Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

Curcumin is effective in managing oral inflammation: An in vitro study.

BACKGROUND: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. METHODS: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. RESULTS: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. CONCLUSION: This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.

The Saudi initiative for asthma - 2024 update: Guidelines for the diagnosis and management of asthma in adults and children.

The Saudi Initiative for Asthma 2024 (SINA-2024) is the sixth version of asthma guidelines for the diagnosis and management of asthma for adults and children that was developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up-to-date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA Panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5-12 years, and children aged <5 years. SINA guidelines have focused more on personalized approaches reflecting a better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. The medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient-doctor partnership in the management that also includes a self-management plan.

Epigenetics in the diagnosis and prognosis of head and neck cancer: A systematic review.

BACKGROUND: Aberrant epigenetic modifications significantly develop and progress human malignancies including head and neck squamous cell carcinoma (HNSCC). Taking into account issues of late diagnosis and poor prognosis associated with HNSCC, this systematic review is designed to provide an up-to-date insight of epigenetic changes in the management of HNSCC. METHODS: All studies that assessed the diagnostic and prognostic utilities of epigenetic changes (DNA methylation and histone modifications) among patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) were considered for inclusion till June 2023. Pre-defined Medical Subject Headings terms were used to search Web of Science, Pubmed, Scopus and Embase Ovid databases. RESULTS: Twenty-five studies were deemed eligible for inclusion with a total number of 3790 samples (2123 HNSCCs, 334 OPMDs and 1333 as controls). DNA methylation was investigated in 18 studies while the role of histone modifications was assessed in seven studies. The most investigated biomarkers among the studies were H3, DAPK and TIMP3. The diagnostic accuracy of the epigenetic biomarkers in detecting HNSCC was assessed in eight studies where the following biomarkers showed the highest area under the curve values: TIPM3, DCC, DAPK, SEPT9, SHOX9, HOXA9 and TRH. None of the studies assessed the predictability of the epigenetic biomarkers in HNSCC and OPMDs. CONCLUSION: Although initial promising results were seen using the epigenetic biomarkers in the early detection of HNSCC, the limited number of patients and the absence of well-designed longitudinal studies limit the clinical applicability of the outcomes.

Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS: gov: NCT02637050; registered December 2015.

Clinical competency of dental health professionals and students in diagnosing oral mucosal lesions.

OBJECTIVE: Proper identification of oral potentially malignant disorders (OPMDs) provides an opportunity for oral cancer prevention. This study aims to assess the competency of dental health professionals in identifying OPMDs and, in turn, reducing the incidence of oral malignancy by early detection. METHODS: A 26-case online questionnaire of oral mucosal lesions was distributed to cohorts of 363 dental health professionals and dental students in Australia. The participants were asked to provide their provisional diagnosis for each case based on the available information. RESULTS: The overall accuracy in identifying oral mucosal lesions was 65.9%. There were no significant differences in the overall diagnostic accuracies between dental specialists, general dental practitioners and final-year dental students (p > 0.05). The lowest diagnostic accuracies were associated with normal mucosal variations and OPMDs. The predoctoral dental curriculum showed statistically significant values in terms of improving skills in diagnosing oral mucosal lesions. CONCLUSIONS: Lack of adequate knowledge in identifying OPMDs was evident among the participants, highlighting a non-promising figure in reducing the incidence of oral cancers in Australia. Comprehensive modifications of the current continuing professional development system are required to ensure adequate knowledge among dental health providers in Australia.

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes.

BACKGROUND: Dysregulation of the hypoxia-aerobic system has been postulated in various malignancies. Nonetheless, the contribution of hypoxia to oral carcinogenesis is yet to be elucidated. Understanding this mechanism is important for improving diagnostic tools and targeted therapies. This study aimed to assess the dysregulation of hypoxia-related factors during different stages of oral squamous cell carcinoma (OSCC) development. METHODS: Ninety-two patients diagnosed clinically with oral leukoplakia or OSCC were included and classified according to their histopathological diagnoses. A panel of seven hypoxia-related antibodies were used for immunohistochemical staining of each case. Automated quantification of immunostaining was used for objective reporting. Microvessel density was also assessed. RESULTS: Significant associations were reported for non-dysplastic epithelial changes and malignancy for Glut1, HIF-1α, vascular endothelial growth factor, and signal transducer and activator of transcription 3(p < 0.005). Similarly, microvessel density significantly increased with the severity of epithelial disorders. A multiple regression model including the H-score of HIF-1α and microvessel density could statistically significantly predict the grade of epithelial disorder (p < 0.005). The associated diagnostic accuracy of this approach was 88%. CONCLUSIONS: Hypoxia-associated events are observed during early epithelial dysplastic changes and have a potential role in oral carcinogenesis. The level of hypoxia may assist in stratifying the severity of epithelial changes among patients with oral leukoplakia.

Salivary-Based Cell-Free Mitochondrial DNA Level Is an Independent Prognostic Biomarker for Patients with Head and Neck Squamous Cell Carcinoma.

Changes in the copy numbers of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) have shown promising diagnostic utilities among patients with head and neck squamous cell carcinoma (HNSCC). Considering the absence of objective prognostic tools for HNSCC surveillance, this study aimed to assess the utility of saliva-based cf-nDNA and cf-mtDNA in predicting the overall survival of patients with HNSCC. The study included ninety-four patients with a confirmed HNSCC diagnosis with a mean follow-up time of 32.04 months (±19.1). A saliva-based liquid biopsy was collected from each patient. A multiplex quantitative PCR was used to determine the absolute number of cf-nDNA and cf-mtDNA. The Kaplan-Meier estimator and Cox proportional hazards regression models were used to assess overall survival. The absolute copy numbers of cf-nDNA and cf-mtDNA were statistically significantly higher among the deceased patients than among the censored ones (p < 0.05). Individuals with elevated levels of cf-nDNA or cf-mtDNA were associated with a significantly poorer overall survival (p ≤ 0.05). A univariate analysis showed that only the absolute copy number of cf-mtDNA was the sole predictor of overall survival. However, the multivariate analysis showed that all the absolute copy numbers of cf-nDNA, the absolute copy numbers of cf-mtDNA, and the stage of HNSCC were predictors of overall survival. Our study confirms that saliva is a reliable and non-invasive source of data that can be used to predict the overall survival of patients with HNSCC, where cf-mtDNA levels act as the sole predictor.

Saliva-based cell-free DNA and cell-free mitochondrial DNA in head and neck cancers have promising screening and early detection role.

BACKGROUND: Cell-free DNA (cfDNA) and cell-free mitochondrial DNA (cf-mtDNA) have been postulated as potential diagnostic and prognostic biomarkers for different human malignancies. Early detection of head and neck malignancies is fundamental for optimal patient management. This study, therefore, aimed to assess the utility of saliva-based liquid biopsy as a noninvasive source of cfDNA and cf-mtDNA for detecting head and neck cancer (HNSCC). METHODS: One hundred thirty-three patients diagnosed with either oral leukoplakia (OLK) or HNSCC were compared with 137 healthy volunteers. An unstimulated whole saliva sample was collected from each participant. The absolute copy numbers of salivary cf-mtDNA and cfDNA were quantified using Multiplex Quantitative PCR. Two diagnostic indices based on the investigated molecules were assessed for their ability to differentiate between different diagnostic categories. RESULTS: The median scores of cfDNA and cf-mtDNA were statistically significantly higher among HNSCC patients (p < 0.05), revealing area under the curve values of 0.758 and 0.826, respectively. The associated accuracy for this test in discriminating HNSCC from other diagnostic categories was 77.37% for the cfDNA-based index and 80.5% for the cf-mtDNA-based index. The median score of cfDNA was statistically significantly higher for patients with severe epithelial dysplasia (OED) compared to those with epithelial keratosis with no OED and mild OED. However, there was no significant difference between controls and OLK individuals. CONCLUSION: cfDNA and cf-mtDNA showed potential for use as precision medicine tools to detect HNSCC. Further multi-centre prospective studies are warranted to assess the prognostic utility of these molecules.

A Curcumin-Based Oral Gel Has Potential Protective Efficacy against Oral Mucositis: In Vitro Study.

Oral mucositis is a common distressing complication of cancer therapy, characterised by painful sores within the oral cavity. Current management options offer limited symptomatic relief. Curcumin, a natural polyphenolic compound with recognised anti-inflammatory and antioxidant properties, has emerged as a potential protective agent against oral mucositis. This study explores the therapeutic potential of curcumin in mitigating the impact of oral mucositis by investigating a commercially available curcumin-based oral gel, PerioGold®. Liquid chromatography-tandem mass spectrometry was used to characterise the main constituents of PerioGold®. The cytotoxicity of curcumin constituent was investigated in four cell lines: primary oral keratinocytes (HOKs), immortalised oral keratinocytes (OKF6), dysplastic oral keratinocytes (DOKs), and oral squamous cell carcinoma cells (PE/CA-PJ15). Concentrations of hydrogen peroxide were optimised to develop in vitro models that mimic oral mucositis. The inhibitory effects of PerioGold® against the production of reactive oxygen species were assessed using a designated kit. OKF6 cells were the most sensitive to oxidative stress, while PE/CA-PJ15 cells showed the highest resistance. Pretreatment of the investigated cells for 24 h with PerioGold® demonstrated a significant antioxidative effect in all cells based on a dose-response pattern. PerioGold® exhibits clinical potential for protecting against oxidative stress, warranting further individualised clinical investigations.

When single-inhaler triple therapy is a preferred option in asthma management?

Asthma control is the main goal of management. Unfortunately, most asthma patients with moderate-severe asthma remain uncontrolled despite receiving standard treatment of inhaled corticosteroids (ICS) with long-acting ß2 agonists (LABA). The addition of long-acting antimuscarinic agents (LAMA) has been shown to improve different aspects of asthma control, including symptoms, lung functions, and probably exacerbations. Such an option could be considered for low-T2 asthma phenotype. Umeclidinium and glycopyrronium bromide are other LAMA agents that have been recently made available in combination with ICS and LABA in single-inhaler triple therapy (SITT) devices. Here, we discuss the position of SITT as a new novel therapeutic option in asthma management and its clinical benefits, potential cost saving, and improved compliance.

Efficacy of Mouth Rinses and Nasal Spray in the Inactivation of SARS-CoV-2: A Systematic Review and Meta-Analysis of In Vitro and In Vivo Studies.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a global and evolving pandemic associated with heavy health and financial burdens. Considering the oral cavity as the major reservoir for SARS-CoV-2, a systematic review and meta-analysis were conducted to assess the efficacy of mouth rinses and nasal sprays in reducing the salivary viral load of SARS-CoV-2. All in vivo and in vitro studies that assessed the virucidal efficacy of mouth rinses and nasal sprays against SARS-CoV-2 and were published in the English language from December 2019 to April 2022 were considered for analyses. Special Medical Subject Headings terms were used to search Pubmed, Scopus, Embase Ovid, and Web of Science databases. The toxicological data reliability assessment tool (ToxRToool) was used to assess the quality of the included studies. Thirty-three studies (11 in vivo and 22 in vitro) were deemed eligible for inclusion in this analysis. Results of the pooled data showed that povidone-iodine is the most efficacious intervention in vivo in terms of reducing the SARS-CoV-2 salivary viral load, followed by chlorhexidine. The mean difference in the viral load was 86% and 72%, respectively. Similarly, povidone-iodine was associated with the highest log10 reduction value (LRV) in vitro, followed by cetylpyridinium chloride, (LRV = 2.938 (p < 0.0005) and LRV = 2.907 (p = 0.009), respectively). Povidone-iodine-based oral and nasal preparations showed favourable results in terms of reducing SARS-CoV-2 viral loads both in vivo and in vitro. Considering the limited number of patients in vivo, further studies among larger cohorts are recommended.

Oral brush biopsy using liquid-based cytology is a reliable tool for oral cancer screening: A cost-utility analysis: Oral brush biopsy for oral cancer screening.

BACKGROUND: This study aimed to assess the diagnostic utility and associated cost of oral liquid-based brush cytology (OLBC) in the diagnosis of oral cancer and oral potentially malignant disorders (OPMDs). METHODS: A total of 284 patients with oral mucosal lesions were included. OLBC samples were collected from all patients immediately before undergoing surgical biopsies. A liquid-based cytology slide was prepared from each OLBC sample for cytological evaluation using the modified 2014 Bethesda cytology system. The results and the cost were compared with the histopathological outcomes. RESULTS: The level of agreement between the two approaches was very good (weighted kappa = 0.824). The accuracy of OLBC in differentiating between the different diagnostic groups was 91.69%, whereas the associated sensitivity and specificity were 79.23% and 94.81%, respectively. The estimated cost of each OLBC sample was at least 26% less than the cost of a single biopsy and more than 42% less in cases of multiple biopsied lesions. CONCLUSIONS: The proposed modifications of the Bethesda system can be adopted as a standardized system for oral cytological assessment. Our findings support OLBC as a reliable adjunct to surgical biopsy in the diagnosis of OPMDs. This tool has potential for oral cancer-finding and surveillance programs.

Immunoexpression of oral brush biopsy enhances the accuracy of diagnosis for oral lichen planus and lichenoid lesions.

BACKGROUND: This study assessed the efficacy of using oral liquid-based brush cytology (OLBC) coupled with immunostained cytology-derived cell-blocks, quantified using machine-learning, in the diagnosis of oral lichen planus (OLP). METHODS: Eighty-two patients diagnosed clinically with either OLP or oral lichenoid lesion (OLL) were included. OLBC samples were obtained from all patients before undergoing surgical biopsy. Liquid-based cytology slides and cell-blocks were prepared and assessed by cytomorphology and immunocytochemistry for four antibodies (Ki-67, BAX, NF-κB-p65, and AMACR). For comparison purposes, a sub-group of 31 matched surgical biopsy samples were selected randomly and assessed by immunohistochemistry. Patients were categorized according to their definitive diagnoses into OLP, OLL, and clinically lichenoid, but histopathologically dysplastic lesions (OEDL). Machine-learning was utilized to provide automated quantification of positively stained protein expression. RESULTS: Cytomorphological assessment was associated with an accuracy of 77.27% in the distinction between OLP/OLL and OEDL. A strong concordance of 92.5% (κ = 0.84) of immunostaining patterns was evident between cell-blocks and tissue sections using machine-learning. A diagnostic index using a Ki-67-based model was 100% accurate in detecting lichenoid cases with epithelial dysplasia. A BAX-based model demonstrated an accuracy of 92.16%. The accuracy of cytomorphological assessment was greatly improved when it was combined with BAX immunoreactivity (95%). CONCLUSIONS: Cell-blocks prepared from OLBC are reliable and minimally-invasive alternatives to surgical biopsies to diagnose OLLs with epithelial dysplasia when combined with Ki-67 immunostaining. Machine-learning has a promising role in the automated quantification of immunostained protein expression.

PD-1/PD-L1, Treg-related proteins, and tumour-infiltrating lymphocytes are associated with the development of oral squamous cell carcinoma.

Cancer immunomodulation has been implicated in the development of oral squamous cell carcinoma (OSCC), however the role of specific immunomodulatory proteins is not completely understood, particularly in the early stages of the disease. Oral potentially malignant disorders such as leukoplakia commonly precede OSCC but not all will undergo malignant transformation. The aim of this study was to evaluate the diagnostic utility of specific immunomodulator proteins and their role in the progression of OSCC. Samples from 101 patients were included in the study. Cases were classified based on histopathology into four groups: non-dysplastic epithelial hyperplasia/keratosis, low-grade dysplasia, high-grade dysplasia, and OSCC. The PD-1/PD-L1 pathway, as well as regulatory T cell (Treg)-related proteins including FOXP3, TGF-ß, IL-6, and IL-10 were immunohistochemically quantified. The number of tumour-infiltrating lymphocytes (TILs) was also assessed for each case. Multinominal regression models were undertaken to assess the significance of each protein in predicting the histopathological grade of oral epithelial disorders, and three diagnostic models were assessed. Significant positive associations were found between the immunoreactive score of each protein and the histopathological grade, p<0.05 suggesting that the PD-1/PD-L1 pathway, Treg-related proteins, and TILs are associated with the development of OSCC. Diagnostic models using the investigated proteins and TILs predicted the grade of oral epithelial disorder, p<0.05. The associated accuracy of this approach was 84.92%. Our findings support the notion that immunomodulation events may play a role in evading the immune system and contributing to potential malignant transformation of oral epithelial disorders. Our data also provide supporting evidence for the potential application of immune checkpoint inhibitors in the chemoprevention of OSCC. Further longitudinal studies to assess individual T-cell populations within the immune microenvironment of various oral potentially malignant disorders are warranted.

Clinical and physiological characteristics of, medically treated, chronic thromboembolic pulmonary hypertension patients in Saudi Arabia: A single center experience.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is uncommon but well-known sequel of venous thromboembolism (VTE). At present, it is the only potential curable subtype of pulmonary hypertension. The aim of this study is to describe the medically treated-CTEPH patients' characteristics in a single specialized PH center in Saudi Arabia. METHODS: This study presents demographic, clinical, physiological, and hemodynamic characteristics of medically treated-CTEPH patients in a single PH center, namely Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Both incident and prevalent cases are included. RESULTS: A total of 20 patients with a confirmed diagnosis of CTEPH were included. Mean age at diagnosis was 43 years with a female preponderance of 75%. Most common presenting symptom was dyspnea (100%) followed by syncope (58%). At diagnosis, a mean of 15 ± 10 months had passed since symptoms onset. About 45% of patients were in WHO functional class IV. At baseline, mean 6-min walk distance was 354.3 meters. Overall, VTE was the most frequent risk factor identified (65% of all patients). Nearly 30% of patients had sickle cell disease. 13 out of 20 patients had radiographic (i.e., computed tomography [CT] pulmonary angiogram) features of chronic thromboembolism. About 75% of patients were found to have distal disease on radiographic imaging. At the time of diagnosis, 7 out of 20 (35%) patients demonstrated right ventricular failure on echocardiography. Mean tricuspid annular plane systolic excursion was 17.7 ± 1.20. Median NT-proBNP levels were found to be 688 pg/ml. Mean diffusing capacity for carbon monoxide was 74.8%. CONCLUSIONS: Diagnosis of CTEPH was established at a relatively younger age. Majority of patients had advanced but distal disease on radiographic imaging, not amenable to surgery.

Unmet need in the management of chronic obstructive pulmonary disease in the Middle East and Africa region: An expert panel consensus.

Chronic obstructive pulmonary disease (COPD) has a significant impact on healthcare systems and health-related quality of life. Increased prevalence of smoking is an important factor contributing to high burden of COPD in the Middle East and Africa (MEA). Several other factors including sedentary lifestyle, urbanization, second-hand smoke, air pollution, and occupational exposure are also responsible for the upsurge of COPD in the MEA. Frequent COPD exacerbations accelerate disease progression, progressively deteriorate the lung function, and negatively affect quality of life. This consensus is based on review of the published evidence, international and regional guidelines, and insights provided by the expert committee members from the MEA region. Spirometry, though the gold standard for diagnosis, is often unavailable and/or underutilized leading to underdiagnosis of COPD in primary care settings. Low adherence to the treatment guidelines and delayed use of appropriate combination therapy including triple therapy are additional barriers in management of COPD in MEA. It is necessary to recognize COPD as a screenable condition and develop easy and simple screening tools to facilitate early diagnosis. Knowledge of the disease symptomatology at patient and physician level and adherence to the international or regional guidelines are important to create awareness about harmful effects of smoking and develop national guidelines to focus on prevention on COPD. Implementation of vaccination program and pulmonary rehabilitation are equally valuable to manage patients with COPD at local and regional level. We present recommendations made by the expert panel for improved screening, diagnosis, and management of COPD in MEA.

A machine-learning algorithm for the reliable identification of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a relatively common oral disorder which shares clinical and histopathological features with other lichenoid lesions, leading to considerable inter-observer disagreement. This negatively impacts understanding of the pathogenesis and malignant transformation potential of this condition. METHODS: Artificial intelligence was employed to create a machine-learning artificial neural network to identify and quantify mononuclear cells and granulocytes within the inflammatory infiltrates in digitized hematoxylin and eosin microscopic slides. Twenty-four regions of interest were extracted from OLP cases for learning purposes and validated on a retrospective cohort of 130 cases. All cases were related to patients with confirmed diagnoses of OLP, oral lichenoid lesions (OLLs), or oral epithelial dysplasia (OED) with lichenoid host response. RESULTS: The number of inflammatory cells was statistically significantly higher in OLP compared to OLLs or OED with lichenoid host response (p < 0.0005). The proposed machine-learning method was reliably capable of detecting OLP cases based on the number of inflammatory cells and the number of mononuclear cells with an area under the curve of 0.982 and 0.988, respectively. Identifying a cut-off point between OLP and other lichenoid conditions based on the number of mononuclear cells showed a sensitivity of 100% and an accuracy of 94.62%. CONCLUSION: Artificial intelligence has shown promising outcomes and provides a robust approach to enhance the accuracy of anatomical pathologists in accurately diagnosing OLP using features of disease pathogenesis.

Patients' and physicians' attitudes and perception about asthma in the Gulf: A subset analysis from the Asthma Insights and Management Survey in the Gulf and Russia.

Background: Asthma is a prevalent disorder in the Gulf region. However, available data concerning asthma control and patients' perception with regard to their disease are still insufficient. Objective: To investigate patients' perception and behavior with regard to the asthma-related burden, the level of asthma control, and asthma management in three Gulf countries. Methods: This study presented a subset analysis of the Asthma Insights and Management survey about the asthma burden and management in the Gulf region and Russia. In this subset analysis, we retrieved the data of the patients from Saudi Arabia, United Arab Emirates, and Kuwait. Results: The current survey's population was composed of 452 patients. One hundred fifty-four patients (34.1%) rated themselves as having poorly controlled asthma, whereas 60.3% of the patients perceived their asthma as completely or well controlled. However, only two patients (0.4%) had controlled asthma according to the global asthma guidelines criteria for asthma control. Most of the patients (67.7%) reported that their asthma got worse when outdoors. Almost 70% of the patients on daily control plus a quick relief regimen reported that their asthma got worse when they were outdoors. Over the past 12 months, 95 patients (21%) reported asthma exacerbation. More than half of the included patients experienced an asthma attack that stopped their activities, whereas 54.2% of the patients were forced to leave work or school due to an asthma attack, and 53.1% had to cancel an appointment or had to go to bed due to the severity of the attack. With concern to asthma management, only 30.5% of the patients were given a lung function test for the assessment of their asthma. A written action plan for asthma treatment was developed by the physician or the practice nurse for only 21.7% of the patients. Conclusion: In the Gulf region, asthma exerts a substantial burden on patients who are affected. Such a burden significantly impacted patients' quality of life.

Observer agreement in the diagnosis of oral lichen planus using the proposed criteria of the American Academy of Oral and Maxillofacial Pathology.

BACKGROUND: Oral lichen planus (OLP) is a common chronic inflammatory condition with an undefined malignant transformation potential. There have been many attempts at providing a specific definition of OLP without conclusive outcomes. A new set of diagnostic criteria was proposed in 2016 by the American Academy of Oral and Maxillofacial Pathology (AAOMP) in an endeavour to resolve this issue, and this has not yet been evaluated. This study aimed to assess the utility of AAOMP proposed criteria for the diagnosis of OLP. METHODS: Five pathologists blindly assessed a cohort of 215 digital whole slide images (WSI) obtained from haematoxylin and eosin-stained microscopic slides. Forty-six WSI were included twice to assess the intra-observer agreement. Included cases were diagnosed clinically as either OLP or oral lichenoid reaction. Each pathologist was asked to utilize the AAOMP histopathological criteria while assessing slides. The variations in diagnoses were assessed by unweighted kappa statistics. RESULTS: The level of intra-observer agreement was very good (0.801 to 0.899). The level of inter-observer agreement among the observers varied from good (0.658) to very good (0.842) when the responses were categorized as evident/compatible OLP versus no OLP and was good (0.62 to 0.725) when the responses were categorized as evident OLP, versus compatible OLP, versus no OLP. The clinico-pathological correlation was 87.6%. CONCLUSION: A reliable level of agreement can be achieved by pathologists for the diagnosis of OLP using the AAOMP criteria for differentiation between lichenoid and other conditions. There are still limitations in discriminating OLP from oral lichenoid lesions microscopically.