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A novel parametric regression model is proposed to fit incidence data typically collected during epidemics. The proposal is motivated by real-time monitoring and short-term forecasting of the main epidemiological indicators within the first outbreak of COVID-19 in Italy. Accurate short-term predictions, including the potential effect of exogenous or external variables are provided. This ensures to accurately predict important characteristics of the epidemic (e.g., peak time and height), allowing for a better allocation of health resources over time. Parameter estimation is carried out in a maximum likelihood framework. All computational details required to reproduce the approach and replicate the results are provided. publishedVersion

Aims Statin liver safety in non-alcoholic fatty liver disease (NAFLD) patients is not well defined. We analysed differences in liver function tests, including alanine transaminase aminotransferase (ALT), aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT) in NAFLD patients treated or not treated with statins. Methods We performed a systematic review of MEDLINE via PubMed and EMBASE databases and metanalysis of clinical studies investigating levels of ALT, AST and GGT in NAFLD according to statin treatment. Mean difference (MD) and percentage MD were calculated between the two groups. Results We included 22 studies with 2345 NAFLD patients. Overall, 16 were before-after interventional, five were cross-sectional and one was combined cross-sectional/interventional study. In all interventional studies, except one, patients had raised ALT, AST and GGT at baseline. Interventional studies showed reduced ALT values with an MD reduction of -27.2 U/L (95% CI -35.25/-19.15) and a percentage MD reduction of -35.41% (95% CI -44.78/-26.04). Also, AST values were reduced after statin treatment in interventional studies with an MD of -18.82 U/L (95% CI -25.63/-12.02) (percentage -31.78%, 95% CI -41.45/-22.11). Similarly, GGT levels were reduced after statin treatment with an MD of -19.93 U/L (95% CI -27.10/-12.77) (percentage -25.57%, 95% CI -35.18/-15.97). Cross-sectional studies showed no difference in AST and GGT values between patients treated with and without statins. Conclusion In interventional studies, ALT, AST and GGT were reduced after statin treatment with a percentage mean difference of -35.41%, -31.78% and -25.57%, respectively, while observational studies showed a null effect, suggesting liver safety of statins in NAFLD patients.

Background: Early diagnosis of Parkinson's disease (PD) is of primary importance. The delayed (3-4 h after injection) Iodine-123-Metaiodobenzylguanidine (123I-mIBG) scintigraphy has been proven to be effective in early differential diagnosis for Lewy body disease. But early imaging (15-30 min after injection) has only been marginally studied for its possible diagnostic role. In this prospective study, a threshold for the early Heart-to-Mediastinum (H/M) count ratio has been investigated, obtaining a diagnostic accuracy analogous to conventional, delayed imaging. Methods: One hundred and eight patients with suspected Parkinson's disease (PD) were acquired after 15 and 240 minutes from the injection of 150-185 MBq of 123I-mIBG. The early and late H/M (He/Me and Hl/Ml) were evaluated by drawing Region-of-Interests on the heart and the upper half of the mediastinum. Optimal threshold (Youden index) and overall predictive performance were determined by receiver operating characteristic curve, classifying tentatively patients having an Hl/Ml lower than 1.6 as suffering from PD. Results: He/Me was not significantly different from Hl/Ml (p-value=0.835). The Area-under-curve was 0.935 (95%CI: 0.845-1.000). The He/Me optimal threshold was 1.66, with sensitivity, specificity, and diagnostic accuracy of 95.5%, 85.7 and 90.7% respectively. Conclusions: The He/Me Ratio is almost as accurate as the widely used delayed 123I-mIBG imaging, reducing the burden of delayed imaging but preserving the diagnostic accuracy of the method. Moreover the differential diagnosis in Parkinson's disease can be made in just 25 minutes against the 4 hours currently needed, lowering costs of the healthcare system and improving patients compliance.

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine (123I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of 123I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words “MIBG”, “metaiodobenzylguanidine”, “heart”, “spect”, and “tomographic”. The included studies had to correlate 123I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced 123I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for 123I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional 123I-mIBG planar myocardial imaging.

Background Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022. Methods We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported from a standardised source over the next one to four weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance. Results Over 52 weeks we collected and combined up to 28 forecast models for 32 countries. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 84% of participating models’ forecasts of incident cases (with a total N=862), and 92% of participating models’ forecasts of deaths (N=746). Across a one to four week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over four weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models. Conclusions Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than two weeks. Code and data availability All data and code are publicly available on Github: covid19-forecast-hub-europe/euro-hub-ensemble.

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, 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 (I 2=98%). A multivariable meta-regression was able to explain significant proportion of heterogeneity (R 2=61.9%, pCONCLUSIONS: 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.

Radium-223 has demonstrated efficacy in improving overall survival (OS) and in delaying symptomatic skeletal-related events (SREs). Bone Health Agents (BHA), i.e. RANK ligand inhibitor (Denosumab) and bisphosphonate such as zoledronic acid, are indicated to prevent SREs without a clear survival benefit. SREs on patient health have a high impact and it is, therefore, important to consider the role of new therapies with BHA to better understand the involvement of combination therapy. The primary aim of this multicentric study is to assess OS in mCRPC patients treated with Radium-223 in combination with BHA.430 consecutive patients treated with Radium-223 alone or in combination with BHA, affected by mCRPC, from January 2015 to July 2019 in six Italian Nuclear Medicine Units, were included. Furthermore, data were collected at baseline, after every Radium-223 administration, and during follow-up, at 3 and 6 months and 1 year after the 6th cycle. Clinical data have been evaluated before starting treatment with Radium-223 and at the end of treatment and/or at progression. Patients who received target bone therapy with BHA before Radium-223 treatment together with patients who did not receive this therapy at all (NO BHA GROUP), were compared to patients treated with concomitant Radium-223 and BHA (BHA GROUP).In univariate models (At univariate analysis, our data showed that NO BHA GROUP and BHA GROUP differ in OS by 7 months (95%CI: (1-16.4)

Socotra Island, in the western Indian Ocean, harbors high biodiversity and endemism and makes up the largest part of the Socotra archipelago UNESCO World Heritage site. Its climatic, pedological, and geomorphological characteristics, together with the long geological isolation and inaccessibility, led to the flourishing of unique tree diversity, with great cultural and ecological value. Lately, trees on Socotra are facing new threats linked to the abandonment of traditional management practices, climate change impacts, and growing human pressure. This study assesses the relative influence of environmental factors and human activity as drivers of tree cover and density, which can be used to support land management policies for the conservation of this key local resource. Tree cover and density were assessed on a total of 3600 plots of 0.5 ha each, laid on a regular grid covering the entire area of the island through Collect Earth, a free open source software tool that allows an augmented visual interpretation of high-resolution satellite images. A total of 770,000 trees, with an average of 2.14 trees/ha, were estimated on the island. The collected data was validated by ground surveys in 26 plots. The relative influence of selected predictors (seven environmental, two anthropic) on tree cover and density was analyzed through logistic and survival regression. Tree cover and density were found to be impacted positively by steeper slopes, higher rainfall, and marked precipitation seasonality and negatively by relatively warmer temperatures and a higher sand content in the soil. Distance of each plot from the nearest road and settlement was calculated and neither of these anthropic predictors emerged as significant, indicating that the limited number of trees present are not currently as affected by anthropic pressure, but, instead, their presence is mostly limited by the harsh climatic and pedological factors. However, as human population and development increase, periods of drought rise, and extreme and random climatic events intensify, these additional stresses on the environment could negatively impact the availability of natural resources in the terrestrial environment. Lastly, potential recommendations to the existing conservation policies and Socotra Conservation Zoning Plan are discussed based on the results.

Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients’ parameters. The whole cohort was divided into two groups based on the age of the patients (