Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).

Healthcare fragmentation, multimorbidity, potentially inappropriate medication, and mortality: a Danish nationwide cohort study.

BACKGROUND: Patients with multimorbidity are frequent users of healthcare, but fragmented care may lead to suboptimal treatment. Yet, this has never been examined across healthcare sectors on a national scale. We aimed to quantify care fragmentation using various measures and to analyze the associations with patient outcomes. METHODS: We conducted a register-based nationwide cohort study with 4.7 million Danish adult citizens. All healthcare contacts to primary care and hospitals during 2018 were recorded. Clinical fragmentation indicators included number of healthcare contacts, involved providers, provider transitions, and hospital trajectories. Formal fragmentation indices assessed care concentration, dispersion, and contact sequence. The patient outcomes were potentially inappropriate medication and all-cause mortality adjusted for demographics, socioeconomic factors, and morbidity level. RESULTS: The number of involved healthcare providers, provider transitions, and hospital trajectories rose with increasing morbidity levels. Patients with 3 versus 6 conditions had a mean of 4.0 versus 6.9 involved providers and 6.6 versus 13.7 provider transitions. The proportion of contacts to the patient's own general practice remained stable across morbidity levels. High levels of care fragmentation were associated with higher rates of potentially inappropriate medication and increased mortality on all fragmentation measures after adjusting for demographic characteristics, socioeconomic factors, and morbidity. The strongest associations with potentially inappropriate medication and mortality were found for ≥ 20 contacts versus none (incidence rate ratio 2.83, 95% CI 2.77-2.90) and ≥ 20 hospital trajectories versus none (hazard ratio 10.8, 95% CI 9.48-12.4), respectively. Having less than 25% of contacts with your usual provider was associated with an incidence rate ratio of potentially inappropriate medication of 1.49 (95% CI 1.40-1.58) and a mortality hazard ratio of 2.59 (95% CI 2.36-2.84) compared with full continuity. For the associations between fragmentation measures and patient outcomes, there were no clear interactions with number of conditions. CONCLUSIONS: Several clinical indicators of care fragmentation were associated with morbidity level. Care fragmentation was associated with higher rates of potentially inappropriate medication and increased mortality even when adjusting for the most important confounders. Frequent contact to the usual provider, fewer transitions, and better coordination were associated with better patient outcomes regardless of morbidity level.

Statins and Risk of Intracerebral Hemorrhage in Individuals With a History of Stroke.

Background and Purpose- It has been suggested that statins increase the risk of intracerebral hemorrhage in individuals with a history of stroke, which has led to a precautionary principle of avoiding statins in patients with prior intracerebral hemorrhage. However, such prescribing reticence may be unfounded and potentially harmful when considering the well-established benefits of statins. This study is so far the largest to explore the statin-associated risk of intracerebral hemorrhage in individuals with prior stroke. Methods- We conducted a population-based, propensity score-matched cohort study using information from Danish national registers. We included all individuals initiating statin treatment after a first-time stroke diagnosis (intracerebral hemorrhage, N=2728 or ischemic stroke, N=52 964) during 2002 to 2016. For up to 10 years of follow-up, they were compared with a 1:5 propensity score-matched group of statin nonusers with the same type of first-time stroke. The difference between groups was measured by adjusted hazard ratios for intracerebral hemorrhage calculated by type of first-time stroke as a function of time since statin initiation. Results- Within the study period, 118 new intracerebral hemorrhages occurred among statin users with prior intracerebral hemorrhage and 319 new intracerebral hemorrhages in users with prior ischemic stroke. The risk of intracerebral hemorrhage was similar for statin users and nonusers when evaluated among those with prior intracerebral hemorrhage, and it was reduced by half in those with prior ischemic stroke. These findings were consistent over time since statin initiation and could not be explained by concomitant initiation of other medications, by dilution of treatment effect (due to changes in exposure status over time), or by healthy initiator bias. Conclusions- This large study found no evidence that statins increase the risk of intracerebral hemorrhage in individuals with prior stroke; perhaps the risk is even lower in the subgroup of individuals with prior ischemic stroke.

Depression and Uptake of Oral Anticoagulation Therapy in Patients With Atrial Fibrillation: A Danish Nationwide Cohort Study.

BACKGROUND: Oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF) is a highly important preventive intervention, perhaps especially in those with comorbid depression, who have a worse prognosis. However, OAT may pose particular challenges in depressed patients. OBJECTIVES: To assess whether AF patients with depression have lower OAT uptake. METHODS: This nationwide register-based 2005-2016 cohort study of all Danes with AF and OAT indication (CHA2DS2VASc stroke risk score ≥2) assessed OAT initiation within 90 days in those with incident AF (N=147,162) and OAT prevalence in those with prevalent AF (N=192,656). The associations of depression with both outcomes were estimated in regression analyses with successive adjustment for socioeconomic characteristics and somatic and psychiatric comorbidity. RESULTS: Comorbid depression was significantly associated with lower frequency of OAT initiation in incident AF patients {adjusted proportion differences (aPDs): -6.6% [95% confidence interval (CI), -7.4 to -5.9]} and lower prevalence of OAT [aPD: -4.2% (95% CI, -4.7 to -3.8)] in prevalent AF patients. Yet, the OAT uptake increased substantially during the period, particularly in depressed patients [aPD for OAT prevalence in 2016: -0.8% (95% CI, -1.6 to -0.0)]. CONCLUSIONS: Comorbid depression was associated with a significantly lower OAT uptake in patients with AF, which questions whether depressed patients receive sufficient support to manage this consequential cardiac condition. However, a substantial increase in the overall OAT uptake and a decrease of the depression-associated deficit in OAT were seen over the period during which OAT was developed through the introduction of new oral anticoagulation therapy.

Does perceived stress increase the risk of atrial fibrillation? A population-based cohort study in Denmark.

BACKGROUND: Psychological stress is associated with increased risk of acute cardiovascular diseases, as myocardial infarction. We recently found a higher risk of atrial fibrillation following an acute stressful life event, but it remains unknown whether this also applies to common and less acute stress exposures. METHODS: We investigated the risk of incident atrial fibrillation in people with high levels of perceived stress by following a population-based cohort of 114,337 participants from the Danish National Health Survey from 2010 to 2014. The survey holds information on lifestyle factors and perceived stress measured by Cohen's 10-item Perceived Stress Scale (PSS). We obtained information on atrial fibrillation, comorbidities and socioeconomic status from Danish nationwide registers. We identified 2172 persons with a first episode of atrial fibrillation during 424,839 person-years of follow-up. The hazard ratio (HR) of atrial fibrillation with 95% confidence interval (CI) was calculated with Cox proportional hazard model. RESULTS: The risk of atrial fibrillation increased with increasing PSS score; persons in the highest perceived stress quintile had 28% (95% CI, 12%-46%) higher risk of atrial fibrillation compared with persons in the lowest perceived stress quintile. However, the association disappeared when adjusting for comorbidities, socioeconomic status and lifestyle factors; HR was 1.01 (95% CI, 0.88-1.16) when comparing persons in the highest and the lowest perceived stress quintile. CONCLUSIONS: This large population-based cohort study did not reveal a higher risk of atrial fibrillation among persons with a high degree of perceived stress after adjustment for participants' baseline characteristics.

Perceived Stress, Multimorbidity, and Risk for Hospitalizations for Ambulatory Care-sensitive Conditions: A Population-based Cohort Study.

BACKGROUND: Psychiatric disorders are associated with an increased risk for ambulatory care-sensitive condition (ACSC)-related hospitalizations, but it remains unknown whether this holds for individuals with nonsyndromic stress that is more prevalent in the general population. OBJECTIVES: To determine whether perceived stress is associated with ACSC-related hospitalizations and rehospitalizations, and posthospitalization 30-day mortality. RESEARCH DESIGN AND MEASURES: Population-based cohort study with 118,410 participants from the Danish National Health Survey 2010, which included data on Cohen's Perceived Stress Scale, followed from 2010 to 2014, combined with individual-level national register data on hospitalizations and mortality. Multimorbidity was assessed using health register information on diagnoses and drug prescriptions within 39 condition categories. RESULTS: Being in the highest perceived stress quintile was associated with a 2.13-times higher ACSC-related hospitalization risk (95% CI, 1.91, 2.38) versus being in the lowest stress quintile after adjusting for age, sex, follow-up time, and predisposing conditions. The associated risk attenuated to 1.48 (95% CI, 1.32, 1.67) after fully adjusting for multimorbidity and socioeconomic factors. Individuals with above reference stress levels experienced 1703 excess ACSC-related hospitalizations (18% of all). A dose-response relationship was observed between perceived stress and the ACSC-related hospitalization rate regardless of multimorbidity status. Being in the highest stress quintile was associated with a 1.26-times insignificantly increased adjusted risk (95% CI, 0.79, 2.00) for ACSC rehospitalizations and a 1.43-times increased adjusted risk (95% CI, 1.13, 1.81) of mortality within 30 days of admission. CONCLUSIONS: Elevated perceived stress levels are associated with increased risk for ACSC-related hospitalization and poor short-term prognosis.

The Association Between Perceived Stress and Mortality Among People With Multimorbidity: A Prospective Population-Based Cohort Study.

Multimorbidity is common and is associated with poor mental health and high mortality. Nevertheless, no studies have evaluated whether mental health may affect the survival of people with multimorbidity. We investigated the association between perceived stress and mortality in people with multimorbidity by following a population-based cohort of 118,410 participants from the Danish National Health Survey 2010 for up to 4 years. Information on perceived stress and lifestyle was obtained from the survey. We assessed multimorbidity using nationwide register data on 39 conditions and identified 4,229 deaths for the 453,648 person-years at risk. Mortality rates rose with increasing levels of stress in a dose-response relationship (P-trend < 0.0001), independently of multimorbidity status. Mortality hazard ratios (highest stress quintile vs. lowest) were 1.51 (95% confidence interval (CI): 1.25, 1.84) among persons without multimorbidity, 1.39 (95% CI: 1.18, 1.64) among those with 2 or 3 conditions, and 1.43 (95% CI: 1.18, 1.73) among those with 4 or more conditions, when adjusted for disease severities, lifestyle, and socioeconomic status. The numbers of excess deaths associated with high stress were 69 among persons without multimorbidity, 128 among those with 2 or 3 conditions, and 255 among those with 4 or more conditions. Our findings suggested that perceived stress contributes significantly to higher mortality rates in a dose-response pattern, and more stress-associated deaths occurred in people with multimorbidity.

Serious Mental Illness and Risk for Hospitalizations and Rehospitalizations for Ambulatory Care-sensitive Conditions in Denmark: A Nationwide Population-based Cohort Study.

BACKGROUND: Hospitalizations for ambulatory care-sensitive conditions (ACSCs) and early rehospitalizations increase health care costs. OBJECTIVES: To determine if individuals with serious mental illnesses (SMIs) (eg, schizophrenia or bipolar disorder) are at increased risk for hospitalizations for ACSCs, and rehospitalization for the same or another ACSC, within 30 days. RESEARCH DESIGN: Population-based cohort study. PARTICIPANTS: A total of 5.9 million Danish persons aged 18 years and older between January 1, 1999 and December 31, 2013. MEASURES: The Danish Psychiatric Central Register provided information on SMI diagnoses and the Danish National Patient Register on hospitalizations for ACSCs and 30-day rehospitalizations. RESULTS: SMI was associated with increased risk for having any ACSC-related hospitalization after adjusting for demographics, socioeconomic factors, comorbidities, and prior primary care utilization [incidence rate ratio (IRR): 1.41; 95% confidence interval (95% CI), 1.37-1.45]. Among individual ACSCs, SMI was associated with increased risk for hospitalizations for angina (IRR: 1.14, 95% CI, 1.04-1.25), chronic obstructive pulmonary disease/asthma exacerbation (IRR: 1.87; 95% CI, 1.74-2.00), congestive heart failure exacerbation (IRR: 1.25; 95% CI, 1.16-1.35), and diabetes (IRR: 1.43; 95% CI, 1.31-1.57), appendiceal perforation (IRR: 1.49; 95% CI, 1.30-1.71), pneumonia (IRR: 1.72; 95% CI, 1.66-1.79), and urinary tract infection (IRR: 1.70; 95% CI, 1.62-1.78). SMI was also associated with increased risk for rehospitalization within 30 days for the same (IRR: 1.28; 95% CI, 1.18-1.40) or for another ACSC (IRR: 1.62; 95% CI, 1.49-1.76). CONCLUSION: Persons with SMI are at increased risk for hospitalizations for ACSCs, and after discharge, are at increased risk for rehospitalizations for ACSCs within 30 days.

Variation in general practice prostate-specific antigen testing and prostate cancer outcomes: an ecological study.

Knowledge is sparse about the consequences of variation in prostate-specific antigen (PSA) testing rates in general practice. This study investigated associations between PSA testing and prostate cancer- related outcomes in Danish general practice, where screening for prostate cancer is not recommended. National registers were used to divide general practices into four groups based on their adjusted PSA test rate 2004-2009. We analysed associations between PSA test rate and prostate cancer-related outcomes using Poisson regression adjusted for potential confounders. We included 368 general practices, 303,098 men and 4,199 incident prostate cancers. Men in the highest testing quartile of practices compared to men in the lowest quartile had increased risk of trans-rectal ultrasound (incidence rate ratio (IRR): 1.20, 95% CI, 0.95-1.51), biopsy (IRR: 1.76, 95% CI, 1.54-2.02), and getting a prostate cancer diagnosis (IRR: 1.37, 95% CI, 1.23-1.52). More were diagnosed with local stage disease (IRR: 1.61, 95% CI, 1.37-1.89) with no differences regarding regional or distant stage. The IRR for prostatectomy was 2.25 (95% CI, 1.72-2.94) and 1.28 (95% CI, 1.02-1.62) for radiotherapy. No differences in prostate cancer or overall mortality were found between the groups. These results show that the highest PSA testing general practices may not reduce prostate cancer mortality but increase the downstream use of diagnostic and surgical procedures with potentially harmful side effects.

The effect of direct access to CT scan in early lung cancer detection: an unblinded, cluster-randomised trial.

BACKGROUND: Lower lung cancer survival rates in Britain and Denmark compared with surrounding countries may, in part, be due to late diagnosis. The aim of this study was to evaluate the effect of direct access to low-dose computed tomography (LDCT) from general practice in early lung cancer detection on time to diagnosis and stage at diagnosis. METHODS: We conducted a cluster-randomised, controlled trial including all incident lung cancer patients (in 19-month period) listed with general practice in the municipality of Aarhus (300,000 citizens), Denmark. Randomisation and intervention were applied at general practice level. A total of 266 GPs from 119 general practices. In the study period, 331 lung cancer patients were included. The intervention included direct access to low-dose CT from primary care combined with a 1 h lung cancer update meeting. Indication for LDCT was symptoms or signs that raised the GP's suspicion of lung cancer, but fell short of satisfying the fast-track referral criteria on red flag' symptoms. RESULTS: The intervention did not significantly influence stage at diagnosis and had limited impact on time to diagnosis. However, when correcting for non-compliance, we found that the patients were at higher risk of experiencing a long diagnostic interval if their GPs were in the control group. CONCLUSION: Direct low-dose CT from primary care did not statistically significantly decrease time to diagnosis or change stage at diagnosis in lung cancer patients. Case finding with direct access to LDCT may be an alternative to lung cancer screening. Furthermore, a recommendation of low-dose CT screening should consider offering symptomatic, unscreened patients an access to CT directly from primary care. TRIAL REGISTRATION: www.clinicaltrials.gov, registration ID number NCT01527214.

Diagnostic intervals before and after implementation of cancer patient pathways - a GP survey and registry based comparison of three cohorts of cancer patients.

BACKGROUND: From 2008, Danish general practitioners could refer patients suspected of having cancer to standardised cancer patient pathways (CPPs). We aimed to compare the length of the diagnostic interval in 2010 with the length of the diagnostic interval before (2004/05) and during (2007/08) the implementation of CPPs in Denmark for all incident cancer patients who attended general practice prior to the cancer diagnosis. METHODS: General practitioner questionnaires and register data on 12,558 patients were used to compare adjusted diagnostic interval across time by quantile regression. RESULTS: The median diagnostic interval was 14 (95% CI: 11;16) days shorter during and 17 (95% CI: 15;19) days shorter after the implementation of CPPs than before. The diagnostic interval was 15 (95% CI: 12;17) days shorter for patients referred to a CPP in 2010 than during the implementation, whereas patients not referred to a CPP in 2010 had a 4 (95% CI: 1;7) days longer median diagnostic interval; the pattern was similar, but larger at the 75(th) and 90(th) percentiles. CONCLUSION: The diagnostic interval was significantly lower after CPP implementation. Yet, patients not referred to a CPP in 2010 tended to have a longer diagnostic interval compared to during the implementation. CPPs may thus only seem to expedite the diagnostic process for some cancer patients.

The epidemiology of microscopic colitis: a 10-year pathology-based nationwide Danish cohort study.

OBJECTIVE: Microscopic colitis (MC) includes two main types: collagenous colitis (CC) and lymphocytic colitis (LC). Previous studies have indicated an increasing incidence, but these have mainly been based on regional databases. We found it important to study the epidemiology based on a comprehensive nationwide cohort. MATERIAL AND METHODS: We studied the epidemiological data of MC in Denmark from 2002 to 2011. The cohort consisted of all patients with a recorded diagnosis of either CC or LC in the Danish Pathology Register during the study period. Data on all patients with a registered colon biopsy were also included. RESULTS: A total of 7777 patients, 4749 (61%) with CC and 3028 (39%) with LC, were identified. Over the study period, the annual incidence of diagnosed cases of CC increased from 2.9/10(5) to 14.9/10(5) and of LC from 1.7/10(5) to 9.8/10(5). In 2011, the incidence of MC was 24.7/10(5) inhabitants. The age-specific incidence showed that the risk of both CC and LC increased with age. The female/male ratio, distribution of the type of colitis and mean age at diagnosis were relatively stable during the study period. The annual number of registered colon biopsies in the pathology register increased from 21.583 in 2002 to 39.733 in 2011, indicating an increased diagnostic activity. CONCLUSION: In a nationwide cohort study, the incidence of CC and LC continued to increase from 2002 to 2011. An increased diagnostic activity could in part explain the increase in the number of diagnosed cases.

The role of general practice in routes to diagnosis of lung cancer in Denmark: a population-based study of general practice involvement, diagnostic activity and diagnostic intervals.

BACKGROUND: Lung cancer stage at diagnosis predicts possible curative treatment. In Denmark and the UK, lung cancer patients have lower survival rates than citizens in most other European countries, which may partly be explained by a comparatively longer diagnostic interval in these two countries. In Denmark, a pathway was introduced in 2008 allowing general practitioners (GPs) to refer patients suspected of having lung cancer directly to fast-track diagnostics. However, symptom presentation of lung cancer in general practice is known to be diverse and complex, and systematic knowledge of the routes to diagnosis is needed to enable earlier lung cancer diagnosis in Denmark. This study aims to describe the routes to diagnosis, the diagnostic activity preceding diagnosis and the diagnostic intervals for lung cancer in the Danish setting. METHODS: We conducted a national registry-based cohort study on 971 consecutive incident lung cancer patients in 2010 using data from national registries and GP questionnaires. RESULTS: GPs were involved in 68.3% of cancer patients' diagnostic pathways, and 27.4% of lung cancer patients were referred from the GP to fast-track diagnostic work-up. A minimum of one X-ray was performed in 85.6% of all cases before diagnosis. Patients referred through a fast-track route more often had diagnostic X-rays (66.0%) than patients who did not go through fast-track (49.4%). Overall, 33.6% of all patients had two or more X-rays performed during the 90 days before diagnosis. Patients whose symptoms were interpreted as non-alarm symptoms or who were not referred to fast-track were more likely to experience a long diagnostic interval than patients whose symptoms were interpreted as alarm symptoms or who were referred to fast-track. CONCLUSIONS: Lung cancer patients followed several diagnostic pathways. The existing fast-track pathway must be supplemented to ensure earlier detection of lung cancer. The high incidence of multiple X-rays warrants a continued effort to develop more accurate lung cancer tests for use in primary care.

Use of primary health care prior to a postpartum psychiatric episode.

OBJECTIVE: Childbirth is a strong trigger of psychiatric episodes. Nevertheless, use of primary care before these episodes is not quantified. The aim was to study the use of general practice in Denmark from two years before to one year after childbirth in women who developed postpartum psychiatric disorders. DESIGN: A matched cohort study was conducted including women who gave birth in the period 1996-2010. Women were divided into four groups: (i) all mothers with postpartum psychiatric episodes 0-3 months after birth, n = 939; 2: All mothers with a postpartum psychiatric episode 3-12 months after birth, n = 1 436; and (iii) two comparison groups of mothers, total n = 6 630 among 320 620 eligible women. SETTING: Denmark. SUBJECTS: Women born in Denmark after 1 January 1960, restricting the cohort to women who gave birth to their first singleton child between 1 January 1996 and 20 October 2010. MAIN OUTCOME MEASURES: The main outcome measures were consultation rates, consultation rate ratios, and rate differences. RESULTS: Women who developed a psychiatric episode after childbirth had higher GP consultation rates before, during, and after the pregnancy. Women with a psychiatric episode 0-3 months postpartum had 6.89 (95% CI 6.60; 7.18) mean number of consultations during pregnancy, corresponding to 1.52 (95% CI 1.22; 1.82) more visits than the comparison group. CONCLUSION: Women with a postpartum psychiatric episode had higher use of GP-based primary health care services years before the childbirth, and in this specific group of patients childbirth itself triggered a marked increase in the number of GP contacts postpartum.

Subsequent cancers, mortality, and causes of death in patients with mycosis fungoides and parapsoriasis: a Danish nationwide, population-based cohort study.

BACKGROUND: Data on subsequent cancers, prognostic factors for mortality, and causes of death are limited in mycosis fungoides (MF) and parapsoriasis. OBJECTIVES: To assess subsequent cancers, mortality, and causes of death in MF and parapsoriasis. METHODS: Using the Danish nationwide population-based registries, we identified 368 MF patients and 582 parapsoriasis patients and compared them with the general Danish population for subsequent cancers, mortality, and causes of death. RESULTS: Subsequent cancers were significantly increased in parapsoriasis patients (standardized incidence ratio [SIR], 2.0 [95% confidence interval {CI}, 1.6-2.5]), and a trend was observed in MF (SIR, 1.2 [95% CI, 0.9-1.5]). Mortality was significantly increased in MF (SIR, 2.0 [95% CI, 1.8-2.3]) and parapsoriasis (SIR, 1.3 [95% CI, 1.1-1.5]). Excess mortality from MF was highest during the first 5 years of follow-up, and causes of increased death included both malignant and nonmalignant diseases. LIMITATIONS: We have no information regarding clinical stage, treatments, and patient lifestyles. CONCLUSION: Patients with parapsoriasis had a significantly increased risk of subsequent cancers and increased mortality. In addition, the highest excess mortality in the MF group was observed during the first 5 years of follow-up, which suggests that MF exists in both an aggressive and a more indolent form.

OPCAB surgery is cost-effective for elderly patients.

OBJECTIVE: To determine the cost-effective operative strategy for coronary artery bypass surgery in patients above 70 years. DESIGN: Randomized, controlled trial of 900 patients above 70 years of age subjected to coronary artery bypass surgery. Patients were randomized to either on-pump or off-pump coronary artery bypass surgery. Data on direct and indirect costs were prospectively collected. Preoperatively and six months postoperatively, quality of life was assessed using EuroQol-5D questionnaires. Perioperative in-hospital costs and costs of re-intervention were included. RESULTS: The Summary Score of EuroQol-5D increased in both groups between preoperatively and postoperatively. In the on-pump group, it increased from 0.75 (0.16) (mean (SD)) to 0.84 (0.17), while the increase in the off-pump group was from 0.75 (0.15) to 0.84 (0.18). The difference between the groups was 0.0016 QALY and not significantly different. The mean costs were 148.940 D.Kr (CI, 130.623 D.Kr-167.252 D.Kr) for an on-pump patient and 138.693 D.Kr (CI, 123.167 D.Kr-154.220 D.Kr) for an off-pump patient. The ICER base-case point estimate was 6,829,999 D.Kr/QALY. The cost-effectiveness acceptability curve showed 89% probability of off-pump being cost-effective at a threshold value of 269,400 D.Kr/QALY. CONCLUSIONS: Off-pump surgery tends to be more cost-effective than on-pump surgery. Long-term comparisons are warranted.

The effect of an active implementation of a disease management programme for chronic obstructive pulmonary disease on healthcare utilization--a cluster-randomised controlled trial.

BACKGROUND: The growing population living with chronic conditions calls for efficient healthcare-planning and effective care. Implementing disease-management-programmes is one option for responding to this demand. Knowledge is scarce about the effect of implementation processes and their effect on patients; only few studies have reported the effectiveness of disease-management-programmes targeting patients with chronic obstructive pulmonary disease (COPD). The objective of this paper was to determine the effect on healthcare-utilization of an active implementation model for a disease-management-programme for patients with one of the major multimorbidity diseases, COPD. METHODS: The standard implementation of a new disease-management-programme for COPD was ongoing during the study-period from November 2008 to November 2010 in the Central Denmark Region. We wanted to test a strategy using Breakthrough Series, academic detailing and lists of patients with COPD. It targeted GPs and three hospitals serving approx. 60,000 inhabitants aged 35 or older and included interventions directed at professionals, organisations and patients. The study was a non-blinded block- and cluster-randomised controlled trial with GP-practices as the unit of randomisation. In Ringkoebing-Skjern Municipality, Denmark, 16 GP-practices involving 38 GPs were randomised to either the intervention-group or the control-group. A comparable neighbouring municipality acted as an external-control-group which included nine GP-practices with 25 GPs. An algorithm based on health-registry-data on lung-related contacts to the healthcare-system identified 2,736 patients who were alive at the end of the study-period. The population included in this study counted 1,372 (69.2%) patients who responded to the baseline questionnaire and confirmed their COPD diagnosis; 458 (33.4%) patients were from the intervention-group, 376 (27.4%) from the control-group and 538(39.2%) from the external-control-group. The primary outcome was adherence to the disease-management-programme measured at patient-level by use of specific services from general practice. Secondary outcomes were use of out-of-hours-services, outpatient-clinic, and emergency-department and hospital-admissions. RESULTS: The intervention practices provided more planned preventive consultations, additional preventive consultations and spirometries than non-intervention practices. A comparison of the development in the intervention practices with the development in the control-practices showed that the intervention resulted in more planned preventive-consultations, fewer conventional consultations and fewer patients admitted without a lung-related-diagnosis. CONCLUSIONS: Use of the active implementation model for the disease-management-programme for COPD changed the healthcare utilization in accordance with the programme. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01228708.

Patient-experienced effect of an active implementation of a disease management programme for COPD - a randomised trial.

BACKGROUND: People living with chronic disease currently account for the majority of the total healthcare costs. The Central Denmark Region implemented a disease management programme (DMP) for chronic obstructive pulmonary disease (COPD) in 2008. This presented an opportunity to examine the effect of an evidence-based, planned and proactive implementation of a DMP compared to the usual implementation strategy. METHODS: We performed a block- and cluster-randomised controlled trial with two groups and an extra external control group. The primary outcome was patients' assessment of their care after using an active implementation model for a DMP for COPD measured with the Patient-Assessment-of-Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to 2,895 patients identified by an algorithm based on health registry data on lung-related contacts to the healthcare system. Patients were asked to confirm or refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed their diagnosis. PACIC data were collected at baseline and at a 12-month follow-up for 744 (51.1%) patients. RESULTS: Comparing the three groups after the implementation of the DMP, we found a statistically significantly higher change in the PACIC score in the intervention group than in the control groups. No statistically significant differences were found between the control and the external control groups in any of the dimensions. CONCLUSIONS: Reinforcing the role of general practice as coordinator for care-and self-management-support with an active implementation of a DMP for COPD made patients score higher on the PACIC instrument, which indicates a better experience of the received healthcare. TRIAL REGISTRATION: NCT01228708.

21 Days head-down bed rest induces weakening of cell-mediated immunity - Some spaceflight findings confirmed in a ground-based analog.

Several studies indicate a weakening of cell-mediated immunity (CMI) and reactivation of latent herpes viruses during spaceflight. We tested the hypothesis that head-down bed rest (HDBR), a ground-based analog of spaceflight, mimics the impact of microgravity on human immunity. Seven healthy young males underwent two periods of 3 weeks HDBR in the test facility of the German Aerospace Center. As a nutritional countermeasure aimed against bone demineralisation, 90 mmol potassium bicarbonate (KHCO(3)) was administered daily in a crossover design. Blood samples were drawn on five occasions. Whole blood was stimulated with antigen i.e. Candida albicans, purified protein derivative (PPD) tuberculin, tetanus toxoid and Cytomegalovirus (CMV) (CMV-QuantiFERON). Flow cytometric analysis included CD4(+)CD25(+)CD127(-)FOXP3(+) regulatory T cells (Tregs), γδ T cells, B cells, NK cells and dendritic cells. In one of the two bed rest periods, we observed a significant decrease in production of interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) following phytohemagglutinin (PHA) stimulation, with a rapid normalization being observed after HDBR. The cytokine levels showed a V-shaped pattern that led to a relativeTh2-shift in cytokine balance. Only three individuals responded to the specific T cell antigens without showing signs of an altered response during HDBR, nor did we observe reactivation of CMV or Epstein-Barr virus (EBV). Of unknown significance, dietary supplementation with KHCO(3) counteracted the decrease in IL-2 levels during HDBR, while there was no impact on other immunological parameters. We conclude that discrete alterations in CMI may be induced by HDBR in selected individuals.

Long-term subjective results of tension-free vaginal tape operation for female urinary stress incontinence.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to evaluate the subjective outcome between 1 and 5 years after tension-free vaginal tape (TVT) operation and the need for follow-up. METHODS: A prospective questionnaire study was performed including questions about incontinence, urinary tract infection, emptying problems, the wish for a clinical control and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS: One hundred seventy-three patients were included. There were more patients with subjective recurrent stress incontinence over the years, but ICIQ-SF was unchanged. There was no rise in patients reporting urge incontinence over the years. Only 11.4% of the patients wished for a clinical control at some time. CONCLUSION: The TVT operation showed a slight degree of subjective deterioration between 1 and 5 years after the operation; however, the ICIQ-SF was unchanged. There seems to be no need for long-term follow-up at the operating department.