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.

Sustainable and personalized nutrition: From earth health to public health.

Sustainable nutrition, equaling earth health, involves a personalized approach designed in terms of precision and avoidance of still cogent but unjustified dogmas, equaling public health. For instance, current dietary recommendations continue to dwell on the need to limit as much as possible the intake of saturated fatty acids (SFA), notwithstanding the mounting evidence that the effects of food on health cannot be predicted from the content of single nutrients without considering the overall macronutrient composition and the role of the food matrix. The traditional recommendation to restrict SFA ignores that their effects on health depend on the interaction between naturally occurring food components and those introduced by food processing. It is warranted to modify the still widely promoted dietary guidelines based upon such single nutrients as SFA and instead personalize dietary habits on the basis of the whole pattern of the food matrix. Accordingly, the double edge of malnutrition, that involves deficiency as well as excess and materializes in many individuals throughout their life course, might be tackled by implementing sustainability, with the additional effect of overcoming global inequalities. Within this context SFA may regain their position of tasty and cheap sources of energy to be adapted to each individual lifestyle.

Use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease in hospitalized older people.

PURPOSE: The aims of this study were to assess the prevalence of use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease (GERD) at hospital admission and discharge. METHODS: Patients aged 65 years or more hospitalized from 2010 to 2016 in 101 Italian internal medicine and geriatric wards in the context of the REPOSI register were scrutinized to assess if they were prescribed with drugs for peptic ulcer and GERD at hospital admission and discharge. Appropriateness of prescription was assessed considering the presence of specific conditions (i.e., history of peptic ulcer or gastrointestinal hemorrhages, advanced age, Helicobacter Pylori) or gastro-toxic drug combinations, according to the criteria provided by the reimbursement rules of the Agenzia Italiana del Farmaco (NOTA 1 and 48). RESULTS: Among 4715 enrolled patients, 3899 were discharged alive. At hospital discharge, 2412 (61.9%, 95%CI: 60.3-63.4%) patients were prescribed with drugs for peptic ulcer and GERD, a 12% of increase from hospital admission. Almost half of the patients (N = 1776, 45.6%, 95%CI: 44.0-47.1%) were inappropriately prescribed or not prescribed: among the drugs for peptic ulcer and GERD users, about 60% (1444/2412) were overprescribed, and among nonusers, 22% (332/1487) were underprescribed. Among patients newly prescribed at hospital discharge, 60% (392/668) were inappropriately prescribed. The appropriateness of drugs for peptic ulcer and GERD therapy decreased by 3% from hospital admission to discharge. CONCLUSIONS: Hospitalization missed the opportunity to improve the quality of prescription of this class of drug.

Inappropriate prescription of benzodiazepines in acutely hospitalized older patients.

Benzodiazepines (BDZs) are widely prescribed in older people. The aims of the study are to assess the prevalence of inappropriate prescription of BZDs and the associated factors in acutely hospitalized older patients. Patients aged 65 years or more hospitalized from 2010 to 2017 in more than 100 Italian internal medicine and geriatric wards in the frame of the REPOSI register were included if prescribed with BDZs at hospital admission or discharge. Appropriateness of prescription was assessed according to the 2015 Beers criteria and their modified French and German versions. Among 4681 patients discharged from hospital, 15% (N = 710) were discharged with BDZs, and 62% of them (N = 441, 95% CI: 58.5%-65.6%) were inappropriately prescribed, being prescribed with BDZ to be always avoided in the elderly (45%), at higher doses than recommended (31%) or with no appropriate clinical conditions (19%). From admission to discharge the prevalence of inappropriate BDZ prescription decreased by 4%, but 62% of patients inappropriately prescribed at admission were still inappropriately prescribed at discharge. Among the 179 patients first prescribed at the time of discharge, half were inappropriately prescribed. Being female (OR 1.32, 95%CI 0.95-1.85), enrolled in REPOSI during the years 2016 and 2017 (OR 1.94, 95%CI 1.10-3.39; OR 1.57, 95%CI 0.95-2.58) and living in nursing homes (OR 2.04, 95%CI 0.95-4.37) were associated with an increased risk to be inappropriately prescribed. This study shows a high prevalence of inappropriate use of BDZ in acutely hospitalized older patients both at hospital admission and discharge.

Antibiotic use and associated factors in a large sample of hospitalised older people.

OBJECTIVES: The aims of this study were to assess (i) the prevalence of antibiotic use, (ii) factors associated with their use and (iii) the association with in-hospital mortality in a large sample of hospitalised older people in Italy. METHODS: Data were obtained from the 2010-2017 REPOSI register held in more than 100 internal medicine and geriatric wards in Italy. Patients aged ≥65 years with at least one antibiotic prescription during their hospitalisation were selected. Multivariable logistic regression models were used to determine factors associated with antibiotic use. RESULTS: A total of 5442 older patients were included in the analysis, of whom 2786 (51.2%) were prescribed antibiotics during their hospitalisation. The most frequently prescribed antibiotic class was ß- lactams, accounting for 50% of the total prescriptions. Poor physical independence, corticosteroid use and being hospitalised in Northern Italy were factors associated with a higher likelihood of being prescribed antibiotics. Antibiotic use was associated with an increased risk of in-hospital mortality (odds ratio=2.52, 95% confidence interval 1.82-3.48) also when accounting for factors associated with their use. CONCLUSION: Hospitalised older people are often prescribed antibiotics. Factors related to poor physical independence and corticosteroid use are associated with increased antibiotic use. Being prescribed antibiotics is also associated with an increased risk of in-hospital death. These results demand the implementation of specific stewardship programmes to improve the correct use of antibiotics in hospital settings and to reduce the risk of antimicrobial resistance.

Implementation of the Frailty Index in hospitalized older patients: Results from the REPOSI register.

BACKGROUND: Frailty is a state of increased vulnerability to stressors, associated to poor health outcomes. The aim of this study was to design and introduce a Frailty Index (FI; according to the age-related accumulation of deficit model) in a large cohort of hospitalized older persons, in order to benefit from its capacity to comprehensively weight the risk profile of the individual. METHODS: Patients aged 65 and older enrolled in the REPOSI register from 2010 to 2016 were considered in the present analyses. Variables recorded at the hospital admission (including socio-demographic, physical, cognitive, functional and clinical factors) were used to compute the FI. The prognostic impact of the FI on in-hospital and 12-month mortality was assessed. RESULTS: Among the 4488 patients of the REPOSI register, 3847 were considered eligible for a 34-item FI computation. The median FI in the sample was 0.27 (interquartile range 0.21-0.37). The FI was significantly predictive of both in-hospital (OR 1.61, 95%CI 1.38-1.87) and overall (HR 1.46, 95%CI 1.32-1.62) mortality, also after adjustment for age and sex. CONCLUSIONS: The FI confirms its strong predictive value for negative outcomes. Its implementation in cohort studies (including those conducted in the hospital setting) may provide useful information for better weighting the complexity of the older person and accordingly design personalized interventions.

Disability, and not diabetes, is a strong predictor of mortality in oldest old patients hospitalized with pneumonia.

BACKGROUND: Pneumonia causes more deaths than any other infectious disease, especially in older patients with multiple chronic diseases. Recent studies identified a low functional status as prognostic factor for mortality in elderly patients with pneumonia while contrasting data are available about the role of diabetes. The aim of this study was to evaluate the in-hospital, 3-month and 1-year mortality in elderly subjects affected by pneumonia enrolled in the RePoSi register. METHODS: We retrospectively analyzed the data collected on hospitalized elderly patients in the frame of the REPOSI project. We analyzed the socio-demographic, laboratory and clinical characteristics of subjects with pneumonia. Multivariate logistic analysis was used to explore the relationship between variables and mortality. RESULTS: Among 4714 patients 284 had pneumonia. 52.8% were males and the mean age was 80 years old. 19.8% of these patients had a Barthel Index ≤40 (p ˂ 0.0001), as well as 43.2% had a short blessed test ≥10 (p ˂ 0.0117). In these subjects a significant CIRS for the evaluation of severity and comorbidity indexes (p ˂ 0.0001) were present. Although a higher fasting glucose level was identified in people with pneumonia, in the multivariate logistic analysis diabetes was not independently associated with in-hospital, 3-month and 1-year mortality, whereas patients with lower Barthel Index had a higher mortality risk (odds ratio being 9.45, 6.84, 19.55 in hospital, at 3 and 12 months). CONCLUSION: Elderly hospitalized patients affected by pneumonia with a clinically significant disability had a higher mortality risk while diabetes does not represent an important determinant of short and long-term outcome.

Miracle of haemophilia drugs: Personal views about a few main players.

INTRODUCTION: In the second decade of the third millennium there have been dramatic developments pertaining to the availability of highly innovative drugs for hemophilia care, notwithstanding a satisfactory previous scenario. AIM: I am going to emphasize the role of 2 main categories of players: scientist physicians who produced important translational research and the pharmaceutical industry, who developed, produced and made commercially available so many improved treatment weapons stemming from the translational research of the forementioned scientist physicians. RESULTS: Pertaining to the role of scientist physicians, I chose to mention first those who were successful in the 1980 in the production of recombinant coagulation factors. In addition, those who more recently helped to produce new non substitutive therapies given by the subcutaneous route, and recombination coagulation factors with an extended half-life. CONCLUSIONS: Current miraculous progress in hemophilia therapy is stemming from the research work of outstanding scientist physicians who acted in close collaboration with small biotechnology companies, leading to the early development of innovative therapeutic products, subsequently taken to the market place by the so called Big Pharma. I shall briefly provide my views to explain the fact that large pharmaceutical companies show more and more interest in such a rare disease as the hemophilias.

Fifth Åland Island conference on von Willebrand disease.

The fifth Åland Island meeting on von Willebrand disease (VWD) was held on the Åland Islands, Finland, from 22 to 24 September 2016-90 years after the first case of VWD was diagnosed in a patient from the Åland Islands in 1926. This meeting brought together experts in the field of VWD to share knowledge and expertise on current trends and challenges in VWD. Topics included the storage and release of von Willebrand factor (VWF), epidemiology and diagnostics in VWD, treatment of VWD, angiogenesis and VWF inhibitors.

Viral safety of coagulation factor concentrates: memoirs from an insider.

The purpose of this essay is to recall the actions taken globally to improve the viral safety of coagulation factor concentrates, mainly in the years 1985-1990, at a time of confusing and often contradictory information on bloodborne viral infections in multitransfused patients with hemophilia (PWHs). I shall first recall the problem of the transmission and control of the hepatitis viruses, and then that of HIV: not only for temporal reasons, but also because understanding the progress of knowledge on hepatitis and the poor success of the early measures taken to tackle this problem in PWHs is essential to understand how the problem of HIV transmission was ultimately dealt with successfully.

Prediction of factor VIII inhibitor development in the SIPPET cohort by mutational analysis and factor VIII antigen measurement.

Essentials A residual factor VIII synthesis is likely to be protective towards inhibitor (INH) development. Mutation type-inhibitor risk association was explored in 231 patients with severe hemophilia A. A 2-fold increase in INH development for in silico null vs. non-null mutations was found. A 3.5-fold increase in INH risk for antigen negative vs. antigen positive mutations was found. SUMMARY: Background The type of F8 mutation is the main predictor of inhibitor development in patients with severe hemophilia A. Mutations expected to allow residual synthesis of factor VIII are likely to play a protective role against alloantibody development by inducing immune tolerance. According to the expected full or partial impairment of FVIII synthesis, F8 variants are commonly classified as null and non-null. Objectives To explore the mutation type-inhibitor risk association in a cohort of 231 patients with severe hemophilia A enrolled in the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) randomized trial. Methods The genetic defects in these patients, consisting of inversions of intron 22 (n = 110) and intron 1 (n = 6), large deletions (n = 16), and nonsense (n = 38), frameshift (n = 28), missense (n = 19) and splicing (n = 14) variants, of which 34 have been previously unreported, were reclassified according to two additional criteria: the functional effects of missense and splicing alterations as predicted by multiple in silico analyses, and the levels of FVIII antigen in patient plasma. Results A two-fold increase in inhibitor development for in silico null mutations as compared with in silico non-null mutations (hazard ratio [HR] 2.08, 95% confidence interval [CI] 0.84-5.17) and a 3.5-fold increase in inhibitor development for antigen-negative mutations as compared with antigen-positive mutations (HR 3.61, 95% CI 0.89-14.74] were found. Conclusions Our findings confirm an association between the synthesis of minute amounts of FVIII and inhibitor protection, and underline the importance of investigating the residual FVIII antigen levels associated with causative variants in order to understand their clinical relevance.

Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: a SIPPET analysis.

Essentials Recombinant factor VIII (rFVIII) was contrasted with plasma-derived FVIII (pdFVIII). In previously untreated patients with hemophilia A, rFVIII led to more inhibitors than pdFVIII. Inhibitors with rFVIII developed earlier, and the peak rate was higher than with pdFVIII. Inhibitors with rFVIII were more severe (higher titre) than with pdFVIII. SUMMARY: Background The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is the most severe complication in the early phases of treatment of severe hemophilia A. Recently, a randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) demonstrated a 2-fold higher risk of inhibitor development in children treated with recombinant FVIII (rFVIII) products than with plasma-derived FVIII (pdFVIII) during the first 50 exposure days (EDs). Objective/Methods In this post-hoc SIPPET analysis we evaluated the rate of inhibitor incidence over time by every 5 EDs (from 0 to 50 EDs) in patients treated with different classes of FVIII product, made possible by a frequent testing regime. Results The highest rate of inhibitor development occurred in the first 10 EDs, with a large contrast between rFVIII and pdFVIII during the first 5 EDs: hazard ratio 3.14 (95% confidence interval [CI], 1.01-9.74) for all inhibitors and 4.19 (95% CI, 1.18-14.8) for high-titer inhibitors. For patients treated with pdFVIII, the peak of inhibitor development occurred later (6-10 EDs) and lasted for a shorter time. Conclusion These results emphasize the high immunologic vulnerability of patients during the earliest exposure to FVIII concentrates, with the strongest response to recombinant FVIII products.