Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults.

BACKGROUND: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available. AIMS: This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy. METHODS: Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE). RESULTS: Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings. CONCLUSION: On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

Drug-Induced Hyponatremia: NSAIDs, a Neglected Cause that Should Be Considered.

Hyponatremia is the most common electrolyte disorder. It may have serious consequences in asyntomatic patients with a mild disease. Therefore, an evaluation of unsual causes is of paramount importance. Polypharmacy is highly prevalent in older people and many drugs can cause hyponatremia as a collateral effect. In our retrospective analysis of geriatric medical records dated 2015 we found that 39 out of the 273 hospitalized patients had hyponatremia. Polipharmacy was highly prevalent, especially in hyponatremic patients. Non-steroidal anti-inflammatory drugs, which are seldom considered as a cause of hyponatremia were instead found to be associated to an increased risk of the disorder (adjustedOR 3.61, 95% CI 1 - 12.99, p = 0.05). In-hospital mortality was higher in patients with moderate or severe hyponatremia at hospital admission. Our study underlines the importance of considering rare but potentially reversible causes of hyponatremia, which can lead to serious consequences.

Screening for unknown atrial fibrillation in older people: a feasibility study in community pharmacies.

INTRODUCTION: Atrial fibrillation (AF) is the most common heart arrhythmia. It is associated with an increased risk of morbidity and mortality and its prevalence rises with age. The arrhythmia is often asymptomatic, and systematic AF screening could help identify asymptomatic individuals to implement therapeutic and preventive strategies. The main study aims were to test the technical feasibility and citizens' acceptance of a freely offered service in older people using community pharmacies. MATERIALS AND METHODS: During 2 months, a 30-s single-lead electrocardiogram (ECG) with a telemedicine device was used for screening in 20 pharmacies in a mixed rural-urban health district of Northern Italy. RESULTS: A total of 289/335 older adults 70 years old or more agreed to participate in the study. A cardiologist considered 80% of the ECG tracings readable and unknown AF was identified in 1.3%. CONCLUSIONS: The screening scheme appears technically feasible and acceptable both to professionals and citizens/participants. Training the pharmacists could ensure broader participation and substantially improve the pharmacies' overall performance.

Pattern of in-hospital changes in drug use in the older people from 2010 to 2016.

PURPOSE: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. METHODS: People aged 65 years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. RESULTS: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. CONCLUSION: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population.

A “burning” therapy for burning mouth syndrome: preliminary results with the administration of topical capsaicin.

Burning mouth syndrome is defined as an intraoral burning sensation for which no medical or dental cause can be found. Recently, researchers have demonstrated an altered trophism of the small nerve fibres and alterations in the numbers of TRPV-1 vanilloid receptors. Capsaicin is a molecule that is contained in hot peppers and is specifically detected by TRPV-1 vanilloid receptors that are distributed in the oral mucosae. We aimed at verifying if topical capsaicin could prove to be an effective treatment of Burning Mouth Syndrome. A group of 99 BMS patients were recruited. We subdivided the BMS patients into two groups: the collaborative patients, who expressed a predominantly neuropathic pattern of symptoms, and the non-collaborative patients, who were characterised by stronger psychogenic patterns of the syndrome. Both groups underwent topical therapy with capsaicin in the form of a mouth rinse 3 times a day for a long period. After 1 year of treatment, the final overall success rate was approximately 78%, but with a significant difference in the success rates of the two groups of patients (87% and 20% among the collaborative and non-collaborative patients, respectively; p=0.000). The use of topical capsaicin can improve the oral discomfort of BMS patients, especially during the first month of therapy, but it is more effective for those patients in which the neuropathic component of the syndrome is predominant. Our hypothesis is that chronic stimulation with capsaicin leads to decreases in burning symptoms. This phenomenon is called desensitisation and is accompanied by substantial improvements in oral symptoms.

Evidence-based and unlicensed indications for proton pump inhibitors and patients' preferences for discontinuation: a pilot study in a sample of Italian community pharmacies.

WHAT IS KNOWN AND OBJECTIVE: Despite the widespread use of proton pump inhibitors (PPIs), little is known about the appropriateness of treatment according to the indications reported by patients and their involvement in the process of treatment discontinuation. In patients who are unlikely to benefit, the medication should be stopped and dose tapering is recommended to reduce the risk of rebound symptoms. The aims of this pilot study were to evaluate the appropriateness of treatment according to the reported indications by PPI users, patients' preferences for drug withdrawal, and the modalities of previous attempts to discontinue the medications. METHODS: This observational study was conducted in nine community pharmacies. Each pharmacist was asked to interview a sample of patients with prescriptions for PPIs and to collect a minimum set of information about socio-demographic characteristics, drug indication, duration of drug treatment, number of drugs used for acid-related disorders, preference about drug withdrawal, previous attempts at drug discontinuation and the method of drug tapering when this was performed. RESULTS AND DISCUSSION: The study included 260 patients, 126 (48·5%) females; 81 patients received more than one drug for acid-related problems and the second medication was more frequently prescribed by a general practitioner, community pharmacist or specialist. Unlicensed indication was reported by 125 patients, and 77 patients did not receive any information about the duration of treatment. Fifty-one patients were in favour of drug discontinuation. PPI withdrawal was attempted but was unsuccessful in 12 cases. Nine patients discussed the method of drug withdrawal with their physician, and abrupt discontinuation was the most frequent suggestion. Many patients were treated with PPIs for unlicensed indications such as gastroprotection because of the number of concomitant drugs used or unspecified gastroprotection. Recommendations about the main indications and the duration of treatment are essential to avoid unnecessary prescriptions and undefined prolongation of drug use. Correct information about the method of drug discontinuation is essential for success. WHAT IS NEW AND CONCLUSION: Many patients using PPIs are treated for unlicensed indications such as non-specific gastroprotection. The use of more than one drug for acid-related disorders is frequent among PPI users although this is not supported by evidence. Patients should be given clear and appropriate information about the duration of treatment and method of drug discontinuation.

Prevalence and Risk Factors Associated with Use of QT-Prolonging Drugs in Hospitalized Older People.

AIMS: The objective of this study was to evaluate the prevalence of the prescription of QT-prolonging drugs at hospital admission and discharge and the risk factors associated with their use in older people (aged 65 years and older). METHODS: Data were obtained from the REPOSI (REgistro POliterapie SIMI [Società Italiana di Medicina Interna]) registry, which enrolled 4035 patients in 2008 (n = 1332), 2010 (n = 1380), and 2012 (n = 1323). Multivariable logistic regression was performed to determine the risk factors independently associated with QT-prolonging drug use. QT-prolonging drugs were classified by the risk of Torsades de Pointes (TdP) (definite, possible, or conditional) according to the Arizona Center for Education and Research on Therapeutics (AzCERT) classification. Specific drug combinations were also assessed. RESULTS: Among 3906 patients prescribed at least one drug at admission, 2156 (55.2%) were taking at least one QT-prolonging drug. Risk factors independently associated with the use of any QT-prolonging drugs were increasing age (odds ratio [OR] 1.02, 95% CI 1.01-1.03), multimorbidity (OR 2.69, 95% CI 2.33-3.10), hypokalemia (OR 2.79, 95% CI 1.32-5.89), atrial fibrillation (OR 1.66, 95% CI 1.40-1.98), and heart failure (OR 3.17, 95% CI 2.49-4.05). Furosemide, alone or in combination, was the most prescribed drug. Amiodarone was the most prescribed drug with a definite risk of TdP. Both the absolute number of QT-prolonging drugs (2890 vs. 3549) and the number of patients treated with them (2456 vs. 2156) increased at discharge. Among 1808 patients not prescribed QT-prolonging drugs at admission, 35.8% were prescribed them at discharge. CONCLUSIONS: Despite their risk, QT-prolonging drugs are widely prescribed to hospitalized older persons. The curriculum for both practicing physicians and medical students should be strengthened to provide more education on the appropriate use of drugs in order to improve the management of hospitalized older people.

Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.

BACKGROUND: It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. METHODS: We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. RESULTS: Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. CONCLUSIONS: Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality.

Role of Community Pharmacies for the Detection of Potentially Inappropriate Xanthine Oxidase Inhibitor Prescriptions.

BACKGROUND: Xanthine oxidase (XO) inhibitors are largely the treatment of choice for gout, but allopurinol is often inappropriately used for asymptomatic hyperuricemia. There is little evidence that allopurinol is useful in preventing cardiovascular diseases and therapeutic decisions must the balance the expected benefit with the potential harm. OBJECTIVE: To investigate the appropriateness of XO inhibitor use in relation to evidence-based indications and examine the role of community pharmacies in the detection of inappropriate prescriptions of these drugs. METHODS: This is an observational study conducted in eight community pharmacies. Each pharmacist was asked to interview a sample of patients who had received prescriptions of XO inhibitors. Patients were asked to complete a structured minimum data set that collected information on drug indication, history of gout, and presence of cardiovascular diseases. RESULTS: The study sample included 74 patients receiving XO inhibitors. About one third of patients reported being treated for asymptomatic hyperuricemia and had never had a gout attack. About half of the patients treated for asymptomatic hyperuricemia had been receiving the drug treatment for more than 3 years. Four asymptomatic hyperuricemic patients received allopurinol to treat hypertension. Among the patients treated for asymptomatic hyperuricemia, there was a higher presence of diabetes mellitus, obesity, previous myocardial infarction, and heart failure than in patients treated for an appropriate indication. CONCLUSIONS: Inappropriate use of XO inhibitors is principally related to the treatment of hyperuricemia in patients with cardiovascular diseases. Community pharmacists have a central role in pharmacovigilance, by contributing to the prevention and identification of potentially inappropriate drug prescriptions.

Understanding adverse drug reactions in older adults through drug-drug interactions.

AIMS: The aims of this study are to evaluate prevalence and characteristics of adverse drug reactions (ADRs) and to evaluate the potential contribution of specific medications, therapeutic categories and drug-drug interactions (DDIs) in older adults. METHODS: All ADR reporting forms of persons aged 65+ years collected by the pharmacovigilance of one of the main hospitals in Italy during 2013 were evaluated. DDIs were analysed by a computerized prescription system (INTERCheck) and based on the interactions' database managed by the Istituto di Ricerche Farmacologiche Mario Negri. DDIs were classified according to their clinical relevance as contraindicated, major, and moderate. RESULTS: Amongst all the ADR reporting forms (n=1014) collected during 2013, 343 affected older adults. The most frequent ADRs were: haemorrhages (n=122, 35.5%), allergic reactions (n=56, 16.3%), and elevated International Normalized Ratio (INR>6, n=54, 15.7%). The specific medications that contributed to ADRs were warfarin (42.5%), acenocumarol (9%), and allopurinol (8.5%); while the therapeutic categories were haematological agents (67%) and proton pump inhibitors (13%). A total of 912 DDIs were found; one third of them were contraindicated or major and 31.5% of them potentially contributed to ADRs; of these, the most frequent were: warfarin and heparin (contraindicated, n=5); warfarin and a statin (major, n=38); warfarin and a proton pump inhibitor (moderate, n=40). At least one DDI contributed to 66 haemorrhages out of 122 (54%) and to 41 elevated INR out of 54 (76%). CONCLUSION: DDIs significantly contribute to the onset of ADRs in older adults and intervention programmes, e.g., the employment of a computerized system, may reduce the burden of iatrogenic illnesses in the elderly.

Inappropriate prescription of allopurinol and febuxostat and risk of adverse events in the elderly: results from the REPOSI registry.

PURPOSE: To investigate the prevalence of xanthine oxidase (XO) inhibitors prescription at admission and discharge in elderly hospital in-patients, to analyze the appropriateness of their use in relation to evidence-based indications, to evaluate the predictors of inappropriate prescription at discharge and the association with adverse events 3 months after hospital discharge. METHODS: This cross-sectional study, based upon a prospective registry, was held in 95 Italian internal medicine and geriatric hospital wards. The sample included 4035 patients aged 65 years or older at admission and 3502 at discharge. The prescription of XO inhibitors was considered appropriate in patients with diagnosis of gout, gout nephropathy, uric acid nephrolithiasis, tophi, and chemotherapy-induced hyperuricemia. In order to evaluate the predictors of inappropriate prescription of XO inhibitors, we compared the characteristics of patients considered inappropriately treated with those appropriately not treated. RESULTS: Among the 4035 patients eligible for the analysis, 467 (11.6 %) were treated with allopurinol or febuxostat at hospital admission and 461 (13.2 %) among 3502 patients discharged. At admission, 39 (8.6 %) of patients receiving XO inhibitors and 43 (9.4 %) at discharge were appropriately treated. Among those inappropriately treated, hyperuricemia, polytherapy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of XO inhibitors. Prescription of XO inhibitors was associated with a higher risk of adverse clinical events in univariate and multivariate analysis. CONCLUSIONS: Prevalence of inappropriate prescription of XO inhibitors remained almost the same at admission and discharge. Inappropriate use of these drugs is principally related to treatment of asymptomatic hyperuricemia and various cardiovascular diseases.

Gender-differences in disease distribution and outcome in hospitalized elderly: data from the REPOSI study.

BACKGROUND AND PURPOSE: Women live longer and outnumber men. On the other hand, older women develop more chronic diseases and conditions such as arthritis, osteoporosis and depression, leading to a greater number of years of living with disabilities. The aim of this study was to describe whether or not there are gender differences in the demographic profile, disease distribution and outcome in a population of hospitalized elderly people. METHODS: Retrospective observational study including all patients recruited for the REPOSI study in the year 2010. Analyses are referred to the whole group and gender categorization was applied. RESULTS: A total of 1380 hospitalized elderly subjects, 50.5% women and 49.5% men, were considered. Women were older than men, more often widow and living alone or in nursing homes. Disease distribution showed that malignancy, diabetes, coronary artery disease, chronic kidney disease and chronic obstructive pulmonary disease were more frequent in men, but hypertension, osteoarthritis, anemia and depression were more frequent in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment evaluated by the Short Blessed Test (SBT), mood disorders by the Geriatric Depression Scale (GDS) and disability in daily life measured by Barthel Index (BI) were worse in women. In-hospital and 3-month mortality rates were higher in men. CONCLUSIONS: Our study showed a gender dimorphism in the demographic and morbidity profiles of hospitalized elderly people, emphasizing once more the need for a personalized process of healthcare.

Prevalence of potentially inappropriate medications and risk of adverse clinical outcome in a cohort of hospitalized elderly patients: results from the REPOSI Study.

WHAT IS KNOWN AND OBJECTIVE: Inappropriate prescribing is highly prevalent for older people and has become a global healthcare concern because of its association with negative health outcomes including ADEs, hospitalization and resource utilization. Beers' criteria are widely utilized for evaluating the appropriateness of medications, and an up-to-date version has recently been published. To assess the prevalence of patients exposed to PIMs at hospital discharge according to the 2003 and 2012 versions of Beers' criteria and to evaluate the risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up. METHODS: This cross-sectional study was held in 66 Italian internal medicine and geriatric wards. The sample included 1380 inpatients aged 65 years or older. Prescriptions of PIM were analysed at hospital discharge. We considered all patients with complete 3-month follow-up. RESULTS AND DISCUSSION: The prevalence of patients receiving at least one PIM was 20·1% and 23·5% according to the 2003 and 2012 versions of the Beers' criteria, respectively. The 2012 Beers' criteria identified more patients with at least one PIM than the 2003 version, although a high percentage of those patients (72·2%) were also identified by the criteria updated in 2003. The main difference in the prevalence of patients receiving a PIM according to the two versions of Beers' criteria involved prescriptions of benzodiazepines for insomnia or agitation, chronic use of non-benzodiazepine hypnotics, prescription of antipsychotics in people with dementia and oral iron at dosage higher than 325 mg/day. Prescription of PIMs was not associated with a higher risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up in both univariate and multivariate analysis, after adjusting for age, sex and CIRS comorbidity index. WHAT IS NEW AND CONCLUSIONS: This study found no significant effect of inappropriate drug use according to Beers' criteria on health outcomes among older adults 3 month after discharge. Even though these criteria have been suggested as helpful in promoting appropriate prescribing, reducing drug-related adverse events and associated healthcare costs, to date there is no clear evidence that their application can achieve objective and quantifiable improvements in clinical outcomes. A possible explanation is that both versions of the Beers' criteria have several recognized limitations, one of the main ones being the restricted availability of some drugs in Europe or their limited prescription in everyday clinical practice.

Medication non-adherence among elderly patients newly discharged and receiving polypharmacy.

BACKGROUND: Poor adherence may have a major impact on clinical outcome, contributing to substantial worsening of disease, increased health care costs and even death. With increasing numbers of medications, low adherence is a growing concern, seriously undermining the benefits of current medical care. Little is known about medication adherence among older adults living at home and requiring complex medication regimens. OBJECTIVE: The aim of this study was to describe adherence to drug prescriptions in a cohort of elderly patients receiving polypharmacy, discharged from an internal medicine ward. METHODS: A sample of elderly patients (65 years of age or older) discharged from an internal medicine ward in Italy throughout 2012 were enrolled. They were followed for 3 months after discharge with a structured telephone interview to collect information on drug regimens and medication adherence 15-30 days (first follow-up) and 3 months (second follow-up) after discharge. Demographic variables including age, sex, marital status and caregiver were collected. RESULTS: Among 100 patients recruited, information on medication adherence was available for, respectively, 89 and 79 patients at the first and second follow-ups. Non-adherence was reported for 49 patients (55.1 %) at the first follow-up and for 55 (69.6 %) 3 months from discharge. Voluntary withdrawal of a drug and change of dosage without medical consultation were the main reasons for non-adherence at both follow-ups. The number of drugs prescribed at discharge was related to medication non-adherence at both follow-up interviews. No association was found between age and non-adherence. Only 25 patients (28.1 %) at the first follow-up and 20 (25.3 %) at the second understood the reasons for their medications. CONCLUSIONS: Low medication adherence is a real, complex problem for older patients receiving polypharmacy. We found that the increasing number of drugs prescribed at hospital discharge is correlated to non-adherence and a high percentage of patients did not understand the purpose of their medications. Simplification of drug regimens and reduction of pill burdens as well as better explanations of the reason for the medications should be targets for intervention.

E-learning to improve the drug prescribing in the hospitalized elderly patients: the ELICADHE feasibility pilot study.

BACKGROUND: E-learning is an efficient and cost-effective educational method. AIMS: This study aimed at evaluating the feasibility of an educational e-learning intervention, focused on teaching geriatric pharmacology and notions of comprehensive geriatric assessment, to improve drug prescribing to hospitalized elderly patients. METHODS: Eight geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control. Clinicians of the two groups had to complete a specific per group e-learning program in 30 days. Then, ten patients (aged ≥75 years) had to be consecutively enrolled collecting clinical data at hospital admission, discharge, and 3 months later. The quality of prescription was evaluated comparing the prevalence of potentially inappropriate medications through Beer's criteria and of potential drug-drug interactions through a specific computerized database. RESULTS: The study feasibility was confirmed by the high percentage (90 %) of clinicians who completed the e-learning program, the recruitment, and follow-up of all planned patients. The intervention was well accepted by all participating clinicians who judged positively (a mean score of >3 points on a scale of 5 points: 0 = useless; 5 = most useful) the specific contents, the methodology applied, the clinical relevance and utility of e-learning contents and tools for the evaluation of the appropriateness of drug prescribing. CONCLUSIONS: The pilot study met all the requested goals. The main study is currently ongoing and is planned to finish on July 2015.