Developing and Validating Entrustable Professional Activities (EPAs) for Rheumatology Fellowship Training Programs in Saudi Arabia: A Delphi Study.

Background: Entrustable professional activities (EPAs) define the core tasks that a graduating rheumatologist needs to perform independently in practice. The objective of this study was to develop and validate EPAs for rheumatology fellowship training programs in Saudi Arabia. Methods: Experts met to develop an initial set of potential end-of-training EPAs by conducting a comprehensive literature review of EPAs and studying the Saudi rheumatology fellowship curriculum. Then, to validate the EPAs, we conducted two rounds of the modified Delphi technique among rheumatology experts in Saudi Arabia. A response rate of 80% was considered and the minimum number of experts needed to be 25 to 30. Descriptive statistics were utilized to describe participants' demographic characteristics and group responses to each statement in all rounds. The experts were asked to rate the relevancy of each EPA using a 5-point Likert scale in both Delphi rounds. Results: In the preliminary phase, four rheumatologists developed an initial set of 36 core EPAs for rheumatology training program in Saudi Arabia. For the two-rounds Delphi techniques, 32 experts were invited to complete the study. The response rate of the first and second round were, 78.12% (25) and 93.75% (30), respectively. The first-round Delphi resulted in a robust consensus on 31 EPAs for rheumatology training. Five EPAs were excluded, and one new EPA was proposed. In the subsequent round, all 32 EPAs achieved strong consensus. The eliminated EPAs likely fell short in one or more of the following areas: relevance to rheumatology practice in Saudi Arabia, overlapping with other EPAs, or practical challenges in the implementation. Conclusion: We have developed and validated a core set of EPAs for rheumatology fellowship training programs in Saudi Arabia. Mapping and identifying milestones for these EPAs are essential steps to follow to enhance workplace curriculum development.

Clinical characteristics and risk factors for mortality of hospitalized cancer patients with COVID-2019 in Mecca, Saudi Arabia.

BACKGROUND: Cancer patients are particularly vulnerable during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to evaluate clinical characteristics and mortality among cancer patients with COVID-19. METHODS: This retrospective, observational cohort study included 53 patients with a malignancy and reverse-transcription polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus-2 infection in a tertiary care center in Mecca, Saudi Arabia, from March 14, 2020, to October 29, 2020. Clinical, laboratory, and radiological data were collected from institutional electronic records and analyzed. RESULTS: Overall, 53 patients (62% male) were enrolled. The mean age of the patients was 54.9 ± 19.0 years, with 76% aged <65 years. The most common symptoms were fever (66%), dry cough (40%), and dyspnea (36%). Most infections (89%) were community acquired. Hematological malignancies (36%) were the most common cancer type. The most common solid tumors were breast cancer (23%) and colon cancer (9%). Just over half (51%) had a stage 4 tumor, and 30% of the patients had received chemotherapy within 2 weeks before the onset of COVID-19 symptoms. Initial chest radiographs showed pneumonia in 43% of patients; 38%, 9%, and 6% required oxygen support, intensive care unit admission, and invasive mechanical ventilation, respectively. The most common complication was secondary bacterial infection (13.2%). The all-cause mortality rate was 17%. In the multivariable logistic regression, dyspnea, leukocytosis, use of systemic steroids, and secondary bacterial infection were found to be risk factors for death. CONCLUSION: Hospitalized cancer patients with COVID-19 have a high mortality rate. Our study finds a correlation between multiple independent risk factors and mortality. Patients with dyspnea, leukocytosis, systemic steroid use, or secondary bacterial infection require more care, attention, and possibly more aggressive treatment.

Impact of COVID-19 Pandemic on Medical Education: A Cross-Sectional Study in the Western Region of Saudi Arabia.

Background: As the Coronavirus Disease 2019 (COVID-19) outbreak has made a tremendous impact on medical education and healthcare institutions, we aimed to measure effects of online classes on medical students' comprehension in comparison with attending campus classes during the COVID-19 pandemic. Methods: A cross-sectional survey has been conducted between September 2020 and June 2021 in the western region of Saudi Arabia. The Convenience sampling technique was conducted to collect the data from medical students in their basic and clinical years, using a questionnaire that involved 45 multiple-choice and multiple-answer questions. Results: Out of 3700 questionnaires, 922 completed the questionnaires from 11 different medical schools. Umm AL-Qura University had the highest response rate with 232 responses (25.2%), followed by King Abdulaziz University with 186 responses (20.2%). The majority of institutions preferred Blackboard and Zoom as platforms for e-learning. A total of 355 (38.5%) believed that it resulted in higher academic achievement, whereas 555 (60.2%) of students believed the limitation of clinical access was one of the biggest disadvantages of e-learning. Overall, 518 (56.2%) of students did not want to continue using e-learning on its own in the future. Whereas 668 (72.5%) wished to keep using e-learning in combination with traditional learning. Conclusion: According to our findings, advantages of e-learning vary among students. Most of the students thought e-learning to be an interactive system that provides a learning opportunity. In contrast, many of the students believed that there were many disadvantages regarding online teaching methods.

A Cross-Sectional Study of Celiac Disease Awareness in the Food Industry in the Western Region of Saudi Arabia.

Background The only treatment available for celiac disease (CD), an autoimmune disease, is a gluten-free diet. Restaurant personnel have major roles in understanding the possible risks to consumers with CD, ensuring the availability of and preparing gluten-free foods. We attempted to evaluate the awareness and knowledge of CD among chefs, cooks, restaurant personnel, and owners and assess the availability of gluten-free diet options in the western region of Saudi Arabia. Methods A cross-sectional, questionnaire-based study was conducted in 126 restaurants based in Makkah al-Mukarramah and Jeddah cities. The chefs and owners of the restaurants were interviewed face-to-face to collect data knowledge about CD, gluten sensitivity, food containing gluten, serving gluten-free food, intention to add gluten-free options in the future, and circumstances related to serving gluten-free food. Result Our study showed that 17.5% and 51.6% of the participants had heard about CD and gluten sensitivity, respectively, and 34.1% checked a right answer of gluten-containing food with a mean of 0.68 (±1.02). About 17.5% of the participating restaurants serve gluten-free meal options (mean: 0.63±1.57), 14.7% had protocols for the preparation of gluten-free food, 7.1% displayed signs or notices that they sell gluten-free products, and 50.8% disclosed an intention to add gluten-free options in the future. Furthermore, 82.5% of gluten-free options were more expensive. Education level, being a trained chef, and experience years were significantly associated with awareness about CD or gluten sensitivity (p<0.05). Conclusion There is a general lack of awareness of CD, and most restaurants lack gluten-free options. We recommend adding more gluten-free food options for patients with CD.

Post COVID-19 Chronic Parenchymal Lung Changes.

INTRODUCTION: Persistent parenchymal lung changes are an important long-term sequela of COVID-19. There are limited data on this COVID-19 infection sequela characteristics and trajectories. This study aims to evaluate persistent COVID-19-related parenchymal lung changes 10 weeks after acute viral pneumonia and to identify associated risk factors. METHODS: This is a retrospective case-control observational study involving 38 COVID-19 confirmed cases using nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) at King Abdullah Medical City (KAMC) Hospital, Makkah. Patients were recruited from the post-COVID-19 interstitial lung disease (ILD) clinic. Referral to this clinic was based on the pulmonology consultant's assessment of hospitalized patients suspected of developing COVID-19-related ILD changes during hospitalization. RESULTS: Thirty-eight patients with parenchymal lung changes were evaluated at the ILD clinic. Nineteen patients who had persistent parenchymal changes 10 weeks after the acute illness (group 1) were compared with 19 control patients who had accelerated clinical and/or radiological improvement (group 2). Group 1 was found to have the more severe clinical and radiological disease, with a higher peak value of inflammatory biomarkers. Two risk factors were identified, neutrophil-lymphocyte ratio (NLR) > 3.13 at admission increases the odds ratio (OR) of chronic parenchymal changes by 6.42 and 5.92 in the univariate and multivariate analyses, respectively. Invasive mechanical ventilation had a more profound effect with ORs of 13.09 and 44.5 in the univariate and multivariate analyses, respectively. CONCLUSION: Herein, we found that only receiving invasive mechanical ventilation and having NLR >3.13 at admission were strong risk factors for persistent parenchymal lung changes. Neither the clinical severity of the acute illness nor the radiological one is found to predict this outcome. None of the medications received during the acute illness were found to alter the risk for this post-COVID-19 infection sequelae.

Persistent Fever and Cough in a Patient With Good's Syndrome: A Case Report.

Good's syndrome is a rare, acquired immunodeficiency condition characterized by thymoma and hypogammaglobulinemia, which increases the risk of recurrent infections. Immunoglobulin replacement therapy (IgRT) is the key treatment for recurrent infections. We describe the case of a 57-year-old male with a history of an anterior mediastinal mass and a persistent cough lasting for a few years. Based on the clinical history and immunological analysis, he was diagnosed with Good's syndrome. He was being managed conservatively with immunoglobulin until he underwent a thymectomy. Subsequently, he developed his first pneumonia. His conditions gradually worsened despite the initiation of IgRT. He was diagnosed to have hypersensitivity pneumonitis based on strong exposure history, consistent radiological images, and good clinical response to antigen avoidance and steroid therapy. To our knowledge, this is the first case of Good's syndrome with hypersensitivity pneumonitis that was unmasked after immune augmentation by the initiation of IgRT. Moreover, surgical intervention should not be considered unless unavoidable. Additionally, close clinical monitoring and laboratory testing are indicated, and IgRT should be considered when the patient begins to exhibit symptoms to prevent severe infections.

Ceftriaxone-induced leukocytoclastic vasculitis: a case report and literature review of antibiotic-induced leukocytoclastic vasculitis.

Leukocytoclastic vasculitis (hypersensitivity vasculitis) is defined as small blood vessel inflammation with skin or other systemic manifestations due to infections, drugs, or neoplastic disease. This clinical case report highlights an association between ceftriaxone and leukocytoclastic vasculitis in a 49-year-old female patient with a history of penicillin allergy, on mirtazapine for anxiety disorder. Articles concerning antibiotic-induced leukocytoclastic vasculitis are also reviewed. The patient reported a symptom of upper respiratory tract infection and fever 5 days previously for which she received ceftriaxone for 2 days before presenting to the emergency department with a pruritic skin rash in the upper and lower extremities and swollen lips for 1 day. The rash was erythematous, maculopapular, itchy, and non-tender, with no mucus membrane involvement. Laboratory investigations revealed leukocytosis (white blood cells, 22.3 × 109/L) that was mainly eosinophilic (18.4%). The patient was administered prednisolone and antihistamine after stopping ceftriaxone empirically. A skin biopsy confirmed the diagnosis of leukocytoclastic vasculitis. Significant clinical improvement was observed after treatment initiation. Upon follow-up, the skin rash was resolved entirely with no scars; however, there was skin-peeling over the lower extremities. Recognition of antibiotic-induced leukocytoclastic vasculitis is crucial as many classes of antibiotics can contribute to this condition. Continuation of the offending drug may lead to life-threatening complications.

Dupilumab: An emerging therapy in allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) is a highly resistant disease and is challenging to treat. Patients with recurrent attacks of the disease despite surgical management can benefit from biologics as adjunct therapies. Dupilumab has shown promising endpoints in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). This case series reports 4 patients with resistant AFRS concomitant with asthma, for which dupilumab therapy was administered. Long-term follow-ups showed that dupilumab improved the symptoms and improved the results of objective tools such as imaging and pulmonary function test.

Lung fibrosis is induced in ADAR2 overexpressing mice via HuR-induced CTGF signaling.

Adenosine deaminase acting on RNA 2 (ADAR2), an RNA editing enzyme is involved in a site-selective modification of adenosine (A) to inosine (I) in double-stranded RNA (dsRNA). Its role in the lungs is unknown. The phenotypic characterization of Adarb1 mice that lacked ADAR2 auto-regulation due to the deletion of editing complementary sequence (ΔECS mice) determined the functional role of ADAR2 in the lungs. ADAR2 protein expression increased in the ΔECS mice. These mice display immune cell infiltration and alveolar disorganization. The lung wet by dry ratio indicates there is no lung edema in ΔECS mice. Bronchoalveolar lavage (BAL) analysis of ΔECS mice reveals a significant increase in neutrophils. Interestingly, ΔECS mice spontaneously develop lung fibrosis as indicated by Sirius red staining of collagen fibers in the lung sections and a significant increase in hydroxyproline level in their lungs. ADAR2 expression increased significantly in a bleomycin mouse model, implicating a role of ADAR2 in lung fibrosis. Furthermore, there is a likely possibility that the genetically modified ΔECS mice does not model the physiological or pathophysiological process of lung fibrosis. Nevertheless, this model is useful in interrogating the role of ADAR2 in the lungs. The Ctgf mRNA and connective tissue growth factor (CTGF) protein significantly increased in ΔECS lungs and occurs in bronchial epithelial cells. There is a significant increase in Human antigen R (ELAVL1; HuR) protein levels in ΔECS lungs and suggests a role in stabilizing Ctgf mRNA. Lung mechanics such as total respiratory resistance, Newtonian resistance and tissue damping were increased, whereas inspiratory capacity was decreased in the ΔECS mice. Taken together, these data indicate that overexpression of ADAR2 causes spontaneous lung fibrosis via HuR-mediated CTGF signaling and implicate a role for ADAR2 auto-regulation in lung homeostasis. The identification of ADAR2 target genes in ΔECS mice would facilitate a mechanistic understanding of the role of ADAR2 in the lungs and provide a therapeutic strategy for lung fibrosis.

Nonrespiratory Comorbidities in Asthma.

Asthma is a chronic heterogeneous airway disease. Common comorbid conditions are often disproportionately present in severe asthma. Optimal care of patients with asthma requires the recognition and treatment of these comorbid conditions. This review outlines the pathophysiological mechanisms between nonrespiratory comorbid conditions and asthma and their effect on asthma outcomes. They include: type 2 diabetes mellitus, hypertension, atherosclerotic cardiovascular disease, adrenal and thyroid gland diseases, pregnancy, osteoporosis, adverse effects from medications, and mental health disorders. Studies indicate how poor glycemic control of type 2 diabetes mellitus is associated with not only greater health care utilization but poorer asthma outcomes. Also, a large health care claims database indicates that a substantial proportion of pregnant women have uncontrolled asthma and are prescribed suboptimal controller therapy. Additional data about these nonrespiratory comorbidities and medications known to benefit both nonrespiratory comorbidities and asthma are necessary.

Public Concerns and Mental Health Changes Related to the COVID-19 Pandemic Lockdown in Saudi Arabia.

BACKGROUND: Public measures to confine the spread of the novel coronavirus disease 2019 (COVID-19) infection involves partial or full lockdown by some countries including Saudi Arabia. Social isolation, and financial insecurity are potential risk factors for mental changes. This study aimed to address public concerns, and assess mental health changes, and the factors associated with mental health burden in response to the COVID-19 outbreak in Saudi Arabia after the full lockdown is widely employed. METHODS: This cross-sectional study was conducted between 30th of April, and 10th of May, 2020 by posting an online survey on social media platforms (WhatsApp, and Twitter) to collect data on participants' demographics, concerns and worries related to the COVID-19 pandemic, and mental health changes using a validated Arabic version of the self-rated Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 1,921 responded to the questionnaire. Of them, 1,429 (74.5%) were ≤ 45 years old, and 967 (50.3%) were males. Reported public concerns included disturbed lifestyle, getting self or family member infected, loss job or part of income, difficult access to routine health care, and 55.8% reported negative impact on their mental health. Hospital anxiety and depression scale revealed high rates of depression [717 (37.3%)], and anxiety [508 (26.4%)]. Binary logistic regression revealed that female gender, working for the private sector, smokers, and people with chronic diseases were at increased risk of mental illnesses (p < 0.05). CONCLUSIONS: This study addressed serious public concerns, and substantially high rates of depression and anxiety related to the COVID-19 pandemic, and lockdown.

Elevated Testosterone Is Associated with Decreased Likelihood of Current Asthma Regardless of Sex.

BACKGROUND: Asthma prevalence decreases postpuberty in males. Testosterone inhibits airway smooth muscle contraction and attenuates type 2 inflammation. OBJECTIVE: To investigate the relationship between serum testosterone and current asthma prevalence and lung function in a nationally representative data set. METHODS: Serum testosterone and self-reported physician-diagnosed current asthma data were obtained from 7584 participants aged 6 to 80 years from the cross-sectional 2011-2012 National Health and Nutrition Examination Survey. We used logistic regression to test associations between testosterone and current asthma, adjusting for demographic characteristics and stratifying by sex and age; linear regression to evaluate correlations between testosterone and lung function among patients with asthma; and interaction terms to test for effect modification by blood eosinophils and fractional exhaled nitric oxide. RESULTS: Serum testosterone inversely associated with odds of current asthma in both men and women, but this association was nonlinear. Similar protective effect sizes were observed for both sexes after log2-transformation of serum testosterone. For every 1-unit increase in log2 testosterone, the odds of current asthma decreased by 11% in men and 10% in women, although the association was statistically significant in women only among those 12 years or older after multiple imputation. Serum testosterone did not associate with current asthma prevalence among those younger than 12 years. Testosterone associated with increases in FEV1 in participants with asthma of both sexes. Neither blood eosinophils nor fractional exhaled nitric oxide modified the association between testosterone and current asthma. CONCLUSIONS: Serum testosterone inversely associates with current asthma prevalence regardless of sex and correlates with better lung function in a nationally representative database. Androgen therapy for asthma should be further investigated.

Approaches to patients with variants in RAG genes: from diagnosis to timely treatment.

Introduction: Patients with primary immunodeficiency secondary to abnormal recombinase activating genes (RAG) can present with broad clinical phenotypes ranging from early severe infections to autoimmune complications and inflammation. Immunological phenotype may also vary from T-B- severe combined immunodeficiency to combined immunodeficiency or antibody deficiencies with near-normal T and B cell counts and even preserved specific antibody response to pathogens. It is not uncommon that RAG variants of uncertain significance are identified by serendipity during a broad genetic screening process and pathogenic RAG variants are increasingly recognized among all age groups, including adults. Establishing the pathogenicity and clinical relevance of novel RAG variants can be challenging since RAG genes are highly polymorphic. This review paper aims to summarize clinical phenotypes of RAG deficiencies and provide practical guidance for confirming the direct link between specific RAG variants and clinical disease. Lastly, we will review the current understanding of treatment option for patients with varying severity of RAG deficiencies. Area covered: This review discusses the different phenotypes and immunological aspects of RAG deficiencies, the diagnosis dilemma facing clinicians, and an overview of current and advancement in treatments. Expert opinion: A careful analysis of immunological and clinical data and their correlation with genetic findings helps to determine the significance of the genetic polymorphism. Advances in functional assays, as well as anti-cytokine antibodies, make it easier to resolve the diagnostic dilemma.

Effects of Exposure to New Car Interiors in Patients With Asthma and Allergic Rhinitis.

RATIONALE: Vehicle interiors are an important microenvironment for atopic subjects. This study evaluated the subjective and objective physiologic and clinical effects of exposing subjects with asthma and allergic rhinitis to new 2017 Mercedes vehicles during 90-minute rides. METHODS: Ten adult asthmatics with allergic rhinitis were assessed before and 45 and 90 minutes into rides in a 2017 Mercedes-Benz S-Class sedan and GLE-Class SUV on 2 separate days. Assessments included spirometry, fractional exhaled nitric oxide, peak nasal inspiratory flow, asthma symptom scores, and physical examinations. RESULTS: Of the 10 subjects, 6 were women, mean age was 32 years, and 6 and 4 were using chronic asthma controllers or intranasal corticosteroids, respectively. None of the subjects had worsening of asthma or rhinitis symptoms during the rides. There were no statistically significant changes from baseline in forced expiratory volume in 1 second, forced expiratory volume in 1 second:forced vital capacity ratio, forced expiratory flow at 25%-75% of vital capacity, fractional exhaled nitric oxide, or peak nasal inspiratory flow at 45 or 90 minutes into the rides with either Mercedes vehicle (all P values > .1 using generalized linear mixed model). CONCLUSION: The interior environment of the tested Mercedes vehicles did not cause changes in subjective or objective measures of asthma and allergic rhinitis. We suggest that this model system can be used to test other vehicles for putatively adverse effects on patients with allergic respiratory disorders.

Biologics in Chronic Urticaria.

Chronic urticaria (CU) is defined as wheals, angioedema, or both, that last more than 6 weeks. Second-generation antihistamines are considered the first-line therapy for CU. Unfortunately, many patients will fail antihistamines and require alternative therapy, including immune response modifiers or biologics. Multiple biological agents have been evaluated for use in antihistamine-refractory CU, including omalizumab, rituximab, and intravenous immunoglobulin; omalizumab is the most efficacious. Because of the success of omalizumab, multiple new biologics that are directed at the IgE pathway are under investigation. This review summarizes the relevant data regarding the efficacy of biologics in antihistamine-refractory CU.

Long-Acting Muscarinic Antagonists for Difficult-to-Treat Asthma: Emerging Evidence and Future Directions.

Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma. These studies led to FDA approval for tiotropium use in asthma. In this review, we discuss how the neurotransmitter acetylcholine itself contributes to inflammation, bronchoconstriction, and remodeling in asthma. We further describe the current clinical studies evaluating LAMAs in adult and adolescent patients with asthma, providing a comprehensive review of the current known physiological benefits of LAMAs in respiratory disease.

The Electronic Cigarette: The Good, the Bad, and the Ugly.

Electronic cigarettes (EC) are battery-powered nicotine delivery systems that have increased in popularity since they entered the US market. EC has been reported to contain less carcinogens than traditional cigarettes, cause less acute lung effects in healthy individuals, and may help with smoking cessation. It has also been viewed as a potential safer alternative for asthmatic smokers, but its effects on lung functions are unclear. However, EC do carry some harmful aspects as they contain formaldehyde and formaldehyde-forming hemiacetals as well as potentially toxic particulate matter that deposits on surfaces. EC are an increasingly popular device that could serve as a gateway into traditional cigarette smoking or illicit drugs. The popularity of EC has brought with it money from large tobacco corporations and mass marketing. Lack of regulation has generated product inconsistency and potential health hazards. This review highlights what is known and what still needs to be answered about EC.

Role of biologics in intractable urticaria.

Chronic urticaria (CU) is a common condition faced by many clinicians. CU has been estimated to affect approximately 0.5%-1% of the population, with nearly 20% of sufferers remaining symptomatic 20 years after onset. Antihistamines are the first-line therapy for CU. Unfortunately, nearly half of these patients will fail this first-line therapy and require other medication, including immune response modifiers or biologics. Recent advances in our understanding of urticarial disorders have led to more targeted therapeutic options for CU and other urticarial diseases. The specific biologic agents most investigated for antihistamine-refractory CU are omalizumab, rituximab, and intravenous immunoglobulin (IVIG). Of these, the anti-IgE monoclonal antibody omalizumab is the best studied, and has recently been approved for the management of CU. Other agents, such as interleukin-1 inhibitors, have proved beneficial for Schnitzler syndrome and cryopyrin-associated periodic syndromes (CAPS), diseases associated with urticaria. This review summarizes the relevant data regarding the efficacy of biologics in antihistamine-refractory CU.