Improving mental health in chronic care in general practice: study protocol for a cluster-randomised controlled trial of the Healthy Mind intervention.

BACKGROUND: Mental health issues are common among patients with chronic physical conditions, affecting approximately one in five patients. Poor mental health is associated with worse disease outcomes and increased mortality. Problem-solving therapy (PST) may be a suitable treatment for targeting poor mental health in these patients. This study protocol describes a randomised controlled trial of the Healthy Mind intervention, a general practice-based intervention offering PST to patients with type 2 diabetes and/or ischaemic heart disease and poor mental well-being. METHODS: A stepped-wedge cluster-randomised controlled trial with 1-year follow-up will be conducted in Danish general practice. At the annual chronic care consultation, patients with type 2 diabetes and/or chronic ischaemic heart disease will be screened for poor mental well-being. Patients in the control group will be offered usual care while patients in the intervention group will be offered treatment with PST provided by general practitioners (GPs) or general practice staff, such as nurses, who will undergo a 2-day PST course before transitioning from the control to the intervention group. The primary outcome is change in depressive symptoms after 6 and 12 months. Secondary outcomes include change in mental well-being, anxiety, and diabetes distress (patients with type 2 diabetes) after 6 and 12 months as well as change in total cholesterol levels, low-density lipoprotein (LDL) levels, and blood glucose levels (patients with diabetes) after 12 months. Process outcomes include measures of implementation and mechanisms of impact. We aim to include a total of 188 patients, corresponding to approximately 14 average-sized general practices. DISCUSSION: The Healthy Mind trial investigates the impact of PST treatment for patients with chronic disease and poor mental well-being in general practice. This will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic diseases in general practice. The results of this study will provide relevant insights to aid GPs, and general practice staff manage patients with poor mental well-being. TRIAL REGISTRATION: ClinicalTrials.gov NCT05611112. Registered on October 28, 2022.

Managing mental health in chronic care in general practice: a feasibility study of the Healthy Mind intervention.

BACKGROUND AND OBJECTIVE: Mental health issues are common among patients with chronic physical conditions. This study aims to evaluate the feasibility of the Healthy Mind intervention, a general practice-based programme that provides problem-solving therapy (PST) to patients with poor mental well-being and type 2 diabetes (T2D) and/or ischaemic heart disease (IHD). DESIGN AND SETTING: A one-arm feasibility study was conducted in three general practices in the Central Denmark Region. INTERVENTION: Eight healthcare providers from the included general practices underwent a two-day course to acquire PST skills. Screening for poor mental health was carried out at the annual chronic care consultation for T2D or IHD, and PST sessions were offered to patients on indication of poor mental health. Nine patients received PST. METHODS: Semi-structured interviews with eight healthcare providers and six patients were conducted. Data were analysed deductively focusing on appropriateness, acceptability and fidelity of the intervention. RESULTS: The intervention was considered appropriate for the patient group and the general practice setting. The providers acknowledged PST as a valuable tool for managing psychological issues in general practice, and the patients perceived PST as an effective and tangible treatment. Since practice nurses' schedules were generally better suited for longer consultations, they were often the preferred intervention providers. The intervention was largely delivered as intended. However, the GPs generally expected patients to prefer a more directive approach, which sometimes challenged their role as facilitator and guide. CONCLUSION: The Healthy Mind intervention was found to be feasible, and the results support proceeding to a full-scale evaluation trial.

Patients with type 2 diabetes and/or ischaemic heart disease often experience poor mental well-being, revealing a shortage of general practice-based interventions targeting this issue.This study evaluates the feasibility of a problem-solving therapy intervention in general practice for patients with poor mental health and type 2 diabetes and/or chronic ischemic heart disease.Both patients and healthcare providers regarded problem-solving therapy as an acceptable intervention for managing psychological issues in general practice.Healthcare providers preferred practice nurses as the providers of problem-solving therapy since their schedules were often more suitable for longer consultations.In problem-solving therapy, the provider is expected to take a facilitating and guiding role, but GPs sometimes struggled remaining in this role due to a preconceived anticipation that patients expected them to take a more directive approach.

Workload and GP burnout: a survey and register-based study in Danish general practice.

BACKGROUND: Burnout is common among GPs. Previous studies have indicated an association between high workload and burnout among doctors. AIM: To assess the risk of burnout among single-handed GPs in Denmark in relation to self-reported and register-based workload. DESIGN & SETTING: Questionnaire data from 312 Danish single-handed GPs and register data on their patients and provided services. METHOD: Burnout was measured using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). A composite burnout score of quartile points was calculated. The questionnaire provided information on working hours. Register data included number of services and patient list size. Association between composite burnout score and workload was estimated with binomial regression analyses adjusting for the GP's age and sex, and social deprivation score of their patient lists. RESULTS: Working >5 days a week in practice increased the risk of a high burnout score (adjusted risk ratio [RR] = 2.34, 95% confidence interval [CI] = 1.62 to 3.37). Spending >7.5 hours a day on patient-related tasks increased the risk of a high burnout score. The highest score was among GPs spending 8.5-9.5 hours a day on patient-related tasks (adjusted RR = 2.01, 95% CI = 0.90 to 4.51), although not statistically significant. There was no association between number of services and risk of burnout. CONCLUSION: Working 5 days a week in practice significantly increased the risk of burnout in Danish single-handed GPs. Spending >7.5 hours a day on patient-related tasks tended to increase the risk. We found no association between a high number of services and increased risk of burnout.

Psychiatric disorders and the cancer diagnostic process in general practice: a combined questionnaire and register study exploring the patients' experiences in Denmark.

OBJECTIVE: Patients with psychiatric disorders are at risk of experiencing suboptimal cancer diagnostics and treatment. This study investigates how this patient group perceives the cancer diagnostic process in general practice. DESIGN: Cross-sectional study using questionnaire and register data. SETTING: General practice in Denmark. SUBJECTS: Patients diagnosed with cancer in late 2016 completed a questionnaire about their experiences with their general practitioner (GP) in the cancer diagnostic process (n = 3411). Information on pre-existing psychiatric disorders was obtained from register data on psychiatric hospital contacts and primary care treated psychiatric disorders through psychotropic medications. Logistic regression was used to analyse the association between psychiatric disorders and the patients' experiences. MAIN OUTCOME MEASURES: Patients' experiences, including cancer worry, feeling being taken seriously, and the perceived time between booking an appointment and the first GP consultation.[Box: see text]. RESULTS: A total of 13% of patients had an indication of a psychiatric disorder. This group more often perceived the time interval as too short between the first booking of a consultation and the first GP consultation. Patients with primary care treated psychiatric disorders were more likely to worry about cancer at the first presentation and to share this concern with their GP compared with patients without psychiatric disorders. We observed no statistically significant association between patients with psychiatric disorders and perceiving the waiting time to referral from general practice, being taken seriously, trust in the GP's abilities, and the patients' knowledge of the process following the GP referral. CONCLUSION: The patients' experiences with the cancer diagnostic process in general practice did not vary largely between patients with and without psychiatric disorders. Worrying about cancer may be a particular concern for patients with primary care treated psychiatric disorders.

It is unknown how patients with psychiatric disorders perceive the cancer diagnostic process in general practice.This study found an association between having a psychiatric disorder and more often perceiving the time interval as too short between the first booking of a consultation and the first GP consultation.An association was found between having a primary care treated psychiatric disorder and being worried about cancer and more often sharing these concerns with the GP.Experiences with the cancer diagnostic process in general practice did not differ between patients with a hospital treated psychiatric disorder and patients with no indication of psychiatric disorders.

Healthcare use and fear of recurrence in adult cancer survivors at 2.5 years after a cancer diagnosis: a nationwide register study in Denmark.

PURPOSE: To investigate the association between fear of cancer recurrence (FCR) and healthcare use in general practice among cancer survivors. METHODS: We linked nationwide register data to survey data on FCR in cancer survivors at 2.5 years after a cancer diagnosis. Multiple regression models were used to analyse the association between high FCR level and quartiles of healthcare use at 18-30 months before the cancer diagnosis (habitual healthcare use) and between high FCR level and healthcare use at 18-30 months after the cancer diagnosis (survivorship healthcare use). RESULTS: We included 1538 cancer survivors in the study. High habitual healthcare use was associated with a high level of FCR (odds ratio = 2.07 (95% confidence interval (CI): 1.36-3.15)) for the 4th quartile of healthcare use compared to the 1st quartile. A high FCR score was also associated with higher healthcare use during cancer survivorship (incidence rate ratio (IRR) = 1.26 (95% CI: 1.14-1.40)). This association remained statistically significant when adjusting for habitual healthcare use (IRR = 1.20 (95% CI: 1.09-1.33)). CONCLUSION: High healthcare use before the cancer diagnosis was associated with high FCR during survivorship. This indicates that FCR is partly explained by a general (pre-diagnostic) health concern. High FCR predicted high healthcare use during cancer survivorship, even when adjusting for habitual healthcare use. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest that FCR in cancer survivors is triggered by a general high level of health concern, and the cancer diagnosis may further exacerbate this concern.

AMH and other markers of ovarian function in patients with Turner syndrome - a single center experience of transition from pediatric to gynecological follow up.

Turner syndrome (TS) is a chromosomal disorder that affects about 1 in 2500 female births and is characterized by the partial or complete absence of the second X chromosome. Depending on karyotype, TS is associated with primary ovarian insufficiency (POI). Approximately 50% of girls with a mosaic 45, X/46, XX karyotype may enter puberty spontaneously, but only 5-10% of women with TS achieve pregnancy without egg donation. In this review, we will evaluate the clinical use of markers of ovarian function in TS patients. Based on longitudinal studies of serum concentrations of reproductive hormones as well as ovarian morphology in healthy females and patients with TS, we will evaluate how they can be applied in a clinical setting. This is important when counseling patients and their families about future ovarian function essential for pubertal development and fertility. Furthermore, we will report on 20 years of experience of transition from pediatric to gynecological and adult endocrinological care in our center at Rigshospitalet, Copenhagen, Denmark.

Factors associated with undertriage and overtriage in telephone triage in Danish out-of-hours primary care: a natural quasi-experimental cross-sectional study of randomly selected and high-risk calls.

OBJECTIVES: We aim to explore undertriage and overtriage in a high-risk patient population and explore patient characteristics and call characteristics associated with undertriage and overtriage in both randomly selected and in high-risk telephone calls to out-of-hours primary care (OOH-PC). DESIGN: Natural quasi-experimental cross-sectional study. SETTING: Two Danish OOH-PC services using different telephone triage models: a general practitioner cooperative with GP-led triage and the medical helpline 1813 with computerised decision support system-guided nurse-led triage. PARTICIPANTS: We included audio-recorded telephone triage calls from 2016: 806 random calls and 405 high-risk calls (defined as patients ≥30 years calling with abdominal pain). MAIN OUTCOME MEASURES: Twenty-four experienced physicians used a validated assessment tool to assess the accuracy of triage. We calculated the relative risk (RR) for clinically relevant undertriage and overtriage for a range of patient characteristics and call characteristics. RESULTS: We included 806 randomly selected calls (44 clinically relevant undertriaged and 54 clinically relevant overtriaged) and 405 high-risk calls (32 undertriaged and 24 overtriaged). In high-risk calls, nurse-led triage was associated with significantly less undertriage (RR: 0.47, 95% CI 0.23 to 0.97) and more overtriage (RR: 3.93, 95% CI 1.50 to 10.33) compared with GP-led triage. In high-risk calls, the risk of undertriage was significantly higher for calls during nighttime (RR: 2.1, 95% CI 1.05 to 4.07). Undertriage tended to be more likely for calls concerning patients ≥60 years compared with 30-59 years (11.3% vs 6.3%) in high-risk calls. However, this result was not significant. CONCLUSION: Nurse-led triage was associated with less undertriage and more overtriage compared with GP-led triage in high-risk calls. This study may suggest that to minimise undertriage, the triage professionals should pay extra attention when a call occurs during nighttime or concerns elderly. However, this needs confirmation in future studies.

Effects of needle puncturing on re-vascularization and follicle survival in xenotransplanted human ovarian tissue.

BACKGROUND: Ovarian tissue transplantation can restore fertility in young cancer survivors, however the detrimental loss of follicles following transplantation of cryopreserved ovarian tissue is hampering the efficiency of the procedure. This study investigates whether needle puncturing prior to transplantation can enhance revascularization and improve follicle survival in xenotransplanted human ovarian cortex. METHODS: Cryopreserved human ovarian cortex pieces (N = 36) from 20 women aged 24-36 years were included. During the thawing process, each piece of tissue was cut in halves; one half serving as the untreated control and the other half was punctured approximately 150-200 times with a 29-gauge needle. The cortex pieces were transplanted subcutaneously to immunodeficient mice for 3, 6 and 10 days (N = 8 patients) and for 4 weeks (N = 12 patients). After 3, 6 and 10 days, revascularization of the ovarian xenografts were assessed using immunohistochemical detection of CD31 and gene expression of angiogenic factors (Vegfα, Angptl4, Ang1, and Ang2), and apoptotic factors (BCL2 and BAX) were performed by qPCR. Follicle density and morphology were evaluated in ovarian xenografts after 4 weeks. RESULTS: A significant increase in the CD31 positive area in human ovarian xenografts was evident from day 3 to 10, but no significant differences were observed between the needle and control group. The gene expression of Vegfα was consistently higher in the needle group compared to control at all three time points, but not statistically significant. The expression of Ang1 and Ang2 increased significantly from day 3 to day 10 in the control group (p < 0.001, p = 0.0023), however, in the needle group this increase was not observed from day 6 to 10 (Ang2 p = 0.027). The BAX/BCL2 ratio was similar in the needle and control groups. After 4-weeks xenografting, follicle density (follicles/mm3, mean ± SEM) was higher in the needle group (5.18 ± 2.24) compared to control (2.36 ± 0.67) (p = 0.208), and a significant lower percentage of necrotic follicles was found in the needle group (19%) compared to control (36%) (p = 0.045). CONCLUSIONS: Needle puncturing of human ovarian cortex prior to transplantation had no effect on revascularization of ovarian grafts after 3, 6 and 10 days xenotransplantation. However, needle puncturing did affect angiogenic genes and improved follicle morphology.

AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence: A long-term longitudinal study of healthy girls.

Background: Anti-Müllerian hormone (AMH) is produced by granulosa cells in small growing ovarian follicles. In adult women, serum concentrations of AMH reflect the ovarian reserve of resting primordial follicles, and low AMH is associated with risk of early menopause. In contrast, patients with polycystic ovary syndrome (PCOS) have elevated AMH. The primary aim of this study was to evaluate the individual tracking of serum AMH concentrations, as well as whether AMH in early childhood reflects ovarian activity in adolescence. Methods: In this large longitudinal study of healthy girls were examined from infancy to adolescence (1997-2019) including physical examination, assessment of serum concentrations of reproductive hormones (in infancy, median age 0.3 yrs; mid-childhood, 7.2 yrs; puberty, 11.3 yrs; and adolescence, 15.9 yrs), transabdominal ultrasound (TAUS, puberty and adolescence) and magnetic resonance imaging (MRI, puberty) of the ovaries. Findings: Each girl maintained her relative AMH concentration (expressed as standard deviation (SD) scores) over time; mean variation of individual age adjusted AMH concentrations was 0.56 ± 0.31 SD.Serum concentrations of AMH in adolescence correlated with AMH in infancy and childhood; infancy: r = 0.347; mid-childhood: r = 0.637; puberty: r = 0.675, all p < 0.001.AMH correlated negatively with FSH concentrations in all age groups (infancy: r = -0.645, p < 0.001; mid-childhood: r = -0.222, p < 0.001; puberty: r = -0.354, p < 0.001; adolescence: n = 275, r = -0.175, p = 0.004).Serum AMH concentrations in mid-childhood correlated with the number of follicles in puberty (TAUS and MRI) as well as in adolescence (TAUS); e.g. total number of follicles: TAUS puberty (r = 0.607), MRI puberty (r = 0.379), TAUS adolescence (r = 0.414), all p < 0.001.AMH concentration in infancy as well as in mid-childhood predicted low AMH (<10 pmol/L) in adolescence; AMH infancy <7.5 pmol/L as predictor of low AMH in adolescence: sensitivity 0.71, specificity 0.70, AUC 0.759; AMH mid-childhood < 8.4 pmol/L as predictor of low AMH in adolescence: sensitivity 0.88, specificity 0.87, AUC 0.949.Girls with high serum AMH concentration in mid-childhood (AMH >30.0 pmol/L vs. other girls) had higher adolescent LH (median 4.53 vs. 3.29 U/L p = 0.041), LH/FSH ratio (1.00 vs 0.67, p = 0.019), testosterone (1.05 vs 0.81 nmol/L, p = 0.005), total number of follicles (23 vs. 19, p = 0.004), and higher prevalence of irregular cycles (10/15 = 67% vs. 28/113 = 25%, p = 0.002). Interpretation: The present findings suggest remarkably stable ovarian activity from small growing follicles in healthy girls, supporting AMH in early life as a useful clinical tool to predict future ovarian activity. Funding: The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065), the EU (QLK4-CT1999-01422; QLK4-2001-00269), the Novo Nordisk Foundation and The Danish Ministry of Science Technology and Innovation (2107-05-0006). A.S.B. is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 464240267. KM receives honoraria from Novo Nordisk A/S for teaching at the Danish annual postgraduate course of pituitary diseases.

Reproductive and Endocrine Outcomes in a Cohort of Danish Women following Auto-Transplantation of Frozen/Thawed Ovarian Tissue from a Single Center.

Ovarian tissue cryopreservation (OTC) is a method of fertility preservation in girls and young women prior to gonadotoxic treatment. It is a safe and promising method to restore fertility. The initial recovery of endocrine function is high, but the longevity of the grafted tissue varies. In this single-center, combined retro- and prospective cohort study, we report the reproductive outcome and hormonal recovery following ovarian tissue transplantation (OTT) and evaluate possible predictors of the chance of pregnancy. The study includes 40 women from eastern Denmark undergoing 53 OTTs between 2003 and 2021. Permission to obtain retrospective data was given by the Danish Patient Safety Authorities and prospective data-collection by informed consent. Initial recovery of endocrine function was seen in 18/19 women with POI, and ongoing function of the grafted tissue in 7/14 two years from OTT. Live birth rate (LBR) was 41%, with 20 children to 39 women trying to conceive. Women who conceived had higher AFC at the time of OTC than women who did not (p ± 0.04). Repeated transplantations were not successful in terms of delivery. Half of all pregnancies were achieved by ART, but PRs were lower after ART than by spontaneous conception. LBRs after OTT are encouraging. Chance of pregnancy after OTT is correlated to ovarian reserve at OTC. Repeated transplantations were not successful in terms of unfulfilled pregnancy wish.

Unplanned cancer presentation in patients with psychiatric disorders: A nationwide register-based cohort study in Denmark.

Unplanned presentation in the cancer pathway is more common in patients with psychiatric disorders than in patients without. More knowledge about the risk factors for unplanned presentation could help target interventions to ensure earlier diagnosis of cancer in patients with psychiatric disorders. This study aims to estimate the association between patient characteristics (social characteristics and coexisting physical morbidity) and cancer diagnosis following unplanned presentation among cancer patients with psychiatric disorders. We conducted a population-based register study including patients diagnosed with cancer in 2014-2018 and also registered with at least one psychiatric disorder in the included Danish registers (n = 26,005). We used logistic regression to assess patient characteristics associated with an unplanned presentation. Almost one in four symptomatic patients (23.6 %) with pre-existing psychiatric disorders presented unplanned in the cancer trajectory. Unplanned presentation was most common for severe psychiatric disorders, e.g. organic disorders and schizophrenia. Old age, male sex, living alone, low education, physical comorbidity, and non-attendance in primary care were associated with increased odds of unplanned presentation. In conclusion, several characteristics of patients with pre-existing psychiatric disorders were associated with unplanned presentation in the cancer trajectory; for some groups more than 40 % had an unplanned presentation. This information could be used to design targeted interventions for patients with pre-existing psychiatric disorders to ensure earlier diagnosis of cancer in this population.

Fear of cancer recurrence at 2.5 years after a cancer diagnosis: a cross-sectional study in Denmark.

PURPOSE: The aim was to investigate the characteristics of cancer survivors with high levels of fear of cancer recurrence, and how such fear is associated with their needs for care. METHODS: This cross-sectional study was based on survey data from Danish cancer survivors at 2.5 years after a cancer diagnosis. These data were linked to nationwide register data. We used the 7-item Fear of Cancer Recurrence Inventory (FCR7) to measure fear of cancer recurrence, focussing on emotional, cognitive and behavioural reactions to such fear. The FCR7 score was dichotomised at the 75th percentile. A logistic regression model was used to analyse the associations between a high level of fear of cancer recurrence and (1) characteristics of patient and primary cancer and (2) cancer survivors' statements concerning follow-up for cancer. RESULTS: We included 1538 cancer survivors in the study. The median FCR7 score was 18 (interquartile interval: 13-21), and 366 (23.8%) respondents had an FCR7 score of > 21, defined as a high level of fear. In the adjusted analyses, a high level of fear was associated with female sex, younger age, comorbidity, advanced tumour stage and negative statements concerning follow-up, including feeling less safe in the follow-up programme. Fear was not related to the professional background of care providers involved in cancer follow-up. CONCLUSION: Fear of cancer recurrence was associated with female sex, younger age, comorbidity, advanced tumour stage and discontent with cancer follow-up.

Routes to cancer diagnosis for patients with pre-existing psychiatric disorders: a nationwide register-based cohort study.

BACKGROUND: Poor cancer prognosis has been observed in patients with pre-existing psychiatric disorders. Therefore, we need better knowledge about the diagnosis of cancer in this patient group. The aim of the study was to describe the routes to cancer diagnosis in patients with pre-existing psychiatric disorders and to analyse how cancer type modified the routes. METHODS: A register-based cohort study was conducted by including patients diagnosed with incident cancer in 2014-2018 (n = 155,851). Information on pre-existing psychiatric disorders was obtained from register data on hospital contacts and prescription medication. Multinomial regression models with marginal means expressed as probabilities were used to assess the association between pre-existing psychiatric disorders and routes to diagnosis. RESULTS: Compared to patients with no psychiatric disorders, the population with a psychiatric disorder had an 8.0% lower probability of being diagnosed through cancer patient pathways initiated in primary care and a 7.6% higher probability of being diagnosed through unplanned admissions. Patients with pre-existing psychiatric disorders diagnosed with rectal, colon, pancreatic, liver or lung cancer and patients with schizophrenia and organic disorders were less often diagnosed through cancer patient pathways initiated in primary care. CONCLUSION: Patients with pre-existing psychiatric disorders were less likely to be diagnosed through Cancer Patient Pathways from primary care. To some extent, this was more pronounced among patients with cancer types that often present with vague or unspecific symptoms and among patients with severe psychiatric disorders. Targeting the routes by which patients with psychiatric disorders are diagnosed, may be one way to improve the prognosis among this group of patients.

A systematic approach for evaluating the role of surface-exposed loops in trypsin-like serine proteases applied to the 170 loop in coagulation factor VIIa.

Proteases play a major role in many vital physiological processes. Trypsin-like serine proteases (TLPs), in particular, are paramount in proteolytic cascade systems such as blood coagulation and complement activation. The structural topology of TLPs is highly conserved, with the trypsin fold comprising two ß-barrels connected by a number of variable surface-exposed loops that provide a surprising capacity for functional diversity and substrate specificity. To expand our understanding of the roles these loops play in substrate and co-factor interactions, we employ a systematic methodology akin to the natural truncations and insertions observed through evolution of TLPs. The approach explores a larger deletion space than classical random or directed mutagenesis. Using FVIIa as a model system, deletions of 1-7 amino acids through the surface exposed 170 loop, a vital allosteric regulator, was introduced. All variants were extensively evaluated by established functional assays and computational loop modelling with Rosetta. The approach revealed detailed structural and functional insights recapitulation and expanding on the main findings in relation to 170 loop functions elucidated over several decades using more cumbersome crystallization and single deletion/mutation methodologies. The larger deletion space was key in capturing the most active variant, which unexpectedly had a six-amino acid truncation. This variant would have remained undiscovered if only 2-3 deletions were considered, supporting the usefulness of the methodology in general protease engineering approaches. Our findings shed further light on the complex role that surface-exposed loops play in TLP function and supports the important role of loop length in the regulation and fine-tunning of enzymatic function throughout evolution.

Burnout, coping strategies and help-seeking in general practitioners: a two-wave survey study in Denmark.

OBJECTIVE: Work pressure remains an issue among general practitioners (GPs). Nevertheless, GPs rarely seek help for symptoms of burnout. The aim of this study was to examine whether burnout level was associated with coping strategies and help-seeking behaviour during time pressure. DESIGN: A two-wave nationwide survey (2016 and 2019) based on questionnaire data from 1059 GPs. SETTING: Primary care in Denmark. METHODS: Burnout was measured by the Maslach Burnout Inventory (MBI), whereas coping strategies and help-seeking behaviour were measured by questions developed for the study. A composite score of quartile points was calculated for the three subscales of the MBI subscales. A score ≥9 was categorised as high level of burnout, and the composite score of 2019 was used as outcome. Data were analysed with logistic regression adjusted for sex, age and composite burnout score in 2016. RESULTS: High scores in 2016 on four key factors were associated with increased risk of high composite burnout score in 2019. These factors were compromising work (ORadjusted=2.27, 95% CI=1.45 to 3.56), postponing decisions (ORadjusted=1.53, 95% CI=1.04 to 2.24), delaying tasks (ORadjusted=1.61, 95% CI=1.16 to 2.25) and reducing breaks (ORadjusted=1.46, 95% CI=1.01 to 2.11) during time pressure. A lower risk of high composite burnout score was seen in 2019 in GPs who had sought help compared with GPs who did not seek help despite a perceived need (ORadjusted=0.59, 95% CI=0.35 to 0.97). CONCLUSION: Certain coping strategies used in 2016 were associated with increased risk of high burnout score in 2019, whereas lower risk of high burnout was seen in the GPs seeking help. These findings are relevant to reduce burnout rates among GPs.

Patients' health literacy is associated with timely diagnosis of cancer-A cross-sectional study in Denmark.

OBJECTIVE: Timely diagnosis of cancer is important for prognosis. Patients' health literacy (HL) may impact differences of diagnostic delays. Thus, we aim to explore the association between HL and diagnostic intervals in cancer. METHODS: Questionnaire data were obtained from patients with cancer diagnosed in 2016 and their general practitioner (n = 3890). The primary care interval (PCI) and the diagnostic interval (DI) were calculated using dates from national registries and questionnaires. A long PCI and DI were defined as ≥75th percentile. HL was assessed using scales from the Health Literacy Questionnaire: engaging with healthcare providers (scale 6:Engagement, n = 3008), navigating in healthcare (scale 7:Navigation, n = 2827) and understanding health information (scale 9:Knowledge, n = 3002). Low HL was defined as a score ≤3. RESULTS: Low HL was reported by 12.2% (Engagement), 27.0% (Navigation) and 9.3% (Knowledge) of the patients and associated with a long PCI after adjustment of socio-economic factors: Engagement (prevalence rate ratio [PRR] 1.27 [95% CI 1.01-1.60]), Navigation (PRR 1.41 [95% CI 1.10-1.80]) and Knowledge (PRR 1.32 [95% CI 1.03-1.68]). No association was found between HL and DI. CONCLUSION: HL may interfere with the diagnostic processes in general practice. Efforts to manage low HL include GPs' awareness of patients' ability to explain and respond to bodily changes and use of corresponding safety-netting strategies.

[Reproductive surgery for female infertility].

Although assisted reproductive technology has reduced the need for surgery for women with infertility, there is evidence to support, that targeted reproductive surgery can improve fertility and pregnancy outcomes. In the last decades, increased access to minimal invasive surgery has brought a new era to reproductive surgery. An integration of reproductive surgery in the fertility treatment is therefore recommended. The patient should be offered detailed information regarding the pros and cons before the surgical treatment, as the evidence in the field is sparse, which is discussed in this review.

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass.

Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combined this with anthropometric measurements and estimated whole-body insulin sensitivity. We found that menopause was associated with changes in adipose tissue phenotype related to metabolic dysfunction. In SAT, postmenopausal women showed adipocyte hypertrophy, increased inflammation, hypoxia and fibrosis. The postmenopausal changes in SAT was associated with increased visceral fat accumulation. In VAT, menopause was associated with adipocyte hypertrophy, immune cell infiltration and fibrosis. The postmenopausal changes in VAT phenotype was associated with decreased insulin sensitivity. Based on these findings we suggest, that menopause is associated with changes in adipose tissue phenotype related to metabolic dysfunction in both SAT and VAT. Whereas increased SAT inflammation in the context of menopause is associated with VAT accumulation, VAT morphology is related to insulin resistance.

Alignment between the patient's cancer worry and the GP's cancer suspicion and the association with the interval between first symptom presentation and referral: a cross-sectional study in Denmark.

BACKGROUND: General practitioners (GPs) have a key role in the diagnosis of cancer. It is crucial to identify factors influencing the decision to refer for suspected cancer. The aim of this study was to investigate the alignment between the patient's cancer worry and the GP's suspicion of cancer in the first clinical encounter and the association with the time interval from the first symptom presentation until the first referral to specialist care, i.e. the primary care interval (PCI). METHOD: The study was performed as a cross-sectional study using survey data on patients diagnosed with incident cancer in 2010 or 2016 and their GPs in Denmark. We defined four alignment groups: 1) patient worry and GP suspicion, 2)  GP suspicion only, 3) patient worry only, and 4) none of the two. A long PCI was defined as an interval longer than the 75th percentile. RESULTS: Among the 3333 included patients, both patient worry and GP suspicion was seen in 39.5%, only GP suspicion was seen in 28.2%, only patient worry was seen in 13.6%, and neither patient worry nor GP suspicion was seen in 18.2%. The highest likelihood of long PCI was observed in group 4 (group 4 vs. group 1: PPR 3.99 (95% CI 3.34-4.75)), mostly pronounced for easy-to-diagnose cancer types. CONCLUSION: Misalignment between the patient's worry and the GP's suspicion was common at the first cancer-related encounter. Importance should be given to the patient interview, due to a potential delayed GP referral among patients diagnosed with "easy-to-diagnose" cancer types presenting with unspecific symptoms.

Use of cryopreserved ovarian tissue in the Danish fertility preservation cohort.

OBJECTIVE: To evaluate the use of cryopreserved ovarian tissue in the Danish fertility preservation cohort. DESIGN: Retrospective cohort study. SETTING: University hospitals and fertility clinics. PATIENT(S): Ovarian tissue cryopreservation (OTC) was performed for 1,186 Danish girls and women from 1999-2020, of whom 117 subsequently underwent ovarian tissue transplantation (OTT). Subgroup 1 included 759 patients with a follow-up period of >5 years. Out of these, OTT rates were further analyzed for those patients who were alive and aged >24 years in July 2020 (subgroup 2; n = 554). INTERVENTION(S): OTC and OTT. MAIN OUTCOME MEASURE(S): OTT, death, donation of tissue. RESULT(S): In subgroup 1, 14% of the patients had undergone OTT, 18% had died, 9% had donated their tissue for research, and 59% still had their tissue stored. In subgroup 2, 19% had undergone OTT and for most diagnoses the OTT rates ranged from 15% to 22% with benign hematologic diseases having the highest OTT rate (35%). On the basis of the entire cohort, stratified age analysis indicated that women aged ≥30 years at OTC were more likely to return for OTT than women aged 18-29 years at OTC; mean storage times were 3.7 and 3.6 years, respectively. Only 4% of the girls aged <18 years at OTC had undergone OTT. CONCLUSION(S): The OTT rates depended on the diagnosis, age at OTC, and follow-up time. Specific criteria are needed for reporting and comparing OTT rates. Six out of 10 patients still had their cryopreserved tissue stored and longer follow-up is needed, especially for younger girls.