Body weight in childhood, adolescence, and young adulthood in relation to later risk of disabilities and early retirement among Danish female nurses.

BACKGROUND: Obesity is now the most common health problem in the younger population in Western societies and obesity rates are higher in lower socioeconomic status (SES) groups. We investigated whether overweight in childhood, independently of overweight in adulthood, influenced adult employment status and later risk of having disabilities. Using data from the Danish Female Nurse Cohort study, we examined associations between overweight in childhood/adolescence, and young adulthood and disabilities and early retirement in later adulthood (>44 years) and whether it was influenced by menopausal age (

Prevalence of cervical human papillomavirus in kidney transplant recipients: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to investigate the prevalence of cervical high-risk human papillomavirus (hrHPV) among kidney transplant recipients (KTRs) and, furthermore to compare it to that in immunocompetent controls. METHODS: A systematic literature search was conducted in PubMed, EMBASE, and Cochrane Library databases from January 2000 to February 2023, to identify studies investigating the prevalence of cervical hrHPV in KTRs. Pooled cervical hrHPV prevalences, odds ratios (ORs) comparing KTRs to controls and corresponding confidence intervals (CIs) were estimated using random effects logistic regression models. Heterogeneity between studies was assessed through the I2 statistic, and the significance was evaluated by the Cochrane's Q test. RESULTS: Altogether, 16 studies covering >1200 KTRs were included. The prevalence of cervical hrHPV in KTRs was 27.7% (95% CI 21.3-35.1) with substantial interstudy heterogeneity. Stratification indicated a higher prevalence in recent years (2019-2023) and in Asia (39% (95% CI 11.2-61.4)). The prevalence of HPV16 and HPV18 in KTRs was 8.0% (95% CI 3.9-15.9) and 1.7% (95% CI 0.8-3.7), respectively. Comparing hrHPV prevalence in KTRs and controls based on six studies including >500 KTRs and 1000 controls, the OR for hrHPV was 2.0 (95% CI 1.1-3.6). CONCLUSIONS: This meta-analysis establishes an increased cervical hrHPV prevalence in KTRs compared to controls. The increased risk may be associated with immunosuppressive therapy post-transplantation. Further research is needed to explore the potential benefits of HPV vaccination, including potential revaccination strategies in KTRs.

Long-Term Health Consequences After Ovarian Removal at Benign Hysterectomy : A Nationwide Cohort Study.

BACKGROUND: More evidence is needed to substantiate current recommendations about removing ovaries during hysterectomy for benign conditions. OBJECTIVE: To compare long-term outcomes in women with and without bilateral salpingo-oophorectomy (BSO) during hysterectomy for benign conditions. DESIGN: Emulated target trial using data from a population-based cohort. SETTING: Women in Denmark aged 20 years or older during 1977 to 2017. PARTICIPANTS: 142 985 women with hysterectomy for a benign condition, 22 974 with BSO and 120 011 without. INTERVENTION: Benign hysterectomy with or without BSO. MEASUREMENTS: The primary outcomes were overall hospitalization for cardiovascular disease (CVD), overall cancer incidence, and all-cause mortality through December 2018. RESULTS: Compared with women without BSO, women with BSO who were younger than 45 years at surgery had a higher 10-year cumulative risk for hospitalization for CVD (risk difference [RD], 1.19 percentage points [95% CI, 0.09 to 2.43 percentage points]). Women with BSO had a higher 10-year cumulative risk for cancer for ages 45 to 54 years (RD, 0.73 percentage point [CI, 0.05 to 1.38 percentage points]), 55 to 64 years (RD, 1.92 percentage points [CI, 0.69 to 3.25 percentage points]), and 65 years or older (RD, 2.54 percentage points [CI, 0.91 to 4.25 percentage points]). Women with BSO had higher 10-year mortality in all age groups, although the differences were statistically significant only for ages 45 to 54 years (RD, 0.79 percentage point [CI, 0.27 to 1.30 percentage points]). The mortality at 20 years was inconsistent with that at 10 years in women aged 65 years or older. LIMITATION: Age was a proxy for menopausal status. CONCLUSION: The authors find that these results support current recommendations for conserving ovaries in premenopausal women without a high risk for ovarian cancer and suggest a cautious approach in postmenopausal women. PRIMARY FUNDING SOURCE: The Danish Cancer Society's Scientific Committee and the Mermaid Project.

Coping and grief symptoms after parental loss in adolescence - a nationwide follow-up study.

Knowledge about effective coping strategies is important to support bereaved adolescents who have lost a parent. We used data on 104 bereaved adolescents (13-17 years) from the FALCON nationwide questionnaire study of parentally bereaved families. We examined associations between adolescents' control-oriented and escape-oriented coping strategies (KidCOPE scale) approximately two months after loss and grief symptoms (PG-13 scale) at six months follow-up. We also examined associations between the perceived efficacy of each coping strategy at baseline and grief symptoms at six months. The use of escape-oriented coping (e.g., distraction, self-criticism and social withdrawal) was associated with higher grief symptoms at six months follow-up (ß = 0.4, 95% CI 0.1-0.9, p = 0.02), but no associations were found for control-oriented coping or perceived coping efficacy. Finding alternatives to the use of escape-oriented coping strategies may be an important part of grief interventions for bereaved adolescents.

Neo-train: study protocol and feasibility results for a two-arm randomized controlled trial investigating the effect of supervised exercise during neoadjuvant chemotherapy on tumour response in patients with breast cancer.

BACKGROUND: Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. METHODS: This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1-2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21-29), at surgery (approximately week 21-30) and 3 months post-surgery (approximately 33-42 weeks from baseline). DISCUSSION: This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

Response to pneumococcal conjugate and polysaccharide vaccination in children with rheumatic disease.

Children with rheumatic disease and compromised immune system have an increased risk of infection. Streptococcus pneumoniae is a frequent pathogen, and immunization is recommended. In this study, we investigated whether immunocompromised children with rheumatic disease do respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. The study was conducted at two tertiary referral hospitals in Denmark from 2015 to 2018. Patients with rheumatic disease and compromised immune system aged 2-19 years were eligible. Patients were vaccinated with 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine. A blood sample was collected before vaccination and after each vaccination. IgG antibodies were quantified for twelve serotypes. Seroprotection for each serotype was defined as IgG ≥0.35 µg/mL. A total of 27 patients were enrolled. After the conjugate vaccine, an increase in antibody titres compared with pre-vaccination was found for all serotypes and 9/12 were significant. After the polysaccharide vaccine, the antibody titres for all serotypes but one was seen to increase but none reached significance. The proportion of patients protected before immunization ranged from 20.8% to 100% for the individual serotypes. Odds ratio for achieving seroprotection after the conjugate vaccine was >1 for 10/12 serotypes but only significant for three serotypes. After the polysaccharide vaccine, the odds ratio was >1 for 9/12 serotypes but none reached significance. In conclusion, children with rheumatic disease and compromised immune system respond to pneumococcal immunization with 13-valent pneumococcal conjugate vaccine and maintain antibody levels upon subsequent immunization with 23-valent pneumococcal polysaccharide vaccine.

The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis.

INTRODUCTION: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD. METHODS: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (µmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM. FINDINGS: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0-1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: -0.1-[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (-7.3 mmol/mol, 95% CI: -10.0-[-4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64). DISCUSSION: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.

Effect of supervised group exercise on psychological well-being among pregnant women with or at high risk of depression (the EWE Study): A randomized controlled trial.

INTRODUCTION: Depression is expected to be the leading cause of disability worldwide by 2030. The prevalence is increasing and is two-fold higher in women than in men, women being at particularly high risk during hormonal transition phases such as pregnancy and the postpartum period. The objective for this trial was to assess the effect of supervised group exercise on psychological well-being and symptoms of depression among pregnant women with or at high risk of depression. MATERIAL AND METHODS: This study was undertaken at the Department of Obstetrics, Copenhagen University Hospital, Rigshospitalet, Denmark, from August 2016 to September 2018. Pregnant women with a current or previous history of depression and/or anxiety requiring treatment within the last 10 years, or use of antidepressants 3 months before or during pregnancy, were randomly assigned to 12 weeks of supervised group exercise from 17 to 22 weeks of gestation twice weekly, or to a control group. The primary outcome was self-reported psychological well-being at 29-34 weeks of gestation, measured by the five-item World Health Organization Well-being Index (WHO-5). Secondary outcomes included delivery outcomes and psychological well-being (WHO-5) 8 weeks postpartum. RESULTS: The intention-to-treat analysis showed no significant effect on psychological well-being on the primary outcome. Mean WHO-5 score in the intervention group was 2.0 (95% CI -1.3 to 5.2, P = .2) higher than in the control group. Per protocol analysis of women who attended ≥75% of the exercise sessions showed a statistically significant higher mean WHO-5 score relative to the control group at gestational weeks 29-34. Eight weeks postpartum the intervention group reported higher psychological well-being than the control group, mean difference in WHO-5 score of 5.5 (95% CI 1.0-10.1, P = .04). CONCLUSIONS: Supervised group exercise did not improve psychological well-being for women with or at high risk of depression at 29-34 weeks of gestation. Eight weeks postpartum the intervention group reported significantly higher psychological well-being than the control group. Based on our results, supervised exercise in groups is a safe complementary course of treatment alongside the existing antenatal care.

Why we succeed and fail in detecting fetal growth restriction: A population-based study.

INTRODUCTION: The objective of this study was to explore the association between detection of fetal growth restriction and maternal-, healthcare provider- and organizational factors. MATERIAL AND METHODS: A historical, observational, multicentre study. All women who gave birth to a child with a birthweight <2.3rd centile from 1 September 2012 to 31 August 2015 in Zealand, Denmark, were included. The population was identified through the Danish Fetal Medicine Database. Medical charts were reviewed to obtain data regarding maternal characteristics and information on the healthcare professionals. Date of authorization for the midwives and obstetricians involved was extracted from the Danish Health Authorization Registry. Multivariable Cox regression models were used to identify predictors of antenatal detection of fetal growth restriction, and analyses were adjusted for hospital, body mass index, parity, the presence of at least one risk factor and experience of the first midwife, number of midwife visits, number of visits to a doctor, the experience of the consultant midwife or the educational level of the doctor, the number of scans and gaps in continuity of midwife-care. Antenatal detection was defined as an ultrasound estimated fetal weight <2.3rd centile (corresponding to -2 standard deviations) prior to delivery. RESULTS: Among 78 544 pregnancies, 3069 (3.9%) had a fetal growth restriction. Detection occurred in 31% of fetal growth-restricted pregnancies. Clinical experience (defined as years since graduation) of the first consultation midwife was positively associated with detection, with a hazard ratio [HR] of 1.15, 95% confidence interval [CI] 1.03-1.28), for every 10 years of additional experience. The hazard of detection increased with the number of midwife consultations (HR 1.15, 95% CI 1.05-1.26) and with multiparity (HR 1.28, 95% CI 1.03-1.58). After adjusting for all covariates, an unexplained difference between hospitals (P = .01) remained. CONCLUSIONS: The low-risk nullipara may constitute an overlooked group of women at increased risk of antenatal non-detection of fetal growth restriction. Being screened by experienced midwives during early pregnancy and having access to multiple midwife consultations may improve future diagnosis.

Wexner score and quality of life in women with obstetric anal sphincter injury.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injury causes anal incontinence in half of the women affected. However, most symptoms are mild. The objective of this study was to evaluate the prevalence of anal incontinence and quality of life in women at long term after delivery with obstetric anal sphincter injury. We also wanted to identify a relevant cutoff level of the Wexner score (also known as the Cleveland Clinic Incontinence Score) to indicate affected quality of life in these women. METHODS: We performed a population-based questionnaire cohort study with prospective follow-up, including all women in Denmark with obstetric anal sphincter injury and one subsequent delivery between 1997 and 2005. We performed uni- and multivariate analyses and calculated the area under the ROC curve. RESULTS: In Denmark, 3885 women had an obstetric anal sphincter injury in their first delivery and a second delivery between 1997 and 2005 and no subsequent deliveries until 2010-2011. Questionnaires were sent to 3259 eligible women, and the response rate was 74.6%. In total, 2004 women could be included in the final analyses. Of these, 29.2% (n = 584) reported affected quality of life due to anal incontinence at long-term follow-up. We found that all symptoms of anal incontinence were associated with affected quality of life. The median age at follow-up was 40.3 years. The area under the ROC curve was 0.96 (95% CI 0.95-0.97) with a sensitivity of 0.94 (95% CI 0.92-0.96) and a specificity of 0.85 (95% CI 0.84-0.87) corresponding to an optimal cutoff level of the Wexner score of ≥ 2 to identify women with affected quality of life due to anal incontinence. CONCLUSIONS: In women with obstetric anal sphincter injury, 29% reported affected quality of life due to anal incontinence at long-term follow-up, and we found a low Wexner score cutoff level of ≥ 2 to identify women with affected quality of life.

Interprofessional versus monoprofessional case-based learning in childhood cancer and the effect on healthcare professionals' knowledge and attitudes: study protocol for a randomised trial.

BACKGROUND: Interprofessional education in childhood cancer is a multifaceted field involving multiple healthcare professionals with general and specialised knowledge and skills. Complex treatment, care and rehabilitation require continuous professional development and maintenance of healthcare professionals' competencies in their field of expertise. However, limited knowledge exists in comparing interprofessional and monoprofessional education. Only a few randomised studies have evaluated the effectiveness and efficiency of interprofessional education. The objective of this single-centre, investigator-initiated cluster randomised trial is to study the effect of interprofessional versus monoprofessional case-based learning on healthcare professionals' knowledge of gastrointestinal side effects and attitudes towards team collaboration. METHODS: This study will randomise healthcare professionals to participate in either the experimental interprofessional group or the control monoprofessional group of case-based learning. The topic of the case-based intervention will be gastrointestinal side effects, one of six categories identified in a three-round Scandinavian Delphi study as relevant for interprofessional education in childhood cancer. The primary outcome is the self-reported questionnaire Assessment of Interprofessional Team Collaboration Scale. Secondary outcomes are measured by the self-reported questionnaires Readiness for Interprofessional Learning Scale Questionnaire, Safety Attitudes Questionnaire, and knowledge will be evaluated using a multiple-choice quiz. Participants will receive the self-reported questionnaires about 2 weeks before and 1 month after the intervention. On the day of the intervention, participants will answer a multiple-choice quiz before and after the case-based learning. Linear mixed models will be used to compare differences between the two groups in mean scores postintervention, adjusting for preintervention scores. DISCUSSION: This study will provide insight into the differences between interprofessional and monoprofessional case-based learning and how it affects healthcare professionals' knowledge of gastrointestinal side effects and attitudes towards team collaboration. TRIAL REGISTRATION: The intervention was registered at Clinical Trials.gov : NCT04204109 on December 102,019 and with the National Committee on Health Research Ethics: H-19087506 December 112,019 and the Danish Data Protection Agency: P-2019-637 October 152,019.

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia.

Analysis of chimerism in blood post-HCT using STR-PCR is routinely applied in parallel with quantification of MRD to predict relapse of leukemia. RQ-PCR chimerism is 10- to 100-fold more sensitive, but clinical studies in children are sparse. We analyzed IMC in blood samples following transplantation for acute lymphoblastic or myeloid leukemia in 56 children. IMC was defined as a minimum increase of (a) 0.1% or (b) 0.05% recipient DNA between two samples. The risk of relapse was higher in children with IMC of both 0.1% and 0.05% compared to children without IMC (HR 12.8 [95% CI: 3.9-41.4; P < .0001] and 7.6 [95% CI: 2.2-26.9; P < .01], respectively). The first IMC was detected at a median of 208 days prior to relapse. The 5-year cumulative incidence of relapse for children with a single IMC was 45.5% (CI 12.3-74.4) and 41.0% (14.2-66.6) for IMC above 0.1% and 0.05%, respectively. However, in 47 and 38 children never attaining IMC > 0.1% and >0.05%, 10 and 8 children relapsed, respectively. In a landmark analysis, no association was found between IMC prior to 90 days post-HCT and subsequent relapse by either classification of IMC and AUC for RQ-PCR chimerism was 54.2% (95 CI 27.7- 84.8). Although limited by a retrospective design, these results indicate that monitoring of RQ-PCR chimerism in peripheral blood may have a role in early detection of relapse in acute childhood leukemia.

Infant nasal nitric oxide over time: natural evolution and impact of respiratory tract infection.

Nasal nitric oxide (NO) discriminates between patients with primary ciliary dyskinesia (PCD) and healthy individuals. We report feasibility of measurement and natural evolution of nasal NO and upon the impact of respiratory tract infection (RTI) on nasal NO in healthy infants (HI), followed from birth until age 2 years, with comparison to nasal NO in infant PCD.Tidal-breathing nasal NO measurements were performed at scheduled visits at 2 weeks old and at 4, 8, 12, 18 and 24 months old, with extra visits during RTIs. Historical nasal NO measurements for infant PCD were included for comparison.Altogether, 224 nasal NO measurements were performed in 44 enrolled infants. Median newborn nasal NO was 46 ppb (interquartile range (IQR) 29-69 ppb), increasing at a rate of 5.4% per month up to 283 ppb (IQR 203-389 ppb) at the age of 2 years. RTIs in 27 out of 44 infants temporarily suppressed nasal NO by 79%. Values for nasal NO in seven infants with PCD ranged from 6-80 ppb. The success rate to accept nasal NO sampling was 223 out of 224 measurements (99.6%).Tidal-breathing nasal NO measurement was indeed feasible in infancy and nasal NO in HI increased significantly up to 2 years of age, in opposition to nasal NO in PCD cases, which stayed low past 2 years of age. RTI episodes caused marked, temporary reductions in nasal NO in HI indistinguishable from that in infant PCD, suggesting that nasal NO should be measured in RTI-free intervals.

Long-term anal incontinence after obstetric anal sphincter injury-does grade of tear matter?

BACKGROUND: Anal incontinence is a major concern following delivery with obstetric anal sphincter injury (OASIS), and has been related to the degree of sphincter tear. OBJECTIVE: The aims of this study were (1) to evaluate whether women with a fourth-degree OASIS in the first delivery have an increased risk of long-term anal and fecal incontinence after a second delivery, and (2) to assess the impact of mode of second delivery on anal incontinence and related symptoms in these patients. MATERIALS AND METHODS: We performed secondary analyses of a national questionnaire study in all Danish women with an OASIS in their first delivery and 1 subsequent delivery, both deliveries in 1997 to 2005. The questionnaires were sent a minimum of 5 years since the second delivery. In Denmark, women with anal incontinence after a delivery with OASIS are recommended elective cesarean deliveries in subsequent pregnancies. We performed uni- and multivariable logistic regression analyses to evaluate the outcomes. RESULTS: In total, 2008 patients had an OASIS, of whom 12.2% (n = 245) had a fourth-degree tear in the first delivery. The median follow-up time since the first delivery with OASIS was 11.6 years (IQR, 10.2-13.2 years) and since the second delivery 8.5 years (IQR, 7.1-10.1 years). Women with a fourth-degree sphincter injury in the first delivery were at higher risk for anal incontinence (58.8%, n = 144) as well as fecal incontinence (30.6%, n = 75) than patients with a third-degree injury in the first delivery (41.0%, n = 723, and 14.6%, n = 258, respectively). The differences between groups persisted after adjustment for important maternal, fetal, and obstetric characteristics (adjusted odds ratio [aOR], 2.14; 95% confidence interval [CI], 1.52-3.02; P < 0.001 for anal incontinence; and aOR, 2.49; 95% CI, 1.73-3.56; P < 0.001 for fecal incontinence). In subgroup analyses of patients with fourth-degree anal sphincter injury in the first delivery, the mode of second delivery was not associated with the risk of anal incontinence (aOR, 0.97; 95% CI, 0.41-1.84; P = 0.71) or fecal incontinence (aOR, 1.28; 95% CI, 0.65-2.52; P = 0.48). The effect of the mode of the second delivery did not differ between women with a fourth-degree OASIS and those with a third-degree injury with regard to both anal (P = 0.09) and fecal (P = 0.96) incontinence. CONCLUSION: After a second delivery, women with a fourth-degree OASIS in the first delivery have a higher risk of long-term anal and fecal incontinence than women with a third-degree sphincter injury. Adjusted odds of long-term anal and fecal incontinence did not differ significantly by mode of second delivery. Women with a fourth-degree OASIS should be informed about the increased risk of long-term anal incontinence and advised that subsequent elective cesarean delivery is not protective.

Confounders other than comorbidity explain survival differences in Danish and Swedish ovarian cancer patients - a comparative cohort study.

OBJECTIVE: Danish ovarian cancer (OC) patients have previously been found to have worse prognosis than Swedish patients, and comorbidity has been suggested as a possible explanation for this survival difference. We aimed to investigate the prognostic impact of comorbidity in surgically treated OC patients in Denmark and Sweden. METHODS: This comparative cohort study was based on data from 3118 surgically treated OC patients diagnosed in 2012-2015. The Swedish subcohort (n = 1472) was identified through the Swedish National Quality Register of Gynecological Surgery, whereas the Danish subcohort (n = 1646) originated from the Danish Gynecological Cancer Database. The clinical databases have high coverage and similar variables included. Comorbidity was classified according to the Ovarian Cancer Comorbidity Index and overall survival was the primary outcome. Data were analyzed using Kaplan Meier and Cox regression analyses. Multiple imputation was used to handle missing data. RESULTS: We found comparable frequencies of the following comorbidities: Hypertension, diabetes and 'Any comorbidity'. Arteriosclerotic cardiac disease and chronic pulmonary disease were more common among Swedish patients. Univariable survival analysis revealed a significant better prognosis for Swedish than for Danish patients (HR 0.84 [95% CI 0.74-0.95], p < .01). In adjusted multivariable analysis, Swedish patients had nonsignificant better prognosis compared to Danish patients (HR 0.91 [95% CI 0.80-1.04], p = .16). Comorbidity was associated with survival (p = .02) but comorbidity did not explain the survival difference between the two countries. CONCLUSIONS: Danish OC patients have a poorer prognosis than patients in Sweden but the difference in survival seems to be explained by other factors than comorbidity.

The Association Between Self-Rated Fitness and Cardiorespiratory Fitness in Adults.

To assess criterion validity of a single item question on self-rated physical fitness against objectively measured cardiorespiratory fitness. From the Health2008 study 749 men and women between 30 and 60 years of age rated their fitness as excellent, very good, good, fair or poor. Cardiorespiratory fitness was estimated with the watt-max test. Agreement between self-rated and objectively measured physical fitness was assessed by Cohen's weighted kappa coefficient. Correlation was determined by Goodman & Kruskal's gamma correlation coefficient. All analyses were stratified according to gender. Data from 323 men and 426 women were analysed. There was a slight agreement between self-rated and objectively measured fitness in men (weighted kappa: 0.18, [95%CI: 0.13;0.23]) and a fair agreement in women (weighted kappa: 0.27, [95%CI: 0.22;0.32]). In both genders, self-rated fitness was positively correlated with objectively measured fitness (moderate correlation; gamma correlation coefficient for men: 0.63 [95%CI: 0.54;0.72] and women: 0.67 [95%CI: 0.59;0.75]). There was a slight to fair agreement and moderate, positive correlations between self-rated physical fitness and watt-max estimated cardiorespiratory fitness. Hence, a single-item question on physical fitness may be a cost-effective method of assessing fitness in large population studies, but is not valid for individual assessments.

The Effects of Simulation-based Transvaginal Ultrasound Training on Quality and Efficiency of Care: A Multicenter Single-blind Randomized Trial.

OBJECTIVE: To explore the effect of adding simulation-based transvaginal ultrasound training to trainees' clinical training compared with only clinical training on quality of and efficiency of care. BACKGROUND: Simulation-based ultrasound training may be an effective adjunct to clinical training, but no studies have examined its effects on quality and efficiency of care. METHODS: Trainees from 4 University Hospitals in East Denmark were included (N = 54). Participants were randomized to either simulation-based ultrasound training and clinical training (intervention group, n = 28), or to clinical training only (control group, n = 26).The primary outcome was patient-reported discomfort during transvaginal ultrasound examinations performed by study participants. Secondary outcomes included patient-reported perceived safety and confidence in ultrasound provider. Finally, the need for trainee supervision or repeated patient examinations was recorded. RESULTS: In total, 1150 patient ratings were collected. The intervention was associated with a reduction of patient discomfort by 18.5% [95% confidence interval (CI), 10.7-25.5; P < 0.001), and with a 7.9% (95% CI, 0.5-14.7; P = 0.04) increase in perceived safety. The intervention group participants received 11.1% (95% CI, 2.5-18.9) higher scores on patients' confidence compared with control group participants (P = 0.01). When the number of days of clinical training was doubled, the odds for trainee supervision or repeated patient examination was reduced by 45.3% (95% CI, 33.5-55.1) and 19.8% (95% CI, 4.1-32.9) in the intervention and control group, respectively (P = 0.005). CONCLUSIONS: Simulation-based ultrasound training improved quality of care and reduced the need for repeated patient examination and trainee supervision.

Recurrent obstetric anal sphincter injury and the risk of long-term anal incontinence.

BACKGROUND: Women with an obstetric anal sphincter injury are concerned about the risk of recurrent obstetric anal sphincter injury in their second pregnancy. Existing studies have failed to clarify whether the recurrence of obstetric anal sphincter injury affects the risk of anal and fecal incontinence at long-term follow-up. OBJECTIVE: The objective of the study was to evaluate whether recurrent obstetric anal sphincter injury influenced the risk of anal and fecal incontinence more than 5 years after the second vaginal delivery. STUDY DESIGN: We performed a secondary analysis of data from a postal questionnaire study in women with obstetric anal sphincter injury in the first delivery and 1 subsequent vaginal delivery. The questionnaire was sent to all Danish women who fulfilled inclusion criteria and had 2 vaginal deliveries 1997-2005. We performed uni- and multivariable analyses to assess how recurrent obstetric anal sphincter injury affects the risk of anal incontinence. RESULTS: In 1490 women with a second vaginal delivery after a first delivery with obstetric anal sphincter injury, 106 had a recurrent obstetric anal sphincter injury. Of these, 50.0% (n = 53) reported anal incontinence compared with 37.9% (n = 525) of women without recurrent obstetric anal sphincter injury. Fecal incontinence was present in 23.6% (n = 25) of women with recurrent obstetric anal sphincter injury and in 13.2% (n = 182) of women without recurrent obstetric anal sphincter injury. After adjustment for third- or fourth-degree obstetric anal sphincter injury in the first delivery, maternal age at answering the questionnaire, birthweight of the first and second child, years since first and second delivery, and whether anal incontinence was present before the second pregnancy, the risk of flatal and fecal incontinence was still increased in patients with recurrent obstetric anal sphincter injury (adjusted odds ratio, 1.68 [95% confidence interval, 1.05-2.70), P = .03, and adjusted odds ratio, 1.98 [95% confidence interval, 1.13-3.47], P = .02, respectively). More women with recurrent obstetric anal sphincter injury reported affected the quality of life because of anal incontinence (34.9%, n = 37) compared with women without recurrent obstetric anal sphincter injury (24.2%, n = 335), although this difference did not reach statistical significance after adjustment (adjusted odds ratio, 1.53 [95% confidence interval, 0.92-2.56] P = .10). CONCLUSION: Women opting for vaginal delivery after obstetric anal sphincter injury should be informed about the risk of recurrence, which is associated with an increased risk of long-term flatal and fecal incontinence.

Hepatotoxicity During Maintenance Therapy and Prognosis in Children With Acute Lymphoblastic Leukemia.

Hepatotoxicity is a known toxicity to treatment of childhood acute lymphoblastic leukemia. Hepatotoxicity occurs during maintenance therapy and is caused by metabolites of 6-Mercaptopurine (6 MP) and Methotrexate (MTX). Our objective was to investigate the association between alanine aminotransferases (ALAT) levels and relapse rate. We included 385 patients enrolled in the NOPHO ALL-92 protocol. Data on ALAT levels, 6 MP and MTX doses, cytotoxic MTX/6 MP metabolites, and thiopurine methyltransferase (TPMT) activity were prospectively registered. In total, 91% of the patients had a mean ALAT (mALAT) level above upper normal limit (40 IU/L) and ALAT levels were positively correlated to 6 MP doses (rs=0.31; P<0.001). In total, 47 patients suffered a relapse, no difference in mALAT levels were found in these compared with nonrelapse patients (median, 107 vs. 98 IU/L; P=0.39). mALAT levels in patients classified as TPMT high activity (TPMT) were higher than in TPMT low-activity patients (median, 103 vs. 82 IU/L; P=0.03). In a Cox regression model risk of relapse was not associated with ALAT levels (P=0.56). ALAT levels increased 2.7%/month during the last year of maintenance therapy (P<0.001). In conclusion, elevated ALAT levels are associated with TPMT and may indicate treatment adherence in these patients. If liver function is normal, elevated ALAT levels should not indicate treatment adaptation.

Mode of delivery after obstetric anal sphincter injury and the risk of long-term anal incontinence.

BACKGROUND: Primiparous women have an increased risk of obstetric anal sphincter injury; because most of these patients deliver again, there are major concerns about mode of delivery: the risk of recurrent obstetric anal sphincter injury and the risk of long-term symptoms of anal incontinence. Although an elective cesarean delivery protects against recurrent obstetric anal sphincter injury, it is uncertain how the second delivery affects the risk of long-term anal incontinence. OBJECTIVE: The purpose of this study was to evaluate whether the mode of delivery for a second pregnancy, after a documented obstetric anal sphincter injury at the time of first delivery, had a significant impact on the prevalence of anal and fecal incontinence in the long term. STUDY DESIGN: We performed a population-based questionnaire cohort study that evaluated anal and fecal incontinence, fecal urgency, and affected quality of life caused by anal incontinence in 1978 patients who had obstetric anal sphincter injury in the first delivery and a second vaginal (n = 1472 women; 71.9%) or elective cesarean delivery (n = 506 women; 24.7%) delivery. We performed uni- and multivariable logistic regression analyses to compare groups. RESULTS: Long-term anal incontinence was reported in 38.9% of patients (n = 573) with second vaginal compared with 53.2% (n = 269) with elective cesarean delivery. The corresponding numbers that reported anal incontinence before the second pregnancy was 29.4% for those with vaginal delivery compared with 56.2% of those with elective cesarean delivery (ie, there was a significantly larger change in the risk of anal incontinence in the group with a second vaginal delivery compared with the change in the group with elective cesarean in second delivery). However, adjusted for important maternal and obstetric characteristics, the risk of long-term anal incontinence was nonsignificantly lower in patients with elective cesarean delivery (adjusted odds ratio, 0.77; 95% confidence interval, 0.57-1.05; P = .09). Furthermore, the risk of fecal incontinence was not affected by mode of delivery in the multivariable analysis (adjusted odds ratio, 1.04; 95% confidence interval, 0.76-1.43; P = .79). Patients with persistent anal incontinence before the second pregnancy (n = 496) had an increased risk of long-term anal incontinence (adjusted odds ratio, 64.70; 95% confidence interval, 42.85-97.68; P < .001) and long-term fecal incontinence (adjusted odds ratio, 13.76, 95% confidence interval, 10.03-18.88, P<0.001) compared with patients without anal incontinence before the second pregnancy. CONCLUSION: Mode of second delivery did not significantly affect the risk of long-term anal or fecal incontinence in multivariable analyses of patients with previous obstetric anal sphincter injury in this population in which patients with anal incontinence before the second pregnancy were recommended to have an elective cesarean delivery in the subsequent delivery. Nonetheless, we found that patients with vaginal delivery had a higher risk of deterioration of anal incontinence symptoms compared with those with an elective cesarean delivery.