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Item Estimating the Impact of Verification Bias on Celiac Disease Testing(Wolters Kluwer, 2021) Hujoel, Isabel A.; Jansson-Knodell, Claire L.; Hujoel, Philippe P.; Hujoel, Margaux L.A.; Choung, Rok Seon; Murray, Joseph A.; Rubio-Tapia, Alberto; Medicine, School of MedicineGoal: The goal of this study was to estimate the impact of verification bias on the diagnostic accuracy of immunoglobulin A tissue transglutaminase (IgA tTG) in detecting celiac disease as reported by an authoritative meta-analysis, the 2016 Comparative Effectiveness Review (CER). Background: Verification bias is introduced to diagnostic accuracy studies when screening test results impact the decision to verify disease status. Materials and methods: We adjusted the sensitivity and specificity of IgA tTG reported by the 2016 CER with the proportion of IgA tTG positive and negative individuals who are referred for confirmatory small bowel biopsy. We performed a systematic review from January 1, 2007, to July 19, 2017, to determine these referral rates. Results: The systematic review identified 793 articles of which 9 met inclusion criteria (n=36,477). Overall, 3.6% [95% confidence interval (CI): 1.1%-10.9%] of IgA tTG negative and 79.2.2% (95% CI: 65.0%-88.7%) of IgA tTG positive individuals were referred for biopsy. Adjusting for these referral rates the 2016 CER reported sensitivity of IgA tTG dropped from 92.6% (95% CI: 90.2%-94.5%) to 57.1% (95% CI: 35.4%-76.4%) and the specificity increased from 97.6% (95% CI: 96.3%-98.5%) to 99.6% (95% CI: 98.4%-99.9%). Conclusions: The CER may have largely overestimated the sensitivity of IgA tTG due to a failure to account for verification bias. These findings suggest caution in the interpretation of a negative IgA tTG to rule out celiac disease in clinical practice. More broadly, they highlight the impact of verification bias on diagnostic accuracy estimates and suggest that studies at risk for this bias be excluded from systematic reviews.Item High seroprevalence of SARS-CoV-2 among high-density communities in Saudi Arabia(Springer, 2022-06) Almudarra, Sami; Kamel, Shady; Saleh, Eman; Alaswad, Rehab; Alruwaily, Amaal; Almowald, Shaza; Alqunaibet, Ada Mohammed; Almudiaheem, Abdullah; Almutlaq, Hind; Alserehi, Haleema; Almalki, Safar; Bahlaq, Mohannad Abdulhafiz; Alsahafi, Abdullah Jaber; Alsaif, Faisal; Khojah, Abdullah T.; Al‑Tawfiq, Jaffar A.; Asiri, Sari Ibrahim; Assiri, Abdullah; Jokhdar, Hani; Medicine, School of MedicineBackground: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection had been investigated utilizing serology. Materials and methods: This community-based sero-survey was carried out in the neighborhoods of three cities in Saudi Arabia. Results: Of 5629 participants, 2766 (49.1%) were women; and 2148 (38.1%) were 18-34 years of age, and 3645 (64.7%) were from South East Asia. Positive serology was seen in 2825 (50.2% (95% CI: 48.8-51.5%) for SARS-CoV-2 anti-S1 IgG antibodies by ECLIA. Being in the age category of 18-34 years and being from Eastern Mediterranean Region (country A) were associated with higher COVID-19 seropositivity with estimated odds ratio of 1.3 [95% CI 1.1-1.8] and 2.5 [95% CI 1.1.5-4.2] respectively. Gender, social status, education, nationality, symptoms, presence of comorbidities and activity style were positively associated with increased seropositivity. Factors associated negatively with the rate of seropositivity were higher education and having outdoor activity with estimated OR of 0.92 [95% CI 0.46-0.95] and 0.59 [95% CI 0.47-0.74], respectively. Conclusion: The study showed high seroprevalence of SARS-CoV-2 among high density population. Health education campaigns should target middle-aged, those with low education, those living in lower standards and indoor workers.Item Toxoplasma gondii-positive human sera recognise intracellular tachyzoites and bradyzoites with diverse patterns of immunoreactivity(Elsevier, 2018-03) Roiko, Marijo S.; LaFavers, Kaice; Leland, Diane; Arrizabalaga, Gustavo; Pathology and Laboratory Medicine, School of MedicineAntibody detection assays have long been the first line test to confirm infection with the zoonotic parasite Toxoplasma gondii. However, challenges exist with serological diagnosis, especially distinguishing between acute, latent and reactivation disease states. The sensitivity and specificity of serological tests might be improved by testing for antibodies against parasite antigens other than those typically found on the parasite surface during the acute stage. To this end, we analysed the reactivity profile of human sera, identified as positive for anti-Toxoplasma gondii IgG in traditional assays, by indirect immunofluorescence reactivity to acute stage intracellular tachyzoites and in vitro-induced latent stage bradyzoites. The majority of anti-Toxoplasma gondii IgG positive sera recognised both intracellularly replicating tachyzoites and in vitro-induced bradyzoites with varying patterns of immune-reactivity. Furthermore, anti-bradyzoite antibodies were not detected in sera that were IgM-positive/IgG-negative. These results demonstrate that anti-Toxoplasma gondii-positive sera may contain antibodies to a variety of antigens in addition to those traditionally used in serological tests, and suggest the need for further investigations into the utility of anti-bradyzoite-specific antibodies to aid in diagnosis of Toxoplasma gondii infection.Item Validity of self-reported history of Chlamydia trachomatis infection(Elsevier, 2017-04) Frisse, Ann C.; Marrazzo, Jeanne M.; Tutlam, Nhial T.; Schreiber, Courtney A.; Teal, Stephanie B.; Turok, David K.; Peipert, Jeffrey F.; Obstetrics and Gynecology, School of MedicineBACKGROUND: Chlamydia trachomatis infection is common and largely asymptomatic in women. If untreated, it can lead to sequelae such as pelvic inflammatory disease and infertility. It is unknown whether a patient's self-reported history of Chlamydia trachomatis infection is a valid marker of past infection. OBJECTIVE: Our objective was to evaluate the validity of women's self-reported history of Chlamydia trachomatis infection compared with Chlamydia trachomatis serology, a marker for previous infection. STUDY DESIGN: We analyzed data from the Fertility After Contraception Termination study. We compared participants' survey responses with the question, "Have you ever been told by a health care provider that you had Chlamydia?" to serological test results indicating the presence or absence of antibodies to Chlamydia trachomatis as assessed by a microimmunofluorescence assay. Prevalence of past infection, sensitivity, specificity, predictive values, and likelihood ratios were calculated. The Cohen's kappa statistic was computed to assess agreement between self-report and serology. RESULTS: Among 409 participants, 108 (26%) reported having a history of Chlamydia trachomatis infection, whereas 146 (36%) had positive serological test results. Relative to positive microimmunofluorescence assay, the sensitivity and specificity of self-reported history of Chlamydia trachomatis infection were 52.1% (95% confidence interval, 43.6-60.4%) and 87.8% (95% confidence interval, 83.3-91.5%), respectively. The positive predictive value of the self-report was 70.4% (95% confidence interval, 60.8-78.8%), and the negative predictive value was 76.7% (95% confidence interval, 71.6-81.4%). The likelihood ratio was found to be 4.28. Agreement between self-report and serology was found to be moderate (kappa = 0.42, P < .001). CONCLUSION: Self-reported history of Chlamydia trachomatis infection commonly yields false-negative and false-positive results. When definitive status of past Chlamydia trachomatis infection is needed, serology should be obtained.