Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Nursing Students’ Reflections on the Death Process

La actitud y el miedo a la muerte en enfermería pueden condicionar la calidad de cuidados del paciente moribundo, por lo que es importante abordar este tema. Es necesario aprender a percibir la muerte como algo natural. Los sanitarios tratan a los moribundos, interpretan el fenómeno de la muerte y la muerte misma bajo su óptica y entendimiento. La formación en tanatología y los cuidados paliativos se trata de forma escasa o al menos de forma irregular en los planes de estudio. El objetivo del presente trabajo es analizar las aportaciones de los alumnos de tercero de enfermería en la asignatura cuidados paliativos a la hora de escribir una reflexión sobre un artículo que trata la visión de una enfermera del proceso de la muerte. Se empleó la fenomenología como instrumento metodológico, con el que se pretendió elaborar inductivamente un marco explicativo del fenómeno estudiado a partir de las expresiones de los estudiantes. En relación a la actitud hacia el trabajo con enfermos terminales y hacia la muerte se pueden resaltar los siguientes datos: escasa preparación, afrontamiento ineficaz, miedos, valores y creencias. Predomina la inquietud relacionada con el encarnizamiento terapéutico y con la actitud obstinada del equipo de salud por salvar lo insalvable. Los resultados ponen de manifiesto un grado muy elevado de implicación emocional de la enfermera en el cuidado del paciente moribundo. Se considera como pilar fundamental una preparación específica para adaptarse mejor al trabajo con los pacientes terminales. Destaca el interés y la preocupación por la excelencia. Es muy importante el analizar los problemas en “entorno de la muerte” en los estudiantes de enfermería. La investigación cualitativa en este campo podría ser una de las herramientas útiles para detectar inquietudes y preocupaciones.ABSTRACT One’s attitude toward and fear of death in the nursing field can determine the quality of care that a dying patient receives, which makes this topic an important one to consider and discuss. It is necessary for one to learn to perceive death as a natural process. Healthcare workers treat dying patients, interpreting the phenomenon of death as well as death itself through their own personal lens and breadth of understanding. Training in thanatology and palliative care is scarcely and irregularly included in regular academic curricula. The objective of this study is to analyze the contributions of 3rd-year nursing students on the subject of palliative care upon writing a reflective journal entry about an article that surrounds a nurse’s view on the process of dying. Phenomenology was used as a methodological instrument which intended to inductively draw up a standardized explanation of the phenomenon of death through the students’ expressed thoughts on the matter. Relating to the attitudes that nurses that work with the terminally ill have towards death, the following facts stand out as impactful: lack of preparation, ineffective coping, and personal fears, values, and beliefs. Additionally, uneasiness associated with the use of life support and the care team’s obstinate insistence on saving what cannot be saved is predominant. The results emphasize a very elevated level of the nurse’s emotional involvement in caring for a dying patient. Specific preparation geared toward a better adaptation in working with terminal patients has been identified as a fundamental pillar for nurses in this line of work. Personal interest and emphasis on occupational excellence also stand out as influential factors. It is very important to analyze the problems regarding this “environment of death” and its impact on nursing students. Qualitative research in this field could be a useful tool in detecting worries and uncertainties surrounding this matter

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research