There is no association between combined oral hormonal contraceptives and depression: a Swedish register-based cohort study.

OBJECTIVE: To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non-users. DESIGN: Register-based cohort study. SETTING: Sweden. SAMPLE: Women aged 15-25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585). METHODS: Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC-users compared with non-users were modelled by Poisson regression. Adjustments included age, medical indication for HC-use and parental history of mental disorders, among others. MAIN OUTCOME MEASURES: Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register. RESULTS: Compared with non-users, women on combined oral contraceptives (COCs) and oral progestogen-only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87-0.91) and 1.03 (95% CI 0.99-1.06) after adjustments, respectively. Age-stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93-0.98), whereas use of progestogen-only pills (RR 1.13, 95% CI 1.07-1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30-1.58), implant (RR 1.38, 95% CI 1.30-1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46-1.73) were associated with increased risks. CONCLUSIONS: This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non-oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results. TWEETABLE ABSTRACT: There is no association between combined hormonal contraceptives and depression.

Association of maternal attention deficit hyperactivity disorder and preterm birth: a cohort study.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) affects 3-7% of women of childbearing age. Whether ADHD is associated with an increased risk of preterm birth is unclear. DESIGN: National register-based cohort study. SETTING: Sweden. POPULATION: Nulliparous women giving birth to singleton infants 2007-2014 (n = 377 381). METHODS: Women were considered to have ADHD if they had been dispensed at least one prescription for ADHD medication, i.e. a central nervous system stimulant or non-stimulant drugs for ADHD, prior to, during or after pregnancy (2005-2014). Women with ADHD were compared with women without ADHD in regard to prevalence, severity and mode of onset of preterm birth. Logistic regression models were used, estimating adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age and country of birth (model 1), and in addition for body mass index (BMI), education, alcohol or substance use disorders, and pre-gestational medical and psychiatric co-morbidity (model 2). MAIN OUTCOME MEASURES: Preterm birth (<37 weeks). RESULTS: During the study period, 6327 (1.7%) women gave birth and had ADHD according to our definition. These women had a higher rate of preterm birth compared with women without ADHD (7.3 versus 5.8%, aOR model 2: 1.17; 95% CI 1.05-1.30). ADHD was particularly associated with very (<32 weeks) preterm births, and associations were seen with both spontaneous and medically indicated onsets. CONCLUSIONS: Women with ADHD (i.e. who had been dispensed ADHD medication at any time in 2005-2014) had an increased risk of preterm birth. TWEETABLE ABSTRACT: Women with ADHD have a higher risk of preterm birth but most of it is due to modifiable risk factors.

SSRI use during pregnancy and risk for postpartum haemorrhage: a national register-based cohort study in Sweden.

OBJECTIVE: Evaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH). DESIGN: National register-based cohort study based on data from the Swedish Pregnancy Register. SETTING: Sweden, nationwide coverage. POPULATION: A total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017. METHODS: Pregnant women with self-reported SSRI use at any time point during pregnancy were compared with non-SSRI-treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use. MAIN OUTCOME MEASURES: Postpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician. RESULTS: Postpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04-1.14 and OR 1.34, 95% CI 1.24-1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g). CONCLUSIONS: Higher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness. TWEETABLE ABSTRACT: SSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.

Massive blood transfusion in relation to delivery: incidence, trends and risk factors: a population-based cohort study.

OBJECTIVE: To estimate incidence, trends over time, and risk factors for massive blood transfusions in obstetric patients. A secondary aim was to evaluate transfusion ratios in relation to massive transfusion. DESIGN: Population-based cohort. SETTING: Five hospitals, in the Stockholm County, Sweden, from 1990 to 2011. POPULATION: All women that gave birth in Stockholm county, Sweden, and who received blood transfusions postpartum between 1990 and 2011. METHODS: Data on pregnancies and deliveries from the Swedish National Medical Birth Registry was cross-linked to the Stockholm transfusion database. Massive blood transfusion was defined as the transfusion of ≥10 units of red blood cells from partus through the next day. MAIN OUTCOME MEASURES: Main primary outcome was massive blood transfusion postpartum. RESULTS: Our cohort comprised 517 874 deliveries. Massive blood transfusion occurred in 277 women, for an incidence of 5.3 per 10 000 deliveries, and increased by 30% (P < 0.001) between the first and the second half of the study period. Major risk factors apparent before delivery were abnormal placentation (odds ratio [OR] 41; 95% CI 29.3-58.1), pre-eclampsia/placental abruption (OR 4; 95% CI 2.8-5.6), and previous caesarean delivery (OR 4; 95% CI 3.1-6.0). Risk factors at time of delivery were uterine rupture, atonic uterus, and caesarean delivery (OR 38, 17, and 3, respectively). CONCLUSION: We found an increasing trend in the postpartum rate of massive transfusion. Women with abnormal placentation were found to have the highest increased risk. Improved antenatal awareness of these women at risk might improve management and reduce the rate of massive transfusion. TWEETABLE ABSTRACT: Risk of massive blood transfusion in obstetric patients increases with placental complications and prior caesarean section.

Rapid determination of anticoagulating effects of dabigatran in whole blood with rotational thromboelastometry and a thrombin-based trigger.

Essentials A rapid test to detect thrombin inhibition by dabigatran would be valuable in acute situations. A thrombin-based trigger was applied in whole blood using rotation thromboelastometry. Effects of dabigatran were assessed in vitro and in samples from patients on dabigatran. The test produced data rapidly and was sensitive to dabigatran concentrations from 20 to 500 ng mL-1 . SUMMARY: Background Rapid determination of the anticoagulant effect of dabigatran is essential in emergency situations. Objective To study a viscoelastic test (rotational thromboelastometry [ROTEM]) for rapid determination of dabigatran effects in whole blood samples. Method ROTEM measurements were performed with comparison of two triggers (thrombin-based versus the commercial tissue factor-based trigger Ex-tem) in samples from 10 healthy donors spiked with dabigatran (20-500 ng mL-1 ) and in samples from 35 patients receiving dabigatran treatment; 10 healthy subjects served as controls. Clotting time (CT) and the difference in CT without versus with addition of the dabigatran antidote idarucizumab (CTdiff ) were measured. Addition of idarucizumab reveals the contribution of dabigatran to ROTEM measurements and its potential reversibility. Results In vitro studies showed that thrombin CT and thrombin CTdiff were more sensitive than Ex-tem CT and Ex-tem CTdiff in detecting dabigatran in whole blood samples. In patient samples, when thrombin CT and thrombin CTdiff were used, it was possible to detect dabigatran with a cut-off of dabigatran at 20 ng mL-1 , whereas, when Ex-tem CT and Ex-tem CTdiff were used, the method was less sensitive. Data from patient samples were obtained within 15 min of blood sampling. Conclusions ROTEM CT with a thrombin-based trigger is more sensitive to dabigatran effects than Ex-tem CT, and detects anticoagulant effects of drug concentrations in the low-very low therapeutic range. Analysis with idarucizumab (CTdiff ) reveals dabigatran-specific effects. As data are rapidly obtained, this method could, with further development and validation of its performance, be suitable for detecting clinically significant dabigatran effects in emergency situations.

Searching for unknown transfusion-transmitted hepatitis viruses: a binational cohort study of 1.5 million transfused patients.

BACKGROUND: Both hepatitis B and C viruses were transmitted through blood transfusion before implementation of donor screening. The existence of additional, yet unknown transfusion transmittable agents causing liver disease could have important public health implications. METHODS: Analyses were based on the Scandinavian Donations and Transfusions (SCANDAT2) database. Cox regression models were used to estimate the hazard ratio (HR) of developing chronic liver disease in recipients of blood from donors who later developed any chronic liver disease compared to recipients who received blood transfusion from healthy donors. We also studied whether the risk of liver disease was increased in patients who received units from 'high-risk' donors, defined as donors who had a higher than expected occurrence of liver disease amongst their previous recipients. All analyses were stratified before and after 1992 to account for the effect of screening for hepatitis C virus. RESULTS: A total of 1 482 922 transfused patients were included in the analyses. Analyses showed evidence of transfusion transmission of liver diseases before, but not after the implementation of hepatitis C virus screening in 1992, with HRs for any liver disease of 1.38 [95% confidence interval (CI), 1.30-1.46] and 0.99 (95% CI, 0.91-1.07), before and after 1992, respectively. Similarly, blood components from 'high-risk' donors conferred increased risks before, but not after 1992. CONCLUSIONS: Our data provide no evidence for transfusion transmission of agents causing liver disease after the implementation of screening for hepatitis B and C, and suggest that if such transmission does occur, it is rare.

Postpartum blood transfusion and hemorrhage as independent risk factors for venous thromboembolism.

INTRODUCTION: Profuse postpartum hemorrhage (PPH) and red blood cell (RBC) transfusion have been suggested to be associated with venous thromboembolic events (VTE). However, it is not fully clear if they are independent major risk factors. METHODS: Women who gave birth in the Stockholm area between 1999 and 2002 were those studied, i.e., before the implementation of guidelines for thromboprophylaxis in pregnancy. In this population-based cohort study the Swedish Medical Birth Registry was linked to the National Discharge Registry and to the transfusion database. Cases with VTE were identified as well as the patient's transfusion history. The main outcome was an assessment of RBC transfusion and PPH as independent risk factors for postpartum thrombosis, analyzed in logistic regression models. RESULTS: Out of the 82,376 deliveries, 56 cases of postpartum VTE were identified (0.7‰). Compared to the control group, the risk of VTE increased with the number of RBC transfusions: 1 to 3 units (OR = 3.3, 95% CI 1.2-8.9) and >3 units (OR = 5.2, 95%CI 1.7-16.1), but PPH was not found to be a major risk factor (OR = 1.4, 95% CI 0.5-3.5). Surprisingly, the small group treated with plasma in addition to RBC transfusion were not at a significantly increased risk (OR = 1.8, 95% CI 0.2-14.0). Preeclampsia and placental abruption were major risk factors. CONCLUSION: We found RBC transfusion, but not PPH alone, to be an independent risk factor for postpartum VTE and propose that it should be included in the thromboprophylaxis algorithm for implementation during pregnancy.

Adding to the complexity of fetal and neonatal alloimmune thrombocytopenia: Reduced fibrinogen binding in the presence of anti-HPA-1a antibody and hypo-responsive neonatal platelets.

BACKGROUND: In fetal and neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies directed against paternally-derived platelet antigens are transported across the placenta to the fetus, where they may cause thrombocytopenia. The most serious complication of FNAIT is an intracranial hemorrhage (ICH), which may cause death or life-long disability of the child. Apart from alloantibody-mediated platelet destruction, the clinical outcome in FNAIT may be affected by properties of neonatal platelets and possible functional effects on platelets caused by maternal alloantibodies. METHODS AND RESULTS: The function of umbilical cord blood platelets was compared with adult platelets in two assays, impedance aggregometry (Multiplate) and rotational thromboelastometry (Rotem). Both revealed a decreased in vitro neonatal platelet function compared to adult platelets. Consistent with this finding, activation using TRAP revealed less pronounced changes in the expression of CD62P, PAC-1, CD41 and CD42a in umbilical cord blood platelets compared to adult platelets. Furthermore, a monoclonal anti-HPA-1a antibody, derived from an immunized mother of two children with FNAIT, blocked fibrinogen binding to resting and activated umbilical cord blood and adult HPA-1aa and HPA-1ab platelets, interfered with platelet activation by TRAP, and impaired the function of umbilical cord blood HPA-1aa platelets in rotational thromboelastometry. DISCUSSION AND CONCLUSIONS: Reduced fibrinogen binding in the presence of anti-HPA-1a antibodies may disturb the neonatal hemostatic balance, characterized by poorly responsive platelets. This effect may operate in parallel to platelet destruction and contribute to the clinical outcome in FNAIT.

Impact of weight loss and eating difficulties on health-related quality of life up to 10 years after oesophagectomy for cancer.

BACKGROUND: Severe weight loss is experienced by patients with eating difficulties after surgery for oesophageal cancer. The aim of this prospective cohort study was to asssess the influence of eating difficulties and severe weight loss on health-related quality of life (HRQoL) up to 10 years after oesophagectomy. METHODS: Data on bodyweight and HRQoL were collected at 6 months, 3, 5 and 10 years in patients who underwent surgery for oesophageal cancer in Sweden between 2001 and 2005. Exposures were percentage weight loss, and eating difficulties defined by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OES18 questionnaire. Outcomes were HRQoL scores from the EORTC QLQ-C30 questionnaire. Repeated-measures ANOVA, adjusting for potential confounders, was used to assess the association between eating difficulties and weight loss (4 exposure groups) and HRQoL scores at each time point. Mean score differences (MDs) between time points or exposure groups were defined as clinically relevant in accordance with evidence-based interpretation guidelines. RESULTS: In total, 92 of 104 10-year survivors (88·5 per cent) responded to the questionnaires. Weight loss was greatest within 6 months of surgery. Patients with eating difficulties with or without weight loss reported clinically and statistically significantly worsened HRQoL in almost all aspects. The largest MD was seen between 5 and 10 years after surgery for global quality of life, physical, role and social function (MD -22 to -30), as well for fatigue, nausea, dyspnoea, insomnia, appetite loss and diarrhoea (MD 24-36). CONCLUSION: Eating difficulties are associated with deterioration in several aspects of HRQoL up to 10 years after surgery for oesophageal cancer.

Patient blood management knowledge and practice among clinicians from seven European university hospitals: a multicentre survey.

BACKGROUND AND OBJECTIVES: The aim of this survey was to evaluate the knowledge about Patient Blood Management (PBM) principles and practices amongst clinicians working in seven European hospitals participating in a European Blood Alliance (EBA) project. MATERIALS AND METHODS: A web-based questionnaire was sent to 4952 clinicians working in medical, surgery and anaesthesiology disciplines. The responses were analysed, and the overall results as well as a comparison between hospitals are presented. RESULTS: A total of 788 responses (16%) were obtained. About 24% of respondents were not aware of a correlation between preoperative anaemia (POA) and perioperative morbidity and mortality. For 22%, treatment of POA was unlikely to favourably influence morbidity and mortality even before surgery with expected blood loss. More than half of clinicians did not routinely treat POA. 29%, when asked which is the best way to treat deficiency anaemia preoperatively, answered that they did not have sufficient knowledge and 5% chose to 'do nothing'. Amongst those who treated POA, 38% proposed red cell transfusion prior to surgery as treatment. Restrictive haemoglobin triggers for red blood cell transfusion, single unit policy and reduction of number and volumes of blood samples for diagnostic purposes were only marginally implemented. CONCLUSION: Overall, the responses indicated poor knowledge about PBM. Processes to diagnose and treat POA were not generally and homogeneously implemented. This survey should provide further impetus to implement programmes to improve knowledge and practice of PBM.

Extracorporeal membrane oxygenation improves coagulopathy in an experimental traumatic hemorrhagic model.

PURPOSE: Hemorrhage is the most common cause of preventable death after trauma. Coagulopathy plays a central role in uncontrolled bleeding and is caused by multiple factors. Extracorporeal Membrane Oxygenation (ECMO) is an established treatment for patients with respiratory failure and has in recent years also been used in severely injured trauma patients with cardiopulmonary failure and coexisting bleeding shock. The aim of this study was to evaluate the effect of ECMO on hypothermia, acidosis, and coagulopathy in a traumatic hemorrhagic rabbit model. METHODS: After anesthesia and tracheostomy, ten New Zealand White rabbits sustained laparotomy, bilateral femur fractures and were hemorrhaged 45% of their estimated blood volume. After 90 min of hemorrhagic shock they were resuscitated with a standard transfusion protocol together with venoarterial ECMO (n = 5) or with a standard transfusion protocol only (n = 5) for 60 min. No systemic heparin was administered. RESULTS: ECMO during 60 min of resuscitation significantly increased heart rate (p = 0.01), mean arterial pressure (p = 0.01), body temperature (p = 0.01) and improved the metabolic acidosis, pH (p = 0.01), and lactate (p = 0.01). ECMO also improved the coagulation capacity measured in vitro by Rotational Thromboelastometry with a significant decrease in clot formation time (p < 0.01). This finding was confirmed in vivo with a significant reduction in the animals' ear bleeding time (p < 0.01) and cuticle bleeding time (p < 0.01); 5/5 animals survived in the ECMO group and 3/5 animals survived in the control group. CONCLUSIONS: Heparin-free ECMO stabilizes circulation, improves coagulation, and may impact short-time survival, during the first 60 min, in an experimental traumatic model with severe hemorrhagic shock.

Characterisation of maternal human leukocyte antigen class I antibodies in suspected foetal and neonatal alloimmune thrombocytopenia.

OBJECTIVES: To investigate the specificities and level of HLA class I antibodies in selected cases referred for suspected foetal and neonatal alloimmune thrombocytopenia (FNAIT). BACKGROUND: FNAIT occurs in 1 : 1-2000 live births, whereas maternal immunisation against human leukocyte antigen (HLA) class I is common. Whether HLA class I antibodies alone can cause FNAIT is debatable. MATERIAL AND METHODS: A total of 260 patient samples were referred between 2007 and 2012. Referrals with maternal HLA class I antibodies and no other cause for the neonatal thrombocytopenia were included for analysis (cases, n = 23). HPA-1a negative mothers were excluded. Control groups were screened positive mothers of healthy neonates (controls, n = 33) and female blood donors (blood donors, n = 19). LABScreen single antigen HLA class I beads was used for antibody analysis. Clinical records were reviewed for cases. RESULTS: All groups had broad antibody reactivity. Cases had more antibodies with high SFI levels compared with the controls (SFI>9999; medians 26, 6 and 0; P < 0·05) and higher overall median HLA-ABC and HLA-B SFI (P < 0·05). Many of the antibodies were reactive with rare alleles. When reviewing the clinical records, several of the cases had other contributing factors to the thrombocytopenia. There was no correlation between foetal platelet count and antibody levels. CONCLUSION: Mothers of thrombocytopenic neonates had higher levels of HLA class I antibodies compared with control groups of women with healthy children and female blood donors. However, clinical outcome and antibody response correlated poorly in the heterogeneous case group, indicating a multifactorial cause to the thrombocytopenia in the majority of cases.

Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.

OBJECTIVES: The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). METHODS: This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. RESULTS: Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). CONCLUSION: The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period.

Patient Blood Management in Europe: surveys on top indications for red blood cell use and Patient Blood Management organization and activities in seven European university hospitals.

BACKGROUND AND OBJECTIVES: Patient Blood Management (PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from the experience and expertise in the participating teams with the further aim of implementing and strengthening these practices in the participating hospitals. METHODS: We conducted two surveys in seven university hospitals in Europe: Survey on top indications for red blood cell use regarding usage of red blood cells during 1 week and Survey on PBM organization and activities. RESULTS: A total of 3320 units of red blood cells were transfused in 1 week at the seven hospitals. Overall, 61% of red cell units were transfused to medical patients and 36% to surgical patients, although there was much variation between hospitals. The organization and activities of PBM in the seven hospitals were variable, but there was a common focus on optimizing the treatment of bleeding patients, monitoring the use of blood components and treatment of preoperative anaemia. CONCLUSION: Although the seven hospitals provide a similar range of clinical services, there was variation in transfusion rates between them. Further, there was variable implementation of PBM activities and monitoring of transfusion practice. These findings provide a baseline to develop joint action plans to further implement and strengthen PBM across a number of hospitals in Europe.

Co-morbidity after oesophageal cancer surgery and recovery of health-related quality of life.

BACKGROUND: Although health-related quality of life (HRQoL) recovers after surgery for oesophageal cancer in most long-term survivors, one in seven patients experiences a deterioration in HRQoL for reasons yet unknown. The aim of this study was to assess whether co-morbidities diagnosed after surgery influence recovery of HRQoL. METHODS: Patients who underwent surgery for cancer of the oesophagus or gastro-oesophageal junction in Sweden between 2001 and 2005 were included. HRQoL was assessed by means of the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OES18 questionnaires. Repeated-measures ANOVA was used to assess mean differences in HRQoL scores between three co-morbidity status groups (healthy, stable and increased) over time. Probabilities of deterioration in HRQoL were calculated based on marginal probabilities from logistic regression models. RESULTS: At 5 years' follow-up, 153 (24·8 per cent) of 616 patients were alive and 137 responded to at least two of three questionnaires. The healthy and increased co-morbidity groups showed deterioration in almost all aspects of HRQoL at 6 months after surgery compared with baseline. The increased co-morbidity group also deteriorated in several aspects from 3 to 5 years after surgery. Patients with an increase in co-morbidity did not have a significantly increased probability of deterioration in HRQoL over time compared with healthy or stable patients, except with respect to cognitive function, loss of appetite, choking and coughing. CONCLUSION: Patients with an increase in co-morbidities after oesophagectomy experience long-term deterioration in HRQoL.

Prevalence and predictors of anxiety and depression among esophageal cancer patients prior to surgery.

This study aims to establish the prevalence and predictors of anxiety and depression among esophageal cancer patients, post-diagnosis but prior to curatively intended surgery. This was a cross-sectional study using data from a hospital-based prospective cohort study, carried out at St Thomas' Hospital, London. Potential predictor variables were retrieved from medical charts and self-report questionnaires. Anxiety and depression were measured prior to esophageal cancer surgery, using the Hospital Anxiety and Depression Scale. Prevalence of anxiety and depression was calculated using the established cutoff (scores ≥8 on each subscale) indicating cases of 'possible-probable' anxiety or depression, and multivariable logistic regression analyses were performed to examine predictors of emotional distress. Among the 106 included patients, 36 (34%) scored above the cutoff (≥8) for anxiety and 24 (23%) for depression. Women were more likely to report anxiety than men (odds ratio 4.04, 95% confidence interval 1.45-11.16), and patients reporting limitations in their activity status had more than five times greater odds of reporting depression (odds ratio 6.07, 95% confidence interval 1.53-24.10). A substantial proportion of esophageal cancer patients report anxiety and/or depression prior to surgery, particularly women and those with limited activity status, which highlights a need for qualified emotional support.

Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

OBJECTIVE: To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. DESIGN: Model based on a population-based cohort study. SETTING: The Swedish health service. POPULATION: Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). METHODS: Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. MAIN OUTCOME MEASURE: Additional cost per RhD immunisation averted. RESULTS: Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. CONCLUSION: Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. TWEETABLE ABSTRACT: Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

Toward improved survivorship: supportive care needs of esophageal cancer patients, a literature review.

The growing prevalence of esophageal cancer survivors represent a population typified by an extensive treatment regime, significant postsurgical long-term effects, and a dismal prognosis. Despite this, little is known of the supportive care needs of this patient group and the extent to which these are being met in practice. This review provides a synthesis of the research evidence to date; emphasizing opportunities for clinical application and setting a future agenda with research priorities. A literature search was performed using Medline/Embase, PsycINFO, and Web of Science. Search headings used included; [esophagus] or [esopohageal] or [upper gastrointestinal] or [upper GI] AND [cancer] or [carcinoma] or [squamous cell] AND [supportive care] or [survivorship] or [psychological] or [emotional] or [information] or [social] or [communication] or [spiritual] or [health-related-quality-of-life] or [HRQL] or [qualitative] or [patient narrative] or [clinical nurse specialist] or [CNS]. Related articles in English were reviewed, with additional articles harvested from reference sections. Esophageal cancer survivors report significant late-term effects posttreatment, encompassing sustained impairment in most areas of health-related quality of life. With a necessitated change in eating behavior, survivors find it particularly challenging to adjust to a new social identity and as a cancer population report high levels of psychological morbidity. Although the determinants of psychological morbidity are largely unknown, illness representations may be a key contributor. Several multidisciplinary supportive care interventions have been developed with promising results. The research summarized in this paper provides valuable insight into the psychosocial well-being of the esophageal cancer survivor. However, knowledge gaps remain, alongside a dearth of applied examples in meeting supportive care need.