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Abstract Background While prior research on the SPC (second primary cancer) risk among pharyngeal carcinoma (PC) patients has been conducted in other regions, the European perspective is underrepresented. Our register-based cohort study aims to assess the subsite-specific risk of SPC among individuals initially diagnosed with a pharyngeal index tumour. Methods Standardized incidence ratios (SIR) of SPC were calculated relative to the general population for all patients diagnosed with a primary oropharyngeal, nasopharyngeal, and hypopharyngeal carcinoma (OPC, NPC, and HPC) in Finland during 1953–2021. Results A total of 4701 PC patients – 3320 men (71%) and 1381 women (29%) – were identified. The average and median follow-up times were 5.7 and 2.8 years, respectively. A SPC was diagnosed in 561 patients (11.9%): in 12.3% of men (n = 410) and 10.9% of women (n = 151). For male PC patients, the overall SIR for an SPC at any primary site was 1.83 (95% CI: 1.65–2.01). For female patients, the corresponding SIR was 1.89 (95% CI: 1.60–2.22). OPC and HPC showed increased risks for SPCs of the mouth/pharynx (SIR 4.41 and 6.91, respectively) and respiratory organs (SIR 3.51 and 4.80). OPC patients also had an increased risk in digestive organs (SIR 1.83). Male NPC patients exhibited increased risks for oral/pharyngeal, brain, and haematolymphoid SPCs (SIRs 5.14, 6.60, and 3.05, respectively). Conclusion PC patients face an 80% higher SPC risk, which persists decades after treatment. Healthcare professionals must be aware of this, providing counselling and encouraging a healthy lifestyle, including smoking cessation, while monitoring symptoms.

Abstract Background Cervical cancer is detectable and preventable in premalignant stages. In 2013, a population-based cervical cancer screening (CCS) programme was set up in Flanders (Belgium) promoting screening by means of sending reminder letters. Yet, in 2021, only a CCS coverage of 63.6% has been reached, which is just a bare increase since the implementation of the programme (62.7% in 2013) (Jaarrapport 2022, Centrum voor Kankeropsporing (CvKO), 2022; Jaarrapport 2015, Centrum voor Kankeropsporing (CvKO), 2015). Objectives To explore the characteristics of under- and neverscreened women in Flanders and to gain a better understanding of the barriers that prevent these women from attending CCS as well as factors that may facilitate CCS uptake. Methods Twelve in-depth interviews and six focus group discussions were conducted with gynaecologists, general practitioners, community health workers and stakeholders providing support to women belonging to potentially underscreened population groups. Reported barriers and facilitators were subsequently classified using the Socio-Ecological Model (SEM). Finally, a causal loop diagram was constructed to visualise the dynamic interrelations among the barriers and facilitators. Results Stakeholders and healthcare professionals confirm the vulnerability for cervical cancer screening in women with a substance use disorder and women with a migration background. The participation in screening among female sex workers is contingent upon their specific work environment. The group of never- or underscreened women is very heterogeneous and includes many women who are either unaware of CCS or have other priorities. A lack of focus on prevention is the most commonly reported barrier at the healthcare system level. Increasing awareness about cervical cancer (screening) and creating more opportunities for healthcare workers to offer prevention services are the primary facilitators. Conclusion To improve screening participation in Flanders, different screening strategies tailored to a diversity of women are needed.

Abstract Background Frail people receiving home care services face an increased risk of developing crisis, which can result in adverse events, coercive measures, and acute institutionalisation. The prevalence of frailty is expected to increase due to the ageing population in most countries. However, our knowledge of the process leading to crises among frail community-dwelling patients remains limited. The aim of our study was to explore how users of home care services and their next of kin experienced crises and how these crises were approached by home care services. Methods A qualitative explorative design with 21 interviews was conducted. We explored crises within the last year that had led to an acute institutionalisation (hospital or nursing home) or to an unstable situation with high risk of institutionalisation. Systematic text condensation (STC) was used to analyse the data. Results Our findings are summarised into one overarching theme; an organisation working mainly reactively instead of proactively, which is supported by four subthemes: (1) insufficient communication—a determinant of crises, (2) the lack of a holistic approach, (3) a sense of being a burden, and (4) the complexity of crises. The reactive approach is demonstrated in the participant’s experience of insufficient communication and the lack of a holistic approach from the service, but also in the user’s sense of being a burden, which seems to be reinforced by the experienced busyness from the staff in the home care services. This reactive approach to crises seems to have contributed to difficulties in detecting the various stressors involved in the complex process leading to crisis. Conclusions Our findings suggest that home care services tend to be characterised by a reactive approach to rising instability and the development of crises for users. This can be interpreted as an emergent property of the organisation and the adaptation towards exceeding demands due to insufficient capacity in health care services. We recommend the use of multicomponent care programmes comprising interdisciplinary case conferences in home care services to implement a cultural change that can shift the service from a reactive, fragmented, and task-oriented approach to a more proactive approach.

Abstract Key message Data acquisition of remote sensing products is an essential component of modern forest inventories. The quality and properties of optical remote sensing data are further emphasised in tree species-specific inventories, where the discrimination of different tree species is based on differences in their spectral properties. Furthermore, phenology affects the spectral properties of both evergreen and deciduous trees through seasons. These confounding factors in both sensor configuration and timing of data acquisition can result in unexpectedly complicated situations if not taken into consideration. This paper examines how the timing of data acquisition and sensor properties influence the prediction of tree species proportions and volumes in a boreal forest area dominated by Norway spruce and Scots pine, with a smaller presence of deciduous trees. Context The effectiveness of remote sensing for vegetation mapping depends on the properties of the survey area, mapping objectives and sensor configuration. Aims The objective of this study was to investigate the plot-level relationship between seasonality and different optical band configurations and prediction performance of common boreal tree species. The study was conducted on a 40-ha study area with a systematically sampled circular field plots. Methods Tree species proportions (0–1) and volumes (m3 ha−1) were predicted with repeated remote sensing data collections in three stages of the growing season: prior (spring), during (summer) and end (autumn). Sensor band configurations included conventional RGB and multispectral (MS). The importance of different wavelengths (red, green, blue, near-infrared and red-edge) and predictive performance of the different band configurations were analysed using zero–one-inflated beta regression and Gaussian process regression. Results Prediction errors of broadleaves were most affected by band configuration, MS data resulting in lower prediction errors in all seasons. The MS data exhibited slightly lower prediction errors with summer data acquisition compared to other seasons, whereas this period was found to be less suitable for RGB data. Conclusion The MS data was found to be much less affected by seasonality than the RGB data. Spring was found to be the least optimal season to collect MS and RGB data for tree species-specific predictions.

Abstract Background Preventing pathogens from entering the broiler premises is the main biosecurity measure at farm level. In conventional broiler production, chickens are kept indoors during the entire production period. Pathogens can enter the broiler-producing unit from sources such as water, equipment, personnel, insects, and rodents. The possible routes must be controlled, and corrective measures applied when necessary. The objective of this study was to (1) develop a hygiene protocol and test the scheme on 30 farms, and (2) compare the results to their Campylobacter-colonised status. A Hygiene Performance Rating protocol at farm level (HPR-F) was developed to systematically review the production to identify risk areas to biosecurity. The HPR-F consists of 13 categories with related questions. For each question, a score was given from 1 to 3, where 1 meant “acceptable”, 2 was “potential for improvements”, and 3 was “not acceptable”. Scores for each question were multiplied with weight factors for hygienic impact and economic consequences describing whether the necessary improvement depends on a significant investment or is a cheap quick-fix and calculated into a percentage where 100% is perfect hygiene. The 30 farms in the study were selected from one county in Norway. The Campylobacter-results for each of the 30 farms in 2019–2021 were given according to rules in the Norwegian Action Plan against Campylobacter faecal sampling on-farm 3–6 days prior to slaughter. Results The overall results from the HPR-F showed that the general hygiene level was high in all farms. The mean total hygiene score was 82% and varied from 70 to 92%. The category Handling dead chicken had the highest hygiene score (93%), and Ventilation had the lowest score (55%). The HPR-F results were compared to the Campylobacter-status for the 30 farms: Campylobacter-negative flocks had slightly higher total scores than Campylobacter-positive flocks (P = 0.19). Among others, the category Outdoor area (vegetation close to the premises’ walls) was identified as the most stable factor in relation to be colonised with Campylobacter. Conclusions The HPR-F tested in this research trial provides a tool for veterinarians, advisors, and poultry farmers to improve biosecurity at farm level and enhance the preventive animal health initiatives.

Abstract Background Case conferences are described as a goal-oriented, systematic method that team members can use to exchange professional opinions and develop treatment actions for a particular care problem. However, not all case conferences have proven to be effective. The Norwegian Targeted Interdisciplinary Model for the Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) is an effective multicomponent model based on case conferences that informs approaches to behavioural and psychological symptoms in residents with dementia in nursing homes. Our aim was to explore how TIME case conferences structured based on cognitive behavioural therapy (CBT) contributed to person-centred actions and how the specific inductive structure of the TIME may have contributed to the effectiveness of the model. Methods We used video observation of six case conferences and analysed these videos by performing a thematic cross-case analysis of the transcripts from the videos and by iteratively watching the videos. According to Habermas’s theory of communicative action, we emphasized the case conference content, i.e., what was talked about in the case conferences, and the display of communication between the participants in the case conferences. Results Our findings showed that the theoretical principles behind the TIME, including both person-centred care and the inductive structure of CBT, reflected many aspects of Habermas’s theory of communicative actions. In particular, the TIME case conferences emphasized the lifeworld perspective for both residents and staff and contributed to what Habermas labelled communicative rationality as a means to develop shared understanding among staff and create person-centred action. Conclusions One causal assumption of how and why the TIME case conferences contributed to the effectiveness of the TIME in reducing BPSD in nursing homes is that the specific inductive structure of the case conferences with the column technique based on the ABC method together with PCC, emphasized the importance of the lifeworld for both the resident and the staff. Even though case conferences have been highlighted as useful, it is not indifferent how these case conferences are structured and conducted. Clinical trial registration The trial TIME was registered January 6, 2016, with clinicaltrials.gov (NCT02655003).

Abstract Background Mental health literacy (MHL) is crucial for early recognition of and coping with mental health problems, and for the use and acceptance of mental health services, leading to better health outcomes, especially in adolescence. The prevalence of mental health problems among adolescents is seen as a major public health concern and MHL is an important factor in facilitating positive mental health outcomes. However, the availability of valid measurement instruments for assessing the multifaceted nature of MHL is limited, hindering the ability to make meaningful comparisons across studies. The Knowledge and Attitudes to Mental Health Scales (KAMHS) is a promising comprehensive instrument for measuring adolescents’ mental health literacy but its psychometric properties have not been explored in any other contexts than the Welsh. The aim of this study was to translate the KAMHS into Dutch, adapt it in this context, and evaluate its psychometric properties. Methods We performed a cross-sectional study with Dutch adolescents between the ages 11–16. We translated the KAHMS and assessed its content validity using cognitive interviewing with n = 16 adolescents. Next, n = 406 adolescents were asked to fill in the translated KAMHS-NL and reference scales, on mental health (SDQ and WHO-5), resilience (BRS), and mental health help-seeking behaviors. We assessed construct validity based on a priori hypotheses regarding convergent and divergent correlations between subscales of KAMHS-NL and the reference scales. Finally, we assessed structural validity via confirmatory factor analysis and exploratory structural equation modeling. Results The KAMHS-NL showed good content validity and satisfactory construct validity. In total, 28 of the 48 hypotheses regarding convergent and divergent correlations between the KAMHS and reference scales were confirmed. Contrary to our expectations, weak, but significant associations were found between MHL and resilience. The KAMHS showed an acceptable to good internal consistency (McDonald’s omega ranging from 0.62 to 0.84). Finally, we could generally confirm the postulated structure of the KAMHS-NL in the Dutch sample with a 5-factor solution (RMSEA = 0.033; CFI = 0.96). Conclusions The Dutch version of the KAMHS is a valid measure for detecting differences in MHL levels in adolescents. The KAMHS is a promising instrument for assessing MHL in adolescents in a multifaceted manner in other countries which may facilitate rigorous global MHL research. The instrument therefore deserves further validation research in other settings and comparisons across various cultural contexts.

Abstract Background Poor oral and dental health due to oral dysbiosis during pregnancy increases the risk for negative pregnancy outcomes. Communicating the importance of oral health is therefore essential in reducing the risk of adverse pregnancy outcomes. Professional guidance could substantially support women’s positive perception of their own competence. Information on oral health should be provided by healthcare professionals such as midwives, obstetricians and dentists. The aim of this study was to assess the needs, wishes and preferences of pregnant women in Germany, regarding interprofessional collaboration and guidance on oral health during pregnancy. Methods Sources of information, preferences regarding information supply as well as the need for interprofessional collaboration of involved healthcare professions were investigated in six online focus groups with pregnant women. In addition, three expert interviews with a midwife, an obstetrician and a dentist were conducted. The focus groups and interviews were analysed using qualitative content analysis according to Kuckartz. Results 25 pregnant women participated in focus groups. Pregnant women in all trimesters, aged 23 to 38 years, were included. Many women did not receive any or received insufficient information on oral health during pregnancy and wished for more consistent and written information from all involved healthcare providers. The extent of oral health counselling women received, heavily relied on their personal initiative and many would have appreciated learning about the scientific connection between oral health and pregnancy outcomes. An overall uncertainty about the timing and safety of a dental visit during pregnancy was identified. Interviews with experts provided additional insights into the working conditions of the involved healthcare professionals in counselling and emphasised the need for improved training on oral health during pregnancy in their respective professional education as well as thematic billing options in relation to this topic. Conclusion Guidance of women on oral health during pregnancy appears to be insufficient. Providing information adapted to the needs, wishes and preferences of women during pregnancy as well as the implementation of this topic in the education of involved healthcare professionals could contribute to an improved prenatal care for pregnant women and subsequently a reduced risk of negative pregnancy outcomes.

Abstract Background Self-harm and suicidal ideation are prevalent among adolescents, cause physical and psychosocial disability, and have potentially life-threatening consequences. Dialectical behavioral therapy for Adolescents (DBT-A) is an evidence-based intervention for reducing self-harm. However, few studies have investigated the effectiveness of DBT-A when delivered in routine clinical practice. Methods A follow-up cohort study, based on data from a quality assessment register of DBT-A in child and adolescent mental health services including seven outpatient clinics. Inclusion criteria were ongoing or a history of self-harming behavior the last 6 months; current suicidal behavior; at least 3 criteria of DSM-IV Borderline personality disorder (BPD), or at least the self-destruction criterion of DSM-IV BPD, in addition to minimum 2 subthreshold criteria; and fluency in Norwegian. Participants received 20 weeks of DBT-A consisting of multifamily skills training groups and individual therapy sessions. Outcomes from 41 participants included frequency of self-harm, suicide attempts and hospitalizations caused by self-harm or suicide attempts, assessed pre-, during, and post-treatment by self-report and reviews of the patient’s medical records. Suicidal ideation, urge to self-harm and perceived feelings of happiness and sadness were assessed by the patients’ diary cards at week 1, 5, 10, 15 and 20 of the treatment program. Results Participants attended an average of 17.9 (SD = 4.7) individual sessions, 14.7 (SD = 3.4) group-based skills training sessions and 4.6 (SD = 4.1) brief intersession telephone consultations. Moderate to large within-group effect sizes (ES) were found in self-harm from pre-treatment to 1–5 weeks (d = 0.64), 6–10 weeks (d = 0.84), 11–15 weeks (d = 0.99), 16–20 weeks (d = 1.26) and post-treatment (d = 1.68). Nine participants were admitted to hospitalization during DBT-A, whereas five had attempted suicide, but no suicides were completed. No statistically significant changes were found in suicidal ideation, urge to self-harm or perceived feelings of happiness or sadness from pre to post treatment. Conclusion The findings of the current study are promising as the participants reported considerably reduced self-harm behavior after DBT-A treatment in a child and adolescent mental health outpatient setting.

Abstract Objective The concept of lines of therapy (LOT) in cancer treatment is often considered for decision making in tumor boards and clinical management, but lacks a common definition across medical specialties. The complexity and heterogeneity of malignancies and treatment modalities contribute to an inconsistent understanding of LOT among physicians. This study assesses the heterogeneity of understandings of the LOT concept, its major dimensions, and criteria from the perspective of physicians of different specialties with an oncological focus in Germany. Semi-structured expert interviews with nine physicians were conducted and evaluated using qualitative content analysis. Results Most interviewees agreed that there is no single definition for LOT and found it difficult to explicate their understanding. A majority of experts stated that they had already encountered misunderstandings with colleagues regarding LOT and that they had problems with deciphering LOT from the medical records of their patients. Disagreement emerged about the roles of the following within the LOT concept: maintenance therapy, treatment intention, different therapy modalities, changing pharmaceutical agents, and therapy breaks. Respondents predominantly considered the same criteria as decisive for the definition of LOT as for a change in LOT (e.g., the occurrence of a progression event or tumor recurrence).

Abstract Background Alcohol-related liver disease is a preventable disease with high mortality. If individuals with alcohol-related liver disease were to be diagnosed earlier by screening and they reduced their alcohol consumption, lives lost to alcohol-related liver disease might be saved. A liver stiffness measurement (FibroScan©) is a key tool to screen for alcohol-related liver disease in asymptomatic individuals. No randomized controlled trials have been conducted to test if screening for liver disease reduces alcohol consumption in individuals with alcohol use disorders, in addition to what can be obtained by motivational interventions. We aimed to assess the feasibility of a randomized controlled trial of a screening for liver disease on the prevalence of alcohol abstinence or light consumption after 6 months in individuals attending outpatient treatment for alcohol use disorder. Methods We used an interdisciplinary approach to develop the format of the randomized controlled trial. Individuals were recruited from one outpatient treatment facility for alcohol use disorders. Study participants were randomized 1:1 to receive a) a liver stiffness measurement in addition to usual care (intervention) or b) usual care (control). Follow-up on alcohol consumption was assessed by telephone interview after 6 months and corroborated by data from records from public hospitals and the alcohol treatment facility. Feasibility was assessed by probabilities of recruitment, retention, and completion and estimated by the exact binominal test, with success defined as > 50% participation for each endpoint. The study design was evaluated at interdisciplinary meetings with staff and researchers from the outpatient alcohol treatment facility and the hospital clinic. Results Forty of 57 invited individuals agreed to participate in the study (recruitment = 70% (95% CI: 57–82)); 19 of 20 participants randomized to the intervention showed up for the screening (retention = 95% (95% CI: 75–100)). Follow-up telephone interviews succeeded for 33 of 39 reachable participants (completion = 85% (95% CI: 69–94)). Treatment records indicated that the 6 participants who were lost to follow-up for the telephone interview had not achieved alcohol abstinence or light consumption. There was no evidence that the intervention increased abstinence or light alcohol consumption at follow-up: 45% (95% CI: 23–68) in the intervention group and 65% (95% CI: 41–85) in the control group had a alcohol consumption below 10 standard drinks/week at 6 months. The main obstacle regarding study feasibility was to avoid disappointment in individuals randomized as controls. Conclusions This feasibility study developed a study design to test the influence of screening for liver disease on abstinence or light alcohol consumption in individuals attending treatment for alcohol use disorder. Trial registration ClinicalTrials.gov identifier: NCT05244720; registered on February 17, 2022.

Abstract Background Demographic changes, with an increasing number and proportion of older people with multimorbidity and frailty, will put more pressure on home care services in municipalities. Frail multimorbid people receiving home care services are at high risk of developing crises, defined as critical challenges and symptoms, which demand immediate and new actions. The crises often result in adverse events, coercive measures, and acute institutionalisation. There is a lack of evidence-based interventions to prevent and resolve crises in community settings. Methods This is a participatory action research design (PAR) in a 6-month cluster randomised controlled trial (RCT). The trial will be conducted in 30 municipalities, including 150 frail community-dwelling participants receiving home care services judged by the services to be at risk of developing crisis. Each municipality (cluster) will be randomised to receive either the locally adapted TIME intervention (the intervention group) or care as usual (the control group). The Targeted Interdisciplinary Model for Evaluation and Treatment of Neuropsychiatric Symptoms (TIME) is a manual-based, multicomponent programme that includes a rigorous assessment of the crisis, one or more interdisciplinary case conferences, and the testing and evaluation of customised treatment measures. PAR in combination with an RCT will enhance adaptations of the intervention to the local context and needs. The primary outcome is as follows: difference in change between the intervention and control groups in individual goal achievement to resolve or reduce the challenges of the crises between baseline and 3 months using the PRACTIC Goal Setting Interview (PGSI). Among the secondary outcomes are the difference in change in the PGSI scale at 6 months and in neuropsychiatric symptoms (NPSs), quality of life, distress perceived by professional carers and next of kin, and institutionalisation at 3 and 6 months. Discussion Through customised interventions that involve patients, the next of kin, the social context, and health care services, crises may be prevented and resolved. The PReventing and Approaching Crises for frail community-dwelling patients Through Innovative Care (PRACTIC) study will enhance innovation for health professionals, management, and users in the development of new knowledge and a new adapted approach towards crises. Trial registration ClinicalTrials.gov identifier: NCT05651659. Registered 15.12.22.

Abstract Background Sinonasal adenocarcinoma is a rare cancer, encompassing two different entities, the intestinal-type sinonasal adenocarcinoma (ITAC) and the non-intestinal-type sinonasal adenocarcinoma (non-ITAC). Occurrence of ITAC is strongly associated with exposure to hardwood dusts. In countries with predominant exposure to softwood dust the occurrence of sinonasal adenocarcinomas is lower and the relative amount of non-ITACs to ITACs is higher. The molecular mechanisms behind the tumorigenic effects of wood dust remain largely unknown. Methods We carried out whole-genome sequencing of formalin-fixed paraffin-embedded (FFPE) samples of sinonasal adenocarcinomas from ten wood dust-exposed and six non-exposed individuals, with partial tobacco exposure data. Sequences were analyzed for the presence of mutational signatures matching COSMIC database signatures. Driver mutations and CN variant regions were characterized. Results Mutation burden was higher in samples of wood dust-exposed patients (p = 0.016). Reactive oxygen species (ROS) damage-related mutational signatures were almost exclusively identified in ITAC subtype samples (p = 0.00055). Tobacco smoke mutational signatures were observed in samples of patients with tobacco exposure or missing information, but not in samples from non-exposed patients. A tetraploidy copy number (CN) signature was enriched in ITAC subtype (p = 0.042). CN variation included recurrent gains in COSMIC Cancer Gene Census genes TERT, SDHA, RAC1, ETV1, PCM1, and MYC. Pathogenic variants were observed most frequently in TP53, NF1, CHD2, BRAF, APC, and LRP1B. Driver mutations and copy number gains did not segregate by subtype. Conclusions Our analysis identified distinct mutational characteristics in ITAC and non-ITAC. Mutational signature analysis may eventually become useful for documentation of occupation-related cancer, while the exact mechanisms behind wood dust-driven carcinogenesis remain elusive. The presence of homologous recombination deficiency signatures implies a novel opportunity for treatment, but further studies are needed.

Abstract Objectives It has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated. Methods For two vaccines currently under development, one against Cloistridioides difficile (C. difficile) infection and one against respiratory syncytial disease (RSV), we estimated their incremental costs with and without productivity value included and compared the results. Results In this analysis, reflecting a UK context, a C. difficile vaccination programme would prevent £12.3 in productivity costs for every person vaccinated. An RSV vaccination programme would prevent £49 in productivity costs for every vaccinated person. Conclusions Considering productivity costs in future cost-effectiveness analyses of vaccines for C. difficile and RSV will contribute to better-informed reimbursement decisions from a societal perspective.

Abstract Background Nonspecific discharge diagnoses after acute hospital courses represent patients discharged without an established cause of their complaints. These patients should have a low risk of adverse outcomes as serious conditions should have been ruled out. We aimed to investigate the mortality and readmissions following nonspecific discharge diagnoses compared to disease-specific diagnoses and assessed different nonspecific subgroups. Methods Register-based cohort study including hospital courses beginning in emergency departments across 3 regions of Denmark during March 2019–February 2020. We identified nonspecific diagnoses from the R- and Z03-chapter in the ICD-10 classification and excluded injuries, among others—remaining diagnoses were considered disease-specific. Outcomes were 30-day mortality and readmission, the groups were compared by Cox regression hazard ratios (HR), unadjusted and adjusted for socioeconomics, comorbidity, administrative information and laboratory results. We stratified into short (3–

Abstract Background Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously. Case presentation A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient’s condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month. Conclusions Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.

Abstract Background Post-stroke cognitive impairment (PSCI) is common. However, the underlying pathophysiology remains largely unknown. Understanding the role of microvascular changes and finding markers that can predict PSCI, could be a first step towards better screening and management of PSCI. Capillary dysfunction is a pathological feature of cerebral small vessel disease and may play a role in the mechanisms underlying PSCI. Extracellular vesicles (EVs) are secreted from cells and may act as disease biomarkers. We aim to investigate the role of capillary dysfunction in PSCI and the associations between EV characteristics and cognitive function one year after acute ischemic stroke (AIS) and transient ischemic attack (TIA). Methods The ENIGMA study is a single-centre prospective clinical observational study conducted at Aarhus University Hospital, Denmark. Consecutive patients with AIS and TIA are included and followed for one year with follow-up visits at three and 12 months. An MRI is performed at 24 h and 12 months follow-up. EV characteristics will be characterised from blood samples drawn at 24 h and three months follow-up. Cognitive function is assessed three and 12 months after AIS and TIA using the Repeatable Battery for the Assessment of Neuropsychological Status. Discussion Using novel imaging and molecular biological techniques the ENIGMA study will provide new knowledge about the vascular contributions to cognitive decline and dementia. Trial registration The study is retrospectively registered as an ongoing observational study at ClinicalTrials.gov with the identifier NCT06257823.

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key player of lipid metabolism with higher plasma levels in women throughout their life. Statin treatment affects PCSK9 levels also showing evidence of sex-differential effects. It remains unclear whether these differences can be explained by genetics. Methods We performed genome-wide association meta-analyses (GWAS) of PCSK9 levels stratified for sex and statin treatment in six independent studies of Europeans (8936 women/11,080 men respectively 14,825 statin-free/5191 statin-treated individuals). Loci associated in one of the strata were tested for statin- and sex-interactions considering all independent signals per locus. Independent variants at the PCSK9 gene locus were then used in a stratified Mendelian Randomization analysis (cis-MR) of PCSK9 effects on low-density lipoprotein cholesterol (LDL-C) levels to detect differences of causal effects between the subgroups. Results We identified 11 loci associated with PCSK9 in at least one stratified subgroup (p

Abstract Background Job boredom has been generally associated with poorer self-rated health but the evidence is mainly cross-sectional and there is a lack of a holistic mental health approach. We examined the temporal relationships between job boredom and mental health indicators of life satisfaction, positive functioning, anxiety, and depression symptoms. Methods We analyzed a two-wave postal survey data of adults aged 23 to 34 that was collected from the Finnish working population between 2021 and 2022 (n = 513). Latent change score modelling was used to estimate the effects of prior levels of job boredom on subsequent changes in mental health indicators, and of prior levels of mental health indicators on subsequent changes in job boredom. Results Job boredom was associated with subsequent decreases in life satisfaction and positive functioning and increases in anxiety and depression symptoms. Of these associations, job boredom was more strongly associated with changes in positive functioning and anxiety symptoms than with changes in life satisfaction. Conclusions Our two-wave study suggests that job boredom, a motivational state of ill-being in the work domain, spills over into general mental health by decreasing life satisfaction and positive functioning and increasing anxiety and depression symptoms. Our findings contribute to the understanding of the potential detrimental effects of job boredom and its nomological network. From a practical perspective, workplaces are adviced to improve working conditions that mitigate job boredom and thus promote employees’ mental health.

Abstract Background The individual woman’s risk of being diagnosed with breast cancer can now be estimated more precisely, and screening can be stratified accordingly. The risk assessment requires that women are willing to provide a blood test, additional personal information, to know their risk, and alter screening intervals. This study aimed to investigate Danish women’s attitudes towards risk-stratified breast cancer screening. Methods An online, cross-sectional survey was conducted among Danish women aged 52–67 years. We used logistic regression analyses to assess how personal characteristics were associated with the women’s attitudes. Results 5,001 women completed the survey (response rate 44%) of which 74% approved of risk estimation to potentially alter their screening intervals. However, only 42% would accept an extended screening interval if found to have low breast cancer risk, while 89% would accept a reduced interval if at high risk. The main determinants of these attitudes were age, education, screening participation, history of breast cancer, perceived breast cancer risk and to some extent breast cancer worry. Conclusion This study indicates that women are positive towards risk-stratified breast cancer screening. However, reservations and knowledge among subgroups of women must be carefully considered and addressed before wider implementation of risk-stratified breast cancer screening in a national program.

Abstract Background Gestational weight gain (GWG) is a routinely monitored aspect of pregnancy health, yet critical gaps remain about optimal GWG in pregnant people from socially marginalized groups, or with pre-pregnancy body mass index (BMI) in the lower or upper extremes. The PROMISE study aims to determine overall and trimester-specific GWG associated with the lowest risk of adverse birth outcomes and detrimental infant and child growth in these underrepresented subgroups. This paper presents methods used to construct the PROMISE cohort using electronic health record data from a network of community-based healthcare organizations and characterize the cohort with respect to baseline characteristics, longitudinal data availability, and GWG. Methods We developed an algorithm to identify and date pregnancies based on outpatient clinical data for patients 15 years or older. The cohort included pregnancies delivered in 2005–2020 with gestational age between 20 weeks, 0 days and 42 weeks, 6 days; and with known height and adequate weight measures needed to examine GWG patterns. We linked offspring data from birth records and clinical records. We defined study variables with attention to timing relative to pregnancy and clinical data collection processes. Descriptive analyses characterize the sociodemographic, baseline, and longitudinal data characteristics of the cohort, overall and within BMI categories. Results The cohort includes 77,599 pregnancies: 53% had incomes below the federal poverty level, 82% had public insurance, and the largest race and ethnicity groups were Hispanic (56%), non-Hispanic White (23%) and non-Hispanic Black (12%). Pre-pregnancy BMI groups included 2% underweight, 34% normal weight, 31% overweight, and 19%, 8%, and 5% Class I, II, and III obesity. Longitudinal data enable the calculation of trimester-specific GWG; e.g., a median of 2, 4, and 6 valid weight measures were available in the first, second, and third trimesters, respectively. Weekly rate of GWG was 0.00, 0.46, and 0.51 kg per week in the first, second, and third trimesters; differences in GWG between BMI groups were greatest in the second trimester. Conclusions The PROMISE cohort enables characterization of GWG patterns and estimation of effects on child growth in underrepresented subgroups, ultimately improving the representativeness of GWG evidence and corresponding guidelines.

Abstract Background Physical activity is identified as a key modifiable factor towards good short- and long-term mental health and has shown positive effects on anxiety and depression in children and adolescents. However, physical activity-based interventions are not a part of standard mental health care and evidence on the effect of such interventions is still lacking. A transdiagnostic, physical activity-based intervention was developed as a supplement to routine clinical care for youth in specialized child and adolescent mental health services. Methods /design. The feasibility of the physical activity intervention (Confident, Active, and Happy Youth) was evaluated in an open-label study by assessing the recruitment process, acceptability, intervention suitability, contentment, and preliminary intervention effects in the form of youth and parent-rated anxiety and depressive symptoms. Physical activity levels were objectively measured using Actigraph™ physical activity sensors, and progression to a definitive study was evaluated in accordance with a priori criteria. Results In total 21 of 25 eligible youth consented to participate, two dropped out of the intervention and 19 completed (76% of eligible participants). The retention rate among consenting participants was 89% and mean attendance to sessions was 83%. The suitability of the intervention was rated as good by the youth and their parents, and intervention contentment was rated high. Changes in youth and parent-rated symptom measures following the intervention were negligible, except for parent-rated anxiety symptoms assessed at 10-month follow-up. Accelerometer data indicated lower levels of moderate to vigorous activity during sessions than intended. No adverse effects were noted. Conclusion This feasibility study met the pre-determined progression criteria to a definitive study. Thus, a larger trial with longer follow-up should be conducted to explore the effect of the intervention. Trial registration ClnicalTrials.gov, NCT05049759. Retrospectively registered, 20.09.2021.

Abstract Background In Norrtälje municipality, within Region Stockholm, there is a joint integrated care organisation providing health and social care, which may have facilitated a more coordinated response to the covid-19 pandemic compared to the otherwise decentralised Swedish system. This study compares the risk of covid-19 mortality among persons 70 years and older, in the municipalities of Stockholm, Södertälje, and Norrtälje, while considering area and individual risk factors. Methods A population-based study using linked register data to examine covid-19 mortality among those 70 + years (N = 127,575) within the municipalities of interest between the periods March-August 2020 and September 2020-February 2021. The effect of individual and area level variables on covid-19 mortality among inhabitants in 68 catchment areas were examined using multi-level logistic models. Results Individual factors associated with covid-19 mortality were sex, older age, primary education, country of birth and poorer health as indicated by the Charlson Co-morbidity Index. The area-level variables associated were high deprivation (OR: 1.56, CI: 1.18–2.08), population density (OR: 1.14, CI: 1.08–1.21), and usual care. Together, this explained 85.7% of the variation between catchment areas in period 1 and most variation was due to individual risk factors in period 2. Little of the residual variation was attributed to differences between catchment areas. Conclusion Integrated care in Norrtälje may have facilitated a more coordinated response during period 1, compared to municipalities with usual care. In the future, integrated care should be considered as an approach to better protect and meet the care needs of older people during emergency situations.

Abstract Background Cancer registries in Nigeria, as well as in other sub-Saharan African countries, face challenges in adhering to international cancer registration standards. We aimed to improve cancer incidence estimation by identifying under-reporting of new cancers through matching patient-reported local government areas (LGAs) in Edo state, Nigeria, to their respective catchment populations. Methods Information on cancers was obtained from records of hospitals, medical clinics, pathology laboratories, and death certificates according to IARC guidelines. We utilized normalized scores to establish consistency in the number of cancers by calendar time, and standardized incidence ratios (SIR) to assess the variation in cancer incidence across LGAs compared to Edo state average. Subsequently, we estimated sex- and site-specific annual incidence using the average number of cancers from 2016 to 2018 and the predicted mid-year population in three LGAs. Age-standardization was performed using the direct method with the World Standard Population of 1966. Results The number of incident cancers consistent between 2016–2018 in Egor, Oredo, and Uhunmwonde showed a significantly increased SIR. From 2016 to 2018 in these three LGAs, 1,045 new cancers were reported, with 453 (42.4%) in males and 592 (57.6%) in females. The average annual age-standardized incidence rate (ASR) was 50.6 (95% CI: 45.2 – 56.6) per 105. In men, the highest incidence was prostate cancer (ASR: 22.4 per 105), and in women, it was breast cancer (ASR: 16.5 per 105), and cervical cancer (ASR: 12.0 per 105). Microscopically verified cancers accounted for 98.1%. Conclusions We found lower age-standardized incidence rates than those reported earlier for the Edo state population. Collecting information on the local government areas of the cancers allows better matching with the respective target population. We recommend using LGA information to improve the evaluation of population-based cancer incidence in sub-Saharan countries.

Abstract Background A healthy nutrition in pregnancy supports maternal health and fetal development, decreasing the risk for adverse pregnancy outcomes. Guidance by prenatal care professionals can increase women’s awareness regarding the importance of nutrition in pregnancy and thereby contribute to a reduced risk for adverse pregnancy outcomes. The aim of this study was to assess the needs, wishes and preferences of pregnant women regarding the interprofessional guidance on nutrition in pregnancy. Methods Using a qualitative approach and a purposive maximum variation sampling strategy, 25 pregnant women were recruited to participate in six semi-structured, guideline-oriented online focus groups. In addition, two semi-structured, guideline-oriented interviews, with a midwife and an obstetrician, were conducted. The focus groups and interviews were audio-recorded and transcribed. Transcripts were analysed using a systematic deductive-inductive approach to qualitative content analysis according to Kuckartz. Results Focus group participants covered diverse perspectives in terms of their age, different models of prenatal care as well as dietary forms from omnivorous to vegan. The majority of women perceived the guidance on nutrition during pregnancy as insufficient. Involved healthcare professionals, namely midwives and obstetricians, should provide more consistent information, especially to avoid uncertainties exacerbated by the internet and social media. There is a need for individual nutrition information regarding dietary supplements and the specifics of different dietary forms during pregnancy, such as a vegan diet. The majority of participants supported the integration of a free-of-charge professional nutrition counselling in prenatal care. Interviews with experts identified time pressure and the complexity of nutrition as a topic as the main obstacles in consultation settings. Both midwife and obstetrician emphasised the need for improved professional education on nutrition in pregnancy in their respective studies. Conclusion Professional guidance for pregnant women on nutrition and uncertainties going along with certain forms of diet during pregnancy could alleviate the burden and overwhelming amount of web-based information. Additionally, information adapted to the needs, wishes and preferences of pregnant women would improve prenatal care through a more personalised approach. The quality of nutrition guidance in pregnancy should be improved by the implementation of this topic in the education of involved healthcare professionals.

Abstract Background Simulation games are effective for acquiring surgical nursing knowledge during education by offering possibilities to learn theoretical knowledge through practical patient scenarios, thus preparing students for demanding surgical nursing care. Game metrics stored in the game system enable assessment of students’ behaviour while gameplaying. Combining game metrics with the assessment of a student’s surgical nursing knowledge allows versatile information to be obtained about the student’s learning outcomes. However, studies on game metrics stored in systems and their relationship with learning outcomes are scarce. Methods The aim here was to evaluate the association between game metrics in a simulation game and nursing students’ surgical nursing knowledge. Nursing students from three universities of applied sciences in Finland participated in a one-week simulation gameplaying intervention that included five surgical nursing scenarios. Students’ surgical nursing knowledge was investigated with a quasi-experimental, one-group, pre- and post-test design using a surgical nursing knowledge test. In total, 280 students filled in the knowledge tests. In addition, cross-sectional game data were collected at a single time point between pre- and post-tests. The data were analysed with descriptive statistics and multivariate analysis methods. Results Students’ surgical nursing knowledge improved with the intervention. The total number of playthroughs was 3562. The mean maximum score was 126.2 (maximum score range 76–195). The mean playing time of all playthroughs by all players was 4.3 minutes (SD = 81.61). A statistically significant association was found between mean score and knowledge test total score (p

Abstract Background Bilberry (Vaccinium myrtillus L.) is one of the most important economic and natural resources in Northern Europe. Despite its importance, the endophytic fungal community of the fruits has rarely been investigated. Biogeographic patterns and determinants of the fungal diversity in the bilberry fruit are poorly understood, albeit fungal endophytes can have a close relationship with the host plants. Here, we investigated the effect of climatic regions, and their weather conditions within growth season and soil properties on fungal endophytic communities of bilberry fruits collected from northern and southern regions of Finland using high-throughput sequencing technology targeting the internal transcribed spacer 2 ribosomal DNA region for fungi. Results Species richness and beta diversity (variation in community structure) were higher in the southern compared to the studied northern region. The weather condition of the growth season drove both fungal richness and community structure. Furthermore, abundance of the genera Venturia, Cladosporium, and Podosphaera was influenced by the weather, being different between the south and north regions. Conclusions We conclude that diversity and assembly structure of the fungal endophytes in bilberry fruits follow similar patterns as for foliar fungal endophytes, being shaped by various environmental factors, such as the climate and surrounding vegetation.

Abstract Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Video Abstract

Abstract Background Urinary tract problems are a common complaint in small animal medicine and urolithiasis is considered to be an important cause of urinary tract disease in dogs. In this study the main aim was to investigate whether the occurrence of cystine urolithiasis increased during a five-year period. A second aim was to evaluate possible risk-factors as breed, age and gender. This study also evaluated how urine specific gravity, pH and level of cystine in urine responded to preventive strategies. Medical records of dogs with urolithiasis presented at nine Norwegian animal clinics and one animal hospital between 2015 and 2020 were retrospectively reviewed. Results The incidence of cystine uroliths increased significantly during the five study years (R2 = 0.72, P = 0.0199). Dogs with cystine uroliths were significantly younger (5.0 years (n = 84, 95% CI [4.4–5.6])) when they were diagnosed with cystine uroliths compared to dogs with other types of uroliths (8.1 years (n = 255, 95% CI[7.8-8.5]) P

Abstract Background In Turku, Finland, we introduced a home oxygen treatment and app-based monitoring program for hospitalized COVID-19 patients to facilitate an early discharge during the Omicron wave. In this case series we explore the clinical parameters of patients enrolled in the program and evaluate the cost–benefit and safety issues of the program. Methods Hospitalized COVID-19 patients with marked hypoxemia but otherwise in stable condition were screened from Turku City Hospital and Turku University Hospital by treating doctors for eligibility in the program. Peripheral oxygen saturation of > 92% and breathing frequency

Abstract Background In the spring of 2020, the Covid-19 outbreak sent a shock wave through the Swedish society and placed an extraordinary pressure on the health and social care system for older people. In the initial phase there were few guidelines for care providers to follow and staff in home care organisations often had to tackle challenges posed by the pandemic as they appeared. The aim of this study was to understand how the spread of Covid-19 was managed in organisations providing home care to older adults in different municipalities in Region Stockholm, and what actions were taken to minimise the spread of the disease among clients and staff. Method A descriptive qualitative study was performed based on eight interviews with managers of home care providers for older adults in three different municipalities in Region Stockholm.Three of the eight providers operate within an integrated care system. Data were analysed using conventional content analysis. Results Three themes were identified covering actions taken to handle the spread of the virus, feelings of insecurity and anxiety, and internal and external factors influencing how the pandemic was tackled. There was no single strategy followed by all municipalities or organisations, however, there were similarities between the organisations. One such example was the introduction of cohort care and the experience of lacking personal protective equipment. Providers in the integrated care system emphasized some advantages with their system that was seen as facilitators for minimising the risk of spreading the virus, like the joint meetings with managers from both health and social care and the close contact with healthcare professionals in relation to dissemination of hygiene instructions. Conclusion Social care workers providing home care to older persons are an important group in preventing dissemination of infectious diseases like Covid-19. For better readiness and preparedness for future pandemics, municipal home care services would need larger stocks of personal protective equipment, clear guidelines and more training on how to reduce dissemination of disease. Ways to achieve closer communication between health and social care providers should also be investigated.

Abstract Background Adolescent hazardous alcohol use is prevalent and has serious short- and long-term consequences. The trial ‘Our Choice’ examines efficacy, feasibility and acceptability of prevention interventions targeting school, parent, and student levels at Danish high schools. We hypothesize that students in a structural intervention (school and parent levels) reduce hazardous alcohol use and related health behaviors compared to students in an assessment only control group 12 months post baseline; and that adding group-based Motivational Interviewing (group MI) yields further improvements. The study examines the efficacy of interventions targeting multiple levels with the aim of providing novel insights into prevention of adolescent hazardous alcohol use and related health outcomes. Method The study employs a parallel group cluster randomized controlled trial design with three conditions: (1) structural condition targeting school and parent levels, (2) structural condition combined with group MI which also targets the student level, and (3) assessment-only control condition. A participatory approach is used to adapt and develop interventions. Sixteen high schools in Denmark and about N = 3100 first-year students (15–18 years) enrolled in high school in August 2023 will be recruited. Data will be collected via online questionnaires pre-interventions (baseline), 2, 6, 9 and 12 month post baseline and analyzed with generalized linear mixed models. The primary outcome is past month high intensity drinking; secondary outcomes are alcohol use, alcohol-related consequences, well-being, tobacco, and illegal substance use. Feasibility and acceptability will be assessed via surveys (students) and interviews (high school staff) to inform future implementation. Discussion ‘Our Choice’ is the first trial to compare the efficacy of a structural intervention targeting school- and parent levels to an intervention targeting these levels and the student level via group MI – on hazardous drinking and related health outcomes among students. Preventing and reducing hazardous alcohol use during adolescence is crucial due to the short- and long-term negative consequences. The tested interventions can be implemented at low cost. The study has significant implications for adolescent health and well-being and has potential to inform evidence-based decisions on alcohol prevention policy, education, and health professions. Trial Registration Number The trial was retrospectively registered at ClinicalTrials.gov on August 24th, 2023. Trial Registration Number: ID NCT06018389.

Abstract Background Persons with disability may have a higher HIV prevalence and be less likely than persons without disability to know their HIV-positive status, access antiretroviral therapy (ART), and suppress their HIV viral load (HIV care cascade). However, studies examining differences between persons with and without disability in HIV prevalence and the HIV care cascade are lacking. Using the Tanzania HIV Impact Survey (THIS) data collected between October 2016 and August 2017, we assessed differences in HIV prevalence and progress towards achieving the 2020 HIV care cascade target between persons with and without disability. Methods Using the Washington Group Short Set (WG-SS) Questions on Disability, we defined disability as having a functional difficulty in any of the six life domains (seeing, hearing, walking/climbing, remembering/ concentrating, self-care, and communicating). We classified respondents as disabled if they responded having either “Some Difficulty”, “A lot of difficulties” or “Unable to” in any of the WG-SS Questions. We presented the sample characteristics by disability status and analyzed the achievement of the cascade target by disability status, and sex. We used multivariable logistic regressions, and adjusted for age, sex, rural-urban residence, education, and wealth quintile. Results A total of 31,579 respondents aged 15 years and older had HIV test results. Of these 1,831 tested HIV-positive, corresponding to an estimated HIV prevalence of 4.9% (CI: 4.5 — 5.2%) among the adult population in Tanzania. The median age of respondents who tested HIV-positive was 32 years (with IQR of 21—45 years). HIV prevalence was higher (5.7%, 95% CI: 5.3—7.4%) among persons with disability than persons without disability (4.3%, 95% CI: 4.0 — 4.6%). Before adjustment, compared to women without disability, more women with disability were aware of their HIV-positive status (n = 101, 79.0%, 95% CI: 68.0—87.0% versus n = 703, 63.0%, 95% CI: 59.1—66.7%) and accessed ART more frequently (n = 98, 98.7%, 95% CI: 95.3—99.7% versus n = 661, 94.7%, 95% CI: 92.6—96.3%). After adjusting for socio-demographic characteristics, the odds of having HIV and of accessing ART did not differ between persons with and without disability. However, PLHIV with disability had higher odds of being aware of their HIV-positive status (aOR 1.69, 95% 1.05—2.71) than PLHIV without disability. Men living with HIV and with disability had lower odds (aOR = 0.23, 95% CI: 0.06—0.86) to suppress HIV viral loads than their counterparts without disability. Conclusion We found no significant differences in the odds of having HIV and of accessing ART between persons with and without disability in Tanzania. While PLHIV and disability, were often aware of their HIV-positive status than their non-disabled counterparts, men living with HIV and with disability may have been disadvantaged in having suppressed HIV viral loads. These differences are correctable with disability-inclusive HIV programming. HIV surveys around the world should include questions on disability to measure potential differences in HIV prevalence and in attaining the 2025 HIV care cascade target between persons with and without disability.

Abstract With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.

Abstract Background Long COVID is suggested to be present in 14 to 43% of COVID 19-survivors. Literature on this new condition states a need for a multidisciplinary approach including physical exercise and nutrition. The aim of the current pilot study is to investigate the feasibility of the proposed protocol to prepare for a randomized controlled study that addresses the effectiveness of a personalized multimodal treatment compared to standard physiotherapy. Methods This is a protocol of the UNLOCK (Nutrition and LOComotoric rehabilitation in long COVID) study, a pragmatic, single center, randomized controlled pilot trial with two groups. Patients with persisting symptoms related to a SARS-CoV-2 infection will receive either standard physiotherapy or a personalized multimodal treatment for a period of 12 weeks, consisting of individualized physical exercise program combined with individualized nutritional therapy. They will be followed-up at 6, 12, and 18 weeks after randomization. Discussion A multidisciplinary approach for dealing with long COVID is needed. Because of the lack of clear data and the fact that this is a very heterogenic group, we aim to prepare and optimize a randomized controlled study that addresses the effectiveness of a personalized multimodal treatment. Trial registration ClinicalTrials.gov Identifier: NCT05254301 (since February 24, 2022).

Abstract Extracellular vesicles (EVs) have considerable potential as diagnostic, prognostic, and therapeutic agents, in large part because molecular patterns on the EV surface betray the cell of origin and may also be used to “target” EVs to specific cells. Cancer is associated with alterations to cellular and EV glycosylation patterns, and the surface of EVs is enriched with glycan moieties. Glycoconjugates of EVs play versatile roles in cancer including modulating immune response, affecting tumor cell behavior and site of metastasis and as such, paving the way for the development of innovative diagnostic tools and novel therapies. Entities that recognize specific glycans, such as lectins, may thus be powerful tools to discover and detect novel cancer biomarkers. Indeed, the past decade has seen a constant increase in the number of published articles on lectin-based strategies for the detection of EV glycans. This review explores the roles of EV glycosylation in cancer and cancer-related applications. Furthermore, this review summarizes the potential of lectins and lectin-based methods for screening, targeting, separation, and possible identification of improved biomarkers from the surface of EVs.

Abstract Objective To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe. Methods This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case–control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching. Results A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure. Conclusions This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017).

Abstract Background Many Australians experience mental health challenges, but only a third access face-to-face psychological services, due to multiple barriers including long waitlists. Additional strategies to prevent or help people de-escalate distress at an early stage are needed. Web-based mental health interventions are becoming increasingly acceptable to consumers and referring General Practitioners (GPs), but most are designed for specific disorders/populations. This study explores consumers’ and health professionals’ preferences and recommendations for the design of a transdiagnostic, Acceptance and Commitment Therapy (ACT)-based, online intervention for Australian adults. Methods Thirty-five people (consumers, carers, GPs, mental health professionals) participated in one or more co-design stages. Stage 1: semi-structured interviews to establish what is wanted from such websites (n = 22). Stage 2: feedback emailed on branding options (n = 20). Stage 3: feedback provided via Zoom or an online survey after testing a website prototype (n = 19). Data were analysed using Thematic Framework Analysis and descriptive statistics. Results Stage 1 highlighted nine key design principles (plus 25 subthemes) that participants emphasised as important to ensure the website would have broad appeal and meet their needs: (1) user choice is valued highly; (2) ACT-based content is acceptable as it is focused on helping people be proactive and ‘get unstuck’; (3) non-pathologising, direct, empowering, lay language is endorsed; (4) a positive look and feel is appreciated; (5) images and videos are important to break up text and maintain engagement; (6) short text messages to aid engagement are valued; (7) provision of tailored psychoeducation for highly distressed and suicidal users is endorsed; (8) personal and proactive brand name is preferred (icanactnow); (9) diverse marketing and training activities are recommended. In Stage 2, icanactnow branding preferences were elicited (simplicity, colours to represent growth and a call to action). Stage 3 resulted in the inclusion of a safety plan template and a tailored entry portal for people referred to icanactnow by health professionals. High levels of satisfaction with the prototype were reported. Conclusions These findings informed icanactnow and provide insights for the development of other online mental health interventions, in ways that appeal to both consumers and professionals recommending them.

Abstract Background Increased levels of physical activity are associated with beneficial health effects for people with type 2 diabetes, cardiovascular disease and/or severe obesity; however, transforming knowledge about these effects into action is challenging. The aim of this paper is to explore lessons learnt from a co-creation process in a partnership project involving local stakeholders, including citizens, and researchers. The purpose of the process was to link a public health care institution with civil society organisations in the local community to make it possible for citizens to continue to be physically active after ending their public rehabilitation. Secondarily, this paper aims to develop a conceptual model of the above process. Methods The study constitutes the first part of Project Active Communities and was based on a partnership between three research institutions and a Danish rural municipality, involving municipal and civil society stakeholders and citizens with type 2 diabetes, cardiovascular disease and/or severe obesity in co-creation of concrete interventions for implementation. The co-creation process was divided into two tracks, one involving citizens (two workshops) and one involving municipal and civil society stakeholders (two workshops). The two tracks were concluded with a final workshop involving all stakeholders, including local politicians. Data sources are focus groups and bilateral meetings, workshop observations, and questionnaires. Results Lessons learnt include the importance of having a flexible timeframe for the co-creation process; giving room for disagreements and matching of mutual expectations between stakeholders; the value of a coordinator in the municipality to achieve acceptance of the project; and the significance of engaging local politicians in the co-creation process to accommodate internal political agendas. We have developed a conceptual model for a co-creation process, where we outline and explain three distinct phases: stakeholder identification and description, co-creation, and prototyping. The model can be adapted and applied to other sectors and settings. Conclusions This study documents lessons learnt in a co-creation process aiming to link a public health care institution with civil society organisations in the local community. Further, this study has specified productive co-creative processes and documented the various phases in a conceptual model.

Abstract Background Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and is one of the deadliest gastrointestinal malignancies. Despite numerous transcriptomics studies to understand its molecular basis, the impact of population-specific differences on this disease remains unexplored. Aims This study aimed to investigate the population-specific differences in gene expression patterns among ESCC samples obtained from six distinct global populations, identify differentially expressed genes (DEGs) and their associated pathways, and identify potential biomarkers for ESCC diagnosis and prognosis. In addition, this study deciphers population specific microbial and chemical risk factors in ESCC. Methods We compared the gene expression patterns of ESCC samples from six different global populations by analyzing microarray datasets. To identify DEGs, we conducted stringent quality control and employed linear modeling. We cross-compared the resulting DEG lists of each populations along with ESCC ATLAS to identify known and novel DEGs. We performed a survival analysis using The Cancer Genome Atlas Program (TCGA) data to identify potential biomarkers for ESCC diagnosis and prognosis among the novel DEGs. Finally, we performed comparative functional enrichment and toxicogenomic analysis. Results Here we report 19 genes with distinct expression patterns among populations, indicating population-specific variations in ESCC. Additionally, we discovered 166 novel DEGs, such as ENDOU, SLCO1B3, KCNS3, IFI35, among others. The survival analysis identified three novel genes (CHRM3, CREG2, H2AC6) critical for ESCC survival. Notably, our findings showed that ECM-related gene ontology terms and pathways were significantly enriched among the DEGs in ESCC. We also found population-specific variations in immune response and microbial infection-related pathways which included genes enriched for HPV, Ameobiosis, Leishmaniosis, and Human Cytomegaloviruses. Our toxicogenomic analysis identified tobacco smoking as the primary risk factor and cisplatin as the main drug chemical interacting with the maximum number of DEGs across populations. Conclusion This study provides new insights into population-specific differences in gene expression patterns and their associated pathways in ESCC. Our findings suggest that changes in extracellular matrix (ECM) organization may be crucial to the development and progression of this cancer, and that environmental and genetic factors play important roles in the disease. The novel DEGs identified may serve as potential biomarkers for diagnosis, prognosis and treatment.

Abstract Background National comprehensive smoke-free legislation has been found to decrease the incidence of several smoking-related diseases. In 2007, Denmark introduced a national smoking ban, which banned smoking indoor in workplaces and public places, although only partial restrictions were applied in certain settings. We examined the impact of the smoking ban on smoking-related diseases and whether this differed across socioeconomic groups. Methods Interrupted time series analyses of nationwide register data were performed using Poisson regression models to examine the differential impact of the smoking ban on monthly incidence rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers from 2002 to 2015. Immediate changes in incidence rates after the smoking ban and long-term changes in disease trends were estimated by comparing data from the pre- and post-ban period. Models were stratified by socioeconomic position. Results Overall, we found neither immediate changes in rates of acute myocardial infarction, chronic obstructive pulmonary disease, and smoking-related cancers following the smoking ban nor long-term post-ban changes in disease trends as compared to before the ban. Results did not differ across socioeconomic groups. A pronounced socioeconomic gradient in incidence rates was observed for all outcomes both before and after the smoking ban. Conclusion The national smoking ban was not associated with a lower incidence of smoking-related diseases in the post-ban period compared to pre-ban levels and no differences between socioeconomic groups were observed. Future tobacco control in Denmark should consider which measures most effectively target the low socioeconomic groups to decrease the current strong socioeconomic inequality in health.

Abstract Background Diversity is a reality in our societies, requiring health professionals to adapt to the unique needs of all patients, including migrants and ethnic minorities. In order to enable health professionals to meet related challenges and reduce health disparities, long and demanding training courses have been developed. But due to busy schedules of professionals and often scarce resources, a need for shorter training courses exists. This study aims to investigate which topics and methods should be prioritised in designing basic diversity training courses that provide health professionals the opportunity to foster this competence. Methods The study provided an expert panel of 31 academic and clinical migrant health experts with the content and methods of an existing diversity training course. The panel was asked to prioritise training topics and teaching methods in a two-stage process, using an adapted Delphi method. In the first stage, experts rated 96 predefined items, commented on those items, provided answers to eight open-ended questions and suggested additional content for a short course. In the second stage, they commented on the ratings from Round 1, and rated new suggested content. Consensus for training topics was set to 80% and for teaching methods 70%. Results The entire panel deemed ‘health effects of migration (pre-, during- and post-migration risk factors)’ to be important or very important to include in a short/online, basic diversity training (100% consensus). Other high-scoring items and therefore topics to be included in trainings were ‘social determinants of health’ (97%) and ‘discrimination within the healthcare sector’ (also 97%). A general trend was to focus on reflective practice since almost all items regarding reflection reached consensus. ‘Reflection on own stereotypes and prejudices’ (97%) was the highest-rated reflection item. ‘Opportunities and best practices in working with interpreters’ was the highest-scoring skills item, both on consensus (96%) and mean value (5.77). Conclusions Experts’ prioritizations of teaching content and methods for diversity training can help the design of short (online) trainings for health professionals and reduce unnecessary course content, thereby fostering professional development and enabling diversity competence trainings to be implemented also when time and/or financial resources are limited.

Abstract Background 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. Methods We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. Results OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG. Conclusions We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.

Abstract Background Denmark, Finland and Sweden pursue equity in health for their citizens through universal health care. However, it is unclear if these services reach the older adult population equally across different socioeconomic positions or living areas. Thus, we assessed geographic and socioeconomic equity in primary health care (PHC) performance among the older adults in the capital areas of Denmark (Copenhagen), Finland (Helsinki) and Sweden (Stockholm) in 2000–2015. Hospitalisations for ambulatory care sensitive conditions (ACSC) were applied as a proxy for PHC performance. Methods We acquired individual level ACSCs for those aged ≥ 45 in 2000–2015 from national hospitalisation registers. To identify whether the disparities varied by age, we applied three age groups (those aged 45–64, 65–75 and ≥ 75). Socioeconomic disparities in ACSCs were described with incidence rate ratios (IRR) and annual rates by education, income and living-alone; and then analysed with biennial concentration indices by income. Geographic disparities were described with biennial ACSC rates by small areas and analysed with two-level Poisson multilevel models. These models provided small area estimates of IRRs of ACSCs in 2000 and their slopes for development over time, between which Pearson correlations were calculated within each capital area. Finally, these models were adjusted for income to distinguish between geographic and socioeconomic disparities. Results Copenhagen had the highest IRR of ACSCs among those aged 45–64, and Helsinki among those aged ≥ 75. Over time IRRs decreased among those aged ≥ 45, but only in Helsinki among those aged ≥ 75. All concentration indices slightly favoured the affluent population but in Stockholm were mainly non-significant. Among those aged ≥ 75, Pearson correlations were low in Copenhagen (-0.14; p = 0.424) but high in both Helsinki (-0.74;

Abstract Background Rapidly progressive forms of Alzheimer’s disease (rpAD) are increasingly recognized and may have a prevalence of up to 30% of patients among all patients with Alzheimer’s disease (AD). However, insights about risk factors, underlying pathophysiological processes, and clinical characteristics of rpAD remain controversial. This study aimed to gain a comprehensive picture of rpAD and new insights into the clinical manifestation to enable a better interpretation of disease courses in clinical practice as well as in future clinical studies. Methods Patients (n = 228) from a prospective observational study on AD were selected and categorized into rpAD (n = 67) and non-rpAD (n = 161) disease groups. Patients were recruited through the German Creutzfeldt-Jakob disease surveillance center and the memory outpatient clinic of the Göttingen University Medical Center, representing diverse phenotypes of the AD population. Biomarkers and clinical presentation were assessed using standardized protocols. A drop of ≥ MMSE 6 points within 12 months defined rapid progressors. Results Lower CSF Amyloid beta 1–42 concentrations (p = 0.048), lower Amyloid beta 42/40 ratio (p = 0.038), and higher Tau/Amyloid-beta 1–42 ratio, as well as pTau/Amyloid-beta 1–42 ratio (each p = 0.004) were associated with rpAD. Analyzes in a subset of the cohort (rpAD: n = 12; non-rpAD: n = 31) showed higher CSF NfL levels in rpAD (p = 0.024). Clinically, rpAD showed earlier impairment of functional abilities (p

Abstract Background Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer’s disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). Methods Two academic memory clinic cohorts were used: the Amsterdam UMC (n = 3001) and the Erasmus MC (n = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n = 500 EHRs from the Amsterdam UMC cohort and in a test set of n = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). Results Internal validation performance of the classifiers was excellent (AUC range: 0.81–0.91), but external validation performance decreased (AUC range: 0.51–0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients

Abstract Background There are debates in acupuncture related systematic reviews and meta-analyses on whether searching Chinese databases to get more Chinese-language studies may increase the risk of bias and overestimate the effect size, and whether the treatment effects of acupuncture differ between Chinese and non-Chinese populations. Methods In this meta-epidemiological study, we searched the Cochrane library from its inception until December 2021, and identified systematic reviews and meta-analyses with acupuncture as one of the interventions. Paired reviewers independently screened the reviews and extracted the information. We repeated the meta-analysis of the selected outcomes to separately pool the results of Chinese- and non-Chinese-language acupuncture studies and presented the pooled estimates as odds ratios (OR) with 95% confidence interval (CI). We calculated the Ratio of ORs (ROR) by dividing the OR of the Chinese-language trials by the OR of the non-Chinese-language trials, and the ROR by dividing the OR of trials addressing Chinese population by the OR of trials addressing non-Chinese population. We explored whether the impact of a high risk of bias on the effect size differed between studies published in Chinese- and in non-Chinese-language, and whether the treatment effects of acupuncture differed between Chinese and non-Chinese population. Results We identified 84 Cochrane acupuncture reviews involving 33 Cochrane groups, of which 31 reviews (37%) searched Chinese databases. Searching versus not searching Chinese databases significantly increased the contribution of Chinese-language literature both to the total number of included trials (54% vs. 15%) and the sample size (40% vs. 15%). When compared with non-Chinese-language trials, Chinese-language trials were associated with a larger effect size (pooled ROR 0.51, 95% CI 0.29 to 0.91). We also observed a higher risk of bias in Chinese-language trials in blinding of participants and personnel (97% vs. 51%) and blinding of outcome assessment (93% vs. 47%). The higher risk of bias was associated with a larger effect estimate in both Chinese-language (allocation concealment: high/unclear risk vs. low risk, ROR 0.43, 95% CI 0.21 to 0.87) and non-Chinese-language studies (blinding of participants and personnel: high/unclear risk vs. low risk, ROR 0.41, 95% CI 0.23 to 0.74). However, we found no evidence that the higher risk of bias would increase the effect size of acupuncture in Chinese-language studies more often than in non-Chinese-language studies (the confidence intervals of all ROR in the high-risk group included 1, Table 3). We further found acupuncture appeared to be more effective in Chinese than in non-Chinese population (Table 4). Conclusions The findings of this study suggest the higher risk of bias may lead to an overestimation of the treatment effects of acupuncture but would not increase the treatment effects in Chinese-language studies more often than in other language studies. The difference in treatment effects of acupuncture was probably associated with differences in population characteristics. Trial registration We registered our protocol on the Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/PZ6XR ).

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12889-024-18629-0.

Abstract Background Colorectal cancer (CRC) patient pathways focus typically on periods after confirmed diagnosis and only limited data are available on pathways prior to cancer diagnosis. The aim of the study was to describe the use of health services (HS) one year before diagnosis among CRC patients in Finland. We also studied the role of sex, age, stage, and university hospital district in relation to the use of HS during the pre-diagnostic phase. This information is expected to bring light on the question why CRC is often not found in its early stages. Methods Incident CRC cases (N = 3115) concerning year 2015 were retrieved from the Finnish Cancer Registry and linked with data from the Finnish Institute for Health and Welfare on primary or specialised care outpatient visits or inpatient episodes over one year prior to CRC diagnosis. We modelled the average number of HS events per patient using Poisson regression model with log-link. Change points for monthly HS event rates and 95% CIs one year before diagnosis were evaluated using Poisson broken line regression models. Results Around 10% of patients diagnosed in 2015 had no events prior to cancer leaving 2816 CRCs in the study. Of all pre-diagnostic events (N = 23268), 86% were outpatient events and 14% inpatient episodes. More than half of the inpatient episodes (65%) started as urgent admissions. The use of HS started to increase 3–4 months before diagnosis. The average number of pre-diagnostic HS events per patient varied by sex, age, stage and university hospital district. Overall, men had more events per patient than women and older patients had more events than younger patients. Conclusions The amount of inpatient episodes starting as urgent admissions indicate potential bottlenecks in the access to health services. An increase in service use only 3–4 months prior to diagnosis reflects a need for advice both for health care professionals and the general population in recognising symptoms of CRC.