohort with expected survival in age and gender-matched general population and standardised mortality ratios (SMR) were calculated.

Results

A total of 608 patients (mean age 45.4±16.7 years) underwent ASD closure (catheter 433(71.2%), surgical 175(28.8%)). There was no 30-day mortality and periprocedural complications were low (n=40, 6.6%). During a median follow-up of 6.7 (IQR 4.2–9.3) years 16 (2.6%) patients died; survival was similar to the general population (p=0.80) including patients >40 or >60 years of age at ASD closure (p=0.58 and p=0.64, respectively). There was no survival difference between gender (male: SMR 0.93; 95% CI 0.52 to 1.64, p=0.76; female: SMR 0.99; 95% CI 0.58 to 1.66, p=0.95) or mode of closure compared with general population (catheter: SMR 1.03; 95% CI 0.68 to 1.55, p=0.89; surgical: SMR 0.65; 95% CI 0.22 to 1.88, p=0.38).

Conclusion

Perioperative mortality and morbidity in a large contemporary adult cohort undergoing ASD closure, catheter or surgical, is extremely low. Mid to longer term survival is excellent irrespective of age, gender and mode of closure, and similar to matched general population.
Indicators for estimating trends in alcohol-related assault: evaluation using police data from Queensland, Australia
Authors: Nepal Smriti , Kypri Kypros , Attia John , Chikritzhs Tanya , Miller Peter G
Published: January 2019

Monitoring levels of alcohol-related harm in populations requires indicators that are robust to extraneous influence. We investigated the validity of an indicator for police-attributed alcohol-related assault. We summarized offence records from Queensland Police, investigated patterns of missing data, and considered the utility of a surrogate for alcohol-related assault. Of 242 107 assaults from 2004–2014, in 35% of cases the drug used by the offender was recorded as ‘unknown’. Under various assumptions about non-random missingness the proportion of assaults judged to be alcohol-related varied from 30%–65%. We found a sharp increase in missing data from 2007 suggesting the downward trend from that point is artefactual. Conversely, we found a stable and increasing trend using a time-based surrogate. The volume of missing data and other limitations preclude valid estimation of trends using the police indicator, and demonstrate how misleading results can be produced. Our analysis supports the use of an empirically-based surrogate indicator.
The annual cannabis holiday and fatal traffic crashes
Authors: Harper Sam , Palayew Adam
Published: January 2019

Background

Cannabis use has been linked to impaired driving and fatal accidents. Prior evidence suggests the potential for population-wide effects of the annual cannabis celebration on April 20th (‘4/20’), but evidence to date is limited.

Methods

We used data from the Fatal Analysis Reporting System for the years 1975–2016 to estimate the impact of ‘4/20’ on drivers involved in fatal traffic crashes occurring between 16:20 and 23:59 hours in the USA. We compared the effects of 4/20 with those for other major holidays, and evaluated whether the impact of ‘4/20’ had changed in recent years.

Results

Between 1992 and 2016, ‘4/20’ was associated with an increase in the number of drivers involved in fatal crashes (IRR 1.12, 95% CI 0.97 to 1.28) relative to control days 1 week before and after, but not when compared with control days 1 and 2 weeks before and after (IRR 1.05, 95% CI 0.92 to 1.28) or all other days of the year (IRR 0.98, 95% CI 0.88 to 1.10). Across all years we found little evidence to distinguish excess drivers involved in fatal crashes on 4/20 from routine daily variations.

Conclusions

There is little evidence to suggest population-wide effects of the annual cannabis holiday on the number of drivers involved in fatal traffic crashes.
Macroeconomic fluctuations, changes in lifestyles and mortality from diabetes: a quasiexperimental study
Authors: Regidor Enrique , Albaladejo Romana , Mateo Alberto , de la Fuente Luis , Barrio Gregorio , Ortega Paloma
Published: January 2019

Background

To evaluate trends in diabetes-related health behaviours and mortality from diabetes and other chronic diseases in the Spanish population before, during and after the 2008 economic crisis.

Methods

Annual population measurements were obtained from national surveys and administrative registries for 2004–2016. Using segmented regression analysis, we calculated the annual percentage change (APC) in 2004–2007, 2008–2010, 2011–2013 and 2014–2016 in risk behaviours (smoking, alcohol consumption, obesity and meals away from home), in healthy behaviours (fruit and vegetable intake and physical activity) and in mortality rates from diabetes, cardiovascular disease and cancer.

Results

In general, during the economic crisis (2008–2013), the Spanish population reduced risk behaviours and improved healthy behaviours as compared with the trend observed before and afterwards. Diabetes mortality decreased more during the crisis than before or afterwards. The APC in each time interval was −3.3, –3.7, −4.4 and −2.6 in all-age mortality and −2.9, –5.2, −6.7 and −1.3 in premature mortality (less than 75 years). Only in older people (≥75 years) diabetes mortality showed similar decline before and during the crisis. Mortality from cardiovascular disease also declined more during the crisis, except for all-age mortality and older people in the second part of the crisis, whereas the downward trend in cancer mortality was smaller during the crisis years.

Conclusions

During the 6 years of the economic crisis in Spain, the favourable changes in health behaviours were accompanied by an important reduction in diabetes mortality in the population.
Features, genetics and their correlation in Jalili syndrome: a systematic review
Authors: Daneshmandpour Yousef , Darvish Hossein , Pashazadeh Fariba , Emamalizadeh Babak
Published: January 2019

Jalili syndrome is a rare genetic disorder first identified by Jalili in Gaza. Amelogenesis imperfecta and cone-rode dystrophy are simultaneously seen in Jalili syndrome patients as the main and primary manifestations. Molecular analysis has revealed that theCNNM4gene is responsible for this rare syndrome. Jalili syndrome has been observed in many countries around the world, especially in the Middle East and North Africa. In the current scoping systematic review we searched electronic databases to find studies related to Jalili syndrome. In this review we summarise the reported clinical symptoms,CNNM4gene and protein structure,CNNM4mutations, attempts to reach a genotype-phenotype correlation, the functional role ofCNNM4mutations, and epidemiological aspects of Jalili syndrome. In addition, we have analysed the reported mutations in mutation effect prediction databases in order to gain a better understanding of the mutation’s outcomes.
Multiple cerebral infarcts: a rare complication of neurosarcoidosis
Authors: Harris Matthew John , Cossburn Mark Daniel , Pengas George
Published: January 2019

A 52-year-old man experienced a relapse of neurosarcoidosis, characterised by obstructive hydrocephalus and multiple posterior circulation infarcts. He was taking methotrexate, but his prednisolone was being weaned because of adverse effects. Stroke is rare in neurosarcoidosis and typically relates to granulomatous inflammation with a predilection for the perforator arteries. Sarcoidosis generally responds well to corticosteroids; however, patients with leptomeningeal involvement usually require additional immunosuppression as relapses can occur on weaning of corticosteroids. It is worth considering tumour necrosis factor-α antagonists for cases that progress despite first-line therapy.
Anatomical study of the innervation of posterior knee joint capsule: implication for image-guided intervention
Authors: Tran John , Peng Philip W H , Gofeld Michael , Chan Vincent , Agur Anne M R
Published: January 2019

Background and objectives

Peripheral nerve block is an important component of the multimodal analgesia for total knee arthroplasty. Novel interventional techniques of ultrasound-guided nerve block supplying the posterior knee joint capsule require knowledge of the innervation of the posterior capsule. The objectives of this cadaveric study were to determine the course, frequency, and distribution of the articular branches innervating the posterior knee joint capsule and their relationships to anatomical landmarks.

Methods

Fifteen lightly embalmed specimens were meticulously dissected. The origin of articular branches was identified, their frequency recorded, and the course documented in relation to anatomical landmarks. The capsular distribution of articular branches was documented and a frequency map generated.

Results

In all specimens, articular branches from the posterior division of the obturator and tibial nerves were found to supply the posterior capsule. Additionally, articular branches from common fibular nerve and sciatic nerve were found in eight (53%) and three (20%) specimens, respectively. The capsular distribution of tibial nerve spanned the entire posterior capsule. The posterior division of obturator nerve supplied the superomedial aspect of the posterior capsule overlapping with the tibial nerve. The superolateral aspect of the posterior capsule was innervated by the tibial nerve and, when present, the common fibular/sciatic nerves.

Conclusions

Frequency map of the course and distribution of the articular branches and their relationship to anatomical landmarks form an anatomical basis for peripheral nerve block approaches that provide analgesia to the posterior knee joint capsule.
Association between perioperative statin use and postoperative pain after total knee arthroplasty
Authors: Oh Tak Kyu , Chang Chong Bum , Shin Hyun-Jung , Han Sunghee , Do Sang-Hwan , Lee Hei-jin , Hwang Jung-Won
Published: January 2019

Background and objectives

Data is insufficient to determine whether perioperative statin use increases or decreases postoperative pain. This study aimed to investigate the association between perioperative statin use and pain outcomes after total knee arthroplasty performed under spinal anesthesia.

Methods

This is a retrospective, observational study based on medical records from a tertiary hospital between January 2005 and October 2017. Medical records of patients who underwent elective total knee arthroplasty under spinal anesthesia as inpatients were analyzed. Pain outcomes were compared through postoperative day (POD) 3 in patients who were taking statins perioperatively versus patients who were not taking statins.

Results

A total of 1088 propensity-matched participants were included in the final analysis (544 patients in the statin group and 544 patients in the non-statin group). The total morphine equivalent consumption through POD 3 was higher in the statin group than in the non-statin group (mean (SD), statin group: 525.4 (119.7) vs non-statin group: 495.3 (115.3), 95% CI of the difference: 15.9 to 44.4, p<0.001). In the linear regression analysis, the total morphine equivalent consumption through POD 3 was 30.14 mg higher in the statin group compared with the non-statin group (95% CI 15.93 to 44.35; p<0.001).

Conclusions

Perioperative statin use is associated with a significant increase in postoperative opioid consumption after total knee arthroplasty performed under spinal anesthesia; however, this increase was so marginal that its clinical importance remains controversial.
How has the introduction of point-of-sale legislation affected the presence and visibility of tobacco retailing in Scotland? A longitudinal study
Authors: Pearce Jamie , Cherrie Mark , Best Catherine , Eadie Douglas , Stead Martine , Amos Amanda , Currie Dorothy , Ozakinci Gozde , MacGregor Andy , Haw Sally
Published: January 2019

Background

Reducing the local availability of tobacco is identified as the ‘next frontier’ in tobacco control. This paper examines the roles of tobacco retail outlet density and tobacco visibility in changing exposure to tobacco retailing before and after the introduction of point-of-sale (POS) legislation in Scotland.

Methods

National tobacco retailer register data were analysed to examine time trends in tobacco retailer density (2012–2017). Results were stratified by local authority, neighbourhood deprivation and urbanity. Next, an annual retail audit using a POS tobacco visibility tool assessed changes in total product visibility in all retail outlets in four study communities between 2013 and 2017. A longitudinal survey (2013–2017) of 5527 adolescents aged 12–17 in the four study communities enabled the calculation of residential and journey-to-school measures of tobacco retailer exposure. Trends were stratified by deprivation, urbanity and socioeconomic status.

Results

Retail provision of tobacco declined following the introduction of the POS legislation in 2013. However, there were strong geographic differences; nationally, one-fifth of local authorities have increased provision since 2015. In the four study communities, tobacco retail provision was generally stable over the study period. Although product visibility of tobacco products reduced for adolescents there was growing socioeconomic disparity in the density of tobacco retailers and the visibility of tobacco storage.

Conclusions

The POS ban reduced exposure to tobacco products in communities across Scotland. However, tobacco products remain widely available, and there is growing socioeconomic disparity in the availability and visibility of tobacco.
Awareness and interest in IQOS heated tobacco products among youth in Canada, England and the USA
Authors: Czoli Christine D , White Christine M , Reid Jessica L , OConnor Richard J , Hammond David
Published: January 2019

Introduction

Heated tobacco products (HTPs), such as IQOS, have been introduced in a growing number of international markets. However, little is known about perceptions of HTP products among youth.

Methods

Data are from wave 1 of the International Tobacco Control Youth Tobacco and E-cigarette Survey (2017), a web-based cohort survey of people aged 16–19 years from Canada, England and the USA. Respondents (n=12 064) were shown an image of IQOS and asked about their awareness, interest in trying and susceptibility to trying the product. Youth awareness, interest in trying and susceptibility to trying IQOS were analysed using descriptive statistics, and logistic regression models were used to examine correlates of these outcomes.

Results

Overall, 7.0% of youth reported awareness of IQOS (England=5.6%, Canada=6.4% and USA=9.1%) and 38.6% expressed interest in trying the product (England=41.8%, Canada=33.0% and USA=40.9%). Within each country, all key outcomes varied by smoking status: greater proportions of youth who were currently smoking or had a history of smoking reported being aware of, interested in trying and susceptible to trying IQOS. Interest and susceptibility to trying IQOS were associated with male sex, current tobacco use and current e-cigarette use. Across all countries, susceptibility to trying IQOS (25.1%) was higher than for tobacco cigarettes (19.3%), but lower than for e-cigarettes (29.1%).

Conclusions

Awareness of HTPs, such as IQOS, is emerging among youth in Canada, England and the USA. Interest in trying these products is very high among smokers, but also present among non-smokers.
Estimating the long-run relationship between state cigarette taxes and county life expectancy
Authors: Baum Aaron , Aguilar-Gomez Sandra , Lightwood James , Bruzelius Emilie , Glantz Stanton A , Basu Sanjay
Published: January 2019

Introduction

While a large body of literature suggests that tobacco control legislation—including fiscal measures such as excise taxes—effectively reduces tobacco smoking, the long-run (10+ years) relationship between cigarettes excise taxes and life expectancy has not been directly evaluated. Here, we test the hypothesis that increases in state cigarette excise taxes are positively associated with long-run increases in population-level life expectancy.

Methods

We studied age-standardised life expectancy among all US counties from 1996 to 2012 by sex, in relation to state cigarette excise tax rates by year, controlling for other demographic, socioeconomic and county-specific features. We used an error-correction model to assess the long-run relationship between taxes and life expectancy. We additionally examine whether the relationship between cigarette taxes and life expectancy was mediated by changes to county smoking prevalence and varied by the sex, income and rural/urban composition of a county.

Results

For every one-dollar increase in cigarette tax per pack (in 2016 dollars), county life expectancy increased by 1 year (95% CI 0.60 to 1.40 years) over the long run, with the first 6-month increase in life expectancy taking 10 years to materialise. The association was mediated by changes in smoking prevalence and the magnitude of the association steadily increased as county income decreased.

Conclusions

Results suggest that increasing cigarette excise tax rates translates to consequential population-level improvements in life expectancy, with larger effects in low-income counties.
Alzheimer’s disease‐like pathological lesions in an aged bottlenose dolphin (Tursiops truncatus)
Authors: Stylianaki Ioanna , Komnenou Anastasia T , Posantzis Dimitrios , Nikolaou Konstantina , Papaioannou Nikolaos
Published: January 2019

Alzheimer’s disease (AD) is the most common neurodegenerative disorder causing dementia. AD‐like pathological lesions have been described in human and in several other animal species. In this study, we report AD‐like pathological changes observed in the brain of a 40‐year‐old dolphin (Tursiups truncatus), boosting dolphins as a promising natural model of AD. The amyloid β (Aβ) was detected immunohistochemically as intraneuronal depositions, parenchymal accumulations and limited deposits in the wall of meningeal and parenchymal vessels. Also, neuronal tau positive labelling was noticed. This is the first report to show ΑpoE immunopositive reaction in dolphins. Glial fibrillary acidic protein positive astrocytes were also observed. Our findings are indicative of early AD or mild cognitive impairment pathology. So, they strongly reinforce the statement that dolphins could be a natural animal model of AD due to their lifespan, brain lesions and Αβ homology with the human peptide.