Sidra Medicine Research Articles

Clostridioides difficile Infections in Children: What Is the Optimal Laboratory Diagnostic Method?

The diagnosis of Clostridioides difficile infection (CDI) in the pediatric population is complicated by the high prevalence of asymptomatic colonization, particularly in infants. Many laboratory diagnostic methods are available, but there continues to be controversy over the optimal laboratory testing approach to diagnose CDI in children. We evaluated commonly used C. difficile diagnostic commercial tests in our pediatric hospital population at Sidra Medicine in Doha, Qatar. Between June and December 2023, 374 consecutive stool samples from pediatric patients aged 0-18 years old were tested using: Techlab C. diff Quik Chek Complete, Cepheid GeneXpert C. difficile, QIAstat-Dx Gastrointestinal Panel, and culture using CHROMagar C. difficile. The results of these tests as standalone methods or in four different testing algorithms were compared to a composite reference method on the basis of turnaround time, ease of use, cost, and performance characteristics including specificity, sensitivity, negative predictive value, and positive predictive value. Our study showed variability in test performance of the different available assays in diagnosing CDI. In our population, a testing algorithm starting with Cepheid GeneXpert C. difficile PCR assay or QIAstat-Dx Gastrointestinal panel as a screening test followed by toxin immunoassay for positive samples using the Techlab C. diff Quik Chek Complete kit showed the best performance (100% specificity and 100% positive predictive value) when combined with clinical review of the patient to assess risk factors for CDI, clinical presentation, and alternative causes of diarrhea.

Qatar’s genetic counseling landscape: Current insights and future prospects

Genetic counseling is a dynamic and rapidly growing field. In Qatar, the significance of genetic counseling is underscored by the distinctive demographic characteristics of the population, including elevated rates of consanguinity and larger family sizes, contributing to the increased incidence of many genetic conditions. This emphasizes the crucial role of genetic counseling in addressing the specific needs of the community. Over the past decade, key health care institutions in Qatar, such as Hamad Medical Corporation and Sidra Medicine, have significantly expanded genetic counseling services encompassing premarital, reproductive, prenatal, pediatric, adult, and cancer care. This multifaceted approach reflects Qatar’s health care system’s commitment to addressing various aspects of genetic health and well-being across different life stages.A pivotal milestone in the field’s development in Qatar was the establishment of a genetic counseling master’s program at Qatar University in 2018, showcasing the country’s dedication to fostering indigenous expertise in genetic counseling with the necessary competencies and cultural sensitivity to address the unique genetic counseling needs of the population. The recognition of genetic counseling as a profession and the licensure by the Ministry of Public Health in Qatar is another key achievement to ensure the high quality of service and protection of the profession. Contributing to global genetic knowledge, various academic and research entities in Qatar are conducting genetic/genomic/genetic counseling research toward advancing precision medicine in the country, and initiatives such as the Qatar Biobank and Qatar Genome Program have played a major role in catalyzing these efforts.

Persistent Obstructive Sleep Apnea Post-adenotonsillectomy in Children.

Background Childhood obstructive sleep apnea (OSA) is a common disorder in children mostly due to adenotonsillar hypertrophy. Therefore, adenotonsillectomy is the mainstay of treatment. However, the outcome of adenotonsillectomy is limited in some patients who develop persistent OSA (POSA). We aim to evaluate the prevalence, risk factors, and treatments of POSA in the pediatric population in Qatar. Methodology This is a retrospective review of medical electronic records of patients aged 1-18 years, who underwent adenoidectomy and/or tonsillectomy at Sidra Medicine (Doha, Qatar) between June 2017 and September 2022. Demographic, clinical, and polysomnography (PSG) data were collected. POSA was defined as the persistence of at least one of the following OSA symptoms: snoring, gasping, mouth breathing or witnessed sleep apnea during post-surgery clinic visits, and/or post-surgical diagnosis of OSA by PSG. The prevalence of POSA was defined as the number of patients who had persistent symptoms divided by patients who were followed at outpatient clinics (ENT/pulmonology) post-surgery. Risk factors for POSA were evaluated using multivariate regression analysis. Results A total of 410 patients (259 males and 151 females) underwent adenotonsillectomy during the study period. The average age at surgery was 3.6 ± 2.5 years. The majority of patients (85.9%) had no history of underlying medical conditions. The rest of the patients (14.1%) were diagnosed with chromosomal abnormalities or neuromuscular disorders. All patients (100%) had a history of snoring before surgery, and 32.4% of patients had a history of witnessed sleep apnea. A total of 52 patients had persistent symptoms four months post-surgery. POSA prevalence was estimated at 15.4%. Univariate analysis showed young age at the time of surgery (p = 0.015), history of asthma (23%, 12/52) (p = 0.002), allergic rhinitis (13%, 7/52) (p = 0.001), gastroesophageal reflux disease ((11%, 6/52) (p < 0.001), and genetic syndromes (17%, 9/52) (p < 0.005) as significant risk factors for POSA. Multiple regression analysis showed that syndromic disorders and allergic rhinitis were significantly correlated with persistent OSA (p = 0.021 and p = 0.000, respectively). Conclusions POSA is prevalent in children post-tonsillectomy and adenoidectomy, especially in patients with genetic syndromes and those with symptoms of allergic rhinitis. Future studies are needed to better define the condition and provide evidence-based diagnostic and therapeutic approaches.

Prevalence, Severity, and Treatment of Obstructive Sleep Apnea in Children with Down Syndrome in Qatar.

Patients with Down syndrome (DS) are at risk for sleep disorder breathing (SDB) due to their abnormal craniofacial anatomy, hypotonia, and propensity for obesity. The prevalence and severity of SDB in this population vary between different cohorts due to the multifactorial nature of these patients and the different diagnostic criteria used. We aim to report the prevalence and severity of SDB in the DS population in Qatar. This study is a retrospective review of all patients with genetically confirmed DS who completed a diagnostic polysomnography (PSG) study at Sidra Medicine in Doha, Qatar, which is the only pediatric sleep center in the country, between September 2019 and July 2022. Clinical and PSG data were collected from the patients' electronic medical records. Central and obstructive events were scored according to the American Academy of Sleep Medicine (AASM) criteria. Obstructive sleep apnea (OSA) diagnosis was made based on apnea-hypopnea index (AHI) and defined as AHI>1.5 events/hour.OSA was considered mild if AHI was ≥ 1.5 but < 5, moderate if AHI was ≥ 5 but < 10, and severe if AHI was ≥ 10 events/hour. Diagnosis with central apnea was considered if the central apnea index was > 5 events/hour. Hypoventilation was considered present if end-tidal/transcutaneous carbon dioxide gas was more than 50 mmHg for more than 25% of total sleep time.Multiple regression analysis was performed to evaluate predictors of high AHI and rapid eye movement (REM)-AHI. A total of 80 patients (49 males and 31 females) were included. Median (range) age was 7.3 years (0.9, 21). The mean (range) BMI z-score was 1.7 (-1.3, 4.3). Sixty-five patients were diagnosed with OSA, with a prevalence rate of 81%. OSA was mild in 25 (38.5%) patients, moderate in 15 (23.1%) patients, and severe in 25 (38.5%) patients. Only one patient was diagnosed with central apnea and five patients (6.9%) with alveolar hypoventilation. Multiple regression analysis showed BMI (P = 0.007) and snoring/apnea symptoms (P=0.023) to be predictive of high AHI. No correlation was found between the same variables and REM-AHI. Treatments used for OSA included anti-inflammatory medications in 37 (46%) patients, tonsillectomy/adenoidectomy in 13 (16.5%) patients, and positive airway pressure support in 10 (15%) patients. Our patient population with DS had a high prevalence of OSA comparable to other reported cohorts. High BMI and symptoms of snoring are predictive of OSA.

Single-Center Experience of Using Liraglutide in Adolescents With Obesity +/- Type 2 Diabetes.

Background Childhood obesity is recognized as a chronic illness with limited therapeutic options. Tackling obesity (BMI; the weight in kilograms divided by the square of the height in meters, at the 95th percentile or higher) with lifestyle interventions, especially in adolescents, has proven to be a daunting task, yielding only modest results. Research on the use of liraglutide for weight reduction in pediatric patients has yielded conflicting results. Notably, there is a lack of studies in the Middle East reporting on the outcomes of glucagon-like peptide 1 (GLP-1)receptor agonists in treating obesity in children and adolescents, with or without diabetes. This study, conducted in the Middle East, represents the first investigation into the utilization of liraglutide for weight reduction in this pediatric population. Methods This retrospective study collected data on 22 consecutive participants, aged 12 to 19 years, who were diagnosed with obesity (defined as having a BMI greater than the 95th percentile for their age and sex) and had either type 2 diabetes mellitus(T2DM)or were non-diabetic who attended endocrine clinics in Sidra Medicine, Doha, Qatar, between 2020 and 2022. The study protocol involved a liraglutide treatment period spanning 18 months (72 weeks), with scheduled follow-up appointments at six-month intervals. The primary endpoints were changes in weight and BMI from baseline to the 72-week mark. Secondary endpoints were safety measures and changes in HbA1c. Results Out of the initial cohort of 22 patients, 12 completed the full 72-weekduration of the study, while 10 patients either discontinued treatment or did not adhere to the prescribed medication regimen due to side effects. Among the 12 patients who completed the study, six had a diagnosis of T2DM. At baseline, the weight, standard deviation score (SDS), BMI, and BMI standard deviation (SD) were 113.9 kg, 2.9, 40.9 kg/m2, and 2.6 respectively. At the 18-month follow-up, the weight, SDS, BMI, and BMI SD were 117.8kg,2.6, 39kg/m2, and 2.5, respectively. Thus, no statistically significant change in the weight parameters was evident at 18 months compared to baseline. Dropout from the study and poor compliance were high (10 out of 22 patients) due to side effects, mainly gastrointestinal (nausea, abdominal pain, diarrhea, and vomiting). No statistically significant differences were observed between obese vs. obese with T2DM. No significant change in HbA1c was found between baseline and treatment follow-up in the diabetes patients. No adverse effects in terms of impairment of liver and kidney function or pancreatitis were observed. Conclusions The administration of liraglutide to adolescents with obesity, regardless of whether they had T2DMor not, in a real-life setting, did not yield statistically significant reductions in BMI/weight parameters, and HbA1c levels at the 72-week mark. Nevertheless, the study findings indicate that liraglutide is deemed safe for utilization within this age group, despite the presence of mild gastrointestinal side effects.

Impact of COVID‑19 pandemic restrictions and subsequent relaxation on the prevalence of respiratory virus hospitalizations in children

BackgroundThe COVID-19 pandemic and the consequently adopted worldwide control measures have resulted in global changes in the epidemiology and severity of other respiratory viruses. We compared the number and severity of viral acute lower respiratory tract infection (ALRTI) hospitalizations and determined changes in causative respiratory pathogens before, during, and after the pandemic among young children in Qatar.MethodsIn this single-center retrospective study, we reviewed data of children ≤ 36 months old who were admitted to Sidra Medicine in Qatar with a viral ALRTI during winter seasons (September–April) between 2019 and 2023. The study period was divided into three distinct seasons based on the pandemic-imposed restrictions as follows: (1) the period between September 2019 and April 2020 was considered the pre-COVID-19 pandemic season; (2) the periods between September 2020 and April 2021, and the period between January and April 2022 were considered the COVID-19 pandemic seasons; and (3) the periods between September 2022 and April 2023 was considered the post-COVID-19 pandemic season.ResultsDuring the COVID-19 season, 77 patients were admitted, compared with 153 patients during the pre-COVID-19 season and 230 patients during the post-COVID-19 season. RSV was the dominant virus during the pre-COVID-19 season, with a detection rate of 50.9%. RSV infection rate dropped significantly during the COVID-19 season to 10.4% and then increased again during the post-COVID-19 season to 29.1% (P < 0.001). Rhinovirus was the dominant virus during the COVID-19 (39.1%) and post-COVID-19 seasons (61%) compared to the pre-COVID-19 season (31.4%) (P < 0.001). The average length of hospital stay was significantly longer in the post-COVID-19 season than in the pre-COVID-19 and COVID-19 seasons (P < 0.001). No significant differences in the pediatric intensive care unit (PICU) admission rate (P = 0.22), PICU length of stay (p = 0.479), or respiratory support requirements were detected between the three seasons.ConclusionOur study showed reduced viral ALRTI hospitalizations in Qatar during the COVID-19 pandemic with reduced RSV detection. An increase in viral ALRTI hospitalizations accompanied by a resurgence of RSV circulation following the relaxation of COVID-19 restrictions was observed without changes in disease severity.

Validation of plasma protein glycation and oxidation biomarkers for the diagnosis of autism

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder in children. It is currently diagnosed by behaviour-based assessments made by observation and interview. In 2018 we reported a discovery study of a blood biomarker diagnostic test for ASD based on a combination of four plasma protein glycation and oxidation adducts. The test had 88% accuracy in children 5–12 years old. Herein, we present an international multicenter clinical validation study (N = 478) with application of similar biomarkers to a wider age range of 1.5–12 years old children. Three hundred and eleven children with ASD (247 male, 64 female; age 5.2 ± 3.0 years) and 167 children with typical development (94 male, 73 female; 4.9 ± 2.4 years) were recruited for this study at Sidra Medicine and Hamad Medical Corporation hospitals, Qatar, and Hospital Regional Universitario de Málaga, Spain. For subjects 5–12 years old, the diagnostic algorithm with features, advanced glycation endproducts (AGEs)—Nε-carboxymethyl-lysine (CML), Nω-carboxymethylarginine (CMA) and 3-deoxyglucosone-derived hydroimidazolone (3DG-H), and oxidative damage marker, o,o’-dityrosine (DT), age and gender had accuracy 83% (CI 79 – 89%), sensitivity 94% (CI 90–98%), specificity 67% (CI 57–76%) and area-under-the-curve of receiver operating characteristic plot (AUROC) 0.87 (CI 0.84–0.90). Inclusion of additional plasma protein glycation and oxidation adducts increased the specificity to 74%. An algorithm with 12 plasma protein glycation and oxidation adduct features was optimum for children of 1.5–12 years old: accuracy 74% (CI 70–79%), sensitivity 75% (CI 63–87%), specificity 74% (CI 58–90%) and AUROC 0.79 (CI 0.74–0.84). We conclude that ASD diagnosis may be supported using an algorithm with features of plasma protein CML, CMA, 3DG-H and DT in 5–12 years-old children, and an algorithm with additional features applicable for ASD screening in younger children. ASD severity, as assessed by ADOS-2 score, correlated positively with plasma protein glycation adducts derived from methylglyoxal, hydroimidazolone MG-H1 and Nε(1-carboxyethyl)lysine (CEL). The successful validation herein may indicate that the algorithm modifiable features are mechanistic risk markers linking ASD to increased lipid peroxidation, neuronal plasticity and proteotoxic stress.

From research genomics to clinical genetics: Insourcing next generation sequencing in a pediatric and women’s hospital

Abstract Introduction/Objective The Sidra Medicine Clinical Genomics Laboratory (CGL) offers rapid and cost-effective next- generation sequencing (NGS) solutions such as Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) which support various research initiatives in Qatar. With the current worldwide trend in precision and personalized medicine, the Pathology Genetics (PG) division is required to provide in-house diagnostic genetic testing to clinical patient groups. The main objective of this quality initiative project is to decrease the cost of NGS send-out tests and to perform patient testing in-house. The CGL NGS workflow and processes must be validated to comply with the clinical accreditation requirements of the College of American Pathologists (CAP). Methods/Case Report Assay performance metrics are considered for the validation of the Illumina NovaSeq 6000 NGS platform. Sample library preparation is performed in PG while sequencing and data analysis is based in CGL. NGS quality assurance in CGL involves the use of Illumina PhiX control mixed with the pooled library. To maintain the high throughput and low-cost NGS approach, Illumina S4 flow cells are used with efficient library pooling techniques. The TAT of clinical samples for WES and WGS analysis in CGL is around 14 days which includes sequencing, data conversion, and bioinformatics. Results (if a Case Study enter NA) A Service Level Agreement (SLA) between Sidra Research and Sidra Pathology was created to define the workflow and services provided by both departments with clear lines of responsibility and accountability. A quality manual is also written to describe the QMS of the genomics laboratory and outlines the various NGS services offered. CGL protocols are transferred to CAP-approved SOP templates for standardization with pathology documentation. For quality improvement, the NGS workflow in CGL is continuously developed to improve the data produced and TAT. Conclusion The collaboration between the two departments maximized the available infrastructures of Sidra Medicine, saved costly send-out tests, improved the TAT of genetic analysis, and most importantly enhanced healthcare outcomes and related clinical diagnostics in alignment with the National Health Strategy (NHS) of the country. Accreditation propels good QMS in laboratory services hence this quality initiative fulfills Sidra Medicine’s vision to provide total precision diagnosis and personalized medicine leading to the delivery of exceptional care to rank amongst the top medical centers internationally.

Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study.

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the functional link between sphingolipid metabolism, asthma, and obesity is not completely understood. This paper describes the protocol of an ongoing study on sphingolipids that aims to examine the pathophysiology of sphingolipids in childhood asthma and obesity. In addition, this study aims to explore the novel biomarkers through a comprehensive multi-omics approach including genomics, genome-wide DNA methylation, RNA-Seq, microRNA (miRNA) profiling, lipidomics, metabolomics, and cytokine profiling. This is a cross-sectional study aiming to recruit 440 children from different groups: children with asthma and normal weight (n = 100), asthma with overweight or obesity (n = 100), overweight or obesity (n = 100), normal weight (n = 70), and siblings of asthmatic children with normal weight, overweight, or obesity (n = 70). These participants will be recruited from the pediatric pulmonology, pediatric endocrinology, and general pediatric outpatient clinics at Sidra Medicine, Doha, Qatar. Information will be obtained from self-reported questionnaires on asthma, quality of life, food frequency (FFQ), and a 3-day food diary that are completed by the children and their parents. Clinical measurements will include anthropometry, blood pressure, biochemistry, bioelectrical impedance, and pulmonary function tests. Blood samples will be obtained for sphingolipid analysis, serine palmitoyltransferase (SPT) assay, whole-genome sequencing (WGS), genome-wide DNA methylation study, RNA-Seq, miRNA profiling, metabolomics, lipidomics, and cytokine analysis. Group comparisons of continuous outcome variables will be carried out by a one-way analysis of variance or the Kruskal-Wallis test using an appropriate pairwise multiple comparison test. The chi-squared test or a Fisher's exact test will be used to test the associations between categorical variables. Finally, multivariate analysis will be carried out to integrate the clinical data with multi-omics data. This study will help us to understand the role of dysregulated sphingolipid metabolism in obesity and asthma. In addition, the multi-omics data from the study will help to identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways that link asthma and obesity in children. Furthermore, the integration of clinical and multi-omics data will help us to uncover the potential interactions between these diseases and to offer a new paradigm for the treatment of pediatric obesity-associated asthma.

Prevalence of Sleep-Disordered Breathing in Prader-Willi Syndrome.

Sleep-disordered breathing (SDB) is common in patients with Prader-Willi Syndrome (PWS). However, the prevalence of SDB varies widely between studies. Early identification of SDB and factors contributing to its incidence is essential, particularly when considering growth hormone (GH) therapy. The aims of the study were to describe the prevalence and phenotypes of sleep-disordered breathing (SDB) in patients with Prader-Willi syndrome (PWS) and to determine the effects of age, gender, symptoms, GH therapy and body mass index on SDB severity. This study was a retrospective chart review of all patients with genetically confirmed Prader-Willi syndrome who underwent diagnostic overnight polysomnography (PSG) in the sleep laboratory at Sidra Medicine. Clinical and PSG data of enrolled patients were collected. We identified 20 patients (nine males, eleven females) with PWS who had overnight sleep polysomnography (PSG) at a median age (IQR) of 5.83 (2.7-12) years. The median apnea-hypopnea index (AHI) was 8.55 (IQR 5.8-16.9) events/hour. The median REM-AHI was 27.8 (IQR 15-50.6) events/hour. The median obstructive apnea-hypopnea index (OAHI) was 7.29 (IQR 1.8-13.5) events/hour. The median central apnea-hypopnea index (CAHI) was 1.77 (IQR 0.6-4.1) events/hour. Nineteen patients (95%) demonstrated SDB by polysomnography (PSG) based on AHI ≥1.5 events/hour. Nine patients (45%) were diagnosed with obstructive sleep apnea (OSA). Three patients (15%) were diagnosed with central sleep apnea (CSA). Seven patients (35%) were diagnosed with mixed sleep apnea. No correlations were observed between AHI and age, gender, BMI, symptoms, or GH therapy. However, REM-AHI was significantly correlated with BMI (P=0.031). This study shows a high prevalence of SDB among our patients with PWS. Obstructive sleep apnea was the predominant phenotype. BMI was the only predictor for high REM-AHI. Further studies of large cohorts are warranted to define SDB in PWS and design the appropriate treatment.

FRI632 Metformin Use In Gdm Is Not Associated With Increased Incidence Of Preterm Labor And Small For Gestational Age Infants Compared To Diet Control Alone

Abstract Disclosure: A. D'Souza: None. F. Badri: None. H. Abdullahi: None. I. Ibrahim: None. Gestational diabetes mellitus (GDM), the most frequent medical complication of pregnancy, is becoming a growing public health issue with its national prevalence of 21.5% greater than the estimated global prevalence of 17%.1,2 Among those who required treatment for GDM in Qatar, 91.8% were on metformin either alone or in combination with insulin.1 Given the limited data on the effects of metformin exposure in pregnancy, the study aimed to investigate the association between the use of metformin in GDM and the incidence of various maternal and neonatal outcomes. It was hypothesized that metformin use in GDM is not associated with increased incidence of adverse maternal and neonatal outcomes in this high-risk population. This retrospective cohort study looked at women with GDM who sought prenatal care at Sidra Medicine, Doha, Qatar between January 2019 and December 2020 and compared the incidence of various maternal and neonatal outcomes in patients on metformin to those on diet control alone. 649 women with GDM were included in the study; of which 438 were on diet control alone and 211 were on metformin. Women in the metformin group were older and heavier at baseline and gained lesser weight during pregnancy (p&amp;lt;.001). Subjects in the metformin-treated arm had a significantly lower gestational age at delivery (37.8 vs. 38.6 weeks, p&amp;lt;.001), higher incidence of C-section (50.7 vs. 42.2%, p=.042), and higher incidence of polyhydramnios (6.6 vs. 2.1%, p=.003) compared to those in the diet-controlled group. The mean birth weight percentile (66.5 vs. 59.9, p=.008), incidence of large for gestational age (LGA) infants (27 vs. 18%, p=.008) and incidence of neonatal jaundice (1.9 vs. 0.2%, p=.041) in the metformin-treated group were higher, but there was no significant difference in the incidence of other neonatal outcomes between the two groups. In particular, metformin was not associated with increased incidence of preterm labor and small for gestational age (SGA) infants in pregnancy as suggested by previous studies. However, women on metformin had a higher incidence of C-section, polyhydramnios, LGA infants, and neonatal jaundice, and increased mean neonatal weight percentile at birth compared to diet control alone. This could be attributed to the higher degree of maternal hyperglycemia and increased severity of disease in the patients on metformin. In conclusion, our study showed that the use of metformin in GDM is not associated with the increased incidence of preterm labor and SGA infants.

Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study

Protection against SARS-CoV-2 symptomatic infection and severe COVID-19 of previous infection, mRNA two-dose vaccination, mRNA three-dose vaccination, and hybrid immunity of previous infection and vaccination were investigated in Qatar for the Alpha, Beta, and Delta variants. Six national, matched, test-negative, case-control studies were conducted between January 18 and December 18, 2021 on a sample of 239,120 PCR-positive tests and 6,103,365 PCR-negative tests. Effectiveness of previous infection against Alpha, Beta, and Delta reinfection was 89.5% (95% CI: 85.5-92.3%), 87.9% (95% CI: 85.4-89.9%), and 90.0% (95% CI: 86.7-92.5%), respectively. Effectiveness of two-dose BNT162b2 vaccination against Alpha, Beta, and Delta infection was 90.5% (95% CI, 83.9-94.4%), 80.5% (95% CI: 79.0-82.0%), and 58.1% (95% CI: 54.6-61.3%), respectively. Effectiveness of three-dose BNT162b2 vaccination against Delta infection was 91.7% (95% CI: 87.1-94.7%). Effectiveness of hybrid immunity of previous infection and two-dose BNT162b2 vaccination was 97.4% (95% CI: 95.4-98.5%) against Beta infection and 94.5% (95% CI: 92.8-95.8%) against Delta infection. Effectiveness of previous infection and three-dose BNT162b2 vaccination was 98.1% (95% CI: 85.7-99.7%) against Delta infection. All five forms of immunity had >90% protection against severe, critical, or fatal COVID-19 regardless of variant. Similar effectiveness estimates were observed for mRNA-1273. A mathematical model accurately predicted hybrid immunity protection by assuming that the individual effects of previous infection and vaccination acted independently. Hybrid immunity, offering the strongest protection, was mathematically predicted by assuming that the immunities obtained from previous infection and vaccination act independently, without synergy or redundancy. The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Population immunity of natural infection, primary-series vaccination, and booster vaccination in Qatar during the COVID-19 pandemic: an observational study

Waning of natural infection protection and vaccine protection highlight the need to evaluate changes in population immunity over time. Population immunity of previous SARS-CoV-2 infection or of COVID-19 vaccination are defined, respectively, as the overall protection against reinfection or against breakthrough infection at a given point in time in a given population. We estimated these population immunities in Qatar's population between July 1, 2020 and November 30, 2022, to discern generic features of the epidemiology of SARS-CoV-2. Effectiveness of previous infection, mRNA primary-series vaccination, and mRNA booster (third-dose) vaccination in preventing infection were estimated, month by month, using matched, test-negative, case-control studies. Previous-infection effectiveness against reinfection was strong before emergence of Omicron, but declined with time after a wave and rebounded after a new wave. Effectiveness dropped after Omicron emergence from 88.3% (95% CI: 84.8-91.0%) in November 2021 to 51.0% (95% CI: 48.3-53.6%) in December 2021. Primary-series effectiveness against infection was 84.0% (95% CI: 83.0-85.0%) in April 2021, soon after introduction of vaccination, before waning gradually to 52.7% (95% CI: 46.5-58.2%) by November 2021. Effectiveness declined linearly by ∼1 percentage point every 5 days. After Omicron emergence, effectiveness dropped from 52.7% (95% CI: 46.5-58.2%) in November 2021 to negligible levels in December 2021. Booster effectiveness dropped after Omicron emergence from 83.0% (95% CI: 65.6-91.6%) in November 2021 to 32.9% (95% CI: 26.7-38.5%) in December 2021, and continued to decline thereafter. Effectiveness of previous infection and vaccination against severe, critical, or fatal COVID-19 were generally >80% throughout the study duration. High population immunity against infection may not be sustained beyond a year, but population immunity against severe COVID-19 is durable with slow waning even after Omicron emergence. The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and Qatar University Internal Grant ID QUCG-CAS-23/24-114.

Pediatric outpatient non-invasive ventilation program: Reflections on the first experience from the Middle East.

Long-term noninvasive ventilation (NIV) is being progressively used in children. The current guidelines recommend NIV initiation in the hospital during overnight polysomnography (PSG) titration study. Due to the logistic, socioeconomic, and financial difficulties including bed availability, an outpatient program for NIV initiation and patients/parents counseling to prevent delay and provide cost-effective care has been commissioned. Hence, this study reports on the clinical outcome of our program as it represents the first reported experience from the middle east. A retrospective review of electronic medical charts was conducted for all patients with PSG-confirmed sleep-related breathing disorders (SRBD) who were evaluated and treated in the NIV clinic in the pediatric pulmonary clinic at Sidra Medicine from January 2020 to November 2021. Patients' data included demographics, PSG results, and NIV clinic records. The results show that twenty-eight patients (17 male, 11 female) were included during the study period. The patients' median age at NIV initiation was 11±5.17 years. The median BMI was 32.72±15.91 kg/m2. The most common diagnosis was morbid obesity in 9 (32%) of the patients. The identified SRBD based on the diagnostic PSG were obstructive sleep apnea in 21 patients, hypoventilation in 3 patients, mixed apnea in 3 patients, and central apnea in 1 patient. The median total Apnea-Hypopnea Index (AHI) was 12.7 (0.7-153.9) events per hour. The main reason for the initial NIV clinic visit was NIV initiation in 19 patients. Upon follow-up, six patients were successfully weaned off NIV support by the treating pulmonologist. Five patients refused to use NIV at home. Fifteen out of the remaining seventeen patients used NIV ≥ 4 hours per night (subjective adherence: 88%). Twelve patients used the NIV for ≥ 24 nights per month (70.6%). All parents reported that the clinic experience was beneficial and helped them to be more comfortable with applying the NIV machine at home. In conclusion, pediatric NIV outpatient programs are achievable and beneficial, especially in developing countries. Pediatric NIV clinics managed by a specialized and experienced team play important role in the initiation and follow-up of NIV support. They provide alternative pathways for the care of pediatric patients, education, and support of their families, and decrease the load on intensive care and sleep laboratory units. Studies about cost-effectiveness are needed to evaluate the impact of implementing outpatient NIV programs on sleep laboratories and hospital admission rates.

Clinical Presentation and Outcome of Multiple Rare Earth Magnet Ingestions in Children of Qatar. A Single-Center Experience.

Rare earth magnets are powerful magnets that can have several negative effects if ingested. The goal of our study is to describe the result of multiple rare earth magnets ingested by children in Qatar. This is observational research. We conducted a retrospective chart review and descriptive analysis of all cases of multiple rare earth magnetic ingestion that werepresented to the Emergency Department of Sidra Medicine between January 2018 and July 2022. We obtained an exemption for this study from our institutional review board (IRB). In our research, we identified 21 children having multiple rare earth magnetic ingestions. The predominant symptoms were abdominal pain and vomiting which were observed in 57% (n=12) and 48% (n=10) of the patients respectively. The most common sign was abdominal tenderness,observed in 14% (n=3) of the patients. In our sample, 38% (n=8) of the patients were managed conservatively whereas 62% (n=13) needed intervention. In our study, 48% (n=10) of the patients sustained complications. The frequent complications were intestinal perforation appreciated in 24% (n=5) and intestinal perforation with fistula formation in 19% (n=4) of the patients. The median age of these patients was two years while the median number of magnets ingested was six. The ingestions were unwitnessed, and the duration of ingestions was unknowninthemajorityofpatientswhoexperiencedcomplications (n=8/10). If numerous rare earth magnetis ingested, children are in high danger of harm. It can be difficult to pinpoint the cases in younger children due to poor communication skills, especially if the intake is unreported. Although Qatar has established restrictions banning the import of rare earth magnets, there are reported cases of children with rare earth magnets ingestions.

Long-term COVID-19 booster effectiveness by infection history and clinical vulnerability and immune imprinting: a retrospective population-based cohort study

Long-term effectiveness of COVID-19 mRNA boosters in populations with different previous infection histories and clinical vulnerability profiles is inadequately understood. We aimed to investigate the effectiveness of a booster (third dose) vaccination against SARS-CoV-2 infection and against severe, critical, or fatal COVID-19, relative to that of primary-series (two-dose) vaccination over a follow-up duration of 1 year. This observational, matched, retrospective, cohort study was done on the population of Qatar in people with different immune histories and different clinical vulnerability to infection. The source of data are Qatar's national databases for COVID-19 laboratory testing, vaccination, hospitalisation, and death. Associations were estimated using inverse-probability-weighted Cox proportional-hazards regression models. The primary outcome of the study is the effectiveness of COVID-19 mRNA boosters against infection and against severe COVID-19. Data were obtained for 2 228 686 people who had received at least two vaccine doses starting from Jan 5, 2021, of whom 658 947 (29·6%) went on to receive a third dose before data cutoff on Oct 12, 2022. There were 20 528 incident infections in the three-dose cohort and 30 771 infections in the two-dose cohort. Booster effectiveness relative to primary series was 26·2% (95% CI 23·6-28·6) against infection and 75·1% (40·2-89·6) against severe, critical, or fatal COVID-19, during 1-year follow-up after the booster. Among people clinically vulnerable to severe COVID-19, effectiveness was 34·2% (27·0-40·6) against infection and 76·6% (34·5-91·7) against severe, critical, or fatal COVID-19. Effectiveness against infection was highest at 61·4% (60·2-62·6) in the first month after the booster but waned thereafter and was modest at only 15·5% (8·3-22·2) by the sixth month. In the seventh month and thereafter, coincident with BA.4/BA.5 and BA.2·75* subvariant incidence, effectiveness was progressively negative albeit with wide CIs. Similar patterns of protection were observed irrespective of previous infection status, clinical vulnerability, or type of vaccine (BNT162b2 vs mRNA-1273). Protection against omicron infection waned after the booster, and eventually suggested a possibility for negative immune imprinting. However, boosters substantially reduced infection and severe COVID-19, particularly among individuals who were clinically vulnerable, affirming the public health value of booster vaccination. The Biomedical Research Program and the Biostatistics, Epidemiology, and the Biomathematics Research Core (both at Weill Cornell Medicine-Qatar), Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, and Qatar University Biomedical Research Center.

P617 Dual biologic therapy in pediatric Inflammatory Bowel Disease

Abstract Background There is paucity of data on the effectiveness of combination biologic agents as an option for children with refractory inflammatory bowel disease (IBD) that is inadequately controlled by biologic monotherapy. The aims of this study were to determine the effectiveness and safety of combination biologic use in pediatrics IBD. Methods A retrospective cohort study of children with IBD seen at Sidra Medicine and who received combination biologic therapy from October 2018 to April 2022. The diagnosis of IBD was established according to the revised Porto criteria. Children with IBD on two or more biologics were identified from our IBD database and their electronic medical records were reviewed. Patients included in the study must have been on combination biologic therapy for at least two months. Relevant clinical and demographic data were collected. Results Out of the 211 patients in our IBD database, we identified a total of 14 patients who had received dual biologic therapy within the study period. 3 patients were excluded because they had received dual biologic therapy for less than 2 months. 11 patients with IBD met our inclusion criteria and were included in this study. All 11 patients had Crohn’s disease. Overall, 7 patients (63%) were male, the median age at the start of starting combination therapy was 15.1 years (IQR 13.9 to 17.4), and the median disease duration was 2.3 years (IQR 1.4 to 3.2). Patients had been on the first biologic for a median of 20.3 months (IQR 13.0 to 32.3) before the addition of the second biologic. The reasons for dual biologic therapy included active disease, failure of single biological therapy, and development of complications. The patients had failed therapy with a median of two (range 1-3) prior biological medications. Concomitant dermatological disease (psoriasis) was present in one patient (9.1%). After a median follow-up of 5.2 months (IQR 2.9-5.5), median PCDAI significantly reduced from 22.5(IQR 16.75-30) to 5(1.25-13.75) {P&amp;lt;0.001}…Figure 1. Median fecal calprotectin reduced from 1534 (1361-1612) to 489 (379-658) {P&amp;lt;0.001}. No adverse events were noted. Conclusion Dual biologic therapy was associated with clinical and biomarker improvements in patients with Crohn’s disease who previously failed at least one single biologic. Dual biologic treatment was not associated with adverse events during the study period. Dual biologic therapy may be an attractive strategy but the lack of randomized controlled trials as well as long-term safety concerns means that there is a need for further trials on this subject. Future studies should assess risk: benefit ratios, safety, and efficacy of specific combinations of biologic use in IBD.

Outcome of Newborns with Tracheoesophageal Fistula: An Experience from a Rapidly Developing Country: Room for Improvement.

This is a retrospective review of the medical electronic charts of patients with TEF that were followed at Sidra Medicine in the state of Qatar. The review included the patients who were operated upon in the period of 2011-2021 but continued to follow at our institution in the period of 2018-2021. Demographic data, associated anomalies, preoperative, operative, and postoperative courses, and growth parameters were collected. A total of 35 patients with TEF (24 males and 11 females) were collected. 49% were full term. We identified seven patients (20%) with isolated TEF, TEF with VACTERL association in 29% of our patients, other chromosomal anomalies in 17%, or associated with other anomalies (not related to VACTERL) in 34% of the patients. The majority of the patients (94%) were of type C-TEF (TEF with esophageal atresia-EA/TEF). All patients were operated except for one patient who died at 2 days of life due to cardiac complications. Median age at which surgery was performed was 2 days (range 1-270 days). Median follow-up was 32 months (range 7-115 months). Immediate postoperative complications were encountered in eleven patients (33%) and included anastomosis leak in 12%, air leak in 6%, sepsis in 6%, chylothorax in 3%, vocal cord palsy and fistula recurrence (combined) in 3%, and failure of TEF closure in 3% of the patients. Long-term respiratory complications were encountered in 43% of our patients. Long-term gastrointestinal complications included gastroesophageal reflux (GERD) in 63%, dysphagia in 31%, and anastomotic stricture in 34% of the patients. Growth was affected in around a quarter of the patients at 6 months after surgery and 22% at 12-month assessment postoperatively. While only five patients died at our institution, only one was directly related to failure of TEF closure and postoperative complications. This descriptive study reports the clinical outcome of TEF from a rapidly developing country. The distribution of the patients' characteristics and postoperative complications was almost comparable to those from developed countries. This study would aid in addressing the prognostic factors and establishment of evidence-based management pathways of newborns with TEF to improve the clinical outcome in our center and other pediatric tertiary centers in developing countries.

Protection from previous natural infection compared with mRNA vaccination against SARS-CoV-2 infection and severe COVID-19 in Qatar: a retrospective cohort study

Understanding protection conferred by natural SARS-CoV-2 infection versus COVID-19 vaccination is important for informing vaccine mandate decisions. We compared protection conferred by natural infection versus that from the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines in Qatar. We conducted two matched retrospective cohort studies that emulated target trials. Data were obtained from the national federated databases for COVID-19 vaccination, SARS-CoV-2 testing, and COVID-19-related hospitalisation and death between Feb 28, 2020 (pandemic onset in Qatar) and May 12, 2022. We matched individuals with a documented primary infection and no vaccination record (natural infection cohort) with individuals who had received two doses (primary series) of the same vaccine (BNT162b2-vaccinated or mRNA-1273-vaccinated cohorts) at the start of follow-up (90 days after the primary infection). Individuals were exact matched (1:1) by sex, 10-year age group, nationality, comorbidity count, and timing of primary infection or first-dose vaccination. Incidence of SARS-CoV-2 infection and COVID-19-related hospitalisation and death in the natural infection cohorts was compared with incidence in the vaccinated cohorts, using Cox proportional hazards regression models with adjustment for matching factors. Between Jan 5, 2021 (date of second-dose vaccine roll-out) and May 12, 2022, 104 500 individuals vaccinated with BNT162b2 and 61 955 individuals vaccinated with mRNA-1273 were matched to unvaccinated individuals with a documented primary infection. During follow-up, 7123 SARS-CoV-2 infections were recorded in the BNT162b2-vaccinated cohort and 3583 reinfections were recorded in the matched natural infection cohort. 4282 SARS-CoV-2 infections were recorded in the mRNA-1273-vaccinated cohort and 2301 reinfections were recorded in the matched natural infection cohort. The overall adjusted hazard ratio (HR) for SARS-CoV-2 infection was 0·47 (95% CI 0·45-0·48) after previous natural infection versus BNT162b2 vaccination, and 0·51 (0·49-0·54) after previous natural infection versus mRNA-1273 vaccination. The overall adjusted HR for severe (acute care hospitalisations), critical (intensive care unit hospitalisations), or fatal COVID-19 cases was 0·24 (0·08-0·72) after previous natural infection versus BNT162b2 vaccination, and 0·24 (0·05-1·19) after previous natural infection versus mRNA-1273 vaccination. Severe, critical, or fatal COVID-19 was rare in both the natural infection and vaccinated cohorts. Previous natural infection was associated with lower incidence of SARS-CoV-2 infection, regardless of the variant, than mRNA primary-series vaccination. Vaccination remains the safest and most optimal tool for protecting against infection and COVID-19-related hospitalisation and death, irrespective of previous infection status. The Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, Weill Cornell Medicine-Qatar; Qatar Ministry of Public Health; Hamad Medical Corporation; Sidra Medicine; Qatar Genome Programme; and Qatar University Biomedical Research Center.

Reagent Lot Variation Assessment: Establishing the Suitable Acceptability Criteria and Implementing an Efficient and Cost-effective Approach

Abstract Introduction/Objective When reagent lot number change for a particular assay it is hoped that the results obtained from the new lot are comparable with those of the old lot and so will not lead to misleading clinical conclusions based on either the reference intervals or previous results on the same patient. This study has criticality evaluated and compared various methods of establishing reagent lot-to-lot verification acceptability criteria to determine the most suitable approach in Sidra Medicine Clinical Biochemistry Department in order to implement an efficient and cost-effective method of verifying new reagent lot numbers. Methods/Case Report Several methods and approach for establishing in-house acceptable criteria for determining reagent variations were critically evaluated. These methods include the use of CLSI EP26-A guidelines, proficiency testing or external quality assessment (EQA) total allowable errors (TeA) and internal quality control (IQC) in-house target SD and CV reflecting the current assay performance. A user friendly statistical template was also produced to be able to improve fhe current workflow, data entry, presentation and documentation of each test with a new reagent lot number approved and implemented for patient testing. Results (if a Case Study enter NA) A full version of Reagent Lot Variation Acceptance Table was produced showing comprehensive established criteria based from methods mentioned above. IQC and patient comparability results are entered in an excel template which automatically calculates the differences and shows if the new lot number passed or failed based on the in-house acceptability criteria established. The reagent lot-to-lot verification template is updated each month using complex excel rules to keep the acceptability limits in accordance with the most current in-house IQC target mean and SD based from the most recent monthly IQC reviews. Conclusion The comparison of different reagent lot variation acceptability criteria indeed raised awareness of the efficiency and practicality of performing reagent lot-to-lot verification. CLSI EP26-A approach was observed to have the least sample number requirement. However, one patient sample for comparison study seems not enough to justify the approval and implementation of the new reagent lot number to consider the assays AMR. The IQC SD and CAP Total Allowable Error (TeA) acceptability criteria are more effective since there is more number of patient samples used for comparability across the assays AMR.