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Abstract Aims A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. Methods and results Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014–2015 entered in the cohort and followed up until 2019. Adherence to evidence‐based recommendations [i.e. renin–angiotensin–aldosterone system (RAS) inhibitors, beta‐blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all‐cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow‐up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person‐year) were compared between adherent and non‐adherent patients. A non‐parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost‐effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta‐blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non‐adherent patients, those who adhered to ECCs, RAS inhibitors, beta‐blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2–14%), 11% (7–14%), 8% (5–11%), and 4% (−1–8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta‐blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta‐blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. Conclusions Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

Cardiovascular disease is associated with progression to severe COVID-19 and patients with the condition are among those in whom early antiviral therapy should be warranted. The combination of nirmatrelvir/ritonavir (Paxlovid®) has been approved for clinical use by the Food and Drug Administration and European Medicines Agency. Because patients with cardiovascular disease are often on polypharmacy, physicians need to be aware of potential drug–drug interactions (DDIs) when treating COVID-19 with nirmatrelvir/ritonavir. Guidance is given for avoiding DDIs, emphasising that preventing and managing potential DDIs with nirmatrelvir/ritonavir requires thorough assessment and knowledge. The present review summarises the clinical pharmacology of nirmatrelvir/ritonavir and provides details on potential DDIs with a focus on daily practice in patients with cardiovascular disease. Particular attention is needed for drugs that are predominantly metabolised by cytochrome P450 3A4, are substrates of P-glycoprotein and have a narrow therapeutic index. Proper management of potential DDIs must balance the benefit of nirmatrelvir/ritonavir to prevent severe disease with the risk of serious adverse events.

BackgroundA sex-based evaluation of prognosis in heart failure (HF) is lacking.Methods and resultsWe analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72–7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women).ConclusionsS-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

BackgroundHeart failure (HF) significantly affects the morbidity, mortality, and quality of life of patients. New therapeutic strategies aim to improve the functional capacity and quality of life of patients while controlling HF-related risks. Real-world data on both the functional and cardiopulmonary exercise capacities of patients with HF with reduced ejection fraction upon sacubitril/valsartan use are lacking.MethodsA multicenter, retrospective, cohort study, called REAL.IT, was performed based on the data collected from the electronic medical records of nine specialized HF centers in Italy. Cardiopulmonary exercise testing was performed at baseline and after 12 months of sacubitril/valsartan therapy, monitoring carbon dioxide production (VCO2) and oxygen consumption (VO2).ResultsThe functional capacities of 170 patients were evaluated. The most common comorbidities were hypertension and diabetes (i.e., 53.5 and 32.4%, respectively). At follow-up, both the VO2 peak (from 15.1 ± 3.7 ml/kg/min at baseline to 17.6 ± 4.7 ml/kg/min at follow-up, p

Abstract Background Radiomorphometric indices measured on Dental Panoramic Radiography (DPR) can reflect Bone Mineral Density (BMD). The aim of our study is to evaluate changes in DPR radiographic markers in patients undergoing antiresorptive therapy with denosumab and correlate them to BMD and serum bone turnover markers (BTM). Methods We evaluated two radiomorphometric indices: Mandibular Cortical Width (MCW) and Panoramic Mandibular Index (PMI), in patients undergoing antiresorptive therapy with denosumab at T0 (before starting the therapy) and at T1 (after 12 months), comparing results with a control group of healthy patients who performed two DPRs at a one-year time distance. Correlation analysis was performed in the denosumab group, as well as ROC curves were obtained for both indices. Results The study included 18 patients and 21 controls according to specific inclusion and exclusion criteria, matched by gender and age. Both MCW and PMI were significantly lower at T0 in the denosumab group, consistently with lower BMD. MCW showed significant correlation with femoral and lumbar DEXA and was significantly lower in patients with osteoporosis compared to osteopenia. Only PMI index increased significantly in the denosumab group from T0 to T1. After one year (T1), there weren’t any differences between patients and controls for both indices. No significant correlations were found with BTMs. Sensitivity and specificity for MCW and PMI were also calculated. Conclusions Our results show how CMW shows sufficient sensitivity and specificity to be used as a radiographic marker to screen and intercept patients with osteoporosis. PMI seems to be able to reflect changes in response to antiresorptive therapy with denosumab. Further studies are needed to confirm our hypothesis.

This study compares the effect of different handpieces (turbine, high-speed electric handpiece and piezoelectric device) on surface roughness of enamel and dentin when using diamond-coated working tips and burs of the same grit size. The experiment was conducted on 15 extracted first molars from patients aged 45 to 60 years. The occlusal portion was removed using a diamond-coated water wheel and then refined with a 120–130 μm grit bur in order to obtain a flat surface with an adequate exposition of the dentin core. Each surface was divided into three portions and every portion was finished with one of the three tested instruments. The rotary burs and piezoelectric tips had the same grit size (60 μm), and the load on handpiece during preparation never exceeded 150 g. Roughness parameters (Ra, Rsk, Rku) were recorded with a profilometer, and a SEM analysis of treated surfaces and working tips was conducted. Ra and Rsk differed significantly between enamel and dentin only after using turbine (p = 0.004 and p = 0.007, respectively). No significant differences were observed in Ra, Rsk and Rku between enamel and dentin when using a high-speed electric handpiece or piezoelectric device. The turbine produced higher Ra and Rsk values on dentin than the other devices, while no significant differences were found between piezoelectric handpiece and high-speed electric contra-angle on both substrates. Summarizing, the findings of the present study demonstrated that turbine generated rougher surfaces on dentin compared to the other handpieces. Moreover, the turbine produced more asymmetrical surface profiles on both enamel and dentin. However, it should be considered that these differences in roughness (Ra) were within the range of 0.25–0.30 μm: it is still unclear if these variations, although statistically significant, will influence final clinical outcomes.

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies.

Abstract Background Machine learning (ML) methods to build prediction models starting from electrocardiogram (ECG) signals are an emerging research field. The aim of the present study is to investigate the performances of two ML approaches based on ECGs for the prediction of new-onset atrial fibrillation (AF), in terms of discrimination, calibration and sample size dependence. Methods We trained two models to predict new-onset AF: a convolutional neural network (CNN), that takes as input the raw ECG signals, and an eXtreme Gradient Boosting model (XGB), that uses the signal’s extracted features. A penalized logistic regression model (LR) was used as a benchmark. Discrimination was evaluated with the area under the ROC curve, while calibration with the integrated calibration index. We investigated the dependence of models’ performances on the sample size and on class imbalance corrections introduced with random under-sampling. Results CNN's discrimination was the most affected by the sample size, outperforming XGB and LR only around n = 10.000 observations. Calibration showed only a small dependence on the sample size for all the models considered. Balancing the training set with random undersampling did not improve discrimination in any of the models. Instead, the main effect of imbalance corrections was to worsen the models’ calibration (for CNN, integrated calibration index from 0.014 [0.01, 0.018] to 0.17 [0.16, 0.19]). The sample size emerged as a fundamental point for developing the CNN model, especially in terms of discrimination (AUC = 0.75 [0.73, 0.77] when n = 10.000, AUC = 0.80 [0.79, 0.81] when n = 150.000). The effect of the sample size on the other two models was weaker. Imbalance corrections led to poorly calibrated models, for all the approaches considered, reducing the clinical utility of the models. Conclusions Our results suggest that the choice of approach in the analysis of ECG should be based on the amount of data available, preferring more standard models for small datasets. Moreover, imbalance correction methods should be avoided when developing clinical prediction models, where calibration is crucial.

Low-Density Lipoprotein (LDL) cholesterol is one of the main target for cardiovascular (CV) prevention and therapy. In the last years, Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9-i) has emerged as a key therapeutic target to lower LDL and were introduced for prevention of CV events. Recently (June 2022) the Italian Medicines Agency (AIFA) modified the eligibility criteria for the use of PCSK9-i. We designed an observational study to estimate the prevalence of eligible subjects and evaluate the effectiveness of PCSK9-i applying a Target Trial Emulation (TTE) approach based on Electronic Health Records (EHR). Subjects meeting the eligibility criteria were identified from July 2017 (when PCSK9-i became available) to December 2020. Outcomes were all-cause death and the first hospitalization. Among eligible subjects, we identified those treated at date of the first prescription. Inverse Probability of Treatment Weights (IPTW) were estimated including demographic and clinical covariates, history of treatment with statins and the month/year eligibility date. Competing risk models on weighted cohorts were used to derive the Average Treatment Effect (ATE) and the Conditional Average Treatment Effect (CATE) in subgroups of interest. Out of 1976 eligible subjects, 161 (8%) received treatment with PCSK9-i. Treated individuals were slightly younger, predominantly male, had more severe CV conditions, and were more often treated with statin compared to the untreated subjects. The latter exhibited a higher prevalence of non-CV comorbidities. A significant absolute and relative risk reduction of death and a lower relative risk for the first hospitalization was observed. The risk reduction for death was confirmed in CATE analysis. PCSk9-i were prescribed to a minority of eligible subjects. Within the TTE framework, the analysis confirmed the association between PCSK9-i and lower risk of events, aligning with findings from randomized clinical trials (RCTs). In our study, PCSK9-i provided protection specifically against all-cause death, expanding upon the evidence from RCTs that had primarily focused on composite CV outcomes.

Background: Sarcopenia poses a risk factor for falls, disability, mortality, and unfavorable postoperative outcomes. Recently, the Ultrasound Sarcopenia Index (USI) has been validated to assess muscle mass, and this study aimed to apply the USI in the clinical setting. Methods: This prospective observational study included 108 patients aged >65 years, hospitalized for proximal femoral traumatic fracture. Patients were divided into two groups based on anamnestic data: patients with independent walking (IW) and patients requiring walking aid (WA) before admission. All the participants received an ultrasound examination. Other parameters evaluated were handgrip strength, limb circumferences, nutrition (MNA), and activity of daily living (ADL) scores. Results: Fifty-six IW patients (83 ± 6 y; 38 females) and 52 WA patients (87 ± 7 y; 44 females) were recruited. The USI was significantly higher in the IW group compared to the WA group (p = 0.013, Cohen’s d = 0.489). Significant correlations were found between the USI and other sarcopenia-associated parameters, such as handgrip strength, MNA, ADLs, other muscle ultrasound parameters, and limb circumferences. Conclusion: The application of the USI in the orthopedic surgery setting is feasible and might support the diagnosis of sarcopenia when combined with other measures of strength and function.

Abstract Background The introduction in the orthodontic field of the digital workflow for guided insertion of palatal TADs and the development of the 1-visit protocol led to the reduction of chair time and the possibility of complete customization of designs and materials. Conversely, the reduction of operative steps implicates a lower tolerance of deviations between the planned and the actual position of the miniscrews, particularly when the orthodontic device is fixed on 4 palatal TADs or has a rigid structure. This study aims to analyze the influence of each step of the digital workflow on the deviation of the miniscrews’ axis of insertion in a bicortical sample. The null hypothesis is that there are no significant differences in the deviations among the operative steps. Methods 33 subjects were selected for insertion of bicortical palatal miniscrews with a 1-visit protocol. Digital files were collected at the three stages of the workflow (i.e., digital planning, laboratory prototype, post-insertion impression). A 3D software analysis was performed on a total of 64 miniscrews. After automatic shape recognition of the guiding holes of the digital plan and the scanbodies of the laboratory prototype and post-insertion impression as geometric cylinders, their three-dimensional longitudinal axis was traced and the deviation among them was calculated. Friedman test with Bonferroni correction was performed to assess the significance of the deviations among the three steps, with significance set at p

Background and Objectives: Special Needs Patients (SNPs) and young non-collaborative children are more predisposed to develop oral pathologies due to poor collaboration and scarce access to dental treatment. The aim of this retrospective study was to analyze a sample of SNPs who received dental treatments either under general anesthesia (GA) or deep sedation (DS) over a period of 6 years. The number and type of procedure were analyzed. Materials and Methods: In total, 131 patients were included and mostly (>90%) treated under GA. Patients were either uncooperative and phobic (Group 1) or affected by mental, behavioral, and neurological disorders (Group 2), diseases of the nervous system (Group 3), or developmental anomalies (Group 4). Results: Patients in Group 2 required more invasive dental treatments than those in the other groups. Therapies were mainly preventive and restorative, except in Groups 3 and 4, where extractions were more frequent. The type of dental treatment significantly varied according to age and systemic condition. Only 5.3% of the patients needed a second intervention, despite only 17.6% of patients respecting the scheduled follow-up. Conclusions: Treatment under GA is effective, but the poor adherence to follow-ups and the risk of reintervention should be contrasted by improving the perception by parents/guardians of the importance of oral hygiene and periodic visits.

In exploring chronic orofacial pain (COFP), this review highlights its global impact on life quality and critiques current diagnostic systems, including the ICD-11, ICOP, and ICHD-3, for their limitations in addressing COFP’s complexity. Firstly, this study outlines the global burden of chronic pain and the importance of distinguishing between different pain types for effective treatment. It then delves into the specific challenges of diagnosing COFP, emphasizing the need for a more nuanced approach that incorporates the biopsychosocial model. This review critically examines existing classification systems, highlighting their limitations in fully capturing COFP’s multifaceted nature. It advocates for the integration of these systems with the DSM-5’s Somatic Symptom Disorder code, proposing a unified, multidisciplinary diagnostic approach. This recommendation aims to improve chronic pain coding standardization and acknowledge the complex interplay of biological, psychological, and social factors in COFP. In conclusion, here, we highlight the need for a comprehensive, universally applicable classification system for COFP. Such a system would enable accurate diagnosis, streamline treatment strategies, and enhance communication among healthcare professionals. This advancement holds potential for significant contributions to research and patient care in this challenging field, offering a broader perspective for scientists across disciplines.

Abstract Background Primary Synovial Chondromatosis (PSC) is a rare benign tumor of the synovial membrane in which cartilage metaplasia produces calcific loose bodies within the articular space. Only a few cases are reported in the pediatric population and its etiology remains unknown. This condition typically affects large weight-bearing joints with pain, swelling and decrease range of motion. Due to its slow progressions, delayed diagnosis is frequent and differential diagnosis should consider other chronic arthritis and malignancies. While arthroscopic removal of loose bodies is the current treatment up to now, the association of partial or complete synovectomy is debated. Case presentation We report about a 14-year-old girl with a long-lasting right shoulder pain, especially during movements or exercise, localized tenderness and hypotonia of the glenohumeral joint. No previous trauma was mentioned. Blood exams, Mantoux test and plain radiography of the right shoulder were unremarkable. Ultrasound imaging revealed echogenic and calcified bodies stretching the glenohumeral joint and dislocating the long head of biceps tendon. Magnetic resonance showed a “rice-grain” pattern of the right shoulder. From an arthroscopic surgery, multiple loose white bodies were removed within the synovial membrane, and synovial chondromatosis was confirmed by histological analysis. At one month follow up visit, the patient completely recovered without pain. Conclusion Synovial chondromatosis is a very uncommon cause of mono articular pain in children, especially when it affects shoulder. Pediatricians should keep in mind this condition to avoid delayed diagnosis and treatment, even in consideration of the low risk of malignant transformation. Through this case, we would highlight common diagnostic pitfalls and treatment of synovial chondromatosis.

Family history for CAD (coronary artery disease) is an established cardiovascular (CV) risk factor and it is progressively acquiring importance in patients' CV risk stratification. Numerous studies have demonstrated that individuals with a first-degree relative affected by CAD have a significantly higher risk of developing the condition themselves; in particular, when CAD occurs at an early age in relatives. Indeed, recently published CCS (chronic coronary syndrome) ESC (European Society of Cardiology) guidelines include family history (FH) as a risk factor to consider when calculating pre-test risk for CAD. ESC guidelines on preventive cardiology (2021) only suggested CV risk assessment in the presence of a positive FH for CV disease, not considering it in the actual risk scores. Evidence suggests that positive anamnesis for relatives affected by CAD correlates with ACS (acute coronary syndrome) and CAD, with slight differences in relative risk as far as the degree of kinship is concerned. Genetic factors contribute to this correlation by influencing key processes that affect heart health, such as cholesterol metabolism, blood pressure regulation, and inflammatory responses. New technologies in the genetics field are increasing the availability of genome sequencing, and new polymorphism panels are being tested as predictive for CAD, objectifying familiarity. Advances in imaging techniques allow the assessment of coronary atherosclerosis and its composition, and these are acquiring strength in evidence and recommendations in ESC guidelines as a way to define coronary disease in low and low-to-intermediate risk patients and to guide medical therapy and interventional procedures. Use of these emerging tools to guide screening is likely to be extended, beyond high CV risk patients, to individuals with FH for early CAD and/or specific genetic profiles, as recent evidence in the literature is suggesting. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the psychological impact of COVID‐19 on burning mouth syndrome (BMS) patients. It focuses on comparing post‐traumatic stress symptoms (PTSS), post‐traumatic growth (PTG), and resilience between BMS patients and Controls. Methods: A total of 100 BMS patients and 100 Controls from five Italian centers participated in this observational cross‐sectional study. They completed several assessments, including the General Health Questionnaire, Depression Anxiety and Stress Scale, Insomnia Severity Index, National Stressful Events Survey Short Scale, Impact of Event Scale‐Revised, Post Traumatic Growth Inventory Short Form, and Connor‐Davidson Resilience Scale. Results: BMS patients had significantly higher stress, anxiety, and depression (DASS‐21 score) and post‐traumatic stress symptoms (IES‐R‐6 score), particularly in terms of intrusive thoughts. They showed lower post‐traumatic growth (PTGI‐SF score) compared to Controls. The resilience scale (CDRS‐10) was a key predictor of PTG in both groups, explaining a significant variance in PTGI‐SF scores. Conclusions: BMS patients experienced heightened post‐traumatic stress, stress, anxiety, and depression during the COVID‐19 pandemic, with reduced post‐traumatic growth. This highlights the need to prioritize their psychological well‐being, focusing on stress management and fostering post‐traumatic growth in challenging times. [ABSTRACT FROM AUTHOR]

Aims: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. Methods and results: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014–2015 entered in the cohort and followed up until 2019. Adherence to evidence‐based recommendations [i.e. renin–angiotensin–aldosterone system (RAS) inhibitors, beta‐blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all‐cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow‐up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person‐year) were compared between adherent and non‐adherent patients. A non‐parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost‐effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta‐blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non‐adherent patients, those who adhered to ECCs, RAS inhibitors, beta‐blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2–14%), 11% (7–14%), 8% (5–11%), and 4% (−1–8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta‐blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta‐blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. Conclusions: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits. [ABSTRACT FROM AUTHOR]

Low-Density Lipoprotein (LDL) cholesterol is one of the main target for cardiovascular (CV) prevention and therapy. In the last years, Proprotein Convertase Subtilisin–Kexin type 9 inhibitors (PCSK9-i) has emerged as a key therapeutic target to lower LDL and were introduced for prevention of CV events. Recently (June 2022) the Italian Medicines Agency (AIFA) modified the eligibility criteria for the use of PCSK9-i. We designed an observational study to estimate the prevalence of eligible subjects and evaluate the effectiveness of PCSK9-i applying a Target Trial Emulation (TTE) approach based on Electronic Health Records (EHR). Subjects meeting the eligibility criteria were identified from July 2017 (when PCSK9-i became available) to December 2020. Outcomes were all-cause death and the first hospitalization. Among eligible subjects, we identified those treated at date of the first prescription. Inverse Probability of Treatment Weights (IPTW) were estimated including demographic and clinical covariates, history of treatment with statins and the month/year eligibility date. Competing risk models on weighted cohorts were used to derive the Average Treatment Effect (ATE) and the Conditional Average Treatment Effect (CATE) in subgroups of interest. Out of 1976 eligible subjects, 161 (8%) received treatment with PCSK9-i. Treated individuals were slightly younger, predominantly male, had more severe CV conditions, and were more often treated with statin compared to the untreated subjects. The latter exhibited a higher prevalence of non-CV comorbidities. A significant absolute and relative risk reduction of death and a lower relative risk for the first hospitalization was observed. The risk reduction for death was confirmed in CATE analysis. PCSk9-i were prescribed to a minority of eligible subjects. Within the TTE framework, the analysis confirmed the association between PCSK9-i and lower risk of events, aligning with findings from randomized clinical trials (RCTs). In our study, PCSK9-i provided protection specifically against all-cause death, expanding upon the evidence from RCTs that had primarily focused on composite CV outcomes. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus (T2DM) have more than twice the risk of developing heart failure (HF) compared to patients without diabetes. The present study is aimed to build an artificial intelligence (AI) prognostic model that takes in account a large and heterogeneous set of clinical factors and investigates the risk of developing HF in diabetic patients. We carried out an electronic health records- (EHR-) based retrospective cohort study that included patients with cardiological clinical evaluation and no previous diagnosis of HF. Information consists of features extracted from clinical and administrative data obtained as part of routine medical care. The primary endpoint was diagnosis of HF (during out-of-hospital clinical examination or hospitalization). We developed two prognostic models using (1) elastic net regularization for Cox proportional hazard model (COX) and (2) a deep neural network survival method (PHNN), in which a neural network was used to represent a non-linear hazard function and explainability strategies are applied to estimate the influence of predictors on the risk function. Over a median follow-up of 65 months, 17.3% of the 10,614 patients developed HF. The PHNN model outperformed COX both in terms of discrimination (c-index 0.768 vs 0.734) and calibration (2-year integrated calibration index 0.008 vs 0.018). The AI approach led to the identification of 20 predictors of different domains (age, body mass index, echocardiographic and electrocardiographic features, laboratory measurements, comorbidities, therapies) whose relationship with the predicted risk correspond to known trends in the clinical practice. Our results suggest that prognostic models for HF in diabetic patients may improve using EHRs in combination with AI techniques for survival analysis, which provide high flexibility and better performance with respect to standard approaches.

The aim of the study was to verify the knowledge on oral cancer and to assess possible differences in awareness and information basing on different demographic and subject-related factors. An anonymous survey was provided to 750 random subjects using online-based questionnaires. Statistical analysis was performed in order to evaluate the influence of demographic variables (gender, age, education) on knowledge of oral cancer and its risk factors. 68.4% of individuals knew about the existence of oral cancer, mostly from media and family/friends. Awareness was significantly influenced by gender and higher education, but not by age. Most participants recognized smoking as a risk factor, but alcohol abuse and sunlight exposure are less known, especially among less educated subjects. On the contrary, our study shows a diffusion of false information: more than 30% of the participants indicated the possible role of amalgam fillings in oral cancer onset, independently of gender, age or education. The results of our study suggest the need for oral cancer awareness campaigns, where school and healthcare professionals should be actively involved in promoting, organizing and finding methods to monitor the medium and long-term efficacy with proper methodological quality.

Abstract This study aims to provide real-world data about starting-dose of NOACs and dose-adjustment in patients with atrial fibrillation (AF). In fact, even if new oral anticoagulation agents (NOACs) have a predictable effect without need for regular monitoring, dose-adjustments should be performed according to the summary of product information and international guidelines. We employed the Italian Medicines Agency monitoring registries comprising data on a nationwide cohort of patients with AF treated with NOACs from 2013 to 2018. Logistic regression analysis was used to evaluate the determinants of dosage choice. During the reference period, treatment was commenced for 866,539 patients. Forty-five percent of the first prescriptions were dispensed at a reduced dose (dabigatran 60.3%, edoxaban 45.2%, apixaban 40.9%, rivaroxaban 37.4%). The prescription of reduced dose was associated with older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, but not with CHA2DS2-VASc and HAS-BLED. A relative reduction of the proportion of patients treated with low dosages was evident overtime for dabigatran and rivaroxaban; whereas prescription of low dose apixaban and edoxaban increased progressively among elderly patients. Evidence based on real-world data shows a high frequency of low dose prescriptions of NOACs in AF patients. Except for older age, renal disease, bleeding risk and the concomitant use of drugs predisposing to bleeding, other factors that may determine the choice of reduced dose could not be ascertained. There may be potential under-treatment of AF patients, but further evaluation is warranted.

Ischemic heart disease is currently the most common cause of mortality and morbidity worldwide. Although myocardial ischemia is classically determined by epicardial coronary atherosclerosis, up to 40% of patients referred for coronary angiography have no obstructive coronary artery disease (CAD). Ischemia with non-obstructive coronary artery disease (INOCA) has typically been underestimated in the past because, until recently, its prognostic significance was not completely clear. This review aims to highlight differences and patterns in myocardial ischemia caused by epicardial obstructive CAD, coronary microvascular dysfunction (CMD) or vasomotor abnormalities and to elucidate the state of the art in correctly diagnosing these different patterns. [ABSTRACT FROM AUTHOR]

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies. [ABSTRACT FROM AUTHOR]