Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study.

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes.

OBJECTIVE: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. METHODS: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI-Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. RESULTS: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). CONCLUSION: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription.

Appropriateness of the Prescription and Use of Medicines: An Old Concept but More Relevant than Ever.

The availability of drugs to treat diseases, control symptoms, or prevent their onset is one of the most important resources for maintaining health [...].

Prescription appropriateness of anticoagulant drugs for prophylaxis of venous thromboembolism in hospitalized multimorbid older patients.

The aims were to assess: the prescription prevalence of anticoagulant drugs for thromboprophylaxis (TP) in hospitalized older patients; the appropriateness of their prescription or non-prescription; the in-hospital mortality in appropriately versus non-appropriately prescribed or not prescribed patients. 4836 patients aged 65 or older, admitted to the Italian internal medicine and geriatric wards participating to the REPOSI register from 2012 to 2019 were assessed for prescription of anticoagulant drugs for TP at admission and/or during hospital stay. The Padua Prediction Score (PPS) and the IMPROVE score were used to assess the thrombotic and bleeding risk. Patients were considered to be appropriately prescribed when had PPS ≥ 4 and IMPROVE < 7, and appropriately not prescribed when PPS < 4. Logistic regression model was used to assess whether appropriateness was associated with in-hospital mortality. Among 4836 patients included, anticoagulants were prescribed for TP in 1233 (25.5%). In all, 4461 patients were assessable for appropriateness: 3136 (70.3%) were appropriately prescribed or non-prescribed according to their thrombotic and bleeding risk. Among 1138 patients receiving prophylaxis, only 360 (31.7%) were appropriately prescribed, while among 3323 non-prescribed patients, 2776 (83.5%) were appropriately non-prescribed. The in-hospital mortality rate was lower in patients appropriately prescribed or non-prescribed than in those inappropriately prescribed or non-prescribed (OR: 0.63; 95% CI: 0.46-0.83). In conclusion, a high prevalence of multimorbid hospitalized patients were appropriately prescribed or non-prescribed for TP with anticoagulants, appropriate non-prescription being mainly driven by a high bleeding risk. The appropriateness of prescription or non-prescription was associated with lower in-hospital mortality.

Canned Fish Consumption and Upper Digestive Tract Cancers.

Canned fish is a widely consumed and affordable food whose effect on cancer risk has been little investigated. We studied its effect on risk of upper digestive tract cancers using data from a network of hospital-based case-control studies from Northern Italy providing information about canned fish consumption as a separate item and including a total of 946 patients with oral cavity and pharynx cancer, 304 patients with esophageal cancer, 230 patients with gastric cancer and 3273 controls. Twenty-three percent of patients with cancer of the oral cavity or pharynx and 26% of those with cancer of the stomach consumed ≥1 serving per week of canned fish, compared to 40% and 49% of the respective control group. Among cases of esophageal cancer and controls 22% consumed ≥1 serving per week of canned fish. Odds ratios for ≥1 vs <1 portion per week were 0.79 (95% Confidence Interval, CI: 0.64-0.97) for cancer of the oral cavity and pharynx, and 0.59 (95% CI: 0.41-0.86) for stomach cancer, whereas there was no inverse association with esophageal cancer. These findings suggest a favorable role of canned fish for selected upper digestive tract cancers.

Epidemiology of Serratia marcescens infections in NICU of a Teaching and Research Hospital in Northern Italy.

BACKGROUND: Serratia marcescens (Sm) is a known cause of infection and colonization in neonates receiving intensive care. The aim of this study was to identify the risk factors for colonization and infection with Sm in Neonatal Intensive Care Unit (NICU) of a tertiary care Hospital. METHODS: A case-control study was conducted from January to December 2011 in neonates admitted to the NICU. Cases are patients with a microbiologically confirmed infection or colonization, controls were randomly chosen among patients admitted to the same NICU. RESULTS: Globally, 39 acquired infections or colonizations were identified. Among factors related to pregnancy, only premature delivery was independently associated to the risk of infection; as well as mechanical ventilation and catheterization for parenteral nutrition, considering indwelling devices. Prolonged administration with antibiotics were also related to the risk of infection. Among Sm strains which have been tested to antibiotics, all have been resistant to amoxicillin/clavulanic acid and to colistin. CONCLUSIONS: This study confirms the association between Sm infection or colonization and low gestational age. Invasive medical devices and medications, strictly necessary in care-support of preterm neonates, are likely related to Sm infection too. Preventive control strategies are expected to be effective in the control of Sm spread in NICUs.

Multiple Medication Adherence and Related Outcomes in Community-Dwelling Older People on Chronic Polypharmacy: A Retrospective Cohort Study on Administrative Claims Data.

Poor medication adherence compromises treatment efficacy and adversely affects patients' clinical outcomes. This study aims to assess (1) multiple medication adherence to the most common drug classes chronically prescribed to older people, (2) the factors associated, and (3) the clinical outcomes. This retrospective cohort study included 122,655 community-dwelling patients aged 65-94 years old, newly exposed to chronic polypharmacy, and recorded in the Lombardy Region (northern Italy) administrative database from 2016 to 2018. Multiple medication adherence was assessed for drugs for diabetes, antithrombotics, antihypertensives, statins, and bisphosphonates, by calculating the daily polypharmacy possession ratio (DPPR). One-year mortality, nursing home, emergency department (ED), and hospital admission rates were calculated for 2019. The most prescribed drugs were antihypertensives (89.0%). The mean (std.dev) DPPR was 82.9% (15.6). Being female (OR = 0.85, 95%CI: 0.84-0.86), age ≥85 years (OR = 0.77, 95%CI: 0.76-0.79), and multimorbidity (≥4 diseases, OR = 0.88, 95%CI: 0.86-0.90) were associated with lower medication adherence. A higher DPPR was associated with clinical outcomes-in particular, improved survival (HR = 0.93 for 10/100-point increase, 95%CI: 0.92-0.94) and lower incidence in nursing home admissions (SDHR = 0.95, 95%CI: 0.93-0.97). Adherence to the most common chronic drugs co-prescribed to the older population was high. Better multiple medication adherence was associated with better clinical outcomes.

Inverse Association between Canned Fish Consumption and Colorectal Cancer Risk: Analysis of Two Large Case-Control Studies.

Fish is among the foods exerting favourable effects on colorectal cancer (CRC), but the possible role of canned fish has been insufficiently investigated. We aimed to investigate the relationship between canned fish consumption and CRC risk. We analysed data from two case−control studies conducted between 1992 and 2010 in several Italian areas, comprising a total of 2419 incident cases and 4723 hospital controls. Canned fish consumption was analysed according to the weekly frequency of consumption as <1 serving per week (s/w) (reference category), 1 < 2 s/w, and ≥2 s/w. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models, adjusting for several recognised confounding factors. Overall, canned fish consumption was lower among cases than among controls (23.8% vs. 28.6%). An inverse association was found between canned fish consumption and CRC risk with a significant trend in risk (OR = 0.81, 95% CI: 0.71−0.92 for intermediate consumption and OR = 0.66, 95% CI: 0.51−0.85 for the highest one), which was consistent across strata of several covariates. This study is the first to offer a basis of support for canned fish consumption as a component of a healthy diet, and it has relevant public health implications given the high ranking of CRC in incidence and mortality worldwide.

Prescription Appropriateness of Drugs for Peptic Ulcer and Gastro-Esophageal Reflux Disease: Baseline Assessment in the LAPTOP-PPI Cluster Randomized Trial.

Background: Drugs for peptic ulcer and gastro-esophageal reflux disease (GERD) are among the most widely prescribed, frequently without appropriate indications. This represents an important issue, as it leads to risk of adverse events for patients and unnecessary costs for National Health Service. Aim: To assess the prescription appropriateness of drugs for GERD, in the frame of the "Evaluation of the effectiveness of a Low-cost informative intervention to improve the Appropriate PrescripTiOn of Proton PumP Inhibitors in older people in primary care: a cluster-randomized controlled study" (LAPTOP-PPI) (Clinicaltrial.gov: NCT04637750). Methods: The appropriateness of drug prescription was assessed on data collected in administrative databases, by integrating information on concomitant medications, outpatient medical and laboratory procedures and hospital discharge diagnoses, according to the reimbursement criteria provided by the Italian Medicine Agency. We analyzed data of community-dwelling people aged 65 years and over, living in the areas of Bergamo (Northern Italy) and Caserta (Southern Italy), from July 1 to 31 December 2019. Results: Among 380,218 patients, 175,342 (46.1%) received at least one prescription of drugs for GERD. All in all, we found that only 41.2% of patients received appropriate prescriptions. Conclusion: Given the potential risk of adverse drug reactions, especially in older people, educational interventions should be prompted for physicians, in order to improve the quality of prescription of drugs for GERD and, in turn, avoid unfavorable health outcomes and unnecessary costs.

Use of Lipid-Lowering Drugs and Associated Outcomes According to Health State Profiles in Hospitalized Older Patients.

OBJECTIVE: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles. DESIGN: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI - Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards. SETTING AND PARTICIPANTS: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018. METHODS: Socio-demographic characteristics, functional abilities, cognitive skills, laboratory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients' health state profiles and with short-term mortality. RESULTS: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76-5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44-0.80). CONCLUSION: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients' health state profiles.

Medication adherence in community-dwelling older people exposed to chronic polypharmacy.

BACKGROUND: To evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people. METHODS: This is a retrospective cohort study on medication adherence in community-dwelling older people (65-94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin-angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPR<80%) and poorly adherent (10%

Pain and Frailty in Hospitalized Older Adults.

INTRODUCTION: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. METHODS: In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. RESULTS: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38-2.07). Somatic pain (OR = 1.59, 95% CI 1.23-2.07) and widespread pain (OR = 1.60, 95% CI 0.93-2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28-0.85). CONCLUSIONS: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people.

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse.

Bortezomib- and lenalidomide-containing regimens are well-established therapies in multiple myeloma (MM). However, despite their extensive use, head-to-head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed-duration therapies. In this open-label, phase III study, we randomized MM patients at first relapse to receive either nine cycles of bortezomib plus cyclophosphamide plus dexamethasone (VCD) or lenalidomide plus cyclophosphamide plus dexamethasone (RCD). The primary endpoint was achievement of a very good partial response (VGPR) or better at six weeks after nine treatment cycles. From March 2011 to February 2015, 155 patients were randomized. VGPR or better was achieved by 12 patients (15%) in the VCD arm and 14 patients (18%) in the RCD arm (P = 0·70). Median progression-free survival (PFS) was 16·3 (95% CI: 12·1-22·4) with VCD and 18·6 months (95% CI: 14·7-25·5) with RCD, and the two-year overall survival (OS) was 75% (95% CI: 66-86%) and 74% (95% CI: 64-85%) respectively. In subgroup analyses, no differences in PFS were observed in bortezomib- and lenalidomide-naïve patients, nor in patients who received a bortezomib-based regimen in first line. Adverse events were consistent with the well-established safety profiles of both drugs. Bortezomib and lenalidomide treatments were equally effective in terms of depth of response, PFS, and OS in MM patients at first relapse.

Long-term survival between total colectomy versus proctocolectomy in patients with FAP: a registry-based, observational cohort study.

BACKGROUND: The best surgical choice for patients with familial adenomatous polyposis (FAP) is still debated. No prospective trials have been carried out to evaluate the pros and cons of the recommended procedures: total colectomy (ileorectal anastomosis [IRA]) vs restorative proctocolectomy (ileal pouch-anal anastomosis [IPAA]). The aim of this study was to provide a basis for tailored precision surgery in patients with FAP. METHODS: We conducted a retrospective review of patients with FAP who underwent surgery and were registered in a dedicated database in Milan, Italy. Twenty-year survival related to surgical approach and prognostic factors were investigated using a Cox regression model. RESULTS: A total of 925 patients underwent surgery between 1947 and 2015: 340 (36.8%) IPAA and 585 (63.2%) IRA. Colorectal cancer (CRC) at surgery was diagnosed in 28.6% of patients and a pathogenic APC variant was identified in 88%. During a median follow-up of 129 months, 150 patients died. The survival probability was significantly higher in the IRA than the IPAA group: 0.82 vs 0.75 (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.42-0.84). Multivariable regression modeling adjusted for propensity scores showed a similar difference, although no longer significant. Multivariable analysis indicated as independent risk factors CRC (HR 4.68, 95% CI 3.04-7.20) and age at surgery (HR 1.03, 95% CI 1.02-1.06). Among patients without cancer, the main risk factor for shorter survival was older age (HR 1.06, 95% CI 1.04-1.09). CONCLUSION: The study confirms excellent long-term results of surgical approaches with IRA and IPAA, suggesting that the best surgical choice may be an individually and clinically tailored approach, preferably at a young age.

Continuity of care for patients with hip fracture after discharge from rehabilitation facility.

Background and aims of the work: Hip fracture is a dramatic event especially in the elderly and the return to the pre-fracture functional and social state is often difficult to achieve. In the post-acute, the intensive rehabilitation period aims to recover as much autonomy as possible to these patients, but not always its duration is sufficient to ensure an effective and lasting result in returning home, hence the need for additional rehabilitation services. Our aim was to evaluate the use of additional rehabilitation services by patients who underwent hip fracture after an intensive rehabilitation treatment period performed at our hospital. METHODS: This is a retrospective cohort study. We involved patients aged 45 years and older, admitted at our intensive rehabilitation, who joined a rehabilitation program for a hip fracture. RESULTS: Our results showed how the use of further physiotherapy is associated with the type of surgical intervention and with higher Cumulative Illness Rating Scale CIRS scores. Similarly, the loss of autonomy is associated with the type of intervention, the increase in CIRS and the duration of the physiotherapy, and negatively associated with the duration of each session. The re-hospitalizations for each cause is positively associated with CIRS and negatively associated with the further use of physiotherapy. CONCLUSIONS: Our conclusion is that rehabilitation needs a personalized schedule, because the real discriminating factor in the management of frail patients should therefore be the quality, and not the quantity (i.e. longer session), of the rehabilitative intervention prescribed.

Appropriateness of prescription of oral anticoagulant therapy in acutely hospitalized older people with atrial fibrillation. Secondary analysis of the SIM-AF cluster randomized clinical trial.

AIMS: To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. METHODS: Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. RESULTS: For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). CONCLUSIONS: A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Simulation-Based Education for Physicians to Increase Oral Anticoagulants in Hospitalized Elderly Patients with Atrial Fibrillation.

PURPOSE: This study was intended to determine whether a simulation-based education addressed to physicians was able to increase the proportion of hospitalized elderly with atrial fibrillation prescribed with oral anticoagulants (OACs) compared with the usual practice. METHODS: We conducted a cluster randomized trial (from April 2015 to September 2018) on 32 Italian internal medicine and geriatric wards randomized 1:1 to intervention or control arms. The physicians of wards randomized to intervention received a computer-based e-learning tool with clinical scenarios (Dr Sim), and those of wards randomized to control received no formal educational intervention. The primary outcome was the OAC prescription rate at hospital discharge in the intervention and control arms. RESULTS: Of 452 patients scrutinized, 247 were included in the analysis. Of them, 186 (75.3%) were prescribed with OACs at hospital discharge. No difference was found between the intervention and control arms in the post-intervention phase (odds ratio, 1.46; 95% confidence interval [CI], 0.81-2.64). The differences from the pre- to post-intervention phases in the proportions of patients prescribed with OACs (15.1%; 95% CI, 0%-31.5%) and with direct oral anticoagulants (DOACs) (20%; 95% CI, 0%-39.8%) increased more in the intervention than in the control arm. CONCLUSIONS: This simulation-based course did not succeed in increasing the rate of elderly patients prescribed with OACs at hospital discharge compared with the usual practice. Notwithstanding, over time there was a greater increase in the intervention than in the control arm in the proportion of patients prescribed with OACs and DOACs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03188211.

Caregivers' misperception of the severity of hip fractures.

PURPOSE: The aim of our study was to evaluate how the caregiver of a hip fracture patient perceives the patient's health status and autonomy in the period immediately preceding the acute event and whether these judgments are actually in line with the prognosis predicted by the medical team caring for the patient in the rehabilitation structure. PATIENTS AND METHODS: We enrolled 147 patients of both sexes, aged ≥65 years, who were referred to our center following surgical treatment of hip fractures of various nature. At the beginning of the rehabilitation program, each patient's caregiver was asked to complete the Blaylock Risk Assessment Screening Score (BRASS) questionnaire. The same questionnaire was compiled contemporaneously by the doctor taking care of the patient. RESULTS: Analysis of the data shows that the caregivers tend to assign lower scores than the doctor, with a mean difference in agreement with the Bland-Altman plot of -2.43, 95% CI=-2.93 to -1.93, t-test P<0.001. Furthermore, differences in objectivity emerge in the evaluation of the clinical problems of the patient in a borderline clinical condition. CONCLUSION: This study revealed that caregivers systematically misperceive the clinical situation of hip fracture patients prior to the acute event. Altered perception of such an important factor can lead to a general lack of satisfaction with the outcome achieved by the patient at the end of the rehabilitation process. We therefore believe that an adequate, effective communication between the people making up the health care team and the patient's social and family network is the foundation of the rehabilitation process. It is precisely on this foundation that the individual's care and assistance need to be assembled.

Dynamics of the hazard for distant metastases after ipsilateral breast tumor recurrence according to estrogen receptor status: An analysis of 2851 patients.

BACKGROUND: Breast cancer (BC) patients with ipsilateral breast tumor recurrence (IBTR) are at high risk of developing distant metastases (DM). We aimed to evaluate the risk pattern of developing DM, with respect to the occurrence of IBTR, in a large series of patients homogeneously treated by conservative surgery (QUART) with a considerably long follow-up. METHODS: Piecewise exponential model was used to investigate DM dynamics conditioning on known prognostic factors and IBTR occurrence as time dependent covariate. The model was extended to account for the timescale induced by IBTR, namely the time elapsed since IBTR to the endpoint. RESULTS: Among 2851 BCE patients receiving QUART, 209 were assessable for IBTR. After a median follow-up of 129 months, 588 patients presented DM (CCI = 27.3%) as first event and 92 (CCI = 48.8%) following IBTR. Primary tumor size and nodal status confirmed their prognostic value. The hazard for DM was early and high in Estrogen Receptor (ER) negative BC patients; while it was initially low but increases during follow-up in ER positive cases. Patients experiencing IBTR showed DM dynamic similar to that following primary tumor, with a sudden increased risk within 24 months from surgery, regardless the time elapsed since QUART. CONCLUSION: BC patients experiencing IBTR showed a sudden and sustained risk of DM following surgery. Our findings are consistent with the hypothesis that IBTR occurrence might act as a "time resector" for risk of DM, and provide a rationale for proper surveillance guidelines and systemic therapy for optimizing BC recurrence and appropriate choice of treatment.