Statins Formulary Selection in Qatar, Based on Multi-Indication Pharmacotherapeutic Multi-Criteria Scoring, and Clinician Preference

Purpose: Statins selection for the largest hospital formulary in Qatar is not systematic, not comparative, not cost saving, and does not consider the multi-indication nature of statins. There are no literature reports of multi-indication based comparative scoring models of statins, or reports of statins selection criteria weights that are primarily based on local clinicians' preference and experiences. The study sought to comparatively evaluate statins for first-line therapy in Qatar, and to evaluate the economic impact of this. Methods: An evidence-based, multi-indication, multi-criteria pharmacotherapeutic model was developed for the scoring of statins. This was from the perspective of the main healthcare provider in Qatar, the Hamad Medical Corporation (HMC). Literature and an expert panel informed the selection criteria of statins. Relative weighting of selection criteria was based on the input of the relevant local clinician population. The targeted clinician population was of all specialists and consultants in the departments of cardiology, internal medicine, and nephrology in HMC. Statins were comparatively evaluated according to their total pharmacotherapeutic selection scores, with only the statins that score more than 95% of the highest scoring statin getting recommended for formulary inclusion. Remaining statins that score more than 90% of the highest scoring statin will also be considered, but as non-formulary alternative. The remaining did not progress. Sensitivity analyses were conducted to investigate the robustness of the study outcomes against variations in study inputs. These included deterministic, probabilistic as well as scenario analyses, via @Risk-5.5 Palisade, USA. Findings: This is the first literature report to inform formulary inclusion in Qatar or the Middle Eastern region, and the first in literature that comparatively score statins based on multiple indications, as compared to the typical pharmacoeconomics evaluation method, comparing differences in cost and effect between two statins for an indication of interest to guide the formulary inclusion decisions. With 95% confidence interval and 5% margin of error, the scoring model was successfully developed. Selection criteria comprised 28 sub-criteria, under the following main criteria: clinical efficacy, best publish evidence and experience, adverse effects, drug interaction, dosing time, and fixed dose combination availability. Outcome measures of multiple indications related to effects on LDL-cholesterol, HDL-cholesterol, triglyceride, total cholesterol, and c-reactive protein. Atorvastatin, pravastatin and rosuvastatin exceeded defined pharmacotherapeutic thresholds. Atorvastatin and pravastatin were suggested for first-line use in HMC, followed by rosuvastatin as a non-formulary alternative. Fluvastatin and simvastatin were recommended for exclusion from any hospital drug lists. This was estimated to produce 17.6% in cost savings, reducing the annual statins expenditure from QAR 152, 118, 200 to QAR 125, 367, 620;. Sensitivity analyses confirmed the robustness of the evaluation outcomes. The comparative criterion that affected the study conclusion was the availability of fixed dose combination. The possibility of 30% non-formulary drug utilization scenario resulted in an annual expenditure of QAR 129, 654, 180, still associated with up to 14.8% cost saving. Implications: Incorporating a comparative evaluation of statins in Qatari practices, based on a locally-developed, transparent, multi-indication, multi-criteria scoring model, has the potential to considerably reduce the expenditure on statins. Atorvastatin and pravastatin should be the first-line statin therapies in the main Qatari healthcare provider, with rosuvastatin as an alternative. Important, is that the study results are consistent with published clinical guidelines, as well as with practices in overseas.qscienc

Middle East respiratory syndrome coronavirus in dromedary camels: An outbreak investigation

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe lower respiratory tract infection in people. Previous studies suggested dromedary camels were a reservoir for this virus. We tested for the presence of MERS-CoV in dromedary camels from a farm in Qatar linked to two human cases of the infection in October, 2013. Methods: We took nose swabs, rectal swabs, and blood samples from all camels on the Qatari farm. We tested swabs with RT-PCR, with amplification targeting the E gene (upE), nucleocapsid (N) gene, and open reading frame (ORF) 1a. PCR positive samples were tested by different MERS-CoV specific PCRs and obtained sequences were used for phylogentic analysis together with sequences from the linked human cases and other human cases. We tested serum samples from the camels for IgG immunofluorescence assay, protein microarray, and virus neutralisation assay. Findings: We obtained samples from 14 camels on Oct 17, 2013. We detected MERS-CoV in nose swabs from three camels by three independent RT-PCRs and sequencing. The nucleotide sequence of an ORF1a fragment (940 nucleotides) and a 4·2 kb concatenated fragment were very similar to the MERS-CoV from two human cases on the same farm and a MERS-CoV isolate from Hafr-Al-Batin. Eight additional camel nose swabs were positive on one or more RT-PCRs, but could not be confirmed by sequencing. All camels had MERS-CoV spike-binding antibodies that correlated well with the presence of neutralising antibodies to MERS-CoV. Interpretation: Our study provides virological confirmation of MERS-CoV in camels and suggests a recent outbreak affecting both human beings and camels. We cannot conclude whether the people on the farm were infected by the camels or vice versa, or if a third source was responsible. Funding: European Union projects EMPERIE (contract number 223498), ANTIGONE (contract number 278976), and the VIRGO consortium

Challenges in diagnosing polyethylene glycol and polysorbate 80 allergies: implications for allergic reactions in COVID-19 mRNA vaccination program: experience from Qatar

IntroductionCOVID-19 vaccination has been a key intervention in reducing the severity of symptoms; however, concerns about vaccine safety, particularly regarding allergic reactions, arose early on. Healthcare workers faced the challenge of addressing these concerns to ensure safe vaccine administration. This study aimed to review the practical aspects of using allergy skin testing for COVID-19 vaccine excipients in patients with a history of allergic reactions developed following mRNA COVID-19 vaccination.MethodsA retrospective chart review was conducted for patients who reported allergic reactions after the COVID-19 vaccine and underwent allergy skin testing for COVID-19 vaccine excipients in the Adult Allergy and Immunology Service at Hamad Medical Corporation, Doha, Qatar. The testing protocol, developed based on published data during the pandemic, included skin prick (SPT) and intradermal (ID) testing using medications containing polysorbate 80 and polyethylene glycol (PEG), the primary excipients in the COVID-19 vaccines suspected of triggering allergic responses.ResultsOf the 88 patients reviewed, 38 reported different types of allergic reactions following mRNA COVID-19 vaccination, with the majority being female. Anaphylaxis was reported in 21.1% of the patients, while the remaining experienced less severe allergic reactions. All patients underwent SPT and ID testing with PEG and polysorbate 80. By SPT, two patients tested positive for PEG and none for polysorbate 80. By ID, seven tested positive for polysorbate 80 and one for PEG. Among patients who experienced anaphylaxis, 50% had positive allergy test results. Twenty-three percent of patients with negative test results could receive additional vaccine doses without adverse reactions.ConclusionManaging patients with a history of allergic reactions to the COVID-19 vaccine is challenging, as the exact mechanisms and accurate and valid allergy testing are yet to be determined. In our cohort, most patients had mild allergic reactions following vaccination. Excipients' allergy skin testing has helped to reduce vaccine hesitancy despite its questionable utility in clinical practice

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities.

The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly (-value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.This work was supported by Qatar University under internal grant (QUCG-BRC-20/21-1) and Qatar National Research Fund grant under grant (RRC-2-039)

Virus-Induced Host Chemokine CCL2 in COVID-19 Pathogenesis: Potential Prognostic Marker and Target of Anti-Inflammatory Strategy

A wide variety of inflammatory mediators, mainly cytokines and chemokines, are induced during SARS CoV-2 infection. Among these proinflammatory mediators, chemokines tend to play a pivotal role in virus-mediated immunopathology. The C-C chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1) is a potent proinflammatory cytokine and strong chemoattractant of monocytes, macrophages and CD4+ T cells bearing C-C chemokine receptor type-2 (CCR2). Besides controlling immune cell trafficking, CCL2 is also involved in multiple pathophysiological processes including systemic hyperinflammation associated cytokine release syndrome (CRS), organ fibrosis and blood coagulation. These pathological features are commonly manifested in severe and fatal cases of COVID-19. Given the crucial role of CCL2 in COVID-19 pathogenesis, the CCL2:CCR2 axis may constitute a potential therapeutic target to control virus-induced hyperinflammation and multi-organ dysfunction. Herein we describe recent advances on elucidating the role of CCL2 in COVID-19 pathogenesis, prognosis, and a potential target of anti-inflammatory interventions.This work is is supported by: - the research grant (MRC-01-21-874) from the Medical Research Centre, Hamad Medical Corporation, Doha, Qatar to AWA. - the Medical Research Centre grant (MRC\u201001\u201021\u2010874), Hamad Medical Corporation, Doha, Qatar to AWA

Epidemiology of respiratory infections among adults in Qatar (2012-2017).

Limited data is available about the etiology of influenza like illnesses (ILIs) in Qatar. This study aimed at providing preliminary estimates of influenza and other respiratory infections circulating among adults in Qatar. We retrospectively collected data of about 44,000 patients who visited Hamad General Hospital clinics, sentinel sites, and all primary healthcare centers in Qatar between 2012 and 2017. All samples were tested for influenza viruses, whereas about 38,000 samples were tested for influenza and a panel of respiratory viruses using Fast Track Diagnostics (FTD) RT-PCR kit. Among all ILIs cases, 20,278 (46.5%) tested positive for at least one respiratory pathogen. Influenza virus was predominating (22.6%), followed by human rhinoviruses (HRVs) (9.5%), and human coronaviruses (HCoVs) (5%). A detection rate of 2-3% was recorded for mycoplasma pneumonia, adenoviruses, human parainfluenza viruses (HPIVs), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ILIs cases were reported throughout the year, however, influenza, RSV, and HMPV exhibited strong seasonal peaks in the winter, while HRVs circulated more during fall and spring. Elderly (>50 years) had the lowest rates of influenza A (13.9%) and B (4.2%), while presenting the highest rates of RSV (3.4%) and HMPV (3.3%). While males had higher rates of HRVs (11.9%), enteroviruses (1.1%) and MERS CoV (0.2%), females had higher proportions of influenza (26.3%), HPIVs (3.2%) and RSV (3.6%) infections. This report provides a comprehensive insight about the epidemiology of ILIs among adults in the Qatar, as a representative of Gulf States. These results would help in improvement and optimization of diagnostic procedures, as well as control and prevention of the respiratory infections.This study was supported by funds from Hamad Medical Corporation (grant # 16335/16) and Qatar University (grant # QUCG-BRC-2018/2019-1)

Darunavir-cobicistat versus lopinavir-ritonavir in the treatment of COVID-19 infection (DOLCI): A multicenter observational study

Background Coronavirus Disease 2019 (COVID-19) is an evolving pandemic that urged the need to investigate various antiviral therapies. This study was conducted to compare efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in treating patients with COVID-19 pneumonia. Methods and findings This retrospective, multicenter, observational study was conducted on adult patients hospitalized in one of the COVID-19 facilities in Qatar. Patients were included if they received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatments. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Descriptive and inferential statistics were used at alpha level of 0.05. A total of 400 patients was analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. Majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (4.89). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement and/or virological clearance than patients received darunavir-cobicistat (4 days [IQR 3-7] vs. 6.5 days [IQR 4-12]; HR 1.345 [95%CI: 1.070-1.691], P = 0.011). Patients received lopinavir-ritonavir had significantly faster time to clinical improvement (5 days [IQR 3-8] vs. 8 days [IQR 4-13]; HR 1.520 (95%CI: 1.2-1.925), P = 0.000), and slower time to virological clearance than darunavir-cobicistat (25 days [IQR 15-33] vs. 21 days [IQR 12.8-30]; HR 0.772 (95%CI: 0.607-0.982), P = 0.035). No significant difference in the incidence or severity of adverse events between groups. The study was limited to its retrospective nature and the possibility of covariates, which was accounted for by multivariate analyses. Conclusion In patients with COVID-19 pneumonia, early treatment with lopinavir-ritonavir was associated with faster time to clinical improvement and/or virological clearance than darunavir-cobicistat. Future trials are warranted to confirm these findings.Scopu