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.

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.

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.

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.

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.

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.

Patient's worry about cancer and the general practitioner's suspicion of cancer or serious illness: A population-based study in Denmark.

OBJECTIVE: A general practitioner's (GP's) suspicion of cancer is important to ensure early diagnosis of cancer. This study aimed to investigate the association between patients' cancer worry and GP's suspicion of cancer or serious illness. METHODS: This population-based study was based on Danish register and questionnaire data from 4,175 incident cancer patients diagnosed in 2010 or 2016 and their GPs. The association between the patient's worry about cancer and their GP's suspicion of cancer or serious illness was estimated by generalised linear models with log link for the Poisson family and presented in prevalence rate ratios (PRR). RESULTS: For 6 in 10 of the cases, the first consultation was categorised by absence of both or either patient worry or GP suspicion. When patients worried about cancer, the GPs were more likely to suspect cancer or serious illness in patients (PRR=1.26, (95%CI: 1.20-1.34)). For all levels of patient worry and most pronounced among very worried patients, GPs less often suspected cancer or serious illness in patients who presented with an ´intermediate´ or ´hard´ to diagnose cancer. CONCLUSION: GPs were more likely to suspect cancer or serious illness in patients who worried about cancer at the first presentation.

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.

Ovarian cortical follicle density in infertile women with low anti-Müllerian hormone.

PURPOSE: To evaluate the association between anti-Müllerian hormone (AMH) and follicle density in infertile women with diminished ovarian reserve (DOR) versus women with normal ovarian reserve? METHODS: Case-control study comparing follicle densities in ovarian cortex from 20 infertile women with DOR (AMH ≤ 5 pmol/L) and 100 controls with presumed normal ovarian reserve. RESULTS: For all women > 25 years, the follicle densities correlated positively with AMH levels. For each single picomole per liter increase in AMH the follicle density increased by 6% (95% CI 3.3-8.5%) when adjusted for age. This was similar for women with DOR and controls. The follicle density was 1.8 follicles/mm3 cortical tissue in women with DOR versus 7.0 in age-paired controls (p = 0.04). The women with DOR had a median AMH of 1.8 pmol/L versus 14.4 pmol/L in the age-paired control group (p < 0.001). The ratio of AMH/follicle density was 1:1 (1.8/1.8) in women with DOR and 2:1 (14.4/7.0) in the age-paired controls. Analyses for gonadotropin receptor polymorphisms could not explain the characteristics of women with DOR. The proportion of secondary follicles was higher in women with DOR compared with controls (4.6% versus 1.4%, p = 0.0003). Pooling all patients, the follicle density decreased significantly by 7.7% for every year added (p < 0.0001). The women with DOR had lower follicle densities than the controls, but the slopes were equal in the two cohorts. CONCLUSIONS: Follicle density and AMH concentrations correlate also when AMH is low. However, AMH is only a reliable marker for the true ovarian reserve when age is included in the estimation and women with DOR may have more follicles than their AMH levels imply.

Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve.

STUDY QUESTION: Can ovarian biopsying per se and/or autotransplantation of fragmented ovarian cortical tissue activate dormant follicles and increase the number of recruitable follicles for IVF/ICSI in women with diminished ovarian reserve (DOR)? SUMMARY ANSWER: Ovarian biopsying followed by immediate autotransplantation of fragmented cortical tissue failed to increase the number of recruitable follicles for IVF/ICSI 10 weeks after the procedure either at the graft site or in the biopsied ovary, but 12 of the 20 women subsequently had a clinical pregnancy during the 1-year follow-up. WHAT IS KNOWN ALREADY: Infertile women with DOR constitute a group of patients with poor reproductive outcome mainly due to the low number of mature oocytes available for IVF/ICSI. Recent studies have shown that in vitro activation of residual dormant follicles by both chemical treatment and tissue fragmentation has resulted in return of menstrual cycles and pregnancies in a fraction of amenorrhoeic women with premature ovarian insufficiency. STUDY DESIGN, SIZE, DURATION: This is a prospective clinical cohort study including 20 women with DOR treated at the fertility clinic, Rigshospitalet, Denmark, during April 2016-December 2017. Non-pregnant patients were on average followed for 280 days (range 118-408), while women who conceived were followed until delivery. Study follow-up of non-pregnant patients ended in September 2018. PARTICIPANTS, MATERIALS, SETTING, METHODS: The study included infertile women aged 30-39 years with preserved menstrual cycles, indication for IVF/ICSI and repeated serum measurements of anti-Müllerian hormone (AMH) ≤ 5 pmol/L. Patients were randomized to have four biopsies taken from either the left or the right ovary by laparoscopy followed by fragmentation of the cortical tissue to an approximate size of 1 mm3 and autotransplanted to a peritoneal pocket. The other ovary served as a control. Patients were followed weekly for 10 weeks with recording of hormone profile, antral follicle count (AFC), ovarian volume and assessment for ectopic follicle growth. After 10 weeks, an IVF/ICSI-cycle with maximal ovarian stimulation was initiated. MAIN RESULTS AND THE ROLE OF CHANCE: No difference in the number of mature follicles after ovarian stimulation 10 weeks after the procedure in the biopsied versus the control ovaries was observed (1.0 vs. 0.7 follicles, P = 0.35). In only three patients, growth of four follicles was detected at the graft site 24-268 days after the procedure. From one of these follicles, a metaphase II (MII) oocyte was retrieved and fertilized, but embryonic development failed. Overall AMH levels did not change significantly after the procedure (P = 0.2). The AFC increased by 0.14 (95% CI: 0.06;0.21) per week (P < 0.005), and the biopsied ovary had on average 0.6 (95% CI: 0.3;-0.88) follicles fewer than the control ovary (P = 0.01). Serum levels of androstenedione and testosterone increased significantly by 0.63 nmol/L (95% CI: 0.21;1.04) and 0.11 nmol/L (95% CI: 0.01;0.21) 1 week after the procedure, respectively, and testosterone increased consecutively over the 10 weeks by 0.0095 nmol/L (95% CI: 0.0002;0.0188) per week (P = 0.045). In 7 of the 20 patients, there was a serum AMH elevation 5 to 8 weeks after the procedure. In this group, mean AMH increased from 2.08 pmol/L (range 1.74-2.34) to 3.94 pmol/L (range 3.66-4.29) from Weeks 1-4 to Weeks 5-8. A clinical pregnancy was obtained in 12 of the 20 (60%) patients with and without medically assisted reproduction (MAR) treatments. We report a cumulated live birth rate per started IVF/ICSI cycle of 18.4%. LIMITATIONS, REASON FOR CAUTION: Limitations of the study were the number of patients included and the lack of a non-operated control group. Moreover, 9 of the 20 women had no male partner at inclusion and were treated with donor sperm, but each of these women had an average of 6.8 (range 4-9) unsuccessful MAR treatments with donor sperm prior to inclusion. WIDER IMPLICATIONS OF THE FINDINGS: Although 12 out of 20 patients became pregnant during the follow-up period, the current study does not indicate that biopsying, fragmenting and autotransplanting of ovarian cortical tissue increase the number of recruitable follicles for IVF/ICSI after 10 weeks. However, a proportion of the patients may have a follicular response in Weeks 5-8 after the procedure. It could therefore be relevant to perform a future study on the possible effects of biopsying per se that includes stimulation for IVF/ICSI earlier than week 10. STUDY FUNDING/COMPETING INTEREST(S): This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER: NCT02792569.

Cancer beliefs in cancer survivors, cancer relatives and persons with no cancer experience.

Aims: Negative cancer beliefs have been associated with late stage at cancer diagnosis. High levels of negative cancer beliefs have been found among individuals with low socioeconomic position and ethnic minority women, but the impact of cancer experience on cancer beliefs is unexamined. The aim of this study was to examine whether cancer beliefs are associated with cancer experience. Methods: This was a cross-sectional population-based study. Telephone interviews of 2992 Danish residents (30+) were carried out using the Awareness and Beliefs about Cancer Measure (ABC). Respondents reported whether they or someone close had been diagnosed with cancer and whether they agreed/disagreed with three positively and three negatively framed cancer beliefs. Results: Respondents with someone close diagnosed was reference group. Compared with these, respondents with no cancer experience (RRadj=0.91, 95% CI=0.84-0.98) or who had had cancer themselves (RRadj=0.87, 0.77-0.98) were less likely to believe that cancer treatment is worse than the cancer itself, and respondents with no cancer experience were less likely to believe that a diagnosis of cancer is a death sentence (RRadj=0.83, 0.70-0.98), but more likely to report that they did not want to know if they had cancer (RRadj=1.31, 1.01-1.71). Conclusions: The results suggest that cancer beliefs are sensitive to cancer experience. This is an important addition to previous results focusing on the association between cancer beliefs and static factors such as socioeconomic position and ethnicity. Since cancer beliefs may determine health-related behaviour, it is important that negative cancer beliefs are addressed and possibly reframed in population-based interventions.

Negative cancer beliefs, recognition of cancer symptoms and anticipated time to help-seeking: an international cancer benchmarking partnership (ICBP) study.

BACKGROUND: Understanding what influences people to seek help can inform interventions to promote earlier diagnosis of cancer, and ultimately better cancer survival. We aimed to examine relationships between negative cancer beliefs, recognition of cancer symptoms and how long people think they would take to go to the doctor with possible cancer symptoms (anticipated patient intervals). METHODS: Telephone interviews of 20,814 individuals (50+) in the United Kingdom, Australia, Canada, Denmark, Norway and Sweden were carried out using the Awareness and Beliefs about Cancer Measure (ABC). ABC included items on cancer beliefs, recognition of cancer symptoms and anticipated time to help-seeking for cough and rectal bleeding. The anticipated time to help-seeking was dichotomised as over one month for persistent cough and over one week for rectal bleeding. RESULTS: Not recognising persistent cough/hoarseness and unexplained bleeding as cancer symptoms increased the likelihood of a longer anticipated patient interval for persistent cough (OR = 1.66; 95%CI = 1.47-1.87) and rectal bleeding (OR = 1.90; 95%CI = 1.58-2.30), respectively. Endorsing four or more out of six negative beliefs about cancer increased the likelihood of longer anticipated patient intervals for persistent cough and rectal bleeding (OR = 2.18; 95%CI = 1.71-2.78 and OR = 1.97; 95%CI = 1.51-2.57). Many negative beliefs about cancer moderated the relationship between not recognising unexplained bleeding as a cancer symptom and longer anticipated patient interval for rectal bleeding (p = 0.005). CONCLUSIONS: Intervention studies should address both negative beliefs about cancer and knowledge of symptoms to optimise the effect.

Androgen Receptor Polymorphism and Female Sexual Function and Desire.

INTRODUCTION: The effect of testosterone depends on the exposure of and the sensitivity of the androgen receptor (AR). It has been shown that a cytosine-adenine-guanine (CAG) trinucleotide repeat polymorphism in the AR gene has an impact on AR functional capacity in men. However, large studies are lacking on the impact of this polymorphism on female sexual function. AIM: To determine whether the CAG repeat length was associated with different aspects of women's sexual function and dysfunction, including desire, arousal, lubrication, orgasm, satisfaction, sexual pain, and sexually related personal distress. METHODS: This cross-sectional study included 529 healthy women, aged 19-65 years. Participants completed a questionnaire to provide demographic and sexual data. The CAG repeat length was analyzed in a blood sample. The correlations between CAG repeat lengths and different aspects of sexual function were calculated. Independent Student t-tests were performed to evaluate differences in the mean number of CAG repeats in the short and long allele and of the biallelic mean length determined by simple calculation and X-inactivation analysis, respectively, between women with sexual problems and women without sexual problems. P values <.05 were considered statistically significant. MAIN OUTCOME MEASURE: We used the Female Sexual Function Index, with 6 subdomains, to distinguish between women without and women with impaired sexual function; low sexual desire; impaired arousal, lubrication, or orgasm; diminished satisfaction; or pain during sex. The Female Sexual Distress Scale was used to measure sexually related personal distress. RESULTS: Overall, we found that increasing numbers of CAG repeats were correlated to increased sexual function. We found that women with problems achieving orgasm had a significantly lower number of CAG repeats than women that reported no problems reaching orgasm. We found no associations between CAG repeat lengths and other aspects of female sexual dysfunction, including hypoactive sexual desire disorder. CLINICAL IMPLICATIONS: The results could indicate an impact of the AR on women's sexual function, including the ability to reach orgasm. STRENGTH & LIMITATIONS: This is a large study using validated sexual questionnaires. A limitation is the cross-sectional design. Owing to the study design, this study is explorative and hypothesis generating. CONCLUSION: In this large cross-sectional study, we demonstrated that CAG repeat length is positively correlated to sexual function and that women with a reduced ability to reach orgasm had smaller numbers of CAG repeats in the AR gene than women with no orgasmic problems. These findings indicated that androgens and ARs might play a role in women's sexual function. Wåhlin-Jacobsen S, Flanagan JN, Pedersen AT, Kristensen E, Arver S, Giraldi A. Androgen Receptor Polymorphism and Female Sexual Function and Desire. J Sex Med 2018;15:1537-1546.

Mental well-being and job satisfaction among general practitioners: a nationwide cross-sectional survey in Denmark.

BACKGROUND: Poor mental well-being and low job satisfaction among physicians can have significant negative implications for the physicians and their patients and may also reduce the cost efficiency in health care. Mental distress is increasingly common in physicians, including general practitioners (GPs). This study aimed to examine mental well-being and job satisfaction among Danish GPs and potential associations with age, gender and practice organisation. METHODS: Data was collected in a nationwide questionnaire survey among Danish GPs in 2016. Register data on GPs and their patient populations was used to explore differences between respondents and non-respondents. Associations were estimated using multivariate logistic regression analysis. RESULTS: Of 3350 eligible GPs, 1697 (50.7%) responded. Lower response rate was associated with increasing numbers of comorbid, aging or deprived patients. About half of participating GPs presented with at least one burnout symptom; 30.6% had high emotional exhaustion, 21.0% high depersonalisation and 36.6% low personal accomplishment. About a quarter (26.2%) experienced more than one of these symptoms, and 10.4% experienced all of them. Poor work-life balance was reported by 16.2%, low job satisfaction by 22.1%, high perceived stress by 20.6% and poor general well-being by 18.6%. Constructs were overlapping; 8.4% had poor overall mental health, which was characterized by poor general well-being, high stress and ≥ 2 burnout symptoms. In contrast, 24.6% had no burnout symptoms and reported high levels of general well-being and job satisfaction. Male GPs more often than female GPs reported low job satisfaction, depersonalisation, complete burnout and poor overall mental health. Middle-aged (46-59 years) GPs had higher risk of low job satisfaction, burnout and suboptimal self-rated health than GPs in other age groups. GPs in solo practices more often assessed the work-life balance as poor than GPs in group practices. CONCLUSION: The prevalence of poor mental well-being and low job satisfaction was generally high, particularly among mid-career GPs and male GPs. Approximately 8% was substantially distressed, and approximately 25% reported positive mental well-being and job satisfaction, which shows huge variation in the mental well-being among Danish GPs. The results call for targeted interventions to improve mental well-being and job satisfaction among GPs.

Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity.

The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic properties. Extensive studies have revealed two putative pathways for this allosteric communication. Here we provide further details of this allosteric communication by investigating FVIIa loop swap variants containing the 170 loop of trypsin that display TF-independent enhanced activity. Using x-ray crystallography, we show that the introduced 170 loop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215-217 and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215-217 conformation is pivotal to the enhanced activity of the FVIIa variants. We speculate that the allosteric regulation of FVIIa activity by TF binding follows a similar path in conjunction with protease domain N terminus insertion, suggesting a more complete molecular basis of TF-mediated allosteric enhancement of FVIIa activity.

Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women∗: ∗2016 ISSM Female Sexual Dysfunction Prize.

INTRODUCTION: The female sexual response is complex and influenced by several biological, psychological, and social factors. Testosterone is believed to modulate a woman's sexual response and desire, because low levels are considered a risk factor for impaired sexual function, but previous studies have been inconclusive. AIM: To investigate how androgen levels and psychosocial factors are associated with female sexual dysfunction (FSD), including hypoactive sexual desire disorder (HSDD). METHODS: The cross-sectional study included 428 premenopausal women 19 to 58 years old who completed a questionnaire on psychosocial factors and had blood sampled at days 6 to 10 in their menstrual cycle. Logistic regression models were built to test the association among hormone levels, psychosocial factors, and sexual end points. MAIN OUTCOME MEASURES: Five different sexual end points were measured using the Female Sexual Function Index and the Female Sexual Distress Scale: impaired sexual function, sexual distress, FSD, low sexual desire, and HSDD. Serum levels of total and free testosterone, androstenedione, dehydroepiandrosterone sulfate, and androsterone glucuronide were analyzed using mass spectrometry. RESULTS: After adjusting for psychosocial factors, women with low sexual desire had significantly lower mean levels of free testosterone and androstenedione compared with women without low sexual desire. None of the androgens were associated with FSD in general or with HSDD in particular. Relationship duration longer than 2 years and mild depressive symptoms increased the risk of having all the sexual end points, including FSD in general and HSDD in particular in multivariate analyses. CONCLUSION: In this large cross-sectional study, low sexual desire was significantly associated with levels of free testosterone and androstenedione, but FSD in general and HSDD in particular were not associated with androgen levels. Length of relationship and depression were associated with FSD including HSDD. Wåhlin-Jacobsen S, Kristensen E, Tønnes Pedersen A, et al. Androgens and Psychosocial Factors Related to Sexual Dysfunctions in Premenopausal Women. J Sex Med 2017;14:366-379.

Measurement properties of the Danish version of the Awareness and Beliefs about Cancer (ABC) measure.

BACKGROUND: The International Cancer Benchmarking Partnership aims to study international differences in cancer survival and the possible causes. Participating countries are Australia, Canada, Norway, Sweden, Denmark and the UK and a particular focus area is differences in awareness and beliefs about cancer. In this connection, the Awareness and Beliefs about Cancer (ABC) measure has been translated into multiple languages. The aim of this study is to appraise the translation process and measurement properties of the Danish version of the ABC measure. METHODS: The translation process included forward and backward translations and a pilot-test. Data quality was assessed using survey data from 3000 Danish respondents and content validity indexes were calculated based on judgments from ten academic researchers. Construct validity was determined by a confirmative factor analysis (CFA) and exploratory factor analyses (EFA) using survey data and a known group comparison analysis including 56 persons. Test-retest reliability was assessed based on responses from 123 person whom completed the interview twice with an interval of 2-3 weeks. RESULTS: The translation process resulted in a Danish ABC measure conceptually equivalent to the English ABC measure. Data quality was acceptable in relation to non-response to individual items which was maximum 0.3%, but the percentage of respondents answering 'don't know' was above 3% for 16 out of 48 items. Content validity indexes showed that items adequately reflected and represented the constructs to be measured (item content validity indexes: 0.9-1.0; construct content validity indexes: 0.8-1.0). The hypothesised factor structure could not be replicated by a CFA, but EFA on each individual subscale showed that six out of seven subscales were unidimensional. The ABC measure discriminated well between non-medical academics and medical academics, but had some difficulties in discriminating between educational groups. Test-retest reliability was moderate to substantial for most items. CONCLUSIONS: The Danish ABC measure is a useful measurement that is accepted and understood by the target group and with accepted measurement criteria for content validity and test-retest reliability. Future studies may further explore the factorial structure of the ABC measure and should focus on improving the response categories.

Mono-ovulation in women with polycystic ovary syndrome: a clinical review on ovulation induction.

Polycystic ovary syndrome (PCOS) affects 5-10% of women of reproductive age and is the most common cause of anovulatory infertility. The treatment approaches to ovulation induction vary in efficacy, treatment duration and patient friendliness. The aim was to determine the most efficient, evidence-based method to achieve mono-ovulation in women diagnosed with PCOS. Publications in English providing information on treatment, efficacy and complication rates were included until September 2015. Systematic reviews, meta-analyses and randomized controlled trials were favoured over cohort and retrospective studies. Clomiphene citrate is recommended as primary treatment for PCOS-related infertility. It induces ovulation in three out of four patients, the risk of multiple pregnancies is modest and the treatment is simple and inexpensive. Gonadotrophins are highly efficient in a low-dose step-up regimen. Ovulation rates are improved by lifestyle interventions in overweight women. Metformin may improve the menstrual cycle within 1-3 months, but does not improve the live birth rate. Letrozole is effective for ovulation induction, but is an off-label drug in many countries. Ovulation induction in women with PCOS should be individualized with regard to weight, treatment efficacy and patient preferences with the aim of achieving mono-ovulation and subsequently the birth of a singleton baby.

Awareness of cancer symptoms and anticipated patient interval for healthcare seeking. A comparative study of Denmark and Sweden.

Background Recent epidemiologic data show that Denmark has considerably poorer survival from common cancers than Sweden. This may be related to a lower awareness of cancer symptoms and longer patient intervals in Denmark than in Sweden. The aims of this study were to: 1) compare population awareness of three possible symptoms of cancer (unexplained lump or swelling, unexplained bleeding and persistent cough or hoarseness); 2) compare anticipated patient interval when noticing any breast changes, rectal bleeding and persistent cough; and 3) examine whether potential differences were noticeable in particular age groups or at particular levels of education in a Danish and Swedish population sample. Method Data were derived from Module 2 of the International Cancer Benchmarking Partnership. Telephone interviews using the Awareness and Beliefs about Cancer measure were conducted in 2011 among 3000 adults in Denmark and 3070 adults in Sweden. Results Danish respondents reported a higher awareness of two of three symptoms (i.e. unexplained lump or swelling and persistent cough or hoarseness) and a shorter anticipated patient interval for two of three symptoms studied (i.e. any breast changes and rectal bleeding) than Swedish respondents. Differences in symptom awareness and anticipated patient interval between these countries were most pronounced in highly educated respondents. Conclusion Somewhat paradoxically, the highest awareness of symptoms of cancer and the shortest anticipated patient intervals were found in Denmark, where cancer survival is lower than in Sweden. Thus, it appears that these differences in symptom awareness and anticipated patient interval do not help explain the cancer survival disparity between Denmark and Sweden.

Social support and non-participation in breast cancer screening: a Danish cohort study.

BACKGROUND: Social support may have an impact on screening participation. We studied the association between social support in 2006, defined as frequencies of contacts, instrumental support and emotional support and participation in breast cancer screening in 2008-09. METHODS: This population-based cohort study included 4512 women who had participated in a Health Survey in 2006 and who also were in the target group for the first round of organized breast cancer screening in the Central Denmark region in 2008-09. RESULTS: Women with infrequent contacts with friends and family in 2006 were more likely not to participate in screening in 2008-09 [prevalence ratio (PR) 1.69, 95% confidence interval (CI) 1.26-2.26, P-value < 0.001 and PR 1.56, 95% CI 1.21-2.20, P-value < 0.001, respectively] as were women who reported not to have someone to look after her home if she was away for some time and women who reported usually not or never having someone to turn to with personal concerns (PR 1.97, 95% CI 1.53-2.54, P-value < 0.001 and PR 1.42, 95% CI 1.14-1.77, P-value = 0.002, respectively). CONCLUSIONS: Low social support, indicated by items in each social support attribute, was associated with non-participation in breast cancer screening in 2008-09. Targeted social interventions may, therefore, have an impact on future screening behaviour, which calls for further research.