bluuebunny/crossref_metadata_2025 huggingface dataset:
Can a tool developed for industry be used to assess fatigue risk in medical rotas? A pilot study of foundation doctors’ rotas in a tertiary centre
Authors: Cumber Elspeth , Greig Paul Robert
Published: February 2019

Objectives

To determine the feasibility and ease of using a pre-existing health and safety executive fatigue risk calculator to assess doctors’ rotas.

Design

Observational.

Setting

A large tertiary-referral teaching hospital in the UK.

Participants

95 anonymised foundation years 1 and 2 rotas in General Medicine, General Surgery and Emergency Medicine covering a 4-month period. All rotas provided by rota coordinators were included and assessed.

Interventions

Rotas were assessed for two indices: relative risk of fatigue-related errors compared with a ‘2-day, two-night, four-off’ shift pattern and percentage chance of a high score on a standardised sleepiness scale.

Primary and secondary outcome measures

Fatigue index (percentage chance of a high score on a standardised sleepiness scale) and risk index (relative risk of fatigue-related errors compared with a ‘2-day, two-night, four-off’ shift pattern) of all shifts on all rotas.

Results

Nearly half of all shifts demonstrated increased risk of fatigue-related errors and increased probability of high levels of sleepiness. There was significant interspeciality variation in both indices. These results are based on rotas as opposed to ‘work as done’ and are therefore likely to slightly universally underestimate actual fatigue risks.

Conclusions

This preliminary study demonstrates that this tool can be used to compare rotas and guide rota design to minimise risk wherever possible. The calculator guidance clearly states there is no ‘ideal risk’ but that values should be minimised, and a maximum fatigue risk agreed which is deemed acceptable given the nature of work undertaken. This study is intended to demonstrate that fatigue can and should be considered during rota design. We do not suggest that it is used to hold either individuals or organisations to account as there is no evidence for it being used in this way. Further work should assess the practicality of designing medical rotas using this tool to minimise fatigue risk.
PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial
Authors: Woodhouse Charlotte Alexandra , Patel Vishal C , Goldenberg Simon , Sanchez-Fueyo Alberto , China Louise , O’Brien Alastair , Flach Clare , Douiri Abdel , Shawcross Debbie
Published: February 2019

Introduction

Patients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune dysfunction which predisposes to infection, and development of complications such as bleeding, sepsis and hepatic encephalopathy. This feasibility study aims to assess the safety of administering faecal microbiota transplantion to patients with cirrhosis and explore the effect of the intervention on their prognosis by achieving restoration of a healthy gut microbiome.

Methods and analysis

A PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation is a single-centre, randomised, single-blinded, placebo-controlled study evaluating faecal microbiota transplantation (FMT) against placebo. Patients with advanced but stable cirrhosis with a Model for End-Stage Liver Disease score between 10 and 16 will be recruited. Twenty-four patients will be randomised to FMT plus standard of care (as per our institutional practice) and eight patients to placebo in a ratio of 3:1. Patients will be evaluated at baseline before the study intervention is administered and at 7, 30 and 90 days post-intervention to assess safety and adverse events. FMT/placebo will be administered into the jejunum within 7 days of baseline. The primary outcome measure will be safety and feasibility as assessed by recruitment rates, tolerability and safety of FMT treatment. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient occurred on 23 May 2018.

Ethics and dissemination

Research Ethics approval was given by the London South East Research Ethics committee (ref 17/LO/2081).

Trial registration number

NCT02862249 and EudraCT 2017-003629-13.
Performance of biological mesh materials in abdominal wall reconstruction: study protocol for a randomised controlled trial
Authors: Carver David A , Kirkpatrick Andrew W , Eberle Tammy L , Ball Chad G
Published: February 2019

Introduction

Abdominal wall hernias are a common source of morbidity and mortality. The use of biological mesh has become an important adjunct in successful abdominal wall reconstruction. There are a variety of biological mesh products available; however, there is limited evidence supporting the use of one type over another. This study aims to compare the performance (eg, the rate of hernia recurrence) of either a crosslinked biological mesh product or a non-crosslinked product in patients undergoing abdominal wall reconstruction.

Methods and analysis

This is a single-centre, dual arm randomised controlled trial. Patients requiring abdominal wall reconstruction will be assessed for eligibility. Eligible patients will then undergo an informed consent process following by randomisation to either (1) crosslinked porcine dermis mesh (Permacol); or (2) non-crosslinked porcine dermis mesh (Strattice). These groups will be compared for the rate of hernia recurrence at 1 and 2 years as well as the rate of postoperative complications (eg, surgical site infections).

Ethics and dissemination

This study has been approved by the institution’s research ethics board and registered with clinicaltrials.gov. All eligible participants will provide informed consent prior to randomization. The results of this study may help guide the choice of biologic mesh for this population. The results of this study will be published in peer-reviewed journals as well as national and international conferences.

Trial registration number

NCT02703662.
Impact of repeated hospital accreditation surveys on quality and reliability, an 8-year interrupted time series analysis
Authors: Devkaran Subashnie , O’Farrell Patrick N , Ellahham Samer , Arcangel Randy
Published: February 2019

Objective

To evaluate whether hospital re-accreditation improves quality, patient safety and reliability over three accreditation cycles by testing the accreditation life cycle model on quality measures.

Design

The validity of the life cycle model was tested by calibrating interrupted time series (ITS) regression equations for 27 quality measures. The change in the variation of quality over the three accreditation cycles was evaluated using the Levene’s test.

Setting

A 650-bed tertiary academic hospital in Abu Dhabi, UAE.

Participants

Each month (over 96 months), a simple random sample of 10% of patient records was selected and audited resulting in a total of 388 800 observations from 14 500 records.

Intervention(s)

The impact of hospital accreditation on the 27 quality measures was observed for 96 months, 1-year preaccreditation (2007) and 3 years postaccreditation for each of the three accreditation cycles (2008, 2011 and 2014).

Main outcome measure(s)

The life cycle model was evaluated by aggregating the data for 27 quality measures to produce a composite score (YC) and to fit an ITS regression equation to the unweighted monthly mean of the series.

Results

The results provide some evidence for the validity of the four phases of the life cycle namely, the initiation phase, the presurvey phase, the postaccreditation slump and the stagnation phase. Furthermore, the life cycle model explains 87% of the variation in quality compliance measures (R2=0.87). The best-fit ITS model contains two significant variables (β1and β3) (p≤0.001). The Levene’s test (p≤0.05) demonstrated a significant reduction in variation of the quality measures (YC) with subsequent accreditation cycles.

Conclusion

The study demonstrates that accreditation has the capacity to sustain improvements over the accreditation cycle. The significant reduction in the variation of the quality measures (YC) with subsequent accreditation cycles indicates that accreditation supports the goal of high reliability.
Quality of reporting of outcomes in trials of therapeutic interventions for pressure ulcers in adults: a protocol for a systematic survey
Authors: Miranda Jessica Steffany , Abbade Luciana Patricia Fernandes , Deonizio Arthur Pollo , Abbade Joelcio Francisco , Mbuagbaw Lawrence , Thabane Lehana
Published: February 2019

Pressure ulcers (PUs) have a high incidence, especially in hospital units. Randomised clinical trials (RCTs) of therapeutic interventions for PU should include a clear description of the outcomes and results to enhance transparency and replicability.

Objectives

The primary objective of this study is to assess the completeness of the descriptions of the outcomes of therapeutic interventions in RCTs in adult patients with PU. The secondary objectives are to evaluate the types of reported primary outcomes, measurement methods or tools used to evaluate the outcomes and the results of reported outcomes.

Methods

We will conduct a systematic survey of RCTs published from January 2006 to April 2018. The selection process of the studies will be done in two stages of screening: title and abstract, and full text revision, always by two researchers independently. The completeness of the outcome will be assessed according to five criteria: domain (outcome title), specific measurement or technique/instrument used, specific metric or format of the outcome data that will be used for analysis, method of aggregation (how data from each group will be summarised) and time-points that will be used for analysis. The quality of the results of the outcome will be classified as either complete, incomplete or unreported. We will conduct a descriptive analysis of the number, type and degrees of outcome specification in the included RCTs. The frequency of categories in each domain of the outcomes will also be reported. The median and IQR will be estimated for each element of the specified outcome (out of five).

Ethics and dissemination

This will be the first systematic assessment of the outcomes of therapeutic interventions used for pressure ulcers. After completion, this review will be submitted to a peer-reviewed journals.
Therapist-guided and parent-guided internet-delivered behaviour therapy for paediatric Tourette’s disorder: a pilot randomised controlled trial with long-term follow-up
Authors: Andrén Per , Aspvall Kristina , Fernández de la Cruz Lorena , Wiktor Paulina , Romano Sofia , Andersson Erik , Murphy Tara , Isomura Kayoko , Serlachius Eva , Mataix-Cols David
Published: February 2019

Objective

Behaviour therapy (BT) for Tourette’s disorder (TD) and persistent (chronic) motor or vocal tic disorder (PTD) is rarely available. We evaluated the feasibility of adapting two existing BT protocols for TD/PTD (habit reversal training (HRT) and exposure and response prevention (ERP)) into a therapist-guided and parent-guided online self-help format.

Design

A pilot, single-blind, parallel group randomised controlled trial.

Setting

A specialist outpatient clinic in Sweden.

Participants

Twenty-three young people with TD/PTD, aged 8–16.

Interventions

Two 10-week therapist-guided and parent-guided internet-delivered programmes (called BIP TIC HRT and BIP TIC ERP).

Outcome

The primary outcome measure was the Yale Global Tic Severity Scale. Blinded evaluators rated symptoms at baseline, post-treatment and 3-month follow-up (primary endpoint). All participants were naturalistically followed up to 12 months after treatment.

Results

Patients and parents rated the interventions as highly acceptable, credible and satisfactory. While both interventions resulted in reduced tic-related impairment, parent-rated tic severity and improved quality of life, only BIP TIC ERP resulted in a significant improvement on the primary outcome measure. Within-group effect sizes and responder rates were, respectively:d=1.12 and 75% for BIP TIC ERP, andd=0.50 and 55% for BIP TIC HRT. The therapeutic gains were maintained up to 12 months after the end of the treatment. Adverse events were rare in both groups. The average therapist support time was around 25 min per participant per week.

Conclusions

Internet-delivered BT has the potential to greatly increase access to evidence-based treatment for young people with TD/PTD. Further evaluation of the efficacy and cost-effectiveness of this treatment modality is warranted.

Trial registration number

NCT02864589; Pre-results.
Burden of non-accidental mortality attributable to ambient temperatures: a time series study in a high plateau area of southwest China
Authors: Deng Changyu , Ding Zan , Li Liujiu , Wang Yanfang , Guo Pi , Yang Shaoyi , Liu Ju , Wang Yue , Zhang Qingying
Published: February 2019

Objective

To examine the total non-accidental mortality burden attributable to ambient temperatures and assess the effect modification of the burden by specific causes of death and individual characteristics in a high plateau area in southwest China.

Methods

Using daily mortality and meteorological data from 2009 to 2016, we applied a quasi-Poisson model combined with a distributed lag non-linear model to estimate the temperature–mortality association with the assessment of attributable fraction and number. We calculated attributable fractions and deaths with 95% empirical CIs (eCIs), that were due to cold and heat, defined as temperatures below and above the median temperature, and for mild and extreme temperatures, defined by cut-offs at the 2.5th and 97.5th temperature percentiles.

Results

We analysed 89 467 non-accidental deaths; 4131 were attributable to overall temperatures, with an attributable fraction of 4.75% (95% eCI 2.33% to 6.79%). Most of the mortality burden was caused by cold (4.08%; 0.86% to 7.12%), whereas the burden due to heat was low and non-significant (0.67%; −2.44% to 3.64%). Extreme cold (1.17%; 0.58% to 1.69%) was responsible for 24.6% (ie, 1.17% divided by 4.75%) of the total death burden. In the stratification analyses, attributable risk due to cold was higher for cardiovascular than respiratory disease (6.18% vs 3.50%). We found a trend of risk of increased death due to ambient temperatures with increasing age, with attributable fractions of 1.83%, 2.27% and 6.87% for age ≤64, 65–74 and ≥75 years old, respectively. The cold-related burden was slightly greater for females, farmers, ethnic minorities and non-married individuals than their corresponding categories.

Conclusions

Most of the burden of death was attributable to cold, and specific causes and individual characteristics might modify the mortality burden attributable to ambient temperatures. The results may help make preventive measures to confront climate change for susceptible population in this region.
Breastfeeding and behavioural problems: Propensity score matching with a national cohort of infants in Chile
Authors: Girard Lisa-Christine , Farkas Chamarrita
Published: February 2019

Importance

Potential effects of breast feeding on children’s behaviour remains an elusive debate given inherent methodological challenges. Propensity score matching affords benefits by ensuring greater equivalence on observable social and health determinants, helping to reduce bias between groups.

Objectives

We examined whether the duration of breast feeding had an impact on children’s externalising and internalising behaviours.

Study design

A cohort study (Encuesta Longitudinal de la Primera Infancia cohort) that included 3037 Chilean families who were enrolled in 2010. Follow-up data was collected in 2012.

Setting

General community.

Participants

Population-based sample. Eligibility criteria: children born full-term with complete data on matching variables. Matching variables included: healthcare system as a proxy of income, presence of a partner/spouse in the household, maternal age, educational level, IQ, working status, type of work, diagnosis of prenatal depression by a healthcare professional, smoking during pregnancy, delivery type, child sex, weight at birth, incubation following delivery, and child age.

Exposure

Duration of breast feeding.

Main outcomes and measures

Externalising and internalising problems assessed using the Child Behaviour Checklist.

Results

Matched results revealed benefits of any breast feeding, up to 6 months, on emotional reactivity and somatic complaints (mean difference of −1.00, 95% CI, −1.84 to −0.16 and −1.02, 95% CI, −1.76 to −0.28, respectively). Children breast fed between 7 and 12 months also had reduced scores on emotional reactivity, in addition to attention problems (mean difference of −0.86, 95% CI, −1.66 to −0.06 and −0.50, 95% CI, −0.93 to −0.07, respectively). No benefits were observed for children breast fed 13 months or more.

Conclusion

Reduced internalising difficulties and inattention were found in children breast fed up to a year, suggesting that breast feeding may have beneficial impacts on these areas of development. The magnitude of effect was modest. Extended durations of breast feeding did not appear to offer any benefits.
Medical management of acute upper respiratory infections in an urban primary care out-of-hours facility: cross-sectional study of patient presentations and expectations
Authors: O’Connor Raymond , O’Doherty Jane , O’Regan Andrew , O’Neill Aoife , McMahon Claire , Dunne Colum P
Published: February 2019

Objectives

The purpose of this study was to examine the expectations of patients attending an urban primary care out-of-hours (OOH) facility with acute upper respiratory tract infection (acute URTI) regarding clinical examination, symptom management, information on their condition, reassurance, antibiotic treatment and other possible options including referral.

Design

Cross-sectional design.

Setting

One urban primary care OOH facility located in the midwest of Ireland.

Participants

457 patients filled out a questionnaire while waiting in the OOH facility; 22 surveys were excluded as the patients did not present with symptoms of acute URTI resulting in 435 patients’ data being included in this study. There were 59.5% female participants and 40.5% male participants.

Results

435 patients with acute URTI symptoms participated in the survey, representing 25.4% of those attending the single branch where the survey was conducted (n=1715). Of the study participants, 43% were aged under 6 years and 60% were women. The most common presenting symptoms were cough (72%), throat ache (46%) and common cold (26%). The most common expectations were for further examination (53%), reassurance (51%), information (49%) and medication for cough (47%), with 34% expecting an antibiotic.

Conclusions

Only one in three patients attending this primary care OOH facility with acute URTI symptoms had an expectation of antibiotics, with most seeking further assessment, information and reassurance. Recognition of such expectations may be important considerations for clinicians when deciding on management options for patients with acute URTI.
Trends in resource use and effectiveness of ultrasound detection of fetal structural anomalies in France: a multiple registry-based study
Authors: Ferrier Clément , Dhombres Ferdinand , Khoshnood Babak , Randrianaivo Hanitra , Perthus Isabelle , Guilbaut Lucie , Durand-Zaleski Isabelle , Jouannic Jean-Marie
Published: February 2019

Objective

To analyse trends in the number of ultrasound examinations in relation to the effectiveness of prenatal detection of birth defects using population-based data in France.

Design

A multiple registry-based study of time trends in resource use (number of ultrasounds) and effectiveness (proportion of cases prenatally diagnosed).

Setting

Three registries of congenital anomalies and claims data on ultrasounds for all pregnant women in France.

Participants

There were two samples of pregnant women. Effectiveness was assessed using data from three French birth defect registries. Resource use for ultrasound screening was based on the French national healthcare database.

Main outcome measures

The main outcome measures were prenatal diagnosis (effectiveness) and the average number of ultrasounds (resource use). Statistical analyses included linear and logistic regression models to assess trends in resource use and effectiveness of prenatal testing, respectively.

Results

The average number of ultrasound examinations per pregnancy significantly increased over the study period, from 2.47 in 2006 to 2.98 in 2014 (p=0.005). However, there was no significant increase in the odds of prenatal diagnosis. The probability of prenatal diagnosis was substantially higher for cases associated with a chromosomal anomaly (91.2%) than those without (51.8%). However, there was no evidence of an increase in prenatal detection of either over time.

Conclusions

The average number of ultrasound examinations per pregnancy increased over time, whereas the probability of prenatal diagnosis of congenital anomalies did not. Hence, there is a need to implement policies such as high-quality training programmes which can improve the efficiency of ultrasound examinations for prenatal detection of congenital anomalies.
Paramedics’ experiences of administering fascia iliaca compartment block to patients in South Wales with suspected hip fracture at the scene of injury: results of focus groups
Authors: Evans Bridie Angela , Brown Alan , Bulger Jenna , Fegan Greg , Ford Simon , Guy Katy , Jones SIan , Keen Leigh , Khanom Ashrafunnesa , Longo Mirella , Pallister Ian , Rees Nigel , Russell Ian T , Seagrove Anne C , Watkins Alan , Snooks Helen
Published: February 2019

Objectives

To explore paramedics’ experience of delivering fascia iliaca compartment block(FICB) to patients with suspected hip fracture at the scene of injury.

Design

Focus groups within a randomised controlled trial.

Setting

Paramedics based at ambulance stations in the catchment area of one Emergency Department in South Wales, recruited and trained in a feasibility study about an alternative to routine prehospital pain management for patients with suspected hip fracture.

Participants

11 paramedics.

Intervention

Paramedic-administered FICB to patients with suspected hip fracture. We randomly allocated eligible patients to FICB, a local anaesthetic injection directly into the hip region—or usual care, most commonly morphine - using audited scratch cards.

Outcomes

Paramedics’ experiences of administering FICB gathered through thematic analysis of interview transcripts by two researchers, one paramedic and one lay member.

Results

Respondents believed that FICB was a suitable intervention for paramedics to deliver. It aligned with routine practice and was within people’s capabilities. They said it took up to 10 minutes longer than usual care to prepare and deliver, in part due to nervousness and unfamiliarity with a new procedure. They praised the training provided but said they were anxious about causing harm by injecting into the wrong location. Confidence increased after one paramedic team successfully treated a patient for local anaesthetic toxicity. Reported challenges related to the emergency context: patients often waited many hours for ambulance arrival; moving patients exacerbated their pain; family and neighbours were present as paramedics administered treatment.

Conclusions

Paramedics are willing and able to administer FICB to patients with suspected hip fracture before ambulance transport to hospital. Feasibility study findings will inform further research.

Trial registration number

ISRCTN60065373; Pre results.
VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients
Authors: Conrad Anne , Boccard Mathilde , Valour Florent , Alcazer Vincent , Tovar Sanchez Aydee-Tamara , Chidiac Christian , Laurent Frédéric , Vanhems Philippe , Salles Gilles , Brengel-Pesce Karen , Meunier Boris , Trouillet-Assant Sophie , Ader Florence
Published: February 2019

Introduction

Immune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT.

Methods and analysis

A prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus,Haemophilus Influenzaetype b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide orStaphylococcus aureusenterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function.

Ethics and dissemination

Ethical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.

Trial registration number

NCT03659773; Pre-results.
Novel use of tranexamic acid to reduce the need for Nasal Packing in Epistaxis (NoPac) randomised controlled trial: research protocol
Authors: Reuben Adam , Appelboam Andrew , Barton Andy , Vickery Patricia Jane , Body Richard , Hilton Malcolm , Coppell Jason , Ewings Paul
Published: February 2019

Introduction

Patients presenting to emergency departments (EDs) with epistaxis uncontrolled by subsequent simple first aid measures or application of topical vasoconstrictors will typically undergo anterior nasal packing. Packing is effective, but can be extremely painful and unpleasant and patients usually need hospital admission. Tranexamic acid (TXA) is a cheap, safe, readily available antifibrinolytic agent known to be beneficial in a variety of clinical settings where uncontrolled bleeding may be a problem. Anecdotal evidence suggests that topical TXA may be of value in persistent epistaxis; however, further evaluation is required.

Methods and analysis

This is a multicentre, double-blind, parallel group, randomised, controlled trial comparing the use of topical intranasal TXA with indistinguishable placebo in adults presenting to UK EDs with persistent atraumatic epistaxis. Follow-up is at 1 week by structured telephone review. The primary outcome measure is the subsequent need for anterior nasal packing in the ED. Key secondary outcomes include the need for hospital admission, blood transfusion and/or further treatment for epistaxis during the index ED attendance. Recruiting 450 patients will provide 90% power to demonstrate an absolute reduction in packing rate from 95% to 85%. An improvement of this magnitude would be of significant benefit to patients and healthcare providers and justify a change to standard practice. Given the low cost of TXA and its short administration time, a full economic evaluation is not being undertaken.

Ethics and dissemination

The study has been approved by the South West—Bristol Research Ethics Committee (reference 17/SW/0010). We aim to publish the findings in a high impact, international peer-reviewed journal. Results will also be shared with the Hereditary Haemorrhagic Telangiectasia foundation and telangiectasia UK for dissemination through appropriate related forums.

Trial registration number

ISRCTN34153772and EudraCT No: 2016-001530-10.
Dispersive viscosurgical devices demonstrate greater efficacy in protecting corneal endothelium in vitro
Authors: Yildirim Timur Mert , Auffarth Gerd U , Son Hyeck-Soo , Khoramnia Ramin , Munro Donald John , Merz Patrick R
Published: February 2019

Objective

During phacoemulsification, the corneal endothelium is protected by an ophthalmic viscosurgical device (OVD). In this in vitro study, we assessed six different OVDs for their effectiveness in protecting the corneal endothelium.

Methods and analysis

Phacoemulsification was performed in cadaver eyes of young pigs. Five syringe units of six different OVDs were tested (Healon EndoCoat, Viscoat, Methylvisc, Healon, Healon GV, ProVisc). After surgery, the area of endothelium coated with OVD was determined in relation to the total endothelial surface. Additionally, an endothelial cell count was obtained. As a control, an endothelial cell count was obtained from freshly trephined corneas. Statistical analysis was performed using the Mann-Whitney U test and the Spearman correlation.

Results

The least postoperative endothelial coating and cell count were observed in the cohesive OVDs while the dispersive OVDs showed statistically significant higher values. Healon EndoCoat and Viscoat yielded a coating area of 86 (85–92)% and 85 (85-90)%, respectively. Endothelial cell count was highest in the two dispersive groups with 4065 (3928–4088) cells/mm2(Methylvisc) and 4032 (4015–4115) cells/mm2(Viscoat). Endothelial coating area and endothelial cell count correlated statistically significantly.

Conclusion

Dispersive OVDs from this study showed greater adherence to the endothelial surface than the cohesive ones. Furthermore, postoperative endothelial cell counts of corneas treated with dispersive OVDs were higher than of corneas treated with cohesive OVDs. Our in vitro results suggest that dispersive OVDs protect the corneal endothelium better during phacoemulsification than cohesive OVDs.
Bandage contact lens and topical steroids are risk factors for the development of microbial keratitis after epithelium-off CXL
Authors: Tzamalis Argyrios , Romano Vito , Cheeseman Robert , Vinciguerra Riccardo , Batterbury Mark , Willoughby Colin , Neal Timothy , Ahmad Sajjad , Kaye Stephen
Published: February 2019

Objective

To investigate the role of bandage contact lenses (BCL) and topical steroids as risk factors for the development of microbial keratitis after epithelium-off corneal collagen cross-linking (CXL).

Methods and Analysis

Patients undergoing CXL between February 2011 and July 2017 were included. Patients were divided into two groups: those who were treated postoperatively with a BCL, topical antimicrobial and steroids (group 1) and those who received only a topical antimicrobial until healing of the epithelial defect before introduction of topical steroids (group 2).

Results

1273 eyes of 964 patients were included. Group 1 comprised 316 eyes and group 2 comprised 957 eyes. There were no significant differences in the presence of persisting corneal haze or scarring between the two groups (p=0.57). Microbial keratitis occurred in nine eyes (0.71% of eyes) of eight (0.83%) patients (one case was bilateral) out of 1273 eyes.Staphylococcus aureuswas cultured from corneal scrapes in seven out of nine (77.8%) cases and from contiguous sites in the two cases. All cases occurred in group 1 (incidence=2.85%) and none in group 2 (p<0.0001). A greater proportion of patients who developed microbial keratitis were atopic (75%, p=0.4).

Conclusion

The use of BCL and topical steroids prior to healing of the epithelium is a significant risk factor for microbial keratitis.S. aureusis the most common micro-organism and is likely to originate from an endogenous site. Not using a BCL and delaying the introduction of topical steroids until epithelial healing significantly reduce the risk of developing microbial keratitis without increasing the risk of persistent corneal haze.
Development and validation of a prediction model for the probability of responding to placebo in antidepressant trials: a pooled analysis of individual patient data
Authors: Shinohara Kiyomi , Tanaka Shiro , Imai Hissei , Noma Hisashi , Maruo Kazushi , Cipriani Andrea , Yamawaki Shigeto , Furukawa Toshi A
Published: February 2019

Background

Identifying potential placebo responders among apparent drug responders is critical to dissect drug-specific and nonspecific effects in depression.

Objective

This project aimed to develop and test a prediction model for the probability of responding to placebo in antidepressant trials. Such a model will allow us to estimate the probability of placebo response among drug responders in antidepressants trials.

Methods

We identified all placebo-controlled, double-blind randomised controlled trials (RCTs) of second generation antidepressants for major depressive disorder conducted in Japan and requested their individual patient data (IPD) to pharmaceutical companies. We obtained IPD (n=1493) from four phase II/III RCTs comparing mirtazapine, escitalopram, duloxetine, paroxetine and placebo. Out of 1493 participants in the four clinical trials, 440 participants allocated to placebo were included in the analyses. Our primary outcome was response, defined as 50% or greater reduction on Hamilton Rating Scale for Depression at study endpoint. We used multivariable logistic regression to develop a prediction model. All available candidate of predictor variables were tested through a backward variable selection and covariates were selected for the prediction model. The performance of the model was assessed by using Hosmer-Lemeshow test for calibration and the area under the ROC curve for discrimination.

Findings

Placebo response rates differed between 31% and 59% (grand average: 43%) among four trials. Four variables were selected from all candidate variables and included in the final model: age at onset, age at baseline, bodily symptoms, and study-level difference. The final model performed satisfactorily in terms of calibration (Hosmer-Lemeshow p=0.92) and discrimination (the area under the ROC curve (AUC): 0.70).

Conclusions

Our model is expected to help researchers discriminate individuals who are more likely to respond to placebo from those who are less likely so.

Clinical implications

A larger sample and more precise individual participant information should be collected for better performance. Examination of external validity in independent datasets is warranted.

Trial registration number

CRD42017055912.
Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery
Authors: Salehi Marzieh , Gastaldelli Amalia , D’Alessio David A
Published: February 2019

Objective

Postprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that β-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB.

Design

Ten non-diabetic subjects with GB, and 9 body mass index (BMI)-matched and age-matched non-surgical controls (CN) with normal glucose tolerance had blood glucose clamped at ~7.8 mM on three separate days. Stepwise incremental infusions of GLP-1 (15, 30, 60, 120 and 300 ng/LBkg/h), GIP (75, 150, 300, 600 and 1200 ng/LBkg/h) or saline were administered from 90 to 240 min and insulin secretion measured.

Results

GB subjects had similar fasting glucose levels but lower fasting insulin compared with CN, likely due to increased insulin clearance. The average insulin secretion rates (ISRs) to 7.8 mM glucose were ~30% lower in GB relative to CN subjects. However, incretin-stimulated ISRs, adjusted for insulin sensitivity and glucose-stimulated insulin secretion, were even more attenuated in the GB subjects, by threefold to fourfold (AUCISR(90−240 min)during GLP-1 and GIP: 47±8 and 44±12 nmol in GB and 116±16 and 161±44 in CN; p<0.01).

Conclusion

After GB, the sensitivity of insulin secretion to both glucose and incretins is diminished.
Trends in surgical and catheter interventions for isolated congenital shunt lesions in the UK and Ireland
Authors: Farooqi Mehreen , Stickley John , Dhillon Rami , Barron David J , Stumper Oliver , Jones Timothy J , Clift Paul F , Brawn William J , Drury Nigel E
Published: February 2019

Objective

To evaluate time trends in the use of catheter and surgical procedures, and associated survival in isolated congenital shunt lesions.

Methods

Nationwide, retrospective observational study of the UK National Congenital Heart Disease Audit database from 2000 to 2016. Patients undergoing surgical or catheter procedures for atrial septal defect (including sinus venosus defect), patent foramen ovale, ventricular septal defect and patent arterial duct were included. Temporal changes in the frequency of procedures, and survival at 30 days and 1 year were determined.

Results

40 911 procedures were performed, 16 604 surgical operations and 24 307 catheter-based interventions. Transcatheter procedures increased over time, overtaking surgical repair in 2003–2004, while the number of operations remained stable. Trends in interventions differed according to defect type and patient age. Catheter closure of atrial septal defects is now more common in children and adults, although surgical interventions have also increased. Patent foramen ovale closure in adults peaked in 2009–2010 before falling significantly since. Surgery remains the mainstay for ventricular septal defect in infants and children. Duct ligation is most common in neonates and infants, while transcatheter intervention is predominant in older children. Excluding duct ligation, survival following surgery was 99.4% and ≈98.7%, and following catheter interventions was 99.7% and ≈99.2%, at 30 days and 1 year, respectively.

Conclusions

Trends in catheter and surgical techniques for isolated congenital shunt lesions plot the evolution of the specialty over the last 16 years, reflecting changes in clinical guidelines, technology, expertise and reimbursement, with distinct patterns according to lesion and patient age.
Valve area and the risk of overestimating aortic stenosis
Authors: González-Mansilla Ana , Martinez-Legazpi Pablo , Prieto Andrea , Gomá Elena , Haurigot Pilar , Pérez del Villar Candelas , Cuadrado Victor , Delgado-Montero Antonia , Prieto Raquel , Mombiela Teresa , Pérez-David Esther , Rodríguez González Elena , Benito Yolanda , Yotti Raquel , Pérez-Vallina Manuel , Fernández-Avilés Francisco , Bermejo Javier
Published: February 2019

Objective

To obtain reference values of aortic valve area (AVA) in a large population and to infer the risk of overestimating aortic stenosis (AS) when focusing on flow-corrected indices of severity.

Methods

We prospectively measured indices of AS in all consecutive echocardiograms performed in a large referral cardiac imaging laboratory for 1 year. We specifically analysed the distribution of AVA, indexed AVA and velocity ratio (Vratio) in patients with and without AS, the latter defined as the coexistence of valvular outflow obstruction (Vmax ≥2.5 m/s) and morphological findings of valve degeneration.

Results

16 156 echocardiograms were analysed, 14 669 of which did not show valvular obstruction (peak jet velocity <2.5 m/s). In the latter group, AVA was 2.6±0.7 cm2in 8190 studies with normal valves and 2.3±0.7 cm2in 6479 studies with aortic sclerosis (AScl). There was a relatively wide overlap between values of AVA, indexed AVA and velocity ratio between studies of patients with AScl and AS. Values of AVA ≤1.0 cm2were found in 0.5% of studies with normal valves and 1.8% of studies with AScl. These proportions were 3.1% and 9.3% for AVA ≤1.5 cm2, respectively. Vratio ≤0.25 were found in 0.1% of patients without obstruction. Risk factors for a small AVA in patients without obstruction were AScl, female sex, small body surface area, low ejection fraction and mitral regurgitation.

Conclusions

Normal values of continuity-equation derived AVA are smaller than previously considered. AVA values below cutoffs of moderate or severe AS can be found in patients without the disease. Flow-corrected indices may overestimate AS in patients with low gradients, particularly in the presence of well-identified risk factors.
Spatio-temporal analysis of colorectal cancer using a geographic information system in the Iranian military community during the period 2007–2016
Authors: Khoshdel Alireza , Alimohammadi M , Sepandi M , Alimohamadi Y , Jalali P , Janani M
Published: February 2019

Introduction

Colorectal cancer (CRC) is one of the most prevalent cancers among Iranian people. The study of spatio-temporal distribution of disease has an important role in the design of disease prevention programmes. The purpose of the current study was to describe the spatio-temporal distribution of CRC in the Iranian military community as a sample of the Iranian population.

Methods

In the current ecological study, all registered cancer cases in the Iranian military community during the period 2007–2016 were considered. To identify hotspots, Getis-Ord Gi statistics were used. All analyses were performed using ArcGIS 10.5 and Excel 2010.

Results

The highest incidences of CRC in 2007–2008, 2009–2010 and 2011–2012 were recorded in Kermanshah province. The highest incidences of CRC in 2013–2014 were seen in Kermanshah, Ghilan, Tehran and North Khorasan. In 2007–2008 and 2009–2010, hotspots were detected in West Azarbayjan. In 2011–2012, hotspots were detected in Zanjan and Qazvin. In 2013–2014, a hotspot was detected in Qazvin. Finally, West Azerbaijan was the hotspot for CRC in 2015–2016.

Conclusions

The incidence of CRC in men was higher than in women. Also it appeared that North and North West Iran were risk areas for this disease, and so these areas should be considered in the design of disease prevention programme for this cancer type. Additionally, the determination of individual risk factors in the aforementioned geographical areas can play an important role in the prevention of this type of cancer.
Using patient-reported outcome measures for primary percutaneous coronary intervention
Authors: Kwong Esther , Neuburger Jenny , Petersen Steffen Erhard , Black Nick
Published: February 2019

Introduction

Routine measurement of the outcome of myocardial infarction is usually limited to immediate morbidity and mortality. Our aim was to determine the response to patient-reported outcome measures (PROMs) 3 months later, identify response bias and explore the feasibility of comparing outcome with their recalled view of their prior health state.

Methods

Patients admitted with ST-segment-elevation myocardial infarction (STEMI) to five percutaneous coronary intervention centres were invited to complete a retrospective questionnaire containing the EQ-5D-3L and short form Seattle Angina Questionnaire (SAQ-7). Response rate for a 3-month mailed follow-up questionnaire and potential response biases were assessed. Patients’ outcomes were compared with their baseline using χ2and paired t-test to assess for differences.

Results

Of 392 patients contacted, 260 (66.3%) responded. Responders were more likely to be older, female, more affluent and have a higher EQ-5D at baseline. Three months after surgery, patients’ SAQ-7 and angina symptom subscale returned to their baseline score. The physical limitation subscale score was worse than at baseline (79.9 vs 73.2, p=0.002), whereas the quality-of-life subscale was better (66.6 vs 73.9; p<0.001). The EQ-5D-3L index score was similar at 3 months to baseline (0.82 vs 0.79). Evidence of bias arising from responders being in better general health at baseline needs further investigation and, if confirmed, needs to be taken into account in interpreting PROMs data.

Conclusion

It is feasible to use PROMs routinely to assess the impact of emergency admissions of patients with STEMI. A larger demonstration project with more sites is needed to confirm these findings.
Productivity costs of cardiovascular disease mortality across disease types and socioeconomic groups
Authors: Carter Hannah Elizabeth , Schofield Deborah , Shrestha Rupendra
Published: February 2019

Background

Cardiovascular disease (CVD) is the single largest contributor to global mortality. Premature mortality due to CVD results in a loss of productivity, with associated economic and policy implications that are often overlooked.

Methods

A human capital approach was adopted to project the long-term impacts of Australian CVD deaths in 2003 on labour force participation and the present value of lifetime income (PVLI) forgone. Impacts were modelled to the year 2030 and accounted for individual characteristics at the time of death including age, sex and socioeconomic status.

Results

Premature deaths due to CVD in 2003 accounted for 51 659 working years and $2.69 billion in PVLI forgone when modelled to 2030 (95% CI $2.63 billion to $2.75 billion). The labour force impacts were highest for individuals aged between 35 and 64 at the time of death, and male deaths accounted for 87% of the total PVLI loss. The most costly disease type was ischaemic heart disease, followed by stroke and inflammatory heart disease. Deaths occurring in individuals residing in the most socioeconomically disadvantaged areas at the time of death had a disproportionately large impact on the total PVLI loss.

Conclusions

This study quantifies the relative productivity costs of CVD mortality across a range of disease types and socioeconomic groups. The magnitude of these costs highlights the scope for investments in effective healthcare interventions to provide positive economic returns and may assist decision makers in allocating resources among competing priorities.