World addiction medicine reports: formation of the International Society of Addiction Medicine Global Expert Network (ISAM-GEN) and its global surveys.

Addiction medicine is a dynamic field that encompasses clinical practice and research in the context of societal, economic, and cultural factors at the local, national, regional, and global levels. This field has evolved profoundly during the past decades in terms of scopes and activities with the contribution of addiction medicine scientists and professionals globally. The dynamic nature of drug addiction at the global level has resulted in a crucial need for developing an international collaborative network of addiction societies, treatment programs and experts to monitor emerging national, regional, and global concerns. This protocol paper presents methodological details of running longitudinal surveys at national, regional, and global levels through the Global Expert Network of the International Society of Addiction Medicine (ISAM-GEN). The initial formation of the network with a recruitment phase and a round of snowball sampling provided 354 experts from 78 countries across the globe. In addition, 43 national/regional addiction societies/associations are also included in the database. The surveys will be developed by global experts in addiction medicine on treatment services, service coverage, co-occurring disorders, treatment standards and barriers, emerging addictions and/or dynamic changes in treatment needs worldwide. Survey participants in categories of (1) addiction societies/associations, (2) addiction treatment programs, (3) addiction experts/clinicians and (4) related stakeholders will respond to these global longitudinal surveys. The results will be analyzed and cross-examined with available data and peer-reviewed for publication.

Diet and Physical Activity in Adult Dominant Polycystic Kidney Disease: A Review of the Literature.

Autosomal polycystic kidney disease is the most common inherited kidney disease determining 5% of all end-stage kidney disease. The only therapy approved for this condition is Tolvaptan, which, with its aquaretic effect, has a strong effect on patients' daily life. Recently, the literature has been enriched with new works that analyze possible non-pharmacological therapeutic strategies to slow cysts' enlargement and chronic kidney disease progression. Among them, dietary schemes reducing carbohydrate intake and inducing ketoses have been demonstrated to have efficacy in several pre-clinical and clinical studies. A ketogenic diet, calorie restriction, intermittent fasting, and time-restricted feeding can reduce aerobic glycolysis and inhibit the mTOR pathway, producing a reduction in cyst cell proliferation, a reduction in kidney volume, and helping to preserve kidney function. ADPKD's burden of disease has an impact on patients' quality of life, and the possibility to play sports or carry out physical exercise can help people in everyday life. The multisystemic character of the disease, especially cardiovascular involvement, needs to be carefully evaluated to establish the quality and quantity of physical activity that patients can safely carry out.

Long-Term Effects of Sacubitril-Valsartan on Cardiac Remodeling: A Parallel Echocardiographic Study of Left and Right Heart Adaptive Response.

Sacubitril/Valsartan (S/V) carries potential anti-remodeling properties, however long-term effects and biventricular adaptive response are poorly described. 76 HFrEF patients who underwent progressive uptitration of S/V, completed the annual scheduled follow-up. After a median follow-up of 11 (8-13) months, left ventricular (LV) reverse remodeling (RR) is defined as (1) absolute increase in LV ejection fraction (EF) ≥ 10% or LVEF ≥ 50% at follow-up and (2) decrease in indexed LV end-diastolic diameter (LVEDDi) of at least 10% or indexed LVEDDi ≤ 33 mm/m2, occurred in 27.6%. Non-ischemic etiology, shorter duration of HF, and absence of a history of AF were independently associated with LVRR (p < 0.05). TAPSE and TAPSE/PASP, a non-invasive index of right ventricular (RV) coupling to the pulmonary circulation, significantly improved at follow-up (0.45 vs. 0.56, p = 0.02). 41% of patients with baseline RV dysfunction obtained favorable RV remodeling despite only a moderate correlation between RV and LV function was observed (r = 0.478, p = 0.002). Our data point to a potential long-term reverse global remodeling effect by S/V, especially in patients who start S/V at an early stage of the disease, and focus our attention on a possible direct effect of the drug in synergistic hemodynamics between RV and pulmonary circulation.

Using oxygen dose histograms to quantify voxelised ultra-high dose rate (FLASH) effects in multiple radiation modalities.

Purpose.To introduce a methodology to predict tissue sparing effects in pulsed ultra-high dose rate radiation exposures which could be included in a dose-effect prediction system or treatment planning system and to illustrate it by using three published experiments.Methods and materials.The proposed system formalises the variability of oxygen levels as an oxygen dose histogram (ODH), which provides an instantaneous oxygen level at a delivered dose. The histogram concept alleviates the need for a mechanistic approach. At each given oxygen level the oxygen fixation concept is used to calculate the change in DNA-damage induction compared to the fully hypoxic case. Using the ODH concept it is possible to estimate the effect even in the case of multiple pulses, partial oxygen depletion, and spatial oxygen depletion. The system is illustrated by applying it to the seminal results by Town (Nat. 1967) on cell cultures and the pre-clinical experiment on cognitive effects by Montay-Gruelet al(2017Radiother. Oncol.124365-9).Results.The proposed system predicts that a possible FLASH-effect depends on the initial oxygenation level in tissue, the total dose delivered, pulse length and pulse repetition rate. The magnitude of the FLASH-effect is the result of a redundant system, in that it will have the same specific value for a different combination of these dependencies. The cell culture data are well represented, while a correlation between the pre-clinical experiments and the calculated values is highly significant (p < 0.01).Conclusions. A system based only on oxygen related effects is able to quantify most of the effects currently observed in FLASH-radiation.

Impact of Right Ventricular-Pulmonary Circulation Coupling on Mortality in SARS-CoV-2 Infection.

Background The COVID-19-related pulmonary effects may negatively impact pulmonary hemodynamics and right ventricular function. We examined the prognostic relevance of right ventricular function and right ventricular-to-pulmonary circulation coupling assessed by bedside echocardiography in patients hospitalized with COVID-19 pneumonia and a large spectrum of disease independently of indices of pneumonia severity and left ventricular function. Methods and Results Consecutive COVID-19 subjects who underwent full cardiac echocardiographic evaluation along with gas analyses and computed tomography scans were included in the study. Measurements were performed offline, and quantitative analyses were obtained by an operator blinded to the clinical data. We analyzed 133 patients (mean age 69±12 years, 57% men). During a mean hospital stay of 26±16 days, 35 patients (26%) died. The mean tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio was 0.48±0.18 mm/Hg in nonsurvivors and 0.72±0.32 mm/Hg in survivors (P=0.002). For each 0.1 mm/mm Hg increase in TAPSE/PASP, there was a 27% lower risk of in-hospital death (hazard ratio [HR], 0.73 [95% CI, 0.59-0.89]; P=0.003). At multivariable analysis, TAPSE/PASP ratio remained a predictor of in-hospital death after adjustments for age, oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen, left ventricular ejection fraction, and computed tomography lung score. Receiver operating characteristic analysis was used to identify the cutoff value of the TAPSE/PASP ratio, which best specified high-risk from lower-risk patients. The best cutoff for predicting in-hospital mortality was TAPSE/PASP <0.57 mm/mm Hg (75% sensitivity and 70% specificity) and was associated with a >4-fold increased risk of in-hospital death (HR, 4.8 [95% CI, 1.7-13.1]; P=0.007). Conclusions In patients hospitalized with COVID-19 pneumonia, the assessment of right ventricular to pulmonary circulation coupling appears central to disease evolution and prediction of events. TAPSE/PASP ratio plays a mainstay role as prognostic determinant beyond markers of lung injury.

Incorporating oxygenation levels in analytical DNA-damage models-quantifying the oxygen fixation mechanism.

Purpose.To develop a framework to include oxygenation effects in radiation therapy treatment planning which is valid for all modalities, energy spectra and oxygen levels. The framework is based on predicting the difference in DNA-damage resulting from ionising radiation at variable oxygenation levels.Methods.Oxygen fixation is treated as a statistical process in a simplified model of complex and simple damage. We show that a linear transformation of the microscopic oxygen fixation process allows to extend this to all energies and modalities, resulting in a relatively simple rational polynomial expression. The model is expanded such that it can be applied for polyenergetic beams. The methodology is validated using Microdosimetric Monte Carlo Damage Simulation code (MCDS). This serves as a bootstrap to determine relevant parameters in the analytical expression, as MCDS is shown to be extensively verified with published empirical data. Double-strand break induction as calculated by this methodology is compared to published proton experiments. Finally, an example is worked out where the oxygen enhancement ratio (OER) is calculated at different positions in a clinically relevant spread out Bragg peak (SOBP) dose deposition in water. This dose deposition is obtained using a general Monte Carlo code (FLUKA) to determine dose deposition and locate fluence spectra.Results.For all modalities (electrons, protons), the damage categorised as complex could be parameterised to within 0.3% of the value calculated using microdosimetric Monte Carlo. The proton beam implementation showed some variation in OERs which differed slightly depending on where the assessment was made; before the SOBP, mid-SOBP or at the distal edge. Environment oxygenation was seen to be the more important variable.Conclusions.An analytic expression calculating complex damage depending on modality, energy spectrum, and oxygenation levels was shown to be effective and can be readily incorporated in treatment planning software, to take into account the impact of variable oxygenation, forming a first step to an optimised treatment based on biological factors.

Citizen Consultation on Problematic Usage of the Internet: Ethical Considerations and Empirical Insights From Six Countries.

Citizens and scientists can work together to improve the collective well-being, if citizens are inspired to help the advancement of science, and researchers motivated to listen to the voices of citizens. The benefits of such collaboration are increasingly recognized by both citizens and scientists, as reflected in the growing number of related publications and initiatives. This is especially relevant for emerging areas of research, where early involvement of citizens could help to envision, prioritize, and plan prospective studies. The Problematic Usage of the Internet (PUI) is one such area, which is fast becoming a public mental health concern. However, there remains a lack of clarity regarding the practical guidelines and ethical requirements for citizen involvement at the earliest stages of PUI. In our paper, we propose a conceptual framework and a template for initial involvement of citizens in PUI. They are derived from our community case studies, conducted in six European countries (Georgia, Greece, Malta, North Macedonia, Portugal, and Spain) and consisting of consultation with diverse groups of interested citizens (students, parents, teachers, and health professionals). Informed by our consultation exercises, we also highlight four ethical aspects for citizen involvement in the research on PUI or novel disciplines in general. They follow simple guiding principles to ensure that scientists will: enable a long-term commitment and inclusive opportunities for citizens, challenge established power hierarchies, and support collaboration, co-production and co-authorship with citizens. We believe that the proposed practical guidelines and ethical considerations, provide a valuable foundation on which to advance our understanding and generate international strategies for citizen involvement in PUI.

Prognostic utility of quantitative offline 2D-echocardiography in hospitalized patients with COVID-19 disease.

PURPOSE: To assess the prognostic utility of quantitative 2D-echocardiography, including strain, in patients with COVID-19 disease. METHODS: COVID-19-infected patients admitted to the San Paolo University Hospital of Milan that underwent a clinically indicated echocardiographic examination were included in the study. To limit contamination, all measurements were performed offline. Quantitative measurements were obtained by an operator blinded to the clinical data. RESULTS: Among the 49 patients, nonsurvivors (33%) had worse respiratory parameters, index of multiorgan failure, and worse markers of lung involvement. Right ventricular (RV) dysfunction (as assessed by conventional and 2-dimensional speckle tracking) was a common finding and a powerful independent predictor of mortality. At the ROC curve analyses, RV free wall longitudinal strain (LS) showed an AUC 0.77 ± 0.08 in predicting death, P = .008, and global RV LS (RV-GLS) showed an AUC 0.79 ± 0.04, P = .004. This association remained significant after correction for age (OR = 1.16, 95%CI 1.01-1.34, P = .029 for RV free wall LS and OR = 1.20, 95%CI 1.01-1.42, P = .033 for RV-GLS), for oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen (OR = 1.28, 95%CI 1.04-1.57, P = .021 for RV free wall-LS and OR = 1.30, 95%CI 1.04-1.62, P = .020 for RV-GLS) and for the severity of pulmonary involvement measured by a computed tomography lung score (OR = 1.27, 95%CI 1.02-1.19, P = .034 for RV free wall LS and OR = 1.30, 95%CI 1.04-1.63, P = .022 for RV-GLS). CONCLUSIONS: In patients hospitalized with COVID-19, offline quantitative 2D-echocardiographic assessment of cardiac function is feasible. Parameters of RV function are frequently abnormal and have an independent prognostic value over markers of lung involvement.

Extracorporeal myocardial shockwave therapy; a precious blast for refractory angina patients.

INTRODUCTION: Refractory Angina Pectoris (RAP) dramatically affects patients' life quality and medical costs. External Shockwave Myocardial Revascularization (ESMR) improves the cardiac blood flow thanks to its pro-angiogenetic action on ischaemic tissues. We hereby describe our experience of ESMR in RAP patients. MATERIALS AND METHODS: This is a retrospective study encompassing all patients referred to OSR for RAP treatment. Efficacy of ESMR was assessed considering the difference between pre and post therapy data in SAQ score and CCS, stress test performance, 24h ECG monitoring, NT-proBNP and echocardiographic measures. RESULTS: From a total of 97 patients with RAP, 19 patients underwent ESMR, whereas 4 were considered as control group. After the end of the treatment, ESWT group showed a significant improvement in CCS class (-1.32±0.58; p<0.001) and in each of the five variables of the SAQ score (p<0.05). Patients also improved their exercise duration (50,74±29.40 seconds; p<0,001) and double product (1340,53±1321,77; p<0,001) and reduced the number of daily ST segment depression (-1,16±1,01; p<0,01). Ejection Fraction (2,05±1,84%; p<0,01) and Cardiac Output (0,20±0,28L, p<0,01) improved too. No changes were documented in the control group. CONCLUSION: ESMR is an efficient therapy for refractory angina capable to improve both symptoms and instrumental tests.

Pregnancy outcomes in substance-misusing pregnant women: A 10-year retrospective study.

In this ten-year retrospective study we were able to show that Maltese substance-misusing mothers (SMMs) have significantly different socio-biological characteristics from mothers in the general population which seem to impact on neonatal outcomes. Significant differences from the general population were noted in the SMM's age, age at first pregnancy, marital status, educational background, number of cigarettes smoked, number of offspring and weight gained in pregnancy. SMMs booked their pregnancy in hospital later than the general population. On the other hand their infants had a lower mean birth weight and head circumference, had lower Apgar scores, were of lesser gestational age and premature. They were less breast-fed and stayed longer in hospital after their birth.