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PURPOSE: Histological grading of tumours is a well-established biomarker used to guide treatment in female breast cancer. However, its significance in male breast cancer remains unclear. This systematic review investigates the prognostic significance of tumour grade in relation to breast cancer-specific survival (BCSS) in male breast cancer patients undergoing surgery. METHODS: MEDLINE, PUBMED Central and EMBASE databases were searched to identify randomised trials and observational studies related to male breast neoplasms, tumour grading, recurrence, and survival. RESULTS: A total of fifteen observational type studies were included in the review. A significant association between tumour grade and BCSS was reported in a majority of studies. This association was most evident with regard to high-grade (grade III) compared to low grade (grade I) tumours, with a significant relationship in 4 out of 4 studies. For intermediate-grade II tumours an association was demonstrated in a minority of studies. CONCLUSIONS: This study confirms an association between high-grade male breast cancers and poorer disease-specific survival, however, the significance of intermediate-grade tumours remains unclear. Further research is required to investigate the biology of male breast cancer in relation to histological grade and optimally define intermediate-grade disease.
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Neoplasias da Mama Masculina , Gradação de Tumores , Humanos , Masculino , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama Masculina/patologia , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
The BPaLM regimen (bedaquiline, pretomanid, linezolid and moxifloxacin) recently recommended by the World Health Organization offers short, safe, and effective treatment for multidrug-resistant/rifampicin-resistant tuberculosis (TB). In a survey with national TB focal points in 18 central and western European countries to explore barriers for the implementation of BPaLM, only three reported full availability of pretomanid, a necessary component of this regimen. Implementation barriers included financing and procurement. Solutions on national and supranational level are needed to guarantee universal access.
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Antituberculosos , Linezolida , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Organização Mundial da Saúde , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Europa (Continente) , Linezolida/uso terapêutico , Rifampina/uso terapêutico , Moxifloxacina/uso terapêutico , Diarilquinolinas/uso terapêutico , Nitroimidazóis/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Acessibilidade aos Serviços de SaúdeRESUMO
PURPOSE: Nausea is a common and unpleasant sensation for which current therapies such as serotonin (5-HT3) antagonists are often ineffective, while also conferring a risk of potential adverse events. Isopropyl alcohol (IPA) has been proposed as a treatment for nausea. We aimed to compare IPA with 5-HT3 antagonists for the treatment of nausea across all clinical settings. METHODS: MEDLINE, EMBASE, PubMed, CENTRAL and CINAHL were searched from inception to 17 July 2023 for randomised controlled trials (RCTs) comparing inhaled IPA and a 5-HT3 antagonist for treatment of nausea. Severity and duration of nausea, rescue antiemetic use, adverse events and patient satisfaction were the outcomes sought. Risk of bias (RoB) was assessed using Cochrane RoB 2. Random-effects model was used for meta-analysis. Combination of meta-analyses and narrative review was used to synthesise findings. The evidence was appraised using GRADE. RESULTS: From 1242 records, 4 RCTs were included with 382 participants. Participants receiving IPA had a significantly lower mean time to 50% reduction in nausea (MD - 20.06; 95% CI - 26.26, - 13.85). Nausea score reduction at 30 min was significantly greater in the IPA group (MD 21.47; 95% CI 15.47, 27.47). IPA led to significantly reduced requirement for rescue antiemetics (OR 0.60; 95% CI 0.37, 0.95; p = 0.03). IPA led to no significant difference in patient satisfaction when compared with a 5-HT3 antagonist. The overall GRADE assessment of evidence quality ranged from very low to low. CONCLUSION: IPA may provide rapid, effective relief of nausea when compared with 5-HT3 antagonists.
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Antieméticos , Serotonina , Humanos , Serotonina/uso terapêutico , 2-Propanol/uso terapêutico , Náusea/tratamento farmacológico , Náusea/induzido quimicamente , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêuticoRESUMO
INTRODUCTION: Non-technical skills complement technical skills in surgeons to provide best possible care for patients. The former is essential to promote patient engagement. Coaching has been introduced to surgeons as a method to improve non-technical skills. We aimed to investigate the impact of coaching for surgeons on patient engagement in the outpatient consultation setting. METHODS: This was a single-centre cohort study conducted in South Australia. Consultant surgeons, suitable coaches, and patients were recruited. Coaches underwent further training by a human factors psychologist on being an effective coach. Outpatient consultations were recorded in an audio-visual format and analysed by investigators. Patient talking time, mutual eye gaze between surgeon and patient, and number of questions asked by the patient were measured as outcomes for patient engagement. RESULTS: 182 patients, 12 surgeons, and 4 coaches participated in the study. Each surgeon underwent 3 coaching sessions, 5 to 6 weeks apart. There were 62 pre-coaching patient consultations, 63 patient consultations after one coaching session, and 57 patient consultations after two coaching sessions. The mean talking time of the patient increased significantly after a single coaching session (P < 0.05) without making significant difference to the total consultation time (p = 0.76). Coaching sessions did not have a significant effect on mutual eye gaze or mean number of questions asked by the patient. CONCLUSION: Coaching of non-technical skills for surgeons appears to objectively improve patient engagement during the outpatient consultation. This would suggest that tailored coaching programs should be developed and delivered to surgeons to improve care delivery.
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Tutoria , Cirurgiões , Humanos , Tutoria/métodos , Participação do Paciente , Estudos de Coortes , Cirurgiões/educaçãoRESUMO
BACKGROUND: Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors. METHODS: PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. REGISTRATION: PROSPERO, CRD42021262345. RESULTS: From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2-58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia-Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not. CONCLUSIONS: Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.
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Depressão , Transtorno Depressivo Maior , Humanos , Depressão/etiologia , Transtornos de Ansiedade , Ansiedade , Qualidade de VidaRESUMO
OBJECTIVE: Rapid response systems designed to detect and respond to clinical deterioration often incorporate a multitiered, escalation response. We sought to determine the 'predictive strength' of commonly used triggers, and tiers of escalation, for predicting a rapid response team (RRT) call, unanticipated intensive care unit admission, or cardiac arrest (events). DESIGN: This was a nested, matched case-control study. SETTING: The study setting involved a tertiary referral hospital. PARTICIPANTS: Cases experienced an event, and controls were matched patients without an event. OUTCOME MEASURES: Sensitivity and specificity and area under the receiver operating characteristic curve (AUC) were measured. Logistic regression determined the set of triggers with the highest AUC. RESULTS: There were 321 cases and 321 controls. Nurse triggers occurred in 62%, medical review triggers in 34%, and RRT triggers 20%. Positive predictive value of nurse triggers was 59%, that of medical review triggers was 75%, and that of RRT triggers was 88%. These values were no different when modifications to triggers were considered. The AUC was 0.61 for nurses, 0.67 for medical review, and 0.65 for RRT triggers. With modelling, the AUC was 0.63 for the lowest tier, 0.71 for next highest, and 0.73 for the highest tier. CONCLUSION: For a three-tiered system, at the lowest tier, specificity of triggers decreases, sensitivity increases, but the discriminatory power is poor. Thus, there is little to be gained by using a rapid response system with more than two tiers. Modifications to triggers reduced the potential number of escalations and did not affect tier discriminatory value.
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Equipe de Respostas Rápidas de Hospitais , Hospitalização , Humanos , Estudos de Casos e Controles , Sensibilidade e Especificidade , Unidades de Terapia IntensivaRESUMO
OBJECTIVES: This study examined the impact of the residential environment, measured by the Healthy Ageing/Vulnerable ENvironment (HAVEN) Index, on risk of mortality or entry into Permanent Residential Aged Care (PRAC). DESIGN: A retrospective cohort study using data from the Registry of Senior Australians (ROSA) was conducted. HAVEN Index values were matched to the ROSA by residential postcode. STUDY SETTING AND PARTICIPANTS: Older individuals living in metropolitan Adelaide and receiving their first eligibility assessment for aged care services between 2014 and 2016 (N = 16,944). MAIN OUTCOME MEASURE: Time to death and entry into PRAC were the main outcomes. RESULTS: A higher HAVEN Index value, which represents a favourable residential environment, was associated with a lower risk of mortality and delayed entry to PRAC. For every 0.1 unit increase in HAVEN Index value, the risk of mortality is 3% lower (adjusted hazard ratio [HR], 95% confidence interval [CI] = 0.97, 0.96-0.99) and the risk of entry to PRAC is 5% lower (adjusted subdistribution HR, 95%CI = 0.95, 0.94-0.97) in the first 2 years following aged care assessment. After 2 years, the HAVEN Index was not associated with the risk of transition to PRAC. CONCLUSION: Place-based health inequalities were identified in Australians seeking aged care services, demonstrating that a better understanding of local neighbourhoods may provide insight into addressing ageing inequalities. Spatial indexes, such as the HAVEN Index, are useful tools to identify areas where populations are more vulnerable to adverse health outcomes, informing responses to prioritise local improvements and health interventions to enable healthy ageing.
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Envelhecimento , Vida Independente , Idoso , Austrália/epidemiologia , Humanos , Estudos Retrospectivos , Austrália do Sul/epidemiologiaRESUMO
The etiology of postfundoplication dysphagia remains incompletely understood. Subtle changes of gastroesophageal junction (GEJ) anatomy may be contributory. Barium swallows have potential for standardization to evaluate postsurgical anatomical features. Using structured barium swallows, we aim to identify reproducible, objectively measured postfundoplication anatomical features that will permit future comparison between patients with/without dysphagia. At 6-12 months of postfundoplication, 31 patients underwent structured barium swallow with video-fluoroscopy recording: standing anteroposterior; standing oblique (×2); prone oblique (×2); and prone oblique with continuous free drinking. A primary observer recorded 11 variables of GEJ anatomy for each view, repeated 3 months later, forming two datasets to assess intraobserver consistency. Interobserver reliability was determined using a dataset each from the primary observer and two medical students (after training). Intraclass correlation coefficients (ICC) were based on two-way mixed-effects model (ICC agreement: 0.40-0.59 'fair'; 0.60-0.74 'good'; 0.75-1.00 'excellent'). Interobserver reliability was good-excellent for 47 of 66 measurements. Measures of maximal esophageal diameter cf. wrap opening diameter and posterior esophageal angle showed high interobserver reproducibility on all views (ICC range 0.84-0.91; 0.68-0.80, respectively). Interobserver agreement was good-excellent for 5/6 views when measuring anterior GEJ displacement and axis deviation (ICC range 0.56-0.79; 0.41-0.77, respectively). Measures of wrap length showed lower reproducibility. Prone oblique measurements showed highest reproducibility (good-excellent agreement in 19/22 measurements). Intraobserver consistency was excellent for 98% of measurements (ICC range 0.74-0.99). Objective measurements of postfundoplication GEJ anatomy using structured barium swallow are reproducible and may allow further interrogation of anatomical features contributing to postfundoplication dysphagia.
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Transtornos de Deglutição , Fundoplicatura , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Fluoroscopia , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
PURPOSE: Prolonged time to diagnosis of primary intracerebral haemorrhage (ICH) can result in delays in obtaining appropriate blood pressure control, reversal of coagulopathy or surgical intervention in select cases. We sought to characterise the time to diagnosis in a cohort of patients with ICH and identify factors associated with delayed diagnosis. METHODOLOGY: The stroke database of our hospital was retrospectively reviewed to identify patients presenting to our hospitals emergency department with ICH over two years (January 2017-December 2018.) Data collected included demographics (age and sex), comorbidities, anticoagulation status, clinical scores (NIHSS, GCS, ICH score), and imaging (anatomical site, haematoma size). Time from symptom onset to diagnosis and hospital presentation were recorded. Factors associated with diagnosis >8 h post ictus were assessed using a univariate and then multivariable analysis. RESULTS: 235 patients were identified with 125 males (53%) and a median age of 76 (range 40-98). For the 200 patients that initially presented to our hospital, median time to presentation was 179 min (IQR 77-584 min), and median time from ictus to imaging diagnosis was 268 min (IQR 114-717 min). 139 (70%) presented within 8 h of symptom onset, and 129 (65%) patients had imaging of the brain performed within 8 h of symptom onset. Factors associated with presentation >8 h post symptom onset included wake up stroke (OR 5.31, 95% confidence interval (CI) 2.36-11.96, p < 0.0001) and age (OR 1.04, 95% CI 1.01-1.08, p = 0.01). Patients with hemiplegia were less likely to present >8 h following ictus (OR 0.41, 95% CI 0.21-0.84, p = 0.01). CONCLUSIONS: The majority of patients with ICH presented within 8 h of ictus. Cases of delayed diagnosis involved patients who had not incurred hemiplegia.
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Hemiplegia , Acidente Vascular Cerebral , Masculino , Humanos , Estudos Retrospectivos , Hemiplegia/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/terapia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Anticoagulantes , HospitaisRESUMO
The accurate measurement of diabetic foot ulcer (DFU) wound size is essential as the rate of wound healing is a significant prognostic indicator of the likelihood of complete wound healing. Mobile phone photography is often used for surveillance and to aid in telemedicine consultations. However, there remains no accurate and objective measurement of wound size integrated into these photos. The NDKare mobile phone application has been developed to address this need and our study evaluates its accuracy and practicality for DFU wound size assessment. The NDKare mobile phone application was evaluated for its accuracy in two- (2D) and three-dimensional (3D) wound measurement. One hundred and fifteen diabetic foot wounds were assessed for wound surface area, depth and volume accuracy in comparison to Visitrak and the WoundVue camera. Thirty five wounds had two assessors with different mobiles phones utilizing both applications to assess the reproducibility of the measurements. The 2D surface area measurements by NDKare showed excellent concordance with Visitrak and WoundVue measurements (ICC: 0.991 [95% CI: 0.988, 0.993]) and between different users (ICC: 0.98 [95% CI: 0.96, 0.99)]. The 3D NDKare measurements had good agreement for depth and fair agreement for volume with the WoundVue camera. The NDKare phone application can consistently and accurately obtain 2D measurements of diabetic foot wounds with mobile phone photography. This is a quick and readily accessible tool which can be integrated into comprehensive diabetic wound care.
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Diabetes Mellitus , Pé Diabético , Pé Diabético/diagnóstico , Humanos , Fotografação , Reprodutibilidade dos Testes , Smartphone , CicatrizaçãoRESUMO
OBJECTIVE: Diabetic foot disease is a serious and common complication of diabetes mellitus. The aim of this study was to assess limb and patient factors associated with key clinical outcomes in diabetic patients with foot ulcers. METHODS: This was a prospective observational study of diabetic patients with foot wounds admitted to a major tertiary teaching hospital in South Australia or seen at associated multidisciplinary foot clinics between February 2017 and December 2018. Patient demographic and clinical data were collected, including limb status severity assessed by the WIfI system and grip strength. Participants were followed up for 12 months. The primary outcomes were major amputation, death, amputation free survival, and completion of healing of the index wound within one year. RESULTS: A total of 153 participants were recruited and outcome data were obtained for 152. Forty-two participants underwent revascularisation during the research period. Eighteen participants (11.8%) suffered major amputation of the index limb and 16 (10.5%) died during follow up. Complete wound healing was achieved in 106 (70%) participants. There was a statistically significant association between WIfI stage and major amputation (subdistribution hazard ratio [SHR] 2.75), mortality (hazard ratio [HR] 2.60), amputation free survival (odds ratio [OR] 0.32), and wound healing (SHR 0.69). There was also a statistically significant association between time to healing and grip strength (SHR 0.50), and previous amputations (major or minor) (SHR 0.57). CONCLUSION: This prospective study supports the ability of the WIfI classification system to predict one year key clinical outcomes in a diabetic population with foot ulcers. It also demonstrated that grip strength may be a useful predictor of wound healing.
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Amputação Cirúrgica/estatística & dados numéricos , Pé Diabético/fisiopatologia , Pé Diabético/cirurgia , Cicatrização , Idoso , Pé Diabético/classificação , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
BACKGROUND: With an ageing population, it is paramount for surgeons to comprehend the implications of age on surgical outcomes. This study aims to identify the effects of age on perioperative outcomes post-hepatectomy. METHODS: Between 2001 and 2017, 357 hepatectomies were performed in our centre for malignancy. Data recorded include demographic, histopathology and perioperative outcomes. Patients were divided into three age groups (Group 1 < 65 years, Group 2 65-74 years, Group 3 ≥ 75 years). RESULTS: With increasing age, there was a trend towards patient having: ASA ≥ 3 (from 32.1% to 60.9%, p < 0.0001), clear margins (from 80.4% to 88.3%, p = 0.2256), days of hospitalisation (from 9.5 ± 6.9 to 12 ± 8.0, p = 0.0003), days of ICU admission (from 2.3 ± 2.8 to 2.8 ± 12.9, p = 0.0790) and morbidity (from 39% to 58.5%, p = 0.0073). Cardiovascular complications and postoperative delirium increase with age. There was no significant difference in mortality across the three groups. Univariate and bivariate binary logistic regressions found no association between mortality and age. When adjusted for age, 30- and 90-day mortality was significantly associated with Clavien-Dindo ≥ 3, length of hospital and cardiac complications. Additionally, 90-day mortality was significantly associated with ASA score ≥3, mass of liver resected, length of ICU stay and hepatobiliary, pulmonary and genitourinary complications. CONCLUSION: Increased age is associated with increased post-hepatectomy complications, prolonged hospital stay and ICU admission. However, age itself is not a contraindication for hepatectomy and is not associated with increased mortality. Good histopathology outcomes and low mortality rates are achievable with careful patient selection and appropriate perioperative management.
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Neoplasias Hepáticas , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: This study evaluated the effectiveness of the Dialectical Behavior Therapy Skills Training Group (DBT-ST) component of DBT. METHOD: Participants (N = 114) attended an 18-20-week DBT-ST. The study utilized a quasi-experimental design with a within-persons control group for a measure of borderline personality disorder (BPD) symptoms (at referral), and emergency department (ED) presentations, and psychiatric bed-days (both assessed for 6 months pre- and post-intervention). Primary outcomes were the number of BPD symptoms, psychological distress, depression, rate of ED presentations, and psychiatric inpatient bed-days. RESULTS: After completing DBT-ST, participants had reduced BPD symptoms, psychological distress, and depression (p < 0.001). The waitlist control group showed no improvement in BPD symptoms (p = 0.085). The rate of ED presentations was reduced (p = 0.001). There was no reduction in psychiatric inpatient bed-days (p = 0.160), likely due to insufficient power. CONCLUSIONS: DBT-ST participation in addition to treatment-as-usual is an effective treatment for people with BPD.
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Transtorno da Personalidade Borderline , Terapia do Comportamento Dialético , Angústia Psicológica , Adulto , Terapia Comportamental , Transtorno da Personalidade Borderline/terapia , Humanos , Projetos de Pesquisa , Resultado do TratamentoRESUMO
BACKGROUND: Legal assisted dying is a rare event, but as legalisation expands, requests for it will likely increase, and the nurse most often receives the informal, initial request. OBJECTIVES: To assess the effects of attitude in interaction with normative and control beliefs on an intention to respond to a request for legal assisted dying. ETHICAL CONSIDERATIONS: The study had the lead author's institutional ethics approval, and participants were informed that participation was both anonymous and voluntary. METHODOLOGY: This was a cross-sectional correlational study of 377 Australian registered nurses who completed an online survey. Generalised linear modelling assessed the effects of independent variables against intended responses to requests for legal assisted dying. RESULTS: Compared to nurses who did not support legal assisted dying, nurses who did had stronger beliefs in patient rights, perceived social expectations to refer the request and stronger control in that intention. Nurses who did not support legal assisted dying had stronger beliefs in ethics of duty to the patient and often held dual intentions to discuss the request with the patient but also held an intention to deflect the request to consideration of alternatives. DISCUSSION: This study advances the international literature by developing quantified models explaining the complexity of nurses' experiences with requests for an assisted death. Attitude was operationalised in interaction with other beliefs and was identified as the strongest influence on intentions, but significantly moderated by ethical norms. CONCLUSION: The complex of determinants of those intentions to respond to requests for an assisted death suggests they are not isolated from each other. Nurses might have distinct intentions, but they can also hold multiple intentions even when they prioritise one. These findings present opportunities to prepare nurses in a way that enhances moral resilience in the face of complex moral encounters.
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Enfermeiras e Enfermeiros , Suicídio Assistido , Atitude do Pessoal de Saúde , Austrália , Estudos Transversais , Humanos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The aim of this study was to compare expatriate and Saudi nursing staff's perceptions of factors that influence their role as preceptors of nursing students. METHODS: Descriptive comparative study using a self-administered survey was completed by a convenience sample of eligible nurses (n=285). It was conducted in five different hospitals within the Ministry of Health in the Kingdom of Saudi Arabia. RESULTS: Most preceptors were expatriate nurses (70.5%), while Saudi preceptors represented only 29.5%. The findings show that there is a difference between Saudi and expatriate nurses in their perception of the role, that cultural factors influence the role of expatriate preceptors and that organisational factors influence both groups. CONCLUSIONS: Expatriate preceptors felt that there were cultural obstacles that hindered their role. These findings will contribute to the development of a more contemporary and culturally sensitive preceptorship model.
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Enfermeiras e Enfermeiros , Estudantes de Enfermagem , Humanos , Preceptoria , Arábia Saudita , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The Oncotype DX 21-gene Recurrence Score is a genomic-based algorithm that guides adjuvant chemotherapy treatment decisions for women with early-stage, oestrogen receptor (ER)-positive breast cancer. However, there are age-related differences in chemotherapy benefit for women with intermediate Oncotype DX Recurrence Scores that are not well understood. Menstrual cycling in younger women is associated with hormonal fluctuations that might affect the expression of genomic predictive biomarkers and alter Recurrence Scores. Here, we use paired human breast cancer samples to demonstrate that the clinically employed Oncotype DX algorithm is critically affected by patient age. METHODS: RNA was extracted from 25 pairs of formalin-fixed paraffin-embedded, invasive ER-positive breast cancer samples that had been collected approximately 2 weeks apart. A 21-gene signature analogous to the Oncotype DX platform was assessed through quantitative real-time PCR, and experimental recurrence scores were calculated using the Oncotype DX algorithm. RESULTS: There was a significant inverse association between patient age and discordance in the recurrence score. For every 1-year decrease in age, discordance in recurrence scores between paired samples increased by 0.08 units (95% CI - 0.14, - 0.01; p = 0.017). Discordance in recurrence scores for women under the age of 50 was driven primarily by proliferation- and HER2-associated genes. CONCLUSION: The Oncotype DX 21-gene Recurrence Score algorithm is critically affected by patient age. These findings emphasise the need for the consideration of patient age, particularly for women younger than 50, in the development and application of genomic-based algorithms for breast cancer care.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica/métodos , Testes Genéticos/métodos , Recidiva Local de Neoplasia/patologia , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Prognóstico , Reprodutibilidade dos TestesRESUMO
BACKGROUND AND AIMS: Surveillance post-endoscopic resection (ER) currently warrants biopsy samples from the resection site scar in most cases, although clinical practice is variable. A classification with standard criteria for scars has not yet been established. We aimed to create and validate a novel classification for post-ER scars by using specific criteria based on advanced imaging. METHODS: Key endoscopic features for scars with and without recurrence were (1) dark brown color, elongated/branched pit pattern, and dense capillary pattern and (2) whitish, pale appearance, round/slightly large pits, and irregular sparse vessels. Scars were first assessed with high-definition white-light endoscopy (HD-WLE) followed by interrogation with narrow-band imaging (NBI). Scars with at least 2 concordant characteristics were diagnosed with "high confidence" for NBI for scar (NBI-SCAR) classification. The final endoscopic predictions were correlated with histopathology. The primary outcome was the difference in sensitivity between NBI-SCAR and HD-WLE predictions. Secondary outcomes included the validation of our findings in 6 different endoscopy settings (Australia, United States, Japan, Brazil, Singapore, and Malaysia). The validation took place in 2 sessions separated by 2 to 3 weeks, each with 10 one-minute videos of post-ER scars on underwater NBI with dual focus. Inter-rater and intrarater reliability were calculated with Fleiss' free-marginal kappa and Bennett et al. S score, respectively. RESULTS: One hundred scars from 82 patients were included. Ninety-five scars were accurately predicted with high confidence by NBI-SCAR in the exploratory phase. NBI-SCAR sensitivity was significantly higher compared with HD-WLE (100% vs 73.7%, P < .05). In the validation phase, similar results were found for endoscopists who routinely perform colonoscopies and use NBI (sensitivity of 96.4%). The inter-rater and intrarater reliability throughout all centers were, respectively, substantial (κ = .61) and moderate (average S = .52) for this subset. CONCLUSIONS: NBI-SCAR has a high sensitivity and negative predictive value for excluding recurrence for endoscopists experienced in colonoscopy and NBI. In this setting, this approach may help to accurately evaluate or resect scars and potentially mitigate the burden of unnecessary biopsy samples.
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Imagem de Banda Estreita , Cicatriz/diagnóstico por imagem , Cicatriz/patologia , Colonoscopia , Humanos , Recidiva Local de Neoplasia , Reprodutibilidade dos TestesRESUMO
Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9% saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement. The primary outcomes, area under the curve over 240 minutes (AUC 240 ) for blood glucose (P < 0.0001) and peak blood glucose (7.65 mM ± 0.34 [mean ± SE] vs 9.53 mM ± 0.63, P < 0.0001), were markedly lower after exenatide than placebo. AUC240 for insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) was also lower after exenatide. Gastric emptying was markedly slower after exenatide, as assessed by time for 10% gastric emptying and peak 13 CO2 excretion. We report for the first time that exenatide corrects postprandial hyperglycaemia in young people with CF and IGT. GLP-1 agonists are a candidate treatment in CF-related diabetes.
Assuntos
Fibrose Cística/tratamento farmacológico , Exenatida/uso terapêutico , Intolerância à Glucose/tratamento farmacológico , Hiperglicemia/prevenção & controle , Período Pós-Prandial/efeitos dos fármacos , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Criança , Estudos Cross-Over , Fibrose Cística/sangue , Fibrose Cística/complicações , Método Duplo-Cego , Exenatida/farmacologia , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Humanos , Hiperglicemia/sangue , Incretinas/uso terapêutico , Masculino , Adulto JovemRESUMO
BACKGROUND AND AIM: Adenoma detection rate (ADR) is an important quality metric in colonoscopy. However, there is conflicting evidence around factors that influence ADR. This study aims to investigate the effect of time of day and endoscopist background on ADR and sessile serrated adenoma/polyp detection rate (SSA/P-DR) for screening colonoscopies. METHODS: Consecutive patients undergoing colonoscopy in 2016 were retrospectively evaluated. Primary outcome was the effect of time of day and endoscopist specialty on screening ADR. Secondary outcomes included evaluation of the same factors on SSA/P-DR and other metrics and collinearity of ADR and SSA/P-DR. Linear regression models were used for association between ADR, time of day, and endoscopist background. Bowel preparation, endoscopist, session, patient age, and gender were adjusted for. Linear regression model was also used for comparing ADR and SSA/P-DR. Chi-square was used for difference of proportions. RESULTS: Two thousand six hundred fifty-seven colonoscopies, of which 558 were screening colonoscopies, were performed. The adjusted mean ADR (screening) was 36.8% in the morning compared with 30.5% in the afternoon (P < 0.0001) and was 36.8% for gastroenterologists compared with 30.4% for surgeons (P < 0.0001). For every 1-h delay in commencing the procedure, there was a reduction in mean ADR by 3.4%. Using a linear regression model, a statistically significant positive association was found between ADR and SSA/P-DR (P < 0.0001). CONCLUSIONS: Morning and afternoon sessions and gastroenterologists and surgeons achieved the minimum standards recommended for ADR. Afternoon lists and surgeons were associated with a lower ADR compared with morning and gastroenterologists, respectively. Additionally, SSA/P-DR showed collinearity with ADR.
Assuntos
Adenoma/diagnóstico , Adenoma/epidemiologia , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Gastroenterologistas/estatística & dados numéricos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/epidemiologia , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/epidemiologia , Programas de Rastreamento/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , TempoRESUMO
This study aimed to provide information regarding key performance indicators (KPIs) for forensic pathology in Australia and New Zealand, focusing on the time to complete a Coronial post-mortem examination report. Data was obtained from the National Coronial Information System (NCIS). The mean and median time to complete a post-mortem examination report in 2015 was determined from a sample of 100 cases from each of the nine Coronial jurisdictions. Results of univariate and multivariable analysis of factors potentially influencing the completion time are presented. The multivariable analysis indicated the time to complete a post-mortem examination report was significantly dependent on if any internal examination had been performed, the Coronial jurisdiction and requesting toxicological analysis. The number of days for Coroners to close cases is also presented as well as the number of days for a post-mortem examination to be performed. A comparison between 2015 and 2010 was instigated. However, this data had to be constrained to eight of the Coronial jurisdictions. Within this dataset, the time to complete a post-mortem examination report when an internal examination had been performed was statistically significant greater in 2015. However, the time to complete reports for all Coronial post-mortem examinations in 2015 was not statistically significantly different to 2010. This could be attributed to a higher proportion of post-mortem examinations without internal examination ('external only') in 2015. The time to perform a post-mortem examination following the death being reported to a Coroner increased, but the time for Coroners to close a case decreased.