Effects of Cervical Rotatory Manipulation (CRM) on Carotid Atherosclerosis Plaque in Vulnerability: A Histological and Immunohistochemical Study Using Animal Model

Background. The safety of cervical rotatory manipulation (CRM) is still controversial, especially in patients with carotid artery atherosclerosis (CAS). The study aimed to investigate the effects of CRM on carotid plaques in vulnerability. Methods. 50 rabbits were randomly divided into four groups: model rabbits with CRM [CAS-CRM (n=15)]; model rabbits without CRM [CAS (n=15)]; normal rabbits with CRM [Normal-CRM (n=10)]; and Blank-control group (n=10). CAS disease models were induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. Then, CRM technique was performed in CAS-CRM and Normal-CRM groups for 3 weeks. In the end, determination of serum level of hs-CRP and Lp-PLA2, histological analysis under HE and Masson trichromic staining, and immunohistochemical analysis with CD34 and CD68 antibody were completed in order. Results. Carotid stenosis rates on successful model rabbits ranged from 70% to 98%. The CAS-CRM group had an increased level of hs-CRP (P

http://bit.ly/2WH0kXc

ADAMTSL1 and mandibular prognathism

Mandibular prognathism is characterized by a prognathic or prominent mandible. The objective of this study was to find the gene responsible for mandibular prognathism. Whole exome sequencing analysis of a Thai family (family 1) identified the ADAMTSL1 c.176C>A variant as the potential defect. We cross‐checked our exome data of 215 people for rare variants in ADAMTSL1 and found that the c.670C>G variant was associated with mandibular prognathism in families 2 and 4. Mutation analysis of ADAMTSL1 in 79 unrelated patients revealed the c.670C>G variant was also found in family 3. We hypothesize that mutations in ADAMTSL1 cause failure to cleave aggrecan in the condylar cartilage, and that leads to overgrowth of the mandible. Adamtsl1 is strongly expressed in the condensed mesenchymal cells of the mouse condyle, but not at the cartilage of the long bones. This explains why the patients with ADAMTSL1 mutations had abnormal mandibles but normal long bones. This is the first report that mutations in ADAMTSL1 are responsible for the pathogenesis of mandibular prognathism.

http://bit.ly/2Bj7rMi

Transcriptomic expression profiling identifies ITGBL1, an epithelial to mesenchymal transition (EMT)-associated gene, is a promising recurrence prediction biomarker in colorectal cancer

Abstract

The current histopathological risk-stratification criteria in colorectal cancer (CRC) patients following a curative surgery remain inadequate. In this study, we undertook a systematic, genomewide, biomarker discovery approach to identify and validate key EMT-associated genes that may facilitate recurrence prediction in CRC. Genomewide RNA expression profiling results from two datasets (GSE17538; N = 173 and GSE41258; N = 307) were used for biomarker discovery. These results were independently validated in two, large, clinical cohorts (testing cohort; N = 201 and validation cohort; N = 468). We performed Gene Set Enrichment Analysis (GSEA) for understanding the function of the candidate markers, and evaluated their correlation with the mesenchymal CMS4 subtype. We identified integrin subunit beta like 1 (ITGBL1) as a promising candidate biomarker, and its high expression associated with poor overall survival (OS) in stage I-IV patients and relapse-free survival (RFS) in stage I-III patients. Subgroup validation in multiple independent patient cohorts confirmed these findings, and demonstrated that high ITGBL1 expression correlated with shorter RFS in stage II patients. We developed a RFS prediction model which robustly predicted RFS (the area under the receiver operating curve (AUROC): 0.74; hazard ratio (HR): 2.72) in CRC patients. ITGBL1 is a promising EMT-associated biomarker for recurrence prediction in CRC patients, which may contribute to improved risk-stratification in CRC.

http://bit.ly/2TtvqiT

Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway

Abstract

Background

CircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. 'MiRNA sponge' is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis.

Methods

We detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models.

Results

We discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models.

Conclusions

We proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC.

http://bit.ly/2BhfUPS

Career Stereotypes and Identities: Implicit Beliefs and Major Choice for College Women and Men in STEM and Female-Dominated Fields

Abstract

The present study examines the gendered nature of implicitly held beliefs related to STEM careers. It tests predictions from balanced identity theory on the relations between implicit STEM gender stereotypes and implicit STEM identity, as well as predictions from the associative-propositional model related to exposure to counter-stereotypical exemplars in a sample of U.S. college-aged heterosexual romantic couples that varied in whether the woman majored in STEM or in female-dominated majors (FDM). Gender-STEM stereotypes and Self-STEM identification, as measured by Implicit Associations Tasks, were examined in 117 college women majoring in STEM or in FDM and in their romantic partners, some of whom were also majoring in STEM. Women in STEM majors evidenced stronger STEM identities while also demonstrating reduced Gender/STEM stereotypes in comparison to women in FDM and men in STEM. For women, implicit STEM stereotypes predicted implicit STEM identity which in turn predicted majoring in STEM, consistent with predictions from balanced identity theory. There was no support for the hypothesis that men's exposure to counter-stereotypical women through their romantic relationships influenced their own implicit stereotypes, inconsistent with the associative-propositional model. Women in STEM fields and their romantic partners also evidenced more similar levels of STEM gender stereotypes when compared to the other couples. Dissemination of these results may encourage other STEM-talented women in similar pursuits.

http://bit.ly/2DTDyE9

Blastic Plasmacytoid Dendritic Cell Neoplasm

Opinion statement

While there is a high initial response rate with standard chemotherapeutic regimens for blastic plasmacytoid dendritic cell neoplasm (BPDCN), the responses are typically not durable and this remains a very aggressive disease with generally poor outcomes. For this reason, the standard approach for eligible patients has been high-dose induction chemotherapy preferably with acute lymphoblastic leukemia (ALL)-based regimens followed by consolidation with allogeneic hematopoietic stem cell transplantation (alloHSCT). Unfortunately, many patients with this disease are elderly and/or frail and cannot tolerate this therapy, and the low-dose regimens being used in this population are generally not as effective. However, this paradigm may be changing with the advent of newer targeted therapies, particularly the exploitation of CD123. SL-401 has shown very promising results with manageable toxicities and durable responses and appears to be a viable option for elderly or frail patients who are not eligible for transplant. The other CD123-directed therapies, especially chimeric antigen receptor-therapy (CAR-T), may also give promising results in trials that are currently underway. CAR-T has shown promise in a number of other hematologic malignancies, and toxicities have become more manageable as its use is becoming more widespread. While SL-401 has shown potential to provide durable responses even without transplant, we do not yet know whether it will be effective as a means to avoid transplant in patients who are otherwise eligible. All transplant-eligible patients should undergo alloHSCT consolidation given the current available data indicating this is the optimal approach to achieve a long-term remission. Once the CD123-directed therapies are established as standard regimens, future studies may be designed to investigate whether these therapies can be utilized without the use of transplant. Furthermore, combination therapy using anti-CD123 agents with high-dose induction chemotherapy or other low-dose regimens for elderly/frail patients should be investigated. Given the promising results in early clinical trials, it appears CD123 is the most viable target for BPDCN, and future studies should continue to exploit its expression on BPDCN cells.

http://bit.ly/2TAoS29

Influences of phosphorus and foliar iron fertilization rate on the quality parameters of whole wheat grain

In this study, the effects of phosphorus and foliar iron fertilization rates on the protein, fiber, and water contents in whole wheat grain were determined by the NIR technique.

Abstract

The objective of this research was to study the effects of phosphorous and foliar iron fertilizations rates on the of protein, fiber, and water contents in wheat grains. Treatments of fertilizers included a combination of three foliar iron rates (0, 1.2, and 2 L/ha, Fusion) and four phosphorus rates (0, 75, 150, and 225 kg/ha, P₂O₅) at three replications. The quality parameters of harvested seeds were measured by the NIR technique. Protein content increased but and fiber and water contents decreased significantly with an increase in the iron and phosphorus fertility rates. As the rates of foliar iron increased from 0 to 2 L/ha the mean values of protein content increased significantly from 13.47% to 15.48%. With increasing the rates of phosphorus from 0 to150 kg/ha, the mean values of protein content increased significantly from 13.56% to 15.53%, however, further increase in phosphorus, causing a decreased trend in the amount of protein. Fiber and water contents of wheat decreased significantly from 13.76% to 11.86% and from 7.36% to 7.28%, respectively, as the phosphorous rate increased from 0 to 225 kg/ha. Those changes were from 13.40% to 12.03% and from 7.57% to 7.21%, respectively, for increasing foliar iron from 0, 1.2, and 2 L/ha. Mathematical relationships composed of phosphorus and iron fertilizers were developed for accurately describing the wheat protein, fiber, and water contents under different fertilization rates.

http://bit.ly/2UCwOjp

High-dose etoposide could discriminate the benefit from autologous peripheral blood stem cell transplantation in the patients with refractory diffuse large B cell lymphoma

Abstract

To evaluate the strategy of using high-dose etoposide mobilization followed by autologous peripheral blood stem cell transplantation (APBSCT) in patients with diffuse large B cell lymphoma (DLBCL) refractory to rituximab-based chemotherapy. Forty patients with refractory DLBCL were treated with high-dose etoposide for stem cell mobilization. All patients were in progressive disease (PD) prior to mobilization and underwent high-dose chemotherapy followed by APBSCT. Successful PBSC mobilization was achieved in all patients. Twenty-three patients (57.5%) showed a clinical response to high-dose etoposide. After APBSCT, 17 patients (42.5%) achieved CR. The 2-year progression-free (PFS) and overall survival (OS) rate were higher in patients responding to high-dose etoposide (64.1% and 77.7%) compared to those without response (11.8% and 11.8%; P < 0.001 for both). The response to high-dose etoposide mobilization therapy was an independent prognostic factor for CR achievement, PFS and OS after APBSCT. High-dose etoposide mobilization chemotherapy followed by APBSCT could rescue a proportion of patients with refractory DLBCL who responded to etoposide mobilization regimen.

http://bit.ly/2SqQXvc

Updated CMAJ policy on undisclosed competing interests [Editorial]

http://bit.ly/2GmeA1A

Many doctors have distorted perceptions of the value of medical tests [News]

http://bit.ly/2SvuhKB

Infertility treatment and risk of severe maternal morbidity: a propensity score-matched cohort study [Research]

BACKGROUND:

The extent to which infertility treatment predicts severe maternal morbidity is not well known. We examined the association between infertility treatment and severe maternal morbidity in pregnancy and the postpartum period.

METHODS:

We conducted a cohort study using population-based registries from Ontario between 2006 and 2012. Pregnancies achieved using infertility treatment (ovulation induction, intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection) were compared with unassisted pregnancies using propensity score matching, based on demographic, reproductive and obstetric factors. The primary outcome was a validated composite of severe maternal morbidity or maternal death from 20 weeks' gestation to 42 days postpartum. We also calculated the odds ratio of a woman having 1, 2, or 3 or more severe maternal morbidity indicators in relation to invasive (e.g., in vitro fertilization) or noninvasive (e.g., intrauterine insemination) infertility treatment.

RESULTS:

We matched 11 546 infertility treatment pregnancies with 47 553 untreated pregnancies. Severe maternal morbidity or maternal death occurred in 356 infertility-treated pregnancies (30.8 per 1000 deliveries) versus 1054 untreated pregnancies (22.2 per 1000 deliveries); relative risk 1.39 (95% confidence interval [CI] 1.23–1.56). The likelihood of a woman having 3 or more severe maternal morbidity indicators was increased in women who received invasive infertility treatment (odds ratio [OR] 2.28, 95% CI 1.56–3.33) but not in those who received noninvasive infertility treatment (OR 0.99, 95% CI 0.57–1.72).

INTERPRETATION:

Women who undergo infertility treatment, particularly in vitro fertilization, are at somewhat higher risk of severe maternal morbidity or death. Efforts are needed to identify patient- and treatment-specific predictors of severe maternal morbidity that may influence the type of treatment a woman is offered.

http://bit.ly/2GkqlFT

Comparing family medicine residency training in Canada and the United Kingdom [Letters]

http://bit.ly/2SpYhY1

Using electronic health records for clinical trials: Where do we stand and where can we go? [Analysis]

http://bit.ly/2GmXwZe

Starting a family during residency? Leave policies complicate the choice [News]

http://bit.ly/2GmvQnj

Transcatheter aortic valve implantation for severe aortic stenosis [Practice]

http://bit.ly/2StgBiU

Role of dietitians in reducing malnutrition in hospital [Letters]

http://bit.ly/2GmplkH

Nipple changes in an 85-year-old man [Practice]

http://bit.ly/2SsVDRa

Prevalence of metabolic syndrome in the Canadian adult population [Correction]

http://bit.ly/2GnAqlA

Heart and head [Humanities]

http://bit.ly/2SsVzAU

Teatro Anatomico [Humanities]

http://bit.ly/2SkNjDj

The challenge of implementing a patient-centric EMR [News]

http://bit.ly/2Gm3UQH

Cant catch my breath [Coda]

http://bit.ly/2Gl54M9

Specific growth rates calculated from CTs in patients with head and neck squamous cell carcinoma: a retrospective study performed in Austria

Objective

To provide data on specific growth rates (SGRs) of primary tumours (PT-SGR) and largest pathological cervical lymph nodes (LN-SGR) for head and neck squamous cell carcinoma (HNSCC). To explore PT-SGR's and LN-SGR's correlation with selected biomarkers epidermal growth factor receptor (EGFR), Ki67 and CD44.

Design and setting

Retrospective study performed at a tertiary oncological referral centre in Innsbruck, Austria.

Participants

Adult patients with incident HNSCC treated with primary radiotherapy (RT) or radiochemotherapy (RCT).

Outcome measures

Volumes of the primary tumour (PT-volume) and largest pathological cervical lymph node (LN-volume) were measured in CT scans obtained at time of diagnosis and subsequent planning CTs immediately prior to RT or RCT. SGRs were calculated assuming an exponential growth function. PT-SGR's and LN-SGR's correlation with EGFR, Ki67 and CD44 were explored.

Results

In 123 patients, mean interval between diagnostic and planning CT was 29±21 days. PT-SGR was 1.8±1.8% (mean±SD) per day and was positively correlated with EGFR, Ki67 and CD44 expression (p=0.02; p=0.02; p=0.03). LN-SGR was 1.7±2.0% per day and increased with larger initial LN-volume, was lower in laryngeal cancer (p=0.003) and slowed down with time. LN-SGR was not correlated with EGFR, Ki67 or CD44 expression in primary tumours (p>0.12). New cartilage or bone infiltration occurred in 10 patients and new central lymph node necrosis in 8 patients.

Conclusions

HNSCCs are fast-growing tumours for which treatment must not be delayed. Clinical tumour growth rates are influences by EGFR, KI67 and CD44 expression.

http://bit.ly/2WEET93

Health assets in a global context: a systematic review of the literature

Objective

To provide an up-to-date overview of health assets in a global context both from a theoretical perspective and its practical applications to address health inequalities and achieve sustainable health.

Design

A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources

A comprehensive search, including 10 electronic bibliographic databases and hand searches, was undertaken to capture the wide range of terms associated with 'health assets' and 'asset-based approaches to health'.

Eligibility criteria

Any peer-reviewed published and grey literature in English related to 'health assets' or 'assets' in a 'health' context was included without any date, country or study design restrictions and the quality of evidence was appraised according to the Oxford Level of Evidence.

Outcomes

A broad consideration of all outcome measures including clinical outcomes, patient-level, community-level and population-level impacts and costs, was adopted.

Results

478 publications were included. Health assets were researched in 40 countries, predominantly in the West such as the USA and the UK. A number of broad health assets were identified including community and individual assets. Even though research was conducted in a number of different settings, most occurred in the community, clinical, care or educational settings. A wide variety of interventions and approaches were implemented, most commonly related to education and/or training, asset mapping or asset approaches.

Conclusions

Globally, authors most often referred to general 'health assets', 'assets' or some form of 'community asset' in relation to health. Overall, the idea of health assets is framed within a positive paradigm focusing on health creation rather than curative approaches. The sustained credibility of the global 'health assets' literature depends on future research on definitional, theoretical and evaluative issues in order to convince policy-makers and service commissioners of its necessity and added value to the traditional deficit approach.

http://bit.ly/2RC4Yli

Does care in a specialised stroke prevention clinic improve poststroke blood pressure control: a protocol for a randomised comparative effectiveness study

Introduction

Hypertension is a major risk factor for recurrent stroke, and blood pressure (BP) reduction is associated with decreased risk of stroke recurrence. However, many stroke survivors have poorly controlled BP after their initial stroke. The Stroke Transitions Education and Prevention (STEP) Clinic was established to provide a comprehensive approach to stroke risk factor reduction.

Methods and analysis

This randomised comparative effectiveness study was designed to assess the impact of care in the STEP clinic versus usual care on poststroke BP reduction. Eligible hospitalised patients with ischaemic stroke, haemorrhagic stroke or transient ischaemic attack are scheduled for a clinic screening visit within 4 weeks of discharge if they meet baseline inclusion criteria. At the clinic visit, patients who have uncontrolled BP, defined as automated office BP ≥135/85 mm Hg are randomised (1:1) to either the STEP clinic or usual care for management. STEP clinic patients receive instructions to self-monitor, a BP monitor, sleep apnoea screening, dietary counselling, review of BP monitoring records and adjustment of medications. Patients are followed by a neurologist and a stroke-trained nurse practitioner. Usual care participants are seen by a neurologist and recommendations for secondary prevention are sent to primary care providers. The primary outcome is the difference in mean daytime ambulatory systolic BP at 6 months, assessed using linear regression analysis. Secondary outcomes include 24 hours ambulatory BP, medication adherence and medication self-efficacy, and composite cardiovascular events.

Ethics and dissemination

This study was approved by the Institutional Review Boards at the McGovern Medical School at the University of Texas Health Sciences Center and the Georgetown University School of Medicine. Uninsured and Spanish-speaking patients are included in the study.

Trial registration number

NCT02591394; Pre-results.

http://bit.ly/2WChrcp

Application of a novel sex independent anthropometric index, termed angle index, in relation to type 2 diabetes: a Trinidadian case-control study

Objective

To develop a novel sex independent anthropometric index, termed as angle index, related to type 2 diabetes.

Design

Case–control.

Participants

The study comprised 121 participants and were divided into two groups. One group had no form of diabetes and served as controls (n=50). The other group had the condition of type 2 diabetes (n=71). 31% (n=37) of the subjects were male and 69% (n=84) were female. 62% (n=75) of the subjects were of East Indian ethnicity, 28% (n=34) were of African ethnicity and 10% (n=12) were of mixed ethnicity.

Setting

Participants of the study were from the island of Trinidad, located in the Caribbean. Patients in the study were selected at random from hospital records.

Primary outcome measure

It was hypothesised that the mean angle index of patients with type 2 diabetes would be higher than the mean angle index of patients without type 2 diabetes.

Results

Patients with type 2 diabetes had a significantly higher angle index value as compared with controls (p<0.001). Angle index was the superior sex independent anthropometric index in relation to type 2 diabetes (area under the curve=0.72; p<0.001) as compared with other sex independent variables. Angle index correlated with glycated haemoglobin (r_s=0.28, p=0.003) and fasting blood glucose (r_s=0.31, p=0.001) levels. Patients with type 2 diabetes were four times more likely to have an angle index greater than 184° (OR 4.2, 95% CI 1.8 to 9.9) as compared with controls.

Conclusion

Angle index was a superior sex independent index for discriminating between patients with and without type 2 diabetes, as compared with waist circumference, abdominal volume index, conicity index, blood pressure readings, triglyceride levels and very low-density lipoprotein levels.

http://bit.ly/2RDMSiO

Multicentre randomised controlled trial to investigate usefulness of the rapid diagnostic {beta}LACTA test performed directly on bacterial cell pellets from respiratory, urinary or blood samples for the early de-escalation of carbapenems in septic intensive care unit patients: the BLUE-CarbA protocol

Introduction

The dramatic increase of the incidence of infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) has led to an increase of 50% of carbapenem consumption all around Europe in only 5 years. This favours the spread of carbapenem-resistant Gram-negative bacilli (GNB), causing life-threatening infections. In order to limit use of carbapenems for infections actually due to ESBL-PE, health authorities promote the use of rapid diagnostic tests of bacterial resistance. The objective of this work conducted in the intensive care unit (ICU) is to determine whether an early de-escalation of empirical carbapenems guided by the result of the βLACTA test is not inferior to the reference strategy of de-escalating carbapenems after the antibiogram result has been rendered.

Methods and analysis

This multicentre randomised controlled open-label non-inferiority clinical trial will include patients suffering from respiratory and/or urinary and/or bloodstream infections documented with GNB on direct examination and empirically treated with carbapenems. Empirical carbapenems will be adapted before the second dose depending on the results of the βLACTA test performed directly on the microbiological sample (intervention group) or after 48–72 hours depending on the definite antibiogram (control group). The primary outcome will combine 90-day mortality and percentage of infection recurrence during the ICU stay. The secondary outcomes will include the number of carbapenems defined daily doses and carbapenem-free days after inclusion, the proportion of new infections during ICU stay, new colonisation of patients' digestive tractus with multidrug-resistant GNB, ICU and hospital length of stay and cost-effectiveness ratio.

Ethics and dissemination

This protocol has been approved by the ethics committee of Paris-Ile-de-France IV, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.

Trial registration number

NCT03147807.

http://bit.ly/2WENvws

Exploring the added value of hospital-registry data for showing local service outcomes: cancers of the ovary, fallopian tube and peritoneum

Objectives

To explore the added value of hospital-registry data on invasive epithelial ovarian, tubal and peritoneal cancers.

Design

Historic cohort analyses.

Methods

Unadjusted and adjusted regression.

Setting

Major South Australian hospitals.

Participants

1596 women (1984–2015 diagnoses).

Results

5-Year and 10-year survival was 48% and 41%, respectively, equivalent to relative survival for Australia and the USA. After adjusting for age, clinical and geographic factors, risk of ovarian cancer death was 25% lower in 2010–2015 than 1984–1989. Women generally had surgical treatment (87%) in their first round of care. This was more common for younger patients (adjusted OR (95% CIs) 0.17 (0.04 to 0.65) for 80+ vs <40 years) and earlier International Federation of Gynecology and Obstetrics stages (adjusted OR 0.48 (0.13 to 1.78) for stage IIIB/C and 0.13 (0.04 to 0.45) for stage IV vs stage IA). Most (74%) had systemic therapy, which was more common for advanced stages (adjusted ORs >15.0 for stages III and IV vs stage IA). Few (9%) had radiotherapy. Women generally had systemic therapy (74%), without difference by service accessibility and socioeconomic disadvantage, suggesting equity. However, surgery was less common for residents of the most compared with least remote areas (adjusted OR 0.49 (0.24 to 0.99)); and more common prior to adjustment in the highest versus lowest socioeconomic category (unadjusted OR 1.55 (1.01 to 2.39)), but this elevation did not apply after adjustment (adjusted OR 0.19 (0.63 to 2.25)), with the difference largely explained by stage.

Conclusions

Hospital-registry data add value for assessing local service delivery. Equivalent survival to Australia-wide and USA survival, and temporal gains after adjusting for stage and other patient characteristics are reassuring. Survival gains may reflect therapeutic benefits of more extensive surgery and improved chemotherapy regimens.

http://bit.ly/2RygC0J

Do baby boomers feel healthier than earlier cohorts after retirement age? The Lausanne cohort Lc65+ study

Objective

Despite the popular belief that baby boomers are ageing in better health than previous generations, limited scientific evidence is available since baby boomers have turned retirement age only recently. This study aimed to compare self-reported health status at ages 65–70 years among three cohorts of older people born before, during and at the end (baby boomers) of the Second World War.

Design

Repeated cross-sectional population-based study.

Setting

Community in a region of French-speaking Switzerland.

Participants

Community-dwelling older adults who enrolled in the Lausanne cohort 65+ study at ages 65–70 years in 2004 (n=1561), 2009 (n=1489) or 2014 (n=1678).

Outcomes

Number of self-reported chronic conditions (from a list of 11) and chronic symptoms (from a list of 11); depressive symptoms; self-rated health (very good, good, average, poor or very poor); fear of disease (not afraid at all, barely afraid, a bit afraid, quite afraid or very afraid); self-perception of ageing; disability in basic and instrumental activities of daily living.

Results

There was no significant difference between cohorts in the number of self-reported chronic conditions and chronic symptoms as well as the presence of difficulty in basic activities of daily living, depressive symptoms, fear of disease and negative self-perception of ageing. In women only, significant differences between cohorts were observed in self-rated health (p=0.005) and disability in instrumental activities of daily living (p=0.003), but these associations did not remain significant in logistic regression models adjusted for sociodemographic characteristics and unhealthy behaviours.

Conclusions

Despite important sociodemographic differences between older baby boomers and earlier cohorts, most health indicators did not suggest any trend towards a compression of morbidity. Future studies comparing these three cohorts at more advanced age are required to further investigate whether differences emerge later in life.

http://bit.ly/2WFcqQv

Place-specific factors associated with adverse maternal and perinatal outcomes in Southern Mozambique: a retrospective cohort study

Objectives

To identify and measure the place-specific determinants that are associated with adverse maternal and perinatal outcomes in the southern region of Mozambique.

Design

Retrospective cohort study. Choice of variables informed by literature and Delphi consensus.

Setting

Study conducted during the baseline phase of a community level intervention for pre-eclampsia that was led by community health workers.

Participants

A household census identified 50 493 households that were home to 80 483 women of reproductive age (age 12–49 years). Of these women, 14 617 had been pregnant in the 12 months prior to the census, of which 9172 (61.6%) had completed their pregnancies.

Primary and secondary outcome measures

A combined fetal, maternal and neonatal outcome was calculated for all women with completed pregnancies.

Results

A total of six variables were statistically significant (p≤0.05) in explaining the combined outcome. These included: geographic isolation, flood proneness, access to an improved latrine, average age of reproductive age woman, family support and fertility rates. The performance of the ordinary least squares model was an adjusted R²=0.69. Three of the variables (isolation, latrine score and family support) showed significant geographic variability in their effect on rates of adverse outcome. Accounting for this modest non-stationary effect through geographically weighted regression increased the adjusted R² to 0.71.

Conclusions

The community exploration was successful in identifying context-specific determinants of maternal health. The results highlight the need for designing targeted interventions that address the place-specific social determinants of maternal health in the study area. The geographic process of identifying and measuring these determinants, therefore, has implications for multisectoral collaboration.

Trial registration number

NCT01911494 .

http://bit.ly/2RDMRLM

Depression and anxiety in pet owners after a diagnosis of cancer in their pets: a cross-sectional study in Japan

Objective

To determine the presence and predictors of depression and anxiety in pet owners after a diagnosis of cancer in their pets.

Design

Cross-sectional study.

Setting

A veterinary medical centre specialised in oncology for dogs and cats and two primary veterinary clinics in Japan.

Participants

The participants for analysis were 99 owners of a pet with cancer diagnosis received in the past 1–3 weeks and 94 owners of a healthy pet.

Main outcome measures

Self-reported questionnaires were used to assess depression and anxiety. Depression was assessed using the Center of Epidemiologic Studies Depression Scale, and anxiety was measured by using the State–Trait Anxiety Inventory-Form JYZ.

Results

Depression scores were significantly higher in owners of a pet with cancer than owners of a healthy pet, even after adjustment for potential confounders (p<0.001). Within the owners of a pet with cancer, depression was significantly more common in those who were employed than those who were unemployed (p=0.048). State anxiety scores were significantly higher in owners of a pet with cancer than owners of a healthy pet, even after adjustment for potential confounders, including trait–anxiety scores (p<0.001). Furthermore, in owners of a pet with cancer, state anxiety was higher in owners with high trait anxiety (p<0.001) and in owners whose pets had a poor prognosis (p=0.027).

Conclusion

The results indicate that some owners tended to become depressed and anxious after their pets had received a diagnosis of cancer. Employment may be a predictor of depression. High trait anxiety and a pet with a poor prognosis may increase owners' state anxiety. Including the pet in a family genogram and attention to the pet's health condition may be important considerations for family practice.

http://bit.ly/2WFcn7h

HORYZONS trial: protocol for a randomised controlled trial of a moderated online social therapy to maintain treatment effects from first-episode psychosis services

Introduction

Specialised early intervention services have demonstrated improved outcomes in first-episode psychosis (FEP); however, clinical gains may not be sustained after patients are transferred to regular care. Moreover, many patients with FEP remain socially isolated with poor functional outcomes. To address this, our multidisciplinary team has developed a moderated online social media therapy (HORYZONS) designed to enhance social functioning and maintain clinical gains from specialist FEP services. HORYZONS merges: (1) peer-to-peer social networking; (2) tailored therapeutic interventions; (3) expert and peer-moderation; and (4) new models of psychological therapy (strengths and mindfulness-based interventions) targeting social functioning. The aim of this trial is to determine whether following 2 years of specialised support and 18-month online social media-based intervention (HORYZONS) is superior to 18 months of regular care.

Methods and analysis

This study is a single-blind randomised controlled trial. The treatment conditions include HORYZONS plus treatment as usual (TAU) or TAU alone. We recruited 170 young people with FEP, aged 16–27 years, in clinical remission and nearing discharge from Early Psychosis Prevention and Intervention Centre, Melbourne. The study includes four assessment time points, namely, baseline, 6-month, 12-month and 18-month follow-up. The study is due for completion in July 2018 and included a 40-month recruitment period and an 18-month treatment phase. The primary outcome is social functioning at 18 months. Secondary outcome measures include rate of hospital admissions, cost-effectiveness, vocational status, depression, social support, loneliness, self-esteem, self-efficacy, anxiety, psychological well-being, satisfaction with life, quality of life, positive and negative psychotic symptoms and substance use. Social functioning will be also assessed in real time through our Smartphone Ecological Momentary Assessment tool.

Ethics and dissemination

Melbourne Health Human Research Ethics Committee (2013.146) provided ethics approval for this study. Findings will be made available through scientific journals and forums and to the public via social media and the Orygen website.

Trial registration number

ACTRN12614000009617; Pre-results.

http://bit.ly/2REnqd8

Retrospective cohort analysis of real-life decisions about end-of-life care preferences in a Southeast Asian country

Objective

To describe the end-of-life care preferences of individuals, and to examine the influence of age and gender on these preferences.

Design, setting and participants

A retrospective cohort study was conducted. Participants included all adults (≥21 years old) (n=3380) who had completed a statement of their preferences as part of a national Advance Care Planning (ACP) programme in Singapore. Data were extracted from the national and Tan Tock Seng Hospital ACP database.

Main measures

End-of-life care preferences were obtained from the ACP document and differentiated by health status (healthy, chronically ill or diagnosed with advanced illnesses). To analyse the data, descriptive statistics and logistic regression analysis were used.

Results

Across healthy and chronically ill patients, the majority did not opt for cardiopulmonary resuscitation (CPR) or other life-sustaining measures. Among individuals with advanced illnesses, 94% preferred not to attempt CPR but 69% still preferred to receive some form of active medical treatment. Approximately 40% chose to be cared for, and to die at home. Age and sex significantly predict preferences in those with advanced illnesses. Older age (>=75 years) showed higher odds for home as preferred place of care (OR 1.52; 95% CI 1.23 to 1.89) and place of death (OR 1.29; 95% CI 1.03 to 1.61) and lower odds for CPR (OR 0.31; 95% CI 0.18 to 0.54) and full treatment (OR 0.32; 95% CI 0.17 to 0.62). Being female was associated with lower odds for home as preferred place of care (OR 0.69; 95% CI 0.57 to 0.84) and place of death (OR 0.70; 95% CI 0.57 to 0.85) and higher odds for full treatment (OR 2.35; 95% CI 1.18 to 4.68).

Conclusion

The majority preferred to not proceed with life-sustaining treatments, but there was still a strong preference to receive some form of limited treatment. Better understanding of end-of-life care preferences through ACP can better guide end-of-life care programme planning, and resource allocation decisions.

http://bit.ly/2WFcgIT

Temporal trends in severe morbidity and mortality associated with ectopic pregnancy requiring hospitalisation in Washington State, USA: a population-based study

Objective

To examine temporal trend in maternal mortality/severe morbidity associated with hospitalisation due to ectopic pregnancy.

Design

A population-based observational study.

Setting and participants

All women hospitalised for ectopic pregnancy in Washington State, USA, 1987–2014 (n=20 418). The main composite outcome of severe morbidity/mortality included death, sepsis, need for transfusion, hysterectomy and systemic or organ failure, identified by diagnostic and procedure codes from hospitalisation files. Severe morbidity/mortality due to ectopic pregnancy were expressed as incidence ratios among women of reproductive age (15–64 years) and among women hospitalised for ectopic pregnancy. Comparisons were made between 1987–1991 (reference) and 2010–2014 using ratios of incidence ratios (RR) and ratio differences (RD). The Cochran-Armitage test for trend assessed statistical significance; logistic regression was used to obtain adjusted OR (AOR) and 95% CI, adjusted for demographic factors and comorbidity.

Results

Hospitalisation for ectopic pregnancy declined from 0.89 to 0.16 per 1000 reproductive age women between 1987–1991 and 2010–2014 (p<0.001). Among reproductive age women, ectopic pregnancy mortality remained stable (0.03 per 100 000); and mortality/severe morbidity increased among women aged 25–34 years (p=0.022). Among women hospitalised for ectopic pregnancy, mortality increased from 0.29 to 1.65 per 1000 between 1987–1991 and 2010–2015 (p=0.06); severe morbidity/mortality increased from 3.85% to 19.63% (RR=5.10, 95% CI 4.36 to 5.98; RD=15.78 per 100 women, 95% CI 13.90 to 17.66; AOR for 1-year change was 1.08, 95% CI 1.07 to 1.08).

Conclusions

Hospitalisation for ectopic pregnancy declined in Washington State, USA, between 1987 and 2014; however, mortality/severe morbidity associated with ectopic pregnancy increased in female population aged 25–34 years.

http://bit.ly/2REnn0W

A trauma-informed substance use and sexual risk reduction intervention for young South African women: a mixed-methods feasibility study

Objectives

Sexual and physical trauma and substance use are intersecting risks for HIV among young women. This study assesses the feasibility, acceptability and preliminary effects of a novel trauma-informed substance use and sexual risk reduction intervention for young South African women.

Design

A single arm feasibility test and qualitative interviews of participants.

Participants

Sixty women, between 18 and 25 years of age, who reported trauma exposure, substance use and recent condom-less sex were recruited. Twenty participants were randomly selected for qualitative interviews.

Intervention

A six-session group-based intervention.

Main outcome measures

We examined the proportion of women who provided consent, completed counselling and were retained in the study. Qualitative interviews explored intervention acceptability. Preliminary effects of the intervention on substance use, mental health (depression, psychological distress and trauma symptoms) and sexual risk outcomes (STI symptoms, number of partners and condomless sex) were explored.

Results

Of the 66 eligible women, 91% were enrolled. Intervention completion rates were low; 35% attended all sessions. On average, participants attended four sessions (M=3.8, SD=1.3). A 93% follow-up rate was achieved at the 3-month endpoint. In this single group design, reductions in the proportion of participants who tested positive for methamphetamine, cannabis and methaqualone were observed at the 3-month endpoint. Symptoms of depression, psychological distress and trauma; number of STI symptoms; and number of sexual partners also decreased. Outcomes were similar for participants who completed up to four and those who completed five or more sessions. Participants thought the intervention was highly beneficial and proposed modifications to enhance acceptability.

Conclusions

This novel intervention seems acceptable and holds potential benefits for trauma-exposed women who use substances. Truncating the intervention may enhance the likelihood of its implementation. The efficacy of the intervention for improving substance use, sexual risk and mental health outcomes requires testing in a controlled design.

http://bit.ly/2Wxqj30

Protocol for a scoping review on the conceptualisation of learning in undergraduate clinical nursing practice

Introduction

Learning in the clinical setting is a major form of learning in undergraduate nursing education. In spite of this, how nursing students learn in clinical practice is still largely unknown. Moreover, there is no conceptual clarity on learning in practice in the current literature. This paper aims to set up a protocol for a scoping review of the literature in order to map different conceptualisations of learning in practice in undergraduate clinical nursing education in the hospital setting. The operationalisations of different concepts will be compared and the findings of the studies will be synthesised.

Methods and analysis

This scoping review will be guided by the methodological framework proposed by Arksey and O'Malley and refined by Levac et al. and the Joanna Briggs Institute. The search strategy will be developed together with a medical information specialist and the search will be performed in electronic databases (PubMed, EBSCO/ERIC and EBSCO/CINAHL). In a first search, we will identify concepts that are used as an equivalent to learning in practice. Next, we will search for studies operationalising these concepts in undergraduate nursing education. Finally, we will check reference lists for additional publications. Abstracts and full-text studies will independently be screened by two researchers. All studies that have 'learning in undergraduate clinical nursing practice' as their main topic and that include a definition and operationalisation of an equivalent to learning in clinical practice, will be considered for inclusion. We will chart different conceptualisations and their theoretical underpinnings, as well as reported learning opportunities, informal and formal aspects of learning, social aspects of learning and gaps in the literature.

Ethics and dissemination

This review will help design future studies on learning in clinical nursing practice using well-defined and agreed on terminology. The results will be disseminated through journal publications and conference presentations.

http://bit.ly/2REnidE

Why are male Chinese smokers unwilling to quit? A multicentre cross-sectional study on smoking rationalisation and intention to quit

Objective

We aimed to describe the rationalisation beliefs endorsed by Chinese male smokers and to examine the association between rationalisation and the intention to quit.

Setting

Questionnaires were conducted among male smokers in three cities (Shanghai, Nanning and Mudanjiang) which represent different geographical locations, economic development levels and legislative status of tobacco control in China.

Design and participants

It was a multicentre cross-sectional survey involved a total of 3710 male smokers over 18 years.

Outcome measures

Primary outcomes were intention to quit, smoking rationalisation scores and sub scores in six dimensions. Smoking rationalisation was assessed using a newly developed Chinese rationalisation scale. Multivariable logistic regression was performed to examine the relationship between rationalisation and intention to quit.

Results

On average, smokers scored 3.3 out of 5 on the smoking rationalisation scale. With a one point increase in total rationalisation scale, the odds for intention to quit in the next 6 months decreased by 48% (OR=0.52, 95% CI: 0.44 to 0.61; p<0.001). Separate logistic regressions for six subscales of rationalisation shown consistent inverse associations with intention to quit (all p values <0.001). Believing that smoking was socially acceptable was the strongest predictor (OR=0.62, 95% CI: 0.55 to 0.71; p<0.001).

Conclusions

Rationalisation beliefs could be important barriers to smoking cessation. Some beliefs have stronger association with quit intention than others. Eroding rationalisation beliefs endorsed by smokers is a potential strategy for smoking cessation intervention.

http://bit.ly/2WFc6RN

Protocol for a prospective, longitudinal cohort study on the effect of arterial disease level on the outcomes of supervised exercise in intermittent claudication: the ELECT Registry

Introduction

Despite guideline recommendations advocating conservative management before invasive treatment in intermittent claudication, early revascularisation remains widespread in patients with favourable anatomy. The aim of the Effect of Disease Level on Outcomes of Supervised Exercise in Intermittent Claudication Registry is to determine the effect of the location of stenosis on the outcomes of supervised exercise in patients with intermittent claudication due to peripheral arterial disease.

Methods and analysis

This multicentre prospective cohort study aims to enrol 320 patients in 10 vascular centres across the Netherlands. All patients diagnosed with intermittent claudication (peripheral arterial disease: Fontaine II/Rutherford 1–3), who are considered candidates for supervised exercise therapy by their own physicians are appropriate to participate. Participants will receive standard care, meaning supervised exercise therapy first, with endovascular or open revascularisation in case of insufficient effect (at the discretion of patient and vascular surgeon). For the primary objectives, patients are grouped according to anatomical characteristics of disease (aortoiliac, femoropopliteal or multilevel disease) as apparent on the preferred imaging modality in the participating centre (either duplex, CT angiography or magnetic resonance angiography). Changes in walking performance (treadmill tests, 6 min walk test) and quality of life (QoL; Vascular QoL Questionnaire-6, WHO QoL Questionnaire-Bref) will be compared between groups, after multivariate adjustment for possible confounders. Freedom from revascularisation and major adverse cardiovascular disease events, and attainment of the treatment goal between anatomical groups will be compared using Kaplan-Meier survival curves.

Ethics and dissemination

This study has been exempted from formal medical ethical approval by the Medical Research Ethics Committees United 'MEC-U' (W17.071). Results are intended for publication in peer-reviewed journals and for presentation to stakeholders nationally and internationally.

Trial registration number

NTR7332; Pre-results.

http://bit.ly/2RzezJD

Medicine authentication technology: a quantitative study of incorrect quarantine, average response times and offline issues in a hospital setting

Objectives

To introduce serialised medicines into an operational hospital dispensary and assess the technical effectiveness of digital medicine authentication (MA) technology under European Union Falsified Medicines Directive (EU FMD) conditions.

Design

Thirty medicine lines were serialised using 2D data matrix labels and introduced into an operational UK National Health Service (NHS) hospital dispensary. Staff were asked to check medicines for two-dimensional (2D) data matrices and scan those products, in addition to their usual medicine preparation and checking processes. Four per cent of the study medicines were labelled with a 2D barcode which generated a pop-up, identifying the medicine as either authenticated elsewhere (falsified), authenticated here, expired or recalled.

Setting

An NHS teaching hospital based in the UK, the same site as the Naughton et al 2016 study.

Participants

General Pharmaceutical Council registered, accredited accuracy checking technicians and pharmacists.

Primary outcome measures

Average response times, offline issues, instances of incorrect quarantine and workarounds. The EU FMD maximum response time is 300 milliseconds (ms).

Results

During the checking stage of medicine preparation, the average response time for MA in this study was 131 ms. However, 4.67% of attempted authentications experienced offline issues, an increase of 4.23% from the previous study. An increase in offline instances existed alongside an increase in incorrect quarantine.

Conclusions

Digital drug screening has the capability of operating with average response times which are below the maximum EU FMD limit of 300 ms. However, there was an increased incidence of offline errors and cases of incorrect quarantine. The practical and legal implications of supplying a substandard or falsified medicine during offline periods without prior authentication or withholding supply until online status resumes are not yet fully understood.

http://bit.ly/2WFc3p5

Association between child maltreatment and central sensitivity syndromes: a systematic review protocol

Introduction

A growing body of evidence is identifying the link between a history of child maltreatment and a variety of adverse health outcomes ultimately leading to significant social and healthcare burden. Initial work has identified a potential association between child maltreatment and the development of a selection of somatic and visceral central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic neck pain, chronic pelvic pain, interstitial cystitis, vulvodynia, chronic prostatitis, tension-type headache, migraine, myofascial pain syndrome, irritable bowel syndrome and restless legs syndrome.

Methods and analysis

Primary electronic searches will be performed in the Embase, MEDLINE, PubMed, Scopus, PyscINFO, CINAHL and Cochrane Library databases and a number of Grey Literature sources including child protection and paediatric conference proceedings. Following independent screening of studies by two review authors, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses template will be used to aid extraction. A meta-analysis will be conducted on the included case-control and cohort studies. The Newcastle-Ottawa grading system will be used to assess the quality of included studies. Results will be expressed as pooled ORs for binary data and mean differences for continuous data.

Ethics and dissemination

Ethics approval will not be required. The final results of the review and meta-analysis will be submitted for peer-review publication and also disseminated at relevant conference presentations.

PROSPERO registration number

CRD42018089258.

http://bit.ly/2REnb1I

Self-harm and social media: thematic analysis of images posted on three social media sites

Objectives

To explore the nature of images tagged as self-harm on popular social media sites and what this might tell us about how these sites are used.

Design

A visual content and thematic analysis of a sample of 602 images captured from Twitter, Instagram and Tumblr.

Results

Over half the images tagged as self-harm had no explicit representation of self-harm. Where there was explicit representation, self-injury was the most common; none of these portrayed images of graphic or shocking self-injury. None of the images we captured specifically encouraged self-harm or suicide and there was no image that could be construed as sensationalising self-harm.

Four themes were found across the images: communicating distress, addiction and recovery, gender and the female body, identity and belonging.

Conclusions

Findings suggest that clinicians should not be overly anxious about what is being posted on social media. Although we found a very few posts suggesting self-injury was attractive, there were no posts that could be viewed as actively encouraging others to self-harm. Rather, the sites were being used to express difficult emotions in a variety of creative ways, offering inspiration to others through the form of texts or shared messages about recovery.

http://bit.ly/2WBlfuy

Making headlines: an analysis of US government-funded cancer research mentioned in online media

Objective

To characterise how online media coverage of journal articles on cancer funded by the US government varies by cancer type and stage of the cancer control continuum and to compare the disease prevalence rates with the amount of funded research published for each cancer type and with the amount of media attention each receives.

Design

A cross-sectional study.

Setting

The United States.

Participants

The subject of analysis was 11 436 journal articles on cancer funded by the US government published in 2016. These articles were identified via PubMed and characterised as receiving online media attention based on data provided by Altmetric.

Results

16.8% (n=1925) of articles published on US government-funded research were covered in the media. Published journal articles addressed all common cancers. Frequency of journal articles differed substantially across the common cancers, with breast cancer (n=1284), lung cancer (n=630) and prostate cancer (n=586) being the subject of the most journal articles. Roughly one-fifth to one-fourth of journal articles within each cancer category received online media attention. Media mentions were disproportionate to actual burden of each cancer type (ie, incidence and mortality), with breast cancer articles receiving the most media mentions. Scientific articles also covered the stages of the cancer continuum to varying degrees. Across the 13 most common cancer types, 4.4% (n=206) of articles focused on prevention and control, 11.7% (n=550) on diagnosis and 10.7% (n=502) on therapy.

Conclusions

Findings revealed a mismatch between prevalent cancers and cancers highlighted in online media. Further, journal articles on cancer control and prevention received less media attention than other cancer continuum stages. Media mentions were not proportional to actual public cancer burden nor volume of scientific publications in each cancer category. Results highlight a need for continued research on the role of media, especially online media, in research dissemination.

http://bit.ly/2REn6Ls

Comparison of 8‐mm and 10‐mm Diameter Fully‐Covered Self‐Expandable Metal Stents: A Multicenter Prospective Study in Patients with Distal Malignant Biliary Obstruction

Abstract

Objectives

The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self‐expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8‐mm and 10‐mm diameter FCSEMS.

Methods

Eighteen tertiary‐care centers participated in the study. Patients were allocated to the 8‐mm and 10‐mm diameter groups. TRBO, non‐inferiority of the 8‐mm FCSEMS, overall survival time, frequency and type of adverse events, and non‐recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups.

Results

Median TRBOs did not differ significantly between the 8‐mm (n=102) and 10‐mm (n=100) groups (275 vs. 293 days, P=0.971). The hazard ratio of the 8‐mm to 10‐mm groups was 0.90 (80% confidence interval 0.77‐1.04, upper limit lower than the acceptable hazard ratio (1.33) of the null hypothesis). Based on these findings, the 8‐mm diameter stent was determined to be non‐inferior to the 10‐mm diameter stent. Survival time, incidence of adverse events, and non‐RBO rate at the time of death did not differ significantly between the two groups.

Conclusions

TRBO with an 8‐mm diameter FCSEMS was non‐inferior to that with a 10‐mm diameter FCSEMS. This finding is important for development of future SEMS.

(UMIN 000013560)

This article is protected by copyright. All rights reserved.

http://bit.ly/2t7eUcA

Small bowel obstruction with multiple perforations post chestnut ingestion

Phytobezoars are a rare cause of small bowel obstruction (SBO), which consists of vegetable matter such as seeds, skins, fibres of fruit and vegetables that have solidified. We present the case of a 61-year-old man with no previous surgery who presented with central abdominal pain, nausea and vomiting. An abdominal CT scan demonstrated SBO with a transition point in the left anterior abdomen. He proceeded to a laparoscopy, which revealed multiple perforations throughout the small bowel, from the proximal jejunum to the terminal ileum. Laparotomy was performed, and undigested chestnuts were milked out through the largest perforation and the perforations were oversewn. While obstruction due to phytobezoars is rare, this case demonstrates the importance of considering small bowel trauma and perforation due to phytobezoars and highlights the need for close inspection of the entire gastrointestinal tract for complications in the setting of phytobezoar-related bowel obstruction.

http://bit.ly/2D85FNX

Maculopathy from an accidental exposure to welding arc

Welding light can cause photic retinal injury. We report binocular maculopathy induced by a brief exposure to electric arc welding light in a patient who could not equipped with protective device because of narrow space. A 47-year-old man performed electric arc welding for approximately 10–15 min without wearing protective device because of narrow space and subsequently experienced eye discomfort and decreased visual acuity. At the initial visit, his best corrected visual acuity was 0.5. Fundus examination, optical coherence tomography (OCT) and multifocal electroretinogram (mfERG) were performed. OCT showed disruption in the ellipsoid zone, and mfERG amplitudes in the central 10° were markedly reduced in both eyes. The decrease in visual acuity had been noted for at least 18 months. Using the proper protective device is essential in welding, despite short time periods of work. For patients with welding-induced photokeratitis, doctors should also consider the possibility of photic retinal injury.

http://bit.ly/2G9EFBS

Adalimumab-induced acute myeloid leukaemia in a patient with Crohns disease

We present a patient with Crohn's disease under treatment with adalimumab who developed acute myeloid leukaemia (AML) with core-binding factor beta gene rearrangement. This case report emphasises the importance of long-term close follow-up of patients receiving adalimumab because of the increased risk of developing AML and other malignancies.

http://bit.ly/2DbY1lI

Novel Approaches for Treating Pain in Children

Abstract

Purpose of Review

Good pain management in children, especially those at end of life, is a crucial component of palliative medicine. The current review assesses some of the new and/or innovative ways to manage pain in children. The article focuses on some recent medications/pharmaceutical options such as cannabinoids and also innovative ways to administer medication to children, such as intranasal and inhalation.

Recent Findings

Current approaches to pain management now include (1) new uses of old drugs such as ketamine and lidocaine, (2) use of new drugs/medications such as cannabinoids, and (3) creative use of old technology such as atomizers, intranasal drops, and inhalation.

Summary

Typically, novel approaches to care rarely start in pediatrics or palliative care. The current review has presented some new and old drugs being utilized in new and old ways.

http://bit.ly/2t4oBJa

Patient Reported Outcome Measures (PROMs) and maintenance events in 2‐implant supported mandibular overdenture patients: A five‐year prospective study

Abstract

Objective

To prospectively evaluate Patient Reported Outcome Measures (PROMs) and treatment outcomes of mandibular two‐implant retained overdentures (IOD) in an edentulous geriatric cohort with history of deficient Complete Dentures (CD).

Materials and Methods

103 patients with deficient CD received new optimal CD. After a period of 3 months, 80 of the patients voluntarily received IOD. Outcomes collected at pre‐, post‐CD/post‐IOD treatment annually up to 5 years, included: A) Clinical outcomes: denture‐quality (Woelfel's index), complications, and maintenance events, B) PROMs: patient complaints (maxillary, mandibular functional complaint scores, generic aesthetic complaint scores, frequency, and intensity of complaints) and patient satisfaction, C) Maintenance events: technical complications and adverse events.

Results

5 years data were collected from 67 patients (mean age at initiation =71.3 years, mean observation=5.9 years) with cumulative implant survival‐rate=98.72%. Multiple comparisons for 8 time‐points showed significant improvements in denture‐quality and PROMs after new CD and IOD delivery. Further significant improvements were only after IOD delivery in: mandibular denture‐quality, mandibular and generic functional complaints, frequency, intensity of complaints, and overall patient satisfaction score. Thereafter, denture‐quality and PROMs remained stable. Maintenance events clustered on 1st year and within a minority of patients. Technical complications and overall maintenance events significantly correlated with overall patient satisfaction score at 1st year.

Conclusions

Mandibular IOD was a beneficial treatment option for seniors with history of deficient CD, improving denture‐quality, patient satisfaction, and reducing patient complaints up to 5 years. Maintenance events clustered on 1st year, showing no significant impact on long‐term patient satisfaction and other PROMs.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Rz9SQ1

Cost Effectiveness of Nusinersen in the Treatment of Patients with Infantile-Onset and Later-Onset Spinal Muscular Atrophy in Sweden

Abstract

Background

Spinal muscular atrophy is a rare neuromuscular disorder with a spectrum of severity related to age at onset and the number of SMN2 gene copies. Infantile-onset (≤ 6 months of age) is the most severe spinal muscular atrophy and is the leading monogenetic cause of infant mortality; patients with later-onset (> 6 months of age) spinal muscular atrophy can survive into adulthood. Nusinersen is a new treatment for spinal muscular atrophy.

Objective

The objective of this study was to evaluate the cost effectiveness of nusinersen for the treatment of patients with infantile-onset spinal muscular atrophy and later-onset spinal muscular atrophy in Sweden.

Methods

One Markov cohort health-state transition model was developed for each population. The infantile-onset and later-onset models were based on the efficacy results from the ENDEAR phase III trial and the CHERISH phase III trial, respectively. The cost effectiveness of nusinersen in both models was compared with standard of care in Sweden.

Results

For a time horizon of 40 years in the infantile-onset model and 80 years in the later-onset model, treatment with nusinersen resulted in 3.86 and 9.54 patient incremental quality-adjusted life-years and 0.02 and 2.39 caregiver incremental quality-adjusted life-years and an incremental cost of 21.9 and 38.0 million SEK (Swedish krona), respectively. These results translated into incremental cost-effectiveness ratios (including caregiver quality-adjusted life-years) of 5.64 million SEK (€551,300) and 3.19 million SEK (€311,800) per quality-adjusted life-year gained in the infantile-onset model and later-onset model, respectively.

Conclusions

Treatment with nusinersen resulted in overall survival and quality-adjusted life-year benefits but with incremental costs above 21 million SEK (€2 million) [mainly associated with maintenance treatment with nusinersen over a patient's lifespan]. Nusinersen was not cost effective when using a willingness-to-pay threshold of 2 million SEK (€195,600), which has been considered in a recent discussion by the Dental and Pharmaceutical Benefits Agency as a reasonable threshold for rare disease. Nonetheless, nusinersen gained reimbursement in Sweden in 2017 for paediatric patients (below 18 years old) with spinal muscular atrophy type I–IIIa.

http://bit.ly/2WFdCn1

The evolution and impact of sarcopenia pre‐ and post‐liver transplantation

Summary

Background

Sarcopenia is associated with both increased wait‐list mortality and mortality following liver transplantation.

Aims

To determine the course of sarcopenia from transplant evaluation until 1 year post‐transplant, and its implications on hospitalisation and mortality following liver transplantation.

Methods

Two hundred and ninety‐three transplant recipients from 2002 to 2006 had pre‐transplant CT scans analysed at the third lumbar region for sarcopenia, myosteatosis and abdominal visceral fat content. Half the recipients had post‐transplant CT scan for interpretation (161/293).

Results

Sarcopenia was present in 146/293 (50%) of the patients pre‐transplant. There was a significant decrease in muscle mass (loss 2.0 ± 4.9 cm²/m²; P < 0.001), and an increase in myosteatosis while awaiting liver transplantation. There was no significant change in abdominal visceral fat. For every 1 cm²/m² decrease in muscle mass there was an increase in post‐transplant length of stay by 0.36 days (P = 0.005). Post‐transplant, 98/161 (61%) of patients with CT imaging had sarcopenia (25 de novo and 73 persistent), with continued increase in myosteatosis, lower Hounsfield units (−5.0 [IQR −8.6 to 0.1]; P < 0.001) and an increase in abdominal visceral fat (4.9 [IQR −4.4 to 15.6] cm²/m²; P < 0.001). There was no statistically significant difference in 1‐year mortality in patients with de novo sarcopenia compared to patients with sarcopenia both pre‐ and post‐transplant (HR 1.88; P = 0.088).

Conclusions

Sarcopenia progresses up to 1 year following liver transplantation and is associated with an increase in post‐transplant length of stay.

http://bit.ly/2GrUKCn

Evaluation of Accepting Kidneys of Varying Quality for Transplantation or Expedited Placement with Decision Trees

Background: Underutilization of marginal-quality kidneys for transplantation produced ideas of expediting kidney placement for populations with decreased opportunities of receiving transplants. Such policies can be less efficacious for specific individuals and should be scrutinized until the decision-making for accepting marginal-quality organs, which has relied on experiential judgment, is better understood at the individual level. There exist rigorous tools promoting personalized decisions with useful and objective information. Methods: This article introduces a decision-tree methodology that analyzes a patient's dilemma: to accept a kidney offer now or reject it. The methodology calculates the survival benefit of accepting a kidney given a certain quality now and the survival benefit of rejecting it. Survival benefit calculation accounts for patients' and donors' characteristics and transplant centers' and organ procurement organizations' performances and incorporates patients' perceived transplant and dialysis utilities. Valuations of rejecting an offer are contingent on future opportunities and subject to uncertainty in the timing of successive kidney offers and their quality and donor characteristics. Results: The decision tree was applied to a realistic patient profile as a demonstration. The tool was tested on 1,000 deceased-donor kidney offers in 2016. Evaluating up to one year of future offers, the tool attains 61% accuracy with transplant utility 1.0 and dialysis utility 0.5. The accuracy reveals potential bias in kidney offer acceptance/rejection at transplant centers. Conclusions: The decision-tree tool presented could aid personalized transplant decision-making in the future by providing patients with calculated, individualized survival benefits between accepting and rejecting a kidney offer. *Corresponding Author: Vikram Kilambi, 20 Park Plaza Suite 920, Boston, MA 02116, E-mail: vkilambi@rand.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2D7WMnz

Donor characteristics, recipient outcomes, and histologic findings of kidney allografts with diffuse donor-derived glomerular fibrin thrombi

Background: Limited data is available regarding whether donor kidneys with diffuse glomerular fibrin thrombi (GFT) are safe to use. In this study, the clincopathologic characteristics of allografts with diffuse donor-derived GFT were examined. Methods: All deceased donor kidney transplant implantation biopsies from our institution between 07/2011 to 02/2018 with diffuse GFT were included. A control group for comparison consisted of all cases with implantation biopsies obtained during the study period without diffuse GFT. Clinical data were extracted from electronic medical records for all study patients, including donor information. Results: Twenty-four recipients received kidneys with diffuse GFT from 16 deceased donors. All donors died from severe head trauma. On average, 79% of glomeruli contained fibrin thrombi. Nineteen cases had subsequent biopsy; all revealed resolution of GFT. Compared to the control group, kidneys with diffuse GFT had longer cold ischemia time (34 versus 27 hours), were more frequently pumped using machine perfusion (100% versus 81%), and recipients experience a higher frequency of delayed graft function (58% versus 27%). Only two grafts with diffuse GFT failed within the first year. Overall graft survival was similar between the diffuse GFT group and control group. Conclusion: Deceased donor kidneys with diffuse GFT appear to be safe to use given that nearly 92% of recipients in this cohort who received such allografts experienced good clinical outcomes. Histologically, GFT demonstrated rapid resolution following transplantation. Interestingly, diffuse GFT only occurred in donors who suffered severe head trauma in this cohort, which may be a predisposing factor. Disclosure: The authors declare no conflicts of interest. Funding: None. Correspondence: Kuang-Yu Jen, MD, PhD, University of California Davis School of Medicine, Department of Pathology and Laboratory Medicine, 4400 V Street, Suite 1224, Sacramento, CA 95817, Phone: (916) 734-2579, Fax: (916) 734-2560, Email: kyjen@ucdavis.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2D7WJIp

Biliary Complications Following Pediatric Living Donor Liver Transplantation: Risk Factors, Treatments and Prognosis

Background: We present retrospective analysis of our 15-year experience with pediatric living donor liver transplantation (LDLT), focusing on the risk factors, treatments and long-term prognosis for post-transplant biliary complications (BCs). Methods: Between May 2001 and December 2017, 290 LDLTs were performed. The median age was 1.4 years old. The median observation period was 8.4 years. Biliary strictures were classified as anastomotic stricture (AS) or non-anastomotic stricture (NAS). Results: Overall incidence of BCs was 18.6%, including AS in 46 cases, NAS in six, and other classifications in two. The mean period to diagnosis of the AS was 641 ± 810 post-operative days. The multivariate analysis showed that hepaticojejunostomy without external stent was an independent risk factor for AS (p=0.011). The first treatments for AS were percutaneous transhepatic biliary drainage (PTBD) in 25 cases, double-balloon enteroscopy (DBE) in 19, and surgical re-anastomosis in 2. The success and recurrence rates of PTBD treatments were 88.9% and 18.8%, respectively. The success and recurrence rates of endoscopic interventions under DBE were 76.8% and 69.9%, respectively. The 15-year graft survival rates in patients with and without AS were 95.7% and 89.1%, respectively (p=0.255), but 2 patients with cholangitis due to multiple NAS underwent re-transplantation. Conclusions: Post-transplant AS can be prevented by hepaticojejunostomy using external stent, and the long-term prognosis is good with early treatments using DBE or PTBD. However, the prognosis of multiple NAS is poor. Disclosures: We have no conflicts of interest to disclose as described by the Transplantation. Funding: We have no finding sources. This abstract of this manuscript was accepted for oral presentation at the 18th Congress of the European Society for Organ Transplantation held in Barcelona in September 2017. Correspondence information: Yukihiro Sanada M.D., Ph.D., Department of Transplant Surgery, Jichi Medical University Address: 3311-1 Yakushiji, Shimotsuke City, Tochigi 329-0498, JAPAN. Telephone and fax: +81-285-58-7069, E-mail: yuki371@jichi.ac.jp Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2G95Ix0

CONTINUOUS MONITORING OF TRANSPLANT CENTER PERFORMANCE: DIFFERENT OPTIONS FOR DIFFERENT GOALS

Background– In France, the need for continuous monitoring of transplant center performance has recently become apparent. CUSUM monitoring of transplantation is already been used to monitor transplant outcomes in the UK and in the US. Because CUSUM monitoring can be applied by different methods, the objective was to assess and compare the performance of different CUSUM methods for detecting higher than expected (that is, excessive) graft failure rates. Methods– Data come from the French transplant registry. Lung and kidney transplants in 2011-2013 constituted the control cohort, and those in 2014-2016 the observed cohort. The performance of CUSUM monitoring, according to center type and predefined control limits, was measured by simulation. The outcome monitored was 3-month graft failure. Results– In a low-volume center with a low failure rate, 3 different types of control limits produced successful detection rates (SDRs) of excessive graft failures of 15, 62, and 73% and false alarm rates (FARs) of 5, 40, and 52%, with 3, 1, and 1 excess failures necessary before a signal occurred. In a high-volume center with a high failure rate, SDRs were 83, 93, and 100%, and FARs were 5, 16, and 69%, with 6, 13, and 17 excess failures necessary before a signal occurred. Conclusions– CUSUM performances vary greatly depending on the type of control limit used. A new control limit set to maximize specificity and sensitivity of detection is an appropriate alternative to those commonly used. Continued attention is necessary for centers with characteristics making it difficult to obtain adequate sensitivity or sufficiently prompt response. Disclosure: The authors declare no conflicts of interest. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Corresponding author contact information: Camille Legeai, Agence de la biomédecine, Direction Prélèvement Greffe Organes-Tissus, Pôle Evaluation, 1 avenue du Stade de France, 93212 Saint-Denis La Plaine cedex, France. Phone: +33 1 55 93 69 02. Fax: +33 1 55 93 69 30. Email: camille.legeai@biomedecine.fr Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2D7WRYp

Conversion from calcineurin inhibitors to belatacept in HLA- sensitized kidney-transplant recipients with low-level donor specific antibodies.

Background. Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to CNI nephrotoxicity. Few studies have described its use in patients with DSA. Methods. We retrospectively evaluated conversion from CNIs to belatacept in 29 HLA-immunized RTRs. Data regarding acute rejection, DSA and renal function were collected. These patients were compared to 42 non-immunized patients treated with belatacept. Results. Patients were converted from CNIs to belatacept a median of 444 days [IQR:85-1200] after transplantation and were followed-up after belatacept conversion, for a median of 308 days [IQR: 125-511]. At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were less than 1000MFI, 7/19 were between 1000 and 3000 MFI , and one was more than 3000 MFI. At last follow-up, pre-existing DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA positive group. In the non-immunized group, one patient developed de novo DSA (A24- MFI 970; biopsy for cause did not show BPAR or microinflammation score). After belatacept conversion, one ABMR was diagnosed. The mean eGFR improved from 31.7 ± 14.2 mL/min/1.73 m2 to 40.7 ± 12.3 mL/min/1.73 m2 (p

http://bit.ly/2G9IOFH

A custom made clamp facilitating stabilization of cuffs in murine heterotopic cervical heart transplantation

No abstract available

http://bit.ly/2G5SEZv

Developing CUSUM Charts for Monitoring Transplant Outcomes: Varied Goals and Many Possible Paths to Success

No abstract available

http://bit.ly/2G9MRC6

Utilization of deceased donor kidneys to initiate living donor chains: practical, ethical and logistical issues

No abstract available

http://bit.ly/2D9eUO7

Can mycophenolic acid-based immunosuppression benefit liver transplant patients with HCC?

No abstract available

http://bit.ly/2G96YAj

Tolerance Biomarkers in Liver Transplantation: Independent External Validation of the Predictive Strength of SENP6 and FEM1C Gene Expression

Background: Numerous studies have emphasized the genetic and phenotypic profiles of tolerant transplant patients. Moreover, different groups have defined several biomarkers, trying to distinguish patients who are going to be tolerant from those who are going to reject. However, most of these biomarkers have not been validated by other groups or even established for clinical practice. Methods: We reanalyzed and stratified the predictive capacity of 20 previously described biomarkers for liver transplantation tolerance in a cohort of 17 liver transplant patients subjected to an independent, nonrandomized, prospective study of immunosuppression drug withdrawal. Results: Only 4 of the 20 studied biomarkers (expression of SENP6, FEM1C, miR31 and miR95) showed a strong predictive capacity in the present study. miR31 and FEM1C presented an area under the ROC curve (AUC) of 96.7 %, followed by SENP1 with 93.3 %. Finally, miR95 had an AUC value below 86.7 %. Conclusions: Even though this independent analysis seems to confirm the predictive strength of SENP6 and FEM1Cin liver transplantation tolerance, there are also risks in establishing biomarkers for clinical phenotypes without an understanding of how they are biologically relevant. Future collaborations between groups should be promoted so that the most promising biomarkers can be validated and implemented in daily clinical practice. † Equal senior authors. Disclosure: The authors of this manuscript have no conflicts of interest to disclose. Funding: This work was supported by a grant from Instituto de Salud Carlos III (PI12/02042 and PI17/00489) for J.A.P. and Fundación Mutua Madrileña (FMM13) for A.B.M. as Principal Investigators. Corresponding Author: Alberto Baroja-Mazo; Murcia's Biohealth Research Institute-Virgen de la Arrixaca; LAIB Building - Lab 4.20; Ctra. Buenavista s/n 30120 Murcia (SPAIN); +34 868885031; alberto.baroja@um.es Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2D7WzAN

Tandem Orthotopic Living Donor Liver Transplantation Followed by Same Donor Haploidentical Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency: Tandem Liver and Bone Marrow Transplant in DOCK8 Deficiency

Background: An 11-year old girl with DOCK8 deficiency was proposed for potentially curative hematopoietic stem cell transplantation (HSCT), the donor being her haploidentical mother. However, end-stage liver disease, caused by chronic Cryptosporidium infection required liver transplantation before HSCT. Methods: Consequently, a staged approach of a sequential liver transplant followed by a HSCT was planned, with her mother as the donor for both liver and HSCT. Results: The patient successfully underwent a left lobe orthotopic liver transplant, however, she developed a biliary leak delaying the HSCT. Notably, the recipient demonstrated 3 percent donor lymphocyte chimerism in her peripheral blood immediately prior to HSCT. Haploidentical related donor HSCT performed two months after liver transplantation was complicated by the development of acyclovir-resistant HSV viremia, primary graft failure, and sinusoidal obstruction syndrome (SOS). The patient died from SOS associated multiorgan failure with Candida sepsis on day +40 following HSCT. Conclusions: We discuss the many considerations inherent to planning for HSCT preceded by liver transplant in patients with primary immunodeficiencies, including the role of prolonged immunosuppression and the risk of infection prior to immune reconstitution. We also discuss the implications of potential recipient sensitization against donor stem cells precipitated by exposure of the recipient to the donor lymphocytes from the transplanted organ. Acknowledgments: This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This trial is registered at Clinicaltrials.gov NCT01176006 Disclosure: The authors declare no conflicts of interest. Corresponding author: Nirali N. Shah , National Institutes of Health, Building 10/CRC, Room 1-5750, 10 Center Drive, Bethesda, MD 20892, USA. Phone 240-760-6199 , Email: shahnn@mail.nih.gov Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2G9INS9

Intraoperative Hemodynamic Parameters and Acute Kidney Injury After Living Donor Liver Transplantation

Background: Acute kidney injury (AKI) after living donor liver transplantation (LDLT) is associated with increased mortality. We sought to identify associations between intraoperative hemodynamic variables and postoperative AKI. Methods: We retrospectively reviewed 734 cases of LDLT. Intraoperative hemodynamic variables of systemic and pulmonary arterial pressure, central venous pressure (CVP), and pulmonary artery catheter-derived parameters including mixed venous oxygen saturation (SvO2), right ventricular end-diastolic volume (RVEDV), stroke volume, systemic vascular resistance, right ventricular ejection fraction, and stroke work index were collected. Propensity score matching analysis was performed between patients with (n= 265) and without (n=265) postoperative AKI. Hemodynamic variables were compared between patients with acute kidney injury (AKI), defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria, and those without AKI in the matched sample. Results: The incidence of AKI was 36.1% (265/734). Baseline CVP, baseline RVEDV and SvO2 at 5 min before reperfusion were significantly different between patients with and without AKI in the matched sample of 265 pairs. Multivariable logistic regression analysis revealed that baseline CVP, baseline RVEDV, and SvO2 at 5 min before reperfusion were independent predictors of AKI (CVP per 5 cmH2O increase: odds ratio [OR] 1.20, 95% confidence interval [CI] 1.09-1.32; SvO2: OR 1.45, 95% CI 1.27-1.71; RVEDV: OR 1.48, 95% CI 1.24-1.78). Conclusion: Elevated baseline CVP, elevated baseline RVEDV after anesthesia induction and decreased SvO2 during anhepatic phase were associated with postoperative AKI. Prospective trials are required to evaluate whether optimization of these variables may decrease the risk of AKI after LDLT. Source of funding: No external fund received. Conflict of interest: The authors declared no conflict of interests. Corresponding Author: Won Ho Kim, MD, PhD, Mailing Address: Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. E-mail: wonhokim.ane@gmail.com; Phone: 82-2-2072-2462; FAX: 82-2-747-5639 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2D7WwVD

Lost in Translation: Converting Empirical Evidence to Organ Acceptance Decision-Making: Lost in Translation

No abstract available

http://bit.ly/2G9xxoP

Racial/ethnic disparities in access and outcomes of simultaneous liver-kidney transplant among liver transplant candidates with renal dysfunction in the United States

Background: Since the Model for End-Stage Liver Disease (MELD) allocation system was implemented, the proportion of simultaneous liver-kidney transplantation (SLKT) has increased significantly. However, whether racial/ethnic disparities exist in access to SLKT and post-SLKT survival remains understudied. Methods: A retrospective cohort of patients age ≥18 with renal dysfunction on the liver transplant (LT) waiting list was obtained from Organ Procurement and Transplantation Network. Renal dysfunction was defined as estimated glomerular filtration rate

http://bit.ly/2D7Wtcp

Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention

Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention

Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention, Published online: 04 February 2019; doi:10.1038/s41416-018-0301-9

Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention

https://go.nature.com/2HOKTsr

Body mass index in early pregnancy and future risk of severe liver disease: a population‐based cohort study

Summary

Background

In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women.

Aim

To study the association between BMI early in life and development of liver disease later in life in women.

Methods

We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education.

Results

During an average follow‐up of 13.8 years, 774 women developed severe liver disease. Compared to women with a low normal BMI (18.5‐22.4), an increased risk of severe liver disease was found in women with BMI between 22.5 and 24.9 kg/m² (adjusted hazard ratio [aHR] 1.25, 95% CI 1.04‐1.50), 25.0 and 29.9 kg/m² (aHR 1.27, 95% CI 1.05‐1.53) and BMI ≥ 30 kg/m² (aHR 1.77, 95% CI 1.40‐2.24). When examining BMI as a continuous variable, the aHR increased by 4% per kg/m² (95% CI 1.02‐1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI.

Conclusion

A high BMI early in life in women is associated with a dose‐dependent, increased risk for future severe liver disease.

http://bit.ly/2Sk4cOr

Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention

https://go.nature.com/2RDSUAh

Shortage of Anxiety Drug Buspirone Creates Alarm Among Patients, Doctors

FRIDAY, Feb. 1, 2019 -- A shortage of the anti-anxiety drug buspirone in the United States has patients and doctors concerned. Buspirone is among one of the generic drugs for which prices have fallen so low that many manufacturers claim they cannot...

http://bit.ly/2Sa1Y4M

NLRP6 suppresses the inflammatory response of human periodontal ligament cells by inhibiting NF‐κB and ERK signal pathways

Abstract

Aim

To explore the function and mechanisms of NLRP6 (NOD‐, LRR‐ and pyrin domain‐containing 6) in the inflammatory response of human periodontal ligament cells (HPDLCs).

Methodology

Apical periodontitis tissues were obtained from 3 patients who received endodontic microsurgery. The expression of NLRP6 in 3 human apical periodontitis tissues and HPDLCs was examined by immunohistochemistry and immunofluorescence, respectively. The expressions of NLRP6, Phospho(p)‐ p65, p65, IκB‐α, p‐ IκB‐α, ERK, p‐ ERK, NLRP3, Pro interleukin (IL)‐1β, Pro caspase‐1 and apoptosis‐associated speck‐like protein containing a CARD (ASC) were examined by western blot. The gene expression and secretion of proinflammatory cytokines were detected by using quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Data were analysed statistically with independent sample t‐tests.

Results

NLRP6 was expressed in inflammatory periapical tissues and HPDLCs. Lipopolysaccharide (LPS) from Escherichia coli induced NLRP6 in HPDLCs (P<0.05). After silencing NLRP6, E. coli LPS‐induced activation of NF‐κB and ERK signaling was enhanced, which was also accompanied by elevated levels of IL‐6 and tumor necrosis factor‐α (TNF‐α) (P<0.05). Moreover, knockdown of NLRP6 led to up‐regulation of NLRP3, Pro IL‐1β and Pro caspase‐1 (P<0.05), whereas down‐regulation of ASC (P<0.05), which may contribute to unchanged levels of IL‐1β in HPDLCs inflammation.

Conclusion

NLRP6 was functionally expressed in inflammatory periapical tissues and HPDLCs. NLRP6 negatively regulated the production of IL‐6 and TNF‐α in HPDLCs inflammation by inhibiting NF‐κB and ERK signal pathways.

This article is protected by copyright. All rights reserved.

http://bit.ly/2D5zkaH

Association between autonomic dysfunction and olfactory dysfunction in Parkinson’s disease in southern Chinese

The aim was to investigate the autonomic dysfunction between Parkinson's disease (PD) patients with olfactory dysfunction and PD patients without olfactory dysfunction in southern Chinese population.

http://bit.ly/2WEUtkR

Nurse Decision Making in Acute Care

Effective nurse decision making is essential for best patient outcomes in the acute care nurse practice environment. The purpose of this study was to explore acute care RNs' perceptions of clinical decision making for a patient who experienced a clinical event. Clinical events include changes in patient condition and are manifested by fever, pain, bleeding, changes in output, changes in respiratory status, and changes in level of consciousness. Naturalistic decision making framework supported the exploration of important contextual factors associated with decision making, provided new information for nursing science, and served as the conceptual framework for this research. Data collected from interviews of 20 acute care nurses were analyzed using qualitative content analysis. The emergent categories included Awareness of Patient Status, Experience and Decision Making, Following Established Routine, Time Pressure, Teamwork/Support From Staff, Goals, Education, Resources, Patient Education, Consideration of Options to Meet Goals, and Nursing Roles. Acute care nurses incorporated a wide variety of complex factors when decision making. This study sought to improve understanding of the factors nurses found important to their decision making for the potential development of improved decision support in the electronic health record. This article is based on the first author's doctoral dissertation. This publication was supported by the National Library of Medicine of the National Institutes of Health under award T15LM011271. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding author: Christine W. Nibbelink, PhD, RN, Department of Biomedical Informatics, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093 (cnibbelink@ucsd.edu). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2Bhk7mF

How to Evaluate Acne in Reproductive-Age Women: An Epidemiological Study in Chinese Communities

Background. Acne is not only a skin condition but also a cardinal component of many systemic diseases or syndromes. This study was aimed to investigate the prevalence of acne in reproductive-age women in Sichuan province, China, and to evaluate acne as a skin problem alone or a symptom of gynecological/endocrinological disease. Methods. From October 2008 to September 2009, 1043 reproductive-age women from 19 to 45 years of age from seven communities of three districts in Sichuan province completed a standardized questionnaire and a physical examination. Acne was classified using the Pillsbury scale, and hirsutism was assessed using a modified Ferriman–Gallwey method. Diagnosis of polycystic ovary syndrome (PCOS) was based on the 2003 Rotterdam criteria. Some endocrine and metabolic markers were detected for the women diagnosed with PCOS related to acne and the control group. Results. The prevalence of acne was 32.5%, and the highest prevalence (9.6%) was seen in the 19–24-year-old age group. Prevalence among women eating dessert frequently, exercising seldom, or among sedentary workers was significantly higher in the acne group (14.1%, 55.6%, and 51.3%, respectively) than in the nonacne group (10.8%, 45.7%, and 35.5%; all P

http://bit.ly/2S36sdo

Stentoplasty of calcaneal fractures: surgical technique and early outcomes

Publication date: Available online 2 February 2019

Source: Injury

Author(s): Giuseppe Toro, Francesco Langella, Michele Gison, Gabriella Toro, Antimo Moretti, Antonio Toro, Giovanni Iolascon

Abstract

Calcaneus is the most common site of hindfoot fracture, frequently caused by fall from height or high energy trauma. The therapeutic strategy ranged from non-operative to ORIF (Open Reduction Internal Fixation). Indications for percutaneous fixation include soft tissue damage or relative contraindications to open surgery. Minimally invasive percutaneous calcaneoplasty should be an alternative to ORIF aiming to reach a stable reduction, early functional recovery and short hospital stay. The aim of our study was to evaluate the clinical and radiographic outcomes of calcaneus fractures treated with balloon calcaneoplasty (BCP) by using a new generation vertebral augmentation system, VBS™-Vertebral Body Stent-DePuy Synthes. A total of 10 patients treated with VBS™ system were recruited for the study. Nine fractures were caused by a fall from height and one case by traffic accident. The mean follow-up was 8.9 months (range 2.6–23.1). The fractures were categorized according to Sanders and Essex-Lopresti classifications (5: type II, 3: type III and 2: type IV; 9: "joint depression" type and 1 case "tongue" type). Radiographic measurement (Böhler's and Gissane's angles) were evaluated at both pre-operative and immediate postoperative time. The American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score as well as a subjective evaluation (Visual Analog Scale, VAS) were used for the clinical assessment at the last follow-up. Mean preoperative Böhler's angle was 12.3 ± 8.41° (95% CI 6.3-18.3°), whereas mean preoperative Gissane's angle was 123.66 ± 20.47° (95% CI 109.0-138.3°). At postoperative follow-up mean Böhler's angle increased to 21.51 ± 4.17° (95% CI 18.5-24.5°; p < 0.01), and mean postoperative Gissane's angle was 121.74°±6.82° (95% CI 116.8°-126.6°). Mean AOFAS at the last follow-up was 70.4 ± 17.44 (95% CI 57.9 -82.8).

Our study demonstrates that percutaneous calcaneoplasty using VBS™ is an effective treatment for calcaneus fracture and capable to implement correction manoeuvre with clinical and radiographic outcomes comparable with other percutaneous stentoplasty.

http://bit.ly/2G6B1IP

Surgical treatment with cannulated screws for pediatric femoral neck fractures: a case series

Publication date: Available online 2 February 2019

Source: Injury

Author(s): Vito Pavone, Gianluca Testa, Maria Riccioli, Antonio Di Stefano, Giuseppe Condorelli, Giuseppe Sessa

Abstract

Introduction

Femoral neck fractures are uncommon injuries in children, but the high incidence of long-term complications makes it important clinical entity. Early surgical treatment to achieve optimal results and to avoid a high rate of complications is widely advised. The purpose of this study was to retrospectively analyze the outcome of 8 children who sustained a femoral neck fracture.

Patients and Methods

The patients (6 boys and 2 girls with an average age of 9.2 years) were treated within 24 hours following admission to hospital by closed reduction and internal fixation. The type of fracture was distinguished according to Delbet's classification system. The outcome was analyzed using Ratliff's criteria, and a detailed record of complications was maintained.

Results

According Delbet's classification system, there were 3 type I, 2 type II, 2 type III, and 1 type IV fractures. The average follow-up was 39.2 months (range 8–95). A satisfactory outcome was obtained in 6 (75%) children. Avascular necrosis was the most notable complication, which was reported in the 2 fair outcomes (25%).

Conclusions

Early and aggressive surgical treatment aimed at anatomical reduction result in a satisfactory outcome in pediatric femur neck fractures. Development of avascular necrosis is the main complication.

http://bit.ly/2D4Oe0Q