Regional Hospital Holstebro

The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.

BACKGROUND: Patients with obstructive sleep apnea (OSA) are at increased risk for hypertension. The mechanisms responsible for the development of hypertension are controversial. We hypothesized that patients with OSA had an abnormal 24-h blood pressure (BP) and an abnormal activity in vasoactive hormones, and that both BP and hormones were normalized during treatment with long-term nasal continuous positive airway pressure (CPAP). METHODS: The 24-h BP and plasma levels of the vasoactive hormones (renin, angiotensin II, aldosterone, atrial natriuretic peptide, brain natriuretic peptide, vasopressin, and endothelin-1) were measured in 24 patients with OSA and in 18 control subjects. Thirteen patients with OSA were reexamined after 14 months of CPAP therapy. RESULTS: Patients with OSA had significantly increased BP and heart rate and a reduced nocturnal BP drop. Both angiotensin II (13.3 +/- 1.6 v 7.8 +/- 1.0 pmol/L) and aldosterone (94.0 +/- 9.4 v 62.2 +/- 4.5 pmol/L) were significantly higher in OSA than in control subjects. Positive correlations were found between angiotensin II and daytime BP (systolic: r = 0.49, P <.01; diastolic: r = 0.52, P <.01). The CPAP therapy resulted in a decrease in BP, and this CPAP-induced reduction in BP was correlated with a decrease in both plasma renin (r = 0.76 to 0.92, all P <.01) and plasma angiotensin II concentration (r = 0.58 to 0.81, all P <.05). CONCLUSIONS: Plasma angiotensin II and aldosterone were elevated in OSA, and plasma angiotensin II was correlated with BP. Long-term CPAP reduced BP, and this decrease in BP was correlated with the reductions in plasma renin and angiotensin II levels. We suggest that OSA mediates hypertension, at least in part, via a stimulation of angiotensin II production.

IMPORTANCE: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear. OBJECTIVE: To systematically review whether supplementation with vitamin D or its analogues reduce BP. DATA SOURCES: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014. STUDY SELECTION: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms. DATA EXTRACTION AND SYNTHESIS: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model. MAIN OUTCOMES AND MEASURES: Difference in SBP and DBP measured in an office setting. RESULTS: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, -0.8 to 0.8] mm Hg; P=.97; I2=21%) or DBP (effect size, -0.1 [95% CI, -0.6 to 0.5] mm Hg; P=.84; I2=20%). Similar results were found analyzing individual patient data for SBP (effect size, -0.5 [95% CI, -1.3 to 0.4] mm Hg; P=.27; I2=0%) and DBP (effect size, 0.2 [95% CI, -0.3 to 0.7] mm Hg; P=.38; I2=0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy. CONCLUSIONS AND RELEVANCE: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.

Since Robert Koch described the cause of tuberculosis in 1882, the natural history of the disease after primary infection has been subject to debate. Only approximately 10% of infected individuals develop active disease, which may appear years to decades after infection. Late onset has been attributed to the endogenous reactivation of dormant bacteria. However, this has not been documented by molecular means for latencies of more than a few years. In Denmark, we have recently recultured 205 freeze-dried Mycobacterium tuberculosis strains obtained from 1961 through 1967. These "historical" strains are analyzed by DNA restriction fragment-length polymorphism testing, and their DNA patterns are compared with those of 4008 recently obtained clinical specimens. This has, surprisingly, yielded molecular evidence of M. tuberculosis reactivation after 33 years of latent infection. A father and son who developed tuberculosis in 1961 and in 1994, respectively, were the only patients infected with strains that share an identical DNA pattern.

BACKGROUND: Accelerated perioperative rehabilitation protocols following total hip and knee arthroplasties are currently being implemented worldwide, but the cost-effectiveness of these protocols from a societal perspective is not known. We compared the cost-effectiveness of an accelerated perioperative care and rehabilitation protocol with that of a more standard protocol for patients treated with total hip and knee arthroplasty. METHODS: A cost-effectiveness study was undertaken as a study piggybacked on a randomized clinical trial comparing early outcomes of an accelerated and intensive postoperative rehabilitation regimen with those of a more standard rehabilitation protocol. We assessed eighty-seven patients (forty-two who received the standard protocol and forty-five who received the accelerated protocol) for a total of twelve months. Costs from the time of the patient's visit immediately before the operation to one year postoperatively were calculated with use of activity-based costing analysis. Postoperative quality-adjusted life-years (QALYs) were calculated from validated patient diaries and questionnaires at fifteen time points. The primary objective was to determine whether one intervention was dominant over the other during a twelve-month period or, if neither was dominant, to determine the incremental cost-effectiveness ratio. RESULTS: The result of the randomized clinical trial showed the accelerated intervention to be effective, with a reduction in the length of the hospital stay and a gain in health-related quality of life at the three-month follow-up time point. The cost-effectiveness study showed the accelerated protocol to be significantly less expensive than the standard protocol (p=0.036), with an average reduction in cost of 18,880 Danish kroner (95% confidence interval, 1899 to 38,152) (approximately US $4000). Patients treated with the accelerated protocol following hip arthroplasty had an additional average gain of 0.08 QALY (95% confidence interval, 0.02 to 0.15) compared with the patients who received the standard protocol (p=0.006); this led to a 98% dominance of the accelerated protocol over the standard protocol. No significant or clinically relevant difference in the numbers of QALYs associated with the two protocols was observed for the patients treated with knee arthroplasty. CONCLUSIONS: An accelerated perioperative care and rehabilitation protocol can be both cost-saving and clinically more effective after total hip arthroplasty, whereas it can be cost-saving with no observed significant difference in effect, from a societal perspective, after knee arthroplasty.

BACKGROUND: Low 25-hydroxy-vitamin D (25(OH)D) levels are inversely related to blood pressure (BP) and have been associated with incident hypertension. In people living at northern latitudes diminished cholecalciferol synthesis in the winter increases the risk of vitamin D deficiency. We wanted to test the hypothesis that daily cholecalciferol supplementation in the winter lowers BP in patients with hypertension. METHODS: We investigated the effect of 75 µg (3,000 IU) cholecalciferol per day in a randomized, placebo-controlled, double-blind study in 130 hypertensive patients residing in Denmark (56º N). Ambulatory BP (24-h BP) and arterial stiffness were measured before and after 20 weeks of treatment, that took place between October and March. RESULTS: A total of 112 patients (mean age 61 ± 10) with a baseline p-25(OH)D of 23 ± 10 ng/ml completed the study. Compared with placebo, a nonsignificant 3/1 mm Hg (P = 0.26/0.18) reduction was found in 24-h BP. In patients with vitamin D insufficiency (<32 ng/ml) at baseline (n = 92), 24-h BP decreased by 4/3 mm Hg (P = 0.05/0.01). Central BP (CBP) estimated by applanation tonometry and calibrated with a standardized office BP was reduced by 7/2 mm Hg (P = 0.007/0.15) vs. placebo. No differences in carotid-femoral pulse wave velocity (PWV) or central augmentation index (AIx) were found between treatment arms. CONCLUSIONS: Cholecalciferol supplementation, by a dose that effectively increased vitamin D levels, did not reduce 24-h BP, although central systolic BP decreased significantly. In a post-hoc subgroup analysis of 92 subjects with baseline p-25(OH)D levels <32 ng/ml, significant decreases in 24-h systolic and diastolic BP occurred during cholecalciferol supplementation.

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007) in the rituximab + dexamethasone group. There was an increased incidence of grade 3 to 4 adverse events in the rituximab + dexamethasone group (P = .04). In conclusion, rituximab + dexamethasone induced higher response rates and longer time to relapse than dexamethasone alone. This study is registered at http://clinicaltrials.gov as NCT00909077.

BACKGROUND: The mechanisms involved in development and maintenance of hypertension in obstructive sleep apnea (OSA) are not clarified. We hypothesize that patients with OSA have an abnormal nocturnal level of some vasoactive hormones during the night. METHODS: We studied 32 patients with OSA and 19 healthy control subjects during The night-time with serial determinations of endothelin-1 (ENDO-1), angiotensin II (Ang II), renin (PRC), aldosterone (ALDO) in plasma, and blood pressure (BP), and oxygen saturation. RESULTS: Patients with OSA had a higher plasma level of ENDO than healthy controls and the mean nocturnal level of ENDO correlated significantly to the apnea-hypopnea index (AHI) as a measure of the severity of OSA. This correlation remained statistically significant after analysis in a general linear model with correction for confounders. Patients with OSA also had a significantly higher BP than healthy controls and the ambulatory BP correlated positively to the AHI in patients with OSA. No significant differences were measured in Ang II, PRC, and ALDO between the two groups. The correlation between AHI and ENDO supports OSA as a stimulus of endothelin release or increased endothelin levels contributing to the severity of OSA. CONCLUSIONS: Endothelin seems to be a pathogenic factor in generating hypertension in OSA.

BACKGROUND: Approximately 12,000 hip and knee replacements were performed in Denmark in 2005. Accelerated perioperative interventions are currently implemented, but there is conflicting evidence regarding the effect. We therefore performed an efficacy study of an accelerated perioperative care and rehabilitation intervention in patients receiving primary total hip replacement, and both total and unicompartmental knee replacement. METHODS: A randomized clinical trial was undertaken in which 87 patients were randomized to either a control group receiving the current perioperative procedure, or an intervention group receiving a new accelerated perioperative care and rehabilitation procedure. Outcome measures were length of stay (LOS) in hospital, and gain in quality of life (QOL) using EQ-5D from baseline to 3-month follow-up. RESULTS: Mean LOS was reduced (p < 0.001) from 8 days (95% CI: 7.1-8.4) in the control group to 5 days (95% CI: 4.2-5.6) in the intervention group. This was accompanied by a greater gain in QOL of 0.08 (95% CI: 0.004-0.16) in the intervention group (p = 0.03). INTERPRETATION: An accelerated perioperative care and rehabilitation intervention in patients undergoing primary total hip replacement, and total or unicompartmental knee replacement is indeed effective-and of advantage to both the hospital and the patient.

Cryptic diversity within bumblebees (Bombus) has the potential to undermine crucial conservation efforts designed to reverse the observed decline in many bumblebee species worldwide. Central to such efforts is the ability to correctly recognise and diagnose species. The B. lucorum complex (Bombus lucorum, B. cryptarum and B. magnus) comprises one of the most abundant and important group of wild plant and crop pollinators in northern Europe. Although the workers of these species are notoriously difficult to diagnose morphologically, it has been claimed that queens are readily diagnosable from morphological characters. Here we assess the value of colour-pattern characters in species identification of DNA-barcoded queens from the B. lucorum complex. Three distinct molecular operational taxonomic units were identified each representing one species. However, no uniquely diagnostic colour-pattern character state was found for any of these three molecular units and most colour-pattern characters showed continuous variation among the units. All characters previously deemed to be unique and diagnostic for one species were displayed by specimens molecularly identified as a different species. These results presented here raise questions on the reliability of species determinations in previous studies and highlights the benefits of implementing DNA barcoding prior to ecological, taxonomic and conservation studies of these important key pollinators.

During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe.

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. RECOMMENDATIONS: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.

Recently, various subtypes of familial hyperinsulinemic hypoglycemia with an autosomal-dominant inheritance have been etiologically characterized. In the present study, we have delineated the genetics and metabolic phenotype of a novel form of hypoglycemia in a large pedigree with an apparent autosomal-dominant transmission. After initial investigations of the proband, her mother, and a sister, the study was extended to 19 family members in three generations. Glucose tolerance was assessed by a 5-h oral glucose tolerance test (OGTT) and insulin sensitivity by euglycemic-hyperinsulinemic clamp in six affected family members and six control subjects. To identify the genetic cause of hypoglycemia, linkage analysis and mutation analysis of genomic DNA from all family members were performed. All affected family members were characterized by postprandial hypoglycemia, fasting hyperinsulinemia, and an elevated serum insulin-to-C-peptide ratio. The 5-h OGTT demonstrated hyperinsulinemic hypoglycemia, and the clamp studies showed reduced insulin sensitivity and clearance of serum insulin in affected family members compared with control subjects. Linkage analysis and subsequent mutation screening revealed a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate the coexistence of severe postprandial hypoglycemia, insulin resistance, and impaired insulin clearance and suggest that hypoglycemia should be considered as a phenotype linked to heterozygote mutations in the insulin receptor gene.

BACKGROUND: The effect of hysterectomy on sexuality is not fully elucidated and until recently total and subtotal hysterectomies have only been compared in observational studies. AIMS: To compare total abdominal hysterectomy (TAH) to subtotal abdominal hysterectomy (SAH) regarding effects on sexuality. METHODS: In a Danish multicenter trial 319 women were randomized to TAH (n = 158) or SAH (n = 161); 185 women had self-selected TAH (n = 80) or SAH (n = 105) in a simultaneously conducted observational study. Women were followed for 1 year by strict data collection procedures, including postal questionnaires. Results were analyzed by intention to treat (ITT) analyses. RESULTS: No significant differences were observed between TAH and SAH at 1-year follow-up in both the randomized trial and the observational study regarding women's desire for sex, frequency of intercourse, frequency of orgasm, quality of orgasm, localization of orgasm, satisfaction with sexual life, and dyspareunia. None of these sexual variables changed significantly from entry to the 1-year follow-up, apart from dyspareunia, which was significantly (p = 0.009) reduced in both intervention groups. Significant (p < 0.05) predictors for satisfaction with sexual life after hysterectomy were the preoperative satisfaction with sexual life [odds ratio (OR) 32, 95% confidence interval (CI) 10-125], good relationship with partner (OR 50, 95% CI 9-354), physical well-being (OR 0.30, 95% CI 0.09-0.88) and hormone replacement therapy (OR 0.23, 95% CI 0.06-0.78). CONCLUSIONS: Both TAH and SAH significantly reduce dyspareunia without having a negative effect on sexual function. The shift toward SAH seems unwarranted.

This randomized, double-blind, multi-centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip. A total of 158 outclinic patients entered the study. Eighty-three patients (mean age 66 years) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily, and 75 patients (mean age 67 years) with paracetamol 1 g 3 times daily. Ibuprofen 400 mg was prescribed as rescue medication. Due to an unexpected high rate of adverse drug reactions, the study was closed before the planned 400 patients had entered. Over weeks 1-4, 87%, 64%, 61% and 52% of patients in the codeine plus paracetamol group, and 38%, 31%, 22% and 29% of patients in the paracetamol group had one or more adverse drug reactions. Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks. Nausea, dizziness, vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group. During the first week of treatment, 30 patients (36%) in the codeine plus paracetamol group and 9 (12%) in the paracetamol group dropped out. As evaluated from patients completing the first week of treatment, the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group. Moreover, during the first week the paracetamol group received rescue medicine significantly more frequently. In conclusion, when evaluated after 7 days of treatment, the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint. However, several adverse drug reactions, mainly of the gastrointestinal tract, and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine cannot be recommended for longer-term treatment of chronic pain in elderly patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is reported to occur after major surgery in as many as 20% of patients, elderly patients may especially experience problems in the weeks and months after surgery. Recent studies vary greatly in methods of evaluation and diagnosis of POCD, and the pathogenic mechanisms are still unclear. We evaluated a large uniform cohort of elderly patients in a standardized approach, after major joint replacement surgery (total hip and knee replacement). Patients were in an optimized perioperative approach (fast track) with multimodal opioid-sparing analgesia, early mobilization, and short length of stay (LOS ≤3 days) and discharged to home. METHODS: In a prospective multicenter study, we included 225 patients aged ≥60 years undergoing well-defined fast-track total hip or total knee replacement. Patients had neuropsychological testing preoperatively and 1 to 2 weeks and 3 months postoperatively. LOS, pain, opioid use, inflammatory response, and sleep quality were recorded. The practice effect of repeated cognitive testing was gauged using data from a healthy community-dwelling control group (n = 161). RESULTS: Median LOS was 2 days (interquartile range 2-3). The incidence of POCD at 1 to 2 weeks was 9.1% (95% confidence interval [CI], 5.4%-13.1%) and 8.0% (95% CI, 4.5%-12.0%) at 3 months. There was no statistically significant difference between patients with and without early POCD, regarding pain, opioid use, sleep quality, or C-reactive protein response, although the CIs were wide. Patients with early POCD had a higher Mini Mental State Examination score preoperatively (difference in medians 0.5 [95% CI, -1.0% to 0.0%]; P = 0.034). If there was an association between early POCD and late POCD, the sample size was unfortunately too small to verify this (23.6% of patients with early POCD had late onset vs 6.7% in non-POCD group; risk difference 16.9 (95% CI, -2.1% to 41.1%; P = 0.089). CONCLUSIONS: The incidence of POCD early after total hip and knee replacement seems to be lower after a fast-track approach than rates previously reported for these procedures, but late POCD occurred with an incidence similar to that in previous studies of major noncardiac elective surgery. No association between early and late POCD could be verified.

"Fast-track" protocols has improved surgical care with a reduction in length of hospital stay (LOS) in total hip (THA) and knee arthroplasty (TKA). However, the effects of continuous refinement of perioperative care lack detailed assessment. We studied time-related changes in LOS and morbidity after THA and TKA within a collaboration with continuous scientific refinement of perioperative care. Prospective multicentre consecutive cohort study between 2010 and 2017 from nine high-volume orthopaedic centres with established fast-track THA and TKA protocols. Prospective collection of comorbidities and complete 90-day follow-up from the Danish National Patient Registry and medical records. Of 36,935 procedures median age was 69 [62 to 75] years and 58% women. LOS declined from three [two to three] days in 2010 to one [one to two] day in 2017. LOS > 4 days due to "medical" or "surgical" complications, and "with no recorded morbidity" declined from 4.4 to 2.7%, 1.5 to 0.6%, and 3.8 to 1.3%, respectively. 90-days readmission rate declined from 8.6 to 7.7%. Our multicentre study in a socialized healthcare setting was associated with a continuous reduction in LOS and morbidity after THA and TKA.

The effect of a continuous infusion of human brain natriuretic peptide (BNP) was studied in 48 healthy men. The study was randomized, placebo controlled, and single blind. BNP was given in doses of 1, 2, or 4 pmol.kg-1.min-1 for 60 min, and peak values of BNP in plasma were 38, 85, and 199 pmol/l, giving increments in plasma as seen in heart or renal failure. BNP infusion increased the urinary flow rate and the excretion of sodium in a dose-dependent way. The maximal effects were +65 and +156%, respectively. GFR increased and RPF decreased, the latter in a dose-dependent manner. Blood pressure, heart rate, angiotensin II, and aldosterone were all unaffected by infusion of BNP, whereas a direct inhibition of renin secretion was seen. With the use of the lithium clearance technique, we concluded that the tubular site of action is in both the proximal and distal segments, and the major effect on sodium handling is in the distal parts of the nephron.

OBJECTIVE/HYPOTHESIS: With the COVID-19 pandemic, chemosensory dysfunction are among the most prevalent symptoms. Most reports are subjective evaluations, which have been suggested to be unreliable. The objective is to test chemosensory dysfunction and recovery based on extensive psychophysical tests in COVID-19 during the course of the disease. STUDY DESIGN: Prospective cohort study. METHODS: A total of 111 patients from four centers participated in the study. All tested positive for SARS-COV-2 with RT-PCR. They were tested within 3 days of diagnosis and 28 to 169 days after infection. Testing included extensive olfactory testing with the Sniffin' Sticks test for threshold, discrimination and identification abilities, and with the Taste Sprays and Taste Strips for gustatory function for quasi-threshold and taste identification abilities. RESULTS: There was a significant difference in olfactory function during and after infection. During infection 21% were anosmic, 49% hyposmic, and 30% normosmic. After infection only 1% were anosmic, 26% hyposmic, and 73% normosmic. For gustatory function, there was a difference for all taste qualities, but significantly in sour, bitter, and total score. Twenty-six percent had gustatory dysfunction during infection and 6.5% had gustatory dysfunction after infection. Combining all tests 22% had combined olfactory and gustatory dysfunction during infection. After infection no patients had combined dysfunction. CONCLUSIONS: Chemosensory dysfunction is very common in COVID-19, either as isolated smell or taste dysfunction or a combined dysfunction. Most people regain their chemosensory function within the first 28 days, but a quarter of the patients show persisting dysfunction, which should be referred to specialist smell and taste clinics for rehabilitation of chemosensory function. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1095-1100, 2021.