Effectiveness of the flash glucose monitoring system in preventing severe hypoglycemic episodes and in improving glucose metrics and quality of life in subjects with type 1 diabetes at high risk of acute diabetes complications.

AIMS: To assess the effectiveness of the intermittent-scanned continuous glucose monitoring (isCGM) system in preventing severe hypoglycemic episodes and in improving glucose parameters and quality of life. METHODS: Four hundred T1D individuals were enrolled in a prospective real-word study with an intermittently scanned continuous glucose monitoring device during the 12-months follow-up. The primary endpoint was the incidence of severe hypoglycemic events. RESULTS: 82% of subjects were naïve to the use of the device (group A) and 18% were already wearing the system (group B). The cumulative incidence of severe hypoglycemia (SH) at 12 months was 12.06 per 100 person-year (95% CI: 8.35-16.85) in group A and 10.14 (95% CI: 4.08-20.90) in group B without inter-group differences. In group A there was a significant decrease in SH at 12 months compared to 3 months period (p = 0.005). Time in glucose range significantly increased in both groups accompanied with a significant decrease in glucose variability. HbA1c showed a progressive significant time-dependent decrease in group A. The use of the device significantly improved the perceived quality of life. CONCLUSION: This study confirmed the effectiveness of the isCGM in reducing hypoglycemic risk without glucose deterioration, with potential benefits on adverse outcomes in T1D individuals. TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT04060732.

Algor-ethics: charting the ethical path for AI in critical care.

The integration of Clinical Decision Support Systems (CDSS) based on artificial intelligence (AI) in healthcare is groundbreaking evolution with enormous potential, but its development and ethical implementation, presents unique challenges, particularly in critical care, where physicians often deal with life-threating conditions requiring rapid actions and patients unable to participate in the decisional process. Moreover, development of AI-based CDSS is complex and should address different sources of bias, including data acquisition, health disparities, domain shifts during clinical use, and cognitive biases in decision-making. In this scenario algor-ethics is mandatory and emphasizes the integration of 'Human-in-the-Loop' and 'Algorithmic Stewardship' principles, and the benefits of advanced data engineering. The establishment of Clinical AI Departments (CAID) is necessary to lead AI innovation in healthcare, ensuring ethical integrity and human-centered development in this rapidly evolving field.

Healthcare Costs and Resource Utilisation of Italian Metastatic Non-Small Cell Lung Cancer Patients.

This study evaluated the economic burden of metastatic non-small cell lung cancer patients before and after the availability of an immuno-oncology (IO) regimen as a first-line (1L) treatment. Patients from 2014 to 2020 were categorized according to mutational status into mutation-positive and negative/unknown groups, which were further divided into pre-1L IO and post-1L IO sub-groups depending on the availability of pembrolizumab monotherapy in 1L. Healthcare costs and HCRU for a 1L treatment and overall follow-up were reported as the mean total and per-month cost per patient by groups. Of 644 patients, 125were mutation-positive and 519 negative/unknown (229 and 290 in pre- and post-1L IO, respectively). The mean total per-patient cost in 1L was lower in pre- (EUR 7804) and post-1L IO (EUR 19,301) than the mutation-positive group (EUR 45,247), persisting throughout overall disease follow-up. However, this difference was less when analyzing monthly costs. Therapy costs were the primary driver in 1L, while hospitalization costs rose during follow-up. In both mutation-positive and post-IO 1L groups, the 1L costs represented a significant portion (70.1% and 66.3%, respectively) of the total costs in the overall follow-up. Pembrolizumab introduction increased expenses but improved survival. Higher hospitalisation and emergency room occupation rates during follow-up reflected worsening clinical conditions of the negative/unknown group than the mutation-positive population.

[Medico-legal and management issues in patient blood management era.] / Aspetti medico-legali e organizzativi nell'era del Patient blood management.

In recent decades, the approach to blood transfusion has changed radically around the world. In the past, transfusion represented the only solution for anemia, today the paradigm has changed: through the implementation of the Patient blood management (Pbm) program it is possible to manage the patient's own blood in order to reduce and, in many cases, eliminate the administration of blood components for transfusion. This approach increases patient safety by reducing clinical risks as well as costs. The implementation of the PBM program in Australia has demonstrated that the use of blood is not strictly necessary but, on the contrary, is largely avoidable. Through change management the traditional attitude of doctors and healthcare facilities can be modified. Law no. 24/2017 focuses on the safety of care by encouraging the necessary implementation of Pbm in hospital settings; the failure to adopt an organized Pbm program may constitute, in the event of an adverse transfusion event, a clear profile of health responsibility on the part of the management and clinicians.

Radiotherapy and palliative care outpatient clinic: a new healthcare integrated model in Italy.

BACKGROUND: On the basis of substantial evidence demonstrate that palliative care combined with standard care improves patient, caregiver, and society outcomes, we have developed a new healthcare model called radiotherapy and palliative care (RaP) outpatient clinic were a radiation oncologist and a palliative care physician make a joint evaluation of advanced cancer patients. METHODS: We performed a monocentric observational cohort study on advanced cancer patients referred for evaluation at the RaP outpatient clinic. Measures of quality of care were carried out. RESULTS: Between April 2016 and April 2018, 287 joint evaluations were performed and 260 patients were evaluated. The primary tumor was lung in 31.9% of cases. One hundred fifty (52.3%) evaluations resulted in an indication for palliative radiotherapy treatment. In 57.6% of cases was used a single dose fraction of radiotherapy (8 Gy). All the irradiated cohort completed the palliative radiotherapy treatment. An 8% of irradiated patients received the palliative radiotherapy treatment in the last 30 days of life. A total of 80% of RaP patients received palliative care assistance until the end of life. CONCLUSION: At the first descriptive analysis, the radiotherapy and palliative care model seem to respond to the need of multidisciplinary approach in order to obtain an improvement on quality of care for advanced cancer patients.

Drip-and-ship toward mothership model for mechanical thrombectomy during COVID-19 pandemic: a retrospective analysis.

INTRODUCTION: During the first wave of the COVID-19 pandemic in spring 2020, our stroke network shifted from a drip-and-ship strategy (transport of acute ischemic stroke patients to the nearest primary stroke centers) toward a mothership model (direct transportation to the Comprehensive Stroke Center). We retrospectively analyzed stroke network performances comparing the two models. PATIENTS AND METHODS: All spoke-district patients treated with endovascular thrombectomy (EVT) between 15th March-15th June 2019 (drip-and-ship) and 2020 (mothership) were considered. We compared onset-to-groin time (OGT) and onset-to-needle time (ONT) between the two periods. Secondarily, we investigated other performances parameters (percentage of IV thrombolysis, timing of diagnostic and treatment) and clinical outcome (3-month modified Rankin Scale). RESULTS: Twenty-four spoke-district patients in 2019 (drip-and-ship) and 26 in 2020 (mothership) underwent EVT. The groups did not differ for age, sex, risk factors, pre-stroke mRS 0-1, NIHSS, and ASPECTS distribution. The MS model showed a significant decrease of the OGT (162.5 min vs 269 min, p = 0.001) without significantly affecting the ONT (140.5 min vs 136 min, p = 0.853), ensuring a higher number of IV thrombolysis in combination with EVT (p = 0.030). The mothership model showed longer call-to-door time (median + 23 min, p < 0.005), but shorter door-to-needle (median - 31 min, p = 0.001), and door-to-groin time (- 82.5 min, p < 0.001). We found no effects of the stroke network model on the 3-month mRS (ordinal shift analysis, p = 0.753). CONCLUSIONS: The shift to the mothership model during the COVID-19 pandemic guaranteed quicker EVT without significantly delaying IVT.

Impact of the COVID-19 Pandemic on the Therapeutic Continuity among Outpatients with Chronic Cardiovascular Therapies.

The COVID-19 pandemic poses major challenges to healthcare systems. We aimed to investigate the impact of the pandemic on prescription and adherence patterns of chronic cardiovascular therapies (lipid-lowering [LL], oral antidiabetic drugs [AD], and antihypertensives [AH]) using administrative pharmaceutical databases. For each treatment, two cohorts of prevalent cases in 2019 and 2020 were compared. We evaluated the percentage change in dispensed packages and treatment adherence as a proportion of days covered (PDC). For all therapies, an increase was observed during March-April 2020 (LL: +4.52%; AD: +2.72%; AH: +1.09%), with a sharp decrease in May-June 2020 (LL: -8.40%; AD: -12.09%; AH: -10.54%) compared to 2019. The impact of the COVID-19 pandemic on chronic cardiovascular treatments appears negligible on adherence: 533,414 patients showed high adherence to LL (PDC ≥ 80%) in January-February 2020, and 2.29% became poorly adherent (PDC < 20%) in the following four-month period (vs. 1.98% in 2019). A similar increase was also observed for AH (1.25% with poor adherence in 2020 vs. 0.93% in 2019). For AD, the increase was restrained (1.55% with poor adherence in 2020 vs. 1.37% in 2019). The rush to supply drugs at the beginning of lockdown preserved the continuity of chronic cardiovascular therapies.

Real-World Outcomes and Treatments Patterns Prior and after the Introduction of First-Line Immunotherapy for the Treatment of Metastatic Non-Small Cell Lung Cancer.

BACKGROUND: This study provides insights into the treatment use and outcomes of metastatic non-small cell lung cancer (NSCLC) patients in a real-world setting prior to and after the availability of immuno-oncology (IO) regimens in the first line (1L). METHODS: Metastatic NSCLC patients, who initiated systemic 1L anticancer treatment from 2014 to 2020, were identified from health records. Patients were grouped into Pre-1L IO and Post-1L IO, according to the availability of pembrolizumab 1L monotherapy at the date of initiating 1L systemic anticancer treatment. Patient characteristics, treatment patterns and outcomes were assessed by the cohort. Overall survival (OS) and real-world progression-free survival (rwPFS) were calculated using the Kaplan-Meier method. RESULTS: The most common 1L treatment was platinum-based chemotherapy regimens in both groups (≥46%), followed by single-agent chemotherapy (27.0%) in Pre-1L IO and pembrolizumab (26.0%) in Post-1L IO. Median OS was 6.2 (95% CI 5.5-7.4) in Pre- and 8.9 months (95% CI 7.5-10.6) in Post-1L IO, while rwPFS was 3.7 (95% CI 3.3-4.2) and 4.7 months (95% CI 3.9-5.7), respectively. CONCLUSIONS: Even if a small proportion of patients received a 1L IO, the data showed an improved survival outcomes in the Post-1L IO group.

Emilia-Romagna Surgical Colorectal Cancer Audit (ESCA): a value-based healthcare retro-prospective study to measure and improve the quality of surgical care in colorectal cancer.

PURPOSE: Surgery is the main treatment for non-metastatic colorectal cancer. Despite huge improvements in perioperative care, colorectal surgery is still associated with a significant burden of postoperative complications and ultimately costs for healthcare organizations. Systematic clinical auditing activity has already proven to be effective in measuring and improving clinical outcomes, and for this reason, we decided to evaluate its impact in a large area of northern Italy. METHODS: The Emilia-Romagna Surgical Colorectal Audit (ESCA) is an observational, multicentric, retro-prospective study, carried out by 7 hospitals located in the Emilia-Romagna region. All consecutive patients undergoing surgery for colorectal cancer during a 54-month study period will be enrolled. Data regarding baseline conditions, preoperative diagnostic work-up, surgery and postoperative course will be collected in a dedicated case report form. Primary outcomes regard postoperative complications and mortality. Secondary outcomes include each center's adherence to the auditing (enrolment rate) and evaluation of the systematic feedback activity on key performance indicators for the entire perioperative process. CONCLUSION: This protocol describes the methodology of the Emilia-Romagna Surgical Colorectal Audit. The study will provide real-world clinical data essential for benchmarking and feedback activity, to positively impact outcomes and ultimately to improve the entire healthcare process of patients undergoing colorectal cancer surgery. CLINICAL TRIAL REGISTRATION: The study ESCA is registered on the clinicaltrials.gov platform (Identifier: NCT03982641).

Economic Burden of Denatured Alcohol-Induced Burns: A 20-Year Retrospective Study.

Burn care has rapidly improved over the past decades, but health innovations are expensive. We present the first study focusing on the economic burden of exclusive denatured alcohol-induced burns. The goal of this study was to determine costs for the public health system due to inpatients' burn care because of these specific burns. Moreover, we aimed to observe the incidence of methylated spirit-related burns in the past 20 years. We performed an observational retrospective study in our burn unit including all patients with a denatured alcohol-related burn injury from 1 January 2001 to 31 December 2020. A total of 503 patients with a mean burn size of 24% were hospitalized; the mean annual total costs per patient was €43,879, varying from €31,518 to €63,274.00€; the total costs for denatured alcohol-related burns during the period 2001-2020 was €21,145,076. We noted an increasing incidence of denatured alcohol-related burns and related costs over the years, especially in the last decade. Our results highlight that burns by methylated spirits are still a real and expanding problem. Therefore, authorities should focus on sales rules, characteristics of the containers, and education of people who misuse denatured alcohol, based on historical habits of use. To reduce the socioeconomic costs of burns, future intervention strategies and studies from the dermatology community and burn specialists should focus on prevention programs and prompt wound healing to shorten the length of hospital stay, enable quick return to work, and improve the outcomes of patients with burns.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

PURPOSE: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. METHODS: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. RESULTS: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. CONCLUSIONS: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas.

EISOR Delivery: Regional experience with sharing equipe, equipment & expertise to increase cDCD donor pool in time of pandemic.

Donation after circulatory death (DCD) programs are expanding in Europe, in the attempt to expand donors pool. Even in controlled DCD donors, however, a protracted warm ischemia time occurring in the perimortem period might damage organs, making these unsuitable for transplantation. Implementing a strategy of extracorporeal interval support for organ retrieval (EISOR), a regional reperfusion with normothermic, oxygenated blood provides a physiologic environment allowing extensive assessment of potential grafts, and potentially promotes recovery of native function. Here we report the results of a multi-center retrospective cohort study including 29 Maastricht Category III controlled DCD donors undergoing extracorporeal support in a regional DCD/EISOR Training Center, and in the network of referring In-Training Centers, under the liaison of the regional Transplant Coordination Center during COVID-19 pandemic, between March 2020 and November 2021. The study aims to understand whether a mobile, experienced EISOR team implementing a consistent technique and sharing its equipe, expertise and equipment in a regional network of hospitals, might be effective and efficient in implementing the regional DCD program activity even in a highly stressed healthcare system.

Description of an Integrated and Dynamic System to Efficiently Deal With a Raging COVID-19 Pandemic Peak.

Background: This study aimed to describe an innovative and functional method to deal with the increased COVID-19 pandemic-related intensive care unit bed requirements. Methods: We described the emergency creation of an integrated system of internistic ward, step-down unit, and intensive care unit, physically located in reciprocal vicinity on the same floor. The run was carried out under the control of single intensive care staff, through sharing clinical protocols and informatics systems, and following single director supervision. The intention was to create a dynamic and flexible system, allowing for rapid and fluid patient admission/discharge, depending on the requirements due to the third Italian peak of the COVID-19 pandemic in March 2021. Results: This study involved 142 COVID-19 patients and 66 non-COVID-19 patients who were admitted; no critical patient was left unadmitted and no COVID-19 severe patients referring to our center had to be redirected to other hospitals due to bed saturation. This system allowed shorter hospital length-of-stay in general wards (5.9 ± 4 days) than in other internistic COVID-19 wards and overall mortality in line with those reported in literature despite the peak raging. Conclusion: This case report showed the feasibility and the efficiency of this dynamic model of hospital rearrangement to deal with COVID-19 pandemic peaks.

3-T magnetic resonance-guided high-intensity focused ultrasound (3 T-MR-HIFU) for the treatment of pain from bone metastases of solid tumors.

INTRODUCTION: Bone metastases (BM) are still the main cause of morbidity and mortality in cancer patients, not only because of their complications, defined as skeletal-related events (SREs), but also because of the negative impact bone pain has on quality of life (QoL) and survival, especially when opioid analgesics and locoregional treatments fail. MATERIALS AND METHODS: A single-center prospective study was carried out on 12 patients with symptomatic BM treated with MRI-guided focused ultrasound (MR-HIFU). The primary endpoint was the effectiveness of MR-HIFU in reducing current and breakthrough cancer pain (BTCP) scores. The main secondary aims were the evaluation of circulating markers at different time-points and their relation to pain and procedure efficacy. Other secondary objectives included temporal evolution of pain response, evaluation of QoL, and side effects of the treatment. Descriptive statistics were used to evaluate primary and secondary endpoints. Questionnaires on pain and QoL completed at baseline and at 30 days were compared using appropriate statistical tests with exploratory intent. RESULTS: MR-HIFU was successfully completed in all 12 patients enrolled between September 2015 and December 2018. On day 30, 6 (50.0%) patients showed a complete response of current pain and 6 a partial response, while 5 (41.7%) obtained a complete BTCP response. A partial response of BM evaluated by MD Anderson criteria was obtained in 9 (81.8%) patients. Only one patient progressed in the target lesion after MR-HIFU. No treatment-related adverse events were recorded. Bone turnover markers CTX/RANK-L (P) do not demonstrate any significant change with the pain or BM response. CONCLUSION: In our patients, targeted therapy of painful BM with MRI-guided focused ultrasound ablation was safe and showed encouraging early-onset and functional results.

Appropriateness and Economic Analysis of Conventional Circulating Biomarkers Assessment in Early Breast Cancer: A Real-World Experience from the E.Pic.A Study.

The risk of relapse for early breast cancer (BC) patients persists even after decades and to date, no specific and sensitive effective circulating biomarker for recurrence prediction has been identified yet. The international guidelines do not recommend the assessment of the serum tumor markers CEA and CA15-3 in the follow-up of asymptomatic early BC patients. In our institute, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", as part of the E.Pic.A study, which was designed to assess the economic appropriateness of integrated care pathways in early BC, the use of CEA and CA15-3 as circulating tumor biomarkers in early BC patients was evaluated in 1502 patients one year after surgery, from 2015 to 2018, with an overall expense of EUR 51,764. A total of EUR 47,780 (92%) was used for execution of circulating tumor markers in early BC patients with stage 0, I and II tumors, neglecting the current guidelines and considered inappropriate by our professional board. We found that no patients with stage I BC experienced relapse in the 365 days after surgery, and in any case examination of the circulating markers CEA and CA15-3 was considered crucial for diagnosis of relapse. Our findings suggest that this inadequacy is a low-value area, supporting the reallocation of economic resources for interventions of a higher value for patients.

Variations of the quality of care during the COVID-19 pandemic affected the mortality rate of non-COVID-19 patients with hip fracture.

INTRODUCTION: As COVID-19 roared through the world, governments worldwide enforced containment measures that affected various treatment pathways, including those for hip fractures (HFs). This study aimed to measure process and outcome indicators related to the quality of care provided to non-COVID-19 elderly patients affected by HF in Emilia-Romagna, a region of Italy severely hit by the pandemic. METHODS: We collected the hospital discharge records of all patients admitted to the hospitals of Emilia-Romagna with a diagnosis of HF from January to May in the years 2019 (pre-pandemic period) and 2020 (pandemic period). We analyzed surgery rate, surgery delays, length of hospital stay, timely rehabilitation, and 30-day mortality for each HF patient. We evaluated monthly data (2020 vs. 2019) with the chi-square and t-test, where appropriate. Logistic regression was used to investigate the differences in 30-day mortality. RESULTS: Our study included 5379 patients with HF. In April and May 2020, there was a significant increase in the proportion of HF patients that did not undergo timely surgery. In March 2020, we found a significant increase in mortality (OR = 2.22). Male sex (OR = 1.92), age ≥90 years (OR = 4.33), surgery after 48 hours (OR = 3.08) and not receiving surgery (OR = 6.19) were significantly associated with increased mortality. After adjusting for the aforementioned factors, patients hospitalized in March 2020 still suffered higher mortality (OR = 2.21). CONCLUSIONS: There was a reduction in the overall quality of care provided to non-COVID-19 elderly patients affected by HF, whose mortality increased in March 2020. Patients' characteristics and variations in processes of care partially explained this increase. Policymakers and professionals involved in the management of COVID-19 patients should be aware of the needs of patients with other health needs, which should be carefully investigated and included in future emergency preparedness and response plans.

Is it time to consider depression as a major complication of type 2 diabetes? Evidence from a large population-based cohort study.

AIMS: Depression in type 2 diabetes may heavily affect the course of the disease. In this study, we investigated, among new cases with type 2 diabetes, the incidence and clinical predictors of depression and determined the extent to which depression constitutes a risk factor for acute and long-term diabetes complications and mortality. METHODS: In this population-based retrospective cohort study, incident cases of type 2 diabetes without a prior history of depression were identified from the administrative databases of the Emilia-Romagna Region, Italy, between 2008 and 2017 and followed up until 2020. Logistic regression models were used to identify the predictors of depression. Cox regression models were used to estimate the risk of acute complications over three years, and the risk of long-term complications and mortality over ten years. RESULTS: Incident cases with type 2 diabetes were 30,815, of whom 5146 (16.7%) developed depression. The predictors of depression onset were as follows: female sex, age > 65 years, living in rural areas and comorbid diseases. Depression in type 2 diabetes was associated with a 2.3-fold risk of developing acute complications, 1.6-fold risk of developing long-term complications and 2.8-fold mortality risk. CONCLUSIONS: Our findings highlight that depression is associated with an increased risk for complications in type 2 diabetes and mortality and should not be neglected. Therefore, it is important to promote screening activities and introduce targeted and personalized treatment for depression in order to reduce the risk of poor short- and long-term outcomes of diabetes.

How has COVID-19 pandemic changed flu vaccination attitudes among an Italian cancer center healthcare workers?

A retrospective study was conducted among Italian cancer healthcare workers (HCWs) to describe how influenza vaccination attitudes have changed during the COVID-19 pandemic. The analysis was conducted on the last three influenza seasons (2018/19, 2019/20 and 2020/21). To account for different relationships and proximity with patients, the study population was grouped into three main professional categories: health personnel, administrative staff and technicians. Moreover, to explore the factors affecting the coverage of influenza vaccine, a multinomial regression analysis was performed.Over the years, the influenza vaccination uptake showed a gradual increase across the overall staff, the highest coverage (53.8%) was observed in the season 2020/21, in particular, for health personnel (57.7%). In general, males resulted in more adherent to vaccination campaigns; nevertheless, this gap decreased in the last season. A total of 28.6% workers were always vaccinated throughout the past three seasons, a remarkable 25.2% (mainly young and females) received for the first time the influenza vaccination in 2020/21.In this dramatic health crisis, the attitudes of HCWs toward flu vaccination have changed. The COVID-19 outbreak increased adherence to flu vaccination, reaching the highest coverage in the campaign 2020/21. However, further efforts should be made to achieve greater vaccination coverage.