Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Increased prevalence of sleep disturbance in psoriatic arthritis is associated with inflammatory and non-inflammatory measures.

OBJECTIVES: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI. METHOD: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures. RESULTS: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment. CONCLUSION: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA.Trial registration: ClinicalTrials.gov (NCT02572700).

Angiogenic potential is reduced in skeletal muscle of aged women.

KEY POINTS: The risk of cardiovascular disease and associated skeletal muscle microvascular rarefaction is enhanced in women after menopause, yet knowledge about the angiogenic potential in ageing women is generally sparse. Aged healthy and sedentary women were found to present a markedly impaired capacity for proliferation of skeletal muscle derived microvascular endothelial cells compared to young women. Vascular endothelial growth factor (VEGF) levels in skeletal muscle myocytes and release of VEGF from myocytes tended to be lower in aged compared to young women. The aged women did not show a detectable increase in skeletal muscle capillarization with 8 weeks of intense aerobic cycle training. Combined, the findings indicate that aged women have a reduced potential for capillary growth in skeletal muscle which, with ageing, may lead to age-induced microvascular rarefaction. ABSTRACT: Skeletal muscle angiogenic potential was examined in cell cultures derived from aged and young women, and the effect of 8 weeks of intense cycle training on muscle capillary growth was determined in the group of aged women. Basal muscle samples were obtained from healthy sedentary aged (n = 12; 64 ± 4.2 years) and young women (n = 5; 24 ± 3.2 years) for endothelial cell and skeletal muscle myocyte isolation and experiments. In addition, the aged women completed an 8-week training intervention. Peak oxygen uptake and muscle samples for histology and protein determination were obtained before and after the training period. Before training, muscle microdialysate was collected from the aged women at rest and during exercise. In Part 1 of the experiments, growth-supplement stimulated proliferation of endothelial cells was ∼75% lower in cells from aged compared to young women (P < 0.001). There was a tendency for a lower vascular endothelial growth factor (VEGF) concentration in muscle conditioned media (P = 0.0696) and for a lower VEGF content in the myocytes (P = 0.0705) from aged compared to young women. Endothelial proliferation was found to be highly dependent on mitochondrial function. Acute exercise resulted in a modest (1.3-fold; P = 0.0073) increase in muscle interstitial VEGF protein in the aged women. In Part 2, 8 weeks of intense training did not change muscle capillarization (P ≥ 0.1502) in the aged women, but led to an increased amount of muscle VEGF (P = 0.0339). In conclusion, aged women have impaired angiogenic potential, which is associated with a compromised response both at the skeletal muscle myocyte and microvascular endothelial cell level.

Determinants for symptomatic gallstone disease readmissions - results from a cohort with screen-detected gallstone disease.

AIM OF THE STUDY: Selection of patients for cholecystectomy is hampered by lack of objective criteria. The objectives of this cohort study were to identify if patient, symptoms, or gallstone disease characteristics determined readmission in an unselected cohort with screen-detected gallstone disease and who had experienced a first admission with symptomatic gallstone disease. METHODS: Data from three random sampled population-based cohorts were used. At baseline, participants were screened with ultrasound and 664 had gallstones of which 84 had a first admission without cholecystectomy performed. A cohort study was performed with follow-up up for hospital readmissions beyond 30 days through central registers. Age adjusted Cox regression analyses were performed. RESULTS: Readmissions occurred in 60.8% and cholecystectomy was eventually performed in 47.7% of patients. Early readmissions were determined by abdominal pain in the epigastrium (Hazard ratio (HR) 3.63, 95% confidence interval (CI) [1.62;8.12]) and of moderate intensity (HR 2.71, 95% CI [1.20;6.16]). Late readmissions were determined by larger gallstone size, especially when above 10mm (HR 4.11, 95% CI [1.18;14.3]) and inversely determined by age (HR 0.97, 95% CI [0.95;0.998]). In patients with initially uncomplicated gallstone disease, cholecystectomy was inversely determined by age (HR 0.96, 95% CI [0.93;0.98]). CONCLUSION: Once gallstones have become symptomatic and caused hospital admission, a persisting high risk for future readmission exists and half of patients end up having cholecystectomy. Pain in the epigastrium, larger gallstones, and younger age determine readmission. These determinants should be tested in future clinical treatment algorithms for gallstone disease.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Are incident gallstones associated to sex-dependent changes with age? A cohort study.

Age and female sex have repeatedly been identified as gallstone determinants but the underlying mechanisms are not clarified. The objectives of this study were to determine if changes with age in physiology, lifestyle, or reproductive hormones were associated with incident gallstones. A cohort study of a general population random sample (N = 2366) aged 30-60 years was performed. Participants were ultrasound screened for gallstones in 1982-84 and again in 1993-94. Lifestyle data and blood samples were obtained and re-analyzed in 2004. Changes with age in physiology (body mass index, blood pressure, blood lipids, self-rated health), lifestyle (smoking, alcohol and coffee consumption, dietary habits, physical activity level), and indices of reproductive function (number of births, oral contraceptive use, hormone replacement therapy, male reproductive hormones) were explored in females and males separately. Adjusted logistic regression analyses were performed. Incident gallstones (gallstones and cholecystectomy) at ultrasound examination in participants initially free of gallstones at baseline occurred in 9.9% of the study population. In females, increasing alcohol consumption (odds ratio (OR) 0.94, 95% confidence interval (CI) [0.90; 0.98]) and the cessation of hormone replacement therapy (OR 0.29, 95% CI [0.10; 0.83]) inversely determined incident gallstones. In males, increasing levels of SHBG (OR 0.97, 95% CI [0.94; 0.998]) inversely determined incident gallstones. Other changes with age in physiology, lifestyle, or reproductive hormones were not associated. High baseline free testosterone determined incident gallstones in males (OR 1.15, 95% CI [1.02; 1.30]). To conclude, changes with age in alcohol consumption in females and in reproductive hormones determined incident gallstones. Male reproductive hormones seem to have an impact on incident gallstones. Sex differences should be explored further in future studies.

Do high participation rates improve effects of population-based general health checks?

The aim is to investigate if the effect of a health check differs between areas with different participation rates. The Inter99 population-based randomized lifestyle intervention study covered 73 areas within the suburbs of Copenhagen, Denmark. Adults aged 30-60years were randomly drawn from a population and were randomized to intervention group (n=11,483) or control group (n=47,122). Participation rates in the health check varied considerably between areas (mean 52%; range 35-85%). In separate survival analyses, area participation rate was included both as a continuous exposure variable and as a categorical variable (tertiles; low: 35-49%, meddle: 50-54%, high: 55-84%). All persons in the intervention and control group were followed in registers for 10-year total mortality and combined events (ischemic heart disease, stroke, or both). In adjusted models (including sociodemographic variables, ethnicity, number of children and comorbidity), among men, there was no difference in risk of death between areas with varying participation rates. Surprisingly, among women living in high-participation areas a significantly higher risk of all-cause mortality (HR: 1.32 [1.03-1.69]) was found in the intervention group (ref=controls). For both men and women, in no areas there was any difference between intervention and control group in incident IHD/stroke. Higher participation rates in population based health checks is probably unlikely to improve the effects of these, and may in worst case be harmful in subgroups of the population. Further well-designed studies within non-participation research should have high priority and are required to establish link between health checks and risk of death in subgroups of the population.

Analysis of Translocation-Competent Secretory Proteins by HDX-MS.

Protein folding is an intricate and precise process in living cells. Most exported proteins evade cytoplasmic folding, become targeted to the membrane, and then trafficked into/across membranes. Their targeting and translocation-competent states are nonnatively folded. However, once they reach the appropriate cellular compartment, they can fold to their native states. The nonnative states of preproteins remain structurally poorly characterized since increased disorder, protein sizes, aggregation propensity, and the observation timescale are often limiting factors for typical structural approaches such as X-ray crystallography and NMR. Here, we present an alternative approach for the in vitro analysis of nonfolded translocation-competent protein states and their comparison with their native states. We make use of hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS), a method based on differentiated isotope exchange rates in structured vs unstructured protein states/regions, and highly dynamic vs more rigid regions. We present a complete structural characterization pipeline, starting from the preparation of the polypeptides to data analysis and interpretation. Proteolysis and mass spectrometric conditions for the analysis of the labeled proteins are discussed, followed by the analysis and interpretation of HDX-MS data. We highlight the suitability of HDX-MS for identifying short structured regions within otherwise highly flexible protein states, as illustrated by an exported protein example, experimentally tested in our lab. Finally, we discuss statistical analysis in comparative HDX-MS. The protocol is applicable to any protein and protein size, exhibiting slow or fast loss of translocation competence. It could be easily adapted to more complex assemblies, such as the interaction of chaperones with nonnative protein states.

Clopidogrel-Paclitaxel Drug-Drug Interaction: A Pharmacoepidemiologic Study.

Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-ß-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age- and sex-matched controls treated with paclitaxel and low-dose aspirin. By a cumulative dose of 1,500 mg paclitaxel, 35% of the patients had developed severe neuropathy. The overall hazard ratio between clopidogrel use and severe paclitaxel neuropathy was 1.7 (95% confidence interval, 0.9-3.0). Among those receiving a high-dose paclitaxel regimen, the hazard ratio was 2.3 (95% confidence interval, 1.1-4.5). Our study indicates that clopidogrel is associated with a clinically relevant increased risk of neuropathy in patients treated with high-dose paclitaxel.

A genetic risk score of 45 coronary artery disease risk variants associates with increased risk of myocardial infarction in 6041 Danish individuals.

BACKGROUND: In Europeans, 45 genetic risk variants for coronary artery disease (CAD) have been identified in genome-wide association studies. We constructed a genetic risk score (GRS) of these variants to estimate the effect on incidence and clinical predictability of myocardial infarction (MI) and CAD. METHODS: Genotype was available from 6041 Danes. An unweighted GRS was constructed by making a summated score of the 45 known genetic CAD risk variants. Registries provided information (mean follow-up = 11.6 years) on CAD (n = 374) and MI (n = 124) events. Cox proportional hazard estimates with age as time scale was adjusted for sex, BMI, type 2 diabetes mellitus and smoking status. Analyses were also stratified either by sex or median age (below or above 45 years of age). We estimated GRS contribution to MI prediction by assessing net reclassification index (NRI) and integrated discrimination improvement (IDI) added to the European SCORE for 10-year MI risk prediction. RESULTS: The GRS associated significantly with risk of incident MI (allele-dependent hazard ratio (95%CI): 1.06 (1.02-1.11), p = 0.01) but not with CAD (p = 0.39). Stratification revealed association of GRS with MI in men (1.06 (1.01-1.12), p = 0.02) and in individuals above the median of 45.11 years of age (1.06 (1.00-1.12), p = 0.03). There was no interaction between GRS and gender (p = 0.90) or age (p = 0.83). The GRS improved neither NRI nor IDI. CONCLUSION: The GRS of 45 GWAS identified risk variants increase the risk of MI in a Danish cohort. The GRS did not improve NRI or IDI beyond the performance of conventional European SCORE risk factors.

Nationwide time trends and risk factors for in-hospital falls-related major injuries.

BACKGROUND: Accidental falls during hospitalisation have a range of complications and more information is needed to improve prevention. We investigated patterns of in-hospital fall-related major injuries in the period 2000-2012 and the association between chronic conditions and in-hospital fall-related major injuries. METHODS: Using administrative databases, patients aged 65+ years with in-hospital falls causing fractures or head injuries with need for surgery or intensive observation were identified as cases and were individually matched with five controls. Joinpoint regression was used to examine time trends and conditional logistic regression was used to analyse odds ratio (OR) for in-hospital falls-related major injuries according to a range of comorbidities. RESULTS: Four thousand seven hundred and fifty-four cases were identified from 2000 to 2012 and the most common injury was femur fracture (61.55%). For individuals aged 65-74 and 75+ years, the incidence of in-hospital falls-related major injuries per 100,000 hospital days increased significantly in 2000-2012 (average annual change: 3.2%, CI: 0.6-5.8) and 2007-2012 (average annual change: 11.4%, CI: 5.7-17.5), respectively. Significantly increased OR for in-hospital fall-related major injuries were found for individuals with dementia (OR = 2.34, CI: 1.87-2.92), osteoporosis (OR = 1.68, CI: 1.43-1.99), stroke (OR = 1.63, CI: 1.41-1.88), depression (OR = 1.24, CI: 1.09-1.41), chronic obstructive pulmonary disease (OR = 1.18, CI: 1.01-1.39) and Parkinson disease (OR = 1.17, CI: 1.01-1.34). CONCLUSIONS: In-hospital falls-related major injuries increased significantly during the study period. Elderly with dementia, osteoporosis, stroke, depression, chronic obstructive pulmonary disease and Parkinson disease were associated with increased OR for in-hospital fall-related major injuries. Increased focus on patients with these comorbidities is warranted to decrease the increasing incidence in in-hospital major injuries.

Filaggrin loss-of-function mutations and incident cancer: a population-based study.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. OBJECTIVES: To investigate the association of the FLG genotype and cancer types in four population-based cohorts. METHODS: A total of 13,376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. RESULTS: There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. CONCLUSIONS: The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses.

Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice.

Most systemic autoimmune diseases occur more frequently in females than in males. This is particularly evident in Sjögren's syndrome, systemic lupus erythromatosis (SLE) and thyroid autoimmunity, where the ratio of females to males ranges from 20:1 to 8:1. Our understanding of the etiology of SLE implies important roles for genetics, environmental factors and sex hormones, but the relative significance of each remains unknown. Using the New Zealand hybrid mouse model system of SLE, we present here a new fetal liver chimera-based system in which we can segregate effects of immune system genes from that of sex hormones in vivo. We show that female hematopoietic cells express an intrinsic capacity to drive lupus-like disease in both male and female recipient mice, suggesting that this capacity is hormone independent. Particularly, only chimeric mice with a female hematopoietic system showed significantly increased numbers of germinal center B cells, memory B cells and plasma cells followed by a spontaneous loss of tolerance to nuclear components and hence elevated serum antinuclear autoantibodies. A protective effect of testosterone was noted with regard to disease onset, but not disease incidence. Thus, genetic factors encoded within the female hematopoietic system can effectively drive lupus-like disease even in male recipients.

The effect of GWAS identified BMI loci on changes in body weight among middle-aged Danes during a five-year period.

OBJECTIVE: Genome-wide association studies have identified genetic variants associating with BMI, however, it is un-clarified whether the same variants also influence body weight fluctuations. METHODS: Among 3,982 adult individuals that attended both a baseline and a five-year follow-up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS. RESULTS: The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33-0.58) kg (P = 2.7 × 10(-12) ), corresponding to a body weight difference of 3.41 (2.21-4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed. CONCLUSION: The GRS associated with body weight cross-sectionally, but not with changes over a five-year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS.

Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele.

We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production. All participants had a 3-h oral glucose tolerance test (OGTT), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels (p = 0.030), reduced first-phase insulin response (p = 0.048), higher peripheral insulin sensitivity (p = 0.050) and lower fasting GIP concentrations (p = 0.003) than CC allele carriers. The latter was also reflected by lower total GIP secretion during the OGTT (p = 0.018). We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1 between the groups. The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.

International Children's Continence Society's recommendations for therapeutic intervention in congenital neuropathic bladder and bowel dysfunction in children.

PURPOSE: We present a consensus view of members of the International Children's Continence Society on the therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. MATERIAL AND METHODS: Discussions were held by a group of pediatric urologists and gastroenterologists appointed by the board. The following draft review document was open to all the ICCS members via the ICCS web site. Feedback was considered by the core authors and by agreement, amendments were made as necessary. The final document is not a systematic literature review. It includes relevant research when available as well as expert opinion on the current understanding of therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. RESULTS: Guidelines on pharmalogical and surgical intervention are presented. First the multiple modalities for intervention that do not involve surgical reconstruction are summarized concerning pharmacological agents, medical devices, and neuromodulation. The non-surgical intervention is promoted before undertaking major surgery. Indicators for non-surgical treatments depend on issues related to intravesical pressure, upper urinary tract status, prevalence of urinary tract infections, and the degree of incontinence. The optimal age for treatment of incontinence is also addressed. This is followed by a survey of specific treatments such as anticholinergics, botulinum-A toxin, antibiotics, and catheters. Neuromodulation of the bladder via intravesical electrical stimulation, sacral nerve stimulation, transcutaneous stimulation, and biofeedback is scrutinized. Then follows surgical intervention, which should be tailored to each individual, based on careful consideration of urodynamic findings, medical history, age, and presence of other disability. Treatments mentioned are: urethral dilation, vesicostomy, bladder, augmentation, fascial sling, artificial urinary sphincters, and bladder neck reconstruction and are summarized with regards to success rates and complications. Finally, the treatment on neuropathic bowel dysfunction with rectal suppositories irrigation and transrectal stimulation are scrutinized.

Insulin-like growth factor I and anthropometric parameters in a Danish population.

During the last decade several studies indicated that low insulin-like growth factor (IGF) I levels are related to higher risk of cardiovascular disease and mortality. Obesity represents one further main cardiovascular risk factor which might also be related to IGF-I. The objective of the present study was to analyse the associations between anthropometric measures and IGF-I levels in a population-based sample. From the Danish cross-sectional Health2006 study 3,328 subjects (1,835 women; 1,493 men) aged 19-72 years were included in the analyses. Serum IGF-I levels were determined by an immunoassay. Body height, weight as well as waist and hip circumferences were measured. Body-mass-index, waist-to-hip ratio and waist-to-height ratio were calculated. Circulating IGF-I levels were inversely associated with all anthropometric markers as evaluated by linear regression adjusting for age, alcohol consumption, smoking and physical activity. Our large cross-sectional study suggests that IGF-I may serve as the link between obesity and mortality although any causal relation cannot be inferred and longitudinal analyses are needed to clarify the causal relation.

Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality.

BACKGROUND: Aims of this study were to describe the prevalence of comorbidity in newly diagnosed elderly cancer cases compared with the background population and to describe its influence on overall and cancer mortality. METHODS: Population-based study of all 70+ year-olds in a Danish province diagnosed with breast, lung, colorectal, prostate, or ovarian cancer from 1 January 1996 to 31 December 2006. Comorbidity was measured according to Charlson's comorbidity index (CCI). Prevalence of comorbidity in newly diagnosed cancer patients was compared with a control group by conditional logistic regression, and influence of comorbidity on mortality was analysed by Cox proportional hazards method. RESULTS: A total of 6325 incident cancer cases were identified. Elderly lung and colorectal cancer patients had significantly more comorbidity than the background population. Severe comorbidity was associated with higher overall mortality in the lung, colorectal, and prostate cancer patients, hazard ratios 1.51 (95% CI 1.24-1.83), 1.41 (95% CI 1.14-1.73), and 2.14 (95% CI 1.65-2.77), respectively. Comorbidity did not affect cancer-specific mortality in general. CONCLUSION: Colorectal and lung cancer was associated with increased comorbidity burden in the elderly compared with the background population. Comorbidity was associated with increased overall mortality in elderly cancer patients but not consistently with cancer-specific mortality.

Determinants of vitamin D status in a general population of Danish adults.

BACKGROUND AND AIMS: Danish legislation regarding food fortification has been very restrictive and vitamin D deficiency is thought to be common in Denmark due to inadequate dietary intakes and the fact that in Denmark (latitude 56°N) vitamin D is only synthesized in the skin after exposure to solar radiation during summertime (April-September). The purpose of this study was to evaluate the vitamin D status of a general adult population in Denmark and, in addition, associations between vitamin D status and distinct lifestyle factors were studied. METHODS: A random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001. Serum samples from all participants were stored and levels of 25-hydroxyvitamin D (25(OH)D) were measured by HPLC in 2009. The method was compared to another HPLC method. Information on dietary intake of vitamin D and other lifestyle factors were obtained by questionnaires. A total of 6146 persons defined as ethnic Danes and with successful measurements of 25(OH)D were included in the analyses. RESULTS: The overall prevalence of vitamin D deficiency (25(OH)D<25 nmol/l) and insufficiency (25(OH)D<50 nmol/l) were 13.8% and 52.2%, respectively. A marked seasonal fluctuation was seen in serum levels of 25(OH)D - median values of 25(OH)D were lowest in February and highest in August. In multiple logistic regression models (n=5506), low vitamin D status was significantly associated with obesity (BMI≥30), daily smoking and a sedentary lifestyle. However, measurements of 25(OH)D were not associated with the estimated dietary intake of vitamin D. Comparison of two HPLC methods demonstrated considerable differences in accuracy. DISCUSSION AND CONCLUSIONS: Our results suggest that poor vitamin D status is common among adults in a Northern European country without food fortification with vitamin D. Methodological issues are, however, of great importance when using cut-off values to define poor vitamin D status. In addition, we demonstrated that low serum levels of 25(OH)D were associated with several lifestyle factors.

[Population-level changes to promote cardiovascular health]. / Zmeny na úrovni populace zamerené na podporu kardiovaskulárního zdraví

BACKGROUND: Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. DESIGN AND METHODS: Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). RESULTS: Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. CONCLUSION: Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.