Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78-0.94) and ischemic stroke (HR 0.68, 95%CI 0.55-0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38-2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43-103) and the NNH to cause major bleeding was 107 (77-193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

The FALD-V: A predictive formula for preoperative volume assessment of adipose tissue transplantation in FALD flap.

BACKGROUND: The fat-augmented latissimus dorsi (FALD) flap is an evolution of the traditional latissimus dorsi (LD) flap, which allows to obtain a total autologous breast reconstruction (BR) avoiding the use of breast implants. The aim of this study was to develop a predictive preoperative formula in order to estimate and optimize the amount of fat to be transferred during FALD flap BR, using only anthropometric measurements. METHODS: We conducted a prospective clinical study between September 2020 and April 2023. All patients underwent back pre-operative ultrasound scan to assess the subcutaneous skin paddle thickness (SPT) and a regression analysis was performed to evaluate which anthropometric variable had a better correlation with this thickness. RESULTS: Data from 66 FALD flaps were collected. The mean SPT was 11.95 mm (SD 4.56). A significant correlation between SPT and body mass index (BMI) was found (r = 0.640, p < 0.0001). Using the fat-to-capacity ratio (113%), the following formula (the FALD-V) was developed to predict the needed fat transfer into FALD flap: [-509 + 12.32 × BMI + 11.71 × skin paddle width + 17.43 × skin paddle height] × 1.13. The considered variables (BMI, skin paddle width and skin paddle height) were statistically significant (p < 0.001, p = 0.0483, p = 0.0154, respectively). The cross-validation confirmed the accuracy of the formula (r = 0.810). CONCLUSION: The FALD-V can be used as an innovative complimentary device in the planning of FALD flap one-stage total autologous BR. To enhance its application, a 3.0 WebApp at www.braflap.com (and www.breast-v.com) is available free of charge for both iOS and Android devices. LEVEL OF EVIDENCE: II.

The Ergonomic FALD Flap for One-stage Total Breast Reconstruction.

Background: The fat-augmented latissimus dorsi (FALD) flap combines this pedicled flap with immediate intraoperative fat transfer. Very little is described concerning its inset at the mammary site. Our efforts have concentrated on seeking the best flap orientation and skin-adipose paddle shaping, to improve the aesthetic outcome and to obtain a complete breast reconstruction (BR) in one stage. Methods: A prospective clinical study was performed in patients who underwent BR with FALD flaps, between December 2020 and March 2022. Patients were randomly enrolled into two groups: ergonomic inset of the FALD flap with vertical orientation of the skin-adipose paddle (group A) and FALD flap with traditional horizontal paddle orientation (group B). The study's endpoints were the evaluation of the aesthetic outcomes (from patients' and surgeon's perspectives) and complications. Results: Thirty-two FALD flaps (23 patients) were performed for group A, and 31 FALD flaps (25 patients) for group B. The two groups were homogeneous in terms of demographic and surgical data (P > 0.05). The overall complication rate was homogeneous among the groups, without statistically significant differences (P = 1.00). The surgeon's assessments showed a statistically significant superior aesthetic outcome in group A regarding volume, symmetry, and shape (P < 0.05). Higher satisfaction was observed in group A patients, in terms of breast size (P < 0.00001), shape (P = 0.0049), and overall satisfaction (P = 0.00061). Conclusions: The ergonomic vertical FALD flap technique enables surgeons to perform one-stage total BR, with excellent breast projection and upper pole fullness. These refinements in flap shaping and molding reduced the need for further autologous fat transfer, obtaining a brilliant totally autologous BR without the need for microsurgical experience.

Role of Functional Neuroimaging with 123I-MIBG and 123I-FP-CIT in De Novo Parkinson's Disease: A Multicenter Study.

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. METHODS: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. RESULTS: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). CONCLUSIONS: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.

Sex differences in 123I-mIBG scintigraphy imaging techniques in patients with heart failure.

BACKGROUND: 123I-mIBG-scintigraphy could be a useful stratifying tool for patients with heart failure (HF). The purpose of this retrospective study is to evaluate whether there are differences between men and women with HF in terms of the prediction of cardiac arrhythmic events (AE). RESEARCH AND METHODS: A total of 306 patients, before implantable-cardioverter-defibrillator (ICD) implantation, were evaluated. They underwent 123I-mIBG-scintigraphy and an evaluation of the results was performed after 85 months of follow-up. Early and late planar and SPECT cardiac images were acquired. Heart-to-mediastinum ratio (HM) for planar images and the sum of the segmental scores (SS) for SPECT were calculated. RESULTS: In the general population, age, early SS (ESS), late SS (LSS), and ejection fraction (EF) were statistically significant for the prediction of AE at Cox regression, while early and late HM (eHM,lHM) were not significative for the prediction of AE. Population was divided into females and males and univariate analysis was conducted separately for the two cohorts: no significant variables for prediction of AE were found in females. For males, ESS, LSS, EF, and late HM were statistically significant predictors of AE. The overall survival was similar in males and females, but the risk of AE is lower in males than in females. CONCLUSIONS: 123I-mIBG represents a more effective tool for the prediction of AE in male patients than in women.

Evaluation of partial pressure CO2 change in the dialyzer blood inlet during hemodialysis as a measure of vascular access recirculation.

INTRODUCTION: Vascular access recirculation during hemodialysis is associated with reduced effectiveness and worse survival outcomes. To evaluate recirculation, an increase in pCO2 in the blood of the arterial line during hemodialysis (threshold of 4.5 mmHg) was proposed. The blood returning from the dialyzer in the venous line has significantly higher pCO2 , so in the presence of recirculation, pCO2 in the arterial blood line may increase (ΔpCO2 ) during hemodialysis sessions. The aim of our study was to evaluate ΔpCO2 as a diagnostic tool for vascular access recirculation in chronic hemodialysis patients. METHODS: We evaluated vascular access recirculation with ΔpCO2 and compared it with the results of a urea recirculation test, which is the gold standard. ΔpCO2 was obtained from the difference in pCO2 in the arterial line at baseline (pCO2 T1) and after 5 min of hemodialysis (pCO2 T2). ∆pCO2 = pCO2 T2-pCO2 T1. FINDINGS: In 70 hemodialysis patients (mean age: 70.52 ± 13.97 years; hemodialysis vintage of 41.36 ± 34.54, KT/V 1.4 ± 0.3), ∆pCO2 was 4 ± 4 mmHg, and urea recirculation was 7% ± 9%. Vascular access recirculation was identified using both methods in 17 of 70 patients, who showed a ∆pCO2 of 10 ± 5 mmHg and urea recirculation of 20% ± 9%; time in months of hemodialysis was the only difference between vascular access recirculation and non-vascular access recirculation patients (22 ± 19 vs. 46 ± 36, p: 0.05). In the non-vascular access recirculation group, the average ΔpCO2 was 1.9 ± 2 (p: 0.001), and the urea recirculation % was 2.8 ± 3 (p: 0.001). The ΔpCO2 correlated with the urea recirculation % (R: 0.728; p < 0.001). DISCUSSION: ΔpCO2 in the arterial blood line during hemodialysis is an effective and reliable diagnostic tool for identifying recirculation of the vascular access but not its magnitude. The ΔpCO2 test application is simple and economical and does not require special equipment.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

BACKGROUND: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. METHODS: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. RESULTS: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). CONCLUSIONS: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study.

BACKGROUND/AIM: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. METHODS: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. RESULTS: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12-14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052-1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040-1.068, p < 0.001). CONCLUSIONS: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Evaluation of Bone Scan Index as a Prognostic Tool in Breast Cancer Patients with Bone Metastasis.

BACKGROUND: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy. OBJECTIVE: The aim of this study was to associate BSI with OS in bone metastatic BC patients. METHODS: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account. RESULTS: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924). CONCLUSION: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population.

Effect of digoxin on all-cause and cardiovascular mortality in patients with atrial fibrillation with and without heart failure: an umbrella review of systematic reviews and 12 meta-analyses.

PURPOSE: To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial fibrillation (AF) with or without heart failure (HF). METHODS: We systematically searched MEDLINE, Embase, and Web of Science databases from inception to 19 October 2021. We included systematic reviews and meta-analyses of observational studies investigating digoxin effects on mortality of adult patients with AF and/or HF. The primary outcome was all-cause mortality; secondary outcome was cardiovascular mortality. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool and the quality of systematic reviews/meta-analyses by the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) tool. RESULTS: Eleven studies accounting for 12 meta-analyses were included with a total of 4,586,515 patients. AMSTAR2 analysis showed a high quality in 1, moderate in 5, low in 2, and critically low in 3 studies. Digoxin was associated with an increased all-cause mortality (hazard ratio [HR] 1.19, 95% confidence interval [95%CI] 1.14-1.25) with moderate certainty of evidence and with an increased cardiovascular mortality (HR 1.19, 95%CI 1.06-1.33) with moderate certainty of evidence. Subgroup analysis showed that digoxin was associated with all-cause mortality both in patients with AF alone (HR 1.23, 95%CI 1.19-1.28) and in those with AF and HF (HR 1.14, 95%CI 1.12-1.16). CONCLUSION: Data from this umbrella review suggests that digoxin use is associated with a moderate increased risk of all-cause and cardiovascular mortality in AF patients regardless of the presence of HF. TRIAL REGISTRATION: This review was registered in PROSPERO (CRD42022325321).

Qualitative and Semiquantitative Parameters of 18F-FDG-PET/CT as Predictors of Malignancy in Patients with Solitary Pulmonary Nodule.

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

Association between Cognitive Impairment and Malnutrition in Hemodialysis Patients: Two Sides of the Same Coin.

Cognitive impairment and malnutrition are prevalent in patients on hemodialysis (HD), and they negatively affect the outcomes of HD patients. Evidence suggests that cognitive impairment and malnutrition may be associated, but clinical studies to assess this association in HD patients are lacking. The aim of this study was to evaluate the association between cognitive impairment evaluated by the Montreal Cognitive Assessment (MoCA) score and nutritional status evaluated by the malnutrition inflammation score (MIS) in HD patients. We enrolled 84 HD patients (44 males and 40 females; age: 75.8 years (63.5-82.7); HD vintage: 46.0 months (22.1-66.9)). The MISs identified 34 patients (40%) as malnourished; the MoCa scores identified 67 patients (80%) with mild cognitive impairment (MCI). Malnourished patients had a higher prevalence of MCI compared to well-nourished patients (85% vs. 70%; p = 0.014). MoCa score and MIS were negatively correlated (rho:-0.317; p < 0.01). Our data showed a high prevalence of MCI and malnutrition in HD patients. Low MoCA scores characterized patients with high MISs, and malnutrition was a risk factor for MCI. In conclusion, it is plausible that MCI and malnutrition are linked by common sociodemographic, clinical, and biochemical risk factors rather than by a pathophysiological mechanism.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

Continuous time-interaction processes for population size estimation, with an application to drug dealing in Italy.

We introduce a time-interaction point process where the occurrence of an event can increase (self-excitement) or reduce (self-correction) the probability of future events. Self-excitement and self-correction are allowed to be triggered by the same event, at different timescales; other effects such as those of covariates, unobserved heterogeneity, and temporal dependence are also allowed in the model. We focus on capture-recapture data, as our work is motivated by an original example about the estimation of the total number of drug dealers in Italy. To do so, we derive a conditional likelihood formulation where only subjects with at least one capture are involved in the inference process. The result is a novel and flexible continuous-time population size estimator. A simulation study and the analysis of our motivating example illustrate the validity of our approach in several scenarios.

Perioperative risk factors associated with increased incidence of postoperative delirium: systematic review, meta-analysis, and Grading of Recommendations Assessment, Development, and Evaluation system report of clinical literature.

BACKGROUND: Systematic reviews to date have neglected to exclusively include studies using a validated diagnostic scale for postoperative delirium and monitoring patients for more than 24 h. Evidence on current risk factors is evolving with significantly heterogeneous study designs, inconsistent reporting of results, and a lack of adjustment for bias. METHODS: This systematic review and meta-analysis aimed to identify risk factors for postoperative delirium in an adult patient population. Study designs suitable for this review included full-text articles, RCTs, observational studies, cohort studies, and case-control studies. Extracted variables from the 169 (7.4%) selected studies were included in qualitative synthesis, quantitative synthesis, and a postoperative delirium checklist. The 16 variables included in the checklist were selected based on consistency, direction of effect, number of studies, and clinical utility as a reference for future studies. RESULTS: A total of 576 variables were extracted, but only six were eligible for meta-analysis. Age (mean difference [MD]=4.94; 95% confidence interval [CI], 2.93-6.94; P<0.001), American Society of Anesthesiologists physical status >2 (odds ratio [OR]=2.27; 95% CI, 1.47-3.52; P<0.001), Charlson Comorbidity Index ≥2 (OR=1.9; 95% CI, 1.11-3.25; P=0.0202), and Mini-Mental State Examination (MD=-1.94; 95% CI, -3.6 to -0.27; P=0.0224) were statistically significant. CONCLUSIONS: Risk factors can assist in clinical decision-making and identification of high-risk patients. Literature analysis identified inconsistent methodology, leading to challenges in interpretation. A standardised format and evidence-based approach should guide future studies.

Bleeding and thrombotic events in atrial fibrillation patients with cancer: a systematic review and meta-analysis.

Atrial fibrillation (AF) and cancer are frequently coexisting in elderly patients. Pooled metanalytic data on the impact of cancer on clinical outcomes in AF patients are lacking. We performed a systematic review and meta-regression analysis of clinical studies retrieved from Medline (PubMed) and Cochrane (CENTRAL) databases according to PRISMA guidelines. Bleeding endpoints included any, major, gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Cardiovascular (CV) endpoints included myocardial infarction (MI), ischemic stroke/systemic embolism (IS/SE), CV and all-cause death. PROSPERO registration number: CRD42022315678. We included 15 studies with 2,868,010 AF patients, of whom 479,571 (16.7%) had cancer. The pooled hazard ratio (HR) for cancer was 1.43 (95% confidence interval [95%CI] 1.42-1.44) for any bleeding, 1.27 (95% CI 1.26-1.29) for major bleeding, 1.17 (95% CI 1.14-1.19) for GI bleeding, and 1.07 (95% CI 1.04-1.11) for ICH. The risk of major bleeding increased with the proportion of breast cancer. Cancer increased the risk of all-cause death (HR 2.00, 95% CI 1.99-2.02) whereas no association with MI and CV death was found. Patients with AF and cancer were less likely to suffer from IS/SE (HR 0.91, 95% CI 0.89-0.94). Cancer complicates the clinical history of AF patients, mainly increasing the risk of bleeding. Further analyses according to the type and stage of cancer are necessary to better stratify bleeding risk in these patients.

A likelihood ratio test for completed sampling in population size estimation studies.

We propose a likelihood ratio test to assess that sampling has been completed in closed population size estimation studies. More precisely, we assess if the expected number of subjects that have never been sampled is below a user-specified threshold. The likelihood ratio test statistic has a nonstandard distribution under the null hypothesis. Critical values can be easily approximated and tabulated, and they do not depend on model specification. We illustrate in a simulation study and three real data examples, one of which involves ascertainment bias of amyotrophic lateral sclerosis in Gulf War veterans.

Spatio-temporal modelling of COVID-19 incident cases using Richards' curve: An application to the Italian regions.

We introduce an extended generalised logistic growth model for discrete outcomes, in which spatial and temporal dependence are dealt with the specification of a network structure within an Auto-Regressive approach. A major challenge concerns the specification of the network structure, crucial to consistently estimate the canonical parameters of the generalised logistic curve, e.g. peak time and height. We compared a network based on geographic proximity and one built on historical data of transport exchanges between regions. Parameters are estimated under the Bayesian framework, using Stan probabilistic programming language. The proposed approach is motivated by the analysis of both the first and the second wave of COVID-19 in Italy, i.e. from February 2020 to July 2020 and from July 2020 to December 2020, respectively. We analyse data at the regional level and, interestingly enough, prove that substantial spatial and temporal dependence occurred in both waves, although strong restrictive measures were implemented during the first wave. Accurate predictions are obtained, improving those of the model where independence across regions is assumed.

Epidemiology of subclinical atrial fibrillation in patients with cardiac implantable electronic devices: A systematic review and meta-regression.

BACKGROUND: In recent years, attention to subclinical atrial fibrillation (SCAF), defined as the presence of atrial high-rate episodes (AHREs), in patients with cardiac implantable electronic devices (CIEDs), has gained much interest as a determinant of clinical AF and stroke risk. We aim to perform a systematic review and meta-regression of the available scientific evidence regarding the epidemiology of SCAF in patients receiving CIEDs. METHODS: PubMed and EMBASE were searched for all studies documenting the prevalence of AHREs in patients (n=100 or more, <50% with history of AF) with CIEDs from inception to 20th August 2021, screened by two independent blind reviewers. This study was registered in PROSPERO: CRD42019106994. RESULTS: Among the 2614 results initially retrieved, 54 studies were included, with a total of 72,784 patients. Meta-analysis of included studies showed a pooled prevalence of SCAF of 28.1% (95%CI: 24.3-32.1%), with high heterogeneity between studies (I2=98%). A multivariable meta-regression was able to explain significant proportion of heterogeneity (R2=61.9%, p<0.001), with age and follow-up time non-linearly, directly and independently associated with occurrence of SCAF. Older age, higher CHA2DS2-VASc score, history of AF, hypertension, CHF, and stroke/TIA were all associated with SCAF occurrence. CONCLUSIONS: In this systematic review and meta-regression analysis, SCAF was frequent among CIED recipients and was non-linearly associated with age and follow-up time. Older age, higher thromboembolic risk, and several cardiovascular comorbidities were associated with presence of SCAF.

Clinical Phenotypes of Atrial Fibrillation and Mortality Risk-A Cluster Analysis from the Nationwide Italian START Registry.

Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The risk of all-cause mortality in each cluster was analyzed. We identified four clusters. Cluster 1 was composed of the youngest patients, with low comorbidities; Cluster 2 of patients with low cardiovascular risk factors and high prevalence of cancer; Cluster 3 of men with diabetes and coronary disease and peripheral artery disease; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular events. During 9857 person-years of observation, 386 deaths (3.92%/year) occurred. Mortality rates increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio (aHR) 3.306, 95% confidence interval (CI) 1.204−9.077, p = 0.020), 4.41%/year (cluster 3, aHR 6.702, 95%CI 2.433−18.461, p < 0.001), and 8.71%/year (cluster 4, aHR 8.927, 95%CI 3.238−24.605, p < 0.001). We identified four clusters of AF patients with progressive mortality risk. The use of clinical phenotypes may help identify patients at a higher risk of mortality.