Anti-coagulation, anti-platelets or no therapy in haemodialysis patients with atrial fibrillation: a decision analysis

BACKGROUND: Optimal treatment of atrial fibrillation (AF) in the haemodialysis population is uncertain due to the exclusion of this group from randomized trials. The risk-benefit profile for anticoagulation and anti-platelet therapy in haemodialysis differs from the general population due to platelet dysfunction from uraemia, altered pharmacokinetics and increased falls risk. METHODS: This decision analysis used a Markov-state transition model that took a patient perspective over a 5 year timeframe. The Markov model compared life-years gained and quality-adjusted life-years gained (QALY) for three AF treatment strategies: warfarin, aspirin and no treatment. The base case was a 70-year-old man on haemodialysis with non-valvular AF. RESULTS: In the base case, the total health outcomes in life-years and QALY were 2.37 and 1.47 respectively for warfarin, 2.38 and 1.61 respectively for aspirin, and 2.39 and 1.61 respectively for no treatment. Thus, warfarin led to 0.14 fewer QALY or 1.7 fewer months of life lived in full health, compared with either aspirin or no therapy. The finding that warfarin generated the lowest expected QALY was robust to one-way, two-way and probabilistic sensitivity analyses. CONCLUSIONS: Our results suggest that warfarin should not be the default choice for older haemodialysis patients with non-valvular AF as it provides the fewest QALY compared with aspirin or no therapy

Biliary stenting in patients with pancreatic cancer: results from a population-based cohort study

We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort.We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice.Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed.Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice

Chemotherapy in patients with unresected pancreatic cancer in Australia: A population-based study of uptake and survival

1 Aim Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival. 2 Methods We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival. 3 Results Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n = 184/414) of patients with localized pancreatic cancer and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended on clinical factors, such as performance status and comorbidity burden, and nonclinical factors, such as age, place of residence, multidisciplinary team review and the type of specialist first encountered. Consultation with an oncologist mitigated most of the sociodemographic and service‐related disparities in chemotherapy use. The receipt of chemotherapy was associated with prolonged survival in patients with inoperable pancreatic cancer, including after adjusting for common prognostic factors. 4 Conclusions These findings highlight the need to establish referral pathways to ensure that all patients have the opportunity to discuss treatment options with a medical oncologist. This is particularly relevant for health care systems covering areas with a geographically dispersed population

Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.

BACKGROUND: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. RESULTS: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19-0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20-0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08-0.49];BCSS: HR 0.12 [95% CI 0.03-0.44]).Transient negative quality-of-life impacts were observed. CONCLUSIONS: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. TRIAL REGISTRATION: ISRCTN 46099296

Prognostic factors for patients with hepatic metastases from breast cancer

Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan–Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16–51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml−1 and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients

Endocrine therapy for breast cancer: a model of hormonal manipulation

Oestrogen receptor (ER) is the driving transcription factor in 70% of breast cancer. Endocrine therapies targeting the ER represent one of the most successful anticancer strategies to date. In the clinic, novel targeted agents are now being exploited in combination with established endocrine therapies to maximise efficacy. However, clinicians must balance this gain against the risk to patients of increased side effects with combination therapies. This article provides a succinct outline of the principles of hormonal manipulation in breast cancer, alongside the key evidence that underpins current clinical practice. As the role of endocrine therapy in breast cancer continues to expand, the challenge is to interpret the data and select the optimal strategy for a given clinical scenario

Bridging the age gap in breast cancer: impact of chemotherapy on quality of life in older women with early breast cancer

Introduction Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study. Materials and methods A prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013–2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching. Results Three thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18–24 months in unmatched and matched cohorts. Conclusions The negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy

Pregnancy outcomes for kidney transplant recipients with transplantation as a child

IMPORTANCE: Pregnancy outcomes for women who received a kidney transplant in childhood are uncertain. OBJECTIVES: To report pregnancy outcomes for women with kidney transplantation in childhood (aged <18 years; child-tx mothers) and to compare them with those for women who received a kidney transplant in adulthood (aged≥18 years; adult-tx mothers). DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study in Australia and New Zealand of all women with a functioning kidney transplant included in the Australia and New Zealand Dialysis and Transplant Registry for whom at least 1 pregnancy was reported between January 1, 1963, and December 31, 2012. MAIN OUTCOMES AND MEASURES: Pregnancy outcomes including live birth rates, gestational age, and proportion of babies who are small for gestational age. RESULTS: A total of 101 pregnancies in 66 child-tx mothers and 626 pregnancies in 401 adult-tx mothers were reported. At the time of pregnancy, child-tx mothers had a mean age of 25 (95%CI, 24-26) years with a functioning transplant for 10 (95%CI, 9-11) years, while adult-tx mothers had a mean age of 31 (95%CI, 31-31) years with a functioning transplant for 6 (95%CI, 5-6) years (both P <.001). Live births occurred in 76%of pregnancies in child-tx mothers and 77%of pregnancies in adult-tx mothers. The mean gestational ages were similar between child-tx and adult-tx mothers (35 [95%CI, 33-37] vs 36 [95%CI, 35-36] weeks, respectively; P =.68). The incidence of prematurity (<37 weeks' gestation) was also similar (child-tx mothers, 45%; adult-tx mothers, 53%). A similar proportion of preterm babies born to child-tx and adult-tx mothers were small for gestational age (22%vs 10%, respectively; odds ratio [OR] = 2.53 [95%CI, 1.13-5.69]). Term babies born to child-tx and adult-tx mothers were frequently small for gestational age (57%vs 38%, respectively; OR = 2.16 [95%CI, 1.23-3.81]), both significantly more frequently than babies born at term in the general population (child-tx mothers, OR = 11.93 [95%CI, 5.56-25.61]; adult-tx mothers, OR = 5.52 [95%CI, 2.56-11.89]). CONCLUSIONS AND RELEVANCE: Pregnancy outcomes for child-tx mothers are similar to those for adult-tx mothers, with no difference in the rate of live births, gestational age, or small for gestational age. Regardless of when women received their kidney transplant, their pregnancies are likely to result in a live, albeit preterm, birth. This work should provide comfort to child-tx mothers and their physicians that their early onset of kidney failure and longer period of transplantation and immunosuppression do not adversely affect their pregnancy outcomes compared with adult-tx mothers

Using a Delphi process to determine optimal care for patients with pancreatic cancer

AIM: Overall 5-year survival for pancreatic cancer is ∼5%. Optimizing the care that pancreatic cancer patients receive may be one way of improving outcomes. The objective of this study was to establish components of care which Australian health professionals believe important to optimally manage patients with pancreatic cancer. METHODS: Using a Delphi process, a multidisciplinary panel of 250 health professionals were invited to provide a list of factors they considered important for optimal care of pancreatic cancer patients. They were then asked to score and then rescore (from one [no importance/disagree] to 10 [very important/agree]) the factors. The mean and coefficient of variation scores were calculated and categorized into three levels of importance. RESULTS: Overall, 63 (66% of those sent the final questionnaire; 25% of those initially invited) health professionals from nine disciplines completed the final scoring of 55 statements/factors encompassing themes of presentation/staging, surgery and biliary obstruction, multidisciplinary team details and oncology. Mean scores ranged from 3.7 to 9.7 with the highest related to communication and patient assessment. There was substantial intra- and interdisciplinary variation in views about MDT membership and roles. CONCLUSION: Overall, the opinions of Australian health professionals reflect international guideline recommended care; however, they identified a number of additional factors focusing on where patients should be treated, the importance of clear communication and the need for multidisciplinary care which were not included in current clinical practice guidelines. Differences in priorities between specialty groups were also identified

Factors associated with quality of care for patients with pancreatic cancer in Australia

OBJECTIVES: To develop a composite score for the quality of care for patients with pancreatic cancer in Australia; to determine whether it was affected by patient and health service-related factors; to assess whether the score and survival were correlated. DESIGN, PARTICIPANTS AND SETTING: We reviewed medical records of patients diagnosed with pancreatic cancer during July 2009 - June 2011 and notified to the Queensland and New South Wales cancer registries. DESIGN AND MAIN OUTCOME MEASURES: Participants were allocated proportional quality of care scores based on indicators derived from a Delphi process, ranging from 0 (lowest) to 1 (highest quality care). Associations between patient and health service-related factors and the score were tested by linear regression, and associations between the score and survival with Kaplan-Meier and Cox proportional hazards methods. RESULTS: Proportional quality of care scores were assigned to 1571 patients. Scores for patients living in rural areas were significantly lower than for those in major cities (adjusted difference, 11%; 95% CI, 8-13%); they were higher for patients in the least socio-economically disadvantaged areas (v most disadvantaged areas: 8% higher; 95% CI, 6-11%), who were younger, had better Eastern Cooperative Oncology Group performance status, or who first presented to a hospital with a high pancreatic case volume. Higher scores were associated with improved survival; after adjusting for patient-related factors, each 10 percentage point increase in the score reduced the risk of dying by 6% (hazard ratio, 0.94; 95% CI, 0.91-0.97). CONCLUSION: Geographic category of residence may influence the quality of care received by patients with pancreatic cancer, and survival could be improved if they received optimal care