The characteristics of CALR mutations in myeloproliferative neoplasms: a clinical experience from a tertiary care center in Qatar and a literature review.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are hematological disorders characterized by abnormal production of myeloid cells due to genetic mutations. Since 2013, researchers have identified somatic mutations in the Calreticulin (CALR) gene, primarily insertions or deletions, in two Philadelphia chromosome-negative MPNs; essential thrombocytosis (ET) and primary myelofibrosis (PMF), and occasionally in chronic myelomonocytic leukemia (CMML). This study aims to identify the various types of CALR mutations and their impact on CALR-positive MPN patients' clinical manifestations and outcomes. METHODS: A single-center retrospective study was conducted. The data was collected from pre-existing records. The study was carried out on Philadelphia-negative MPN patients who were being followed up on at the NCCCR (National Center for Cancer Care and Research) to assess the clinical manifestation and outcome of disease treatment. All patients included, were followed in our center between January 1, 2008, and November 20, 2021. RESULTS: A total of 50 patients with CALR-positive MPN were reviewed with a median follow-up of three years (1-11). This cohort included 31 (62%) patients with ET, 10 (20%) patients with PMF, and 9 (18%) patients with prefibrotic myelofibrosis (pre-MF). The study involved 38 (76%) male and 12 (24%) female patients. There were 16 (32%) patients diagnosed before the age of 40, 24 (48%) patients diagnosed between the ages of 40 and 60; and 10 (20%) patients diagnosed after the age of 60. Molecular analysis showed 24 (48%) patients with CALR type 1, 21 (42%) patients with CALR type 2, and 5 (10%) patients with none Type 1, none Type 2 CALR mutations. Two patients have double mutations; 1(2%) with none Type 1, none Type 2 CALR and JAK2 mutations, and 1(2%) with CALR type 1 and MPL mutations. The thrombotic events were 3 (6%) venous thromboembolisms, 3 (6%) abdominal veins thromboses, 2 (4%) strokes, and 4 (8%) ischemic cardiac events. Only 4 (8%) patients progressed to Myelofibrosis and were carrying CALR 1 mutations, and 1 (2%) patient progressed to AML with CALR 2 mutation. CONCLUSION: The data shows a significant rise in CALR-positive MPN diagnoses in younger people, emphasizing the need for a better assessment tool to improve disease management and reduce complications.

Development and validation of a multi-dimensional COVID-19 vaccine hesitancy questionnaire.

Background: Since the emergence of the COVID-19 pandemic, vaccines have been developed to tackle the disease. However, many people worldwide were not confident enough to take the vaccines. Developing a questionnaire to measure COVID-19 vaccine hesitancy will give the health authorities and policymakers a clear picture to establish appropriate interventions addressing vaccine hesitancy among the community. Methods: In this study, we used a mixed-method design over two phases. Phase 1 entailed a qualitative approach to developing the questionnaire, including a literature search, expert panel review, and focus group discussion. Phase 2 used a quantitative method for establishing the content and construct validity of the questionnaire via exploratory and confirmatory factor analysis (EFA & CFA). Internal consistency was checked using Cronbach's Alpha and intraclass correlation coefficient. Results: We developed a 50-item instrument designed to measure COVID-19 vaccine hesitancy among adults in the state of Qatar. The study involved 545 adult participants. In terms of content validity, our study showed a value of 0.92 for the scale-level content validity index based on the average and a value of 0.76 for the scale-level content validity index - universal agreement. In the EFA, the Kaiser-Meyer-Olkin measure of sampling adequacy was calculated at 0.78, with statistical significance (P = 0.001). Regarding model fit indices of the seven-factor model, our findings showed an acceptable model-data-fit, with a relative chi-square: 1.7 (<3), Root mean square error of approximation: 0.05 (<0.08), PCLOSE = 0.41, Comparative fit index: 0.909, Tucker-Lewis index: 0.902, Incremental Fit Index: 0.910 and, Standardized Root mean square residual: 0.067 (<0.08). The seven-factor model of the questionnaire met the criterion of good internal consistency (Cronbach's alpha = 0.73). Conclusion: This tool is deemed of methodological merits in terms of validity, reliability, and determining the underlying conceptual structure of COVID-19 vaccine hesitancy and its associating factors.

Validation of rapid antibody (IgG-IgM) test kit for SARS-CoV-2 infection in Qatar.

BACKGROUND: In response to the growing coronavirus disease 2019 (COVID-19) pandemic and the shortage of laboratory based molecular testing capacity and reagents, multiple diagnostic test manufacturers have developed rapid and easy to use devices to facilitate testing outside laboratory settings. These kits are either based on detection of proteins from SARS-CoV-2 virus or detection of antigen or human antibodies generated in response to the infection. However, it is important to understand their performance characteristics and they must be validated in the local population setting. DESIGN AND METHODS: The objective is to assess the validity of the rapid test for IgG and IgM immunoglobulins compared to the current gold standard reverse transcription polymerase chain reaction (RT-PCR) test. A total of 16951 asymptomatic individuals were tested by the Ministry of Public Health track-and-trace team using both rapid immunodiagnostic test and RT-PCR as part of screening across various random settings with potential risk of community interaction prior to gradual lifting of restrictions in Qatar.  Rapid test was considered to be posiive if both IgG and IgM are positive, while only IgG/IgM positive was considered as rapid test negative. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: The sensitivity of rapid test kit was found to be 0.9%, whereas the specificity was found to be 97.8%. the PPV was found to be 0.3% whereas the NPV was found to be 99.4%. CONCLUSIONS: Based on the outcome and results of the study, it appears that the sensitivity and PPV of the rapid antibody test are low. As such, this test is not recommended for use to assist in taking clinic-based decisions or decisions related to quarantine/isolation.

Can the cycle threshold (Ct) value of RT-PCR test for SARS CoV2 predict infectivity among close contacts?

BACKGROUND: COVID-19 global pandemic is an unprecedented health emergency. Rapid identification and isolation of infected individuals is crucial. Qatar's National Health Strategic Command Group adopted a cut off 30 for Ct value of RT-PCR result of a positive case to decide on duration of isolation and quarantine period for their close contacts. AIM: To test if Ct value cut off 30 reflects on the infectivity potential among close contacts. METHODOLOGY: All positive cases reported during July' 2020 whose contacts had been traced and swabbed were extracted from database after removing personal identifiers. Close-contact was defined as anybody who has been within 2 m distance of a confirmed positive case for 15 min or more, without any personal protection equipment. Descriptive analysis was done and test of significance of difference in positivity among the contacts of those with ct < 30 and >30 was done. RESULTS: 2308 COVID-19 positive cases were followed up. More than three-quarters had a Ct value < 30, with a mean Ct value of 24.05(+6.48). On an average 6 contacts were swabbed per case. More than half the positive cases followed up had at least one secondary case, with median positivity rate 12.5%. A significant relation was noted between Ct value cut-off 30 and secondary transmission (1.5 times more risk among those with Ct value < 30). A significant difference was noted in median positivity rate between close contacts of positive cases with Ct value > 30 or <30. CONCLUSION: Further studies combining PCR assays, culture studies and contact tracing are needed to define which factors can be used to reliably predict the infectious status of patients with COVID-19.