Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

PURPOSE: Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. PATIENTS AND METHODS: The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of Cb (AUC 6) + D (75mg/m2) given every 21 days × 6 cycles. Pathological complete response (pCR: no evidence of invasive tumor in the breast and axilla) and Residual Cancer Burden (RCB) were evaluated. RESULTS: Among 190 patients, median tumor size was 35mm, 52% Lymph Node positive and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0+1 rates were 55% and 68%, respectively. pCR in patients with BRCA associated and wild-type TNBC were 59% and 56%, respectively (p=0.83). On multivariable analysis stage III disease was the only factor associated with a lower likelihood of achieving a pCR. 21% and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSION: The CbD regimen was well tolerated and yielded high pCR rates in both BRCA associated and wildtype TNBC. These results are comparable to pCR achieved with addition of Cb to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies

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

Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients

The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from \u201cRegistro Politerapia Societ\ue0 Italiana di Medicina Interna (REPOSI)\u201d. Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR < 60 ml/min/1.73 m2 was associated with unfavorable outcomes, although with a poor level of accuracy (AUC 0.60\u20130.66). No difference in predictive power between different equations was found. Physicians should be aware of the prognostic role of eGFR in a comprehensive assessment of elderly in-patients

Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards

Background: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic. Objective: We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards. Methods: Taking advantage of the “REgistro POliterapie Società Italiana Medicina Interna” (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain. Results: Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p <.0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p <.0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p =.172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p <.0001). Conclusions: Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge

Living alone as an independent predictor of prolonged length of hospital stay and non-home discharge in older patients.

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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\u20130.37). The FI was significantly predictive of both in-hospital (OR 1.61, 95%CI 1.38\u20131.87) and overall (HR 1.46, 95%CI 1.32\u20131.62) 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

Prevalence and Determinants of the Use of Lipid-Lowering Agents in a Population of Older Hospitalized Patients: the Findings from the REPOSI (REgistro POliterapie Societ\ue0 Italiana di Medicina Interna) Study

Background: Older patients are prone to multimorbidity and polypharmacy, with an inherent risk of adverse events and drug interactions. To the best of our knowledge, available information on the appropriateness of lipid-lowering treatment is extremely limited. Aim: The aim of the present study was to quantify and characterize lipid-lowering drug use in a population of complex in-hospital older patients. Methods: We analyzed data from 87 units of internal medicine or geriatric medicine in the REPOSI (Registro Politerapie della Societ\ue0 Italiana di Medicina Interna) study, with reference to the 2010 and 2012 patient cohorts. Lipid-lowering drug use was closely correlated with the clinical profiles, including multimorbidity markers and polypharmacy. Results: 2171 patients aged >65\ua0years were enrolled (1057 males, 1114 females, mean age 78.6\ua0years). The patients treated with lipid-lowering drugs amounted to 508 subjects (23.4%), with no gender difference. Atorvastatin (39.3%) and simvastatin (34.0%) were the most widely used statin drugs. Likelihood of treatment was associated with polypharmacy ( 655\ua0drugs) and with higher Cumulative Illness Rating Scale (CIRS) score. At logistic regression analysis, the presence of coronary heart disease, peripheral vascular disease, and hypertension were significantly correlated with lipid-lowering drug use, whereas age showed an inverse correlation. Diabetes was not associated with drug treatment. Conclusions: In this in-hospital cohort, the use of lipid-lowering agents was mainly driven by patients\u2019 clinical history, most notably the presence of clinically overt manifestations of atherosclerosis. Increasing age seems to be associated with lower prescription rates. This might be indicative of cautious behavior towards a potentially toxic treatment regimen

Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study

Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the \u2018Registro Politerapie SIMI\u2019 study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p\ua0=\ua00.002), had a higher Short Blessed Test (SBT; p\ua0=\ua00.022) and a lower Barthel Index (p\ua0=\ua00.047). Polypharmacy (p\ua0=\ua00.001), heart failure (p\ua0=\ua00.005) and diabetes (p\ua0=\ua00.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p\ua0=\ua00.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94\u20131.00, p\ua0=\ua00.037], diabetes (OR 0.48, 95% CI 0.26\u20130.87, p\ua0=\ua00.016) and polypharmacy (OR 0.58, 95% CI 0.34\u20130.99, p\ua0=\ua00.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p\ua0=\ua00.89; and 15.9 vs. 14.1%, p\ua0=\ua00.70, respectively). Conclusion: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up