Prepare Romania: study protocol for a randomized controlled trial of an intervention to promote pre-exposure prophylaxis adherence and persistence among gay, bisexual, and other men who have sex with men.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBMSM) represent a high-risk group for HIV transmission in Romania, yet they possess few resources for prevention. Despite having no formal access to pre-exposure prophylaxis (PrEP) through the health system, GBMSM in Romania demonstrate a high need for and interest in this medication. In anticipation of a national rollout of PrEP, this study tests the efficacy of a novel strategy, Prepare Romania, that combines two evidence-based PrEP promotion interventions for GBMSM living in Romania. METHODS: This study uses a randomized controlled trial design to examine whether GBMSM living in Romania receiving Prepare Romania, a culturally adapted counseling and mobile health intervention (expected n = 60), demonstrate greater PrEP adherence and persistence than those assigned to a PrEP education control arm (expected n = 60). Participants from two main cities in Romania are prescribed PrEP and followed-up at 3 and 6 months post-randomization. PrEP adherence data are obtained through weekly self-report surveys and dried blood spot testing at follow-up visits. Potential mediators (e.g., PrEP use motivation) of intervention efficacy are also assessed. Furthermore, Prepare Romania's implementation (e.g., proportion of enrolled participants attending medical visits, intervention experience) will be examined through interviews with participants, study implementers, and healthcare officials. DISCUSSION: The knowledge gained from this study will be utilized for further refinement and scale-up of Prepare Romania for a future multi-city effectiveness trial. By studying the efficacy of tools to support PrEP adherence and persistence, this research has the potential to lay the groundwork for PrEP rollout in Romania and similar contexts. Trial registration This study was registered on ClinicalTrials.gov, identifier NCT05323123 , on March 25, 2022.

Age, comorbidity burden and late presentation are significant predictors of hospitalization length and acute respiratory failure in patients with influenza.

Influenza viruses are responsible for a high number of infections and hospitalizations every year. In this study, we aimed to identify clinical and host-specific factors that influence the duration of hospitalization and the progression to acute respiratory failure (ARF) in influenza. We performed an analysis of data from a prospective active influenza surveillance study that was conducted over five seasons (2018/19 to 2022/23). A total of 1402 patients with influenza were included in the analysis, the majority of which (64.5%) were children (under 18 years), and 9.1% were elderly. At least one chronic condition was present in 29.2% of patients, and 9.9% of patients developed ARF. The median hospital stay was 4 days (IQR: 3, 6 days). The most important predictors of prolonged hospital stay and development of ARF were extremes of age (infants and elderly), presence of chronic diseases, particularly the cumulus of at least 3 chronic diseases, and late presentation to hospital. Among the chronic diseases, chronic obstructive pulmonary disease, cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease were strongly associated with a longer duration of hospitalization and occurrence of ARF. In this context, interventions aimed at chronic disease management, promoting influenza vaccination, and improving awareness and access to health services may contribute to reducing the impact of influenza not only in Romania but globally. In addition, continued monitoring of the circulation of influenza viruses is essential to limit their spread among vulnerable populations.

Hybrid Immunity and the Incidence of SARS-CoV-2 Reinfections during the Omicron Era in Frontline Healthcare Workers.

During the coronavirus disease (COVID-19) pandemic healthcare workers (HCWs) acquired immunity by vaccination or exposure to multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study is a comparative analysis between subgroups of HCWs constructed based on the number of SARS-CoV-2 infections, vaccination, and the dominant variant of SARS-CoV-2 in the population. We collected and analyzed data using the χ2 test and density incidence of reinfections in Microsoft Excel for Mac, Version 16.84, and MedCalc®, 22.026. Of the 829 HCWs, 70.1% (581) had only one SARS-CoV-2 infection and 29.9% (248) had two infections. Of the subjects with two infections, 77.4% (192) worked in high-risk departments and 93.2% (231) of the second infections were registered during Omicron dominance. The density incidence of reinfections was higher in HCWs vaccinated with the primary schedule than those vaccinated with the first booster, and the incidence ratio was 2.8 (95% CI: 1.2; 6.7). The probability of reinfection was five times lower (95% CI: 2.9; 9.2) in HCWs vaccinated with the primary schedule if the first infection was acquired during Omicron dominance. The subjects vaccinated with the first booster had a density incidence of reinfection three times lower (95% CI: 1.9; 5.8) if the first infection was during Omicron. The incidence ratio in subgroups constructed based on characteristics such as gender, age group, job category, and department also registered significant differences in density incidence. The history of SARS-CoV-2 infection by variant is important when interpreting and understanding public health data and the results of studies related to vaccine efficacy for hybrid immunity subgroup populations.

Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D.

BACKGROUND: In a phase 3 trial, bulevirtide monotherapy led to a virologic response in patients with chronic hepatitis D. Pegylated interferon (peginterferon) alfa-2a is recommended by guidelines as an off-label treatment for this disease. The role of combination therapy with bulevirtide and peginterferon alfa-2a, particularly with regard to finite treatment, is unclear. METHODS: In this phase 2b, open-label trial, we randomly assigned patients to receive peginterferon alfa-2a alone (180 µg per week) for 48 weeks; bulevirtide at a daily dose of 2 mg or 10 mg plus peginterferon alfa-2a (180 µg per week) for 48 weeks, followed by the same daily dose of bulevirtide for 48 weeks; or bulevirtide at a daily dose of 10 mg alone for 96 weeks. All the patients were followed for 48 weeks after the end of treatment. The primary end point was an undetectable level of hepatitis D virus (HDV) RNA at 24 weeks after the end of treatment. The primary comparison was between the 10-mg bulevirtide plus peginterferon alfa-2a group and the 10-mg bulevirtide monotherapy group. RESULTS: A total of 24 patients received peginterferon alfa-2a alone, 50 received 2 mg and 50 received 10 mg of bulevirtide plus peginterferon alfa-2a, and 50 received 10 mg of bulevirtide monotherapy. At 24 weeks after the end of treatment, HDV RNA was undetectable in 17% of the patients in the peginterferon alfa-2a group, in 32% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. For the primary comparison, the between-group difference was 34 percentage points (95% confidence interval, 15 to 50; P<0.001). At 48 weeks after the end of treatment, HDV RNA was undetectable in 25% of the patients in the peginterferon alfa-2a group, in 26% of those in the 2-mg bulevirtide plus peginterferon alfa-2a group, in 46% of those in the 10-mg bulevirtide plus peginterferon alfa-2a group, and in 12% of those in the 10-mg bulevirtide group. The most frequent adverse events were leukopenia, neutropenia, and thrombocytopenia. The majority of adverse events were of grade 1 or 2 in severity. CONCLUSIONS: The combination of 10-mg bulevirtide plus peginterferon alfa-2a was superior to bulevirtide monotherapy with regard to an undetectable HDV RNA level at 24 weeks after the end of treatment. (Funded by Gilead Sciences; MYR 204 ClinicalTrials.gov number, NCT03852433.).

An mHealth Intervention for Gay and Bisexual Men's Mental, Behavioral, and Sexual Health in a High-Stigma, Low-Resource Context (Project Comunica): Protocol for a Randomized Controlled Trial.

BACKGROUND: The World Health Organization reported that 80% of new HIV diagnoses in Europe in 2014 occurred in Central and Eastern Europe. Romania has a particularly high HIV incidence, AIDS prevalence, and number of related deaths. HIV incidence in Romania is largely attributed to sexual contact among gay and bisexual men. However, homophobic stigma in Romania serves as a risk factor for HIV infection for gay and bisexual men. The Comunica intervention aims to provide a much-needed HIV risk reduction strategy, and it entails the delivery of motivational interviewing and cognitive behavioral therapy skills across 8 live text-based counseling sessions on a mobile platform to gay and bisexual men at risk of HIV. The intervention is based on the information-motivation-behavior and minority stress models. There is preliminary evidence suggesting that Comunica holds promise for reducing gay and bisexual men's co-occurring sexual (eg, HIV transmission risk behavior), behavioral (eg, heavy alcohol use), and mental (eg, depression) health risks in Romania. OBJECTIVE: This paper describes the protocol for a randomized controlled trial designed to test the efficacy of Comunica in a national trial. METHODS: To test Comunica's efficacy, 305 gay and bisexual men were randomized to receive Comunica or a content-matched education attention control condition. The control condition consisted of 8 time-matched educational modules that present information regarding gay and bisexual men's identity development, information about HIV transmission and prevention, the importance of HIV and sexually transmitted infection testing and treatment, heavy alcohol use and its associations with HIV transmission risk behavior, sexual health communication, finding social support, and creating sexual health goals. Participants undergo rapid HIV and syphilis testing and 3-site chlamydia and gonorrhea testing at baseline and the 12-month follow-up. Outcomes are measured before the intervention (baseline) and at the 4-, 8-, and 12-month follow-ups. RESULTS: The study was funded in September 2018, and data collection began in May 2019. The last participant follow-up was in January 2024. Currently, the data analyst is cleaning data sets in preparation for data analyses, which are scheduled to begin in April 2024. Data analysis meetings are scheduled regularly to establish timelines and examine the results as analyses are gradually being conducted. Upon completion, a list of manuscripts will be reviewed and prioritized, and the team will begin preparing them for publication. CONCLUSIONS: This study is the first to test the efficacy of an intervention with the potential to simultaneously support the sexual, behavioral, and mental health of gay and bisexual men in Central and Eastern Europe using motivational interviewing support and sensitivity to the high-stigma context of the region. If efficacious, Comunica presents a scalable platform to provide support to gay and bisexual men living in Romania and similar high-stigma, low-resource countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT03912753; https://clinicaltrials.gov/study/NCT03912753. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52853.

The Dynamic Risk of COVID-19-Related Events in Vaccinated Healthcare Workers (HCWs) from a Tertiary Hospital in Bucharest, Romania: A Study Based on Active Surveillance Data.

Our study describes the frequency and severity of COVID-19 in HCWs and estimates the dynamic risk of COVID-19-related events. We actively surveyed all HCWs from a tertiary infectious disease hospital from 26 February 2020 to 31 May 2023. Of 1220 HCWs, 62.9% (767) had at least one COVID-19 episode. The under 29 years (p = 0.0001) and 40-49 years (p = 0.01) age groups, nurses (p = 0.0001), and high-risk departments (p = 0.037) were characteristics significantly more frequent in HCWs with COVID-19 history. A higher percentage of boosters (53.2%; p < 0.0001) were registered in the uninfected group. The second episode of COVID-19 was significantly milder than the first. Data regarding clinical outcomes from 31 January 2021 to 31 May 2023 were analyzed in a follow-up study to determine the risk of COVID-19-related events. The Cox regression analysis revealed that HCWs with booster shots had a lower risk of COVID-19 across all events, symptomatic events, and moderate to severe events as adjusted hazard ratio (aHR) were: 0.71 (95%CI: 0.54-0.96), 0.23 (95%CI: 0.12-0.46), and 0.17 (95%CI: 0.07-0.43), respectively. Within the vaccinated subgroup, the HCWs with hybrid immunity and booster had aHR for all followed-up events of 0.42 (95%CI: 0.30-0.58), for symptomatic events of 0.52 (95%CI: 0.36-0.74), and 0.15 (95%CI: 0.03-0.66) for moderate to severe events. The risk of COVID-19 clinical events was lower for HCWs with at least one booster than those completely vaccinated.

Antibiotic Prescribing in Dental Medicine-Best Practices for Successful Implementation.

With rising rates of antimicrobial resistance throughout the world, it is time to revisit antibiotic prescribing policies and practices, and dentistry is an important area for focused intervention, as it accounts for up to 15% of all antimicrobial prescriptions. In this narrative review, we have analyzed the current state of the knowledge, attitudes, and practice regarding antimicrobial use among dental professionals, and we have identified a set of seven recurring themes that drive inappropriate antibiotic prescribing in dental medicine. These include: 1. Prescribing antibiotics to delay or avoid dental treatment. 2. Overlooking the 5Ds-dental treatment (source control), dental condition (indication), drug (antibiotic choice), dose, and duration. 3. Relying on education from the distant past and on previous experience. 4. The heterogeneity of (too many) guideline recommendations leads to confusion and over-prescribing. 5. Decreased access to guideline information in private practice. 6. Psychological factors such as pressure to prescribe, comfort prescribing and the weekend effect, and 7. Feeling removed from antimicrobial resistance and externalizing responsibility. Based on the existing knowledge, we propose a framework based on four key pillars for focused intervention: 1. Education. 2. Internalizing responsibility. 3. Recognizing recurring counter-productive practices, and 4. Addressing recurring counter-productive practices. This framework can be applied in different dental settings to ensure best practices for the successful implementation of rational antimicrobial prescribing.

The Impact of Obesity on the Host-Pathogen Interaction with Influenza Viruses - Novel Insights: Narrative Review.

After exposure to a viral pathogen, the host-pathogen interaction is essential to determine whether or not infection will ensue, and what the clinical outline of the infection will be. Recent research has shown that the patient with obesity presents a set of particular pathophysiological changes that lead to higher severity of viral infections, and this is particularly true for infection with influenza viruses. Herein, we describe the main metabolic, endocrine, and immune dysregulations that occur in the presence of obesity and their impact on driving intra-host viral diversity, leading to heightened severity and virulence of influenza. We show that obesity is linked to modified responses of both the innate and adaptive immune systems during viral infections, including influenza. Due to chronic inflammation and metabolic, endocrine, and signaling pathway disruptions, individuals with obesity have a suboptimal immune response. This results in longer illness duration, increased virus shedding, higher risk of hospitalization and complications, and greater mortality rates. Additionally, they may have a blunted response to vaccination and a higher likelihood of genetic mutation selection. Understanding the intricate interplay between obesity and viral pathogenesis is crucial for developing efficacious therapeutic approaches and public health policies, particularly in light of the escalating worldwide incidence of obesity.

A randomized controlled trial of an mHealth intervention for gay and bisexual men's mental, behavioral, and sexual health in a high-stigma, low-resource context: Project Comunica protocol.

Background: The World Health Organization (WHO) reported that 80% of new HIV diagnoses in 2014 in Europe occurred in Central and Eastern Europe (CEE). Romania has particularly high HIV incidence, AIDS prevalence, and AIDS-related deaths. HIV incidence today in Romania is largely attributed to sexual contact among gay and bisexual men (GBM). However, homophobic stigma in Romania keeps GBM out of reach of the scant available prevention services and serves as a risk factor for HIV. The Comunica intervention delivers motivational interviewing and cognitive-behavioral therapy skills across eight live text-based counseling sessions. Preliminary evidence suggests that Comunica possesses promise for reducing GBM's co-occurring mental (e.g., depression), behavioral (e.g., heavy alcohol use), and sexual (e.g., HIV-transmission-risk behavior) health risks in Romania and perhaps other similar high-stigma national contexts. This paper describes a randomized controlled trial (RCT) designed to test the efficacy of Comunica. Methods: To test Comunica's efficacy, 305 GBM were randomized to receive Comunica or a content-matched education attention control condition. The control condition consists of eight time-matched educational modules that present information regarding GBM identity development, information about HIV transmission and prevention, the importance of HIV/STI testing and treatment, heavy alcohol use and its associations with HIV-transmission-risk behavior, sexual health communication, finding social support, and creating sexual health goals. Outcomes are measured pre-intervention (baseline), and at 4-, 8-, and 12-month follow-ups. The primary outcome is frequency of condomless anal sex acts with HIV-positive or unknown-status partners outside of the context of one's own adherent PrEP use or primary partner's adherent PrEP use or undetectable viral load in the past 30 days at each follow-up. Secondary outcomes include depression, anxiety, suicidal thoughts, heavy alcohol use, and HIV/STI testing; motivational and stigma-related mechanisms of intervention efficacy will also be examined. Discussion: If found to be efficacious, Comunica presents a scalable platform to provide mental, behavioral, and sexual health support to GBM living in Romania and similar high-stigma, low-resource areas within the CEE region and beyond. Trial registration: Registered April 11, 2019 to ClinicalTrials.gov Identifier: NCT03912753.

Etiology and Multi-Drug Resistant Profile of Bacterial Infections in Severe Burn Patients, Romania 2018-2022.

Infections in severe burns and their etiology are and will remain a big concern for the medical field. The multi-drug resistant strains of bacteria are a challenge of today's medicine. The aim of our study was to identify the etiological spectrum of bacterial infections in severe burn patients in Romania and their multi-drug resistant patterns. We performed a prospective study that included 202 adult patients admitted to the intensive care unit (ICU) of the Clinical Emergency Hospital of Plastic, Reconstructive Surgery and Burns, Bucharest, Romania (CEHPRSB), from 1 October 2018 to 1 April 2022, a period which includes the first 2 years of the outbreak of COVID-19. From each patient, wound swabs, endotracheal aspirates, blood for blood culture, and urine were collected. The most frequently isolated bacterium was Pseudomonas aeruginosa (39%), followed by Staphylococcus aureus (12%), Klebsiella spp. (11%), and Acinetobacter baumannii (9%). More than 90% of Pseudomonas aeruginosa and Acinetobacter baumannii were MDR, regardless of the clinical specimen from which they were isolated.

Vaccination and Factors Related to the Clinical Outcome of COVID-19 in Healthcare Workers-A Romanian Front-Line Hospital's Experience.

The study aims to describe the frequency of COVID-19 in healthcare workers (HCWs) in a designated hospital for COVID-19 treatment in Bucharest, Romania, and to explore COVID-19 vaccination and other factors associated with the clinical outcome. We actively surveyed all HCWs from 26 February 2020 to 31 December 2021. Cases were laboratory-confirmed with RT-PCR or rapid test antigen. Epidemiological, demographic, clinical outcomes, vaccination status, and co-morbidities data were collected. Data were analyzed using Microsoft Excel, SPSS, and MedCalc. A total of 490 cases of COVID-19 in HCWs were diagnosed. The comparison groups were related to the severity of the clinical outcome: the non-severe group (279, 64.65%) included mild and asymptomatic cases, and the potentially severe group included moderate and severe cases. Significant differences between groups were registered for high-risk departments (p = 0.0003), exposure to COVID-19 patients (p = 0.0003, vaccination (p = 0.0003), and the presence of co-morbidities (p < 0.0001). Age, obesity, anemia, and exposure to COVID-19 patients predicted the severity of the clinical outcomes (χ2 (4, n = 425) = 65.69, p < 0.001). The strongest predictors were anemia and obesity (OR 5.82 and 4.94, respectively). In HCWs, mild COVID-19 cases were more frequent than severe cases. Vaccination history, exposure, and individual risk influenced the clinical outcome suggesting that measures to protect HCWs and occupational medicine are important for pandemic preparedness.

Therapeutic developments for SARS-CoV-2 infection-Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice.

This article systematically presents the current clinically significant therapeutic developments for the treatment of COVID-19 by providing an in-depth review of molecular mechanisms of action for SARS-CoV-2 antivirals and critically analyzing the potential targets that may allow the selection of resistant viral variants. Two main categories of agents can display antiviral activity: direct-acting antivirals, which act by inhibiting viral enzymes, and host-directed antivirals, which target host cell factors that are involved in steps of the viral life cycle. We discuss both these types of antivirals, highlighting the agents that have already been approved for treatment of COVID-19, and providing an overview of the main molecules that are currently in drug development. Direct-acting antivirals target viral enzymes that are essential in the viral life cycle. Three direct-acting antivirals are currently in use: two are nucleoside analogs that inhibit the RNA-dependent RNA polymerase of SARS-CoV-2, i.e., remdesivir and molnupiravir, and the third one, nirmatrelvir/ritonavir, is an inhibitor of SARS-CoV-2 main protease. The potential for induction of viral resistance is discussed for each of these antivirals, along with their clinical activity on each of the SARS-CoV-2 variants and sublineages that have been dominant over the course of the pandemic, i.e., Alpha, Delta, as well as Omicron and its sublineages BA.1, BA.2, BA.5, BQ.1 and XBB. Host-directed antivirals are currently in preclinical or clinical development; these agents target host cell enzymes that are involved in facilitating viral entry, replication, or virion release. By blocking these enzymes, viral replication can theoretically be effectively stopped. As no SARS-CoV-2 host-directed antiviral has been approved so far, further research is still needed and we present the host-directed antivirals that are currently in the pipeline. Another specific type of agents that have been used in the treatment of COVID-19 are neutralizing antibodies (NAbs). Their main binding site is the spike protein, and therefore their neutralization activity is influenced by mutations occurring in this region. We discuss the main changes in neutralization activity of NAbs for the most important dominant SARS-CoV-2 variants. Close monitoring of emerging variants and sublineages is still warranted, to better understand the impact of viral mutations on the clinical efficiency of antivirals and neutralizing antibodies developed for the treatment of COVID-19.

Liver Transaminases in Pediatric Adenovirus Infection-A Five-Year Study in Two Major Reference Centers from Romania.

Human adenovirus causes infections with a very heterogeneous clinical picture, and children are often the most frequently affected group. Interest in adenovirus has increased with the 2022 outbreak of severe acute hepatitis of unknown etiology as human adenovirus was considered as one of the possible etiological agents. We conducted a retrospective study over a 5-year period in two major tertiary hospitals in the Romanian capital with the aim to characterize the clinical picture and the dynamics of liver function tests in children with confirmed adenovirus infection. The study included 1416 children with a median age of 1.1 years (IQR: 0.3, 2.3 years). Digestive symptoms were predominant in 95.2% of children, mainly diarrhea (90.5%) and vomiting (50.5%), and 38.0% had respiratory symptoms. Increased transaminases were identified in 21.5% of patients. Age over 1 year, lethargy, vomiting and dehydration significantly increased the odds of liver cytolysis independent of other risk factors such as chronic conditions or co-infections. Aspartate aminotransferase (AST) was more commonly increased compared to alanine aminotransferase (ALT). Only six children had transaminase increases above 500 U/L, three of which had co-infections with rotavirus, Epstein-Barr virus (EBV), or respiratory syncytial virus (RSV). Liver function tests should be part of routine monitoring for pediatric patients with adenovirus infection. The current study fills a gap in current knowledge related to the frequency and the extent of liver involvement in human adenovirus infection among pediatric patients.

Omicron in Infants-Respiratory or Digestive Disease?

The Omicron variant of SARS-CoV-2 has caused a large number of cases and hospitalizations in the pediatric population. Infants due to their age are susceptible to viral infections that may have a worse prognosis. Therefore, the aim of the current study has been to characterize the clinical features and the outcome of infants hospitalized with confirmed SARS-CoV-2 infection during the Omicron wave. We conducted a retrospective study of all consecutive infants hospitalized with symptomatic COVID-19 and no other co-infections, from January to September 2022 in one of the largest infectious diseases hospitals from Bucharest, Romania. A total of 613 infants were included in the analysis. The median age was 5 months (IQR: 3, 8 months). The clinical features were dominated by fever (96.4%), cough (64.8%) and loss of appetite (63.3%), and overall, respiratory symptoms were the most numerous (76.0%). Infants between 1-3 months old had a 1.5-fold increased risk of elevated alanine aminotransferase (ALT) values, and a longer length of hospitalization as compared to older infants. Infants between 7-9 months of age had 1.5-fold higher odds of loss of appetite, 1.7-fold more frequent cough and 1.6-fold more frequent digestive symptoms compared to infants in other age groups. The presence of digestive symptoms increased the probability of hepatic cytolysis (increased ALT) by 1.9-fold. Continued monitoring of COVID-19 among infants is very necessary, given the progressive character of SARS-CoV-2, in order to take correct and rapid therapeutic measures and to adapt to clinical changes driven by viral variant change.

Prevalence of undiagnosed hepatitis B virus infection in patients with COVID-19A single center retrospective study.

At its onset, the coronavirus disease 2019 (COVID-19) pandemic brought significant challenges to healthcare systems, changing the focus of medical care on acute illness. Disruptions in medical service provision have impacted the field of viral hepatitis, with screening programs paused throughout much of 2020 and 2021. We performed a retrospective study on consecutive outpatients with COVID-19 during the second and third wave of COVID-19 in Romania, from November 2020 to April 2021, aiming to characterize the prevalence of undiagnosed hepatitis B virus (HBV) infection among patients presenting with acute illness. Overall, 522 patients had available records during the study timespan. Their mean ±â€…standard deviation age was 51 ±â€…13 years; 274 (52.5%) were male. We identified 16 (3.1%) cases of active HBV infection; only six of these patients were aware of their HBV status, and 3 of the newly diagnosed cases were identified as candidates for HBV treatment. A total of 96 patients (18.4%) had serological markers suggestive for prior HBV vaccination. A large proportion of patients (n = 120, 23.0%) had positive HBV core antibodies; among these, 90 (17.2%) had cleared a previous HBV infection (being positive for HBV surface antibodies and HBV core antibodies). We identified the following parameters that were significantly more frequent in patients with a history of HBV infection: older age (P < .001), hypoalbuminemia (P = .015), thrombocytopenia (P < .001), thrombocytopenia followed by thrombocytosis (P = .041), increased blood urea nitrogen (P < .001) and increased creatinine (P = .011). In conclusion, the COVID-19 pandemic has taught us essential lessons about the importance of maintaining access to screening programs and of ensuring active monitoring of patients with chronic infections such as hepatitis B, even during a medical crisis.

Particularities of Telework Applicable to the Health System in the Context of the COVID-19 Pandemic.

The paper aims to highlight how physician-patient relationships have evolved amid the COVID-19 pandemic by considering telework implementation into the healthcare sector. The article presents the peculiarities of using telework within the medical system given the recent epidemiological context, by pointing out the advantages and disadvantages of its adoption. To achieve this goal, a qualitative marketing research was conducted to identify physicians' opinions and perceptions on telework. The main objectives were identifying the ways of using telework, the effects that telework has on the quality of the medical services and on patient relationships, as well as the strengths and weaknesses of telework for the medical field. The study revealed that while face-to-face consultations decreased as the outbreak continued, different methods of remote consultations emerged, which was both beneficial in interactions with chronic patients and detrimental, as medical staff became more and more overworked. For these reasons, our research shows that healthcare professionals consider a hybrid system much more adequate for patients with stable chronic conditions, as ongoing monitoring is done through this remote mechanism.

A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019.

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant. Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients). Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo). Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant. Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT).

Analysis of virological response to therapy and resistance profile in treatment-experienced and naive HIV-1 infected Romanian patients receiving regimens containing darunavir boosted with ritonavir or cobicistat.

77% of Romanians infected with HIV receive antiretroviral therapy, with the challenge of maintaining long-term therapeutic success (the viral load becoming/remaining undetectable). The main purpose of this study was to provide comparative analysis of the long-term virological response to therapeutic regimens containing pharmacokinetically enhanced darunavir (DRV) with ritonavir (RTV) or cobicistat (COBI). The second aim was to evaluate the viral resistance profile to therapy, by number/type/frequency of viral mutations. This retrospective study was conducted on 462 patients infected with subtype F HIV-1, registered at the "Matei Bals" National Institute of Infectious Diseases, between 2018 and 2021: 384 patients received (among other ARV) DRV 600 mg, enhanced with RTV 100 mg (twice daily) and 78 patients received DRV 800 mg boosted with COBI 150 mg (once daily). The virological response was measured by determining the viral load (HIV-1 RNA copies/mL), while the incidence of viral resistance to therapy was assessed by genotyping tests. Comparing the patients with undetectable viremia, from the 1st visit to the 3rd one, the outcomes showed that at the last visit, 84.6% subjects in the DRV/c group achieved virological efficiency over those from DRV/r group (76.8%). The differences observed between this time points are statistically significant p < 0.05. DRV/c administered in combination with other ARV, in subtype F HIV-1 infected patients, proved to be more virologically effective, maintaining a favorable long-time result. When comparing the outcomes of the two groups, a statistically significant difference of p < 0.05 was obtained. 32 patients (27 from DRV/r group and 5 from DRV/c group) were evaluated with persistent HIV-1 ARN plasma load > 1000 copies/mL, during all 3 clinical visits. They formed a research sub-group evaluated in terms of resistance to therapy and were reported as virological failures. 28.12% of the sub-group with persistent HIV-1 RNA > 1000 copies/mL were from the DRV/r group and only 3.12% from the DRV/c group. Drug mutations (DRM) involved in antiretroviral resistance/sensitivity occurred both in the protease gene, and in the reverse transcriptase gene, with the involved ARV classes being protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors. 16 different types of mutations were evaluated in the PR gene and 20 mutations were evaluated in RT gene.

Efficacy and Safety of Regdanvimab (CT-P59): A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial in Outpatients With Mild-to-Moderate Coronavirus Disease 2019.

Background: Regdanvimab (CT-P59) is a monoclonal antibody with neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on part 1 of a 2-part randomized, placebo-controlled, double-blind study for patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Methods: Outpatients with mild-to-moderate COVID-19 received a single dose of regdanvimab 40 mg/kg (n = 100), regdanvimab 80 mg/kg (n = 103), or placebo (n = 104). The primary end points were time to negative conversion of SARS-CoV-2 from nasopharyngeal swab based on quantitative reverse transcription polymerase chain reaction (RT-qPCR) up to day 28 and time to clinical recovery up to day 14. Secondary end points included the proportion of patients requiring hospitalization, oxygen therapy, or mortality due to COVID-19. Results: Median (95% CI) time to negative conversion of RT-qPCR was 12.8 (9.0-12.9) days with regdanvimab 40 mg/kg, 11.9 (8.9-12.9) days with regdanvimab 80 mg/kg, and 12.9 (12.7-13.9) days with placebo. Median (95% CI) time to clinical recovery was 5.3 (4.0-6.8) days with regdanvimab 40 mg/kg, 6.2 (5.5-7.9) days with regdanvimab 80 mg/kg, and 8.8 (6.8-11.6) days with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with regdanvimab 40 mg/kg (4.0% [1.6%-9.8%]) and regdanvimab 80 mg/kg (4.9% [2.1%-10.9%]) vs placebo (8.7% [4.6%-15.6%]). No serious treatment-emergent adverse events or deaths occurred. Conclusions: Regdanvimab showed a trend toward a minor decrease in time to negative conversion of RT-qPCR results compared with placebo and reduced the need for hospitalization and oxygen therapy in patients with mild-to-moderate COVID-19. Clinical trial registration : NCT04602000 and EudraCT 2020-003369-20.

Undetected Omicron Transmission in Romania-Report of the First Detected Case of Locally Acquired Omicron Infection and Complete Epidemiological Investigation.

The occurrence of the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has importantly impacted surveillance and diagnosis, and has changed the therapeutic landscape of coronavirus disease 2019 (COVID-19). We present the first documented case of locally acquired SARS-CoV-2 omicron variant in Romania in a patient with no recent travel outside the country. We also present the full results of the epidemiological investigation that led to the identification of the index case in a co-worker who had developed mild symptoms shortly after returning from the UK and who had undergone multiple rapid antigen tests with negative results prior to being tested by RT-PCR. We highlight potential lessons learned and describe further directions for actionable research and development in the field of COVID-19.