Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels.

BACKGROUND: Serotonin syndrome is a rare and potentially fatal adverse drug reaction caused by serotonergic drugs and is due to an increase in serotonin concentration or activation of the 5-HT receptor in the central nervous system. We analysed adverse events in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data set to investigate the main drug classes related to reports of serotonin syndrome and the reporting risk in relation to age and sex. METHODS: We analysed data from the FAERS database to evaluate the main drug classes related to reports of the serotonin syndrome, and the reporting risk in relation to age and sex. RESULTS: We found 8,997 cases of serotonin syndrome; selective serotonin reuptake inhibitors (SSRIs) was the class of drugs with most reports, followed by opioids and other antidepressants. The highest Reporting Odds Ratios (ROR) for drug classes was for monoamine oxidase (MAO) inhibitors (45.99, 95% confidence interval (CI): 41.21-51.33) and SSRIs (32.66, 95% CI: 31.33-34.04), while the ten active substances with the highest ROR were moclobemide, isocarboxazid, oxitriptane, tranylcypromine, melitracen, phenelzine, linezolid, amoxapine, reboxetine and tryptophan; with values of ROR ranging from 44.19 (95% CI: 25.38-76.94) of tryptophan to 388.36 (95% CI: 314.58-479.46) of moclobemide. The ROR for the most commonly involved drugs was higher in the group of older adults (65 > years old), and higher in males. CONCLUSION: Prescribers need to be vigilant about drugs that can raise serotonin concentration or influence serotonergic neurotransmission, also when using drugs with less well-known risk for serotonin syndrome, like linezolid and triptans.

Potentially Inappropriate Psychotropic Drugs in Nursing Homes: An Italian Observational Study.

BACKGROUND AND OBJECTIVES: Physicians often face difficulties in selecting appropriate medications for older adults with multiple comorbidities. As people age, they are more likely to be living with a number of chronic conditions (multimorbidity) and be prescribed a high number of medications (polypharmacy). Multimorbidity is frequent in nursing home (NH) residents and the use of potentially inappropriate medications, especially psychotropic drugs, is widespread. This retrospective cross-sectional cohort study examined the frequency of potentially inappropriate psychotropic drugs using the Beers, Screening Tool of Older Persons' Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Fit fOR The Aged (FORTA) criteria, and their association with mortality. METHODS: This retrospective cross-sectional cohort study was conducted on a sample of long-term care NHs across Italy. Of the 34 NHs with an electronic medical records system, 27 met the inclusion criteria, with complete web-based case report forms (CRFs). Residents under the age of 65 years were excluded. We calculated the prevalence of potentially inappropriate psychotropics drugs (antipsychotics, antidepressants and anxiolytics/hypnotics) according to three criteria for prescriptive appropriateness. Univariate and multivariate correlations were examined, taking into account age, sex, comorbidities, and the number of psychotropic drugs, to analyse the relationship between inappropriate psychotropic use and mortality rates. The rate of inappropriate psychotropic prescriptions was calculated with the prevalence of residents receiving potentially inappropriate psychotropic drugs according to the three criteria. We used a logistic model to check for a possible predictive relationship between inappropriate use of psychotropics and mortality. The study evaluated differences in prescriptive appropriateness among NHs by analysing the proportions of potentially inappropriately treated residents at the last visit. Differences were compared with the overall sample mean using confidence intervals (CIs) calculated using Wald's method. RESULTS: This study involved 2555 residents, of whom 1908 (74.7% of the total) were treated with psychotropic drugs; 186 (7.3% of the total) were exposed to at least one psychotropic drug considered potentially inappropriate according to the FORTA criteria. Analysis using the Beers criteria showed that 1616 residents (63.2% of the total) received at least one psychotropic drug considered potentially inappropriate. In line with the Beers recommendation, patients receiving at least three psychotropic drugs were also included and 440 were identified (17.2% of the total sample). According to the STOPP criteria, 1451 residents (56.8% of the total sample) were prescribed potentially inappropriate psychotropic drugs. No correlation was found between potentially inappropriate use of psychotropic drugs and mortality, in either univariate analysis or in a multivariate model adjusted for age, sex and comorbidity index. CONCLUSIONS: Different criteria for appropriate drug prescription identify very different percentages of patients in NHs exposed to psychotropics considered potentially inappropriate. The Beers and STOPP/START criteria identified a larger percentage of patients exposed in NHs than FORTA.

Anticholinergic Burden and Cognitive Impairment in Nursing Homes: A Comparison of Four Anticholinergic Scales.

BACKGROUND: Medications with anticholinergic effects are commonly used in nursing homes, and their cumulative effect is of particular concern for the risk of adverse effects on cognition. OBJECTIVE: The relation between cognitive function and anticholinergic burden measured with four scales, the Anticholinergic Cognitive Burden (ACB) Scale, the Anticholinergic Risk Scale, the German Anticholinergic Burden Scale, and the CRIDECO Anticholinergic Load Scale, is assessed according to the hypothesis that a higher anticholinergic burden is associated with reduced cognitive performance. METHODS: This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term-care nursing homes (NH). Sociodemographic details, diagnosis, and drug treatments of each NH resident were collected using medical records four times during 2018 and 2019. Cognitive status was rated with the Mini-Mental State Examination (MMSE). The prevalence of anticholinergic use and its burden were calculated referring to the last time point for each patient. A longitudinal analysis was done on NH residents with at least two MMSE between 2018 and 2019 to assess the relation between the anticholinergic load and decline in MMSE. The relationship between drug-related anticholinergic burden and cognitive performance was analyzed using Poisson regression model theory. Multivariate analyses were adjusted according to the known risk factors of reduced cognitive performance available [age, sex, history of stroke or transient ischemic attack (TIA), and number of non-anticholinergic drugs] and for cholinesterase inhibitors. In view of the high number of subjects with an MMSE score = 0 among residents with dementia, for this group a zero-inflated Poisson regression model was used to give more consistent results. The association of anticholinergic burden with mortality was examined from each patient's last visit using a multivariate logistic model adjusted for age, sex, and Charlson Comorbidity Index (CCI). RESULTS: Among 1412 residents recruited, a clear direct relationship was found between higher anticholinergic burden and cognitive impairment only for the Anticholinergic Cognitive Burden Scale. Residents taking an anticholinergic who scored 5 or more had 2.5 points more decline than those not taking them (p < 0.001). Among residents without dementia there was a trend toward direct relationship for the Anticholinergic Cognitive Burden Scale and the Anticholinergic Risk Scale. Residents with higher scores had about 2 points more decline than residents not taking anticholinergic drugs. No relation was found between anticholinergic burden and cognitive decline or mortality. CONCLUSIONS: The cumulative effect of medications with modest antimuscarinic activity may influence the cognitive performance of NH residents. The anticholinergic burden measured with the ACB scale should help identify NH residents who may benefit from reducing the anticholinergic burden. A clear direct relationship between anticholinergic burden and cognitive impairment was found only for the ACB Scale.

Adherence and Persistence to Medical Therapy in Glaucoma: An Overview.

Glaucoma is a group of progressive optic neuropathies characterized by loss of retinal ganglion cells and visual field deterioration. Despite the fact that the underlying pathophysiology of glaucoma remains unknown, elevated intraocular pressure (IOP) is a well-established risk factor, and the only factor that can be modified. Robust evidence from epidemiological studies and clinical trials has clearly demonstrated the benefits of IOP control in reducing the risk of glaucoma progression. IOP-lowering therapy by the means of eye drops remains a first-line treatment option. However, like other chronic and asymptomatic conditions, many patients with glaucoma have difficulties in maintaining high rates of adherence persistence to prescribed medications. On average, patients with chronic medical conditions take 30-70% of the prescribed medication doses, and on average 50% discontinue medications in the first months of therapy. The ophthalmic literature shows similarly low rates of adherence to treatment. Indeed, poor adherence is associated with disease progression and increased complication rates, as well as healthcare costs. The present review analyzes and discusses the causes of variability of the adherence to the prescribed drugs. The education of patients about glaucoma and the potential consequences of insufficient adherence and persistence seems fundamental to maximize the probability of treatment success and therefore prevent visual disability to avoid unnecessary healthcare costs.

Factors Associated with a High-Risk Profile for Developing Pressure Injuries in Long-Term Residents of Nursing Homes.

OBJECTIVES: Pressure injuries are a health problem of special concern for older adults, and different scales are used to assess the risk of developing these ulcers. We assessed the prevalence of residents at high risk of pressure injuries using a Norton scale and examined its relationships with the most important risk factors in a large sample of Italian nursing homes (NHs). METHOD: This was a cross-sectional cohort study in a sample of Italian long-term care NHs with data collected between 2018 and 2020. RESULTS: We recruited 2,604 NH residents; 1,252 had Norton scale scores, 41 (3.3%) had a diagnosis of pressure injuries, 571 (45.6%) had a Norton score ≤9, and 453 (36.2%) had a score between 10 and 14. The univariate model showed a relationship between female sex, age, dementia, and cerebrovascular disease with a Norton scale score ≤9. The significant associations were confirmed in the multivariate model with stepwise selection. CONCLUSION: The prevalence of NH residents at high risk of pressure injuries was very high using the Norton scale, but the percentage of residents who develop these ulcers is lower. Female NH residents with advanced age, dementia, and a history of cerebrovascular disease should be carefully monitored.

Prevalence of Pharmacologic Treatments for Chronic Obstructive Pulmonary Disease in Relation of Diagnosis of Dementia Among Nursing Homes Residents.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a chronic disease affecting millions of older adults. We investigated the prevalence of nursing home (NH) residents with COPD and their pharmacologic treatment in relation to the diagnosis of dementia and the prevalence of potentially severe drug-drug interactions (DDIs) of COPD medications with drugs prescribed to treat comorbidities. DESIGN: Retrospective cross-sectional multicentre study. SETTING AND PARTICIPANTS: Individuals living in long-term care NHs. METHODS: This cross-sectional cohort study was conducted in a sample of Italian long-term care NHs located throughout the country. Information on drug prescriptions, diseases, and sociodemographic characteristics was collected using medical records between 2018 and 2020. Potentially severe DDIs were analyzed using INTERCheck, developed by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS. RESULTS: Among the 2604 residents living in 27 NHs (mean age 86.4 ± 8.5 years; women 1995, 76.6%; number of drugs 7.3 ± 3.6), 306 had a diagnosis of COPD (11.8%) and 84 (27.5%) of them were treated with at least 1 medication for COPD (27.5%). Those without dementia had a higher prevalence of drugs for COPD than those with dementia (48% vs 20%, P < .0001). The most used classes for COPD were adrenergics in combination with corticosteroids (16.7%) and inhalant anticholinergics (14.7%). Among those receiving medications for COPD, 45 had at least 1 potentially severe DDI with medications for comorbidities (53.6%) and most of them were associated with an increased risk of QTc prolongation, as beta2 agonists with diuretics, antipsychotics or antidepressants. CONCLUSIONS AND IMPLICATIONS: Most NH residents with COPD did not receive any medication for this disease despite the potential benefits. Residents with dementia received fewer COPD medications probably because of their compromised physical and cognitive status. One-half of the NH residents taking medication for COPD were exposed to an increased risk of QTc prolongation and torsades de pointe because of pharmacodynamic DDIs with medication for comorbidities. Close monitoring of electrocardiograms for NH residents with COPD is recommended.

Anemia in nursing homes, proton pump inhibitors and prescribing cascade of antianemic drugs.

PURPOSE: Some medications can cause anemia through their effect on gastrointestinal function, such as proton pump inhibitors and H2-antagonists, and on the risk of bleeding, such as anticoagulants and antiplatelet agents. The main aim of this study is to evaluate how anemia is related with the most commonly used drugs in a large sample of NH residents. METHODS: This retrospective cross-sectional multicenter study was conducted in a sample of Italian long-term care NHs distributed throughout the country. RESULTS: In all, 2602 NH residents recruited from 27 Italian long-term NHs (mean age ± SD: 88.4 ± 8.5) and 441 (16.9%) had a diagnosis of anemia. The unadjusted model showed a significant relation with PPI (OR 1.71, 95% CI 1.39-2.11, p < 0.0001). This relation was maintained in the model adjusted for age, sex, CKD, atrophic gastritis, peptic ulcer and rheumatic disease (OR 1.61, 95% CI 1.31-1.99, p < 0.0001). PPI users were also at higher risk of being treated with antianemic drugs-iron supplements, folate, vitamin B12 and erythropoietin (OR 2.03, 95% CI 1.67-2.48, p < 0.0001)-even if they did not have anemia (OR 1.94, 95% CI 1.55-2.42, p < 0.0001). CONCLUSION: Proton pump inhibitors are associated with anemia in NH residents. PPIs are also related with an increased probability of receiving drugs to treat anemia, such as iron supplements, folate or cyanocobalamin and erythropoietin, as the effect of a prescribing cascade. Optimization of PPI prescription is needed to avoid adverse events and promote rational drug prescription.

Prevalence of Delirium in End-of-Life Palliative Care Patients: An Observational Study.

OBJECTIVES: The aim of this study was to assess the prevalence of delirium, using the Assessment Test for Delirium and Cognitive Impairment (4AT) in end-of-life palliative care patients. SUBJECTS AND METHODS: This retrospective cross-sectional study was conducted on end-of-life patients in a hospice or at home. All patients were evaluated with the 4AT for the presence of delirium. RESULTS: Of the 461 patients analyzed, 76 (16.5%) were inpatients and 83.5% (385) outpatients. The median age was 79.5 (72-86) years, and 51.0% were female. According to the 4AT score, 126 patients (27.3%) had delirium (A4T ≥4) at admission, 28 (36.8%) were inpatients, and 98 (25.5%) outpatients. Around 33.8% of the cancer inpatients had delirium, while 20.6% of the cancer outpatients had delirium. The prevalence of delirium varied according to the setting, clinical condition, and life expectancy. In addition, 55.0% (11) actively dying inpatients, within 3 days, had delirium, and 56.7% (17) outpatients had delirium; while among those with life expectancy longer than 4 days, 30.4% (17) inpatients and 22.8% (81) outpatients were with delirium. CONCLUSIONS: Our study confirms that delirium is common in cancer and noncancer palliative care patients. Further research on delirium in end-of-life palliative care patients should consider the complexity of palliative care of this population as well as of the characteristics of the settings.

Laxative Agents in Nursing Homes: An Example of Prescribing Cascade.

OBJECTIVES: Laxatives are among the most prescribed medications to nursing home (NH) patients, and we evaluated the hypothesis that laxative agents could be prescribed as a result of a prescribing cascade. The aims of the study are (1) to investigate the use of laxative drugs in a large sample of Italian NHs and (2) to assess the relationship between medications that can induce constipation and laxative use. DESIGN: Retrospective cross-sectional multicenter study. SETTING AND PARTICIPANTS: Individuals living in long-term care NHs. METHODS: Study conducted in a sample of Italian long-term care NHs distributed throughout the country. Information on drug prescriptions, diseases and sociodemographic characteristics collected 4 times during 2018 and 2019. RESULTS: Among the 2602 patients recruited from 27 NHs (mean age ± standard deviation: 88.4 ± 8.5; women: 1994, 76.6%), 1248 were receiving laxatives (48%). Parkinson disease, cerebrovascular disease, and hemiplegia were associated with laxative prescription, and diabetes was associated with a decrease. Benzodiazepines, anti-Parkinson dopaminergic agents, and antidepressants (tricyclic antidepressants and mirtazapine) were associated with laxative treatment in univariate and adjusted models. Tricyclic antidepressants users were 3 times more likely to be taking laxatives than nonusers (odds ratio 2.98, 95% confidence interval 1.31-6.77, P = .0093). A larger number of drugs that can induce constipation was associated with laxative use (P = .0003). In all, 2002 individuals had at least 2 different prescription times: from the first to the last visit laxative use rose from 46.1% to 49.9%. Time of stay was also associated with laxative use (P = .016). CONCLUSIONS AND IMPLICATIONS: Laxatives are among the most prescribed medications in Italian NHs. Medications that can induce constipation, such as antidepressants, anti-Parkinson dopaminergic agents, and benzodiazepines, are often used together with laxatives, and combinations of these drugs further increase the use of laxatives. Optimizing the prescription of psychotropic drugs could help reduce the "prescribing cascade" with laxatives. The length of stay in NHs is often proportional to laxative use and chronic treatment is very common.

Use of preventive drugs during the last year of life in older adults with cancer or chronic progressive diseases.

PURPOSE: To evaluate the prescription of preventive medications with questionable usefulness in community dwelling elderly adults with cancer or chronic progressive diseases during the last year of life. METHODS: Through the utilization of the healthcare databases of the Lombardy region, Italy, we identified two retrospective cohorts of patients aged 65 years or more, who died in 2018 and had a diagnosis of either a solid cancer (N = 19 367) or a chronic progressive disease (N = 27 819). We estimated prescription of eight major classes of preventive drugs 1 year and 1 month before death; continuation or initiation of preventive drug use during the last month of life was also investigated. RESULTS: Over the last year of life, in both oncologic and non-oncologic patients, we observed a modest decrease in the prescription of blood glucose-lowering drugs, anti-hypertensives, lipid-modifying agents, and bisphosphonates, and a slight increase in the prescription of vitamins, minerals, antianemic drugs, and antithrombotic agents (among oncologic patients only). One month before death, the prescription of preventive drugs was still common, particularly for anti-hypertensives, antithrombotics, and antianemics, with more than 60% of patients continuing to be prescribed most preventive drugs and an over 10% starting a therapy with an antithrombotic, an antianemic, or a vitamin or mineral supplement. CONCLUSION: These findings support the need for an appropriate drug review and improvement in the quality of drug prescription for vulnerable populations at the end-of-life.

Anticholinergic load and delirium in end-of-life patients.

BACKGROUND: Delirium is a neuropsychiatric syndrome associated with negative outcomes, including worsening of cognitive and functional status and an increased burden on patients and caregivers. Medications with anticholinergic effect have been associated with delirium symptoms, but the relationship is still debated. OBJECTIVE: To assess the relation between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium. METHODS: This retrospective cross-sectional study was conducted in a sample of end-of-life patients in a hospice or living at home between February and August 2019. Delirium was diagnosed on admission using the 4 'A's Test (4AT) and each patient's anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. RESULTS: Of the 461 eligible for analysis, 124 (26.9%) had delirium. Anticholinergic medications were associated with an increased risk of delirium in univariate (OR (95% CI) 1.26 (1.16-1.38), p < 0.0001) and multivariate models adjusted for age, sex, dementia, tumors, Karnofsky Performance Status (KPS) score, days of palliative assistance, and setting (OR (95% CI) 1.16 (1.05-1.28), p < 0.0001). Patients with delirium had a greater anticholinergic burden than those without, with a dose-effect relationship between total ACB score and delirium. Patients who scored 4 or more had 2 or 3 times the risk of delirium than those not taking anticholinergic drugs. The dose-response relationship was maintained in the multivariate model. CONCLUSIONS: Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity.

Drug-Drug Interactions and Prescription Appropriateness at Hospital Discharge: Experience with COVID-19 Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) are often elderly, with comorbidities, and receiving polypharmacy, all of which are known factors for potentially severe drug-drug interactions (DDIs) and the prescription of potentially inappropriate medications (PIMs). OBJECTIVE: The aim of this study was to assess the risk of DDIs and PIMs in COVID-19 patients at hospital discharge. METHOD: Patients with a proven diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were hospitalized between 21 February and 30 April 2020, treated with at least two drugs, and with available information regarding pharmacological treatments upon admission and at discharge were considered. The appropriateness of drug prescriptions was assessed using INTERcheck®. RESULTS: A significant increase in the prescription of proton pump inhibitors and heparins was found when comparing admission with hospital discharge (from 24 to 33% [p < 0.05] and from 1 to 17% [p < 0.01], respectively). The increased prescription of heparins at discharge resulted in a highly significant increase in the potentially severe DDIs mediated by this class of drugs. 51% of COVID-19 patients aged > 65 years had at least one PIM upon admission, with an insignificant increment at discharge (58%). CONCLUSION: An increased number of prescribed drugs was observed in COVID-19 patients discharged from our hospital. The addition of heparins is appropriate according to the current literature, while the use of proton pump inhibitors is more controversial. Particular attention should be paid to the risk of bleeding complications linked to heparin-based DDIs.

Darunavir/Cobicistat Is Associated with Negative Outcomes in HIV-Negative Patients with Severe COVID-19 Pneumonia.

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150 mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p > .05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p = .9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p < .0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p = .03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.

Pharmacist-driven medication recognition/ reconciliation in older medical patients.

BACKGROUND: In older medical patients polypharmacy is often associated with poor prescription appropriateness and harmful drug-drug interactions. An effort that jointly involved hospital pharmacists and clinicians attending multimorbid older patients acutely admitted to medical wards was implemented for medication recognition and reconciliation aided by the use of a computerized support system. METHODS: Six internal medicine wards enrolled consecutively 90 acutely admitted multimorbid patients aged 75 years or more taking 5 or more different drugs. Two hospital pharmacists carried out the recognition of medications taken at hospital ward admission, and interacted with the clinicians in a process of drug reconciliation, using also the computerized support system to evaluate drug related problems, prescription inappropriateness or drug-drug interactions. The process was repeated at hospital discharge. RESULTS: Among a total number of 911 drugs prescribed to 90 older medical patients at ward admission, the pharmacists identified during their recognition/reconciliation 455 drug-related problems, mainly due to prescription of medications inappropriate for older multimorbid patients and clinically harmful drug-drug interactions. When these drug-related problems were identified by the pharmacist, the attending clinicians accepted and implemented the suggestions for changes for approximately two thirds of the discrepancies, thereby leading to deprescribing the implicated drugs or at least to their closer monitoring. CONCLUSIONS: This interventional prospective study based upon the integrated expertise of hospital pharmacists and clinicians confirms that drug-related problems are frequent in multimorbid older patients acutely admitted to hospital medical wards, and demonstrates afresh the feasibility and mutual acceptance of a trajectory of recognition/reconciliation based upon an integrated collaboration between hospital pharmacists and ward clinicians in the process of medication optimization.

Comparison between drug therapy-based comorbidity indices and the Charlson Comorbidity Index for the detection of severe multimorbidity in older subjects.

BACKGROUND: To know burden disease of a patient is a key point for clinical practice and research, especially in the elderly. Charlson's Comorbidity Index (CCI) is the most widely used rating system, but when diagnoses are not available therapy-based comorbidity indices (TBCI) are an alternative. However, their performance is debated. This study compares the relations between Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), Chronic Disease Score (CDS), and severe multimorbidity, according to the CCI classification, in the elderly. METHODS: Logistic regression and Receiver Operating Characteristic (ROC) analysis were conducted on two samples from Italy: 2579 nursing home residents (Korian sample) and 7505 older adults admitted acutely to geriatric or internal medicine wards (REPOSI sample). RESULTS: The proportion of subjects with severe comorbidity rose with TBCI score increment, but the Area Under the Curve (AUC) for the CDS (Korian: 0.70, REPOSI: 0.79) and MCI (Korian: 0.69, REPOSI: 0.81) were definitely better than the DDCI (Korian: 0.66, REPOSI: 0.74). All TBCIs showed low Positive Predictive Values (maximum: 0.066 in REPOSI and 0.317 in Korian) for the detection of severe multimorbidity. CONCLUSION: CDS and MCI were better predictors of severe multimorbidity in older adults than DDCI, according to the CCI classification. A high CCI score was related to a high TBCI. However, the opposite is not necessarily true probably because of non-evidence-based prescriptions or physicians' prescribing attitudes. TBCIs did not appear selective for detecting of severe multimorbidity, though they could be used as a measure of disease burden, in the absence of other solutions.

Inappropriate prescribing in intermediate care facilities.

Inappropriate prescribing for older people is a global healthcare problem. This study aimed to determine the prevalence of older patients receiving potentially inappropriate medications (PIMs) at admission and discharge at the intermediate care facility of ASP Pio Albergo Trivulzio. We consecutively enrolled 100 patients aged ≥ 65 from December 2017 to May 2018 and evaluated PIMs with the 2015 version of the Beers criteria. We found a significant reduction in the prescription of drugs to avoid and proton pump inhibitors (PPIs), while patients with at least one psychotropic drug to avoid or to use with caution significantly increased. The inappropriate prescription of PPIs was mainly associated with the use of heparin. Optimizing PPI and psychotropic drug prescriptions should be considered for deprescribing inappropriate polypharmacy in intermediate care facilities.

Initiation of Psycholeptic Medication During Hospitalization With Recommendation for Discontinuation After Discharge.

OBJECTIVES: Psycholeptic drugs have been used in the older population for years, especially to control delirium and neuropsychiatric symptoms (NPS) of dementia. However, data from the literature confirm that the prolonged use of psycholeptics may be responsible for adverse reactions in older patients. The aim of this study was (1) to identify how many patients receive the first prescription of a psycholeptic drug during the hospital stay; (2) to evaluate the main sociodemographic and clinical characteristics of these patients; and (3) to verify if the prescribed psycholeptic drugs are continued after 3 months from the hospital discharge. DESIGN: Our retrospective study was based on data from the REPOSI (REgistro POliterapie SIMI) registry, a cohort of older patients hospitalized in internal medicine and geriatric wards throughout Italy from 2010 to 2018. SETTING AND PARTICIPANTS: Patients aged 65 years or older who were not on home therapy with psycholeptic drugs were considered in the analyses. METHODS: We did both univariate and multivariate analyses in order to find the variables associated independently to an increased risk for first psycholeptic prescription at hospital discharge. RESULTS: At hospital discharge, 193 patients (5.8%) out of a total sample of 3322 patients were prescribed at least 1 psycholeptic drug. Cognitive impairment was the main risk factor for the introduction of psycholeptic drugs at discharge. Among them, 89.1% were still on therapy with a psycholeptic drug after 3 months from the hospital discharge. CONCLUSIONS AND IMPLICATIONS: Cognitive impairment represents the main risk factor for psycholeptic initiation in hospitalized older patients. The vast majority of these treatments are chronically continued after the discharge. Therefore, special attention is needed in prescribing psycholeptics at discharge, because their prolonged use may lead to cognitive decline. Moreover, their continued use should be questioned by physicians providing post-acute care, and deprescribing should be considered.

Drug-Drug Interactions and Prescription Appropriateness in Patients with COVID-19: A Retrospective Analysis from a Reference Hospital in Northern Italy.

BACKGROUND: Patients hospitalised with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2; coronavirus 2019 disease (COVID-19)] infection are frequently older with co-morbidities and receiving polypharmacy, all of which are known risk factors for drug-drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for COVID-19. OBJECTIVE: The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in patients with COVID-19 treated at our hospital. METHODS: We retrospectively analysed 502 patients with COVID-19 (mean age 61 ± 16 years, range 15-99) treated at our hospital with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. RESULTS: Overall, 68% of our patients with COVID-19 were exposed to at least one potential DDI, and 55% were exposed to at least one potentially severe DDI. The proportion of patients experiencing potentially severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of potentially severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The majority of potentially severe DDIs carried an increased risk of cardiotoxicity. No potentially severe DDIs were identified in relation to tocilizumab and remdesivir. CONCLUSIONS: Among hospitalised patients with COVID-19, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of potentially severe DDIs. Given the high risk of cardiotoxicity and the scant and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in patients with COVID-19 with polypharmacy needs to be carefully considered.