Prescribing cascades in ambulatory care: A structured synthesis of evidence

The strength of evidence for specific ambulatory care prescribing cascades, in which a marker drug is used to treat an adverse event caused by an index drug, has not been well characterized. To perform a structured, systematic, and transparent review of the evidence supporting ambulatory care prescribing cascades. Ninety-four potential prescribing cascades identified through a previously published systematic review. Systematic search of the literature to further characterize prescribing cascades. (1) Grading of evidence based on observational studies investigating associations between index and marker drugs, including: Level I—strong evidence [i.e. multiple high-quality studies]; Level II—moderate evidence [i.e. single high-quality study]; Level III—fair evidence [no high-quality studies but one or more moderate-quality studies]; and Level IV—poor evidence [other]. (2) Listing of the adverse event associated with the index drug in the product's United States Food and Drug Administration (FDA) label. (3) Synthesis of the evidence supporting mechanisms linking index drugs and associated adverse events. Of 99 potential cascades, 94 were supported by one or more confirmatory observational studies and were therefore included in this review. The 94 cascades related to 30 types of adverse drug reactions affecting 10 different anatomic/physiologic systems and were investigated by a total of 88 confirmatory studies, including prescription sequential symmetry analysis (n = 51), cohort (n = 30), and case–control (n = 7) studies. Overall, the evidence from observational studies was strong for 18 (19.1%) prescribing cascades, moderate for 61 (64.9%), fair for 13 (13.8%), and poor for 2 (2.1%). Although the evidence supporting mechanisms that link index drugs and associated adverse events was variable, FDA labels included information about the adverse event associated with the index drug for most (n = 86) but not all of the 94 prescribing cascades. Although we identified 18 of 94 prescribing cascades supported by strong clinical evidence and most adverse events associated with index drugs are included in FDA label, the evidentiary basis for prescribing cascades varies, with many requiring further evidence of clinical relevance

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

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

Sales of macrolides, lincosamides, streptogramins, and amoxicillin/clavulanate in the in- and outpatient setting in 10 European countries, 2007-2010

Monitoring the use of antibiotics is relevant due to the public health impact of microbial resistance, adverse effects, and costs. We present data on the consumption of macrolides, lincosamides, streptogramins and amoxicillin/clavulanate (AMC) between 2007 and 2010 in the in-and outpatient healthcare setting in 10 European countries provided by IMS Health. Antibiotics were classified according to the anatomical therapeutic chemical classification and consumption was expressed in defined daily doses/1000 inhabitants/day (DIDs). We analysed the number of prescriptions by diagnostic codes between 2008 and 2010, based on the International Classification of Diseases, 10th revision (ICD-10). These ICD-10 codes were grouped into four main categories: respiratory infections, genitourinary infections, other infections and other diagnoses. In 2010, the consumption of macrolides and lincosamides ranged from 0.45 DIDs (Sweden) to 5.46 DIDs (Italy),and from 0.04 DIDs (Denmark) to 1.00 DID (Germany),respectively. Streptogramins were available in France, Germany, Italy, Norway, Spain and United Kingdom with a consumption of < 0.001 DID exclusively in the hospital setting. The consumption of AMC ranged from < 0.001 DIDs (Norway) to 11.67 DIDs (Spain). During the study period, the consumption of macrolides decreased, the consumption of AMC increased in most of European countries, and lincosamides varied very slightly. Macrolides and AMC were mainly prescribed for respiratory infections in all countries but United Kingdom, where most of the prescriptions were assigned to diagnostic codes not clearly related with an infection. Lincosamides were prescribed for the respiratory infections and other infections groups. There was a wide inter-country variability in the percentage of the prescriptions assigned to each of the diagnostic categories. The inter-country differences in the consumption of these antibiotics and their prescription by diagnostic categories point to an inappropriate use of antibiotics

История изучения имен прилагательных в крымскотатарском языке

Целью данной статьи является рассмотрение степени изученности имени прилагательного в крымскотатарском языке как самостоятельной части речи в лингвистических трудах XIX – XX вв., а также анализ основных грамматических категорий имени прилагательного

Етнологія релігії – актуальна сфера українського релігієзнавства

Background: Inhaled long-acting beta-2-adrenoceptor agonists (LABA) are frequently used in patients suffering from asthma and chronic obstructive pulmonary disease (COPD). For evaluation of real-life data, drug consumption studies are needed but results might be widely influenced due to methodological differences in particular regarding inter-country comparisons. Objectives: This study aims to compare the LABA prescribing in the general population and specifically in patients suffering from asthma and/or COPD in five European countries. Methods: Crude and age- and sex-standardized (European 2008 reference population) annual period prevalence rates per 10,000 persons were calculated for the period 2002-2009 based on seven European electronic health record databases (Denmark, Germany, Spain, the Netherlands (2), and the United Kingdom (2)). Stratification by sex, age, and indication were performed for the annual period prevalence rates. Results: In all databases, we observed an increase in LABA prescriptions during the study period for the general population and for patients suffering from asthma and/or COPD. In 2008, the highest standardized period prevalence was observed in the Dutch Mondriaan-AHC and the Spanish BIFAP database (443.3 and 395.5 per 10,000 persons), and the lowest in the German Bavarian Claims and Dutch Mondriaan- NPRCD database (278.7 and 290.6 per 10,000 persons). Prevalence rates for LABA increased with age and were highest in patients over 70 years. Patients with a combined diagnosis of asthma and COPD had higher prevalence rates of LABA compared to patients with a single diagnosis of asthma or COPD. The proportion of patients with one inhaled LABA prescription only ranged from 14% (UK databases) to 35% (Spanish BIFAP database) in 2008 in the general population. Conclusions: By using a standardized protocol, we demonstrated inter- and intra-country differences in LABA prescriptions. A general increase of LABA prescriptions during the study period was observed in all databases

A patient-centred web-based adverse drug reaction reporting system identifies not yet labelled potential safety issues

Purpose!#!Reporting of adverse drug reactions (ADRs) by patients is essential for a comprehensive risk-benefit evaluation of drugs after marketing, but only few data are available regarding patient-centred web-based ADR reporting systems. Hence, we aimed to analyze ADRs reported by patients with a particular emphasis on novel drugs and serious ADRs not yet labelled in the respective summary of product characteristics (SPC).!##!Methods!#!All ADR reports received by a web-based, patient-centred platform ( www.nebenwirkungen.de ) between April 1, 2019, and September 1, 2020, were descriptively analyzed. ADRs and drugs were coded automatically according to MedDRA and ATC classification system. SPC labelling of reported ADRs for novel drugs marketed since 2015 was checked manually.!##!Results!#!In total, 13,515 patient reports including 29,529 ADRs were received during the study period (serious ADRs [SADRs] n = 1,318; 4.5%). Women were affected in more than two-thirds of ADR reports. The most common patient-reported ADRs were nausea, dizziness and headache, whereas arrhythmia, intestinal obstruction and erectile dysfunction were the most frequent SADRs. Ciprofloxacin, levothyroxine and venlafaxine were the compounds most frequently suspected for causing both ADRs and SADRs. Regarding novel compounds, 289 reports including 739 ADRs were received (mainly fatigue, headache and myalgia). Three hundred thirty-one (44.8%) out of those ADRs were not yet labelled in the respective SPC, whereof twelve were SADRs.!##!Conclusion!#!The majority of patient-reported ADRs were non-serious. However, a relevant number of non-labelled even serious ADRs was reported for novel compounds by patients. Despite well-known limitations of patient-reported ADRs, this web-based ADR reporting system contributes to the identification of new ADRs and thus can help to improve patients' safety complementing other pharmacovigilance instruments

Prescribing cascades: how to detect them, prevent them, and use them appropriately

Dreischulte T, Shahid F, Muth C, Schmiedl S, Haefeli WE. Prescribing cascades: how to detect them, prevent them, and use them appropriately. Deutsches Ärzteblatt international. 2022;119:745-52

Utilisation and Off-Label Prescriptions of Respiratory Drugs in Children

Respiratory drugs are widely used in children to treat labeled and non-labeled indications but only some data are available quantifying comprehensively off-label usage. Thus, we aim to analyse drug utilisation and off-label prescribing of respiratory drugs focusing on age- and indication-related off-label use. Patients aged ≤18 years documented in the Bavarian Association of Statutory Health Insurance Physicians database (approx. 2 million children) between 2004 and 2008 were included in our study. Annual period prevalence rates (PPRs) per 10,000 children and the proportion of age- and indication-related off-label prescriptions were calculated and stratified by age and gender. Within the study period, highest PPRs were found for the fixed combination of clenbuterol/ambroxol (between 374-575 per 10,000 children) and the inhaled short acting beta-2-agonist salbutamol (between 378-527 per 10,000 children). Highest relative PPR increase was found for oral salbutamol (approx. 39-fold) whereas the most distinct decrease was found for oral long-acting beta-2-agonist clenbuterol (−97%). Compound classes most frequently involved in off-label prescribing were inhaled bronchodilative compounds (91,402; 37.3%) and oral beta-2-agonists (26,850; 22.5%). The highest absolute number of off-label prescriptions were found for inhaled salbutamol (n = 67,084; 42.0%) and oral clenbuterol/ambroxol (fixed combination, n = 18,897; 20.7%). Off-label prescribing due to indication was of much greater relevance than age-related off-label use. Most frequently, bronchodilative compounds were used off-label to treat respiratory tract infections. Highest off-label prescription rates were found in the youngest patients without relevant gender-related differences. Off-label prescribing of respiratory drugs is common especially in young children. Bronchodilative drugs were most frequently used off-label for treating acute bronchitis or upper respiratory tract infections underlining the essential need for a more rational prescribing in this area