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Abstract Background Suicidal ideation may be a warning sign for suicide and previous work has indicated a higher prevalence of suicidal ideation during the COVID-19 pandemic. Job loss and job insecurity are potential risk factors for suicidal ideation, but their importance during the pandemic, and the role of organizational changes for suicidal ideation, is unclear. This study examined the association between various experiences associated with job loss and job insecurity during the pandemic and thoughts of suicide/self-harm in Sweden. Methods The study sample was drawn from the Swedish Longitudinal Occupational Survey of Health (SLOSH). Auxiliary data collections in February 2021 and 2022 assessed exposure to job loss/unemployment, furlough, workplace downsizing, or increased job insecurity versus stable employment and thoughts of suicide or self-harm (PHQ-9) during the pandemic. The analyses were based on 1558 individuals (2 349 observations) participating in either or both waves and who had been working before the pandemic. Logistic regression models with cluster-robust standard errors were fitted, including sociodemographic factors and prior mental health problems to control for potential confounding. Measures of personality based on a brief version of the Big-Five personality inventory were also added. Results The results indicated an association between all experiences, except furlough, and thoughts of suicide/self-harm, when adjusting for sex, age, civil status, socioeconomic status and prior mental health (job loss odds ratio (OR) = 3.70, 95% confidence interval (CI) 1.79–7.63, downsizing OR = 2.41, CI 1.24–4.70, job insecurity OR = 2.77, CI 1.15–6.67). The associations for job loss and insecurity were attenuated by adjustment for personality, although it remained statistically significant for downsizing. Conclusions The results suggested a higher risk of suicidal ideation connected with loss of employment and survival of a downsizing, but not a forced reduction in working times/pay during the COVID-19 pandemic. The association for subjective job insecurity was less robust and may be partly explained by personality.

Abstract Glycosaminoglycan (GAG) and sialic acid (total and free) assays are used as first‐line screening tests for the diagnosis of mucopolysaccharidoses and glycoproteinoses, respectively. There is a pronounced age‐dependent variation in the urinary concentrations of these metabolites in the normal population, and the stratification of the reference values into discrete age ranges may lead to an undesirably high number of false‐positive or false‐negative results. The aim of this study was to design a method for calculating continuous reference intervals as a function of age and its application to the analysis of GAGs and sialic acid (total, free, and conjugated) in urine. In the postpubertal period, concentrations of urinary GAGs and sialic acid have reached a plateau, so a traditional calculation of the reference range in this specific age group was considered appropriate. In the prepubertal period, a nonlinear regression performed with the Excel add‐in Solver was used to fit the logarithmized concentrations of the controls to a curve that represents the mean values as a function of age. A uniform distribution of the residuals was obtained, which allowed the calculation of the reference intervals by adding the values of their 2.5 and 97.5 percentiles to the independent variable of the regression curve to calculate the upper and lower reference curves. The main advantages of the developed method are (1) a reduction in the number of control samples needed to obtain adequate reference intervals and (2) an improvement in the reliability of diagnostic screening by reducing the uncertainty generated by the gaps in the traditional age‐stratified method.

Abstract Background Infants requiring neonatal care often face initial breastfeeding challenges, leading them to receive expressed breast milk from their mother or donor milk. While emphasizing the mother’s own milk as the gold standard for infant nutrition, the utilization of donor milk stands as the preferred alternative over infant formula due to its numerous benefits. To facilitate the provision of donor milk to preterm and ill infants in neonatal units, the active participation of women willing to contribute their breast milk is crucial. This study aims to enhance the understanding of women’s experiences in the donation process, thereby contributing to efforts aiming at alleviating the shortage of donated breast milk by improve the care and support for breast milk donors. Methods This descriptive qualitative study took an inductive approach based on individual semi-structured interviews conducted during 2021 with 15 breast milk donors in Sweden. The data were analysed with thematic analysis. Results Two themes were identified in the analysis: motivation to donate and challenges to overcome. Many of the women struggled to overcome the apparent challenges of not only starting the process of donating breast milk but also maintaining it. Despite the strain, they were motivated to donate their breast milk and seeking information by themselves to do something important for someone else. Only a few of the women talked about the financial benefits of donating breast milk; donating seemed to be mostly based on altruistic reasons. Conclusions Despite the challenges posed by COVID-19 restrictions, time consumption, and the hard work of sterilizing pump utensils, women continued to donate their milk driven by altruism. To enhance donor support and increase milk donation, several improvements are suggested: providing comprehensive information and resources, simplifying the donation process, offering flexible scheduling, and recognizing donors’ contributions.

Abstract Background and Aims Digital smoking cessation interventions have been shown to be effective in helping individuals achieve prolonged smoking abstinence. Nonetheless, the mechanisms that drive such effects are unclear. The current study aimed to estimate a digital smoking cessation intervention's natural direct and indirect effects. Methods This secondary analysis of mediated effects uses data from a randomised controlled trial which included participants who smoked at least one cigarette a week, had access to a mobile phone, and were 18 years or older. The comparator was existing smoking cessation support available to all members of the Swedish public. Primary outcomes were prolonged smoking abstinence and point prevalence of smoking abstinence, measured at 3- and 6-months post-randomisation. A counterfactual framework was used to estimate three hypothesised mediators of the intervention's effects: importance, knowledge of how to change (know-how), and confidence. Results Between 18/09/20 and 16/06/22, 1012 participants were randomised. The intervention led to improved confidence and know-how, which both partially mediated the effects of the digital intervention on smoking abstinence at 3- and 6 months post-randomisation. Conclusions A digital smoking cessation intervention was found to partially affect smoking abstinence by improving individuals’ confidence in their ability to quit smoking and developing knowledge on how to quit. Face-value single-item mediator measures, lack of blinding, and attrition limit the study. Future studies should address these limitations and assess additional mechanisms mediating intervention effects. Trial registration ISRCTN13455271.

Influences of upstream wastewater treatment on the process combination of granular activated carbon (GAC) and ultraviolet (UV) disinfection were studied and the implications of this for wastewater reuse were assessed. GAC is an efficient chemical barrier but contributes little to the removal of indicator bacteria, and generally increases total bacteria concentrations, necessitating disinfection with UV radiation, for example, to ensure the safe reuse of wastewater. The efficiency of UV disinfection is impacted by factors such as particle concentration and UV absorbance of the water and is thus affected by upstream treatment processes. A full-scale wastewater treatment plant with a membrane bioreactor (MBR) followed by GAC filtration was compared to a treatment plant with a conventional activated sludge process and sand filtration, followed by GAC filtration. The removal of indicator bacteria was higher by the GAC filter that was preceded by an MBR. A UV fluence of 400 J/m2 was sufficient to reach irrigation water quality for both process combinations and to meet the criteria for microbial drinking water quality in the MBR + GAC effluent. One sample was selected for chemical analysis, comprising approximately 100 parameters, demonstrating that the MBR + GAC + UV (400 J/m2) effluent met all drinking water criteria except for nitrate levels. HIGHLIGHTS Reuse of wastewater from the full-scale GAC process with subsequent ultraviolet (UV) disinfection.; Removal of indicator bacteria and fungi by GAC filters.; Higher removal of microbial contaminants by a GAC filter downstream membrane bioreactor (MBR) versus CAS + sand filtration.; Chemical and microbial drinking water criteria were met for effluent from MBR + GAC + UV.; UV fluence of 400 J/m2 on MBR + GAC effluent sufficient to meet drinking water criteria.;

Abstract Background Pediatric delirium causes prolonged hospital stays, increased costs, and distress for children and caregivers. Currently, there is no delirium screening tool available in Sweden that has been translated, culturally validated, and tested for reliability. This study aimed to translate, culturally adapt, and assess the suitability of the Cornell Assessment of Pediatric Delirium (CAPD) for implementation in Swedish healthcare settings. Methods The CAPD was translated and culturally adapted to Swedish context following the ten-step process recommended by the International Society for Pharmacoeconomics and Outcomes Task Force for Translation and Cultural Adaptation. The Swedish CAPD was tested in the pediatric intensive care unit of Uppsala University Hospital, a tertiary hospital in Sweden. Inter-rater reliability was tested using intraclass correlation coefficient (ICC), with both Registered Nurses (RNs) and Assistant Nurses (ANs) conducting parallel measurements using the Swedish CAPD. A reliability score of ICC > 0.75 was considered indicative of good reliability. Results After translation of the CAPD into Swedish, 10 RNs participated in the cultural adaptation process. Issues related to word choice, education, and instructions were addressed. Wording improvements were made to ensure accurate interpretation. Supplementary training sessions were organized to strengthen users’ proficiency with the Swedish CAPD. Additional instructions were provided to enhance clarity and usability. Inter-rater reliability testing resulted in an ICC of 0.857 (95% CI: 0.708–0.930), indicating good reliability. Conclusion This study successfully translated and culturally adapted the CAPD to align with Swedish contextual parameters. The resulting Swedish CAPD demonstrated good inter-rater reliability, establishing its viability as a tool for measuring delirium among pediatric patients in Swedish pediatric intensive care units. Trail registration Not applicable.

PurposeA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.MethodsWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.ResultsThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.ConclusionAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants may have different characteristics, e.g., in transmission, mortality, and the effectiveness of vaccines, indicating the importance of variant detection at the population level. Wastewater-based surveillance of SARS-CoV-2 RNA fragments has been shown to be an effective way to monitor the COVID-19 pandemic at the population level. Wastewater is a complex sample matrix affected by environmental factors and PCR inhibitors, causing insufficient coverage in sequencing, for example. Subsequently, results where part of the genome does not have sufficient coverage are not uncommon. To identify variants and their proportions in wastewater over time, we utilized next-generation sequencing with the ARTIC Network's primer set and bioinformatics pipeline to evaluate the presence of variants in partial genome data. Based on the wastewater data from November 2021 to February 2022, the Delta variant was dominant until mid-December in Helsinki, Finland’s capital, and thereafter in late December 2022 Omicron became the most common variant. At the same time, the Omicron variant of SARS-CoV-2 outcompeted the previous Delta variant in Finland in new COVID-19 cases. The SARS-CoV-2 variant findings from wastewater are in agreement with the variant information obtained from the patient samples when visually comparing trends in the sewerage network area. This indicates that the sequencing of wastewater is an effective way to monitor temporal and spatial trends of SARS-CoV-2 variants at the population level.

Abstract Ultra-low-dose computed tomography (ULD-CT) may combine the high sensitivity of conventional computed tomography (CT) in detecting sarcoma pulmonary metastasis, with a radiation dose in the same magnitude as chest X-ray (CXR). Fifty patients with non-metastatic high-grade soft tissue sarcoma treated with curative intention were recruited. Their follow-up involved both CXR and ULD-CT to evaluate their different sensitivity. Suspected findings were confirmed by conventional CT if necessary. Patients with isolated pulmonary metastases were treated with surgery or stereotactic body radiation therapy (SBRT) with curative intent if possible. The median effective dose from a single ULD-CT study was 0.27 mSv (range 0.12 to 0.89 mSv). Nine patients were diagnosed with asymptomatic lung metastases during the follow-up. Only three of them were visible in CXR and all nine in ULD-CT. CXR had therefore only a 33% sensitivity compared to ULD-CT. Four patients were operated, and one had SBRT to all pulmonary lesions. Eight of them, however, died of the disease. Two patients developed symptomatic metastatic recurrence involving extrapulmonary sites+/−the lungs between two imaging rounds. ULD-CT has higher sensitivity for the detection of sarcoma pulmonary metastasis than CXR, with a radiation dose considerably lower than conventional CT. Clinical trial registration: NCT05813808. 04-14-2023.

Abstract Background Population-based cancer quality registries are of great importance for the improvement of cancer care. However, little is known about the quality of recurrence data in cancer quality registries. The aim of this study was to evaluate data quality in the regional Breast Cancer Quality Registry of Central Sweden, with emphasis on the validity of recorded information on recurrence. Methods Validation by re-abstraction was performed on a random sample of 800 women with primary invasive breast cancer stage I-III diagnosed between 1993 and 2010, of which 400 had at least one registered recurrence and 400 had no registered recurrence. Registry data were compared with data from medical records. Exact agreement, correlation and kappa values, sensitivity and specificity were calculated. Results Seven hundred forty-seven women (93%) were available for analysis. Exact agreement was high for diagnostics, tumor characteristics, surgery, and adjuvant oncological treatment (90% or more for most variables). The registry’s sensitivity was low for regional recurrence (47%), but higher for local and distant recurrence (80% and 75%), whereas specificity was overall high (≥ 95%). Combining all recurrence categories irrespective of localization improved sensitivity to 90% with a specificity of 91%. In 87% of women, the date of first recurrence according to medical records fell within ± 90 days of the date recorded in the registry. Conclusions While the quality of data in the regional Breast Cancer Quality Registry was generally high, data accuracy on recurrences was lower. The overall precision of identifying any recurrence, irrespective of localization, was high. However, the accuracy of classification of recurrences (local, regional or distant) was lower, with evidence of underreporting for each of the recurrence categories. Given the importance of recurrence-related outcomes in the assessment of quality of care, efforts should be made to improve the reporting of recurrences.

BackgroundLow-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.MethodsWe evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.ResultsIn European ancestry samples, 14 genes were significantly associated (q

Background and purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions. Material and methods: The study participants were examined with [68Ga]PSMA-PET/mpMRI prior to radical prostatectomy. Four radiation oncologists delineated GTVs in 15 study participants, on four different image types; T2-weighted (T2w), diffusion weighted imaging (DWI), dynamic contrast enhanced (DCE) and PSMA-PET scans separately. The simultaneous truth and performance level estimation (STAPLE) algorithm was used to generate combined GTVs. GTVs were subsequently compared to histopathology. We analysed how Dice similarity coefficient (DSC) and lesion coverage are affected by using single versus multiple image types as well as by adding a clinical target volume (CTV) margin. Results: Median DSC (STAPLE) for different GTVs varied between 0.33 and 0.52. GTVPSMA-PET/mpMRI generated the highest median lesion coverage at 0.66. Combining different image types achieved similar lesion coverage as adding a CTV margin to contours from a single image type, while reducing non-malignant tissue inclusion within the target volume. Conclusion: The combined use of mpMRI or PSMA-PET/mpMRI shows promise, achieving higher DSC and lesion coverage while minimizing non-malignant tissue inclusion, in comparison to the use of a single image type with an added CTV margin.

Objective: This study aimed to assess perceptions and actions taken by Finnish dental professionals in suspected cases of child physical abuse (CPA) and to describe changes over 10 years. Material and methods: Data collected from two child abuse and neglect (CAN) surveys among Finnish dental professionals, working in public health care, covering suspicions of CPA and actions taken as well as training on CPA issues, were compared. The chi-squared (χ2) test was used to analyze associations. Results: In total, 625 (2008) and 1,025 (2019) questionnaires were completed. Respondents reported that they suspected CPA more frequently in 2008 than in 2019 (21.0% vs. 8.7%, p

Background: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology. Materials and methods: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold. Results: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm. Interpretation: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.

ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

BackgroundPredict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).MethodThe prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.ResultsHaving a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.ConclusionThe inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.

Abstract Background Physical inactivity and a sedentary lifestyle are common among people with heart failure (HF), which may lead to worse prognosis. On an already existing mHealth platform, we developed a novel tool called the Activity coach, aimed at increasing physical activity. The aim of this study was to evaluate the usability of the Activity coach and assess feasibility of outcome measures for a future efficacy trial. Methods A mixed-methods design was used to collect data. People with a HF diagnosis were recruited to use the Activity coach for four weeks. The Activity coach educates the user about physical activity, provides means of registering daily physical activity and helps the user to set goals for the next week. The usability was assessed by analysing system user logs for adherence, reported technical issues and by interviews about user experiences. Outcome measures assessed for feasibility were objective physical activity as measured by an accelerometer, and subjective goal attainment. Progression criteria for the usability assessment and for the proposed outcomes, were described prospectively. Results Ten people with HF were recruited, aged 56 to 78 with median age 72. Data from nine of the ten study participants were included in the analyses. Usability: The Activity coach was used 61% of the time and during the first week two study participants called to seek technical support. The Activity coach was found to be intuitive and easy to use by all study participants. An increased motivation to be more physically active was reported by six of the nine study participants. However, in spite of feeling motivated, four reported that their habits or behaviours had not been affected by the Activity coach. Feasibility: Data was successfully stored in the deployed hardware as intended and the accelerometers were used enough, for the data to be analysable. One finding was that the subjective outcome goal attainment, was challenging to collect. A proposed mitigator for this is to use pre-defined goals in future studies, as opposed to having the study participants be completely free to formulate the goals themselves. Conclusions It was confirmed that the Activity coach was easy to use. Furthermore, it might stimulate increased physical activity in a population of people with HF, who are physically inactive. The outcomes investigated seem feasible to include in a future efficacy trial. Trial registration ClinicalTrials.gov identifier: NCT05235763. Date of first registration: 11/02/2022.