The pharmacological deprescription in elderly patients

The demographic of individuals aged 65 and above represents one of the fastest-growing populations globally. As of 2020, there were 727 million individuals (9.3%) aged 65 years or older worldwide. Projections indicate that the number of older adults will double to reach 1.5 billion (16%) by 2050.1 At that point, 1 in 6 people globally will be over 65, and in Europe and North America, 1 in 4 individuals may fall into this age bracket. [...

Reduction in unplanned hospitalizations associated with a physician focused intervention to reduce potentially inappropriate medication use among older adults: a population-based cohort study

BACKGROUND: A multimodal general practitioner-focused intervention in the Local Health Authority (LHA) of Parma, Italy, substantially reduced the prevalence of potentially inappropriate medication (PIM) use among older adults. Our objective was to estimate changes in hospitalization rates associated with the Parma LHA quality improvement initiative that reduced PIM use. METHODS: This population-based longitudinal cohort study was conducted among older residents ( \u3e 65 years) using the Parma LHA administrative healthcare database. Crude and adjusted unplanned hospitalization rates were estimated in 3 periods (pre-intervention: 2005-2008, intervention: 2009-2010, post-intervention: 2011-2014). Multivariable negative binomial models estimated trends in quarterly hospitalization rates among individuals at risk during each period using a piecewise linear spline for time, adjusted for time-dependent and time-fixed covariates. RESULTS: The pre-intervention, intervention, and post-intervention periods included 117,061, 107,347, and 121,871 older adults and had crude hospitalization rates of 146.2 (95% CI: 142.2-150.3), 146.8 (95% CI: 143.6-150.0), and 140.8 (95% CI: 136.9-144.7) per 1000 persons per year, respectively. The adjusted pre-intervention hospitalization rate was declining by 0.7% per quarter (IRR = 0.993; 95% CI: 0.991-0.995). The hospitalization rate declined more than twice as fast during the intervention period (1.8% per quarter, IRR = 0.982; 95% CI: 0.979-0.985) and was nearly constant post-intervention (IRR: 0.999; 95% CI: 0.997-1.001). Contrasting model predictions for the intervention period (Q1 2009 to Q4 2010), the intervention was associated with 1481 avoided hospitalizations. CONCLUSION: In a large population of older adults, a multimodal general practitioner-focused intervention to decrease PIM use was associated with a decline in the unplanned hospitalization rate. Such interventions to reduce high risk medication use among older adults warrant consideration by health systems seeking to improve health outcomes and reduce high-cost acute care utilization

Appropriate medication prescribing in elderly patients: how knowledgeable are primary care physicians? A survey study in Parma, Italy.

What is known and Objective:  Increasing attention is being paid to inappropriate medication prescribing for the elderly. A growing body of studies have detected a prevalence of inappropriate prescribing ranging from 12% to 40% worldwide, including Regione Emilia-Romagna, Italy. To improve quality of prescribing, a multi-phase pilot project in the Local Health Unit (LHU) of Parma, Regione Emilia-Romagna, was established. This phase aimed to assess primary care physicians\u27 knowledge of appropriate prescribing in elderly patients. Methods:  In total, 155 primary care physicians (51% of the total), convened by the LHU of Parma for an educational session, were asked to complete anonymously a 19-item paper survey. Knowledge of inappropriate medication use in the elderly was assessed using seven clinical vignettes based on the 2002 Beers Criteria. Topics tested included hypertension, osteoarthritis, arrhythmias, insomnia and depression. Data regarding physician\u27s perceived barriers to appropriate prescribing for elderly patients were also collected. To evaluate the relationship between physician knowledge scores and physician characteristics, physicians were classified as having a \u27low score\u27 (three or below) or a \u27high score\u27 (six or more) with respect to their knowledge of prescribing for the elderly. Results and Discussion:  All physicians completed the survey. Most physicians (88%) felt confident in their ability to prescribe appropriate medications for the elderly. Thirty-nine physicians (25%) received a \u27high score\u27 compared to 26 (17%) who received a \u27low score\u27. \u27Lower score\u27 respondents had been in practice for a longer time (P \u3c 0·05) than \u27higher score\u27 respondents. Perceived barriers to appropriate prescribing included potential drug interactions (79% of respondents) and the large number of medications a patient is already taking (75%). What is new and Conclusion:  The study results show an unsatisfactory knowledge of appropriate prescribing among primary care physicians in the LHU of Parma, especially among older physicians. Educational strategies tailored to primary care physicians should be establish to enhance knowledge in this area and improve quality of prescribing

Did a physician-targeted intervention that reduced potentially inappropriate prescribing to elderly patients also reduce related hospitalizations?

Objectives: To determine whether a general practitioner focused intervention aimed at decreasing PIM prescribing in the elderly can decrease the risk of PIM-related hospitalizations. Poster presented at 2016 ISPOR conference in Washington DC.https://jdc.jefferson.edu/jcphposters/1005/thumbnail.jp

Molecular insights into cell toxicity of a novel familial amyloidogenic variant of β2-microglobulin

The first genetic variant of β(2)‐microglobulin (b2M) associated with a familial form of systemic amyloidosis has been recently described. The mutated protein, carrying a substitution of Asp at position 76 with an Asn (D76N b2M), exhibits a strongly enhanced amyloidogenic tendency to aggregate with respect to the wild‐type protein. In this study, we characterized the D76N b2M aggregation path and performed an unprecedented analysis of the biochemical mechanisms underlying aggregate cytotoxicity. We showed that, contrarily to what expected from other amyloid studies, early aggregates of the mutant are not the most toxic species, despite their higher surface hydrophobicity. By modulating ganglioside GM1 content in cell membrane or synthetic lipid bilayers, we confirmed the pivotal role of this lipid as aggregate recruiter favouring their cytotoxicity. We finally observed that the aggregates bind to the cell membrane inducing an alteration of its elasticity (with possible functional unbalance and cytotoxicity) in GM1‐enriched domains only, thus establishing a link between aggregate‐membrane contact and cell damage

Modeling the contribution of male testosterone levels to the duration of positive COVID testing among hospitalized male COVID-19 patients

Background: A growing body of evidence is emerging suggesting testosterone can affect all cells involved in the immune response to both bacterial and viral infections, and the testosterone effect on the immune response could explain the greater susceptibility of men to infections including COVID-19. We aimed to explore the predictive role of male serum total testosterone (TT) levels on the time till viral negativity testing among hospitalized COVID-19 patients. Methods: The univariate effect of risk factors for the duration of COVID-19 viral positivity was evaluated using the log-rank test and Kaplan-Meier estimates. A multivariable Cox regression model was developed to test the role of TT levels and the subsequent odds for shorter viral positivity intervals. Results: Increasing serum TT levels and the need for an oxygen administration strategy were independently predictive for respectively reduced and increased days to negativization (Hazard Ratio [HR]: 1.39, 95% CI: 0.95-2.03 and HR: 0.19, 95% CI: 0.03-1.18). Conclusion: Baseline higher TT levels for male COVID-19 patients at hospital admission are associated with shorter durations of positive COVID-19 testing and thus viral clearance. Our preliminary findings might play a relevant to help pandemic control strategies if these will be verified in future larger multicentric and possibly randomized trials

Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis

PURPOSE: (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains.METHODS: NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naive and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR.RESULTS: n=422 Ta-T1 patients (Connaught, n=146; TICE, n=112 and RIVM, n=164) with a median (IQR) follow-up of 72 (60-85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HRRFS: 0.63; 95% CI 0.46-0.86; HRPFS: 0.55; 95% CI 0.31-0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HRTICE: 0.58, 95% CI 0.39-0.86; HRRIVM: 0.61, 95% CI 0.42-0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n=190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM.CONCLUSION: Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes