Discrepancies among equations to estimate the glomerular filtration rate for drug dosing decision making in aged patients: a cross sectional study.

BACKGROUND: Patients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations. AIM: To determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care. METHOD: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland-Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison. RESULTS: A total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations. CONCLUSION: Clinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average.

A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity.

Anticholinergic burden tools have relevant pharmacological gaps that may explain their limited predictive ability for clinical outcomes. The aim of this study was to provide a universal pharmacological-based list of drugs with their documented affinity for muscarinic receptors. A comprehensive literature review was performed to identify the anticholinergic burden tools. Drugs included in these instruments were searched in four pharmacological databases, and the investigation was supplemented with PubMed. The evidence regarding the potential antagonism of the five muscarinic receptors of each drug was assessed. The proportion of drugs included in the tools with an affinity for muscarinic receptors was evaluated. A universal list of drugs with anticholinergic activity was developed based on their documented affinity for the different subtypes of muscarinic receptors and their ability to cross the blood-brain barrier. A total of 23 tools were identified, including 304 different drugs. Only 48.68%, 47.70%, 48.03%, 43.75%, and 42.76% of the drugs had an affinity to the M1, M2, M3, M4, and M5 receptor, respectively, reported in any pharmacological database. The proportion of drugs with confirmed antagonism varied among the tools (36.8% to 100%). A universal pharmacological-based list of 133 drugs is presented. It should be further validated in different clinical settings.

Pharmacist-led medication reconciliation on admission to an acute psychiatric hospital unit.

Background: Therapy management in patients suffering from mental health disorders is complex and the risks derived from changes or interruptions of treatment should not be ignored. Medication reconciliation in psychiatry may reduce medication errors and promote patient safety during transitions of care. Objective: To identify the influence of complementary information sources in the construction of the best possible medication history, and to ascertain the potential clinical impact of discrepancies identified in a medication reconciliation service. Methods: An observational study was conducted in an acute mental hospital unit, with a further validation in an internal medicine unit. Adult patients taking at least one medicine admitted in the unit were included. Patients/caregivers were interviewed upon admission and the information gathered was compared with hospital medical and shared electronic medical records. Once the best possible medication history was gathered, therapeutic information was reconciled against the prescription on admission to identify discrepancies. Potential clinical impact of medication errors was classified using the International Safety Classification. Results: During the study period, 148 patients were admitted, 50.7% females, mean age 54.6 years (SD=16.3). Collaboration of a caregiver was a needed in 74% of the interviews. In total, 1,147 drugs were considered to obtain patients' best possible medication history. After reconciliation, 560 clinically sound intentional discrepancies were identified and 359 discrepancies required further clarification from prescribers: 84.12% "drug omission", 5.57% "drug substitution", 6.96% "dose change", and 3.34% "dosage frequency change". Potential clinical impact of these medication discrepancies was classified as: 95 mild, 100 moderate, and 29 severe medication errors. Conclusion: About 1 in three intentional discrepancies observed in a pharmacists-led medication reconciliation service required further clarification from prescribers, being 80% of them unintentional discrepancies. Results highlight the importance of the caregiver as source of information for the psychiatric patient, the relevance of analyzing shared electronic health records until 6 months before, and the need to use hospital medical records efficiently. Additionally, 29 discrepancies were classified as errors with potentially severe clinical impact. A medication reconciliation service is concluded to be feasible and necessary in a mental health unit.

Size of the associations between anticholinergic burden tool scores and adverse outcomes in older patients.

Background Several anticholinergic scales and equations to evaluate the anticholinergic burden have been previously created. Association of these instruments with the anticholinergic outcomes are usually estimated by means of hypothesis contrast tests, which ignore the size of the association effect. Objective To evaluate the effect size of the associations between the scores on cumulative anticholinergic burden instruments with peripheral or central anticholinergic adverse outcomes in older patients. Setting Internal medicine ward of a Tertiary University Hospital. Methods A case-control study was conducted in patients over 65 years who were admitted to two internal medicine wards of a Portuguese university hospital. The Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden scale and Drug Burden Index were used to calculate the patients' anticholinergic burden. Peripheral (dry mouth-swab technique; dry eye-Schirmer test) and central (falls and cognitive impairment-Mini-Mental State Examination) anticholinergic adverse outcomes were investigated. The Barthel Index was used to assess overall physical functionality. The Mann-Whitney test was used to evaluate probabilistic differences in the anticholinergic scores between case and control individuals. To establish the effect size of the associations, the area under the curve of the receiver operating characteristics curve was calculated. Main outcome measure Anticholinergic adverse effects. Results A total of 250 patients (mean age 81.67 years, standard deviation 7.768; 50% females) were included. In total, 148 patients (59.2%) presented with dry mouth, 85 (34%) with dry eye, 141 (56.4%) with impaired functionality, 44 (17.6%) with a history of falls and 219 (87.6%) with cognitive impairment. Significant differences (p < 0.05) were obtained for the majority of the associations between Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden and Drug Burden Index and adverse effects. Conversely, the effect sizes of these associations ranged from "fail" (area under the curve 0.5 to 0.6) to "fair" (area under the curve 0.7 to 0.8). Conclusion Although significant differences in the scores of anticholinergic burden instruments and adverse outcomes may exist, the effect sizes of these associations ranged from 'fail' to 'fair', which limits their utility in preventing anticholinergic adverse outcomes with medication review interventions.

Association between anticholinergic burden and anticholinergic adverse outcomes in the elderly: Pharmacological basis of their predictive value for adverse outcomes.

The use of anticholinergic drugs and other drugs with anticholinergic activity is highly prevalent in older people. Cumulative anticholinergic effects, known as anticholinergic burden, are associated with important peripheral and central adverse effects and outcomes. Several methods have been developed to quantify anticholinergic burden and to estimate the risk of adverse anticholinergic effects. Serum anticholinergic activity (SAA) and anticholinergic burden scoring systems are the most commonly used methods to predict the occurrence of important negative outcomes. These tools could guide clinicians in making more rational prescriptions to enhance patient safety, especially in older people. However, the literature has reported conflicting results about the predictive ability of these tools. The majority of these instruments ignore relevant pharmacologic aspects such as the doses used, differential muscarinic receptor subtype affinities, and blood-brain barrier permeability. To increase the clinical relevance of these tools, mechanistic and clinical pharmacology should collaborate. This narrative review describes the rational and pharmacological basis of anticholinergic burden tools and provides insight about their predictive value for adverse outcomes.

Patients' clinical information requirements to apply the STOPP/START criteria.

Background The STOPP/START criteria are an explicit tool to detect potentially inappropriate medications (PIMs). Patient clinical information may not be available in all settings. Objective To identify patient clinical information needed to apply the STOPP/START criteria. Setting: Four nursing homes in Portugal. Methods First, a theoretical analysis was performed to identify the patient information required to apply the STOPP/START criteria (v2), according to the following categories: patients' current medication, medication history (previous medication and duration), medical records (current and past medical conditions), and laboratory test results. A verification of the information requirements was conducted through a cross-sectional study on a nursing home population with patients over 65 years old. Patients' medical records were appraised to extract only demographic data and current medication profiles. Main outcome measure Information requirements of STOPP/START. Results For only 29 of the 81 STOPP criteria and 1 of the 34 START criteria, a judgement could be made with only the information in the patient's medication profile. 52 STOPP and 33 START criteria require additional information, (i.e. duration of therapy, previous medication, current and past medical conditions, and laboratory data). The 208 evaluated persons (87 years; 68.75% female) used 1770 medications, with 989 (55.9%) potentially involved in 1629 STOPP criteria. Sufficient information to judge STOPP criteria was available for only 529 (32.5%) potential STOPP criteria situations, with a positive identification of a STOPP PIM in 397 instances (75.0%). Conclusions Although STOPP/START criteria can be considered a high-level tool to identify PIMs, their use may be compromised in scenarios where access to patients' clinical information is limited.

Consequences of ignoring patient diagnoses when using the 2015 Updated Beers Criteria.

BACKGROUND: Beers Criteria are one of the best known explicit criteria to identify inappropriate medication in elderly that can be used in medication review. The access to patients' medical records may be different among healthcare professionals and settings and, subsequently, the identification of patients' diagnoses may be compromised. OBJECTIVE: To assess the consequences of ignoring patient diagnoses when applying 2015 Beers Criteria to identify potentially inappropriate medication (PIM). SETTING: Three nursing homes in Central Portugal. METHOD: Medical records of nursing home residents over 65 years old were appraised to identify medication profile and medical conditions. 2015 Beers Criteria were used with and without considering patients' diagnoses. To compare the number of PIM and PIM-qualifying criteria complied in these two judgements, Wilcoxon signed-rank tests were performed. MAIN OUTCOME MEASURE: Number of PIMs and number of PIM-qualifying criteria. RESULTS: A total of 185 patients with a mean age of 86.7 years (SD = 7.8) with a majority of female (70.3%) were studied. When assessing the patients with full access to the diagnoses, median number of PIMs was 4 (IQR 0-10) and number of PIM-qualifying criteria was 5 (IQR 0-15). When evaluating only patient current medication, median number of PIMs was 4 (IQR 0-10) and PIM-qualifying criteria was 4 (IQR 0-12). Statistical difference was found in the number of PIM-qualifying criteria identified (p < 0.001), but not in the number of PIMs per patient (p = 0.090). In 171 patients (92.4%) PIMs identified were identical when using or ignoring their medical diagnoses. However, in 80 patients (43.2%) the PIM-qualifying criteria complied were different with and without access to patient diagnoses. CONCLUSION: Although restricted access to patients' diagnoses may limit the judgement of Beers PIM-qualifying criteria, this limitation had no effect on the number of PIM identified.

Identification of inhaler technique errors with a routine procedure in Portuguese community pharmacy

Background: A correct selection of drugs prescribed, but also the choice of the appropriate inhaler device, is crucial for the control of respiratory diseases. Objective: To evaluate the inhaler technique and identify potential errors of patients when treated with inhalers by testing a routinary procedure to be implemented in any community pharmacy. Methods: Adults with asthma/COPD and under inhalation therapy were invited to demonstrate how they use their inhalers. After direct observation it was registered whether all the sequential steps included in the summary of product characteristics (SmPC) were performed. Results: The study involved 67 patients from 4 community pharmacies (Portugal central region): 34 (50.7%) males, 65.4 (SD=18.28) years old, 42 (62.7%) with COPD, and 23 (34.3%) using more than one inhaler. The 67 patients used 95 inhalers, comprising: 57 (60.0%) multiple dose DPI (dry powder inhalers), 18 (18.9%) single dose DPI, 16 (16.8%) pMDI (pressurized metered dose inhalers), 2 (2.1%) pMDI+spacer and 2 (2.1%) SMI (soft mist inhalers). No errors were made only by 9 (13.4%) patients. In the 75 DPIs techniques, the most frequent errors were ‘no previous forced expiration’ (46=61.3%) and ‘no 10s apnea after inhalation’ (51=68.0%); in the 16 pMDIs techniques common errors were ‘lack of hand-lung coordination’ (7=43.8 %), ‘no previous forced exhalation’ (8=50.0%) and ‘no apnea after inhalation’ (10=62.5%). After inhaling from 56 devices containing corticosteroids, 34 (60.7%) of the patients did not wash their mouth. Conclusion: The study demonstrated the possibility of performing this procedure routinely in Portuguese community pharmacies and also its utility, since 58 (87%) of patients had at least one error during the inhalers use (AU)

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Identification of inhaler technique errors with a routine procedure in Portuguese community pharmacy.

BACKGROUND: A correct selection of drugs prescribed, but also the choice of the appropriate inhaler device, is crucial for the control of respiratory diseases. OBJECTIVE: To evaluate the inhaler technique and identify potential errors of patients when treated with inhalers by testing a routinary procedure to be implemented in any community pharmacy. METHODS: Adults with asthma/COPD and under inhalation therapy were invited to demonstrate how they use their inhalers. After direct observation it was registered whether all the sequential steps included in the summary of product characteristics (SmPC) were performed. RESULTS: The study involved 67 patients from 4 community pharmacies (Portugal central region): 34 (50.7%) males, 65.4 (SD=18.28) years old, 42 (62.7%) with COPD, and 23 (34.3%) using more than one inhaler. The 67 patients used 95 inhalers, comprising: 57 (60.0%) multiple dose DPI (dry powder inhalers), 18 (18.9%) single dose DPI, 16 (16.8%) pMDI (pressurized metered dose inhalers), 2 (2.1%) pMDI+spacer and 2 (2.1%) SMI (soft mist inhalers). No errors were made only by 9 (13.4%) patients. In the 75 DPIs techniques, the most frequent errors were 'no previous forced expiration' (46=61.3%) and 'no 10s apnea after inhalation' (51=68.0%); in the 16 pMDIs techniques common errors were 'lack of hand-lung coordination' (7=43.8 %), 'no previous forced exhalation' (8=50.0%) and 'no apnea after inhalation' (10=62.5%). After inhaling from 56 devices containing corticosteroids, 34 (60.7%) of the patients did not wash their mouth. CONCLUSION: The study demonstrated the possibility of performing this procedure routinely in Portuguese community pharmacies and also its utility, since 58 (87%) of patients had at least one error during the inhalers use.