Distress and Wellbeing among General Practitioners in 33 Countries during COVID-19: Results from the Cross-Sectional PRICOV-19 Study to Inform Health System Interventions.

Emerging literature is highlighting the huge toll of the COVID-19 pandemic on frontline health workers. However, prior to the crisis, the wellbeing of this group was already of concern. The aim of this paper is to describe the frequency of distress and wellbeing, measured by the expanded 9-item Mayo Clinic Wellbeing Index (eWBI), among general practitioners/family physicians during the COVID-19 pandemic and to identify levers to mitigate the risk of distress. Data were collected by means of an online self-reported questionnaire among GP practices. Statistical analysis was performed using SPSS software using Version 7 of the database, which consisted of the cleaned data of 33 countries available as of 3 November 2021. Data from 3711 respondents were included. eWBI scores ranged from -2 to 9, with a median of 3. Using a cutoff of ≥2, 64.5% of respondents were considered at risk of distress. GPs with less experience, in smaller practices, and with more vulnerable patient populations were at a higher risk of distress. Significant differences in wellbeing scores were noted between countries. Collaboration from other practices and perception of having adequate governmental support were significant protective factors for distress. It is necessary to address practice- and system-level organizational factors in order to enhance wellbeing and support primary care physicians.

Immunogenicity and Reactogenicity of the Booster Dose of COVID-19 Vaccines and Related Factors: A Panel Study from the General Population in Serbia.

The Republic of Serbia applied the booster dose of the following COVID-19 vaccines: BNT162b2 mRNA (Pfizer-BioNTech), Sinopharm BBIBP-CorV (Vero Cell®), Gam-COVID-Vac (Sputnik V) and ChAdOk1 nCoV-19 (AstraZeneca). We aimed to examine the immunogenicity and reactogenicity of the booster dose and identify factors related to immune response and adverse events. Panel study, conducted during August and September 2021, included 300 persons receiving the booster dose at the Institute of Public Health of Serbia. Blood samples were taken on the day of receiving the booster dose, and after 7 and 28 days. When applying homologous regimen, the average increase in anti-spike immunoglobulin G was 8782.2 (after 7 days), 1213.9 after 28 days, while 9179.5 (after 7 days) and 16,728.1 after 28 days of heterologous regimen. Sinopharm BBIBP-CorV (p < 0.001) and Sputnik V (p < 0.001), age 65 and over (p = 0.001) and currently smoking (p < 0.001) were independently associated with lower levels of anti-spike immunoglobulin G. Female sex (OR = 1.77; 95%CI = 1.01-3.12), previous COVID-19 infection (OR = 3.62; 95%CI = 1.13-11.63) and adverse events after the second dose (OR = 2.66; 95%CI = 1.33-5.32) were independently associated with intense systemic adverse events 7 days after. Booster dose significantly increased antibodies titers, especially 28 days after heterologous regimen, without a significant increase in reactogenicity.

Immunogenicity and Reactogenicity of the Booster Dose of COVID-19 Vaccines and Related Factors: A Panel Study from the General Population in Serbia

The Republic of Serbia applied the booster dose of the following COVID-19 vaccines: BNT162b2 mRNA (Pfizer-BioNTech), Sinopharm BBIBP-CorV (Vero Cell®), Gam-COVID-Vac (Sputnik V) and ChAdOk1 nCoV-19 (AstraZeneca). We aimed to examine the immunogenicity and reactogenicity of the booster dose and identify factors related to immune response and adverse events. Panel study, conducted during August and September 2021, included 300 persons receiving the booster dose at the Institute of Public Health of Serbia. Blood samples were taken on the day of receiving the booster dose, and after 7 and 28 days. When applying homologous regimen, the average increase in anti-spike immunoglobulin G was 8782.2 (after 7 days), 1213.9 after 28 days, while 9179.5 (after 7 days) and 16,728.1 after 28 days of heterologous regimen. Sinopharm BBIBP-CorV (p < 0.001) and Sputnik V (p < 0.001), age 65 and over (p = 0.001) and currently smoking (p < 0.001) were independently associated with lower levels of anti-spike immunoglobulin G. Female sex (OR = 1.77;95%CI = 1.01–3.12), previous COVID-19 infection (OR = 3.62;95%CI = 1.13–11.63) and adverse events after the second dose (OR = 2.66;95%CI = 1.33–5.32) were independently associated with intense systemic adverse events 7 days after. Booster dose significantly increased antibodies titers, especially 28 days after heterologous regimen, without a significant increase in reactogenicity.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.

Distress and Wellbeing among General Practitioners in 33 Countries during COVID-19: Results from the Cross-Sectional PRICOV-19 Study to Inform Health System Interventions

Emerging literature is highlighting the huge toll of the COVID-19 pandemic on frontline health workers. However, prior to the crisis, the wellbeing of this group was already of concern. The aim of this paper is to describe the frequency of distress and wellbeing, measured by the expanded 9-item Mayo Clinic Wellbeing Index (eWBI), among general practitioners/family physicians during the COVID-19 pandemic and to identify levers to mitigate the risk of distress. Data were collected by means of an online self-reported questionnaire among GP practices. Statistical analysis was performed using SPSS software using Version 7 of the database, which consisted of the cleaned data of 33 countries available as of 3 November 2021. Data from 3711 respondents were included. eWBI scores ranged from −2 to 9, with a median of 3. Using a cutoff of ≥2, 64.5% of respondents were considered at risk of distress. GPs with less experience, in smaller practices, and with more vulnerable patient populations were at a higher risk of distress. Significant differences in wellbeing scores were noted between countries. Collaboration from other practices and perception of having adequate governmental support were significant protective factors for distress. It is necessary to address practice- and system-level organizational factors in order to enhance wellbeing and support primary care physicians.

Predictors of Clinical Inertia and Type 2 Diabetes: Assessment of Primary Care Physicians and Their Patients.

With the growing prevalence and complex pathophysiology of type 2 diabetes, many patients fail to achieve treatment goals despite guidelines and possibilities for treatment individualization. One of the identified root causes of this failure is clinical inertia. We explored this phenomenon, its possible predictors, and groups of patients affected the most, together with offering potential paths for intervention. Our research was a cross-sectional study conducted during 2021 involving 52 physicians and 543 patients of primary healthcare institutions in Belgrade, Serbia. The research instruments were questionnaires based on similar studies, used to collect information related to the factors that contribute to developing clinical inertia originating in both physicians and patients. In 224 patients (41.3%), clinical inertia was identified in patients with poor overall health condition, long diabetes duration, and comorbidities. Studying the changes made to the treatment, most patients (53%) had their treatment adjustment more than a year ago, with 19.3% of patients changing over the previous six months. Moreover, we found significant inertia in the treatment of patients using modern insulin analogues. Referral to secondary healthcare institutions reduced the emergence of inertia. This assessment of primary care physicians and their patients pointed to the high presence of clinical inertia, with an overall health condition, comorbidities, diabetes duration, current treatment, last treatment change, glycosylated hemoglobin and fasting glucose measuring frequency, BMI, patient referral, diet adjustment, and physician education being significant predictors.

SOD2 rs4880 and GPX1 rs1050450 polymorphisms do not confer risk of COVID-19, but influence inflammation or coagulation parameters in Serbian cohort.

Objectives: Due to the role of oxidative stress in the pathophysiology of COVID-19, it is biologically plausible that inter-individual differences in patients' clinical manifestations might be affected by antioxidant genetic profile. The aim of our study was to assess the distribution of antioxidant genetic polymorphisms Nrf2 rs6721961, SOD2 rs4880, GPX1 rs1050450, GPX3 rs8177412, and GSTP1 (rs1695 and rs1138272) haplotype in COVID-19 patients and controls, with special emphasis on their association with laboratory biochemical parameters.Methods: The antioxidant genetic polymorphisms were assessed by appropriate PCR methods in 229 COVID-19 patients and 229 matched healthy individuals.Results: Among examined polymorphisms, only GSTP1 haplotype was associated with COVID-19 risk (p = 0.009). Polymorphisms of SOD2 and GPX1 influenced COVID-19 patients' laboratory biochemical profile: SOD2*Val allele was associated with increased levels of fibrinogen (p = 0.040) and ferritin (p = 0.033), whereas GPX1*Leu allele was associated with D-dimmer (p = 0.009).Discussion: Our findings regarding the influence of SOD2 and GPX1 polymorphisms on inflammation and coagulation parameters might be of clinical importance. If confirmed in larger cohorts, these developments could provide a more personalized approach for better recognition of patients prone to thrombosis and those for the need of targeted antiox-idant therapy.

GSTO1, GSTO2 and ACE2 Polymorphisms Modify Susceptibility to Developing COVID-19.

Based on the close relationship between dysregulation of redox homeostasis and immune response in SARS-CoV-2 infection, we proposed a possible modifying role of ACE2 and glutathione transferase omega (GSTO) polymorphisms in the individual propensity towards the development of clinical manifestations in COVID-19. The distribution of polymorphisms in ACE2 (rs4646116), GSTO1 (rs4925) and GSTO2 (rs156697) were assessed in 255 COVID-19 patients and 236 matched healthy individuals, emphasizing their individual and haplotype effects on disease development and severity. Polymorphisms were determined by the appropriate qPCR method. The data obtained showed that individuals carrying variant GSTO1*AA and variant GSTO2*GG genotypes exhibit higher odds of COVID-19 development, contrary to ones carrying referent alleles (p = 0.044, p = 0.002, respectively). These findings are confirmed by haplotype analysis. Carriers of H2 haplotype, comprising GSTO1*A and GSTO2*G variant alleles were at 2-fold increased risk of COVID-19 development (p = 0.002). Although ACE2 (rs4646116) polymorphism did not exhibit a statistically significant effect on COVID-19 risk (p = 0.100), the risk of COVID-19 development gradually increased with the presence of each additional risk-associated genotype. Further studies are needed to clarify the specific roles of glutathione transferases omega in innate immune response and vitamin C homeostasis once the SARS-CoV-2 infection is initiated in the host cell.

ECMO Predictors of Mortality: A 10-Year Referral Centre Experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a specialised life support modality for patients with refractory cardiac or respiratory failure. Multiple studies strived to evaluate the benefits of ECMO support, but its efficacy remains controversial with still inconsistent and sparse information. METHODS: This retrospective analysis included patients with ECMO support, admitted between January 2010 and December 2019 at a tertiary university ECMO referral centre in Austria. The primary endpoint of the study was overall all-cause three-month mortality with risk factors and predictors of mortality. Secondary endpoints covered the analysis of demographic and clinical characteristics of patients needing ECMO, including incidence and type of adverse events during support. RESULTS: In total, 358 patients fulfilled inclusion criteria and received ECMO support due to cardiogenic shock (258, 72%), respiratory failure (88, 25%) or hypothermia (12, 3%). In total, 41% (145) of patients died within the first three months, with the median time to death of 9 (1-87) days. The multivariate analysis identified hypothermia (HR 3.8, p < 0.001), the Simplified Acute Physiology Score III (HR 1.0, p < 0.001), ECMO initiation on weekends (HR 1.6, p = 0.016) and haemorrhage during ECMO support (HR 1.7, p = 0.001) as factors with higher risk for mortality. Finally, the most frequent adverse event was haemorrhage (160, 45%) followed by thrombosis. CONCLUSIONS: ECMO is an invasive advanced support system with a high risk of complications. Nevertheless, well-selected patients can be successfully rescued from life-threatening conditions by prolonging the therapeutic window to either solve the underlying problem or install a long-term assist device. Hypothermia, disease severity, initiation on weekends and haemorrhage during ECMO support increase the risk for mortality. In the case of decision making in a setting of limited (ICU) resources, the reported risk factors for mortality may be contemplable, especially when judging a possible ECMO support termination.

Effectiveness of technology-enhanced teaching methods of undergraduate dental skills for local anaesthesia administration during COVID-19 era: students' perception.

BACKGROUND: Traditional face-to-face clinical learning became problematic for final year dental students during the COVID-19 pandemic. Distance-learning may help mitigate the immediate impact of dental school closures. Integrating e-learning technologies into the learning process helps bridge the gap between pre-clinical and clinical training. Simulation allows students to repeat procedures until they demonstrate acceptable levels of skill. This study aimed to determine the effectiveness of a serious game as an additional teaching tool during the COVID-19 era to improve dental students' local anaesthesia administration technique and confidence. METHODS: This study applied a simulation-based serious game as an additional learning tool for training and educating dental students in local anaesthesia. Students used a mobile simulator in Serbian for 10 days from their homes. To evaluate the learning process, the students completed a post-training questionnaire. RESULTS: All respondents felt comfortable using the simulator. Over 90% of respondents believed that the application facilitated the learning process and had advantages in terms of accessibility and ease of use. Also, students found augmented reality (AR) technology particularly interesting to use. The use of a mobile simulator designed as a 3D and AR environment allows for simpler localisation and identification of anatomical structures and reference points, which is a good base for clinical practice. CONCLUSION: Serious games of local anaesthesia procedures as an additional e-learning tool during the COVID-19 era could improve students' knowledge and skills.

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19.

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

Evaluation of the Use of Blood Products in ICU Hospitalized COVID-19 Patients

(1) Background: The COVID-19 pandemic tested the public health system’s readiness for crises and highlighted the importance of knowing the demand for blood products and the maintenance of the blood supply chain. The aim of this study was to evaluate blood product usage in a series of patients that were hospitalized due to COVID-19 and to analyze their demographics and clinical characteristics. (2) Methods: In this retrospective cohort study, we analyzed data from transfused COVID-19 patients that were treated in the University Hospital Medical Center Bezanijska Kosa in Belgrade, Serbia during the second wave of the epidemic. (3) Results: This study included 90 patients. The median age of the patients was 72 (range 23–95) years. The median time of hospitalization was 23 days (range 3–73 days). In intensive care units (ICUs) the median time of hospitalization was 9 days (range 0–73). One or more comorbidities were observed in 86 individuals (95.6%). The total number of transfused red blood cell concetrates (RBC) was 304 (139 in ICU, 165 in other wards), with a mean of 3 units/patient (range 1–14). Comorbidities, severity of illness and hospital duration in the ICU were statistically significant predictors of higher RBC use. (4) Conclusion: Knowledge of the transfusion profile of COVID-19 patients allowed better management of the hospital’s blood stocks during the COVID-19 pandemic.

Factors Associated with Intention of Serbian Public Health Workers to Leave the Job: A Cross-Sectional, Population-Based Study.

Recruitment and retention of public health workers (PHWs) is crucial for the optimal functioning of the public health system at a time of budget cuts and the threat of a pandemic. Individual and job-related variables were examined by univariate and multivariate logistic regression to identify predictors of the intention to leave a job during the COVID-19 outbreak among Serbian PHWs in 25 institutes of public health (n = 1663 respondents, of which 73.1% were female). A total of 20.3% of PHWs intended to leave their current job within the next five years. Males and persons aged younger than 55 years who had additional practice were more likely to report an intention to leave their job than females, those older than 54 years and those without additional work. While uncertainty and fear of infection during the COVID-19 pandemic were almost perceived as job attractiveness, other job-related characteristics were identified as significant barriers to maintaining the sufficient capacity of qualified PHWs in the future. Authorities need to address these factors, including the following: the feeling of tension, stress or pressure, and unavailability of information during the COVID-19 pandemic, as well as dissatisfaction with respect, valuation, and the job in general.

Acute leukemia and SARS-CoV-2 infection: clinical characteristics and risk factors for mortality.

Patients with acute leukemia (AL) have a high mortality rate from coronavirus disease 2019 (COVID-19). However, studies including patients with AL and COVID-19 are few. Fifty-one patients with AL and COVID-19 were included in our study. The mortality rate was 17/51 (29.4%). In all cases, death was associated with COVID-19 pneumonia. The major driver of outcome was the disease status (worse outcome was observed in newly diagnosed (OR, 6.00; 95% CI, 1.133 - 15.188) and patients with bone marrow aplasia (OR 4.148 [95% CI 1.133 - 15.188])). Higher mortality rate was associated with lower platelet count, prolonged PT, higher ISTH DIC score, CRP and LDH. Moreover, careful risk-benefit assessment regarding the continuation of anticancer therapy is required in patients receiving nonintensive and supportive therapy. Considering the high frequency of intrahospital viral transmission (50.98%), isolation of AL patients in single rooms, and permanent symptom monitoring and testing should be prioritized.

Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings.

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients' redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and DNA during the course of acute disease, as well as their association with CT pulmonary patterns. In order to obtain more insight into the origin of the systemic oxidative stress, the observed parameters were correlated with inflammatory biomarkers and biomarkers of multiorgan impairment. In this prospective study, we included 58 patients admitted between July and October 2020 with COVID-19 pneumonia. Significant changes in malondialdehyde, 8-hydroxy-2'-deoxyguanosine and advanced oxidation protein products levels exist during the course of COVID-19. Special emphasis should be placed on the fact that the pattern of changes differs between non-hospitalized and hospitalized individuals. Our results point to the time-dependent relation of oxidative stress parameters with inflammatory and multiorgan impairment biomarkers, as well as pulmonary patterns in COVID-19 pneumonia patients. Correlation between redox biomarkers and immunological or multiorgan impairment biomarkers, as well as pulmonary CT pattern, confirms the suggested involvement of neutrophils networks, IL-6 production, along with different organ/tissue involvement in systemic oxidative stress in COVID-19.

Influence of COVID-19 pandemic on quality of life in patients with epilepsy - Follow-up study.

OBJECTIVE: To perform a follow-up study of the quality of life in patients with epilepsy in the era of the COVID-19 crisis. METHODS: Two months before the first case of the COVID-19 in Serbia, we obtained the Serbian Version of Quality of Life Inventory for Epilepsy 31 (SVQOLIE-31) and Neurological Disorders Depression Inventory for Epilepsy scores (SVNDDI-E) for another study. We retested the same patients one year after in COVID-19 pandemic. In addition to SVQOLIE-31, and SVNDDI-E we used a generic questionnaire compiled from items related to the COVID-19. RESULTS: We retested 97 out of 118 patients (82.2%) for the follow-up analysis. The average age was 36.1 ±â€¯12.2 (range: 18-69), and 49 were women (50.5%). The median duration of epilepsy was 13 years (range: 1.5-48). The structural etiology of epilepsy was noted in 41 (42.3%), unknown etiology in 41 (42.3%), and genetic etiology in 15 (15.4%) patients. Fewer patients (27.8%) experienced at least one seizure three months before follow-up testing when compared to patients who experienced at least one seizure three months in initial testing (36.0%) (p = 0.15). All patients reported full compliance with anti-seizure medication in the follow-up. The SVQOLIE-31 score during the COVID-19 pandemic visit (64.5 ±â€¯14.6) was significantly lower than the SVQOLIE-31 score before the pandemic (p < 0.001). The SVNDDI-E score during the COVID-19 pandemic (10.5 ±â€¯3.5) was significantly higher than the SVNDDI-E score before it (p < 0.001). Multiple linear regression analyses revealed fear of seizures, and fear of a reduction in household income, significantly associated with SVQOLIE-31 and SVNDDI-E overall score. These variables accounted for 66% and 27% of the variance of SVQOLIE-31 and SVNDDI-E overall score. SIGNIFICANCE: Lower quality of life, higher prevalence of depression, healthcare availability issues, and perceived fears during pandemic all suggest COVID-19 has negatively impacted lives of patients with epilepsy.

Are There Differences in Arteriovenous Fistulae Created for Hemodialysis between Nephrologists and Vascular Surgeons?

OBJECTIVE: Many studies have reported insufficient support from surgical services, resulting in nephrologists creating arteriovenous fistulas in many centers. The aim of this study was to compare risk factors of arteriovenous fistula dysfunction in patients whose fistulas were created by nephrologists versus vascular surgeons. METHODS: This was a retrospective, analytical study of interventions by nephrologists and vascular surgeons during a period of 15 years. Out of a total of 1,048 fistulas, 764 (72.9%) were created by nephrologists patients, while vascular surgeons were responsible for 284 (27.1%) fistulae. Laboratory, demographic, and clinical parameters which might affect functioning of these arteriovenous fistulae were analyzed. RESULTS: Patients whose arteriovenous fistula was formed by nephrologists differed significantly from those created by vascular surgeons in relation to the preventive character of the arteriovenous fistula (p = 0.011), lumen of the vein (p < 0.001) and systolic blood pressure (p = 0.047). Multivariate logistic regression of arteriovenous fistula dysfunction showed that risk factors were female gender (odds ratio [OR] = 1.56, 95% CI 1.16-2.07), whether the fistulae were created by vascular surgeons or nephrologists (OR = 1.38; 95% CI 1.01-1.89) and the site of the arteriovenous fistula (OR = 0.64; 95% CI 0.48-0.85). CONCLUSIONS: Arteriovenous fistulae created by vascular surgeons, female gender, and the location are risk factors of dysfunction.