Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients—Real-World Data From Hungary

Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.

A New Mathematical Model of COVID-19 with Quarantine and Vaccination

A mathematical model revealing the transmission mechanism of COVID-19 is produced and theoretically examined, which has helped us address the disease dynamics and treatment measures, such as vaccination for susceptible patients. The mathematical model containing the whole population was partitioned into six different compartments, represented by the SVEIQR model. Important properties of the model, such as the nonnegativity of solutions and their boundedness, are established. Furthermore, we calculated the basic reproduction number, which is an important parameter in infection models. The disease-free equilibrium solution of the model was determined to be locally and globally asymptotically stable. When the basic reproduction number (Formula presented.) is less than one, the disease-free equilibrium point is locally asymptotically stable. To discover the approximative solution to the model, a general numerical approach based on the Haar collocation technique was developed. Using some real data, the sensitivity analysis of (Formula presented.) was shown. We simulated the approximate results for various values of the quarantine and vaccination populations using Matlab to show the transmission dynamics of the Coronavirus-19 disease through graphs. The validation of the results by the Simulink software and numerical methods shows that our model and adopted methodology are appropriate and accurate and could be used for further predictions for COVID-19. © 2022 by the authors.

Knowledge, perceived risk, and attitudes towards COVID-19 protective measures amongst ethnic minorities in the UK: A cross-sectional study

BackgroundMinority ethnic groups are at increased risk of COVID-19 related mortality or morbidity yet continue to have a disproportionally lower uptake of the vaccine. The importance of adherence to prevention and control measures to keep vulnerable populations and their families safe therefore remains crucial. This research sought to examine the knowledge, perceived risk, and attitudes toward COVID-19 among an ethnically diverse community. MethodsA cross-sectional self-administered questionnaire was implemented to survey ethnic minority participants purposefully recruited from Luton, an ethnically diverse town in the southeast of England. The questionnaire was structured to assess participants knowledge, perceived risk, attitudes toward protective measures as well as the sources of information about COVID-19. The questionnaire was administered online via Qualtrics with the link shared through social media platforms such as Facebook, Twitter, and WhatsApp. Questionnaires were also printed into brochures and disseminated via community researchers and community links to individuals alongside religious, community and outreach organisations. Data were analysed using appropriate statistical techniques, with the significance threshold for all analyses assumed at p = 0.05. Findings1,058 participants (634;60% females) with a median age of 38 (IQR, 22) completed the survey. National TV and social networks were the most frequently accessed sources of COVID-19 related information;however, healthcare professionals, whilst not widely accessed, were viewed as the most trusted. Knowledge of transmission routes and perceived susceptibility were significant predictors of attitudes toward health-protective practises. Conclusion/recommendationImproving the local information provision, including using tailored communication strategies that draw on trusted sources, including healthcare professionals, could facilitate understanding of risk and promote adherence to health-protective actions.

Acute Limb Ischemia among COVID-19 Patients in Hospital Kuala Lumpur

BACKGROUND: Acute arterial thromboembolism among the novel coronavirus 2019 (COVID-19) patients is worrying as it can result in significant thrombotic events. AIM: The research aimed to determine the clinical results of COVID-19-infected patients who had acute limb ischemia (ALI) during the COVID-19 epidemic. METHOD(S): ALI patients who had a positive COVID-19 were included in the observational cohort study, which was conducted at a single center. The primary outcomes were 30 days mortality, limb salvage, and successful revascularization. RESULT(S): From May to October 2021, data from 21 ALI subjects who had positive COVID-19 were analyzed. Of the 21 included subjects, 10 were male (48%). Their mean age was 65 +/- 5 years. In 9 subjects (42%), revascularization was done. Four (19%) of the 21 persons died while they were hospitalized. Twelve patients underwent major amputation, and among them, one patient died after a month of hospitalization for COVID-19-related pneumonia. Among the 12 patients that underwent amputation, 10 of them presented with ALI during the 1st week of COVID-19 illness. Only one patient developed acute limb ischemia despite being on heparin thromboprophylaxis. CONCLUSION(S): Despite attempts at revascularization, ALI associated with COVID-19 has high mortality and high rates of limb loss. In our experience, major amputation is required in up to a third of patients. This poor result appears to confirm that these infected individuals have a marked hypercoagulable condition. However, adhering to the treatment protocol of heparin thromboprophylaxis confers a benefit in this patient group. Copyright © 2022 Karthigesu Aimanan, Nurul Nadiah Nazurah Mohd Ali, Mohd Nurhisham Azmi Abdul Rahman, Putra Mas Pian, Kumaraguru V. K. Pillay, Firdaus Hayati, Hanif Hussein.

Covid-19 Vaccine Protection among Children and Adolescents in Qatar.

BACKGROUND: The BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) has been authorized for use in children 5 to 11 years of age and adolescents 12 to 17 years of age but in different antigen doses. METHODS: We assessed the real-world effectiveness of the BNT162b2 vaccine against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents in Qatar. To compare the incidence of SARS-CoV-2 infection in the national cohort of vaccinated participants with the incidence in the national cohort of unvaccinated participants, we conducted three matched, retrospective, target-trial, cohort studies - one assessing data obtained from children 5 to 11 years of age after the B.1.1.529 (omicron) variant became prevalent and two assessing data from adolescents 12 to 17 years of age before the emergence of the omicron variant (pre-omicron study) and after the omicron variant became prevalent. Associations were estimated with the use of Cox proportional-hazards regression models. RESULTS: Among children, the overall effectiveness of the 10-µg primary vaccine series against infection with the omicron variant was 25.7% (95% confidence interval [CI], 10.0 to 38.6). Effectiveness was highest (49.6%; 95% CI, 28.5 to 64.5) right after receipt of the second dose but waned rapidly thereafter and was negligible after 3 months. Effectiveness was 46.3% (95% CI, 21.5 to 63.3) among children 5 to 7 years of age and 16.6% (95% CI, -4.2 to 33.2) among those 8 to 11 years of age. Among adolescents, the overall effectiveness of the 30-µg primary vaccine series against infection with the omicron variant was 30.6% (95% CI, 26.9 to 34.1), but many adolescents had been vaccinated months earlier. Effectiveness waned over time since receipt of the second dose. Effectiveness was 35.6% (95% CI, 31.2 to 39.6) among adolescents 12 to 14 years of age and 20.9% (95% CI, 13.8 to 27.4) among those 15 to 17 years of age. In the pre-omicron study, the overall effectiveness of the 30-µg primary vaccine series against SARS-CoV-2 infection among adolescents was 87.6% (95% CI, 84.0 to 90.4) and waned relatively slowly after receipt of the second dose. CONCLUSIONS: Vaccination in children was associated with modest, rapidly waning protection against omicron infection. Vaccination in adolescents was associated with stronger, more durable protection, perhaps because of the larger antigen dose. (Funded by Weill Cornell Medicine-Qatar and others.).

Colorectal cancer in patients with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Patients with colorectal cancer (CRC) are more likely to develop severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience increased risk of mortality compared to SARS-CoV-2 patients without CRC. OBJECTIVES: To estimate the prevalence of SARS-CoV-2 infection in CRC patients and analyse the demographic parameters, clinical characteristics and treatment outcomes in CRC patients with COVID-19 illness. METHODS: For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature for studies on the incidence of SARS-CoV-2 infection in CRC patients, published from December 1, 2019 to December 31, 2021, with English language restriction. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). Sub-group analyses were performed to minimize heterogeneity. Binary logistic regression model was used to explore the effect of various demographic and clinical characteristics on patient's final treatment outcome (survival or death). RESULTS: Of the 472 papers that were identified, 69 articles were included in the systematic review and meta-analysis (41 cohort, 16 case-report, 9 case-series, 2 cross-sectional, and 1 case-control studies). Studies involving 3362 CRC patients with confirmed SARS-CoV-2 (all patients were adults) were analyzed. The overall pooled proportions of CRC patients who had laboratory-confirmed community-acquired and hospital-acquired SARS-CoV-2 infections were 8.1% (95% CI 6.1 to 10.1, n = 1308, 24 studies, I2 98%, p = 0.66), and 1.5% (95% CI 1.1 to 1.9, n = 472, 27 studies, I2 94%, p < 0.01). The median patient age ranged from 51.6 years to 80 years across studies. The majority of the patients were male (n = 2243, 66.7%) and belonged to White (Caucasian) (n = 262, 7.8%), Hispanic (n = 156, 4.6%) and Asian (n = 153, 4.4%) ethnicity. The main source of SARS-CoV-2 infection in CRC patients was community-acquired (n = 2882, 85.7%; p = 0.014). Most of those SARS-CoV-2 patients had stage III CRC (n = 725, 21.6%; p = 0.036) and were treated mainly with surgical resections (n = 304, 9%) and chemotherapies (n = 187, 5.6%), p = 0.008. The odd ratios of death were significantly high in patients with old age (≥ 60 years) (OR 1.96, 95% CI 0.94-0.96; p < 0.001), male gender (OR 1.44, 95% CI 0.41-0.47; p < 0.001) CRC stage III (OR 1.54, 95% CI 0.02-1.05; p = 0.041), CRC stage IV (OR 1.69, 95% CI 0.17-1.2; p = 0.009), recent active treatment with chemotherapies (OR 1.35, 95% CI 0.5-0.66; p = 0.023) or surgical resections (OR 1.4, 95% CI 0.8-0.73; p = 0.016) and admission to ICU (OR 1.88, 95% CI 0.85-1.12; p < 0.001) compared to those who survived. CONCLUSION: SARS-CoV-2 infection in CRC patient is not uncommon and results in a mortality rate of 26.2%. Key determinants that lead to increased mortality in CRC patients infected with COVID-19 include older age (≥ 60 years old); male gender; Asian and Hispanic ethnicity; if SARS-CoV-2 was acquired from hospital source; advanced CRC (stage III and IV); if patient received chemotherapies or surgical treatment; and if patient was admitted to ICU, ventilated or experienced ARDS.

Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections.

BACKGROUND: The protection conferred by natural immunity, vaccination, and both against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the BA.1 or BA.2 sublineages of the omicron (B.1.1.529) variant is unclear. METHODS: We conducted a national, matched, test-negative, case-control study in Qatar from December 23, 2021, through February 21, 2022, to evaluate the effectiveness of vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), natural immunity due to previous infection with variants other than omicron, and hybrid immunity (previous infection and vaccination) against symptomatic omicron infection and against severe, critical, or fatal coronavirus disease 2019 (Covid-19). RESULTS: The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). The effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible (-1.1%; 95% CI, -7.1 to 4.6), but nearly all persons had received their second dose more than 6 months earlier. The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9). The effectiveness of previous infection and two doses of BNT162b2 was 55.1% (95% CI, 50.9 to 58.9), and the effectiveness of previous infection and three doses of BNT162b2 was 77.3% (95% CI, 72.4 to 81.4). Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection. Similar results were observed in analyses of effectiveness against BA.1 infection and of vaccination with mRNA-1273. CONCLUSIONS: No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. (Funded by Weill Cornell Medicine-Qatar and others.).

The Era of the Coronavirus Disease 2019 Pandemic: A Review on Dynamics, Clinical Symptoms and Complications, Diagnosis, and Treatment.

Coronavirus disease 2019 (COVID-19) displays a broad spectrum of clinical presentations ranging from lack of symptoms to severe multiorgan system complications and death. Various laboratory assays have been employed in the diagnosis of COVID-19, including: nucleic acid-based tests; antigen tests; and serum testing for anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies. The disease can also be diagnosed based on suggestive clinical features and radiological findings. Until now, remdesivir is the only medication approved for the treatment of COVID-19 by the U.S. Food and Drug Administration (FDA); however, it is anticipated that several anti-SARS-CoV-2 monoclonal antibodies will gain soon approval. Other methods of treatment include supportive care directed toward treating the symptoms. Nevertheless, many studies have recently emerged, showing controversial preliminary results with the off-label medication hydroxychloroquine. Given that all results are still preliminary, including those seen by remdesivir, additional evidence and research are required to identify effective medications that are broadly effective and well tolerated. Importantly, two RNA-based vaccines have recently gained approval from Pfizer and Moderna, with many others still in clinical trials. This article reviews various aspects of COVID-19, including its epidemiology; its evolution and mutational spectrum; and its clinical dynamics, symptoms and complications, diagnosis, and treatment.

COVID-19 as a Recognized Work-Related Disease: The Current Situation Worldwide.

Coronavirus disease 2019 (COVID-19), which is a newly emerging infectious disease worldwide, can be categorized as an occupational disease, because employees, particularly in the healthcare system, can be infected at the workplace. As of December 15, 2020, we summarized the occupational safety and health practices in selected countries on the recognition of COVID-19 as one of the occupational risks. The situation has differed among countries, including the recognition status and whether a specific regulation existed. International organizations, namely the International Labour Organization, World Health Organization, and European Union, should plan and conduct studies on the work-relatedness of COVID-19, propose criteria for recognition, and add the infection to the occupational disease list to provide a basis for specific country regulations. Stakeholders should also act to adjust country-level legislation.

Epidemiological investigation of the first 5685 cases of SARS-CoV-2 infection in Qatar, 28 February-18 April 2020.

OBJECTIVE: To define the epidemiological curve of COVID-19 in Qatar and determine factors associated with severe or critical illness. DESIGN: Case series of first 5685 COVID-19 cases in Qatar. SETTING AND PARTICIPANTS: All confirmed COVID-19 cases in the State of Qatar between 28 February and 18 April 2020. MAIN OUTCOME MEASURES: Number of total and daily new COVID-19 infections; demographic characteristics and comorbidity burden and severity of infection; factors associated with severe or critical illness. RESULTS: Between 28 February and 18 April 2020, 5685 cases of COVID-19 were identified. Median age was 34 (IQR 28-43) years, 88.9% were male and 8.7% were Qatari nationals. Overall, 83.6% had no concomitant comorbidity, and 3.0% had three or more comorbidities. The overwhelming majority (90.9%) were asymptomatic or with minimal symptoms, with 2.0% having severe or critical illness. Seven deaths were observed during the time interval studied. Presence of hypertension or diabetes was associated with a higher risk of severe or critical illness, but age was not. The epidemiological curve indicated two distinct patterns of infection, a larger cluster among expatriate craft and manual workers and a smaller one among Qatari nationals returning from abroad during the epidemic. CONCLUSION: COVID-19 infections in Qatar started in two distinct clusters, but then became more widespread in the population through community transmission. Infections were mostly asymptomatic or with minimal symptoms and associated with very low mortality. Severe/critical illness was associated with presence of hypertension or diabetes but not with increasing age.

Characterization of the SARS-CoV-2 outbreak in the State of Qatar, February 28-April 18, 2020 (preprint)

Objective To define the epidemiologic curve of COVID-19 in Qatar, determine factors associated with severe or critical illness, and study the temporal relation between public health measures and case finding Design Epidemiologic investigation Setting and Participants All confirmed COVID-19 cases in the State of Qatar between February 28 and April 18, 2020 Main Outcome Measures Number of total and daily new COVID-19 infections; demographic characteristics and comorbidity burden and severity of infection; factors associated with severe or critical illness Results Between February 28 and April 18, 2020 (11:00AM local time), 5,685 cases of COVID-19 were identified. Mean age (SD) was 35.8(12.0) years, 88.9% were male and 8.7% were Qatari nationals. Overall, 83.6% had no concomitant comorbidity, and 3.0% had 3 or more comorbidities. The overwhelming majority (90.9%) were asymptomatic or with minimal symptoms, with 2.0% having severe or critical illness. Presence of hypertension or diabetes were associated with a higher risk of severe or critical illness. Seven deaths were observed during the time interval studied. The epidemiologic curve indicated two distinct patterns of infection, a larger cluster among expatriate craft and manual workers, and a smaller one among Qatari nationals returning from abroad during the epidemic. Conclusion COVID-19 infections in Qatar started in two distinct clusters, but then became more widespread in the population through community transmission. Infections were mostly asymptomatic or with minimal symptoms and associated with very low mortality. Severe/critical illness was associated with presence of hypertension or diabetes.