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

Associations of Vaccination and of Prior Infection with Positive PCR Test Results for SARS-CoV-2 in Airline Passengers Arriving in Qatar

The SARS-CoV-2 pandemic has severely affected international travel. With efficacious COVID-19 vaccines available, Qatar implemented a pilot program between February 18 and April 26, 2021, to ease travel restrictions by waiving the quarantine requirement for vaccinated residents who received their second vaccine dose at least 14 days before arrival. The program still required a polymerase chain reaction (PCR) test to be performed on each passenger on arrival at Hamad International Airport, Qatar’s international travel gate. We investigated the incidence of PCR-positive test results in arriving passengers

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)

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)

COVID-19 Disease Severity in Persons Infected with Omicron BA.1 and BA.2 Sublineages and Association with Vaccination Status

[No abstract available

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

Darunavir-Cobicistat versus Lopinavir-Ritonavir for COVID-19 Pneumonia: Qatar's Experience

Background: Coronavirus Disease 2019 (COVID-19) was first discovered in China and resulted in a pandemic crisis. 1,2 Many agents were investigated with inconclusive outcomes. 3 This study was conducted to compare the efficacy and safety outcomes of darunavir-cobicistat versus lopinavir-ritonavir in the treatment of patients with COVID-19. Methods: This retrospective, multicenter, observational study was conducted on adult patients hospitalized in COVID-19 facilities in Qatar. Patients were included if they had pneumonia and received darunavir-cobicistat or lopinavir-ritonavir for at least three days as part of their COVID-19 treatment. Data were collected from patients' electronic medical records. The primary outcome was a composite endpoint of time to clinical improvement and/or virological clearance. Data were analyzed descriptively and inferential statistics were applied at alpha level of 0.05. Results: A total of 400 patients' medical records were analyzed, of whom 100 received darunavir-cobicistat and 300 received lopinavir-ritonavir. The majority of patients were male (92.5%), with a mean (SD) time from symptoms onset to start of therapy of 7.57 days (SD 4.89). Patients who received lopinavir-ritonavir had a significantly faster time to the primary composite endpoint of clinical improvement and/or virological clearance than patients who 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) [Figure 1]. Patients who received lopinavir-ritonavir had a 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 those who received 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) [Figure 2]. No significant difference in adverse events incidence or severity was observed. Conclusion: In patients with COVID-19, early treatment with lopinavir-ritonavir was associated with faster time to reach the primary composite endpoint of clinical improvement and/or virological clearance than treatment with darunavir-cobicistat. Future trials are warranted to confirm these findings.qscienc

Effectiveness of the SARS-CoV-2 mRNA Vaccines in Pregnant Women

Pregnancy may increase the risk of adverse maternal and neonatal outcomes in SARS-CoV-2 infection. Effectiveness of SARS-CoV-2 vaccines in pregnant women is not known. Using a test-negative case-control study, we determined the vaccine effectiveness of mRNA vaccines in preventing confirmed SARS-CoV-2 infection in pregnant women at a national referral hospital, which handles > 75% of the deliveries in Qatar. Among 2,020 pregnant women who met the study criteria, 397 had a positive SARS-CoV-2 RT-PCR and 1,623 had a negative test. Vaccine effectiveness ≥ 14 days after the second dose was 67.7% (95%CI 30.5–86.9), while vaccine effectiveness ≥ 14 days after the first dose but before the second dose was 40.3% (95%CI 0.0-80.4). There were nine severe/critical disease cases, and no deaths in the PCR-positive pregnant women, all among unvaccinated. The mRNA vaccines provide high level of protection against documented SARS-CoV-2 infection, which supports including pregnant women in vaccination campaigns

Molecular epidemiology of influenza, RSV, and other respiratory infections among children in Qatar: A six years report (2012–2017)

Background: Studies on the etiology of respiratory infections among children in Qatar and surrounding countries are limited. Objectives: To describe the prevalence and seasonality of RSV, influenza, and other respiratory pathogens among children in Qatar. Methods: We retrospectively collected and analyzed data of 33,404 children (<15 years) presented with influenza-like illness from 2012 to 2017. Results: At least one respiratory pathogen was detected in 26,138 (78%) of patients. Together, human rhinoviruses (HRV), respiratory syncytial virus (RSV), and influenza viruses comprised nearly two-thirds of all cases, affecting 24%, 19.7%, and 18.5%, respectively. A prevalence of 5-10% was recorded for adenovirus, parainfluenza viruses (PIVs), human bocavirus (HboV), and human coronaviruses (HCoVs). Human metapneumovirus (HMPV), enteroviruses, M. pneumonia, and parechovirus had prevalences below 5%. While RSV, influenza, and HMPV exhibited strong seasonal activity in the winter, HRV was active during low RSV and influenza circulation. The burden of RSV exceeds that of influenza among young age groups, whereas influenza correlated positively with age. Further, HRV, adenovirus, influenza, and RSV infection rates varied significantly between male and females. Conclusion: This comprehensive multi-year study provides insights into the etiology of ILI among children in Qatar, which represents the Gulf region. Our results reinforce the significance of active surveillance of respiratory pathogens to improve infection prevention and control strategies, particularly among children

Outcomes Among Patients with Breakthrough SARS-CoV-2 Infection After Vaccination.

BACKGROUND: Breakthrough infections after SARS-CoV-2 vaccination have been reported. Clinical outcomes in these persons are not widely known. METHODS: We evaluated all vaccinated persons with breakthrough infection ≥14 days after the second vaccine dose and unvaccinated controls matched on age, sex, nationality, and reason for testing between December 23, 2020 and March 28, 2021 in Qatar. Our primary outcome was severe disease defined as hospitalization, mechanical ventilation, or death. RESULTS: Among 456 persons cases of breakthrough infection and 456 unvaccinated matched controls with confirmed infection, median age was 45 years, 60.7% were males, and ≥1 comorbid condition was present in 61.2% of the vaccinated and 47.8% of the unvaccinated persons (P=0.009). Severe disease was recorded in 48 (10.5%) of the vaccinated and 121 (26.5%) of the unvaccinated group (P40-60 years, HR 2.32; >60-70 years, HR 4.34; >70 years, HR 5.43); presence of symptoms at baseline (HR 2.42, 95%CI 1.44-4.07); and being unvaccinated (HR 2.84, 95%CI 1.80-4.47). CONCLUSIONS: In persons with breakthrough SARS-CoV-2 infection, increasing age is associated with a higher risk of severe disease or death, while vaccination is associated with a lower risk. Presence of comorbidities was not associated with severe disease or death among persons with breakthrough infection