Warfarin-Rifampin-Gene (WARIF-G) Interaction: A Retrospective, Genetic, Case-Control Study.

Warfarin is extensively metabolized by cytochrome P450 2C9 (CYP2C9). Concomitant use with the potent CYP2C9 inducer, rifampin, requires close monitoring and dosage adjustments. Although, in theory, warfarin dose increase should overcome this interaction, most reported cases over the last 50 years have not responded even to high warfarin doses, but some have responded to modest doses. To investigate the genetic polymorphisms' impact on this unexplained interpatient variability, we performed genotyping of CYP2C9, VKORC1, and CYP4F2 for warfarin and rifampin concomitant receivers from 2016 to 2022 at Hamad Medical Corporation, Doha, Qatar. We identified and included 36 patients: 22 responders and 14 nonresponders. Warfarin-responders were significantly more likely to have one or more warfarin-sensitizing CYP2C9/VKORC1 alleles than nonresponders (odds ratio = 23.2, 95% confidence interval = 3.2-195.6; P = 0.0001). The mean genetic-based pre-interaction calculated dose was significantly lower for responders than for nonresponders (P < 0.001); and was negatively correlated with warfarin sensitivity index (WSI) (r = -0.58; P = 0.0002). The median percentage time in therapeutic range and mean WSI were significantly higher in the warfarin-sensitizing CYP2C9/VKORC1 alleles carriers than noncarriers (P = 0.017 and 0.0004, respectively). Whereas the warfarin-sensitizing CYP2C9/VKORC1 genotypes were associated with modest on-rifampin warfarin dose requirements, the noncarriers would have required more than double these doses to respond. Warfarin-sensitizing CYP2C9/VKORC1 genotypes and low genetic-based warfarin calculated doses were associated with higher warfarin sensitivity and better anticoagulation quality in patients receiving rifampin concomitantly.

The Role of Post-Bronchoscopy Sputum Examination in Screening for Active Tuberculosis.

Early diagnosis is a fundamental component of global tuberculosis control. The objective of this study was to evaluate the diagnostic yield of post-bronchoscopy sputum (PBS) testing as part of a tuberculosis diagnostic work-up. All new residents in the State of Qatar undergo a tuberculosis (TB) screening program. Those with abnormal chest radiology, negative sputum acid-fast bacilli (AFB) smears, and nucleic acid amplification testing (NAAT) for M. tuberculosis, undergo an additional bronchoscopic evaluation for TB. We prospectively enrolled individuals who were going to undergo bronchoscopy to provide two PBS samples for AFB smears and mycobacterial cultures between 18 September 2018 and 12 March 2021. A total of 495 individuals, with a median age of 31 years, were included. The majority of the patients were males (329, 66.5%). The most frequent country of origin was India (131, 26.5%) followed by the Philippines (123, 24.8%). The addition of PBS to bronchoalveolar lavage (BAL) testing allowed microbiological confirmation of tuberculosis in an additional 13 patients (3.9%), resulting in improved sensitivity (from 77.9% to 81.9%), negative predictive value (from 69.2% to 73.2%), and negative likelihood ratio (from 0.22 to 0.18). Where resources are available, the incorporation of routine PBS examination as part of tuberculosis diagnostic work-up can enhance the diagnostic yield.

Prevalence and clinical significance of antiphospholipid antibodies in patients with coronavirus disease 2019 admitted to intensive care units: a prospective observational study.

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-ß2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1-6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

COVID-19 unfolding filariasis: The first case of SARS-CoV-2 and Wuchereria bancrofti coinfection.

With the evolution of the Coronavirus Disease 2019 (COVID-19) pandemic, the number of patients brought to medical attention has increased. This has led to the unmasking of many coexisting occult infections and comorbidities such as tuberculosis, dengue, human immunodeficiency viral infection, diabetes, and hypertension. We report the first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, unveiling the diagnosis of asymptomatic filariasis. A 37-year-old gentleman presented with shortness of breath, fever, and cough. He was found to have COVID-19 pneumonia. During his stay, microfilaria of Wuchereria bancrofti was detected incidentally on a blood smear exam. Consequently, the patient received appropriate treatment for both conditions. In order not to miss relevant concomitant diagnoses, it is prudent to keep a broad differential diagnosis when faced with SARS-CoV-2-infected patients; this is especially true when atypical symptoms are present or in areas endemic with other infections.

Drug-resistant tuberculosis: an experience from Qatar.

This study was conducted to evaluate the characteristics, treatment outcome and risk factors associated with 223 drug-resistant tuberculosis (DR-TB) cases in the State of Qatar. A descriptive records-based retrospective study was conducted on patients registered at Communicable Disease Centre (CDC), Qatar to all consecutive microbiologically confirmed tuberculosis cases for the period January 2010 - March 2015. Demographic, clinical data, drug-resistance pattern of isolated mycobacteria and treatment outcome was assessed for the patient who completed their treatment in Qatar. Of 3301 patients with positive M. tuberculosis culture were analyzed; 223 (6.7%) were resistant to at least one drug. The overall prevalence of multi-d rug resistant TB (MDR-TB) was 1.2% (n = 38) of patients. A former resident of Indian sub contents was the most common demographic characteristic observed (64.1%). The outcome of treatment was assessed for 85 resistant cases with follow-up after completion of treatment. Cure and relapse rates were 97.6%, and 2.4%, respectively. Drug-resistant TB in Qatar is influenced by migration where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation, and drug-susceptibility testing should be the standard of care.

Acinetobacter Infections among Adult Patients in Qatar: A 2-Year Hospital-Based Study.

This retrospective study was conducted at Hamad General Hospital, Qatar, to describe the demographic data, clinical features underlying diseases, antimicrobial susceptibility, and outcome of A. baumannii infection. It involved all adult patients 15 years of age or older who were managed at Hamad General Hospital for A. baumannii infection from January 1, 2012, to December 31, 2013. We identified a total of 239 patients with A. baumannii infection, of which 182 (76.2%) were males. The mean age was 49.10 ± 19.57 years. The majority of the episodes (25.1%) occurred in elderly patients (≥65 years) and the most commonly identified site of A. baumannii infection was the respiratory tract, 117 (48.9%). Most episodes of infection, 231 (96.7%), were hospital-acquired and high rate of nosocomial infections occurred in the medical intensive care unit, 66 (28.6%). All patients had underlying medical conditions. Maximum resistance was seen to cefotaxime, 147 (58.3%), and minimum resistance was seen to colistin, 2 (1.4%). Of the 239 isolates, 102 (42.7%) were susceptible and 137 (57.3%) were multidrug-resistant. The in-hospital mortality in our study was 31%. Male gender, multidrug resistance, and septic shock were found to be independent mortality predictors.