We aimed to develop and validate machine learning (ML) -based algorithms to predict COVID-19 diagnosis as well as to identify new biomarkers associated with the disease.

Initially, 96 blood samples of patients diagnosed with COVID-19 (Thaizhou Hospital, China) were analyzed through liquid chromatography coupled to mass spectrometry. Samples of patients presenting other pneumonias or severe acute respiratory syndrome, but with negative RT-PCR for SARS-CoV-2, were used as positive controls. Samples from healthy volunteers were used as negative controls. The final database included around 1000 metabolites. Exploratory analyses for the development of ML-based models using principal component analysis (PCA) were performed. Leverage plot versus studentized residuals method was used to detect outliers. Three supervised ML-based models were developed: discriminant analysis by partial least squares (PLS-DA), artificial neural networks discriminant analysis (ANNDA) and k-nearest neighbors (KNN). Samples for the training (70%) and testing sets (30%) were randomly selected using the Kenrad Stone algorithm. Models’ performance was evaluated considering accuracy, sensitivity and specificity. Analyses were conducted in SOLO (Eigenvector-Research).

The PCA model was able to distinguish the three classes of patients’ samples (positive for COVID-19, negative controls, positive controls) with an overall accumulated variance of 94.27 percent. The PLS-DA model presented the best performance (accuracy, sensitivity, and specificity of 93%, 98% and 88%, respectively). Increased levels of the biomarkers uridine (linked to glucose homeostasis, lipid, and amino acid metabolisms), 4-hydroxyphenylacetoylcarnitine (metabolite from the tyrosine metabolism; probably associated with anorexia) and ribothymidine (resulting from oral and fecal microbiota alterations) were significantly associated with COVID-19.

Three different and updated ML-based algorithms were developed to predict COVID-19 diagnosis; PLS-DA led to the most accurate results. High levels of some metabolites were found as potentially predictors of the disease. These biomarkers should be further evaluated as potential therapeutic targets in well-designed clinical trials. These ML-based models can help the early diagnosis of COVID-19 and guide the development of tailored interventions.

Patients with hematological malignancies are likely to develop hypogammaglobulinemia. Immunoglobulin (Ig) is commonly given to prevent infections, but its overall costs and cost-effectiveness are unknown.

A systematic review was conducted following the PRISMA guidelines to assess the evidence on the costs and cost-effectiveness of Ig, administered intravenously (IVIg) or subcutaneously (SCIg), in adults with hematological malignancies.

Six studies met the inclusion criteria, and only two economic evaluations were identified; one cost-utility analysis (CUA) of IVIg versus no Ig, and another comparing IVIg with SCIg. The quality of the evidence was low. Compared to no treatment, Ig reduced hospitalization rates. One study reported no significant change in hospitalizations following a program to reduce IVIg use, and an observational study comparing IVIg with SCIg suggested that there were more hospitalizations with SCIg but lower overall costs per patient. The CUA comparing IVIg versus no Ig suggested that IVIg treatment was not cost-effective, and the other CUA comparing IVIg to SCIg found that home-based SCIg was more cost-effective than IVIg, but both studies had serious limitations.

Our review highlighted key gaps in the literature: the cost-effectiveness of Ig in patients with hematological malignancies is very uncertain. Despite increasing Ig use worldwide, there are limited data regarding the total direct and indirect costs of treatment, and the optimal use of Ig and downstream implications for healthcare resource use and costs remain unclear. Given the paucity of evidence on the costs and cost-effectiveness of Ig treatment in this population, further health economic research is warranted.

For the assessment of videorasterstereography compared with radiography for monitoring idiopathic scoliosis, new tools given by the INTEGRATE-HTA methodology were included within the frame set by the authority. In contrast to the usual linear approach by covering the single domains' safety and efficacy, costs, and ethical, legal, socio-cultural and organizational issues (ELSOI) separately, the methodology is based on the assumption of interactions of different aspects of the domains. From the very beginning, these interactions are captured systematically using various tools and are repeatedly discussed with stakeholders.

Relevant databases were systematically searched for studies and question catalogues were processed in order to be able to search for specific aspects in orienting bibliographic research. An initial logic model was developed and successively expanded. A synoptic table showing multiple mapping of aspects to domains, a complexity checklist, and a semantic complex highlighting the socio-cultural impact of the disease were newly developed.

Four diagnostic studies with high risk of bias were included. For the clinical outcome, Cobb angle standard deviations up to 8.2 degrees and average measurement differences up to 8.8 degrees were determined. These differences in measurement accuracy correspond to those observed for purely radiographic measurements in other studies. In addition to freedom from radiation as the greatest advantage, there were clear arguments in favor of videorasterstereography when considering ELSOI, for example less harm.

Using INTEGRATE-HTA contributes to identify interactions between domains and to significantly expand the perspective on a technology. It improves patient-centered understanding and facilitates discussions.

The experience of implementing a hospital-based health technology assessment (HB-HTA) system in Kazakhstan is currently represented by only one organization, an independent HB-HTA unit established in 2015 in the Medical Center Hospital of the President's Affairs Administration (the Hospital). Despite the demonstrated positive experience of the Hospital, the widespread implementation of the HB-HTA system in Kazakhstan has experienced some barriers that must be considered before further development can occur.

To determine the barriers to developing and implementing HB-HTA in Kazakhstani hospitals, data from the Hospital's experience were obtained through a survey of Kazakhstan hospitals, conducted on behalf of the Ministry of Health Care. An official response was received from 29 hospitals. During the survey and discussions with hospital staff using the “brainstorming” method, several barriers to the development of HB-HTA in Kazakhstan were identified.

Barriers at the system level included the lack of monitoring of the HB-HTA system at the national and regional levels and a lack of methodological support. Organizational barriers included a critically small number of HTA experts and the need for additional logistical support and funding from hospitals. The subjective factors we attributed to the rejection of the HB-HTA system by hospital management were the underestimation of lost profits and that HTA is a tool for promoting a transparent and open system for making managerial decisions.

Despite some barriers, the development of HB-HTA in Kazakhstan is a promising area. The heads of key hospitals in Kazakhstan demonstrated a readiness and understanding of the need to use the principles of health technology assessment and clinical and economic analysis to promote the active transfer and implementation of innovative medical technologies.

Uveitis is inflammation inside the eye whose underlying cause may be infectious or non-infectious. The objective of our study was to assess the cost-effectiveness of the dexamethasone implant and adalimumab compared with current practice (immunosuppressants and systemic corticosteroids) in patients with non-infectious intermediate, posterior or pan-uveitis.

A Markov model was built to estimate costs and benefits of the interventions. Systematic reviews were performed to identify the relevant evidence. Quality of life data collected in three key randomized-controlled trials (1-3) was used to estimate the interventions effectiveness compared with the trials comparator arms, which consisted of placebo plus limited current practice (LCP). An indirect treatment comparison between adalimumab and dexamethasone was considered inappropriate due to lack of necessary evidence. For adalimumab, patients with active and inactive uveitis were considered separately. Due to the short duration of the trials, the rate of blindness, an important complication of uveitis, was highly uncertain. Substantial exploratory analyses were therefore undertaken. The analysis was performed from the perspective of the National Health Service (NHS) and Personal Social Services (PSS). Costs were calculated based on standard United Kingdom sources.

The estimated incremental cost-effectiveness (ICER) of dexamethasone compared with LCP was GBP19,509 per quality-adjusted life year (QALY) gained. The estimated ICER of adalimumab compared with LCP was GBP94,523 and GBP317,547 per QALY in patients with active and inactive uveitis respectively. The factors with the largest impact upon the ICERs were the rate of blindness and the proportion of cases of blindness avoided by interventions.

Dexamethasone and adalimumab resulted in health gains, but at significant extra costs, especially adalimumab which is unlikely to be considered a cost-effective use of NHS resources. The results of the analysis are highly uncertain due to the limited availability of evidence on: the comparative effectiveness of dexamethasone, adalimumab and current practice; the effectiveness of treatments in avoiding blindness; and, the effectiveness of interventions in different subgroups.

Sudden cardiac arrest (SCA) is the most common cause of death in patients with coronary artery disease. Mostly, ventricular tachycardia (VT) and ventricular fibrillation (VF) are the underlying aetiology of SCA, which is claimed to be successfully treated by a novel therapy, a wearable cardioverter defibrillator (WCD, LifeVest®).

The assessment, performed within the European Network for HTA (EUnetHTA), aimed to provide valid data on clinical effectiveness and safety of the WCD. Furthermore, the project intended to elicit patients views on aspects regarding their cardiac disease and the WCD therapy as well as to identify neglected outcomes.

A synthesis of evidence on the basis of a systematic literature search in Medline via Ovid, Embase, the Cochrane Library, and the Centre for Reviews and Dissemination (CRD) databases was performed. The search was complemented by citation tracking and handsearch.

A face-to-face semi-structured focus group interview was performed with five cardiac disease patients in the scoping phase.

Since no prospective controlled trials were found, no assessment of effectiveness could be performed. With regard to safety, five prospective studies were included, but the quality of the body of evidence was very low. Adverse events (AEs) reported were skin rash/itching (6 percent), false alarms (14 percent), palpitations/lightheadedness/fainting (9 percent) and discontinuation due to comfort/lifestyle issues (16-22 percent). Serious adverse events (SAEs) were inappropriate shocks (0-2 percent) and unsuccessful shocks (0-.7 percent). Frequency of SAEs leading to death was 0-.3 percent.

Patients of the focus group reported that experiencing a sense of security was crucial to them. The WCD therapy was not considered an option for weeks or months, due to expected restrictions in living a ‘normal’ and secure life.

No statement can be made about the device effectiveness – further research is needed. More data and more adequate reporting of AEs and SAEs are needed in order to establish the device safety. In particular, more data is needed for risk stratification of high risk patients in order to further narrow down the wide range of indications for the WCD use.

Inhibitors of Vascular Endothelial Growth Factor (VEGF) have made possible the treatment of the Retinal Vascular Diseases (RVD) for which there were limited therapeutic resources. The aim of this work was to estimate annual direct costs of major macular edema diseases in Italy in particular Choroidal Neovascularization (CNV), Diabetic Macular Edema (DME) and Retinal Vein Occlusions (RVO) from the hospital perspectives.

This descriptive study was aimed at quantifying direct costs incurred by five hospitals in Italy. Administrative and clinical databases of Policlinico Tor Vergata in Rome were analyzed for a 6-year period. In this context, it was possible to stratify patients depending on the disease and number of eyes treated. From these results, a survey with structured questionnaires was developed involving four other hospitals in Italy. Thanks to that, direct costs (drugs and specialist) were estimated from the hospitals perspective in 2016.

Interviews included 7,356 individuals of which 1,860 were treated in both eyes. Within the considered five hospitals, 64 percent of treated patients had CNV, 21 percent DME, and 15 percent RVOs. The average annual administration rate of anti-VEGF treatment resulted in 4.03 (Standard Deviation, SD 3.46) per patient eye: 4.69 (SD 1.75) for cases enrolled for less than one year (naïve) and 3.38 (SD 0.82) per patients treated for more than one year (experienced). Naïve patients had a mean per capita annual cost of EUR2,368 per eye (EUR2,536 for CNV; EUR2,280 RVO; EUR1,986 DME) of which EUR2,952 was related to the administration of on-label drugs mainly Eylea, Lucentis, Macugen, Ozurdex and EUR49 due to off-labels such as Avastin. Experienced patients average annual cost per eye was EUR1,689: EUR2.179 for the on-label drugs, EUR34 due to off-labels (EUR1,839 for CNV; EUR1,327 RVO; EUR1,399 DME). The average rate of the specialist annual visit was four times; the most frequent types were Optical Coherence Tomography (OCT), Angiography, and Fundus Photography (FP).

This is a first attempt to study direct costs incurred from the hospital perspective associated with RVD with overexpression of VEGF in Italy. This might represent a first step for further analysis assessing the burden of RVD diseases from the Italian National Health System perspective globally.

Following a first field evaluation conducted in 2013, we found that hemolysis can be induced by infusion pumps during blood transfusion. Actually, limited data is available on the risk of hemolysis associated with the most used infusion pumps in Quebec hospitals: InfusomatSpace (peristaltic), Plum A+TM (piston) and ColleagueCXE (shuttle).

Staff from the blood bank and the Health Technology Assessment (HTA) unit in our hospital collaborated in 2016 to assess the hemolysis and potassium level (that is, a blood test sensitive to hemolysis) induced by the use of the three infusion pumps mentioned above. Measurements were taken for each pump at five flow rates, from 30 to 450 ml/hour, and were compared with measurements taken before using the pumps. Tests were conducted with 135 red blood cell (RBC) units. RBC units were aged from 10 to 28 days.

The shuttle- and piston-type pumps resulted in low hemolysis levels. The peristaltic-type pump produced significantly more hemolysis. However, the absolute value of hemolysis remained within the range recommended by the regulatory agencies in North America and Europe. Potassium levels did not increase with the use of the pumps.

The collaboration between the blood bank and the HTA unit led to the conclusion that modern infusion pumps widely used in Quebec hospitals produce non-threatening levels of hemolysis during blood transfusion. This finding is important to ensure safe practices.