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Background: The representation of women in heart failure studies has been inadequate, resulting in a knowledge gap regarding the prognostic impact of coronary artery disease (CAD) on all-cause mortality in women with newly diagnosed heart failure and reduced ejection fraction (HFrEF)., Objectives: This study aims to assess the prognostic impact of CAD in women with HFrEF., Methods: Using the Western Denmark Heart Registry, the authors identified 891 women and 2,403 men referred for first-time coronary angiography because of HFrEF. The authors stratified for presence of CAD, estimated 10-year all-cause mortality, and calculated crude and adjusted HRs (aHRs) with 95% CIs., Results: The 10-year mortality was 60% in women with CAD and 27% in women without CAD; for men, the corresponding numbers were 54% and 36%. When adjusted for comorbidities, women without CAD had a lower relative 10-year mortality than men without CAD (aHR: 0.73; 95% CI: 0.58-0.91), whereas women with CAD had similar relative mortality as men with CAD (aHR: 1.00; 95% CI: 0.81-1.24) (P interaction  = 0.037). Assessed by the number of coronary vessels with significant stenosis, CAD extent was associated with mortality for both women (P < 0.01) and men (P < 0.01). However, compared to those without CAD, the aHR was higher for women with any degree of CAD (aHR ranging from 1.61 [95% CI: 1.09-2.38] for diffuse CAD to 2.01 [95% CI: 1.19-3.40] for 3-vessel disease) than for men with 3-vessel disease (aHR: 1.51; 95% CI: 1.19-1.91)., Conclusions: In patients with newly diagnosed HFrEF, the presence and extent of CAD has significantly greater prognostic impact among women than among men., Competing Interests: Funding Support and Author Disclosures This study was funded by the Research Unit, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of our study was to investigate whether current eGFR equations in clinical use might systematically over-estimate the kidney function, and thus misclassify CKD status, of Black Americans with HIV. Specifically, we evaluated the impact of removing the race coefficient from the MDRD and CKD-EPI equations on comparisons between Black and White HIV-infected veterans related to: 1) the prevalence of reduced eGFR; 2) the distribution of eGFR values; and 3) the relationship between eGFR and all-cause mortality., Design: Retrospective cohort study., Setting: The Department of Veterans Affairs (VA) HIV Clinical Case Registry (CCR), which actively monitors all HIV-infected persons receiving care in the VA nationally., Patient/participants: 21,905 treatment-naïve HIV-infected veterans., Main Outcome Measures: Estimated glomerular filtration rate (eGFR) using the abbreviated Modification of Diet in Renal Disease (MDRD) formula with and without (MDRD-RCR) the race coefficient and all-cause mortality., Results: Persons with eGFR <45 mL/min/1.73m(2) had a higher risk of death compared with those with eGFR >80 mL/min/1.73m(2) among both Blacks (HR=2.8, 95%CI: 2.4-3.3) and Whites (HR=1.9, 95%CI: 1.4-2.6), but the association appeared to be stronger in Blacks (P=.038, test for interaction). Blacks with eGFR 45-60 mL/min/1.73m(2) also had a higher risk of death (HR=1.7, 95%CI: 1.4-2.1) but Whites did not (HR=.86, 95%CI: .67-1.10; test for interaction: P<.0001). Racial differences were substantially attenuated when eGFR was re-calculated without the race coefficient., Conclusions: Our findings suggest that clinicians may want to consider estimating glomerular filtration rate without the race coefficient in Blacks with HIV.

Background: Pneumonia is a frequent lung infection and a serious illness, which is often diagnosed among patients hospitalized with acute exacerbations of COPD. The aim of this study was to estimate the attributable costs due to pneumonia among patients hospitalized with pneumonia compared to a matched general population control group without pneumonia hospitalization., Methods: This study includes citizens older than 18 years from three municipalities (n=142,344). Based on national registers and municipal data, the health and social care costs of pneumonia in the second half of 2013 are estimated and compared with propensity score-matched population controls., Results: The average health care costs of 383 patients hospitalized with pneumonia in the second half of 2013 were US$34,561 per patient. Among pneumonia patients with COPD, the costs were US$35,022. The attributable costs of patients with pneumonia compared to the population control group for the 6-month period were US$24,155 per case. Overall, the attributable costs for the 383 pneumonia cases amounted to US$9.25 million. Subgroup analyses showed that costs increased with age. The attributable costs due to pneumonia were highest among the 18-59-year-old and the 70-79-year-old patients. This difference is likely to reflect an increased risk of mortality among the pneumonia patients. Men have higher costs than women in the pneumonia group., Conclusion: The costs of pneumonia are considerable. In three Danish municipalities, the attributable costs due to pneumonia were US$24,155 per case or US$64,992 per 1,000 inhabitants in the second half of 2013. Similar high health care and social care costs were found for pneumonia patients with COPD - the largest group having pneumonia episodes. The municipalities are responsible for 49% of the costs, while a closer focus on the prevention of pneumonia may be advisable, eg, starting with citizens having COPD.

Introduction: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder affecting approximately 1% of the population above 65 years of age. The aim of this study was to define the estimated Danish IPD population and to elucidate source of income and labour market affiliation for working-age IPD patients., Material and Methods: IPD cases were included through the Danish Register of Medicinal Product Statistics. The participants had to be alive by the end of 2010 and at least twice have cashed in prescriptions on IPD medication in the 2009-2010 period. Information on employment status and transfer income was retrieved through the DREAM database under the Danish Ministry of Employment., Results: A total of 7,033 estimated IPD patients were identified. The mean age at time of registration (2010, week 50) was 72 years. Overall, 7% of the IPD patients were employed and 5% were self-supportive. In the working age range (18-64 years), 25% were employed and 10% enrolled in supported employment. Compared with the age-adjusted general population, twice as many IPD patients were outside the ordinary labour market and, furthermore, the proportion receiving anticipatory pension was increased threefold. The majority (89%) of the patients were living at home with a spouse (59%). 11% were nursing home residents., Conclusion: The working age IPD population was more prone to be outside employment and to receive public transfer income than an age-adjusted population sample., Funding: The study was funded by the Danish Parkinson Association., Trial Registration: not relevant.

Introduction: Spirometric studies of the general population estimate that 430 000 Danes have chronic obstructive pulmonary disease (COPD). COPD is mainly caused by smoking, and smoking cessation is the most important intervention to prevent disease progression. Cost-of-illness studies conclude that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed., Objectives: To analyse the societal costs associated with prescription medicine for COPD in Denmark., Methods: The study was designed as a nationwide retrospective register study of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who had been either hospitalised with a COPD diagnosis or had at least one prescription for drugs primarily used for COPD., Results: The study population comprised 166 462 individuals of which 97 916 were alive on 31 December 2010. The average annual drug costs (R03) were DKK 7842 (EUR 1055) per patient in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70 000-75 000 (EUR 9416-10 089) per patient (2010 prices)., Conclusion: The costs associated with prescription medicine for COPD in Denmark are significant., (© 2012 John Wiley & Sons Ltd.)

The SAR of the lead compound 3, a novel ligand for the alpha(2)delta subunit of voltage-gated calcium channels, was rapidly explored. Utilizing a parallel solution-phase Sn2Ar coupling approach, a focused library was obtained. The library was evaluated in vitro and afforded a series of analogues with improved potencies. The SAR trends of the library are also described.

The anticonvulsant gabapentin (GBP) has been shown effective for the treatment of neuropathic pain, although its mechanism of action remains unclear. A recent report has suggested that binding to the alpha(2)delta subunit of voltage-gated calcium channels contributes to its antinociceptive effect, based on the stereoselective efficacy of two analogs: (1S,3R)3-methylgabapentin (3-MeGBP) (IC(50) = 42 nM), which is effective in neuropathic pain models; and (1R,3R)3-MeGBP (IC(50) > 10,000 nM), which is ineffective (Field et al., 2000). The present study was designed to further examine the profiles of GBP and 3-MeGBP in rat models of acute and persistent pain. Systemic administration of GBP or (1S,3R)3-MeGBP inhibited tactile allodynia in the spinal nerve ligation model of neuropathic pain, whereas (1R,3R)3-MeGBP was ineffective. The antiallodynic effect of GBP, but not (1S,3R)3-MeGBP, was blocked by i.t. injection of the GABA(B) receptor antagonist [3-[[(3,4-dichlorophenyl)methyl]amino]propyl](diethoxymethyl)phosphinic acid (CGP52432). Systemic GBP or (1S,3R)3-MeGBP also inhibited the second phase of formalin-evoked nociceptive behaviors, whereas (1R,3R)3-MeGBP was ineffective. However, both (1S,3R)3-MeGBP and (1R,3R)3-MeGBP, but not GBP, inhibited first phase behaviors. In the carrageenan model of inflammatory pain, systemic GBP or (1R,3R)3-MeGBP failed to inhibit thermal hyperalgesia, whereas (1S,3R)3-MeGBP had a significant, albeit transient, effect. Systemic (1S,3R)3-MeGBP, but not GBP or (1R,3R)3-MeGBP, also produced an antinociceptive effect in the warm water tail withdrawal test of acute pain. These data demonstrate that GBP and 3-MeGBP display different antinociceptive profiles, suggesting dissimilar mechanisms of antinociceptive action. Thus, the stereoselective efficacy of 3-MeGBP, presumably related to alpha(2)delta binding, likely does not completely account for the mechanism of action of GBP.

A novel class of 6-aryl-6H-pyrrolo[3,4-d]pyridazine ligands for the alpha2delta subunit of voltage-gated calcium channels has been described. Substitutions in the aryl ring of the molecule were generally not tolerated, and resulted in diminished binding to the alpha2delta subunit. Modifications to the pyridazine ring revealed numerous permissive substitutions, and detailed SAR studies were carried out in this portion of the molecule. Replacement of the pyridazine ring methyl group with an aminomethyl functionality provided greatly improved potency over the initial lead. The initial lead compound displayed good rat pharmacokinetic properties, and was shown to be efficacious in the Chung model for neuropathic pain in rats.

The course of disease in two women with bioptically verified lymphangioleiomyomatosis (LAM) is demonstrated. One was oestrogen- and progesterone-receptor negative, but responded promptly to hysterosalpingo-oophorectomy and has had no symptoms later. The other was receptor positive, but in spite of hysterosalpingo-oophorectomy and hormonal manipulation with tamoxifen and medroxyprogesterone, has had a complicated course of the disease with symptoms for ten years. LAM is a hormone dependent disease, but our knowledge is still incomplete. Hormonal manipulation should be tried in receptor positive as well as negative patients. Tamoxifen seems to have deleterious effects on the course of disease.

A specific and quantitative immunological method for determination of human erythrocyte carbonic anhydrase isoenzyme B has been used to ascertain the contents of this enzyme in the erythrocytes of healthy persons and of subjects with chronic metabolic and respiratory acidosis. The investigations have shown significant increase of carbonic anhydrase type B in the erythrocytes of patients suffering from renal failure with chronic acidosis, and in patients with chronic obstructive lung disease and chronic respiratory acidosis. The erythrocytes of acidotic uremic patients have a significantly higher content of erythrocyte carbonic anhydrase isoenzyme B than do the erythrocytes of uremic subjects without chronic acidosis. In chronic obstructive lung disease, the content of this enzyme in erythrocytes was significantly higher in the hypercapnic patients than in the normocapnic ones. In renal failure, significant correlation was found between carbonic anhydrase isoenzyme B and standard bicarbonate. In chronic obstructive lung disease no significant correlation was found between carbonic anhydrase and pCO2.

A specific and quantitative immunological method for the determination of human erythrocyte carbonic anhydrase (HCA) isoenzyme B has been used to determine the contents of enzyme in the erythrocytes from healthy persons and from subjects with chronic obstructive lung disease. The investigations have shown a statistically significant increase of HCA type B in the erythrocytes of subjects suffering from chronic obstructive lung disease and hypercapnia. Subjects with chronic obstructive lung disease and normal PaCO2 showed no difference from normal subjects. No correlation was found between PaCO2 and human erythrocyte carbonic anhydrase.

A specific and quantitative immunological method for the determination of human erythrocyte carbonic anhydrase isoenzymes B and C has been used to determine these enzymes in erythrocytes of umbilical cord blood. The investigations have shown a content of both isoenzymes less than a tenth of that in adults. The isoenzyme content correlated significantly with the estimated gestational age. The ratio between isoenzyme B and C rose with gestational age, reaching adult level at term. A group of 19 "small-for-date" infants had isoenzyme levels in the same range as normal full-term infants, significantly higher than the levels in the same range as normal full-term infants, significantly higher than the levels in truly premature infants. It is concluded that the determination of carbonic anhydrase isoenzymes is an aid in distinguishing "small-for-date" infants from the truly premature.

A specific and quantitative immunological method for determination of human erythrocyte carbonic anhydrase (HCA) isoenzyme B has been used to determine the contents of enzyme in the erythrocytes from healthy persons and from subjects with different types of anemia. The investigations have shown a statistically significant increase of HCA type B in the erythrocytes of subjects suffering from uremic anemia, cancer anemia, megaloblastic anemia while in sideropenic anemia the content was normal. In erythrocytes from patients with acute bleeding anemia the content of HCA type B was significantly decreased. An inverse relationship was found between B-hemoglobin and HCA type B in megaloblastic anemia but not in the other types of anemia.

A 28-year-old woman suffering from diabetes, malabsorption and pulmonary tuberculosis was treated successfully with ethambutol and rifampicin intravenously for 4 months. The drugs were given through a catheter placed in the upper caval vein. One month after the treatment was started the sputum cultures became negative. During oral therapy the patient suffered from characteristic "flu" syndrome which surprisingly disappeared during the intravenous treatment. The possible causes are discussed. Allergic reactions to rifampicin appeared among the staff. The results of the allergological examinations are mentioned and directions for handling rifampicin powder are suggested.

A specific and quantitative immunological method for the determination of human erythrocyte carbonic anhydrase isoenzymes B and C has been used to determine these enzymes in erythrocytes of umbilical cord blood. The investigations have shown a content of both isoenzymes less than 1:10 of that in adults. Premature infants have significantly lower values than full-term infants. The influence of carbonic anhydrase in the respiratory distress syndrome is discussed. No conclusions are drawn. The content of carbonic anhydrase in erythrocytes has been suggested as a laboratory parameter of maturity. In our investigations it does not seem to be useful for the evaluation of muturity.

The anticonvulsive properties of pregnanolone (as an emulsion) were evaluated in mice and compared with similar properties of Althesin and thiopentone. Pregnanolone emulsion was found to antagonize convulsions induced by the GABA antagonists pentetrazole, bicuculline and picrotoxin and by the specific glycine receptor antagonist, strychnine. The drug was effective in all four convulsive tests at subanaesthetic doses with maximal activity appearing within less than 1 min. The anticonvulsive therapeutic indices of pregnanolone emulsion were superior when compared with the therapeutic indices of Althesin and thiopentone in all four tests. Pregnanolone emulsion might be a useful alternative drug in the management of convulsive states resistant to conventional therapy.

A specific and quantitative immunological method for determination of human erythrocyte carbonic anhydrase isoenzyme B has been used to determine the contents of this enzyme in the erythrocytes from healthy persons and anemic and non-anemic subjects with renal insufficiency. The investigations have shown significant increase of carbonic anhydrase type B in the erythrocytes of patients with renal failure. The erythrocytes of anemic uremic patients have a significantly higher content of erythrocyte carbonic anhydrase isoenzyme B than the erythrocytes of non-anemic uremic subjects. Significant correlations were found between human erythrocyte carbonic anhydrase type B and hemoglobin and between it and plasma bicarbonate. No correlation was found between human erythrocyte carbonic anhydrase and plasma creatinine or creatinine clearance and serum zinc.