Improving neuromuscular monitoring and reducing residual neuromuscular blockade via e-learning: A multicentre interrupted time-series study (INVERT study).

BACKGROUND: Neuromuscular monitoring should be applied routinely to avoid residual neuromuscular block. However, anaesthetists often refrain from applying it, even when the equipment is available. We aimed to increase neuromuscular monitoring in six Danish anaesthesia departments via e-learning. METHODS: Interrupted time series study, with baseline data from a previous study and prospective data collection after implementation of the module, which was available for 2 weeks from 21 November 2016. We included all patients receiving general anaesthesia with muscle relaxants until 30 April 2017. Main outcome was application of acceleromyography, grouped as succinylcholine only and non-depolarising relaxants. Secondary outcomes were last recorded train-of-four ratio (non-depolarising) relaxants and score on a ten-question pre- and post-course multiple-choice test. RESULTS: The post-intervention data consisted of 6525 cases (3099 (48%) succinylcholine only, 3426 (52%) non-depolarising relaxants). Analysing all departments, we found a positive pre-intervention trend in application of acceleromyography for both groups, of estimated 7.5% and 4.8% per year, respectively (p < .001). The monitoring rate increased significantly for succinylcholine in two departments post-intervention (p = .045 and .010), and for non-depolarising relaxants in one department (p = .041), but followed by a negative trend of -37.0% per year (p = .041). The rate was already close to 90% at the time of the intervention and the mean last recorded train-of-four ratio was 0.97 (SD 0.21), also without a significant change. The median score on the post-course test increased from 7 (IQR 5-8) to 9 (IQR 8-10) (p < .001, Wilcoxon Signed-Ranks Test). CONCLUSION: We found no overall effect of the e-learning module on application of neuromuscular monitoring, although the post-course test indicated an effect on anaesthetists' knowledge in this field. TRIAL REGISTRATION: Trial registration: Clinicaltrials.gov identifier: NCT02925143. https://clinicaltrials.gov/ct2/show/NCT02925143.

Pregabalin alleviates clinical signs of syringomyelia-related central neuropathic pain in Cavalier King Charles Spaniel dogs: a randomized controlled trial.

OBJECTIVE: We aimed to assess the efficacy and benefit-risk profile of pregabalin (PGN) to reduce the clinical signs of central neuropathic pain (CNeP) as reflected by scratching episodes in dogs with symptomatic syringomyelia (SM). STUDY DESIGN: Randomized, double-blind, placebo-controlled crossover study. ANIMALS: A total of 12 client-owned Cavalier King Charles Spaniels (age, 1.1-7.4 years, bodyweight, 8.2-10.8 kg) with magnetic resonance imaging-confirmed SM and clinical signs of CNeP. METHODS: Dogs were randomized to either PGN 150 mg or placebo for 25 days, followed by 48 hour washout period before crossover to the alternate phase of 25 days. The primary outcome was defined as number of scratching events during 10 minutes of video-recorded physical activity. Treatment effect was estimated using a generalized estimation equation model. Benefit-risk and quality of life assessments were obtained through owner interviews focusing on potential adverse events. RESULTS: The treatment effect estimate was an 84% (95% confidence interval = 75-89%) reduction in mean number of scratching events relative to baseline compared with placebo (p < 0.0001). Owner-assessed satisfactory quality of life was status quo and rated as 'good' or 'could not be better' in six/11 dogs and improved in four/11 dogs. The most prevalent adverse events were increased appetite in nine/12 dogs and transient ataxia in nine/12 dogs. There was one dog withdrawn by the owner 7 days after crossover to PGN owing to persistent ataxia. No dogs needed rescue analgesia during the trial. CONCLUSIONS AND CLINICAL RELEVANCE: PGN is superior to placebo in the reduction of clinical signs of SM-related CNeP in dogs. At a dose range of 13-19 mg kg-1 orally twice daily, the encountered adverse events were acceptable to all but one owner.

Levcromakalim, an Adenosine Triphosphate-Sensitive Potassium Channel Opener, Dilates Extracerebral but not Cerebral Arteries.

BACKGROUND: ATP-sensitive potassium (KATP ) channel opener levcromakalim induces migraine attacks in migraine patients. Underlying mechanisms responsible for headache and migraine induction after levcromakalim infusion are unknown. OBJECTIVE: To investigate the effect of levcromakalim on the cranial arteries and to explore the possible relationship between the middle meningeal artery (MMA) dilation and headache. METHODS: In a double-blind, randomized, placebo-controlled study, 20 healthy volunteers were scanned at the baseline and repeatedly after infusion of levcromakalim (n = 14) and placebo (n = 6). All participants received a subcutaneous injection of sumatriptan 6 mg before the last scanning. RESULTS: The MMA circumference was significantly larger after levcromakalim compared with placebo (P < .0001). The MMA dilation lasted over 5 hours during observational period. We found a significant association between headache and MMA dilation (P < .0001). The superficial temporal artery (STA) circumference was significantly larger after levcromakalim compared with placebo (P = .03) over the initial period (110 minutes). Over the entire observational period, there was no difference in circumference of the STA and the middle cerebral artery (MCA) between levcromakalim and placebo. CONCLUSION: Levcromakalim dilated the MMA but not MCA. The MMA dilation was associated with headache. Future studies should investigate whether opening of KATP channels can activate and sensitize the perivascular nociceptors.

An Equine Wound Model to Study Effects of Bacterial Aggregates on Wound Healing.

Objective: Relevant animal models to study effects of bacterial aggregates on wound healing are lacking. We aimed at establishing an equine wound model with bacterial aggregates to investigate the impact of bacterial inoculation on normal (thorax) and impaired (limb) wound healing. Approach: Wounds were created on three limbs and both thorax sides of six horses. Twelve out of 20 wounds per horse were inoculated with 104 Staphylococcus aureus and 105 Pseudomonas aeruginosa on day 4. Healing was monitored until day 27 by clinical assessment, including wound scoring, surface pH measurements, and digital photography for area determination. Biopsies were used for bacterial culture and for peptide nucleic acid fluorescence in situ hybridization to detect bacterial aggregates. Results: Inoculated limb wounds healed slower than noninoculated limb wounds from day 10 onward (p < 0.0001). Inoculated and noninoculated thorax wounds healed equally well and faster than limb wounds. The odds ratio of detecting bacterial aggregates in inoculated limb wounds was 7.1 (2.4-21.0, p = 0.0086) compared with noninoculated limb wounds and 36.2 (3.8-348, p = 0.0018) compared with thorax wounds. Innovation: This equine wound model with bacterial aggregates might be superior to other animal wound models, as both normal and impaired healing can be studied simultaneously. In this model, many aspects of wound healing, including novel treatments, may be studied. Conclusions: The impaired healing observed in inoculated limb wounds may be related to the persistent bacterial aggregates. Both in capability of clearing inoculated bacteria from the wounds and in healing pattern, thorax wounds were superior to limb wounds.

Precision of automated QRS duration measurement in patients treated with cardiac resynchronization therapy.

PURPOSE: Shortening of the QRS duration (QRSd) is often used to guide device optimization and reprogramming in patients with cardiac resynchronization therapy (CRT). Detecting the small changes expected during reprogramming requires that the QRSd can be measured with high precision, but this has never been studied in patients with CRT. In this study, we wanted to assess the precision of automated QRSd measurement in patients treated with CRT using two commonly available electrocardiographs. METHODS: Patients treated with CRT were recruited during routine follow-up in our pacemaker clinic. In all participants, a number of immediate successive ECGs were recorded with the GE MAC 5500 (Mac55) and the GE MAC 1600 (Mac16). Data were analyzed with a linear mixed model. RESULTS: A total of 785 12-lead ECGs were recorded in 36 patients with an average of 11.2 and 10.6 ECGs per patient with the Mac55 and Mac16, respectively. The Mac55 measured the QRSd longer by 10.3 milliseconds (ms) (95% CI 7.1-13.5 ms, p < 0.001) and with significantly smaller standard deviation for repeated measurements (6.3 vs. 10.4 ms, p < 0.001). Limits of agreement were ± 17.5 and ± 28.8 ms for the Mac55 and Mac16, respectively. CONCLUSIONS: Automated measurement of QRSd in patients with CRT shows low precision with limits of agreement of ± 17.5 and ± 28.8 ms for repeated measurements in two commercially available electrocardiographs. Device programming solely by QRSd changes should be done with caution, and clinical effects should be demonstrated in future trials. Device programming based on QRSd changes should be done with caution until the ability of this measure to predict clinical outcome can be demonstrated in prospective study.

Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial.

OBJECTIVES: Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. METHODS: From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. RESULTS: AUCs of 0.826-0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. CONCLUSIONS: High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. KEY POINTS: • High accuracy in logistic modelling for lung cancer risk stratification of nodules. • Lung cancer risk prediction is primarily based on size of pulmonary nodules. • Nodule spiculation, age and family history of lung cancer are significant predictors. • Sex does not appear to be a useful risk predictor.

Analysis of FEV1 decline in relatively healthy heavy smokers: implications of expressing changes in FEV1 in relative terms.

Progressive decline in lung function has been widely accepted as the hallmark of chronic obstructive pulmonary disease (COPD); however, recent evidence indicates that the rate of decline measured as decline in forced expiratory volume in one second (FEV1) is higher in mild to moderate COPD than in severe COPD. Usually changes in FEV1 are measured in ml that is "absolute"; however, changes can also be measured "relative" as a percentage of the actual FEV1. We hypothesize that relative measurements could be more appropriate than absolute measurements for describing changes in lung function. We analyzed data from 3,218 relatively healthy heavy smokers who participated in the Danish Lung Cancer Screening Trial. The influences of age, sex, height, body mass index, smoking, and severity of airflow limitation on FEV1 were analyzed in mixed effects models. In absolute terms those with the best lung function consistently showed the steepest decline, whereas in relative terms most fast decliners are found among those with low lung function. Measuring changes in relative terms implied statistically significant acceleration of decline with advancing age, smoking (pack-years) and severity of airflow limitation. Relative measurements may lead to a better understanding of changes in lung function. Smoking and severity of airflow limitation speed up the loss of lung function, and this emphasizes the importance of abstaining from smoking the sooner the better. Measuring changes in relative terms could have important implications for the interpretation of results from clinical trials where FEV1 is the primary outcome. DLCST; www.ClinicalTrials.org , registration number: NCT00496977.

Sildenafil and diastolic dysfunction after acute myocardial infarction in patients with preserved ejection fraction: the Sildenafil and Diastolic Dysfunction After Acute Myocardial Infarction (SIDAMI) trial.

BACKGROUND: Diastolic dysfunction is frequently seen after myocardial infarction and is characterized by a disproportionate increase in filling pressure during exercise to maintain stroke volume. We hypothesized that sildenafil would reduce filling pressure during exercise in patients with diastolic dysfunction after myocardial infarction. METHODS AND RESULTS: Seventy patients with diastolic dysfunction and near normal left ventricular ejection fraction on echocardiography were randomly assigned sildenafil 40 mg thrice daily or matching placebo for 9 weeks. Before randomization and after 9 weeks of treatment patients underwent simultaneous echocardiography and right heart catheterization at rest and during exercise. Primary end point was pulmonary capillary wedge pressure, and secondary end points comprised cardiac index and pulmonary arterial pressure at rest and during exercise after 9 weeks. After 9 weeks there were no differences in pulmonary capillary wedge pressure at rest (13±4 versus 13±3 mm Hg, P=0.25) or at peak exercise (35±8 mm Hg versus 31±7 mm Hg, P=0.07). However, with treatment cardiac index increased at rest (P=0.006) and peak exercise (P=0.02) in the sildenafil group, and systemic vascular resistance index (resting, P=0.0002; peak exercise, P=0.007) and diastolic blood pressure (resting, P=0.005; peak exercise, P=0.02) were lower in the sildenafil group. Resting left ventricular end-diastolic volume index increased (P=0.001) within the sildenafil group but was unchanged in the placebo group. CONCLUSIONS: Sildenafil did not decrease filling pressure at rest or during exercise in post-myocardial infarction patients with diastolic dysfunction. However, there were effects on secondary end points, which require further studies.

Low frequency oscillations in cephalic vessels assessed by near infrared spectroscopy.

BACKGROUND AND METHODS: Low frequency oscillations (LFO) of cerebral vessels are believed to reflect cerebral autoregulation. We investigated day-to-day and hemispheric variations in 0.1 Hz LFO with near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) to determine phase shift and gain of oxygenated haemoglobin (oxyHb) and the velocity of the middle cerebral artery (Vmca) to the arterial blood pressure (ABP). The direct left-right phase shifts of oxyHb and Vmca were also assessed. We examined 44 healthy volunteers by simultaneous recordings of ABP, oxyHb and Vmca during spontaneous and paced breathing at 6 breaths per minute on two separate days. RESULTS: The variation between hemispheres had a prediction interval (PI) of ± 39° for ABP-oxyHb phase shift and ± 69% for gain. ABP-Vmca showed ± 57° PI phase shift and ± 158% PI for gain. The variation from day to day showed ± 61° PI for ABP-oxyHb phase shift and ± 297% PI for gain. ABP-Vmca showed ± 45° PI phase shift and ± 166% PI for gain. We found a linear relation between phase shift of oxyHb and Vmca at paced breathing (P=0.0005), but not at rest (P=0.235). CONCLUSION: Our results show that LFO phase shift ABP-oxyHb may be used as a robust measurement of differences in autoregulation between hemispheres and over time. In addition, we found a strong relation between oxyHb and Vmca during paced breathing. Gain showed too large variation for clinical use, as the SD was up to 100-fold of mean values.

A prospective comparison of 18F-FDG PET/CT and CT as diagnostic tools to identify the primary tumor site in patients with extracervical carcinoma of unknown primary site.

BACKGROUND: The aim of the present study was to evaluate prospectively the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and conventional CT regarding the ability to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP) site. PATIENTS AND METHODS: From January 2006 to December 2010, 136 newly diagnosed CUP patients with extracervical metastases underwent (18)F-FDG PET/CT. A standard of reference (SR) was established by a multidisciplinary team to ensure that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP), true-negative, false-negative, and false-positive results. RESULTS: SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between (18)F-FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy. CONCLUSION: In the general CUP population with multiple extracervical metastases (18)F-FDG PET/CT does not represent a clear diagnostic advantage over CT alone regarding the ability to detect the primary tumor site.

Factors influencing the decline in lung density in a Danish lung cancer screening cohort.

Lung cancer screening trials provide an opportunity to study the natural history of emphysema by using computed tomography (CT) lung density as a surrogate parameter. In the Danish Lung Cancer Screening Trial, 2,052 participants were included. At screening rounds, smoking habits were recorded and spirometry was performed. CT lung density was measured as the volume-adjusted 15th percentile density (PD15). A mixed effects model was used with former smoking males with <30 pack-yrs and without airflow obstruction (AFO) at entry as a reference group. At study entry, 893 (44%) participants had AFO. For the reference group, PD15 was 72.6 g·L(-1) with an annual decline of -0.33 g·L(-1). Female sex and current smoking increased PD15 at baseline, 17.3 g·L(-1) (p<0.001) and 10 g·L(-1) (p<0.001), respectively; and both increased the annual decline in PD15 (female: -0.3 g·L(-1); current smoking: -0.4 g·L(-1)). The presence and severity of AFO was a strong predictor of low PD15 at baseline (Global Initiative for Chronic Obstructive Lung Disease (GOLD) I: -1.4 g·L(-1); GOLD II: -6.3 g·L(-1); GOLD III: -17 g·L(-1)) and of increased annual decline in PD15 (GOLD I: -0.2 g·L(-1); GOLD II: -0.5 g·L(-1); GOLD III: -0.5 g·L(-1)). Female sex, active smoking and the presence of AFO are associated with accelerated decline in lung density.

Maternal use of nicotine replacement therapy during pregnancy and offspring birthweight: a study within the Danish National Birth Cohort.

Smoking is a well-established risk factor for fetal growth restriction and other adverse pregnancy outcomes, and nicotine may be one of the chemical compounds that drive these associations. Nicotine replacement therapy (NRT) is a smoking cessation aid, which can facilitate smoking cessation. It is, however, unknown whether NRT used during pregnancy impairs fetal growth. The aim of this study was to estimate the association between the use of NRT during pregnancy and offspring birthweight. The study population consisted of 72 761 women enrolled in the Danish National Birth Cohort between 1996 and 2002. Information on NRT and potential confounders was obtained from two computer-assisted telephone interviews conducted in the second and third trimesters, respectively. Multiple linear regression in a multilevel model was used to estimate the association between NRT use and birthweight adjusted for gestational age and potential confounders. The adjusted analyses showed no significant association between the duration of NRT use and birthweight (b = 0.25 g per week of NRT use [95% CI -2.31, 2.81]) and neither was the type of NRT product (patch, gum, inhaler) associated with reduced birthweight. However, simultaneous use of more than one NRT product was associated with reduced birthweight (b = -10.73 g per week of NRT use [95% CI -26.51, 5.05]), although the association was not statistically significant. The results of this study suggest that maternal use of NRT in pregnancy does not seriously affect birthweight, but there could be a negative effect on birthweight associated with simultaneous use of more than one type of NRT product.

Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study.

RATIONALE: Early diagnosis and treatment is considered important to prevent lung damage in primary ciliary dyskinesia (PCD). OBJECTIVES: Few studies have addressed long-term evolution of lung function after PCD diagnosis. We investigated whether long-term lung function was dependent on age or level of lung function at PCD diagnosis. METHODS: An observational, single-center, cross-sectional, and three-decade longitudinal study of FEV(1) and FVC related to age at diagnosis until current age was performed. Linear regression was used to describe the relation between first measured lung function values and age at diagnosis across the cohort. Courses of lung function after diagnosis and the according slopes were used to group patients into increasing, stable, or decreasing courses. Additionally, slopes from courses of 10 years of follow-up were related to age at diagnosis and initial level of lung function, respectively, using linear regression. MEASUREMENTS AND MAIN RESULTS: Seventy-four children and adults with PCD were observed for median 9.5 (range, 1.5-30.2) years during which 2,937 lung function measurements were performed. First measured FEV(1) was less than 80% of predicted in one-third of preschool-diagnosed children. During observation, 34% of patients lost more than 10 percentage points, 57% were stable, and 10% improved more than 10 percentage points in FEV(1). Courses of lung function after diagnosis were related to neither age at diagnosis nor initial level. CONCLUSIONS: Our study strongly suggests that PCD is a disease of serious threat to lung function already at preschool age, and with a high degree of variation in courses of lung function after diagnosis that was not linked to either age or level of lung function at diagnosis. Early diagnosis did not protect against decline in lung function.

The effect of inhaled corticosteroids on the development of emphysema in smokers assessed by annual computed tomography.

The objective was to evaluate the effect of inhaled corticosteroids on disease progression in smokers with moderate to severe chronic obstructive pulmonary disease (COPD), as assessed by annual computed tomography (CT) using lung density (LD) measurements. Two hundred and fifty-four current smokers with COPD were randomised to treatment with either an inhaled corticosteroids (ICS), budesonide 400 microg bid, or placebo. COPD was defined as FEV(1) < or = 70% pred, FEV(1)/FVC < or = 60% and no reversibility to beta(2)-agonists and oral corticosteroids. The patients were followed for 2-4 years with biannual spirometry and annual CT and comprehensive lung function tests (LFT). CT images were analysed using Pulmo-CMS software. LD was derived from a pixel-density histogram of the whole lung as the 15th percentile density (PD15) and the relative area of emphysema at a threshold of -910 Hounsfield units (RA-910), and both were volume-adjusted to predicted total lung capacity. At baseline, mean age was 64 years and 64 years; mean number of pack-years was 56 and 56; mean FEV(1) was 1.53 L (51% pred) and 1.53 L (53% pred); mean PD15 was 103 g/L and 104 g/L; and mean RA-910 was 14% and 13%, respectively, for the budesonide and placebo groups. The annual fall in PD15 was -1.12 g/L in the budesonide group and -1.81 g/L in the placebo group (p = 0.09); the annual increase in RA-910 was 0.4% in the budesonide group and 1.1% in the placebo group (p = 0.02). There was no difference in annual decline in FEV(1) between ICS (-54 mL) and placebo (-56 mL) (p = 0.89). Long-term budesonide inhalation shows a non-significant trend towards reducing the progression of emphysema as determined by the CT-derived 15th percentile lung density from annual CT scans in current smokers with moderate to severe COPD.

Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study.

Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants. This 1-year-long randomised double-blinded placebo-controlled intervention with vitamin D3 (10 and 20 microg/d) included girls (10.1-14.7 years), women (18.1-52.7 years) and men (17.9-63.5 years) of Pakistani origin living in Denmark. The main endpoints were serum 25-hydroxyvitamin D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone concentrations decreased at 6 months, but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine.

Cerebral 5-HT2A receptor binding is increased in patients with Tourette's syndrome.

Experimental and clinical data have suggested that abnormalities in the serotonergic neurotransmissions in frontal-subcortical circuits are involved in Tourette's syndrome. To test the hypothesis that the brain's 5-HT2A receptor binding is increased in patients with Tourette's syndrome, PET imaging was performed. Twenty adults with Tourette's syndrome and 20 healthy control subjects were investigated with PET-[18F]altanserin using a bolus-infusion protocol. Regions of interest were delineated automatically on co-registered MRI images, and partial volume-corrected binding parameters were extracted from the PET images. Comparison between control subjects and Tourette's syndrome patients showed increased specific [18F]altanserin binding, not only in the a-priori selected brain regions hypothesized to be involved in Tourette's syndrome, but also post-hoc analysis showed a global up-regulation when testing for a overall difference with a randomization test (p<0.03). Increased 5-HT2A receptor binding was found not only in regions closely related to subcortical regions in patients with Tourette's syndrome, but also in most other brain regions. Our data suggest that the serotonergic transmitter system is pathophysiologically involved in Tourette's syndrome and that a clinical trial with 5-HT2A receptor antagonists may be justified.

Prevalence and bother of nocturia, and causes of sleep interruption in a Danish population of men and women aged 60-80 years.

OBJECTIVE: To study the prevalence and bother of nocturia, and sleep interruptions in an unselected population of Danish men and women aged 60-80 years. SUBJECTS AND METHODS: A postal questionnaire was sent to 2000 women and 2000 men aged 60, 65, 70, 75, and 80 years. The population was selected at random from The Danish Civil Registration System, in which every person living in Denmark is identified. The Nocturia, Nocturnal Enuresis and Sleep-interruption Questionnaire (NNES-Q) was used to evaluate nocturia and bother, and sleep interruptions. Nocturia was defined as waking at night to void, according to the International Continence Society definition. RESULTS: In all, 92% (3664) subjects returned the questionnaire; 71% completed the questionnaire satisfactorily and were included in the study. The prevalence of nocturia increased with age. The overall prevalence of nocturia was 77% and there was no difference between men and women (P = 0.11), but men had slightly more severe nocturia than women. The bother caused by nocturia in men and women increased with the severity of nocturia, and women were slightly more bothered than men when the degree of nocturia was >2 voids/night. Nocturia was the most frequent self-reported reason for waking at night, followed by thirst. CONCLUSION: The prevalence of nocturia increased with age. There was no difference between the genders in the overall prevalence of nocturia, but nocturia of > or = 2 voids/night was more frequent in men. The degree of bother increased with the severity of nocturia, even after correcting for generic quality of life, and the younger groups were the most bothered. Nocturia was the major reason for waking at night, followed by thirst.

A 72-year-old Danish puzzle resolved--comparative analysis of phenotypes in families with different-sized HOXD13 polyalanine expansions.

A phenotype-genotype correlation was previously described for carriers of different sized of polyalanine expansions in HOXD13. We report on a detailed comparison of 55 members (approximately 220 limbs) from 4 Danish families with duplications of 21 or 27 bp, expanding the polyalanine repeat from 15 to 22 and 24 residues, respectively. Two of these were previously described by Danish pioneers of human genetics, Tage Kemp and Oluf Thomsen. A clinical score was assigned to each limb based on manifestations assumed to represent different degrees of a duplication defect in hand rays 3-4 and foot rays 4-5. The length of metacarpals and phalangeal bones in rays 1, 2, and 5 was measured on hand radiographs and converted to Z-scores. The relative difference between corresponding right and left bones and directional, total, and fluctuating asymmetry was calculated for each individual. All of these parameters were compared between carriers of the +9 alanine expansion, the +7 alanine expansion, and non-mutation carriers with affected parents from the two families. Upper limb scores and the rate of abnormal bones (>2SD) were significantly higher in the first group than in the others. The first metacarpal and the middle phalanx of the little finger were significantly shorter, and the proximal phalanx of the index finger was significantly longer in this group than in the others. An increased level of total and fluctuating asymmetry was observed in long expansion carriers. Thus, our data have added evidence to the phenotype-genotype correlation previously reported, which was further extended to include lesser involvement of bones in ray 1, 2, and 5.

Late urologic morbidity in 177 consecutive patients after radiotherapy for cervical carcinoma: a longitudinal study.

PURPOSE: To provide longitudinal data on urologic morbidity after radiotherapy and brachytherapy for cervical carcinoma. METHODS AND MATERIALS: Five-year longitudinal urologic morbidity data were recorded from 177 consecutive patients of median age 59 years (range: 22-86 years) with cervical carcinoma receiving radiotherapy with curative intent at the Copenhagen University Hospital, Denmark. FIGO stages (%) were as follows: Stage I (15), Stage II (30), Stage III (54), and Stage IV (1). Late morbidity was calculated as cumulative incidence based on actuarial estimates. RESULTS: The 5-year cumulative incidence based on actuarial estimates of urologic morbidity Grades 1 + 2 + 3, Grades 2 + 3, and Grade 3 were 62%, 32%, and 5%, respectively. Frequencies of urologic morbidity in the 54 recurrence-free survivors at the end of follow-up indicated some reversibility in the case of Grades 1 and 2 morbidity. CONCLUSION: With the longitudinal design used in the present study, a rate of mild and moderate morbidity higher than that found in most of the previously reported literature was observed, giving cause for concern and underlining the importance of further longitudinal studies on this subject, specifically studies that relate to the background urologic morbidity in the female population, as well as to the fact that urologic morbidity might regress.

Persistent high incidence of tuberculosis in immigrants in a low-incidence country.

Immigration from areas of high incidence is thought to have fueled the resurgence of tuberculosis (TB) in areas of low incidence. To reduce the risk of disease in low-incidence areas, the main countermeasure has been the screening of immigrants on arrival. This measure is based on the assumption of a prompt decline in the incidence of TB in immigrants during their first few years of residence in a country with low overall incidence. We have documented that this assumption is not true for 619 Somali immigrants reported in Denmark as having TB. The annual incidence of TB declined only gradually during the first 7 years of residence, from an initial 2,000 per 100,000 to 700 per 100,000. The decline was described by an exponential function with a half-time of 5.7 (95% confidence interval 4.0 to 9.7) years. This finding seriously challenges the adequacy of the customary practice of screening solely on arrival.