Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients

Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 ± 6.4 to 39.7 ± 3.6% (mean ± SD, P = 0.02) and 12.8 ± 2.2 to 13.5 ± 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 ± 3.8 to 20.6 ± 8.0%, P < 0.05 and from 14.3 ± 12.4 to 29.3 ± 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed

Феномен веры в мистическом опыте просветления

В статье исследуется феномен религиозной веры и делается вывод о существовании двух ее уровней. Первый из них - "вера просительная" (со многим количеством условий), характерна для человека, воспринимающего себя как смертное Тело-Эго и ориентированного на страх. Совершенной формой религиозной веры может считаться только "вера абсолютная" (безусловная), достижение которой является основной целью мистической практики просветления. Она характеризуется полным уничтожением Эго, формированием безусловного доверия и любви к Богу. Вера в имманентных мистических учениях приобретает форму доверия к своему истинному "Я"-Атману. Вера в трансцендентно-имманентной мистике приобретает форму доверия к трансцендентной силе, что подразумевает безусловную отдачу Ее воле.У статті проводиться дослідження феномену релігійної віри. Робиться висновок про існування двох її рівнів. Перший з них - "віра прохальна" (з багатьма умовами), характерна для людини, що сприймає себе як смертне Тіло-Его та зорієнтована на страх. Досконалою формою релігійної віри можна вважати тільки "віру абсолютну" (безумовну), досягнення якої постає основною метою містичної практики просвітлення. Цей рівень віри характеризується повним знищенням Его, формуванням безумовної довіри та любові до Бога. Віра у іманентних містичних ученнях має форму довіри до свого істинного "Я"-Атману. Віра в трансцендентно-іманентній містиці приймає форму довіри до трансцендентної сили, що вимагає безумовної віддачі Її волі.The phenomenon of religious faith is investigated in the article. The conclusion is that there are two levels of it. First of them is "faith-request" (with a number of conditions), it is typical for a person who perceives oneself as a mortal Body - Ego and who is orientated on fear. Just "absolute faith" (unconditional) can be considered to be a perfect form of religious faith, and the achievement of it is the main purpose of mystical practice of enlightening. It is characterized with complete destroying of Ego, with forming of unconditional trust and love to God. Faith in immanent mystical teachings acquires the form of trust to own true "I" - Atman. Faith in transcendental immanent mystics acquires the form of trust to transcendental power that means unconditional exposing to His will

Prescribing of long-acting beta-2-agonists/inhaled corticosteroids after the SMART trial

Background After the SMART trial evaluating the safety of salmeterol (long-acting beta-2-agonist (LABA)) in asthma patients, regulatory actions were taken to promote a guideline-adherent prescribing of LABA only to patients receiving inhaled corticosteroids (ICS). We aim to analyse LABA- and ICS-related prescription patterns after the SMART trial in Germany. Methods Patients documented in the Bavarian Association of Statutory Health Insurance Physicians database (approximately 10.5 million people) were included if they had a diagnosis of asthma and at least one prescription of LABA and/or ICS between 2004 and 2008. Annual period prevalence rates (PPRs) were estimated and Cochrane Armitage tests were used for time trend analyses. Results Highest annual PPRs were found for budesonide and the fixed combination of salmeterol/fluticasone. The proportion of “concomitant LABA and ICS users” increased from 52.0 to 57.6% within the study period, whereas for “LABA users without ICS” a slight decrease from 6.5 to 5.4% was found. In 2008, the proportion of patients with at least one quarter with a LABA prescription without concomitant ICS was highest in elderly, male patients (≈20%). In the majority of these patients, a concomitant diagnosis of COPD (i.e. asthma-COPD overlap syndrome [ACOS]) was present. Conclusions Between 2004 and 2008, we found a moderate increase in guideline-adherent LABA prescribing in a representative German population. Elderly men received a significant number of LABA prescriptions without concomitant ICS probably due to ACOS

Sex Differences in Clinical Course and Intensive Care Unit Admission in a National Cohort of Hospitalized Patients with COVID-19

Males have a higher risk for an adverse outcome of COVID-19. The aim of the study was to analyze sex differences in the clinical course with focus on patients who received intensive care. Research was conducted as an observational retrospective cohort study. A group of 23,235 patients from 83 hospitals with PCR-confirmed infection with SARS-CoV-2 between 4 February 2020 and 22 March 2021 were included. Data on symptoms were retrieved from a separate registry, which served as a routine infection control system. Males accounted for 51.4% of all included patients. Males received more intensive care (ratio OR = 1.61, 95% CI = 1.51–1.71) and mechanical ventilation (invasive or noninvasive, OR = 1.87, 95% CI = 1.73–2.01). A model for the prediction of mortality showed that until the age 60 y, mortality increased with age with no substantial difference between sexes. After 60 y, the risk of death increased more in males than in females. At 90 y, females had a predicted mortality risk of 31%, corresponding to males of 84 y. In the intensive care unit (ICU) cohort, females of 90 y had a mortality risk of 46%, equivalent to males of 72 y. Seventy-five percent of males over 90 died, but only 46% of females of the same age. In conclusion, the sex gap was most evident among the oldest in the ICU. Understanding sex-determined differences in COVID-19 can be useful to facilitate individualized treatments

Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Pharmacokinetic and pharmacodynamic interaction trial after repeated oral doses of imdapril and digoxin in healthy volunteers

Aims To investigate the potential pharmacokinetic and pharmacodynamic interaction between imidapril and digoxin

Welche Faktoren begünstigen die Anwendung potenziell ungeeigneter Medikamente bei älteren Menschen?

Hintergrund Aktuelle Untersuchungen belegen den Zusammenhang zwischen der Verordnung potenziell inadäquater Medikamente (PIM) an Patienten ab 65 Jahren und einem erhöhten Risiko dieser Patienten für unerwünschte Ereignisse, insbesondere Krankenhausaufnahmen. Die bevölkerungsrepräsentative Stichprobe der DEGS1-Studie („Studie zur Gesundheit Erwachsener in Deutschland“ des RKI) bietet die Möglichkeit, die mit der Anwendung von PIM assoziierten Faktoren zu identifizieren. Fragestellungen Was charakterisiert ältere Menschen in Deutschland, die aktuell PIM anwenden, und gibt es Subpopulationen, bei denen eine PIM-Anwendung besonders häufig ist? Material und Methoden Im Rahmen der DEGS1-Studie wurden 175 Variablen zu gesundheitlichen und sozialen Aspekten von 1392 im eigenen Haushalt lebenden Personen im Alter von 65 bis 79 Jahren erhoben und die Medikation der letzten sieben Tage dokumentiert. PIM konnten mit Hilfe der PRISCUS-Liste identifiziert werden. Mögliche Zusammenhänge zwischen PIM-Einnahme und den erhobenen Variablen wurden in einem multivariablen Modell überprüft. Ergebnisse und Diskussion In den letzten sieben Tagen vor Befragung wurden von 13,0 % (95 %-KI: 10,7–15,6) der Befragten PIM eingenommen. Folgende Faktoren begünstigen signifikant die PIM-Einnahme: Gesamtzahl der in den letzten sieben Tagen eingenommenen Medikamente; Zahl niedergelassener Arztgruppen, die in den letzten 12 Monaten aufgesucht worden sind; Einschlafstörungen; die Krankheitsgruppen Psyche und Gelenke/Knochen. Die am häufigsten eingenommenen PIM-Wirkstoffe kommen aus der Gruppe der Antidepressiva und Anxiolytika/Sedativa. Besonders betroffen von einer erhöhten PIM-Einnahme sind ältere Frauen mit Depressionen, Einschlafstörungen und Analgetikabedarf. Sie bedürfen einer besonderen Aufmerksamkeit.Peer Reviewe

Influence of pharmacist intervention on drug safety of geriatric inpatients: a prospective, controlled trial

Background: Demographic shift leads to an increasing number of geriatric patients suffering from multimorbidity and resulting polypharmacy. Polypharmacy is shown to be associated with drug-related problems (DRPs) and increased morbidity. For Germany, a hospital-based intervention may be successful optimizing of polypharmacy. The aim of this study was to reduce DRPs in geriatric inpatients by a structured pharmacist’s intervention and to measure the acceptance rate of pharmaceutical recommendations. Methods: This study followed an open, prospective, quasi-randomized, controlled design and was conducted in a geriatric department in a teaching hospital in Germany. Patients of all sexes were included, with a minimum age of 70 years, a written informed consent and a regular intake of at least five drugs daily. Primary outcome was the percentage of patients having a DRP at admission and discharge. A DRP was defined as a prescription without indication or a relevant drug–drug interaction or prescription of a potentially inappropriate medication or presence of an adverse drug reaction. Recommendations were classified and discussed face to face. Statistical analyses were performed using a full-set analysis and a matched-pairs design. Results: Within 12 months, 411 patients were recruited with median age of 82 years (intervention: n = 209; control: n = 202). Median number of drugs at admission was 10 (range 5–24), at discharge 9 (range 3–21). In the intervention group, the percentage of patients with a DRP was reduced from 86.6% to 56.0%; in the control group, from 76.7% to 76.2% (p value < 0.001). Medication appropriateness index score was reduced by 56% in the intervention group and by 0.2% in the control group (p value < 0.001). Implementation rate of the pharmaceutical recommendation was 80%. Conclusion: This prospective controlled trial showed that a pharmacist’s intervention was successful in optimizing polypharmacy in geriatric inpatients