PERCEIVED STRESS AND HEPATIC PARAMETERS

Introduction: The aim of the study is to evaluate work-related subjective stress in a group of employees, of both sexes, operating in the healthcare and welfare, through the administration of a questionnaire (HSE "Indicator Tool"), specifically developed and officially validated, and to analyze any possible correlations between stress levels taken from the questionnaire scores and the concentrations of three main hepatic parameters (GOT, GPT, GGT). Materials and Methods: We studied a final sample of 232 subjects (143 males and 89 females) operating in the health and welfare sector. For research purposes during the medical examination each subject underwent the HSE indicator tool, a collection of information about relevant clinical and medical history and a venous blood sample for the assay of GOT, GPT and GGT. All questionnaires were analyzed using special software provided by the HSE. The results obtained from the questionnaires were statistically compared with the blood concentrations of hepatic parameters. Results: The dimensions found to be critical, associated with a stressful condition (yellow area) or a highly stressful condition (red area), are: managers support, colleagues support, quality of relationships and changes. The Pearson’s correlation showed a statistically significant negative correlation (p <0.05) between the mean values of all the critical dimensions and the concentrations of the hepatic parameters, both on the total sample and after subdivision by gender. These results were confirmed in the multiple linear regression analysis, which indicated that the critical dimensions are the main significant variables contributing to the liver parameters alterations. Discussion: Preliminary results indicate that a critical perception of stress at work can be statistically associated with increases in mean concentrations of GOT, GPT and GGT in a working asymptomatic population. These results provide a starting point for future studies on this topic, to a greater definition of the link between stress and liver injury, to confirm the effects on the parameters of liver injury (GOT, GPT, GGT) and to investigate possible correlations with the cholestasis parameters (bilirubin, alkaline phosphatase) and serum albumin

Endothelin-1 induces proliferation of human lung fibroblasts and IL-11 secretion through an ET(A) receptor-dependent activation of MAP kinases

Endothelin-1 (ET-1) is implicated in the fibrotic responses characterizing interstitial lung diseases, as well as in the airway remodeling process occurring in asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal human lung fibroblasts (NHLFs), the ET-1 receptor subtypes, and the intracellular signal transduction pathways involved in the proliferative effects of this peptide. Therefore, cells were exposed to ET-1 in the presence or absence of an overnight pre-treatment with either ET(A) or ET(B) selective receptor antagonists. After cell lysis, immunoblotting was performed using monoclonal antibodies against the phosphorylated, active forms of mitogen-activated protein kinases (MAPK). ET-1 induced a significant increase in MAPK phosphorylation pattern, and also stimulated fibroblast proliferation and IL-6/IL-11 release into cell culture supernatants. All these effects were inhibited by the selective ET(A) antagonist BQ-123, but not by the specific ET(B) antagonist BQ-788. The stimulatory influence of ET-1 on IL-11, but not on IL-6 secretion, was prevented by MAPK inhibitors. Therefore, such results suggest that in human lung fibroblasts ET-1 exerts a profibrogenic action via an ET(A) receptor-dependent, MAPK-mediated induction of IL-11 release and cell proliferation

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

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

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 β- 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

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–drug interactions involving CYP3A4 and p-glycoprotein in hospitalized elderly patients

Polypharmacy is very common in older patients and may be associated with drug-drug interactions. Hepatic cytochrome P450 (notably 3A4 subtype, CYP3A4) is a key enzyme which metabolizes most drugs; P-glycoprotein (P-gp) is a transporter which significantly influences distribution and bioavailability of many drugs. In this study, we assess the prevalence and patterns of potential interactions observed in an hospitalized older cohort (Registro Politerapia Societa Italiana di Medicina Interna) exposed to at least two interacting drugs involving CYP3A4 and P-gp at admission, during hospitalization and at discharge. Individuals aged 65 and older (N-4039; mean age 79.2; male 48.1%), hospitalized between 2010 and 2016, were selected. The most common combinations of interacting drugs (relative frequency > 5%) and socio-demographic and clinical factors associated with the interactions were reported. The prevalence of interactions for CYP3A4 was 7.9% on admission, 10.3% during the stay and 10.7% at discharge; the corresponding figures for P-gp interactions were 2.2%, 3.8% and 3.8%. The most frequent interactions were amiodarone-statin for CYP3A4 and atorvastatin-verapamil-diltiazem for P-gp. The prevalence of some interactions, mainly those involving cardiovascular drugs, decreased at discharge, whereas that of others, e.g. those involving neuropsychiatric drugs, increased. The strongest factor associated with interactions was polypharmacy (OR 6.7, 95% CI 5.0-9.2). In conclusion, hospital admission is associated with an increased prevalence, but also a changing pattern of interactions concerning CYP3A4 and P-gp in elderly. Educational strategies and appropriate use of dedicated software seem desirable to limit drug interactions and the inherent risk of adverse events in older patients

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