bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1–3 D4Z4 reduced alleles: experience of the FSHD Italian National Registry
Authors: Nikolic Ana , Ricci Giulia , Sera Francesco , Bucci Elisabetta , Govi Monica , Mele Fabiano , Rossi Marta , Ruggiero Lucia , Vercelli Liliana , Ravaglia Sabrina , Brisca Giacomo , Fiorillo Chiara , Villa Luisa , Maggi Lorenzo , Cao Michelangelo , D'Amico Maria Chiara , Siciliano Gabriele , Antonini Giovanni , Santoro Lucio , Mongini Tiziana , Moggio Maurizio , Morandi Lucia , Pegoraro Elena , Angelini Corrado , Di Muzio Antonio , Rodolico Carmelo , Tomelleri Giuliano , Grazia D'Angelo Maria , Bruno Claudio , Berardinelli Angela , Tupler Rossella
Published: February 2016

Objectives

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers (≤8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1–3 repeats (1–3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1–3 DRA.

Setting

Italy.

Participants

66 index cases and 33 relatives carrying 1–3 DRA.

Outcomes

The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk.

Results

No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1–3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment.

Conclusions

The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity.
The efficacy and safety of complete pericardial drainage by means of intrapericardial fibrinolysis for the prevention of complications of pericardial effusion: a systematic review protocol
Authors: Kakia Aloysious , Wiysonge Charles S , Ochodo Eleanor A , Awotedu Abolade A , Ristic Arsen D , Mayosi Bongani M
Published: February 2016

Introduction

Intrapericardial fibrinolysis has been proposed as a means of preventing complications of pericardial effusion such as cardiac tamponade, persistent and recurrent pericardial effusion, and pericardial constriction. There is a need to understand the efficacy and safety of this procedure because it shows promise.

Methods and analysis

We aim to assess the effects of intrapericardial fibrinolysis in the treatment of pericardial effusion. We will search PubMed, the Cochrane Library, African Journals online, Cumulative Index to Nursing and Allied Health Literature, Trip database, Clinical trials.gov and the WHO International Clinical Trials Registry Platform for studies that evaluate the efficacy and/or safety of complete pericardial fluid drainage by intrapericardial fibrinolysis irrespective of study design, geographical location, language, age of participants, aetiology of pericarditis or types of fibrinolytics. Two authors will do the search independently, screen the search outputs for potentially eligible studies and assess whether the studies meet the inclusion criteria. Discrepancies between the two authors will be resolved through discussion and arbitration by a third author. Data from the selected studies shall be extracted using a standardised data collection form which will be piloted before use. The methodological quality of studies will be assessed using the Cochrane Collaboration's tools for assessing risk of bias for experimental studies and non-randomised studies, respectively. The primary meta-analysis will use random effects models due to expected interstudy heterogeneity. Dichotomous data will be analysed using relative risk and continuous with data mean differences, both with 95% CIs.

Ethics and dissemination

Approval by an ethics committee is not required for this study as it is a protocol for a systematic review of published studies. The results will be disseminated through a conference presentation and peer-reviewed publication.

Review registration number

PROSPERO, CRD42014015238.
Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study
Authors: Wade C , Wang L , Zhao W J , Cardini F , Kronenberg F , Gui S Q , Ying Z , Zhao N Q , Chao M T , Yu J
Published: February 2016

Objective

To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments.

Setting

A Menstrual Disorder Centre at a public hospital in Shanghai, China.

Participants

Chinese women aged 14–25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation.

Interventions

A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit.

Primary and secondary outcome measures

The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles.

Results

Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (−0.71, CI −1.37 to −0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment.

Conclusions

Acupuncture point injection of vitamin K3 relieves menstrual pain rapidly and is a useful treatment in an urban outpatient clinic.

Trial registration number

NCT00104546; Results.
Diffusion-weighted MRI in differentiating malignant from benign thyroid nodules: a meta-analysis
Authors: Chen Lihua , Xu Jian , Bao Jing , Huang Xuequan , Hu Xiaofei , Xia Yunbao , Wang Jian
Published: February 2016

Objectives

To perform a meta-analysis to evaluate the diagnostic efficacy of diffusion-weighted imaging (DWI) in differentiating malignant from benign thyroid nodules.

Design

A meta-analysis.

Data sources and study selection

Medical and scientific literature databases were searched for original articles published up to August 2015. Studies were selected if they (1) included diagnostic DWI for differentiating malignant from benign thyroid lesions, (2) included patients who later underwent biopsy and (3) presented sufficient data to enable the construction of contingency tables.

Data synthesis

For each study, the true-positive, false-positive, true-negative and false-negative values were extracted or derived, and 2×2 contingency tables were constructed. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) instrument. The heterogeneity test, threshold effect test, subgroup analyses and publication bias analyses were performed.

Results

From the 113 identified search results, 15 studies, representing a total of 765 lesions, were included in the meta-analysis. We detected heterogeneity between studies but found no evidence of publication bias. The methodological quality was moderate. The pooled weighted sensitivity was 0.90 (95% CI 0.85 to 0.93); the specificity was 0.95 (95% CI 0.88 to 0.98); the positive likelihood ratio was 16.49 (95% CI 7.37 to 36.86); the negative likelihood ratio was 0.11 (95% CI 0.08 to 0.16); and the diagnostic OR was 150.73 (95% CI 64.96 to 349.75). The area under the receiver operator characteristic curve was 0.95 (95% CI 0.93 to 0.97).

Conclusions

Quantitative DWI may be a non-invasive, non-radiative and accurate method of distinguishing malignant from benign thyroid nodules. Nevertheless, large-scale trials are necessary to assess its clinical value and to establish standards regarding b values and cut-off values for DWI-based diagnosis.
Admission to psychiatric hospital in the early and late postpartum periods: Scottish national linkage study
Authors: Langan Martin Julie , McLean Gary , Cantwell Roch , Smith Daniel J
Published: February 2016

Objective

To describe weekly admission rates for affective and non-affective psychosis, major depression and other psychiatric disorders in the early and late postpartum periods. To assess the impact of socioeconomic status, age and parity on admission rates.

Methods

Scottish maternity records were linked to psychiatric hospital admissions. 3290 pregnancy-related psychiatric admissions were assessed. Weekly admission rates were calculated for the pregnancy period, early postpartum period (6 weeks after birth) and late postpartum period (up to 2 years after birth), and compared with pre-pregnancy rates (up to 2 years before pregnancy). Admission rates were generated by calculating the total number of admissions for each time period divided by the number of weeks in the period. Incidence rate ratios (IRRs) were generated for each time period, using deprivation, age, parity and record of previous psychiatric hospital care-adjusted Poisson regression models.

Results

Women from more deprived social quintiles accounted for the largest proportion of admissions across all time periods. Compared with pre-pregnancy period, admission rates fell during pregnancy, increased markedly during the early postpartum period, and remained elevated for 2 years after childbirth. Within the most affluent quintile, admission IRRs were higher in the early postpartum period (IRR=1.29, 95% CI 1.02 to 1.59) than in the late postpartum period (IRR=0.87, 95% CI 0.74 to 0.98). For the late postpartum period, there was a positive association between higher maternal age and admission IRRs (ages 20–35 years, IRR=1.35, 95% CI 1.16 to 1.54 and age>40 years IRR=1.72, 95% CI 1.41 to 2.09).

Conclusions

Rates of psychiatric admission fell during pregnancy and increased in the early postpartum period (particularly during the first 2 weeks after birth), and remained elevated above baseline during the 2-year late postpartum period. An understanding of how social deprivation, age and parity might influence risk of psychiatric admission at different time points could help to target perinatal mental health services more effectively.
Trends of vital signs with gestational age in normal pregnancies: a systematic review protocol
Authors: Loerup Lise , Pullon Rebecca M , Birks Jacqueline , Fleming Susannah , Mackillop Lucy H , Watkinson Peter J
Published: February 2016

Introduction

Vital signs (blood pressure, heart rate, temperature, oxygen saturation and respiratory rate) are thought to undergo changes during and immediately after pregnancy. However, these physiological changes are not taken into account in the normal ranges, which themselves are not evidence-based, used in routine and acute care monitoring. We aim to synthesise the existing evidence base for changes in vital signs during pregnancy, in order to derive new centile charts for each stage of pregnancy and the immediate postpartum period.

Methods and analysis

We will search the MEDLINE, EMBASE and CINAHL databases from their inception to April 2015 for vital signs from pregnant, intrapartum or postpartum women who were recruited as ‘healthy’. Assessment of bias will be conducted using a predefined set of independently agreed methodological criteria, which assigns an overall quality score to each study. We will record whether the vital sign measurements were made with measurement devices validated for use in pregnancy and in a standard posture. We will use regression methods to construct centile charts of vital signs across pregnancy and the immediate postpartum period for each vital sign. We will compare existing reference ranges to those derived from our centile charts.

Dissemination

The systematic review will be published in a peer-reviewed journal and disseminated electronically and in print.

PROSPERO reference

CRD42014009673.
Implementation of the guidelines for targeted temperature management after cardiac arrest: a longitudinal qualitative study of barriers and facilitators perceived by hospital resuscitation champions
Authors: Kim Young-Min , Lee Seung Joon , Jo Sun Jin , Park Kyu Nam
Published: February 2016

Objectives

To identify the barriers to and facilitators of implementing guidelines for targeted temperature management (TTM) after cardiac arrest perceived by hospital resuscitation champions and to investigate the changes in their perceptions over the early implementation period.

Design

A longitudinal qualitative study (up to 2 serial semistructured interviews over 1 year and focus groups). The individual interviews and focus groups were transcribed and coded by 2 independent assessors. Contents were analysed thematically; group interaction was also examined.

Setting

21 hospitals, including community and tertiary care centres in South Korea.

Participants

21 hospital champions (14 acting champions and 7 managerial champions).

Results

The final data set included 40 interviews and 2 focus groups. The identified barriers and facilitators could be classified into 3 major themes: (1) healthcare professionals’ perceptions of the guidelines and protocols, (2) interdisciplinary and interprofessional collaboration and (3) organisational resources. Lack of resources was the most commonly agreed on barrier for the acting champions, whereas lack of interdisciplinary collaboration was the most common barrier for the managerial champions. Educational activities and sharing successfully treated cases were the most frequently identified facilitators. Most of the participants identified and agreed that cooling equipment was an important barrier as well as a facilitator of successful TTM implementation. Perception of the guidelines and protocols has improved with the accumulation of clinical experience over the study period.

Conclusions

Healthcare professionals’ internal barriers to TTM implementation may be influenced by new guidelines and can be changed with the accumulation of successful clinical experiences during the early implementation period. Promoting interprofessional and interdisciplinary collaboration through educational activities and the use of cooling equipment with an automated feedback function can improve adherence to guidelines in hospitals with limited human resources in critical care.
Analysis of health service amenable and non-amenable mortality before and since China's expansion of health coverage in 2009
Authors: Feng Xiaoqi , Liu Yunning , Astell-Burt Thomas , Yin Peng , Page Andrew , Liu Shiwei , Liu Jiangmei , Wang Lijun , Zhou Maigeng
Published: February 2016

Objective

To explore early impacts of China's health reforms in 2009 on mortality.

Methods

Annual mortality counts were obtained from 161 counties across all 31 provinces of mainland China between 2006 and 2012. We examined time-series of health service amenable mortality counts, including separate analyses for deaths from stroke and ischaemic heart diseases (IHD). Non-amenable mortality counts, including separate models for oesophageal and pancreatic cancers, were also analysed as part of a negative-outcome strategy to provide stronger foundations for falsification. Deaths due to amenable causes were hypothesised to decrease, whereas non-amenable causes of mortality would remain uninfluenced. All analyses were conducted using multilevel negative binomial regression.

Results

Geographical variation was observed for each mortality indicator, especially for IHD, oesophageal and pancreatic cancers. Negative covariances in all models indicated slight degrees of convergence in these geographic variations over time (but not significantly for deaths from oesophageal and pancreatic cancers). Linear and square functions of time indicated a curvilinear inverted parabolic trend between 2006 and 2012 for stroke and IHD mortality. Reduction in health-service amenable mortality over time was observed, but also for health service non-amenable mortality, including deaths from oesophageal cancer. Pancreatic cancer was found to increase across the study period. In counties where residents had more years of education, mortality from stroke was lower and reducing faster over time. A similar spatiotemporal patterning was observed for deaths from oesophageal cancer, and health service amenable and non-amenable causes. Counties with higher mean education years had higher mortality from IHD and pancreatic cancer, but also larger reductions in mortality were evident in areas with greater years of education.

Conclusions

Although there was no clear evidence of an early impact of China's health reform on mortality, this does not rule out potentially important contributions to reducing the burden of disease in the longer term.
Psychological factors and DNA methylation of genes related to immune/inflammatory system markers: the VA Normative Aging Study
Authors: Kim Daniel , Kubzansky Laura D , Baccarelli Andrea , Sparrow David , Spiro Avron , Tarantini Letizia , Cantone Laura , Vokonas Pantel , Schwartz Joel
Published: February 2016

Objectives

Although psychological factors have been associated with chronic diseases such as coronary heart disease (CHD), the underlying pathways for these associations have yet to be elucidated. DNA methylation has been posited as a mechanism linking psychological factors to CHD risk. In a cohort of community-dwelling elderly men, we explored the associations between positive and negative psychological factors with DNA methylation in promoter regions of multiple genes involved in immune/inflammatory processes related to atherosclerosis.

Design

Prospective cohort study.

Setting

Greater Boston, Massachusetts area.

Participants

Samples of 538 to 669 men participating in the Normative Aging Study cohort with psychological measures and DNA methylation measures, collected on 1–4 visits between 1999 and 2006 (mean age=72.7 years at first visit).

Outcome measures

We examined anxiety, depression, hostility and life satisfaction as predictors of leucocyte gene-specific DNA methylation. We estimated repeated measures linear mixed models, controlling for age, smoking, education, history of heart disease, stroke or diabetes, % lymphocytes, % monocytes and plasma folate.

Results

Psychological distress measured by anxiety, depression and hostility was positively associated, and happiness and life satisfaction were inversely associated with average Intercellular Adhesion Molecule-1 (ICAM-1) and coagulation factor III (F3) promoter methylation levels. There was some evidence that hostility was positively associated with toll-like receptor 2 (TLR-2) promoter methylation, and that life satisfaction was inversely associated withTLR-2and inducible nitric oxide synthase (iNOS) promoter methylation. We observed less consistent and significant associations between psychological factors and average methylation for promoters of the genes for glucocorticoid receptor (NR3C1), interferon-γ (IFN-γ) and interleukin 6 (IL-6).

Conclusions

These findings suggest that positive and negative psychological factors affect DNA methylation of selected genes involved in chronic immune/inflammatory processes and inflammation-related endothelial dysfunction. Such epigenetic changes may represent biological pathways that mediate the effects of psychological factors on CHD.
Persistent spatial clusters of high body mass index in a Swiss urban population as revealed by the 5-year GeoCoLaus longitudinal study
Authors: Joost Stéphane , Duruz Solange , Marques-Vidal Pedro , Bochud Murielle , Stringhini Silvia , Paccaud Fred , Gaspoz Jean-Michel , Theler Jean-Marc , Chételat Joël , Waeber Gérard , Vollenweider Peter , Guessous Idris
Published: February 2016

Objective

Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether and how BMI clusters evolve over time in a population is currently unknown. We aimed to determine the spatial dependence of BMI and its 5-year evolution in a Swiss general adult urban population, taking into account the neighbourhood-level and individual-level characteristics.

Design

Cohort study.

Setting

Swiss general urban population.

Participants

6481 georeferenced individuals from the CoLaus cohort at baseline (age range 35–74 years, period=2003–2006) and 4460 at follow-up (period=2009–2012).

Outcome measures

Body weight and height were measured by trained healthcare professionals with participants standing without shoes in light indoor clothing. BMI was calculated as weight (kg) divided by height squared (m2). Participants were geocoded using their postal address (geographic coordinates of the place of residence). Getis-Ord Gi statistic was used to measure the spatial dependence of BMI values at baseline and its evolution at follow-up.

Results

BMI was not randomly distributed across the city. At baseline and at follow-up, significant clusters of high versus low BMIs were identified and remained stable during the two periods. These clusters were meaningfully attenuated after adjustment for neighbourhood-level income but not individual-level characteristics. Similar results were observed among participants who showed a significant weight gain.

Conclusions

To the best of our knowledge, this is the first study to report longitudinal changes in BMI clusters in adults from a general population. Spatial clusters of high BMI persisted over a 5-year period and were mainly influenced by neighbourhood-level income.
Antimicrobial lock solutions for the prevention of catheter-related infection in patients undergoing haemodialysis: study protocol for network meta-analysis of randomised controlled trials
Authors: Zhang Jun , Li Rong-Ke , Chen Kee-Hsin , Ge Long , Tian Jin-Hui
Published: February 2016

Introduction

Catheter-related infection (CRI) is a difficult clinical problem in renal medicine, with blood stream infections occurring in up to 40% of patients with haemodialysis (HD) catheters, conferring significant rates of morbidity and mortality. Several approaches have been assessed as a means to prevent CRI. Currently, an intervention that is the source of much discussion is the use of antimicrobial lock solutions (ALS). A number of past conventional meta-analyses have compared different ALS with heparin. However, there is no consensus recommendation regarding which type of ALS is best. The purpose of our study is to carry out a network meta-analysis comparing the efficacy of different ALS for prevention of CRI in patients with HD and ranking these ALS for practical consideration.

Methods and analysis

We will search six electronic databases, earlier relevant meta-analyses and reference lists of included studies for randomised controlled trials (RCTs) that compared ALS for preventing episodes of CRI in patients with HD either head-to-head or against control interventions using non-ALS. Study selection and data collection will be performed by two reviewers independently. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcome of efficacy will be catheter-related bloodstream infection (CRBSI). We will perform a Bayesian network meta-analysis to compare the relative efficacy of different ALS by WinBUGS (V.1.4.3) and STATA (V.13.0). The quality of evidence will be assessed by GRADE.

Ethics and dissemination

Ethical approval is not required given that this study includes no confidential personal data and no data on interventions on patients. The results of this study will be submitted to a peer-review journal for publication.

Trial registration number

CRD42015027010.
Neighbourhood environment, physical activity, quality of life and depressive symptoms in Hong Kong older adults: a protocol for an observational study
Authors: Cerin Ester , Sit Cindy H P , Zhang Casper J P , Barnett Anthony , Cheung Martin M C , Lai Poh-chin , Johnston Janice M , Lee Ruby S Y
Published: February 2016

Introduction

The neighbourhood environment can assist the adoption and maintenance of an active lifestyle and affect the physical and mental well-being of older adults. The psychosocial and behavioural mechanisms through which the environment may affect physical and mental well-being are currently poorly understood.

Aim

This observational study aims to examine associations between the physical and social neighbourhood environments, physical activity, quality of life and depressive symptoms in Chinese Hong Kong older adults.

Methods and analyses

An observational study of the associations of measures of the physical and social neighbourhood environment, and psychosocial factors, with physical activity, quality of life and depressive symptoms in 900 Hong Kong older adults aged 65+ years is being conducted in 2012–2016. The study involves two assessments taken 6 months apart. Neighbourhood walkability and access to destinations are objectively measured using Geographic Information Systems and environmental audits. Demographics, socioeconomic status, walking for different purposes, perceived neighbourhood and home environments, psychosocial factors, health status, social networks, depressive symptoms and quality of life are being assessed using validated interviewer-administered self-report measures and medical records. Physical functionality is being assessed using the Short Physical Performance Battery. Physical activity and sedentary behaviours are also being objectively measured in approximately 45% of participants using accelerometers over a week. Physical activity, sedentary behaviours, quality of life and depressive symptoms are being assessed twice (6 months apart) to examine seasonality effects on behaviours and their associations with quality of life and depressive symptoms.

Ethics and dissemination

The study received ethical approval from the University of Hong Kong Human Research Ethics Committee for Non-Clinical Faculties (EA270211) and the Department of Health (Hong Kong SAR). Data are stored in a password-protected secure database for 10 years, accessible only to the named researchers. Findings will be submitted for publication in peer-reviewed journals.
Inappropriate prescribing of preventative medication in patients with life-limiting illness: a systematic review
Authors: Todd Adam , Husband Andy , Andrew Inga , Pearson Sallie-Anne , Lindsey Laura , Holmes Holly
Published: February 2016

Objectives

To systematically review the literature to examine the methods used to identify inappropriate prescribing of preventative medication in patients with life-limiting illness and to detail the nature of medications prescribed.

Methods

A systematic literature search of 4 databases was undertaken (MEDLINE, EMBASE, CINAHL, PsycINFO) from inception to April 2015 to identify peer-reviewed, observational studies assessing inappropriate prescribing of preventative medication in patients with life-limiting illness. Inclusion criteria were: participants had a life-limiting illness; prescribed/dispensed/using preventative medication; medication appropriateness assessed as a specific study aim or outcome.

Results

We found 19 studies meeting our eligibility criteria. The methods used to assess medication appropriateness included criteria developed for the elderly such as the Beers Criteria, and Screening Tool of Older Persons’ potentially inappropriate Prescriptions (STOPP) criteria, Delphi consensus and expert clinical opinion. Lipid-regulating drugs (12 studies), antihypertensive (11 studies) and antidiabetic medications (9 studies) were the most common classes of inappropriate medication identified.

Conclusions

Patients with life-limiting illnesses are prescribed preventative medications considered inappropriate in the context of diminished life expectancy. The way in which preventative medication appropriateness is assessed in patients with life-limiting illness varies considerably—with some methodologies utilising criteria previously developed for elderly populations. Given this lack of standardisation, improving the prescribing in this context requires an approach that is specifically designed and validated for populations with life-limiting illness.
A proposal for cellularity assessment for EGFR mutational analysis with a correlation with DNA yield and evaluation of the number of sections obtained from cell blocks for immunohistochemistry in non-small cell lung carcinoma
Authors: da Cunha Santos Gilda , Wyeth Tyler , Reid Allie , Saieg Mauro Ajaj , Pitcher Bethany , Pintilie Melania , Kamel-Reid Suzanne , Tsao Ming Sound
Published: February 2016

Aims

Different approaches have been described for reporting specimen adequacy for epidermal growth factor receptor (EGFR) mutation analysis. We aimed: (1) to conduct cellularity assessment and to investigate its association with DNA yield, (2) to compare the H&E slides taken before and after the thick sections (curls) obtained forEGFRtesting and (3) to evaluate the number of ancillary studies performed.

Methods

Cell block (CB) slides of 110 non-small cell lung carcinoma cases submitted to EGFR analysis from 2010 to 2012 were reviewed for total cellularity (ranges 1–100, 100–250, 250–500, 500–750, 750–1000 and >1000 cells), tumour cellularity (ranges 1–50, 50–100, 100–300 and >300 cells) and the percentage of tumour cells. Precurl and postcurl H&E slides were compared using the three criteria. The number of immunohistochemistry (IHC) markers and special stains and DNA yield were recorded.

Results

DNA yield was significantly associated with the total cellularity, number and percentage of tumour cells. For 46 cases with precurl and postcurl slides, only three (6.5%) were classified as being different and in two of them the postcurl slide had greater cellularity than the precurl. IHC was performed in 83 cases, with a minimum of 1 and a maximum of 11 markers (median of 3) per case.

Conclusions

An association between the total cellularity and the tumour cellularity with the DNA yield was demonstrated using the ranges described. Evaluation of a postcurl slide is an unnecessary practice. The majority of the CB had sufficient material for ancillary studies (up to 11 markers) and mutation testing.
Professional patienthood and mortality: Seán Ó Ríordáin's diaries 1974–1977
Authors: Breathnach Ciara
Published: February 2016

Unwieldy by nature, unsolicited diaries and their study, this article contends, have the potential to offer deeper insights into the experience of illness but only if they receive due consideration from scholars. This article uses a series of historic diaries to examine the concept of ‘professional patienthood’ or being a full-time patient, and, while it found the narrative medicine approach to be very useful, it also found it limiting. The recent methodological trends in biomedicine and social sciences towards structured mechanisms like questionnaires—surveying and evaluating performance, satisfaction and experience—can only go so far. This article makes a case for the unsolicited, the unorthodox and the unstructured.
Comparison of outcomes of patients with inpatient or outpatient onset ischemic stroke
Authors: Bekelis Kimon , Missios Symeon , Coy Shannon , MacKenzie Todd A
Published: February 2016

Background

Reperfusion times for ischemic stroke occurring in the outpatient setting have improved significantly in recent years. However, quality improvement efforts have largely ignored ischemic stroke occurring in patients hospitalized for unrelated indications.

Methods

We performed a cohort study involving patients with ischemic stroke (with inpatient or outpatient onset) from 2009 to 2013 who were registered in the Statewide Planning and Research Cooperative System (SPARCS) database. A propensity score-adjusted regression analysis was used to assess the association of location of onset and outcomes. Mixed effects methods were employed to control for clustering at the hospital level.

Results

Of the 176 571 ischemic strokes, 160 157 (90.7%) occurred outside of a hospital and 16 414 (9.3%) occurred in patients hospitalized for unrelated indications. Using a logistic regression model with propensity score adjustment, we demonstrated that inpatient stroke onset was associated with increased inpatient mortality (OR 3.09; 95% CI 2.81 to 3.38), rate of discharge to rehabilitation (OR 2.57; 95% CI 2.37 to 2.79), and length of stay (LOS) (β=11.58; 95% CI 10.73 to 12.42). In addition, it was associated with lower odds (OR 0.69; 95% CI 0.62 to 0.77) of undergoing stroke-related interventions (mechanical thrombectomy and intravenous tissue plasminogen activator) compared with outpatient stroke onset.

Conclusions

Using a comprehensive all-payer cohort of patients with ischemic stroke in New York State, we identified an association of inpatient stroke onset with fewer stroke-related interventions and increased mortality, rate of discharge to rehabilitation, and LOS.
Integrated Patient Coordination System (IntPaCS): a bespoke tool for surgical patient management
Authors: Chopra Shiv , Hachach-Haram Nadine , Baird Daniel L H , Elliott Katherine , Lykostratis Harry , Renton Sophie , Shalhoub Joseph
Published: February 2016

Background

Efficient handover of patient information is fundamental for patient care and service efficiency. An audit exploring surgeons' views on written handover within a Trust's surgical specialties concluded that clear deficiencies existed. Such concerns have been echoed in the General Medical Council's guidance on safe surgical handover.

Aims

To design and implement bespoke software for surgical handover using the audit results of surgeons' perceptions of existing processes. To gain feedback from the surgical department on this new software and implement a long-term sustainability strategy.

Methods

Following an initial review, a proposal was presented for a new patient management tool. The software was designed and developed in-house to reflect the needs of our surgeons. The bespoke programme used open-source coding and was maintained on a secure server. A review of surgical handover occurred 12 and 134 weeks post-implementation of the new software.

Results

Integrated Patient Coordination System (IntPaCS) was successfully developed and delivered. The system is a centralised platform that enables the visualisation, handover and audit/research of surgical inpatient information in any part of the hospital. Feedback found that clinicians found it less stressful to create a post-take handover (60% vs 36%) than using a Word document. IntPaCS was found to be quicker to use too (15 min (SD 4) vs 24 min (SD 7.5)). Finally, the new system was considered safer with less reported missing/incorrect patient data (48% vs 9%).

Conclusions

This study has shown that careful use of emerging technology and innovation over time has the potential to improve all aspects of clinical governance.
A suspected case of hepatogenous chronic copper toxicity in a Charolais heifer
Authors: Newcomer Benjamin W. , Wolfe Dwight , Chamorro Manuel , Passler Thomas , Joiner Kellye
Published: February 2016

A six‐month‐old, orphaned Charolais heifer presented for a five‐day‐history of lethargy and inappetence. On examination, the calf was severely icteric and exhibited haemoconcentration and methaemoglobinaemia. The heifer developed haemolysis and haemoglobinuria the following day leading to the performance of a whole blood transfusion. Liver biopsy revealed evidence of a plant‐based toxic hepatopathy and an elevated copper concentration. Analysis of the calf's feedstuffs did not reveal the source of the excess copper, although one milk replacer sample was above recommended levels for preruminants. No history of access to exogenous copper sources was reported. Hepatogenous chronic copper toxicity results after ingestion of hepatotoxic plants leading to an increase in hepatocyte affinity for copper. A suspected diagnosis of hepatogenous chronic copper toxicity was made. This case demonstrates the disease can be a diagnostic challenge and should be included on the differential list for patients exhibiting methemoglobinaemia and/or signs of liver disease.
IPR Centered Institutional Service and Tools for Content and Metadata Management
Authors: Bellini Pierfrancesco , Bruno Ivan , Nesi Paolo , Paolucci Michela
Published: February 2016

Multimedia services of cultural institutions need to be supported by content, metadata and workflow management systems to efficiently manage huge amount of content items and metadata production. Online digital libraries and cultural heritage institutions, as well as portals of publishers need an integrated multimedia back office in order to aggregate content collection and provide them to national and international aggregators, with respect to Intellectual Property Rights, IPR. The aim of this paper is to formalize and discuss requirements, modeling, design and validation of an institutional aggregator for metadata and content, coping with IPR Models for conditional access and providing content towards Europeana, the European international aggregator. This paper presents the identification of the Content Aggregator requirements for content management and IPR, and thus the definition and realization of a corresponding distributed architecture and workflow solution satisfying them. The main contributions of this paper consist of the formalization of IPR Model that enable the shortening of the activities for the IPR resolution, and avoid the assignment of conflicting rights/permissions during IPR model formalization, and thus of licensing. The proposed solution, models and tools have been validated in the case of the ECLAP service and results are reported in the paper. ECLAP Content Aggregator has been established by the European Commission to serve Europeana for the thematic area of Performing Arts institutions.
Knowledge Adaptability Evaluation in View of Patent Citation in Technological Evolutionary Process: A Case Study of Fuel Cell
Authors: Xu Qi , Gu Xinjian , Feng Yujing
Published: February 2016

This work uses patents as agent and proposes the concept of knowledge adaptation factor in view of the objective law of survival of the fittest in technological evolutionary process. Knowledge genetic decomposition of a patent citation network is executed based on the Mendel law. And the contributions of early patents on current patents along patent citations are quantified to evaluate knowledge adaptability. Then the feasibility and effectiveness of the knowledge adaptability evaluation method are verified with the case study of fuel cell. This study collects 3054 patents related to fuel cell which were granted between 1873 to 2002 from the database of United States Patent and Trademark Office, queries from the patent data set of National Bureau of Economic Research to get 14214 patent citations, and uses the network analysis software Pajek to build the patent citation network. The results of the knowledge adaptability evaluation of fuel cell reflect that the knowledge dissemination process is composed of knowledge inheritance, knowledge innovation and knowledge recombinant. The patents whose knowledge adaptation factors are relatively high are subordinate to the technological evolutionary process of fuel cell. It is consistent with the central idea of knowledge adaptation factor, which is technological-evolution-oriented.
Linear Software Models: Decoupled Modules from Modularity Matrix Eigenvectors
Authors: Exman Iaakov
Published: February 2016

Modularity Matrices for software systems can be put in block-diagonal form, where blocks are higher-level software modules, in a hierarchy of modules. But the exact module boundaries are often blurred by the uncertainty whether given matrix elements are module members or outliers. This paper provides an algorithm to determine module sizes. As a consequence the algorithm also decides which matrix elements are outliers. Matrix elements are weighted by their Affinity — an exponential function of the off-diagonality. The module size is given by the positive consecutive elements of the eigenvectors corresponding to the largest eigenvalues of this weighted symmetrized Modularity Matrix. By means of case studies, we illustrate the idea that outliers not only indicate the need for system redesign, but explicitly point out to problematic design spots. This work extends the applicability of linear algebra spectral methods to Modularity Matrices, at higher software abstraction levels than previously shown.
Lissajous and Fourier knots
Authors: Soret Marc , Ville Marina
Published: February 2016

We prove that any knot of [Formula: see text] is isotopic to a Fourier knot of type [Formula: see text] obtained by deformation of a Lissajous knot.
Dynamic Changes in Heart Rate Variability and Nasal Airflow Resistance during Nasal Allergen Provocation Test
Authors: Seppänen Tiina M. , Alho Olli-Pekka , Seppänen Tapio
Published: February 2016

Allergic rhinitis is a major chronic respiratory disease and an immunoneuronal disorder. We aimed at providing further knowledge on the function of the neural system in nasal allergic reaction. Here, a method to assess simultaneously the nasal airflow resistance and the underlying function of autonomic nervous system (ANS) is presented and used during the nasal provocation of allergic and nonallergic subjects. Continuous nasal airflow resistance and spectral heart rate variability parameters show in detail the timing and intensity differences in subjects’ reactions. After the provocation, the nasal airflow resistance of allergic subjects showed a positive trend, whereas LF/HF (Low Frequency/High Frequency) ratio and LF power showed a negative trend. This could imply a gradual sympathetic withdrawal in allergic subjects after the allergen provocation. The groups differed significantly by these physiological descriptors. The proposed method opens entirely new opportunities to research accurately concomitant changes in nasal breathing function and ANS.
Glucagonoma and Glucagonoma Syndrome: A Case Report with Review of Recent Advances in Management
Authors: Al-Faouri Ashraf , Ajarma Khaled , Alghazawi Samer , Al-Rawabdeh Sura , Zayadeen Adnan
Published: February 2016

The rarity of glucagonoma imposes a challenge with most patients being diagnosed after a long period of treatment for their skin rash (months-years). Awareness of physicians and dermatologists of the characteristic necrolytic migratory erythema often leads to early diagnosis. Early diagnosis of glucagonoma even in the presence of resectable liver metastases may allow curative resection. Herein, we present a typical case of glucagonoma treated at our center and review the literature pertinent to its management.
Efficient Alternative for Construction of the Linear System Stemming from Numerical Solution of Heat Transfer Problems via FEM
Authors: Romão Estaner Claro
Published: February 2016

This paper proposes an efficient alternative to construction of the linear system coming from a solution via the Finite Element Method that is able to significantly decrease the time of construction of this system. From the presentation of the methodology used and a numerical application it will be clear that the purpose of this work is to be able to decrease 6-7 times (on average) the linear system building time.
Immunological Aspects of Fulminant Type 1 Diabetes in Chinese
Authors: Wang Zhen , Zheng Ying , Tu Yiting , Dai Zhijie , Lin Jian , Zhou Zhiguang
Published: February 2016

Background.Fulminant type 1 diabetes (FT1D) is a novel subtype of type 1 diabetes characterized by extremely rapid onset and complete deficiency of insulin due to the destruction of pancreaticβcells. However, the precise mechanisms underlying the etiology of this disease remain unclear.Methods.A total of 22 patients with FT1D and 10 healthy subjects were recruited. Serum antibodies to GAD, IA2, and ZnT8 in patients were tested. And peripheral T cell responses to GAD65, insulin B9–23 peptide, or C peptide were determined in 10 FT1D patients and 10 healthy controls. The mRNA levels of several related cytokines and molecules, such as IFN-γ, IL-4, RORC, and IL-17 in PBMCs from FT1D patients were analyzed by qRT-PCR.Result.We found that a certain proportion of Chinese FT1D patients actually have developed islet-related autoantibodies after onset of the disease. The GAD, insulin, or C peptide-reactive T cells were found in some FT1D patients. We also detected a significant increase for IFN-γexpression in FT1D PBMCs as compared with that of healthy controls.Conclusion.Autoimmune responses might be involved in the pathogenesis of Chinese FT1D.
The Relationship between Alcohol Consumption and Incidence of Glycometabolic Abnormality in Middle-Aged and Elderly Chinese Men
Authors: Zhang Siwen , Liu Yujia , Wang Gang , Xiao Xianchao , Gang Xiaokun , Li Fei , Sun Chenglin , Gao Ying , Wang Guixia
Published: February 2016

Aim. The relationship between alcohol consumption and glycometabolic abnormality is controversial, especially in different ethnic population. In this study, a cross-sectional survey was carried out to examine the relationship between alcohol consumption and glycometabolic abnormality in middle-aged and elderly Chinese men. Methods. Using cluster random sampling, Chinese men aged more than 40 years from Changchun, China, were given standardized questionnaires. In total, 1996 individuals, for whom complete data was available, were recruited into the study. We calculated the incidence of prediabetes and newly diagnosed diabetes by three levels of alcohol consumption: light, moderate, and heavy. Multivariate logistic regression models adjusted for socioeconomic variables and diabetes-related risk factors were used to analyze the association between alcohol consumption and the onset of prediabetes and diabetes. Results. The univariate analysis revealed higher incidence of prediabetes among drinkers (32.8%) compared with nondrinkers (28.6%), particularly in heavy alcohol consumers. The logistic regression analysis showed that alcohol consumption, especially heavy consumption, was an independent risk factor for prediabetes. Conclusions. Alcohol consumption, heavy consumption in particular, is an independent risk factor for the development of prediabetes, but not for diabetes.