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Background: Chronic diseases and multimorbidity are common in western countries and associated with increased breast cancer mortality. This study aims to investigate non-participation in breast cancer screening among women with chronic diseases and multimorbidity and the role of time in this association.Method: This population-based cohort study used regional and national registries. Women who were invited to the first breast cancer screening round in the Central Denmark Region in 2008-09 were included (n = 149,234). Selected chronic diseases and multimorbidity were assessed up to 10 years before the screening date. Prevalence ratios (PR) were used as an association measure.Results: The results indicated that women with at least one chronic condition were significantly more likely not to participate in breast cancer screening. In adjusted analysis, a significantly higher likelihood of non-participation was found for women with cancer (PR = 1.50, 95% CI: 1.40-1.60), mental illness (PR = 1.51, 95% CI: 1.42-1.60), chronic obstructive pulmonary disease (PR = 1.51, 95% CI: 1.42-1.62), neurological disorders (PR = 1.24, 95% CI: 1.12-1.37) and kidney disease (PR = 1.70, 95% CI 1.49-1.94), whereas women with chronic bowel disease (PR = 0.75, 95% CI 0.65-0.88) were more likely to participate than women without these disease. Multimorbidity was associated with increased non-participation likelihood. E.g. having 3 or more diseases was associated with 58% increased non-participation likelihood (95% CI: 27-96%). Higher non-participation was also observed for women with severe multimorbidity (PR = 1.53, 95% CI: 1.23-1.90) and mental-physical multimorbidity (PR = 1.54, 95% CI: 1.36-1.75).Conclusion: In conclusion, we found a strong association between non-participation in breast cancer screening for some chronic diseases and for multimorbidity. The highest propensity not to participate was observed for women with hospital contacts related to the chronic disease in the period closest to the screening date. [ABSTRACT FROM AUTHOR]

Background: People suffering from Borderline Personality Disorder (BPD) seem to have incoherent autobiographical narratives. Tentative evidence suggests that reduced narrative coherence of autobiographical memories is associated with insecure attachment. However, it remains unknown whether incoherent autobiographical narratives in people with BPD are coupled to experiences of childhood trauma, which is highly prevalent in BPD., Method: We examined if written autobiographical memories in 26 female participants with BPD had reduced narrative coherence relative to 28 healthy female controls and whether more incoherent narratives were associated with childhood trauma., Results: As hypothesized, results showed that compared to controls, the autobiographical memories in participants with BPD had reduced narrative coherence, specifically inadequate orientation about the narrative and lack of narrative structure. More self-reported childhood adversity was coupled to lower orientation across groups whereas increased childhood adversity showed a specific relationship to lowered narrative structure in BPD participants., Conclusion: Women with BPD had incoherent autobiographical narratives, and reduced narrative coherence was associated with more self-reported childhood adversity, which appeared to explain the group differences.

Background: Herpes zoster (HZ) may result in severe complications requiring hospital treatment, particularly in patients with comorbidity. Nevertheless, data on HZ from nationwide population-based hospital registries are sparse., Methods: We conducted a cohort study describing first-time hospital-based (inpatient, outpatient, and emergency room) HZ diagnoses in the Danish National Patient Registry, 1994-2012. We computed the diagnosis rate; prevalence of demographic characteristics, comorbidities, and complications; length of hospital stay; and standardized mortality ratios (SMRs) using the Danish population as reference. We classified comorbidity using the Charlson Comorbidity Index (CCI) scoring system and categorized patients in groups of no (score 0), moderate (score 1), severe (score 2), and very severe comorbidity (score ≥3). In addition, we computed the prevalence of certain conditions associated with immune dysregulation (stem cell or bone marrow transplantation, solid organ transplantation, HIV infection, primary immunodeficiency, any cancer, and autoimmune diseases)., Results: The diagnosis rate increased almost exponentially from 6 to 91.9 per 100,000 person-years between age 50 and ≥90 years. The age-standardized rate was stable throughout the study period. The median length of hospital stay was 4 days (interquartile range: 1-8 days) for inpatients with HZ as the main reason for admission. According to the CCI, 44.3 % of patients had no comorbidity, 17.3 % moderate comorbidity, 17.4 % severe comorbidity, and 21.0 % very severe comorbidity. Comorbidities involving immune dysregulation, such as malignant (21 %) and autoimmune diseases (17 %), were particularly prevalent. Thirty percent had neurological, ophthalmic, or other complications. HZ was associated with increased all-cause mortality overall (SMR 1.8, 95 % CI: 1.7-1.8), but not in analyses restricted to patients without comorbidity (SMR 1.0, 95 % CI: 0.9-1.0)., Conclusions: This study provides estimates of the epidemiology of hospital-based (severe) HZ. The diagnosis rate increased substantially with age. Complications and comorbidities were prevalent, likely resulting in increased mortality.

Background: Conceptualisation and classification of functional disorders appear highly inconsistent in the health-care system, particularly in primary care. Numerous terms and overlapping diagnostic criteria are prevalent of which many are considered stigmatising by general practitioners and patients. The lack of a clear concept challenges the general practitioner's decision-making when a diagnosis or a treatment approach must be selected for a patient with a functional disorder. This calls for improvements of the diagnostic categories. Intense debate has risen in connection with the release of the fifth version of the 'Diagnostic and Statistical Manual of Mental Disorders' and the current revision of the 'International Statistical Classification of Diseases and Related Health Problems'. We aim to discuss a new evidence based diagnostic proposal, bodily distress syndrome, which holds the potential to change our current approach to functional disorders in primary care. A special focus will be directed towards the validity and utility criteria recommended for diagnostic categorisation., Discussion: A growing body of evidence suggests that the numerous diagnoses for functional disorders listed in the current classifications belong to one family of closely related disorders. We name the underlying phenomenon 'bodily distress'; it manifests as patterns of multiple and disturbing bodily sensations. Bodily distress syndrome is a diagnostic category with specific criteria covering this illness phenomenon. The category has been explored through empirical studies, which in combination provide a sound basis for determining a symptom profile, the diagnostic stability and the boundaries of the condition. However, as bodily distress syndrome embraces only the most common symptom patterns, patients with few but impairing symptoms are not captured. Furthermore, the current lack of treatment options may also influence the acceptance of the proposed diagnosis. Bodily distress syndrome is a diagnostic category with notable validity according to empirical studies. Nevertheless, knowledge is sparse on the utility in primary care. Future intervention studies should investigate the translation of bodily distress syndrome into clinical practice. A particular focus should be directed towards the acceptability among general practitioners and patients. Most importantly, it should be investigated whether the new category may provide the basis for better treatment and improved clinical outcome.

Background: In Staphylococcus aureus sub-populations of slow-growing cells forming small colony variants (SCVs) are associated with persistent and recurrent infections that are difficult to eradicate with antibiotic therapies. In SCVs that are resistant towards aminoglycosides, mutations have been identified in genes encoding components of the respiratory chain. Given the high frequencies of SCVs isolated clinically it is vital to understand the conditions that promote or select for SCVs., Results: In this study we have examined how exposure to sub-inhibitory concentrations of antibiotics with different mechanism of action influence the formation of SCVs that are resistant to otherwise lethal concentrations of the aminoglycoside, gentamicin. We found that exposure of S. aureus to fluoroquinolones and mitomycin C increased the frequency of gentamicin resistant SCVs, while other antibiotic classes failed to do so. The higher proportion of SCVs in cultures exposed to fluoroquinolones and mitomycin C compared to un-exposed cultures correlate with an increased mutation rate monitored by rifampicin resistance and followed induction of the SOS DNA damage response., Conclusion: Our observations suggest that environmental stimuli, including antimicrobials that reduce replication fidelity, increase the formation of SCVs through activation of the SOS response and thereby potentially promote persistent infections that are difficult to treat.

Background: The importance of proactive chronic care has become increasingly evident. Yet, it is unknown whether the use of general practice (GP) during daytime may affect the use of Out-of-Hours (OOH) Primary Care Service for people with chronic disease. We aimed to analyse the association between use of daytime general practice (GP) and use of OOH services for heart disease, lung disease, diabetes, psychiatric disease, or cancer. In particular, we intended to study the association between OOH contacts due to chronic disease exacerbation and recent use of daytime GP., Methods: Data comprised a random sample of contacts to the OOH services ('LV-KOS2011'). Included patients were categorised into the following chronic diseases: heart disease, lung disease, diabetes, psychiatric disease, or cancer. Information on face-to-face contacts to daytime GP was obtained from the Danish National Health Insurance Service Registry and information about exacerbation or new episodes from the LVKOS2011 survey. Associations between number of regular daytime consultations and annual follow-up consultations during one, three, six, and 12 months prior to index contacts, and outcomes of interest were estimated by using logistic regression., Results: In total, 11,897 patients aged ≥ 18 years were included. Of these, 2,665 patients (22.4%) were identified with one of the five selected chronic diseases; 673 patients (5.7%) had two or more. A higher odds ratio (OR) for exacerbation as reason for encounter (RFE) at the index contact was observed among patients with psychiatric disease (OR = 2.15) and cancer (OR = 2.17) than among other patients for ≥2 daytime recent contacts. When receiving an annual follow-up, exacerbation OR at index contact lowered for patients with lung disease (OR = 0.68), psychiatric disease (OR = 0.42), or ≥2 diseases (OR = 0.61)., Conclusion: Recent and frequent use of daytime GP for patients with the selected chronic diseases was associated with contacts to the OOH services due to exacerbation. These findings indicate that the most severely chronically ill patients tend to make more use of general practice. The provision of an annual follow-up daytime GP consultation may indicate a lower risk of contacting OOH due to exacerbation.

Background: The general practitioner (GP) plays an important role for chronic disease care. Continuous and close contact with daytime general practice is intended to prevent medical problems arising outside office hours due to already diagnosed chronic disease. However, previous studies indicate that patients with chronic diseases are frequent users of out-of-hours primary care services (OOH), but knowledge is limited on reasons for encounter (RFE), severity of symptoms, and OOH patient handling. We aimed to describe contacts to the OOH services from patients with chronic heart disease, lung disease, severe psychiatric disorders, diabetes, and cancer in terms of RFE, OOH GP diagnosis, assessed severity of symptoms, and actions taken by the GP., Methods: Eligible patients (aged 18 years and older) were randomly sampled from a one-year cross-sectional study comprising 15,229 contacts to the OOH services in the Central Denmark Region. A cohort of patients with one or more of the five selected chronic diseases were identified by linking data on the Danish civil registration number (CPR) through specific nationwide Danish health registers., Results: Out of 13,930 identified unique patients, 4,912 had at least one of the five chronic diseases. In total, 25.9% of all calls to the OOH services came from this chronic disease patient group due to an acute exacerbation; 32.6% of these calls came from patients with psychiatric diagnoses. Patients with chronic disease were more likely to receive a face-to-face contact than the remaining group of patients, except for calls from patients with a psychiatric disorder who were more often completed through a telephone consultation. Patients with heart disease calling due to a new health problem formed the largest proportion of all OOH referrals to hospital (13.3%) compared to calls from the other groups with chronic disease (3.4-6.7%)., Conclusions: A third of the patients randomly sampled by their OOH call had one or more of the five selected chronic diseases (i.e. chronic lung disease, heart disease, diabetes, psychiatric disease, or cancer). Patients with chronic disease were more often managed by OOH GPs than other patients.

Background: About 30% of the Danish population has one or more chronic conditions, and general practitioners (GPs) play a key role in effective chronic care management. However, little is known about these encounters in general practice. The aim was to describe the frequency of patients with one or more chronic conditions in general practice and how these consultations were experienced by the GPs., Methods: All GPs in the Central Denmark Region were invited to register all contacts during one day in the 12-month study period from December; 404 (46%) accepted. For each patient contact, the GPs were asked to fill in a one-page registration form covering information on chronic disease, reason for encounter, diagnosis, number of additional psychosocial problems raised by the patient during the consultation, time consumption, experienced burden of the consultation, referral to specialized care, and whether a nurse could have substituted the GP. Patients were categorized according to the number of chronic conditions (none, one, two, three or more) and the categories compared with regard to the GP-experienced burden of the contacts. Moreover, we examined which chronic conditions posed the the greatest challenge to the GPs., Results: Patients aged 40 years or more had a total of 8,236 contacts. Among these patients 2,849 (34.6%; 95% CI 33.6-35.6) had one and 2,596 (31.5%; CI 30.5-32.5) had more than one chronic disease. The time consumption and the burden of their contacts tended to rise with the number of chronic conditions. Being present in 22.9% (CI 21.6-24.3) of all face-to-face contacts, hypertension was the most common chronic condition. The burden of the contacts was experienced as particularly heavy for patients with depression and dementia due to more additional psychosocial problems and the time consumption., Conclusion: General practitioners considered consultations with multimorbid patients demanding and not easily delegated to nurses. As the number of patients with chronic conditions and multimorbidity is increasing, GPs can be expected to face a heavier workload in the future.

Background: The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia., Methods: First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion., Results: Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours., Conclusions: Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.

Background: Low birth weight is associated with an increased risk of neonatal and infant mortality and morbidity, as well as with other adverse conditions later in life. Since the birth weight-specific mortality of a second child depends on the birth weight of an older sibling, a failure to achieve the biologically intended size appears to increase the risk of adverse outcome even in babies who are not classified as small for gestation. In this study, we aimed at quantifying the risk of neonatal death as a function of a baby's failure to fulfil its biologic growth potential across the whole distribution of birth weight., Methods: We predicted the birth weight of 411,957 second babies born in Denmark (1979-2002), given the birth weight of the first, and examined how the ratio of achieved birth weight to predicted birth weight performed in predicting neonatal mortality., Results: For any achieved birth weight category, the risk of neonatal death increased with decreasing birth weight ratio. However, the risk of neonatal death increased with decreasing birth weight, even among babies who achieved their predicted birth weight., Conclusion: While a low achieved birth weight was a stronger predictor of mortality, a failure to achieve the predicted birth weight was associated with increased mortality at virtually all birth weights. Use of family data may allow identification of children at risk of adverse health outcomes, especially among babies with apparently "normal" growth.