scholarly journals Organizing Pneumonia in Rheumatoid Arthritis Patients: A Case-Based Review

2015 ◽  
Vol 9s1 ◽  
pp. CCRPM.S23327 ◽  
Author(s):  
Shunsuke Mori ◽  
Yukinori Koga ◽  
Mineharu Sugimoto
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Systemic Steroid ◽  
First Year ◽  
Organizing Pneumonia ◽  
Low Disease Activity ◽  
Dmard Therapy ◽  
Systemic Steroid Therapy ◽  
Citrullinated Peptide

We treated 21 patients with organizing pneumonia (OP) associated with rheumatoid arthritis (RA) or related to biological disease-modifying antirheumatic drugs (DMARDs) at our institution between 2006 and 2014. Among these cases, 3 (14.3%) preceded articular symptoms of RA, 4 (19.0%) developed simultaneously with RA onset, and 14 (66.7%) occurred during follow-up periods for RA. In the case of OP preceding RA, increased levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor were observed at the OP onset. RA disease activity was related to the development of OP in the simultaneous cases. In the cases of OP developing after RA diagnosis, 10 of 14 patients had maintained low disease activity with biological DMARD therapy at the OP onset, and among them, 6 patients developed OP within the first year of this therapy. In the remaining four patients, RA activity was not controlled at the OP onset. All patients responded well to systemic steroid therapy, but two patients suffered from relapses of articular and pulmonary symptoms upon steroid tapering. In most of the RA patients, DMARD therapy was introduced or restarted during the steroid tapering. We successfully restarted a biological DMARD that had not been previously used for patients whose RA would otherwise have been difficult to control. In this study, we also perform a review of the literature on RA-associated or biological DMARD-related OP and discuss the pathogenesis and management of OP occurring in RA patients.

Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic Review

2015 ◽  
Vol 42 (11) ◽  
pp. 2012-2022 ◽  
Author(s):  
T. Martijn Kuijper ◽  
Femke B.G. Lamers-Karnebeek ◽  
Johannes W.G. Jacobs ◽  
Johanna M.W. Hazes ◽  
Jolanda J. Luime
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
First Year ◽  
Low Disease Activity ◽  
Dmard Therapy ◽  
Disease Flare ◽  
Medical Databases ◽  
Tnf Blockers ◽  
Biologic Dmard ◽  
Necrosis Factor

Objective.To evaluate the risk of having a disease flare in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD) therapy.Methods.A search in medical databases including publications from January 1950 to February 2015 was performed. Included were trials and observational studies in adults with RA who were in LDA or remission, evaluating ≥ 20 patients tapering or stopping DMARD. Flare rates had to have been reported. A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF) blockers.Results.Four studies evaluated synthetic DMARD. Flare rates ranged from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies reported on TNF blockers. Estimated flare rates by metaanalysis on studies tapering or stopping TNF blockers were 0.26 (95% CI 0.17–0.39) and 0.49 (95% CI 0.27–0.73) for good-quality and moderate-quality studies, respectively. Flare rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year, and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1 year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic progression in patients deescalating treatment all found limited to no progression.Conclusion.Results suggest that more than one-third of patients with RA with LDA or in remission may taper or stop DMARD treatment without experiencing a disease flare within the first year. Dose reduction of TNF blockers results in lower flare rates than stopping and may be noninferior to continuing full dose. Radiological progression after treatment deescalation remains low, but may increase slightly.

OP129 Predictors Of Effectiveness In Patients With Rheumatoid Arthritis

2017 ◽  
Vol 33 (S1) ◽  
pp. 59-60
Author(s):  
Jéssica dos Santos ◽  
Haliton Oliveira ◽  
Francisco Acurcio Michael da Silva ◽  
Alessandra Almeida ◽  
Flávia Rodrigues ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Univariate Analysis ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Chi Square ◽  
Low Disease Activity ◽  
Gender Education

INTRODUCTION:Biological disease-modifying anti-rheumatic drugs (bDMARDs) have become firmly established in the management of patients with rheumatoid arthritis (RA), but some patients do not improve despite therapy. This study evaluated the predictors of effectiveness of the bDMARDs on a cohort of patients with rheumatoid arthritis (RA) in the Brazilian Public Health System.METHODS:RA individuals treated with bDMARDs, were included in the open prospective cohort study. The Clinical Disease Activity Index (CDAI) was used to assess the effectiveness comparing results at baseline and after 6 months of follow-up. The association between socio-demographic and clinical characteristics with the disease activity measured by the CDAI was also investigated. The bDMARDs was considered effective when the patient achieved remission or low disease activity and considered not effective when there was still moderate or high disease activity. Pearson's chi-square was applied for the univariate analysis to evaluate the association of effectiveness measured by the CDAI with the socio-demographic (gender, education, marital status and race) and clinical variables (type of drug, EuroQol (EQ)-5D and Health Assessment Questionnaire (HAQ)). Logistic regression was applied in the multivariate analysis of the variables that presented a p< .20 value during the univariate analysis.RESULTS:All 266 RA patients completed six months of follow-up. The most widely used bDMARDs was adalimumab (57.1 percent), with etanercept used by 22.2 percent, golimumab by 7.5 percent, abatacept by 4.5 percent, tocilizumab by 3.4 percent, infliximab by 2.6 percent, certolizumab by 1.5 percent, and rituximab by 1.1 percent. The bDMARDs reduced disease activity as measured by CDAI at six months of follow-up (p<.001). The percentage of patients achieving remission or low disease activity was 40.6 percent. bDMARDs were more effective in patients with better functionality (Odds Ratio, OR = 2.140 / 95 percent Confidence Interval, CI 1.219 - 3.756) at beginning of treatment and in patients who not had a previous bDMARDs (OR = 2.150 / 95 percent CI 1.144 - 4.042).CONCLUSIONS:In this real-world study, functionality and use of previous bDMARDs are predictors in patients with RA treated with bDMARDs.

scholarly journals Organizing Pneumonia Preceding Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Yoshiaki Kinoshita ◽  
Atsuhiko Sakamoto ◽  
Kouko Hidaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Factor ◽  
First Year ◽  
Organizing Pneumonia ◽  
Peptide Antibody ◽  
High Prevalence ◽  
One Year ◽  
Almost All ◽  
Citrullinated Peptide ◽  
Anticyclic Citrullinated Peptide Antibodies

Rheumatoid arthritis patients are susceptible to interstitial lung disease, and joint manifestations of rheumatoid arthritis usually precede lung involvements by several years. Organizing pneumonia, as the first manifestation of rheumatoid arthritis, is extremely rare, and its clinical features remain currently unknown. We present a case and a literature review of patients who were pathologically diagnosed with organizing pneumonia first and met the diagnostic criteria of rheumatoid arthritis later. In this review, we observed the following: (1) patients with organizing pneumonia preceding rheumatoid arthritis have a high prevalence of rheumatoid factor or anticyclic citrullinated peptide antibodies; (2) almost all patients developed rheumatoid arthritis within one year after the diagnosis of organizing pneumonia. We suggest that patients with organizing pneumonia and positive for either rheumatoid factor or anticyclic citrullinated peptide antibody should be cautiously followed up regarding the development of rheumatoid arthritis, particularly during the first year after the diagnosis of organizing pneumonia.

scholarly journals Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts

2019 ◽  
Vol 8 (10) ◽  
pp. 1548 ◽  
Author(s):  
Mueller ◽  
Hasler ◽  
Popp ◽  
Mattow ◽  
Durmisi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Randomized Clinical Trials ◽  
Liver Enzymes ◽  
Real Life ◽  
Gastrointestinal Symptoms ◽  
Janus Kinase ◽  
Secondary Outcome ◽  
Low Disease Activity

: Introduction: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Methods: Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). Results: A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d–3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection (n = 5), myalgia (n = 2), remission (n = 2), headache (n = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all n = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Conclusions: Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.

scholarly journals Imputing missing data of function and disease activity in rheumatoid arthritis registers: what is the best technique?

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e000994 ◽  
Author(s):  
Denis Mongin ◽  
Kim Lauper ◽  
Carl Turesson ◽  
Merete Lund Hetland ◽  
Eirik Klami Kristianslund ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Missing Data ◽  
Disease Activity ◽  
Multiple Imputation ◽  
Mixed Effects ◽  
Attrition Bias ◽  
Low Disease Activity ◽  
True Value ◽  
The Mean

ObjectiveTo compare several methods of missing data imputation for function (Health Assessment Questionnaire) and for disease activity (Disease Activity Score-28 and Clinical Disease Activity Index) in rheumatoid arthritis (RA) patients.MethodsOne thousand RA patients from observational cohort studies with complete data for function and disease activity at baseline, 6, 12 and 24 months were selected to conduct a simulation study. Values were deleted at random or following a predicted attrition bias. Three types of imputation were performed: (1) methods imputing forward in time (last observation carried forward; linear forward extrapolation); (2) methods considering data both forward and backward in time (nearest available observation—NAO; linear extrapolation; polynomial extrapolation); and (3) methods using multi-individual models (linear mixed effects cubic regression—LME3; multiple imputation by chained equation—MICE). The performance of each estimation method was assessed using the difference between the mean outcome value, the remission and low disease activity rates after imputation of the missing values and the true value.ResultsWhen imputing missing baseline values, all methods underestimated equally the true value, but LME3 and MICE correctly estimated remission and low disease activity rates. When imputing missing follow-up values at 6, 12, or 24 months, NAO provided the least biassed estimate of the mean disease activity and corresponding remission rate. These results were not affected by the presence of attrition bias.ConclusionWhen imputing function and disease activity in large registers of active RA patients, researchers can consider the use of a simple method such as NAO for missing follow-up data, and the use of mixed-effects regression or multiple imputation for baseline data.

AB0315 RETENTION RATE OF ABATACEPT MONOTHERAPY IN AN ITALIAN MULTICENTRIC RHEUMATOID ARTHRITIS COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1456.1-1457
Author(s):  
D. Iacono ◽  
I. Pantano ◽  
D. Birra ◽  
G. Scalise ◽  
M. A. Coscia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Median Duration ◽  
Retention Rate ◽  
Real Life ◽  
Physician Global Assessment ◽  
Low Disease Activity ◽  
Baseline Activity ◽  
Disease Modifying

Background:EULAR recommendations focus the importance of Methotrexate (MTX) therapy as a key element in the treatment of patients with Rheumatoid Arthritis (RA), alone as first line therapy and in combination with biological Disease Modifying Anti-rheumatic Drug (bDMARDs). Abatacept (CTLA4-Ig) in Europe is approved for the treatment of moderate to severe active RA in combination with MTX. Several patients, however, discontinue MTX for intolerance, side effects or contraindications, and real-life data demonstrate how, even in patients receiving therapy with MTX, compliance could be suboptimal. The only data on the use of abatacept in monotherapy come from the ORA-Registry, where a worse performance is observed in monotherapy patients.Objectives:To evaluate a multicenter cohort of RA patients treated with Abatacept in patients underwent combined MTX therapy vs monotherapy.Methods:We retrospectively evaluated RA patients, referring to 2 Italian rheumatology centers, treated with Abatacept monotherapy or in combination with MTX. We compared both persistence in therapy and the rate of remission/low disease activity according to Clinical Disease Activity Index (CDAI) between the 2 groups.Results:We enrolled 147 patients, out of them 66 patients were on monotherapy with Abatacept due to intolerance or controindications and 81 in therapy with Abatacept plus MTX. The two cohorts appeared homogeneous in age, gender, disease duration and baseline activity indexes, with the only difference being higher baseline Physician Global assessment (PhGA) values in monotherapy patients. During the follow-up (median duration 24±14 months), the retention rate of Abatacept treatment was 71.2% in MTX patients (median duration 27–15.6 months) and 62.1% in monotherapy patients (median duration 25.2–17.5; p=ns). No differences between the two groups in terms of retention rate, low-disease activity and CDAI remission (log rank p=ns), Breslow p=ns) were detected.Conclusion:In patients with RA with intolerance or contraindication to MTX use, Abatacept monotherapy could be an efficient and safe option even in the long term follow-up.References:[1]Abatacept monotherapy compared with abatacept plus disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients: data from the ORA registry.Truchetet ME et al. Arthritis Res Ther. 2016 Mar 30;18:72.Disclosure of Interests:DANIELA IACONO Speakers bureau: PFIZER, BRISTOL MAYERS SQUIBB, SANOFI, Ilenia Pantano: None declared, domenico birra: None declared, GIUSEPPE SCALISE: None declared, Melania Alessia Coscia: None declared, VALENTINA MESSINITI: None declared, Gabriella Loi: None declared, Anna Merchionda: None declared, Paolo Moscato: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvie

scholarly journals P06 Driving up quality: local observations from the National Early Inflammatory Arthritis Audit

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Jack Loh ◽  
Joshua Withers ◽  
Sarah FIsh ◽  
Elizabeth MacPhie
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Arthritis ◽  
First Year ◽  
Drug Education ◽  
Dmard Therapy ◽  
North West ◽  
Patient Pathway ◽  
The North ◽  
Early Inflammatory Arthritis

Abstract Background The National Early Inflammatory Arthritis Audit (NEIAA) provides the opportunity for rheumatology services to benchmark the care they provide against NICE quality standards (QS) 33. It provides a mechanism to identify where improvements can be made. This project assessed compliance against QS2: patients are seen in a rheumatology clinic within 3 weeks of referral and QS3: patients with newly diagnosed RA should be offered short-term glucocorticoids and a combination of DMARDs within 6 weeks of referral. Methods Data submitted to the NEIAA online tool during the first year of the audit were downloaded for analysis. Results were presented to the Rheumatology Multi-Disciplinary Team. The patient pathway was mapped, driver diagrams were developed by the team and areas for improvement identified. Results In total 246 patients were recruited to the audit, 71(29%) had confirmed rheumatoid arthritis (RA) and were included in the follow-up cohort. All patients had a baseline form completed, and 61 (86%) had a 3-month follow-up form completed. The mean patient age in the RA cohort was 62 years (range: 26-88). Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) status was recorded in 69 (97%) and 63 (88%) respectively with, 33 (52%) positive for RF and 26 (38%) for ACPA. Twenty-two patients (8.9%) were seen within 3 weeks of being referred and 5 patients (7%) started DMARD therapy within 6 weeks of referral. On average, patients waited 66 days (range: 5-138) to be seen and diagnosed, and if sent for investigations on average a further 50 days (range: 37-69) to diagnosis. There was an additional wait for drug education, with patients waiting a mean of 25 days and 39 days if they had been sent for investigations to confirm diagnosis. Prior to starting DMARD therapy 65 (90%) patients were given bridging steroids. Sixty-five (92%) patients started DMARDs, and in those that didn’t there was justification. A higher proportion of patients &gt;65years started DMARD monotherapy in sero-positive patients and those with a high DAS28 we found more use of combination DMARD therapy. Process mapping and driver diagrams highlighted areas for improvement, both clinician and patient in origin. Regarding QS2 these include developing referral guidelines for primary care, increasing triage capacity, simplifying the booking process, increasing new appointment capacity (additional consultant, upskilling extended scope practitioner and specialist nurse) and introducing text reminders. In relation to QS3 these include: one-stop clinic with access to ultrasound, increasing drug education and monitoring clinic capacity, improve sign-posting to National Rheumatoid Arthritis Society. Conclusion The NEIAA has provided detailed information about the patient pathway which has enabled the team to identify priority areas for improvement. The prospective nature of the audit will allow the team to determine if changes are improving performance. Disclosures J. Loh None. J. Withers None. S. FIsh None. E. MacPhie Other; EM is the secretary of the North West Rheumatology Club; meetings are supported by an unrestricted educational grant from UCB.

scholarly journals AB0177 RHEUMATOID ARTHRITIS SAUDI DATABASE (RASD): A SINGLE CENTER EXPERIENCE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1388.2-1388
Author(s):  
R. Hassan ◽  
M. Cheikh ◽  
H. Almoallim ◽  
H. Faruqui ◽  
R. Alquraa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treat To Target ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Research Support ◽  
Low Disease Activity ◽  
American College Of Rheumatology ◽  
Disease Modifying

Background:National Registries are essential to direct current practice and design appropriate management strategies1. Rheumatoid arthritis (RA) registries in the middle east and north Africa remain scarcely represented2.Objectives:Our objective is to describe the Saudi RA population and to compare the findings to internationally reported data.Methods:This is a cross sectional, analytical study that was conducted at Doctor Soliman Fakeeh Hospital (DSFH). The study ran from December of 2014 and concluded in December of 2018 using a pool of 433 patients. Inclusion criteria included adults older than 18 years of age who fulfilled the 2010 American College of Rheumatology criteria for diagnosis of RA3. Data were collected from patients and entered in a specially designed program for this registry. They included main demographic details,, lag times to final disease diagnosis. Disease Activity Score-28-C Reactive Protein (DAS-28-CRP) was calculated on presentation and on subsequent visits with intervals ranging from three to six months between them. Multiple regression model was used to assess the predictors of disease activity. We charted the lines of medications given, including conventional and biologic disease modifying antirheumatic drugs (DMARDs), following treat to target strategies4.Results:Out of 430 patients, 76.68% were female, while only 23.32% were male and the mean age was found to be 49.26 years with SD±11.At initial presentation, 45.5% had demonstrated active disease (moderate or high disease activity) based on DAS-28-CRP scores while 54.5% were in remission or low disease activity. Out of the total number of clinic visitors, 330 had regular follow ups for more than 1 year while 103 patients were either irregularly visiting the rheumatology clinic or had lost follow up. The remission rates after 1 year had increased to 79.7% (263 patients), while 9.7% (32 patients) had low disease activity and no patients had sustained high disease activity at the end of follow up. It was also found that the female gender, higher Health Assessment Questionnaire-Disability Index (HAQ-DI) and a longer lag1/lag2 period were associated with higher disease activity in our population. Biologic medications had been used by 129 patients (29.7%) while conventional DMARDs were given to 304 patients (70.3%).Conclusion:We described a population of RA patients in a single center in SA. We detected higher remission rates at one year of follow up. This could be attributed to many factors, including good referral systems and treat to target strategies with easier access to biologic medications.References:[1]Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O’Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.Arthritis Rheumatol.2016 Jan;68(1):1-26.[2]Smolen, Josef S., et al. “EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update.”Annals of the rheumatic diseases73.3 (2014): 492-509.[3]Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis.Arthritis Rheum2008;59: 762–84.[4]Hussain W, Noorwali A, Janoudi N. From symptoms to diagnosis: an observational study of the journey of rheumatoid arthritis patients in Saudi Arabia.Oman Med J.2016;31(1):29.Disclosure of Interests:Rola Hassan Grant/research support from: Pfizer pharmaceuticals, Mohamed Cheikh Grant/research support from: Pfizer pharmaceuticals, Hani Almoallim Grant/research support from: Pfizer pharmaceuticals, Hanan Faruqui Grant/research support from: Pfizer pharmaceuticals, Reem AlQuraa Grant/research support from: Pfizer pharmaceuticals, Ayman Eissa Grant/research support from: Pfizer pharmaceuticals, Aous Alhazmi Grant/research support from: Pfizer pharmaceuticals, Nahid Janoudi Grant/research support from: Pfizer pharmaceuticals

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