Chronic fatigue in long-term survivors of head and neck cancer treated with radiotherapy.

BACKGROUND: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). MATERIAL AND METHODS: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. RESULTS: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. CONCLUSIONS: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.

Haemodynamic effects of remifentanil during induction of general anaesthesia with propofol. A randomised trial.

BACKGROUND: Remifentanil may have a dose-dependent haemodynamic effect during the induction of general anaesthesia combined with propofol. Our objective was to investigate whether systolic arterial blood pressure (SAP) was reduced to a greater extent when the remifentanil dose was increased. METHODS: This randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. Ninety-nine healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1 ratio to receive remifentanil induction with a low, medium or high dose corresponding to maximum effect-site concentrations (Ce) of 2, 4 and 8 ng/mL. The induction dose of propofol was 1.8 mg/kg, with a Ce of 2.9 µg/mL. Anaesthesia was induced using target-controlled infusion. After 150 s of sedation, a bolus of remifentanil and propofol was administered. Baseline was defined as 55-5 s before the bolus dose, and the total observation time was 450 s. We used beat-to-beat haemodynamic monitoring with LiDCOplus. The primary outcome variable was the maximum decrease in SAP within 5 min after bolus administration of remifentanil and propofol. Absolute and relative changes from baseline to minimal values and the area under the curve (AUC) were used as effect measures. Comparisons of groups were performed using analysis of variance (ANOVA). RESULTS: Median remifentanil doses were 0.75, 1.5 and 3.0 µg/kg in the low-, medium- and high-dose groups, respectively. The absolute changes (mean ± standard deviation) in SAP in the low-, medium- and high-dose groups of remifentanil were -39 ± 9.6 versus -43 ± 9.1, and -41 ± 10 mmHg, respectively. No difference (95% confidence interval) in the absolute change in SAP was observed between the groups (ANOVA, p = .29); medium versus low dose 3.7 (-2.0, 9.4) mmHg, and high versus medium dose -2.2 (-8.0; 3.5) mmHg. The relative changes from baseline to minimum SAP values were -30% versus -32% versus -32% (p = .52). The between-group differences in the AUC were not statistically significant. Relative changes in heart rate (-20% vs. -21% vs. -21%), stroke volume (-19% vs. -16% vs. -16%), cardiac output (-32% vs. -32% vs. -32%), systemic vascular resistance (-24% vs. -27% vs. -28%), and AUC were not statistically significant. CONCLUSION: This trial demonstrated major haemodynamic changes during the induction of anaesthesia with remifentanil and propofol. However, we did not observe any statistically significant differences between low, medium or high doses of remifentanil when using continuous invasive high-accuracy beat-to-beat monitoring.

Ipilimumab and nivolumab combined with anthracycline-based chemotherapy in metastatic hormone receptor-positive breast cancer: a randomized phase 2b trial.

BACKGROUND: Immune checkpoint inhibitors have shown minimal clinical activity in hormone receptor-positive metastatic breast cancer (HR+mBC). Doxorubicin and low-dose cyclophosphamide are reported to induce immune responses and counter regulatory T cells (Tregs). Here, we report the efficacy and safety of combined programmed cell death protein-1/cytotoxic T-lymphocyte-associated protein 4 blockade concomitant with or after immunomodulatory chemotherapy for HR+mBC. METHODS: Patients with HR+mBC starting first-/second- line chemotherapy (chemo) were randomized 2:3 to chemotherapy (pegylated liposomal doxorubicin 20 mg/m2 every second week plus cyclophosphamide 50 mg by mouth/day in every other 2-week cycle) with or without concomitant ipilimumab (ipi; 1 mg/kg every sixth week) and nivolumab (nivo; 240 mg every second week). Patients in the chemo-only arm were offered cross-over to ipi/nivo without chemotherapy. Co-primary endpoints were safety in all patients starting therapy and progression-free survival (PFS) in the per-protocol (PP) population, defined as all patients evaluated for response and receiving at least two treatment cycles. Secondary endpoints included objective response rate, clinical benefit rate, Treg changes during therapy and assessment of programmed death-ligand 1 (PD-L1), mutational burden and immune gene signatures as biomarkers. RESULTS: Eighty-two patients were randomized and received immune-chemo (N=49) or chemo-only (N=33), 16 patients continued to the ipi/nivo-only cross-over arm. Median follow-up was 41.4 months. Serious adverse events occurred in 63% in the immune-chemo arm, 39% in the chemo-only arm and 31% in the cross-over-arm. In the PP population (N=78) median PFS in the immune-chemo arm was 5.1 months, compared with 3.6 months in the chemo-only arm, with HR 0.94 (95% CI 0.59 to 1.51). Clinical benefit rates were 55% (26/47) and 48% (15/31) in the immune-chemo and chemo-only arms, respectively. In the cross-over-arm (ipi/nivo-only), objective responses were observed in 19% of patients (3/16) and clinical benefit in 25% (4/16). Treg levels in blood decreased after study chemotherapy. High-grade immune-related adverse events were associated with prolonged PFS. PD-L1 status and mutational burden were not associated with ipi/nivo benefit, whereas a numerical PFS advantage was observed for patients with a high Treg gene signature in tumor. CONCLUSION: The addition of ipi/nivo to chemotherapy increased toxicity without improving efficacy. Ipi/nivo administered sequentially to chemotherapy was tolerable and induced clinical responses. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03409198.

Radiation-induced long-term dysphagia in survivors of head and neck cancer and association with dose-volume parameters.

BACKGROUND: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. METHODS: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. RESULTS: Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia. CONCLUSIONS: Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.

Impact of hyperfractionated re-irradiation on quality of life in patients with recurrent or second primary head and neck cancer, a prospective single institutional study.

Purpose: Describe the clinical outcome of hyperfractionated re-irradiation (HFRT) in patients with recurrent or second primary (SP) head and neck cancer (HNC). Methods: This prospective observational study included HNC patients eligible for HFRT. Inclusion criteria: age ≥18 years, recurrent or SP HNC, planned re-irradiation and ability to respond to questionnaires. Patients received 1.5 Gy twice daily, five days a week for three (palliative) or four (curative/local control) weeks, total dose 45/60 Gy. Toxicity was scored with CTCAE v3 at baseline, end of treatment, at three, six, 12 and 36 months follow-up. Health-related quality of life (HRQoL) was measured with EORTC QLQ-C30 and EORTC QLQ-H&N35, pre-treatment and eight times until 36 months. In the main outcome (Global quality of life and H&N Pain), a change score of ≥10 was considered clinically significant, and p-values < 0.05 (two-sided) statistically significant. The Kaplan-Meier method was used for survival analyses. Results: Over four years from 2015, 58 patients were enrolled (37 recurrent and 21 SP). All, but two patients completed treatment as planned. Toxicity (≥grade 3) increased from pre-treatment to end of treatment with improvement in the follow-up period. The mean Global quality of life (QoL) and H&N Pain scores were stable from pre-treatment to three months. Maintained/ improved Global QoL was reported by 60% of patients at three months and 56% of patients at 12 months. For patients with curative, local control and palliative intent, the median survival (range) was 23 (2-53), 10 (1-66) and 14 (3-41) months respectively. Of those alive, the proportion of disease-free patients at 12 and 36 months, were 58% and 48%, respectively. Conclusion: Most HNC patients reported maintained HRQoL at three and 12 months after HFRT despite serious toxicity observed in many patients. Long-term survival can be achieved in a limited proportion of the patients.

Hemodynamic effects of a low versus a high dose of propofol during induction of anesthesia. A randomized trial.

BACKGROUND: Hypotension is common after anesthesia induction with propofol and is associated with increased morbidity. It is important to examine the effects of the proposed interventions to limit preventable hypotension, as suggested by the reduction in the dose of propofol. Our objective was to investigate whether a high dose of propofol is inferior to a low dose with respect to changes in systolic arterial blood pressure (SAP). METHODS: This randomized, double-blind, dose-controlled, non-inferiority study included 68 healthy women scheduled for gynecological surgery at the Day Surgery Unit, Haugesund Hospital, Norway. The patients were randomly allocated 1:1 to a low or high dose (1.4 mg/kg total body weight (TBW) versus 2.7 mg/kg TBW of propofol corresponding to maximal effect site concentrations (Ce) of 2.0 µg/mL versus 4.0 µg/mL. The dose of remifentanil was 1.9-2.0 µg/kg TBW, with maximal Ce of 5.0 ng/mL. The patients were observed for 450 s from the start of the infusions. The first 150 s was the sedation period, after which a bolus of propofol and remifentanil was administered. Baseline was defined as 55-5 s before the bolus doses. LiDCOplus was used for invasive beat-to-beat hemodynamic monitoring of changes in SAP, heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR). A difference of 10 mmHg in the change in SAP was considered to be clinically important. RESULTS: The SAP change difference for low versus high dose was -2.9 mmHg (95% CI -9.0-3.1). The relative changes for low versus high dose were SAP -31% versus -36%, (p < .01); HR -24% versus -20%, (p = .09); SVR -20% versus -31%, (p < .001); SV -16% versus -20%, (p = .04); and CO -35% versus -32%, (p = .33). CONCLUSION: A high dose of propofol was not inferior to a low dose, and a reduction in the dose of propofol did not result in clinically important attenuation of major hemodynamic changes during induction in healthy women. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03861364, January 3, 2019.

Alterations in inflammatory markers after a 12-week exercise program in individuals with schizophrenia-a randomized controlled trial.

Background: In individuals with schizophrenia, inflammation is associated with depression, somatic comorbidity and reduced quality of life. Physical exercise is known to reduce inflammation in other populations, but we have only limited knowledge in the field of schizophrenia. We assessed inflammatory markers in plasma samples from individuals with schizophrenia participating in an exercise intervention randomized controlled trial. We hypothesized that (i) physical exercise would reduce levels of inflammatory markers and (ii) elevated inflammatory status at baseline would be associated with improvement in cardiorespiratory fitness (CRF) following intervention. Method: Eighty-two individuals with schizophrenia were randomized to a 12-week intervention of either high-intensity interval training (HIIT, n = 43) or active video gaming (AVG, n = 39). Participants were assessed at baseline, post intervention and four months later. The associations between exercise and the inflammatory markers soluble urokinase plasminogen activator receptor, c-reactive protein, tumor necrosis factor (TNF), soluble TNF receptor 1 and interleukin 6 (IL-6) were estimated using linear mixed effect models for repeated measures. For estimating associations between baseline inflammation and change in CRF, we used linear regression models. Results: Our main findings were (i) TNF and IL-6 increased during the intervention period for both groups. Other inflammatory markers did not change during the exercise intervention period; (ii) baseline inflammatory status did not influence change in CRF during intervention, except for a positive association between baseline IL-6 levels and improvements of CRF to post intervention for both groups. Conclusion: In our study, HIIT and AVG for 12-weeks had no reducing effect on inflammatory markers. Patients with high baseline IL-6 levels had a positive change in CRF during intervention. In order to increase our knowledge regarding association between inflammatory markers and exercise in individuals with schizophrenia, larger studies with more frequent and longer exercise bout duration are warranted.

Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures.

Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.

Fear of cancer recurrence eight years after early-stage breast cancer - results from a national survey.

BACKGROUND: Fear of cancer recurrence (FCR) in breast cancer survivors (BCSs) is common, associated with reduced quality of life and effective interventions exist. There are knowledge gaps concerning FCR among long-term, early-stage BCSs and its associations with other late effects. Within a national cohort, we explored these knowledge gaps, with the ultimate aim of improved care for BCSs experiencing long-term FCR. METHODS: In this cross-sectional study, all BCSs aged 20-65 years with early-stage breast cancer in 2011-2012 (n = 2803), were identified by the Cancer Registry of Norway in 2019 and mailed a survey including the Assessment of Survivor Concerns used to measure FCR. Factors associated with moderate/high FCR (defined as a sum score of ≥ 6 of a possible range 3-12, or a single score on one of the items of ≥ 3) were explored using a three-block regression analyses including relevant sociodemographic-, health- and cancer-related variables. RESULTS: In total, 1311 BCSs were included (47%). Median age at survey was 60 years. Fifty-six % reported moderate-to-high FCR, associated with younger age (OR 0.96, 95% CI 0.95-0.97) and receiving chemo- and endocrine therapy (OR 1.59, 95% CI 1.15-2.20). After adding late effects into the model, FCR remained significantly associated with these variables, in addition to sleep disturbances (OR 1.58, 95% CI 1.18-2.10). In the final block, adding mental distress, FCR remained significantly associated with younger age (OR 0.97, 95% CI 0.96-0.99), receiving chemo- and endocrine therapy (OR 1.14, 95% CI 1.00-1.97), sleep disturbances (OR 1.44, 95% CI 1.08-1.94) and anxiety (OR 2.67, 95% CI 1.38-5.19). CONCLUSIONS: FCR was prevalent eight years after early-stage breast cancer. Being younger, receiving intensive treatment, experiencing sleep disturbances and/or anxiety were associated with moderate/high FCR. Addressing FCR should be part of standard follow-up care of long-term BCSs.

Single-arm studies involving patient-reported outcome data in oncology: a literature review on current practice.

Patient-reported outcomes (PROs) are increasingly used in single-arm cancer studies. We reviewed 60 papers published between 2018 and 2021 of single-arm studies of cancer treatment with PRO data for current practice on design, analysis, reporting, and interpretation. We further examined the studies' handling of potential bias and how they informed decision making. Most studies (58; 97%) analysed PROs without stating a predefined research hypothesis. 13 (22%) of the 60 studies used a PRO as a primary or co-primary endpoint. Definitions of PRO objectives, study population, endpoints, and missing data strategies varied widely. 23 studies (38%) compared the PRO data with external information, most often by using a clinically important difference value; one study used a historical control group. Appropriateness of methods to handle missing data and intercurrent events (including death) were seldom discussed. Most studies (51; 85%) concluded that PRO results supported treatment. Conducting and reporting of PROs in cancer single-arm studies need standards and a critical discussion of statistical methods and possible biases. These findings will guide the Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Data in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) in developing recommendations for the use of PRO-measures in single-arm studies.

The impact of recommending iron supplements to women with depleted iron stores in early pregnancy on use of supplements, and factors associated with changes in iron status from early pregnancy to postpartum in a multi-ethnic population-based cohort.

BACKGROUND: We aimed to evaluate the impact of recommending supplementation to pregnant women with serum ferritin (SF) < 20 µg/L in early pregnancy on use of supplements, and to explore which factors were associated with changes in iron status by different iron indicators to 14 weeks postpartum. METHODS: A multi-ethnic population-based cohort study of 573 pregnant women examined at mean gestational week (GW) 15 (enrolment), at mean GW 28 and at the postpartum visit (mean 14 weeks after delivery). Women with SF < 20 µg/L at enrolment were recommended 30-50 mg iron supplementation and supplement use was assessed at all visits. Change of SF, soluble transferrin receptor and total body iron from enrolment to postpartum were calculated by subtracting the concentrations at the postpartum visit from that at enrolment. Linear and logistic regression analyses were performed to assess associations between use of supplements in GW 28 and changes in iron status and postpartum iron deficiency/anaemia. Change of iron status was categorized into 'steady low', 'improvement', 'deterioration', and 'steady high' based on SF status at enrolment and postpartum. Multinomial logistic regression analyses were performed to identify factors associated with change of iron status. RESULTS: At enrolment, 44% had SF < 20 µg/L. Among these women (78% non-Western European origin), use of supplements increased from 25% (enrolment) to 65% (GW 28). Use of supplements in GW 28 was associated with improved iron levels by all three indicators (p < 0.05) and with haemoglobin concentration (p < 0.001) from enrolment to postpartum, and with lower odds of postpartum iron deficiency by SF and TBI (p < 0.05). Factors positively associated with 'steady low' were: use of supplements, postpartum haemorrhage, an unhealthy dietary pattern and South Asian ethnicity (p ≤ 0.01 for all); with 'deterioration': postpartum haemorrhage, an unhealthy dietary pattern, primiparity and no use of supplements (p < 0.01 for all), and with 'improvement': use of supplements, multiparity and South Asian ethnicity (p < 0.03 for all). CONCLUSIONS: Both supplement use and iron status improved from enrolment to the postpartum visit among women recommended supplementation. Dietary pattern, use of supplements, ethnicity, parity and postpartum haemorrhage were identified as factors associated with change in iron status.

Exploring trends of severe postpartum haemorrhage: a hospital-based study.

BACKGROUND: Over the past two decades several high-income countries have reported increased rates of postpartum haemorrhage (PPH). Many of the studies are registry studies with limited access to detailed information. We aimed to explore trends of severe PPH in the largest labour ward in Norway during a 10-year period with a hospital based study. Our population constituted all women who gave birth after week 22 at Oslo University Hospital between 2008 and 2017. The main outcome measure was severe PPH, defined as registered blood loss greater than 1500 ml, or transfusion of blood products due to PPH. METHODS: We estimated the incidence of severe PPH and blood transfusions, and performed temporal trend analysis. We performed Poisson regression analysis to investigate associations between pregnancy characteristics and severe PPH, presented using crude incidence rate ratios (IRR) with 95% confidence intervals (CI)s. We also estimated annual percentage change of the linear trends. RESULTS: Among 96 313 deliveries during the 10-year study period, 2621 (2.7%) were diagnosed with severe PPH. The incidence rate doubled from 17.1/1000 to 2008 to 34.2/1000 in 2017. We also observed an increased rate of women receiving blood transfusion due to PPH, from 12.2/1000 to 2008 to 27.5/1000 in 2017. The rates of invasive procedures to manage severe PPH did not increase, and we did not observe a significant increase in the number of women defined with maternal near miss or massive transfusions. No women died due to PPH during the study period. CONCLUSION: We found a significant increasing trend of severe PPH and related blood transfusions during the 10-year study period. We did not find an increase in massive PPH, or in invasive management, and we suspect that the rise can be at least partly explained by increased awareness and early intervention contributing to improved registration of severe PPH.

Sexual well-being and penile appearance in adolescents operated for distal hypospadias in childhood.

BACKGROUND: The importance of patient-reported outcomes (PRO) in hypospadias is increasing. However, more knowledge is needed concerning genital self-perception on appearance and function in adolescents. The complication rates for distal hypospadias is different from that for severe hypospadias, and expected outcomes related to sexual well-being and cosmetics may also differ. OBJECTIVE: To investigate 16-year-olds' self-reported outcomes on penile appearance, sexual well-being, and voiding function in distal hypospadias, and compare with that of healthy male adolescents and a surgeon's view. STUDY DESIGN: Sixteen-year-old patients operated for distal hypospadias were included in this cross-sectional study and compared to a group of healthy adolescents. The assessment tools included the adolescents' self-perception on genital appearance and function measured by Pediatric Penile Perception Score (PPPS) and their responses to a structured interview. We also included information on clinical data from the electronic medical records, together with a physical examination and an uroflowmetry. RESULTS: Seventy patients and 61 healthy adolescents participated. Patients and the comparison group reported no differences on sexual well-being. The patients were satisfied with penile appearance, however their overall PPPS was significantly lower (8.9), compared to the comparison group (9.6, p = 0.03). Thirty-nine percent of patients had complications leading to re-interventions and reported lower scores on genital self-perception on appearance and function compared to those who had not re-interventions. Voiding function was normal. The surgeon's score on appearance was comparable to the patients' score. DISCUSSION: A key finding in our study is the patients' high satisfaction on sexual well-being, which was similar to healthy adolescents. The patients were also satisfied with penile appearance but scored significantly lower than the comparison group. Surgeons and patients had comparable scores on appearance; however, they seemed to emphasize different aspects of appearance. Our results on penile appearance and sexual well-being are comparable to those of other studies on distal hypospadias. In our study, re-interventions were associated with more negative genital self-perception on appearance and function, similar to findings in other studies. CONCLUSION: Our results show overall positive satisfaction on sexual well-being, voiding function and penile appearance despite less satisfaction on penile appearance when compared with the comparison group. Satisfaction was reported to be good also in patients experiencing re-interventions.

Factors associated with changes in students' self-reported nursing competence after clinical rotations: a quantitative cohort study.

BACKGROUND: The quality of nursing care in different healthcare contexts can be associated with the level of available nursing competence. Physical assessment skills are vital in nurses' assessment of patient care needs. However, in nursing education, using physical assessment skills is challenging for nursing students who struggle to apply these skills comprehensively in a clinical rotation. Therefore, this study explores changes in nursing competence, factors associated with changes after clinical rotations, and whether a Suite of Mobile Learning Tools supports changes in confident use of basic physical assessment skills. METHODS: A quantitative cohort study with an explorative pre-and post-test design. During autumn 2019 and spring 2020, 72 s-year nursing students and 99 third-year students participated in the study. The Nurse Professional Competence scale short form was used to investigate students' self-reported changes in nursing competence, and a study-specific questionnaire was used to investigate students' confidence concerning performing physical assessments. The students voluntarily used the Suite of Mobile Learning Tools for the learning of physical assessment. Linear regression analysis was used to identify factors associated with changes in nursing competence after clinical rotation. The STROBE guidelines for cohort studies were followed for study reporting. RESULTS: After the clinical rotation, both student groups reported changes in nursing competence and confidence in performing physical assessment skills, with statistically significant moderate or large changes in all areas. The Suite of Mobile Learning Tools was evaluated as being useful for learning physical assessment. The regression analysis showed that confidence in performing physical assessment skills, the usefulness of the Suite of Mobile Learning Tools, and a higher nursing competence at the start of clinical rotation were positively associated with overall nursing competence. CONCLUSION: Basic physical assessment skills are an important component of nursing competence and can be considered one of the pillars of person-centered care, as proposed by the Fundamentals of Care framework. Spaced repetition and access to digital resources are suggested pedagogical approaches to enhance student confidence in the use of assessment skills within academic and clinical contexts.

Translation and cross-cultural adaptation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire.

OBJECTIVE: There is a paucity of international data regarding self-reported lower extremity lymphedema and quality of life after surgery for gynecological cancer. Validated questionnaires are emerging, but translated versions are lacking. Cross-cultural adaptation is important to reduce the risk of introducing bias into a study. OBJECTIVE: To translate and culturally adapt the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for a Norwegian population. METHODS: Permission to use the original English versions of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for translation was obtained. The questionnaires were translated using a procedure based on standard guidelines, including forward translation by native speakers of the target language, synthesis, back translation, and review. Seventeen patients from the Norwegian Radium Hospital gynecological cancer outpatient clinic, all expected to have stable disease, were invited for questionnaire test-retest by completing the same questionnaires twice at 3-4-week intervals. Internal consistency was assessed by calculating Cronbach's alpha. Test-retest reliability was assessed using an intra-class correlation coefficient. RESULTS: Twelve patients completed the questionnaires twice. Cronbach's alpha was 0.75 for the Gynecologic Cancer Lymphedema Questionnaire and 0.89 for the Lower Extremity Lymphedema Screening Questionnaire. The intra-class correlation coefficient was 0.86 for the Gynecologic Cancer Lymphedema Questionnaire and 0.91 for the Lower Extremity Lymphedema Screening Questionnaire. CONCLUSIONS: Translation and cross-cultural adaptation of these internationally validated patient-reported outcomes questionnaires for survivors of lower extremity lymphedema in gynecological cancer was feasible. The Norwegian translation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire showed acceptable internal consistency and the test-retest reliability was excellent.

Intrapartum pudendal nerve block analgesia and childbirth experience in primiparous women with vaginal birth: A cohort study.

BACKGROUND: A negative childbirth experience has short- and long-term consequences for both mother and child. This study aimed to investigate the association between intrapartum pudendal nerve block (PNB) analgesia and childbirth experience. METHODS: Primiparous women with a singleton cephalic vaginal live births at term at Oslo University Hospital from January 1, 2017, to June 1, 2019, were eligible for inclusion. The main outcome was total score on a childbirth experience questionnaire (range 1.0-4.0, higher score indicates better childbirth experience). An absolute risk difference of 0.10 was considered clinically relevant. Propensity score matching was used to adjust for differences in baseline characteristics between women with and without PNB. The analyses were stratified by spontaneous vs instrumental birth. Subanalyses of the questionnaire's domains (own capacity, professional support, perceived safety, and participation) were performed. RESULTS: Of 979 participating women, mean age was 32 years. Childbirth experience did not differ between women with and without PNB, either in spontaneous (absolute risk difference of the mean: -0.05, P value 0.36) or in instrumental birth (absolute risk difference of the mean: 0.03, P value 0.61). There were no statistically significant differences between PNB group scores for the separate domains. CONCLUSIONS: Women's childbirth experiences did not differ between birthing people with or without PNB, either in spontaneous or in instrumental births. The clinical implications of our study should be interpreted in light of the pain-relieving effects of PNB.PNB should be provided on clinical indication, including for individuals with severe labor pain.

A multicenter international prospective study of the validity and reliability of a COVID-19-specific health-related quality of life questionnaire.

PURPOSE: To develop and validate a health-related quality of life (HRQoL) questionnaire for patients with current or previous coronavirus disease (COVID-19) in an international setting. METHODS: This multicenter international methodology study followed standardized guidelines for a four-phase questionnaire development. Here, we report on the pretesting and validation of our international questionnaire. Adults with current or previous COVID-19, in institutions or at home were eligible. In the pretesting, 54 participants completed the questionnaire followed by interviews to identify administration problems and evaluate content validity. Thereafter, 371 participants completed the revised questionnaire and a debriefing form to allow preliminary psychometric analysis. Validity and reliability were assessed (correlation-based methods, Cronbach's α, and intra-class correlation coefficient). RESULTS: Eleven countries within and outside Europe enrolled patients. From the pretesting, 71 of the 80 original items fulfilled the criteria for item-retention. Most participants (80%) completed the revised 71-item questionnaire within 15 min, on paper (n = 175) or digitally (n = 196). The final questionnaire included 61 items that fulfilled criteria for item retention or were important to subgroups. Item-scale correlations were > 0.7 for all but nine items. Internal consistency (range 0.68-0.92) and test-retest results (all but one scale > 0.7) were acceptable. The instrument consists of 15 multi-item scales and six single items. CONCLUSION: The Oslo COVID-19 QLQ-W61© is an international, stand-alone, multidimensional HRQoL questionnaire that can assess the symptoms, functioning, and overall quality of life in COVID-19 patients. It is available for use in research and clinical practice. Further psychometric validation in larger patient samples will be performed.

Exploring the impact of indication on variation in rates of intrapartum caesarean section in six Palestinian hospitals: a prospective cohort study.

BACKGROUND: Caesarean section rates are rising globally. No specific caesarian section rate at either country-level or hospital-level was recommended. In Palestinian government hospitals, nearly one-fourth of all births were caesarean sections, ranging from 14.5 to 35.6%. Our aim was to assess whether variation in odds for intrapartum caesarean section in six Palestinian government hospitals can be explained by differences in indications. METHODS: Data on maternal and fetal health were collected prospectively for all women scheduled for vaginal delivery during the period from 1st March 2015 to 30th November 2016 in six government hospitals in Palestine. Comparisons of proportions in sociodemographic, antenatal obstetric characteristics and indications by the hospital were tested by χ2 test and differences in means by one-way ANOVA analysis. The odds for intrapartum caesarean section were estimated by logistic regression. The amount of explained variance was estimated by Nagelkerke R square. RESULTS: Out of 51,041 women, 4724 (9.3%) underwent intrapartum caesarean section. The prevalence of intrapartum caesarean section varied across hospitals; from 7.6 to 22.1% in nulliparous, and from 5.8 to 14.1% among parous women. The most common indications were fetal distress and failure to progress in nulliparous, and previous caesarean section with an additional obstetric indication among parous women. Adjusted ORs for intrapartum caesarean section among nulliparous women ranged from 0.42 (95% CI 0.31 to 0.57) to 2.41 (95% CI 1.70 to 3.40) compared to the reference hospital, and from 0.50 (95% CI 0.40-0.63) to 2.07 (95% CI 1.61 to 2.67) among parous women. Indications explained 58 and 66% of the variation in intrapartum caesarean section among nulliparous and parous women, respectively. CONCLUSION: The differences in odds for intrapartum caesarean section among hospitals could not be fully explained by differences in indications. Further investigations on provider related factors as well as maternal and fetal outcomes in different hospitals are necessary.

Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial.

Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1positive disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 , 24 May 2017) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n = 40) or placebo (placebo-chemo; n = 28). Primary endpoints were descriptive assessment of progression-free survival in the per-protocol population (>3 atezolizumab and >2 PLD doses; n = 59) and safety in the full analysis set (FAS; all patients starting therapy; n = 68). Adverse events leading to drug discontinuation occurred in 18% of patients in the atezo-chemo arm (7/40) and in 7% of patients in the placebo-chemo arm (2/28). Improvement in progression-free survival was indicated in the atezo-chemo arm in the per-protocol population (median 4.3 months versus 3.5 months; hazard ratio (HR) = 0.57; 95% confidence interval (CI) 0.33-0.99; log-rank P = 0.047) and in the FAS (HR = 0.56; 95% CI 0.33-0.95; P = 0.033). A numerical advantage was observed for both the PD-L1positive (n = 27; HR = 0.65; 95% CI 0.27-1.54) and PD-L1negative subgroups (n = 31; HR = 0.57, 95% CI 0.27-1.21). The progression-free proportion after 15 months was 14.7% (5/34; 95% CI 6.4-30.1%) in the atezo-chemo arm versus 0% in the placebo-chemo arm. The addition of atezolizumab to PLD/cyclophosphamide was tolerable with an indication of clinical benefit, and the findings warrant further investigation of PD1/PD-L1 blockers in combination with immunomodulatory chemotherapy.

Prevalence of postpartum anaemia and iron deficiency by serum ferritin, soluble transferrin receptor and total body iron, and associations with ethnicity and clinical factors: a Norwegian population-based cohort study.

Worldwide, there are limited data on the prevalence of postpartum anaemia and iron status. The aims of the present study were to assess the prevalence of anaemia and iron deficiency (ID) by three iron indicators 14 weeks postpartum, their relations to haemoglobin (Hb) and associations with ethnicity and clinical factors in a multi-ethnic population. We conducted a population-based cohort study of 573 women followed from early pregnancy. The prevalence of postpartum anaemia (Hb <12·0 g/dl) was 25 %. ID prevalence varied from 39 % by serum ferritin (SF <15 µg/l), to 19 % by soluble transferrin receptor (sTfR >4·4 mg/l) and 22 % by total body iron (TBI < 0 mg/kg). The mean Hb concentration was 12·8 g/dl in women with no ID, 12·6 g/dl in those with ID by SF only and 11·6 g/dl in those with ID by SF, sTfR and TBI. ID by sTfR and TBI defined by the current threshold values probably identified a more severe iron-deficient population compared with ID assessed by SF. Compared with Western Europeans, the prevalence of anaemia was at least the double in ethnic minorities (26-40 % v. 14 %; P < 0·01-0·05), and the prevalence of ID by sTfR and TBI, but not of ID by SF < 15 µg/l, was significantly higher in some minority groups. After adjustment for covariates, only South Asians had lower Hb and higher sTfR concentration. Insufficient iron intake, gestational anaemia or ID, and postpartum haemorrhage were associated with lower postpartum Hb concentration and poorer iron status.