A Retrospective Analysis of Disease Epidemiology, Comorbidity Burden, Treatment Patterns, and Healthcare Resource Utilization of Migraine in the United Arab Emirates.

INTRODUCTION: Migraine is a recurrent, disabling neurological disorder with a substantial global disease burden. However, limited real-world data are available on the patient characteristics, treatment patterns, comorbidities, and economic burden of migraine in the United Arab Emirates (UAE). In this study, we evaluated the disease burden, comorbidities, treatment patterns, specialties involved in migraine diagnosis, and healthcare resource utilization (HCRU) and associated costs in patients with migraine in Dubai, UAE. METHODS: A retrospective, secondary database cohort study was conducted from 01 January 2014 to 31 March 2022 using the Dubai Real-World Database. Patients aged ≥ 18 years with at least one diagnosis claim for migraine with continuous enrollment during the study period were included. Patients were stratified into treatment sub-cohorts. Outcomes were evaluated in terms of clinical characteristics, comorbidities, specialists visited, treatment patterns, and HCRU. RESULTS: The study included 203,222 patients (mean age: 40 years), with male predominance (55.4%). About 13.4% of patients had specific cardiovascular comorbidities. Frequently prescribed drug classes were nonsteroidal anti-inflammatory drugs (84.4%), triptans (29.8%), and beta-blockers (12.8%), while only 1.0% of patients with migraine were prescribed newer medications like calcitonin gene-related peptide antagonists. General medicine was the most frequently visited specialty on the index date (51.5%). The all-cause and migraine-specific median gross costs during the 12-month post-index period were US $1252.6 (2.4-564,740.7) and US $198.1 (0-168,903.3) respectively, with maximum contribution from inpatients. The contribution of migraine-specific median costs to all-cause median costs was highest for the diagnosis-related group (64.9%), followed by consumables (35.2%), medications (32.0%), procedures (24.5%), and services (24.5%). CONCLUSION: Migraine significantly impacts healthcare costs in the UAE. The role of newer therapies in migraine management should be explored to reduce the associated socioeconomic burden and improve patients' quality of life.

Optimization of Advanced Molecular Genetic Testing Utilization in Hematopathology: A Goldilocks Approach to Bone Marrow Testing.

PURPOSE: This study investigated the effectiveness of algorithmic testing in hematopathology at the Brigham and Women's Hospital and Dana-Farber Cancer Institute (DFCI). The algorithm was predicated on test selection after an initial pathologic evaluation to maximize cost-effective testing, especially for expensive molecular and cytogenetic assays. MATERIALS AND METHODS: Standard ordering protocols (SOPs) for 17 disease categories were developed and encoded in a decision support application. Six months of retrospective data from application beta testing was obtained and compared with actual testing practices during that timeframe. In addition, 2 years of prospective data were also obtained from patients at one community satellite site. RESULTS: A total of 460 retrospective cases (before introduction of algorithmic testing) and 109 prospective cases (following introduction) were analyzed. In the retrospective data, 61.7% of tests (509 of 825) were concordant with the SOPs while 38.3% (316 of 825) were overordered and 30.8% (227 of 736) of SOP-recommended tests were omitted. In the prospective data, 98.8% of testing was concordant (244 of 247 total tests) with only 1.2% overordered tests (3 of 247) and 7.6% omitted tests (20 of 264 SOP-recommended tests; overall P < .001). The cost of overordered tests before implementing SOP indicates a potential annualized saving of $1,347,520 in US dollars (USD) in overordered testing at Brigham and Women's Hospital/DFCI. Only two of 316 overordered tests (0.6%) returned any additional information, both for extremely rare clinical circumstances. CONCLUSION: Implementation of SOPs dramatically improved test ordering practices, with a just right number of ancillary tests that minimizes cost and has no significant impact on acquiring key informative test results.

Prevalence of Gene Rearrangement by Multiplex PCR in De Novo Acute Myeloid Leukemia in Adult Iraqi Patients.

Introduction: Gene rearrangements of acute myeloid leukemia (AML) play a significant role in categorizing patients and provide valuable information about prognosis and treatment choices. However, in Iraq, the prevalence and prognostic significance of gene rearrangements in AML have not been previously examined. Methods: This study utilized a multiplex reverse transcription real-time PCR (RT-qPCR) system to identify gene rearrangements in a group of 115 adult patients from Iraq who had been diagnosed with De Novo AML. The diagnosis of AML was confirmed through blood film and flow cytometry. The ethical committee of the College of Medicine at the University of Baghdad provided approval for this research study. Results: In this study, 66.1% of the patients diagnosed with acute myeloid leukemia (AML) exhibited distinct genetic abnormalities. Among these abnormalities, the most frequent was the rearrangement involving the KMT2A gene, observed in 19.9% of the patients. The risk stratification analysis revealed that 40% of the patients were classified as having a favorable risk, 4.3% as intermediate risk, and 25.2% as adverse risk. A subtype of AML known as core-binding factor (CBF) AML was identified in 21.7% of the cases, with 84% of these patients achieving complete remission. The NPM-RARA gene rearrangement, found in 43% of acute promyelocytic leukemia (APL) cases, was associated with a 71% complete remission rate. Among patients with KMT2A rearrangement, which accounted for 19.9% of all AML cases, the MLL-AF10 rearrangement was the most common, although only one patient with KMT2A rearrangement achieved complete remission. Furthermore, the analysis of demographic data revealed a significant association between increased risk and advanced age, presence of comorbidities, and FAB classification (M0 subtype). Conclusion: The prevalence of genetic rearrangements in Iraqi De Novo AML patients is higher than the global trend, highlighting the importance of genetic characterization in risk assessment and treatment decisions.

Autopsy findings from patients diagnosed with COVID-19 demonstrate unique morphological patterns in bone marrow and lymph node.

AIMS: The identification of haemophagocytosis in bone marrow (BM) is recurrently identified in patients with severe COVID-19. These initial COVID-19 autopsy studies have afforded valuable insight into the pathophysiology of this disease; however, only a limited number of case series have focused on lymphoid or haematopoietic tissues. METHODS: BM and lymph node (LN) specimens were obtained from adult autopsies performed between 1 April 2020 and 1 June 2020, for which the decedent had tested positive for SARS-CoV-2. Tissue sections (H&E, CD3, CD20, CD21, CD138, CD163, MUM1, kappa/lambda light chains in situ hybridisation) were examined by two haematopathologists, who recorded morphological features in a blinded fashion. Haemophagocytic lymphohistiocytosis (HLH) was assessed based on HLH 2004 criteria. RESULTS: The BM demonstrated a haemophagocytic pattern in 9 out of 25 patients (36%). The HLH pattern was associated with longer hospitalisation, BM plasmacytosis, LN follicular hyperplasia and lower aspartate aminotransferase (AST), as well as ferritin at demise. LN examination showed increased plasmacytoid cells in 20 of 25 patients (80%). This pattern was associated with a low absolute monocyte count at diagnosis, lower white cell count and lower absolute neutrophil count at demise, and lower ferritin and AST at demise. CONCLUSIONS: Autopsy results demonstrate distinct morphological patterns in BM, with or without haemophagocytic macrophages, and in LN, with or without increased plasmacytoid cells. Since only a minority of patients met diagnostic criteria for HLH, the observed BM haemophagocytic macrophages may be more indicative of an overall inflammatory state.

Efficacy and safety of topical agents in the treatment of melasma: What's evidence? A systematic review and meta-analysis.

BACKGROUND: Various topical agents have been used to treat melasma; however, a large-scale evaluation among the currently available treatment is lacking. OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of topical agents for melasma. METHODS: The MEDLINE, Embase, Web of Science, Cochrane, and Alt-Healthwatch databases were searched in November 2021. Original studies that reported pre- and post-treatment Melasma Area Severity Index (MASI)/modified Melasma Area Severity Index (mMASI) scores and/or adverse effects (AEs) were eligible for inclusion. The main outcome was the efficacy analyzed by the changes in the pre- and post-treatment with standardized mean difference (SMD) of MASI/mMASI scores; the AEs were calculated with incidence proportion by the reported percentage of skin irritations. RESULTS: A total of 45 studies (2359 patients) and 55 studies (4539 patients) met the inclusion criteria for efficacy and AEs, respectively. Hydroquinone (HQ) monotherapy (SMD -1.3, 95% CI [-1.6 to -1.0]), HQ-containing combination therapy (-1.4, [-1.7 to -1.1]), cysteamine (-1.6, [-2.0 to -1.2]), tranexamic acid (-1.5, [-2.0 to -1.1]), azelaic acid (-1.3, [-1.7 to -1.0]), and kojic acid (-0.9, [-1.3 to -0.5]) demonstrated comparable efficacy, while zinc sulfate did not exhibit statistically significant improvement (-1.2, [-2.7 to 0.4]). HQ-containing combination therapy (50.9%) and cysteamine (42.2%) demonstrated the highest incidence of irritation, while azelaic acid (18.7%), kojic acid (5.3%), and tranexamic acid (0.8%) revealed a lower risk. CONCLUSIONS: In this meta-analysis, non-HQ agents except zinc sulfate may be considered as an alternative to HQ-containing agents. However, treatment should be guided by patient's tolerance, availability, and physicians' experience.

Long-Term Adherence to Etanercept in Treatment Effectiveness of Patients with Spondyloarthritis: 7-Year Data from the Iraq National Registry.

INTRODUCTION: The diagnosis and treatment of spondyloarthritis (SpA) is a global challenge, with no cure available. Adherence to treatment with biologic disease-modifying antirheumatic drugs, such as the tumor necrosis factor-α inhibitor etanercept, varies among patients with SpA. Inadequate or poor adherence to treatment may have a negative effect on clinical outcome and quality of life and may lead to greater health-related expense. METHODS: This observational, retrospective study used real-world patient data from the Iraq National Center of Rheumatology database to retrospectively assess long-term adherence to etanercept, specifically evaluating 1- and 7-year adherence to etanercept among Iraqi patients with SpA. RESULTS: In total, data from 763 patients were included in the analysis. The majority of patients were men (82.2%). Mean disease duration at baseline was 5.85 years; 84.0% of patients received concomitant steroids, and 14.2% were treated with concomitant methotrexate. Measures of disease activity and functional status (mean ± SD) at baseline based on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) were 8.06 ± 0.83 (range 6.0-9.5) and 7.75 ± 1.12 (range 4.1-9.7), respectively. Around 30% of patients initiated etanercept treatment within 1 year of diagnosis. After 1 and 7 years, 91.7% (700/763) and 60.6% (80/132) of patients were adherent to etanercept treatment. Mean (± SD) changes from baseline in BASDAI and BASFI scores for adherent versus non-adherent patients at 1 year were 6.73 (± 1.90) versus 4.20 (± 1.85) (p = 0.0001) and 6.43 (± 2.04) versus 4.18 (± 1.88) (p = 0.0001), respectively. CONCLUSIONS: These results suggest that Iraqi patients with SpA benefit from long-term adherence to etanercept treatment; however, additional analyses are needed to further assess the reasons for treatment discontinuation, which may include disease remission. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04507776.

The Clinical Impact of Seropositivity on Treatment Response in Patients with Rheumatoid Arthritis Treated with Etanercept: A Real-World Iraqi Experience.

Purpose: To assess the clinical impact of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA)'s seropositivity on treatment response in patients with rheumatoid arthritis (RA) treated with etanercept. Patients and Methods: A retrospective analysis of patients with RA registered in Baghdad Teaching Hospital Registry from May 2012 to August 2019 was conducted. Patients aged ≥18 years, meeting the ACR/EULAR 2010 criteria for RA, being treated with etanercept, and followed up at ≥1 year after etanercept initiation were included; patients who received any other biologics for RA were excluded. Patients were classified as seropositive (RF- and ACPA-positive), seronegative (RF- and ACPA-negative), RF-positive, RF-negative, ACPA-positive, and ACPA-negative. The primary outcomes included Clinical Disease Activity Index (CDAI) and Disease Activity Score 28 (DAS28) which were measured at one year after treatment initiation. Results: At baseline, a total of 1318 (88.3%) patients were seropositive; 1122 (75.2%) and 1054 (70.6%) patients were RF- and ACPA-positive, respectively. Baseline mean CDAI scores were significantly (P = 0.001) higher among seropositive patients compared with seronegative patients. The baseline mean DAS28 score was also significantly higher in ACPA-positive group compared with the ACPA-negative group (P = 0.021). At baseline, the number of patients who had high CDAI scores was significantly higher among the seropositive, RF-positive, and ACPA-positive groups (P = 0.001, P = 0.001, and P = 0.002, respectively). After one year of treatment with etanercept, among seropositive versus seronegative and ACPA-positive versus ACPA-negative groups, there was a significant improvement in terms of the mean CDAI score (P = 0.004 and P = 0.017, respectively) and CDAI response (P = 0.011 and P = 0.048, respectively). At one year, the proportion of patients among the seropositive versus seronegative group who reached remission were 566 (42.9%) versus 78 (44.6%) and 642 (47.3%) versus 83 (47.4%), for CDAI and DAS28 response, respectively. Conclusion: The results imply that seropositivity and ACPA-positivity may influence the treatment response in patients with RA, who were treated with etanercept.

Clinical Outcomes in Iraqi Patients with Rheumatoid Arthritis Following Earlier or Later Treatment with Etanercept.

PURPOSE: The development of evidence-based guidelines on early pharmacotherapeutic treatment of rheumatoid arthritis (RA) could be useful in Middle Eastern nations striving to improve outcomes in patients with this chronic, debilitating disease. Evidence obtained from local populations should inform such guidelines and therefore our aim was to use real-world data to evaluate the clinical responses of Iraqi patients with RA who received earlier or later treatment with the TNF inhibitor etanercept. PATIENTS AND METHODS: Data from patients registered in the Iraq National Center of Rheumatology database from May 2012 to December 2018, inclusive, were analyzed retrospectively. Inclusion criteria were age ≥18 years, meeting the ACR/EULAR 2010 criteria for RA, referral for etanercept treatment, and ≥1 year of follow-up after etanercept initiation. Patients were excluded if they had received another biologic for RA. Included patients were categorized according to two separate stratifications: whether duration of RA symptoms prior to etanercept initiation was ≤10 or >10 years (10 years represented the mean duration for the entire analysis population); and according to whether duration of RA symptoms prior to etanercept initiation was ≤1, >1 to ≤4, >4 to ≤10, >10 to ≤20, or >20 years. The evaluated outcomes were mean change from baseline in Clinical Disease Activity Index (CDAI) and 28-joint Disease Activity Score (DAS28) after 1 year of etanercept treatment. RESULTS: A total of 979 patients were included. CDAI and DAS28 were significantly reduced (p<0.001 for both) after 1 year of etanercept treatment irrespective of whether duration of RA symptoms prior to treatment was ≤10 or >10 years. Patients with RA symptoms for ≤1 year prior to etanercept initiation showed a significant reduction in CDAI after 1 year of treatment (p=0.01). CONCLUSION: Iraqi patients with RA who received earlier treatment with etanercept had superior outcomes compared with those who received later treatment.