Emergency general surgery 'Hot Clinic': Efficiency, prevention of hospital admissions and factors influencing patient experience.

Objective: The constant pressure facing hospitals to reduce emergency inpatient admissions has led towards more consultant-led 'Hot Clinics' (HC). The patient experience in these settings remains poorly understood. This study evaluates the efficiency and ability of the HC to prevent unnecessary emergency surgical admissions and factors influencing the patient experience.

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors.

Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts.

Background: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC).

Methods: We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.

The benefits of non-invasive ventilation for Community-Acquired Pneumonia: A meta-analysis.

Background: There is an observed international increase in NIV application as an alternative to endotracheal intubation in non-COPD patients admitted with community acquired pneumonia despite the lack of strong evidence for its use. The aim of this study is the meta-analysis of data from randomised-controlled trials on the effectiveness of non-invasive ventilation versus standard medical care in adults admitted with severe community-acquired pneumonia.

Methods: Monthly electronic searches on CENTRAL and MEDLINE were performed between September 2017 and October 2019.

Identification of atrial fibrillation in secondary care diabetes and vascular clinics: a pilot study.

To determine the feasibility and utility of the AliveCor handheld ECG device in screening for asymptomatic atrial fibrillation in high-risk patients attending secondary care clinics. Patients were recruited from diabetes and vascular outpatient clinics, and the AliveCor device used to store a 30-second ECG recording. Clinical risk stratification systems (CHADS-VAS and HAS-BLED) assessed individual suitability for oral anticoagulation.

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.

Prediction and clinical utility of a contralateral breast cancer risk model.

Background: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making.

Methods: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.

Two truncating variants in FANCC and breast cancer risk.

Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies.

Disrupted biographies and balancing identities: A qualitative study of cancer patients' communication with healthcare professionals about dependent children.

Objective: About 14% of cancer patients live with dependent children. Healthcare professionals are well placed to help patients support their children as part of a patient-centred practice. Children tend to appreciate open communication during the course of illness, but patients often find this difficult.

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets.

Long-term outcomes following surgical repair of giant paraoesophageal hiatus hernia.

Introduction: There are limited data regarding long-term outcomes after surgical repair of giant paraoesophageal hiatus hernia (GPHH). The aim of this study was to assess symptomatic recurrence and patient-reported outcomes following GPHH repair.

Methods: 178 patients undergoing elective (127) and emergency (51) GPHH repair between 1994 and 2015 were identified from the prospectively collected Lothian Surgical Audit database.

Renal and Blood Pressure Response to a High-Salt Diet in Mice With Reduced Global Expression of the Glucocorticoid Receptor.

Salt-sensitive hypertension is common in glucocorticoid excess. Glucocorticoid resistance also presents with hypercortisolemia and hypertension but the relationship between salt intake and blood pressure (BP) is not well defined. GR mice have global glucocorticoid receptor (GR) haploinsufficiency and increased BP.

A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas.

E-cadherin breast tumor expression, risk factors and survival: Pooled analysis of 5,933 cases from 12 studies in the Breast Cancer Association Consortium.

E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium.

The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity.

Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3.

- a novel candidate breast cancer susceptibility locus on 6q14.1.

Most non- breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.

Body mass index and breast cancer survival: a Mendelian randomization analysis.

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.

Temperature Variability in a Modern Targeted Temperature Management Trial.

Objectives: The Eurotherm3235 trial showed that therapeutic hypothermia was deleterious in patients with raised intracranial pressure following traumatic brain injury. We sought to ascertain if increased temperature variability within the first 48 hours, or for 7 days post randomization, were modifiable risk factors associated with poorer outcome.

Design: Eurotherm3235 was a multicenter randomized controlled trial.

Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study.

Background: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis.

Methods: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC).

Association analysis identifies 65 new breast cancer risk loci.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry.

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

Purpose: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe.

Methods: We undertook a mixed-methods, situational analysis.