Search

Background The obesity paradox is a well-documented phenomenon in cardiovascular disease, however it remains poorly understood. We aimed to investigate the relationship between body mass (as measured by body mass index [BMI]) and 1-year amputation-free survival (AFS) for patients undergoing lower limb revascularisation for chronic limb-threatening ischaemia (CLTI). Methods A retrospective analysis was undertaken of all consecutive patients undergoing lower limb revascularisation for CLTI at the Leicester Vascular Institute between February 2018–19. Baseline demographics and outcomes were collected using electronic records. BMI was stratified using the World Health Organization criteria. One-year AFS (composite of major amputation/death) was the primary outcome. Kaplan-Meier survival analysis and adjusted Cox's proportional hazard models were used to compare groups to patients of normal mass. Results One-hundred and ninety patients were included. Overall, no difference was identified in 1-year AFS across all groups (pooled P = 0.335). Compared to patients with normal BMI (n = 66), obese patients (n = 43) had a significantly lower adjusted combined risk of amputation/death (aHR 0.39, 95% CI 0.16–0.92, P = 0.032), however no significant differences were observed for overweight (aHR 0.89, 95% CI 0.47–1.70, P = 0.741), morbidly obese (aHR 1.15, 95% CI 0.41–3.20, P = 0.797) and underweight individuals (aHR 1.86, 95% CI 0.56–6.20, P = 0.314). Conclusions In the context of CLTI, obesity is potentially associated with favourable amputation-free survival at 1 year, compared to normal body mass. The results of this study support the notion of an obesity paradox existing within CLTI and question whether current guidance on weight management requires a more patient-specific approach.

We sought to determine if a novel online health tool, called Down Syndrome Clinic to You (DSC2U), could improve adherence to national Down syndrome (DS) guidelines. We also sought to determine if primary care providers (PCPs) and caregivers are satisfied with this personalized online health tool. In a national, randomized controlled trial of 230 caregivers who had children or dependents with DS without access to a DS specialist, 117 were randomized to receive DSC2U and 113 to receive usual care. The primary outcome was adherence to five health evaluations indicated by national guidelines for DS. DSC2U is completed electronically, in all mobile settings, by caregivers at home. The outputs—personalized checklists—are used during annual wellness visits with the patient’s PCP. A total of 213 participants completed a 7-month follow-up evaluation. In the intention-to-treat analysis, the intervention group had a 1.6-fold increase in the number of indicated evaluations that were recommended by the primary care provider or completed compared with controls. Both caregivers and PCPs reported high levels of satisfaction with DSC2U. DSC2U improved adherence to the national DS health-care guidelines with a novel modality that was highly valued by both caregivers and PCPs.

BACKGROUND Anemia is potentially associated with increased morbidity and mortality following vascular surgery procedures. This study investigated whether peri-procedural anemia is associated with reduced 1-year amputation-free survival (AFS) in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI). METHODOLOGY A retrospective analysis of patients diagnosed with CLTI between February 2018-February 2019, who subsequently underwent revascularization, was conducted. Hemoglobin concentration measured at index assessment was recorded and stratified by WHO criteria. Subsequent peri-procedural red blood cell transfusions (RBC) were also recorded. The primary outcome was 1-year AFS. Kaplan Meier survival analysis and Cox's proportional hazard modelling were conducted to assess the effect of anemia and peri-procedure transfusion on outcomes. RESULTS 283 patients were analyzed, of which 148 (52.3%) were anemic. 53 patients (18.7%) underwent RBC transfusion. Patients with anemia had a significantly lower 1-year AFS (64.2% vs. 78.5%, P = 0.009). A significant difference in 1-year AFS was also observed based upon anemia severity (P = 0.008) and for patients who received RBC transfusion (45.3% vs 77.0%, P < 0.001). On multivariable analysis, moderately severe anemia was independently associated with increased risk of major amputation/death (aHR 1.90, 95% CI 1.06-3.38, P = 0.030). After adjusting for severity of baseline anemia, peri-procedural RBC transfusion was associated with a significant increase in the combined risk of major amputation/death (aHR 3.15, 95% CI 1.91-5.20, P < 0.001). CONCLUSION Moderately severe peri-procedural anemia and subsequent RBC transfusion are independently associated with reduced 1-year AFS in patients undergoing revascularization for CLTI. Future work should focus on investigating alternative measures to managing anemia in this cohort.

An amendment to the 1962 Coroner’s Act in the Republic of Ireland mandated that all stillbirths and neonatal deaths were to be reported to the local coroner’s office. In response to this, the bereavement team and department of anatomic pathology modified the pathway for placental examination following stillbirth and reporting deaths to the coroner. This paper is a review of the effect of this practice. This study is a review of all cases of stillbirths for 9 months following the amendment of the Coroner’s Act. A descriptive, exploratory design was used involving a retrospective chart review. Twenty-nine cases of stillbirth occurred during the study period. In cases where a placental examination was performed (n = 22), a cause of death was identified in the placenta or cord for seventeen (68%) of these cases. Seven cases had a consented autopsy with six cases confirming the initial diagnosis made at the time of gross placental examination. In one case, the cause of the stillbirth remained unexplained following placental examination and a full autopsy. No new information was gained from the autopsy in these seven cases. A further two cases had an autopsy directed by the coroner; the cause of death in these cases will be decided by the coroner. The introduction of the pathway has improved the care provided to bereaved parents by providing parents with timely information about the potential cause of stillbirth and thereby reduces the need for an autopsy examination.

Background Working in maternity hospital is usually a rewarding experience for staff. However, it can also be stressful and emotionally difficult work. Schwartz Rounds are a multidisciplinary forum which provides staff with an opportunity to reflect on the emotional impact of their work and support each other. Aims This paper will discuss the implementation of Schwartz Rounds in a maternity hospital and gives details of a pilot study to evaluate the initiative. Methods Schwartz Rounds were commenced in the hospital in September 2019, and an evaluation is in progress. A pilot study which evaluated 2 rounds has been completed. Staff who attended Schwartz Rounds were asked to complete an anonymous feedback form immediately following the Round. The data from feedback forms were analysed using descriptive statistics. Results Seventy-eight members of staff from almost all departments attended the rounds. Feedback forms were completed by 55 members of staff. Overall, the rounds were very positively evaluated by those who participated in the study. Conclusions Schwartz Rounds are an effective way to support staff working in a maternity hospital.

Perinatal autopsy is one the most valuable investigations to ascertain the cause of death (Nijkamp et al., Seminars in Fetal & Neonatal Medicine. 22:167-175, 2017; Korteweg et al., AJOG 53, e1-12, 2012; Late Interuterine Death and Stillbirth’ RCOG Green-top Guideline No.55, 2015). Discussions about perinatal autopsy can be difficult for parents and healthcare professionals. Perinatal staff need a good level of knowledge and understanding regarding perinatal autopsy in order to discuss the procedure with parents. This study aims to investigate healthcare professionals’ knowledge regarding perinatal autopsy. An audit conducted in a large teaching hospital using a questionnaire was developed and distributed to healthcare professionals in the hospital. Seventy healthcare professionals participated in the audit. Of those surveyed, 64% (n = 45) have discussed perinatal autopsy with a mother and the majority of healthcare professionals (67%) found this difficult. Self-reported levels of understanding were found to be low with just 10% reporting ‘excellent understanding’. The results of this audit highlight the need for further education among all healthcare professionals working with bereaved families.

To improve the confidence in student Midwives to provide bereavement careto parents following pregnancy loss and perinatal death.The one-day interactive Educational Training Workshop in Bereavement Care (ETWBC) was developed for student midwives in their final year of their B.Sc. Midwifery Degree Programme and those completing a Higher Diploma in Midwifery to help improve their confidence to provide bereavement care in clinical practice.A longitudinal sequential mixed-methods design was used to evaluate the outcome and processes of participation in the Workshop. This paper reports on the outcome evaluation.Participants completed the study questionnaires at all 3 time points: pre/post workshop and 3 month follow-up. Thirty nine of the 41 student midwives (Higher Diploma and 4th year B.Sc.) participated in the workshop. 97.44% (n = 38) of the participants completed all the questionnaires.Participation in the ETWBC increased student's midwives confidence (measured using knowledge and skills scales); Bereavement support skills [F(2,72) = 21.150, p .000, partial eta squared = 0.370] and Bereavement support knowledge [F(1.6,60) = 48.460, p .000, partial eta squared = 0.567]to provide bereavement care. Improvement in Student Midwives' level of self-awareness of the needs of bereaved parents [F(2,72 )= 20.311, p .000, partial eta squared = 0.361] and of their own personal needs [F (1.7, 61) = 30.387, p .000, partial eta squared = 0.458] in relation to providing bereavement support were also found.Participation in the Education Training Workshop on Bereavement Care helped increase student midwives confidence to provide bereavement care to grieving parents and to increase their self-awareness around their clinical practice in this area. The ETWBC is recommended as a brief effective educational intervention for inclusion in Midwifery curricula which could be modified for use with other relevant professional groups.

Treatment of EGFR-mutant lung cancer with erlotinib results in dramatic tumor regression but it is invariably followed by drug resistance. In characterizing early transcriptional changes following drug treatment of mutant EGFR-addicted cells, we identified the stem cell transcriptional regulator SOX2 as being rapidly and specifically induced, both in vitro and in vivo. Suppression of SOX2 sensitizes cells to erlotinib-mediated apoptosis, ultimately decreasing the emergence of acquired resistance, whereas its ectopic expression reduces drug-induced cell death. We show that erlotinib relieves EGFR-dependent suppression of FOXO6, leading to its induction of SOX2, which in turn represses the pro-apoptotic BH3-only genes BIM and BMF. Together, these observations point to a physiological feedback mechanism that attenuates oncogene addiction-mediated cell death associated with the withdrawal of growth factor signaling and may therefore contribute to the development of resistance. DOI: http://dx.doi.org/10.7554/eLife.06132.001, eLife digest Tumors can form when cells gain mutations in genes that enable them to grow and divide rapidly. In some human lung cancers, genetic mutations are found in a gene that makes a protein called EGFR. This protein encourages cells to divide and the mutations can lead to the cancer cells producing more EGFR, or producing a form of the protein that is more active. Treating these cancers with a drug called erlotinib inhibits EGFR and makes the tumors shrink dramatically, but the tumors will usually re-grow because any tumor cells that survive often become resistant to the drug. There are several ways that the tumor cells can become resistant, which makes the task of developing a solution to this problem more difficult. It has been suggested that the tumor cells may enter a temporary ‘drug-tolerant’ state that helps them to survive and makes it more likely that they will develop resistance to the drug. However, it is not clear how this drug-tolerant state might work. To address this question, Rothenberg et al. examined which genes are switched on (or ‘expressed’) in tumor cells with a mutant version of EGFR after they were treated with the erlotinib drug. The experiments show that a gene called SOX2 is expressed in these cells. Cells that had lower levels of SOX2 expression were more sensitive to the effects of the drug and fewer cells developed resistance. On the other hand, cells that had higher levels of SOX2 expression were less sensitive to the drug and resistance was more likely to develop. A protein called FOXO6—which is usually suppressed by EGFR—activates the SOX2 gene in these cells. Therefore, using erlotinib to inhibit EGFR to kill the cancer cells increases the activity of FOXO6, which in turn promotes the survival of some of the cells by activating the SOX2 gene. A better understanding of the ways in which cancer cells adapt to erlotinib and other drugs may help us to design more effective treatments with better outcomes for patients. DOI: http://dx.doi.org/10.7554/eLife.06132.002

Sensory experience is influenced by emotional context. Although perception of emotion and unpleasant visceral sensation are associated with activation within the insula and dorsal and ventral anterior cingulate gyri (ACG), regions important for attention to and perception of sensory and emotional information, the neural mechanisms underlying the effect of emotional context upon visceral sensation remain unexplored. Using functional MRI, we examined neural responses to phasic, non-painful oesophageal sensation (OS) in eight healthy subjects (seven male; age range 27-36 years) either during neutral or negative emotional contexts produced, respectively, by presentation of neutral or fearful facial expressions. Activation within right insular and bilateral dorsal ACG was significantly greater (P < 0.01) during OS with fearful than with neutral faces. In a second experiment, we measured anxiety, discomfort and neural responses in eight healthy male subjects (age range 22-41 years) to phasic, non-painful OS during presentation of faces depicting either low, moderate or high intensities of fear. Significantly greater (P < 0.01) discomfort, anxiety and activation predominantly within the left dorsal ACG and bilateral anterior insulae occurred with high-intensity compared with low-intensity expressions. Clusters of voxels were also detected in this region, which exhibited a positive correlation between subjective behaviour and blood oxygenation level-dependent effect (P < 0.05). We report the first evidence for a modulation of neural responses, and perceived discomfort during, non-painful visceral stimulation by the intensity of the negative emotional context in which the stimulation occurs, and suggest a mechanism for the effect of negative context on symptoms in functional pain disorders.

Background The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. Methods Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. Results In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with different patterns of activation: provocation of washing-relevant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant anxiety predominantly activated ventral prefrontal regions and the left amygdala. Conclusions Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with different symptom dimensions is associated with differential patterns of activation of these neural systems. Further investigation of the neural basis of OCD symptom dimensions is required.

Mid-trimester loss (MTL) is an area that is poorly defined in the literature and often under reported in clinical practice. The prevalence of MTL in Ireland is uncertain and has a huge impact on the woman, her family and maternity care services. To explore the prevalence and patterns of care for women with MTL in a large Maternity hospital in Ireland. A descriptive, exploratory study was used involving a retrospective chart audit. 220 women presented with MTL over the 3 year data collection period (January 2011–December 2013), giving a rate of 0.8 % of all deliveries. The majority of women had no previous pregnancy losses and were multiparous (i.e., had a previous pregnancy >500 g). The mean gestational age was 17.69 weeks (SD = 2.73). The mean length of hospital stay was 1.89 days. Intra muscular (IM) analgesia was the most commonly (58.5 %) used medication. Follow up hospital care was received in over 78 % of cases. The majority of women were referred the CMS Bereavement and Chaplain services, with a small number (approx. 5 %) referred to the social worker. Over 46.4 % of families availed of the hospital burial service. Results suggest the incidence of mid-trimester loss may be slightly lower than the 1 or 2 % of pregnancies reported in the literature. The incidence of mid-trimester loss in multiparous women is approximately twice that of nulliparous women. The referral services offered in the study were utilised by most of the women, as were follow-up clinic appointments.