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The novel coronavirus disease 2019 (COVID-19), which caused Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was appeared at the end of 2019 in wuhan city in china. Covid-19 has high ability of transmission from human to another human, and due to its fast spread globally, the World Health Organization (WHO) announced that Covid-19 is pandemic disease on March 11, 2020. Several articles have reported many common ENT-related symptoms as an early sign of COVID19. To measure the prevalence of insomnia and dysgeusia in COVID19 patients in Saudi Arabia and investigate their functional and psychological effects on patients. This study evaluated the impact of insomnia and dysgeusia on COVID-19 patients' quality of life using the short version of the Olfactory Disorders-Negative Statements (sQODNS) Questionnaire. It was done from 5 June to 30 July 2020, in the Eastern region of Saudi Arabia. A total of 274 laboratory-confirmed COVID-19 patients were participated. The most common ENT-related symptoms were headache 69%, insomnia 65.3%, and dysgeusia 64.6%. Interestingly, insomnia can greatly affect patients' daily life, as around 37.6% of our patients had problems with taking part in daily activities, 42% felt isolated, 68.1% had changes in appetite, 51.4% had more stress, and 28.2% had increased anger secondary to loss of smell. In Addition, 62% (110) of patients who lost their taste declared that their daily activities were affected. ENT-related symptoms are one of the most COVID19 manifestations. The duration of both insomnia and dysgeusia is an important contributing factor on the patients' functional & psychological state as it may prolong their isolation period. Therefore, Otolaryngologists considered the first-line physicians for many of Covid-19 patients, which makes us at higher risk to be infected with Covid-19 too. It is also particularly important for Otolaryngologists to develop a management guideline to reduce the duration and severity of all ENT-related features.

الملخص: أهداف البحث: دراسة العلاقة بين مقدار معامل زاوية ''كوب'' ومختلف كثافات العظم لدى المرضى الإناث المصابات بجنف العمود الفقري لدى اليافعات في السعودية، وقياس مدى كثافة العظام في مختلف مناطق أجسامهن. طرق البحث: استخدم البحث نموذج دراسة مقطعية كمية بعدد مناسب من المشاركات. شملت العينة المدخلة ٥٤ مريضة بجنف العمود الفقري لدى اليافعات تراوحت أعمارهن بين ١٠-٢٠ عاما. تم تسجيل معامل زاوية كوب ودرجات ''زد'' في مقياس امتصاص الأشعة السينية ثنائي البواعث لكل من عظمة الفخذ وعظمة الفقرة القطنية، وتم جمعها بين الأعوام ٢٠٠٨-٢٠١٨. النتائج: من بين ٥٤ مريضة، ٤١ منهن كان معامل زاوية كوب لديهن يتراوح بين ٤٠°-٧٠°، و١٣ بمعامل زاوية كوب ٧٠° مقارنة بالمرضى اللاتي معامل زاوية كوب 70°. The mean lumbar bone, right femur, and left femur BMDs were markedly higher in those with Cobb angles ≤70° compared with BMDs in those with Cobb angles >70°. Of the group with Cobb angles ≤70°, six (14.6%) and nine (22.0%) exhibited low BMD according to their lumbar and femoral Z-scores, respectively. Of the group with Cobb angles >70°, eight (61.5%) and nine (69.2%) exhibited low BMD according to their lumbar and femoral Z-scores, respectively. Conclusions: Female AIS patients with greater higher Cobb angles exhibited a significantly higher frequency of low BMDs.

Ahmed Y Sayed, Nasr Y Khalil, Aliyah Almomen, Nourah Z Alzoman, Abdulrahman A Almehizia, Ibrahim A Darwish Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Ibrahim A DarwishDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi ArabiaTel +966-114677348Fax +966-114676220Email idarwish@ksu.edu.saBackground: Duvelisib (DUV) is a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor. It has been recently granted an accelerated approval for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is also effective in therapy of T-cell lymphoma, solid tumors, and non-Hodgkin’s lymphoma. In literature, there is no method valid for quantitation of DUV in human plasma for its therapeutic monitoring and pharmacokinetic studies.Purpose: The purpose of this study is the establishment of a highly sensitive HPLC method with fluorescence detection for quantitation of DUV in plasma for its therapeutic monitoring and pharmacokinetic studies of DUV.Methods: The resolution of DUV and the internal standard (IS) olaparib (OLA) was achieved on Nucleosil CN column, with a mobile phase composed of acetonitrile:water (25:75, v/v) at a flow rate of 1.7 mL min– 1. The fluorescence of both DUV and OLA was detected at 410 nm after excitation at 280 nm. The method was validated according to the guidelines of bioanalytical method validation.Results: The method was linear in the range of 5– 100 ng mL– 1, and its limit of detection (LOD) and limit of quantitation (LOQ) were 2.12 ng mL– 1 and 7 ng mL– 1, respectively. The precisions of the method were ≤ 8.26%, and its accuracies were ≥ 95.32%. All the other validation parameters were satisfactory. The proposed method was successfully employed to the investigation of the pharmacokinetic profile of DUV in rats following a 25 mg/kg single dose of oral administration.Conclusion: The method is characterized with high sensitivity, accuracy, simple sample pretreatment, rapidity, eco-friendly as it consumes low volumes of organic solvent in the mobile phase and has high analysis throughput as its run time was short (~ 10 min).Keywords: leukemia, phosphoinositide-3-kinase, duvelisib; DUV, human plasma, therapeutic drug monitoring, pharmacokinetic study

The goal of this research was to prepare and characterize nanonized particles of the antifungal drug, fluconazole (FLZ) using antisolvent precipitation nanonization technique to improve its ocular permeation. The impact of various concentrations of different stabilizers, namely Pluronic F-127 (PL F 127), Kollicoat IR (KL), hydroxypropyl methylcellulose E3 (HPMC), xanthan gum (XG), polyvinyl pyrrolidone K30 (PVP), and sodium lauryl sulfate (SLS) upon the resulting nanoparticles was investigated. Additionally, the ex vivo release of the FLZ nanonized particles from ophthalmic gel bases was studied by using goat cornea, and the ocular pharmacokinetics of appropriate ophthalmic gel base containing optimized drug nanoparticle formula compared to the untreated drug were studied in rabbits. FLZ nanoparticles were successfully prepared with different concentrations of stabilizers. However, the effects of these stabilizers on nanoparticle size and zeta potential values varied according to the concentration and type of stabilizer used. Based on differential scanning calorimetry, the drug was in its amorphous state in the tested nanoparticle formulations. The results of ex vivo ocular diffusion of the FLZ nanoparticle gel formulations revealed an improvement compared to that with the FLZ untreated gel. Nanoparticle formula (F3) prepared by using 5% PL F127 showed small particle size (352 ± 6.1 nm) with zeta potential value of −18.3 mV with highest ex vivo release rate from goat cornea (100% after 6 h). Moreover, the AUC0-8h from ocular application of FLZ from sodium alginate gel containing nanoparticle formula F3 was 1.4-fold higher than that after its administration in the untreated formula. Based on our findings, the ophthalmic gel formulations containing FLZ nanoparticles enhanced drug corneal permeation and improved the ocular pharmacokinetic parameters.

Background/Introduction Despite advances in the diagnosis and management of breast cancer (BC), it is still associated with high mortality rates. New biomarkers are being developed for the diagnosis, treatment, and prediction of responses of BC. Ceramide (CER), a bioactive sphingolipid, has emerged recently as a useful diagnostic tool in several types of tumors. In this study, we evaluated CER expression in invasive BC and assessed its relation to the molecular subtypes of BC. Materials and methods The clinical data and histopathological slides of 50 patients with invasive ductal carcinoma were retrieved and reviewed. The cases were then stained with a mouse monoclonal anti-ceramide antibody. Pearson correlation was used to assess the correlation between CER percentage and intensity and other clinical and pathological variables. Results CER expression showed a direct relationship with estrogen and progesterone receptors Allred scores. However, it showed an inverse relation with tumor grade, HER2/neu status and Ki-67 index. Conclusions CER expression is likely to be associated with luminal BC molecular subtypes. However, more research is needed to confirm these results and to explore its relation to the different clinical outcomes, including response to treatment and prognosis.

People living with HIV (PLWH) often have worse health outcomes compared to HIV-uninfected individuals. We characterized PLWH followed at a tertiary care clinic in Montreal who acquired COVID-19 and described their outcomes during the first wave of the pandemic. A retrospective chart review was performed for PLWH followed at the Chronic Viral Illness Service with a positive COVID-19 nasopharyngeal PCR or symptoms suggestive of COVID-19 between 1 March and 15 June 2020. Data on demographics, socioeconomic status, co-morbidities and severity of COVID-19 and outcomes were extracted. Of 1702 individuals, 32 (1.9%) had a positive COVID-19 test (n = 24) or symptoms suspicious for COVID-19 (n = 3). Median age was 52 years [IQR 40, 62]. Nearly all (97%) earned $34,999 Canadian dollars or less. Eleven (34%) individuals worked in long-term care (LTC) homes while 5 (6%) lived in LTC homes. Median CD4 count was 566 cells/mm3 [347, 726] and six had detectable plasma HIV viral loads. Median duration of HIV was 17 years [7, 22] and 30 individuals had been prescribed antiretroviral therapy. Five persons were asymptomatic. Of symptomatic persons, 21 (12%), 1 (4%) and 3 (12%) individuals had mild, moderate and severe disease, respectively. Three individuals died with COVID-19. In one case, the cause of death was due to COVID-19, whereas in the other two cases, the individuals died with positive COVID-19 test results but the immediate cause of death is unclear. PLWH who tested positive for COVID-19 had low socioeconomic status and had employment or living conditions that put them at high risk. PLWH may be disproportionately impacted by the social determinants of health which predispose them to COVID-19.

Objectives Purchasing medicinal products from the internet has become more popular in the last three decades. Understanding consumers’ use and perception of the safety of medicinal products obtained online is essential. Therefore, this study aims to evaluate the extent of medicines purchased from the internet in Saudi Arabia, types of products, sources of information, the satisfaction, the motivational factors, and estimate consumers’ vigilance and tendency to report ADRs if occurred. Design A prospective cross-sectional study using a custom-designed questionnaire was conducted among community adults in Saudi Arabia, age ≥ 18. Setting Evaluation of community subjects' perception towards buying medicinal products was done through the internet in Saudi Arabia from 1st July 2020 until the end of August 2020. Main outcome measure(s) The main outcome of the study was purchasing medicinal products from the internet (Yes, No). Results Overall, 36% of the study participants (n = 643) have ever bought medicinal products from the internet ( Table 2 ). Of those, the most obtained was herbal medicine, supplements, or cosmetics (61.3%). Motivational factors towards purchasing medicinal products from the internet were mostly positive, with the most commonly reported agreed motivational factors were lower cost (55.7%), easy online access (54.1%), a wide variety of products (52.6%), and more privacy (43.6%). Around 60.4% of participants believed that buying medicinal products from the internet can be safe. The most perceived risk was the difficulty of distinguishing between registered online pharmacies and other unlicensed commercial websites, with only 32.7% of the participants distinguishing between registered and unlicensed commercial websites. Conclusions This study sheds light on the consumers’ use and perception of the safety and risks of medicinal products purchased from the internet. The study findings noticeably describe the great need to increase safety awareness about obtaining medicinal products from the internet among the Saudi community.

The introduction of image guidance navigation system in endoscopic sinus surgeries has been highly advocated in the recent past era. Ever since its introduction in the 1980s and 1990s in Germany it has been asserted that the image-guided navigation enhances surgical outcomes and diminished perioperative morbidities. The objective of this study is to reflect the experience of our institute with the image guidance navigation system in the frontal sinus endoscopic surgeries, specifically due to its constricted anatomy and proximity to vital structures. Retrospective chart review was performed for all image guided endoscopic frontal sinus procedures Performed at a tertiary referral center of King Fahad Specialist Hospital Dammam during the period from 2010 to 2019. A total of 450 endoscopic sinus and skull base procedures were performed using different image guidance systems. Out of the 450 cases, 231 cases were indicated for frontal sinus involvement. The fundamentals of anatomical knowledge are essential for the success of any surgery including image-guided surgeries. Utilization of image-guidance in endoscopic frontal surgeries assists in portraying the way to targeted frontal disease. It aids in localizing vital structures in distorted anatomy thus avoiding undesirable complications.

Myonecrosis is a condition that results in muscle tissue necrosis, and it is rarely seen in sickle cell patients and often missed because more common manifestations of sickle cell can overlap like vaso-occlusive crises (VOC), which results in pain in the extremities or spine; also osteomyelitis is commonly seen in sickle cell patients. In this article, we present a case of myonecrosis in a sickle cell-diseased patient who presented with left acute atraumatic left foot pain and MRI with contrast showing characteristic image of muscle infarction supportive therapy initiated, and 2-year follow-up did not reveal any physical disabilities; further study and follow-up are needed to know the nature of the disease and avoid improper management of those patients.

The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (Tgel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. Tgel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a Tgel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS). In-vivo ocular pharmacokinetics indicated a significant improvement in ophthalmic bioavailability of epinephrine (active form of DV). F8 was non-irritant to the eyes and showed a successful, continuous and superior ability to reduce IOP compared to DV-AqS in rabbits. In conclusion, our developed system could be an appropriate substitute to the conventional DV eye preparations in the management of elevated IOP.

First described by Green in 1832, persistent sciatic artery (PSA) is a rare anomaly classified into 2 types, namely complete and incomplete. We report the case of bilateral PSAs diagnosed by computed tomography angiography (CTA) in a 45-year-old female who presented with a 2-week history of pain and numbness in the left lower limb. Specifically, the CTA showed an incomplete PSA of the right lower limb and a complete PSA of the left lower limb complicated by an aneurysm. Complications of PSA, including aneurysmal rupture, occlusive thrombosis, and distal embolization, are critical as they impose serious hazards to the viability of the lower limbs. Asymptomatic patients with PSA require close surveillance for early detection and proper management of PSA-related complications, as they are prone to early atheromatous degeneration and aneurysm formation.

Highlights • Mucormycosis is a rare disease and is often fatal in the immunocompromised. • We present a series of 3 patients with poorly controlled diabetes and mucormycosis. • Diagnosing mucormycosis requires microbiologic and microscopic evidence. • Combined medical and surgical management yields better outcomes for mucormycosis., Introduction Mucormycosis is a rare, aggressive, and invasive disease with a fatal outcome. It most commonly affects patients with compromised immunity, particularly those with poorly controlled diabetes. We present a case series of patients with uncontrolled diabetes and mucormycosis. Presentation of case We present a series of three patients with uncontrolled diabetes, with main symptoms of paranasal sinusitis, nasal discharge, ophthalmic changes, and facial nerve involvement. Diagnoses of mucormycosis were made via microbiological testing and computed tomography. These cases were managed by combination therapy of tight glycemic control, urgent endoscopic sinus debridement, and antifungal therapy. Discussion Diagnosing rhino-orbito-cerebral mucormycosis requires a high degree of suspicion and both microbiologic and microscopic evidence. Better clinical outcomes can be obtained by combining medical and surgical management. Conclusion We describe our experience in handling three cases of poorly controlled diabetes with rhino-orbito-cerebral mucormycosis.

The aim of this study is to illustrate the managements of different clinical and radiological presentations of serious complications of frontal sinusitis diagnosed and managed at the tertiary referral hospital. A case series study conducted at the tertiary referral in the period from 2012 to 2019. Four different cases of serious complications of frontal sinusitis namely orbital abscess, frontal meningitis, subdural empyema and frontal lobe abscess will be presented and discussed. Despite the generous use of antibiotics, the serious complications of frontal sinusitis still develop. The serious complications of frontal sinusitis ranges from orbital abscess to frank frontal lobe abscess. The management is a combination of systemic antibiotics and surgical drainage with excellent outcomes.

Background Cancer remains the leading cause of human morbidity universally. Hence, we sought to assess the in vitro antiproliferative activity of new isatin-based conjugates (5a-s) against three human cancer cell lines. Methods The antiproliferative activities of compounds 5a-s were evaluated in vitro and their ADME (absorption, distribution, metabolism and excretion) was carried out using standard protocols. Subsequently, Western blot analysis was conducted to elucidate the potential antiproliferative mechanism of compounds 5a-s. Results The in vitro antiproliferative activities of compounds 5a-s against the tested cancer cell lines ranged from 20.3 to 95.9%. Compound 5m had an IC50 value of 1.17 µM; thus, its antiproliferative potency was approximately seven-fold greater than that of sunitinib (IC50 = 8.11 µM). In-depth pharmacological testing was conducted with compound 5m to gain insight into the potential antiproliferative mechanism of this class of compounds. Compound 5m caused an increase in the number of cells in the G1 phase, with a concomitant reduction of those in the G2/M and S phases. Additionally, compound 5m significantly and dose-dependently reduced the amount of phosphorylated retinoblastoma protein detected. Compound 5m enhanced expression of B cell translocation gene 1, cell cycle-associated proteins (cyclin B1, cyclin D1, and phosphorylated cyclin-dependent kinase 1), and a pro-apoptotic protein (Bcl-2-associated X protein gene), and activated caspase-3. ADME predictions exposed the oral liability of compounds 5a-s. Conclusion Herein, we revealed the antiproliferative activity and ADME predictions of the newly-synthesized compounds 5a-s and provided a detailed insight into the pharmacological profile of compound 5m. Thus, compounds 5a-s can potentially be exploited as new antiproliferative lead compounds for cancer chemotherapeutic.

Highlights • Surgery is the modality of choice to achieve complete evacuation of the mucocele and reestablishing the normal sinus outflow. • In determining the surgical approach to mucoceles, two main factors are considered: the patency of the ipsilateral frontal sinus outflow and the accessibility of the sinus via endoscope. • The endonasal endoscopic image guided approach is a safe, accurate, and reliable approach with no complications. • The concept behind the utility of image guidance in endoscopic marsupialization. • It is the approach of choice in managing large frontal mucopyocele with brain extension., Objective To demonstrate the effectiveness of the endonasal endoscopic approach in managing a large bilateral frontal mucopyocele causing a mass effect on the brain. Case presentation A 17 year old chronic sinusitis patient, presented with bilateral nasal obstruction and increasing left sided headache; was found to have a very large bilateral frontal mucopyoceles with extensive intracranial extradural brain involvement on CT scan and MRI of the sinuses and brain which was drained and evacuated completely using the endonasal endoscopic image guided approach with no complications. Conclusion The endonasal endoscopic image guided approach is the approach of choice in managing large frontal mucopyocele with brain extension. It is a safe, accurate, reliable approach with no complications.

Highlights • Pituitary metastasis is rare, and it is the least common intracranial site of metastases. • Majority of cases of pituitary metastasis the patient is known to have a primary malignancy. • The clinical presentation and radiological features of pituitary metastasis are not specific making diagnosis difficult. • Management may include endoscopic trans-sphenoidal resection, chemotherapy, radiotherapy and hormone replacement. • Definitive diagnosis can be achieved through surgical resection., Introduction Pituitary metastasis is rare, and it is the least common site of intracranial metastases. It is mostly asymptomatic but can present with diabetes insipidus, headache, ophthalmoplegia, visual disturbance and anterior pituitary dysfunction and in majority of cases patients known to have a primary malignancy. Case Presentation This study presents a 54-year-old male presented with a few months history of headache and drooping of both eyelids and after proper investigations and endoscopic resection of the sellar mass the diagnosis was confirmed to be pituitary metastasis of lung adenocarcinoma. Conclusion Diagnosis and management of pituitary metastases are complex and depend on many factors. Endoscopic surgical resection and debulking alleviates symptoms and provides the definitive diagnosis which has great importance in cases with clinical presentation that does not strongly point to pituitary metastasis to avoid unnecessary radiotherapy and chemotherapy when possible.

The conventional physical and chemical synthetic methods for the preparation of metal nanoparticles have disadvantages as they use expensive equipment and hazardous chemicals which limit their applications for biomedical purposes, and are not environment friendly. However, for the synthesis of biocompatible nanomaterials, plant-based techniques are eco-friendly and easy to handle. Herein a simple, single-step biosynthesis of gold nanoparticles using aqueous extracts of Nigella sativa (NSE) and Zingiber officinale (GE) as a reducing and capping agent has been demonstrated. The formation of gold nanoparticles (Au NPs) was confirmed by X-ray diffraction, UV-Vis, and EDS spectroscopies. Spectroscopic and chromatographic analysis of GE and NSE revealed the presence of bioactive phytochemical constituents, such as gingerol, thymoquinone, etc., which successfully conjugated the surface of resulting Au NPs. TEM analysis indicated the formation of smaller-sized, less-aggregated, spherical-shaped Au NPs both in the case of GE (~9 nm) and NSE (~11 nm). To study the effect of the concentration of the extracts on the quality of resulting NPs and their anticancer properties, three different samples of Au NPs were prepared from each extract by varying the concentration of extracts while keeping the amount of precursor constant. In both cases, high-quality, spherical-shaped NPs were obtained, only at a high concentration of the extract, whereas at lower concentrations, larger-sized, irregular-shaped NPs were formed. Furthermore, the as-prepared Au NPs were evaluated for the anticancer properties against two different cell lines including MDA-MB-231 (breast cancer) and HCT 116 (colorectal cancer) cell lines. GE-conjugated Au NPs obtained by using a high concentration of the extract demonstrated superior anticancer properties when compared to NSE-conjugated counterparts.

Introduction Cerebrospinal fluid (CSF) rhinorrhea is the result of a bony defect at the skull base with disruption of the arachnoid, dura mater, and sinonasal mucosa that leads to an active CSF leak and flow of clear fluid from the nose. The endoscopic repair of CSF leaks and skull defects have been used by an increasing number of surgeons and is the standard of care for repairing CSF leaks. Materials and methods We conducted a retrospective study of all cases of CSF leaks managed via the endonasal endoscopic approach from 2010 to 2020 at a tertiary referral hospital of King Fahad Specialist Hospital, Dammam (KFSH-D). Results Over 10 years, 61 procedures were performed on a total of 56 patients (average age, 39.9 years) with 26 spontaneous CSF leaks and 30 traumatic CSF leaks. The leak sites were frontal bone in 14% of the cases, the roof of the ethmoid in 25%, the cribriform plate of ethmoid in 39%, and the walls of sphenoid sinus in 21%; multiple site defects were found in eight patients. The defect was localized by high-resolution computed tomography (CT) of the paranasal sinuses and skull base and magnetic resonance imaging (MRI) in all patients. CT cisternography, intrathecal fluorescein injection, and topical application of fluorescein dye were used in patients as required. A combination of free grafts and flaps materials were used in most patients. A middle and inferior turbinate graft was used in 12 patients, a septal cartilage graft in 18 patients, and a pedicled nasoseptal flap in 12 patients. The success rate was 92% after the first closure attempt. A recurrence of CSF leaks was observed in four patients. The mean hospitalization time was 6.5 days. The postoperative follow-up period ranged from one year to 10 years with a mean postoperative follow-up time of three years. Conclusions The endonasal endoscopic approach is the current standard of care for repairing most CSF leaks and skull base defects. We have had an excellent experience with endonasal endoscopic CSF leak repair, with high success rates and low morbidity. Our results support the effectiveness and safety of this technique and should encourage otolaryngologists to apply the procedure in cases of CSF leak.

BackgroundErlotinib (ERL) and Gefitinib (GEF) are considered first line therapy for the management of non-small cell lung carcinoma (NSCLC). Like other tyrosine kinase inhibitors (TKIs), ERL and GEF are mainly metabolized by the cytochrome P450 (CYP450) CYP3A4 isoform and are substrates for transporter proteins with marked inter-/intra-individual pharmacokinetic (PK) variability. Therefore, ERL and GEF are candidates for drug-drug and food-drug interactions with a consequent effect on drug exposure and/or drug-related toxicities. In recent years, the consumption of flavoured water (FW) has gained in popularity. Among multiple ingredients, fruit extracts, which might constitute bioactive flavonoids, can possess an inhibitory effect on the CYP450 enzymes or transporter proteins. Therefore, in this study we investigated the effects of different types of FW on the PK parameters of ERL and GEF in Wistar rats.MethodsERL and GEF PK parameters in different groups of rats after four weeks consumption of different flavours of FW, namely berry, peach, lime, and pineapple, were determined from plasma drug concentrations using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS).ResultsData indicated that tested FWs altered the PK parameters of both ERL and GEF differently. Lime water had the highest impact on most of ERL and GEF PK parameters, with a significant increase in Cmax(95% for ERL, 58% for GEF), AUC0–48(111% for ERL, 203% for GEF), and AUC0–∞(200% for ERL, 203% for GEF), along with a significant decrease in the apparent oral clearance of both drugs (65% for ERL, 67% for GEF). The order by which FW affected the PK parameters for ERL and GEF was as follows: lime > pineapple > berry > peach.ConclusionThe present study indicates that drinking FW could be of significance in rats receiving ERL or GEF. Our results indicate that the alteration in PKs was mostly recorded with lime, resulting in an enhanced bioavailability, and reduced apparent oral clearance of the drugs. Peach FW had a minimum effect on the PK parameters of ERL and no significant effect on GEF PKs. Accordingly, it might be of clinical importance to evaluate the PK parameters of ERL and GEF in human subjects who consume FW while receiving therapy.

Trigeminal schwannoma is the second most common schwannoma after vestibular schwannoma. Symptoms vary depending on the anatomical structures affected by the tumor, including facial pain, paresthesia, dizziness and ataxia. The primary goals are controlling the symptoms and the maintenance of cranial nerves’ integrity perioperatively. We report a 39-year-old lady who was complaining of mild right-sided headache, vision and hearing loss, right facial weakness and dysphagia. CT and MRI showed a large dumbbell-shaped tumor originating from the trigeminal fossa abutting the petrous and cavernous carotid artery and extending to the infratemporal fossa. An image-guided endonasal endoscopic removal was successfully done. Image-guided endonasal endoscopic removal of a trigeminal schwannoma abutting the petrous and cavernous carotid artery and extending to the infratemporal fossa is a safe, effective approach, as it offers excellent visualization, accurate localization and safe dissection of the tumor from the critical anatomical neurovascular structures surrounding it.

Highlights • Tornwald’s cyst is a rare benign disease of the nasopharynx. • The disease has a diverse clinical presentation, with the majority of cases being discovered incidentally. • Nasoendoscopy, imaging studies and pathological examination can be used to confirm the disease. • Endoscopic surgical removal is an excellent safe measure for disease management., Background Tornwaldt cyst (TC) is a relatively rare but benign disease. Although these lesions are asymptomatic and found incidentally during routine ENT examination, the can present with unexplained sinonasal symptoms, such as nasal obstruction, post nasal drip and occipital headache. Aim To study the clinical presentations and outcome of Tornwaldt nasopharyngeal cyst cases diagnosed and managed in our center. Methods Patients with symptomatic TC who were operated and followed up at our center were selected for this study. Results 3 patients with a diagnosis of TC by naso-endoscopy, CT and MRI were included in this study. All patients were males, with age ranging from 54 to 86 years. A trans-nasal endoscopic surgical removal of the cyst was done for all patients with no intra or post-operative complications. All patients were free of symptoms and disease reassurance at follow up. Conclusion Although relatively rare, TC should be suspected in any patient complaining of unexplained sinonasal symptoms. Endoscopic surgical excision is a safe and effective maneuver with no cyst recurrence.

Melanoma remains the most lethal form of skin cancer and most challenging to treat despite advances in the oncology field. Our work describes the utilization of nanotechnology to target melanoma locally in an attempt to provide an advanced and efficient quality of therapy. Amino-functionalized mesoporous silica nanoparticles (MSN-NH2) were developed in situ through the utilization of anionic surfactant and different volumes of 3-aminopropyltriethoxysilane (APTES) as a co-structure directing agent (CSDA). Prepared particles were characterized for their morphology, particles size, 5-flurouracol (5-FU) and dexamethasone (DEX) loading capacity and release, skin penetration, and cytotoxicity in vitro in HT-144 melanoma cells. Results of transmission electron microscopy (TEM) and nitrogen adsorption&ndash, desorption isotherm showed that using different volumes of APTES during the functionalization process had an impact on the internal and external morphology of the particles, as well as particle size. However, changing the volume of APTES did not affect the diameter of formed mesochannels, which was about 4 nm. MSN-NH2 showed a relatively high loading capacity of 5-FU (12.6 &plusmn, 5.5) and DEX (44.72 &plusmn, 4.21) when using drug: MSN-NH2 ratios of 5:1 for both drugs. The release profile showed that around 83% of 5-FU and 21% of DEX were released over 48 h in pH 7.4. The skin permeability study revealed that enhancement ratio of 5-Fu and DEX using MSN-NH2 were 4.67 and 5.68, respectively, relative to their free drugs counterparts. In addition, the accumulation of drugs in skin layers where melanoma cells usually reside were enhanced approximately 10 times with 5-FU and 5 times with DEX when delivering drugs using MSN-NH2 compared to control. MSN-NH2 alone was nontoxic to melanoma cells when incubated for 48 h in the range of 0 to 468 &micro, g/mL. The combination of 5-FU MSN-NH2 and DEX MSN-NH2 showed significant increase in toxicity compared to their free dug counterparts and exhibited a synergetic effect as well as the ability to circumvent DEX induced 5-FU resistance in melanoma cells.

Ewing’s sarcoma (ES) is a malignant small round cell tumor that belongs to the primitive neuroectodermal tumor class. ES generally arises in the long bones of the extremities (skeletal form) and less frequently in the soft tissue of the trunk and extremities (extra-skeletal form). Sinonasal localization of ES is an extremely rare event. About 80% of the patients are less than 20 years old with the highest incidence in the second decade of life. The combination of histopathological examination and ancillary methods (such as immunohistochemistry and molecular genetics) is extremely important to establish the diagnosis of ES. The most effective treatment plan for ES includes a multidisciplinary approach with surgery, radiotherapy and chemotherapy. This is a report of two challenging cases of sinonasal ES in two different age groups. The first case is a 13-years old female patient who presented with right nasal obstruction, anosmia, intermittent epistaxis and hearing loss. The second case is a 24-years old male patient who presented with a history of right nasal obstruction, right eye pain and periorbital edema. We present these cases due to the rarity of the disease and the difficulty of diagnosis.

Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing panels. We identified 4 patients with mutations in SPG7 and 3 patients with SPAST mutations, representing 50% of the cohort and indicating a very high diagnostic yield. In the SPG7 group, we identified novel variants in two patients. We have also identified two novel mutations in the SPAST group. We present sequencing data from cDNA and RT-qPCR to support the pathogenicity of these variants, and provide observations regarding the poor genotype-phenotype correlation in these conditions that should be the subject of future study.

Highlights • Ectopic teeth are commonly seen in palate. • The pathogenesis of ectopic teeth eruption is not fully recognized. • In children, intranasal ectopic teeth occur more frequent in patients with cleft lip and alveolus. • Most cases of the ectopic tooth are asymptomatic and identified incidentally. • The management of the ectopic teeth is tooth extraction., Introduction Intranasal teeth are a rare form of ectopic teeth. Their clinical manifestation are truly variable. In children, intranasal teeth are typically associated with cleft lip and alveolus. Presentation of case Here, we report a case of 11 years –old girl presented with right nasal obstruction and occasional headache without any obvious etiology. 0Computed tomography of the paranasal sinuses (coronal and axial view) revealed displaced right upper maxillary tooth with the crown oriented inferiorly and medially toward and within the lower right anterior nasal cavity. She underwent surgery by anterior rhinoscopy and endoscopic guidance. The patient’s symptoms were resolved completely post-operatively and remained symptom-free for 18 months postoperatively. Discussion Ectopic intranasal tooth is a rare phenomenon, with a male predominance and around half of all patients are diagnosed before adulthood. Ectopic intranasal tooth arising from inferior turbinate is very rare. No clear etiological factor has been suggested in most of the reported cases. Idiopathic etiology has been described as an etiologic factor for ectopic teeth. The treatment of intranasal teeth is early surgical extraction to alleviate the symptoms and prevent the possible morbidities. Conclusion Intranasal teeth are a rare form of ectopic teeth encountered to otolaryngology clinic and may cause a variety of symptoms and complications. CT is very useful; it confirms the diagnosis and facilitates surgical planning. Early diagnosis and treatment are very important to avoid their possible complications.

Key Clinical Message This article reports on the use of Botox preoperatively for the treatment of a complex ventral hernia which would have typically been treated with component separation technique. The case demonstrates that using the recently developed technique can aid in performing a tension‐free hernia repair with potentially lower complication and recurrence rates.

Pyruvate carboxylase (PC) is a biotin-containing enzyme that is responsible for the adenosine triphosphate-dependent carboxylation of pyruvate to oxaloacetate, a key intermediate in the tricarboxylic acid cycle. PC deficiency (OMIM 266150) is a rare autosomal recessive metabolic disease, causing elevation of pyruvate, lactate, and alanine. Three types of PC deficiency have been described in the literature; A, B, and C. Type A PC deficiency, also called infantile or North American type, is characterized by infantile onset acidosis, failure to thrive, and developmental delay. The second subtype or type B, the neonatal or French form, presents usually in the neonatal period, mostly in the first 72 hours of life with severe lactic acidosis, truncal hypotonia, and seizures. The third type is called type C, is extremely rare with few cases published in the literature. In this case report, we present an 11-month-old girl who presented with acute flaccid paralysis, lethargy, and constipation with elevated ketones and lactate. She was confirmed genetically and biochemically to have PC deficiency type C. The patient's unusual presentation expands the clinical phenotype of this extremely rare disease.

The importance of so called variants of undetermined significance in the development of Infantile Epileptic Encephalopathy is discussed and an illustrative case is presented.

Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each others molecular and biological roles. Estrogen receptor α (ER) and glucocorticoid receptor(GR) are co-expressed in the uterus and their ligands have opposing effects on uterine growth and morphology, with estrogens inducing growth and corticosteroids inhibiting growth. In endometrioid-type endometrial tumors expressing ER, we surprisingly found that the expression of GR is associated with poor prognosis and higher tumor grade. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished once estrogen-induced endometrial hyperplasia was established and cancer cells increased growth when treated with dexamethasone and estradiol. To understand the underlying molecular crosstalk between ER and GR in endometrial cancer cells, we measured their genomic binding following treatment with estradiol, dexamethasone, and the combination. We found 20% overlap in bound loci when ER and GR are induced with their respective ligands individually; however, upon induction with both ligands simultaneously they co-occupy significantly more sites (47%). ER binding is only slightly affected by the presence of dexamethasone, while GR binding is significantly altered by the presence of estradiol with GR being recruited to loci bound by ER that contain estrogen response elements. The GR sites gained in the presence of estradiol consist of loci that become more accessible upon estradiol induction, supporting a model where ER assists in the chromatin loading of GR. The crosstalk in genomic binding is associated with gene expression changes upon co-treatment being more similar to estradiol than dexamethasone, but with novel regulated genes including a decrease in cell-cell adherens junction genes. Our results suggest both a phenotypic and molecular interplay between ER and GR in endometrial cancer.

Highlights • Allergic fungal rhinosinusitis nature in children is more aggressive when compared to adults. • Endoscopic sinus surgery is an important therapeutic step in the treatment of allergic fungal rhinosinusits. • The reason for this contralateral development of AFRS not clear, but it may be part of the natural disease process. • Involvement of the contralateral sinuses in children is uncommon. The normal uninvolved sinus should be involved in the routine endoscopic examination and the post-operative treatment in order to minimize the risk of disease recurrence., Objectives to report the alternating nature of allergic fungal rhinosinusitis in children in the Eastern part of Saudi Arabia and to review the experience of King Fahad Specialist Hospital in the diagnosis and management of alternating allergic fungal rhinosinusitis in children. An 8 years old Saudi girl with alternating allergic fungal rhinosinusitis was diagnosed and managed. The patient was diagnosed to have unilateral left allergic fungal rhinosinusitis and underwent endoscopic sinus surgery and cleaning of the left sinuses from polyps, mud and mucin. One year postoperatively the patient developed AFRS in the contralateral right side. Conclusion involvement of the contralateral sinuses in children with AFRS is uncommon. The normal uninvolved sinus should be involved in the routine endoscopic examination and the post-operative treatment in order to minimize the risk of disease recurrence.

Highlights • Schwannoma is a benign nerve sheath tumor that can arise from any myelinated nerve fiber. • Nasal septal schwannoma is rare, and only 32 cases have been reported in the literature. • The diagnosis of the nasal septal schwannoma primarily depends on histopathological examination. • Endoscopic endonasal excision of the mass is considered the ideal treatment for such pathology, with rare postoperative recurrence., Introduction: Sinonasal schwannoma accounts for only 4% of head and neck nerve sheath tumors. Schwannoma of the nasal septum is still the rarest, with only few cases previously reported. Case presentation: This study presents the case of a 64-year-old Saudi female of the Eastern Province who presented a several-month history of unilateral progressive nasal obstruction and recurrent episodes of epistaxis. The diagnosis of nasal septal schwannoma was made on the basis of a histopathological examination. The case was managed successfully by endoscopic endonasal excision with no postoperative recurrence. Discussion: Nasal septal schwannoma is rare and has only 32 reported cases. Diagnosis primarily depends on histopathological examination. Endoscopic endonasal excision of the mass is considered the ideal treatment for such pathology. Conclusion: Schwannoma of the nasal septum is rare. However, it should be included as a differential diagnosis in a patient presenting with a unilateral nasal mass.

Fibrous dysplasia is a rare condition. We present a case of a 34-years-old man presented with left-sided facial pain, headache and nasal obstruction for a long duration. CT scan of the sinuses showed a mass occupying the left ethmoidal region abutting the orbit and skull base obstructing the left frontal sinus. The patient was treated successfully by image-guided endoscopic endonasal removal of the tumor with no recurrence after 3 years of follow-up. This report aims to show the usefulness of endoscopic endonasal removal of a large fibrous dysplasia of paranasal sinuses and skull base.

Hepatitis C virus (HCV) is the main cause of chronic hepatitis and probably liver cirrhosis. Dasabuvir (DSV) is a direct-acting antiviral agent with efficiency in managing HCV. The anti-viral activity of the anti-estrogen drug tamoxifen (TAM) suggested the synergistic effect of DSV and TAM for blocking the replication of HCV. However, being substrates and inhibitors of efflux transporters (TAM inhibits P-gp, DSV inhibits P-gp and BCRP), there is a possibility for a pharmacokinetic (PK) drug-drug interaction. In this work, a new UPLC-MS/MS method was developed and validated for the simultaneous determination of TAM, its active metabolite 4-hydroxy tamoxifen (TOH), and DSV in rat plasma. The method was applied to investigate the PK interaction between DSV and TAM/TOH following the co-administration of DSV and TAM to Wistar rats. Chromatographic analysis was performed on Waters BEHTM C18 column using a mobile phase of acetonitrile/water containing 0.1% formic acid (80: 20, v/v). The method allowed the determination of concentration ranges 20–1000, 0.1–500, 0.5–500 ng/mL for DSV, TAM, and TOH, respectively. Unexpectedly, results revealed the absence of PK interactions between DSV and TAM/TOH, compared with their single administration, suggesting the safety of co-administering DSV/TAM as an anti-viral combination without the need of dosage adjustment.

The increasing incidence of endometrial cancer (EC), in younger age at diagnosis, calls for new tissue-sparing treatment options. This work aims to evaluate the potential of imiquimod (IQ) in the treatment of low-grade EC. Effects of IQ on the viabilities of Ishikawa and HEC-1A cells were evaluated using MTT assay. The ability of IQ to induce apoptosis was evaluated by testing changes in caspase 3/7 levels and expression of cleaved caspase-3, using luminescence assay and western blot. Apoptosis was confirmed by flow cytometry and the expression of cleaved PARP. Western blot was used to evaluate the effect of IQ on expression levels of Bcl-2, Bcl-xL, and BAX. Finally, the in vivo efficacy of IQ was tested in an EC mouse model. There was a decrease in EC cell viability following IQ treatment as well as increased caspase 3/7 activities, cleaved caspase-3 expression, and Annexin-V/ 7AAD positive cell population. Western blot results showed the ability of IQ in cleaving PARP, decreasing Bcl-2 and Bcl-xL expressions, but not affecting BAX expression. In vivo study demonstrated IQ’s ability to inhibit EC tumor growth and progression without significant toxicity. IQ induces apoptosis in low-grade EC cells in vitro, probably through its direct effect on Bcl-2 family protein expression. In, vivo, IQ attenuates EC tumor growth and progression, without an obvious toxicity. Our study provides the first building block for the potential role of IQ in the non-surgical management of low-grades EC and encouraging further investigations.

BackgroundDental offices are among the highest risk for transmission of the COVID-19, having the potential to transmit the virus via routine dental procedures. This cross-sectional study assessed the preparedness and perception of infection control measures against the COVID-19 pandemic by dentists in Saudi Arabia.Materials and methodsThis online survey addressed the impact and perception of the COVID-19 pandemic on dental practice in Saudi Arabia. The questionnaire comprised 26 closed-ended questions. Descriptive statistics included frequency distributions with percentages. In addition, the significance between the different demographic variables and questions about dentists' perception of the COVID-19 pandemic was tested using the Chi-square test.ResultsCOVID-19 management in dental clinics varied in terms of adherence to the Ministry of Health (MOH) guidelines. Dental clinics' screening questionnaire for patients showed good adherence (67%), while the lowest agreement was detected with the question on the existence of an airborne infection in the isolation room (15%). Almost two-thirds of the respondents agreed that the dental reception area adopted the proper COVID-19 preventive measures. Greatest accord was observed in their answers on questions about dentists' perception of the COVID-19 pandemic, ranging from 64%-89%. In addition, there were statistically significant differences in questions about the perception of dentists towards the COVID-19 pandemic by different demographic variables such as age and years of work experience (p < 0.05).ConclusionThe response of most dentists regarding the preparedness and perception of infection control measures against the COVID-19 pandemic was positive. Dental clinics need to adhere more to the MOH recommendations in preparedness of their facilities or by educating their dentists and staff.

Iced teas (ITs), also known as ready-to-drink teas, have gained much popularity among many nations. The modulatory effect of tea beverages on CYP3A4 increases the possibility of their potential interactions with many coadministered medications. Being a substrate of CYP3A4, sorafenib (SOR), the first-line therapy for the treatment of hepatocellular carcinoma, shows a great probability to exhibit pharmacokinetic (PK) interaction with ITs. For this purpose, different groups of Wistar rats were given oral doses of SOR (40 mg/kg), along with different types of ITs. The concentration of SOR in rat plasma was determined using UPLC-MS/MS. Chromatographic analysis was performed on a C18 analytical column, Acquity UPLC BEH™ (100 × 1.0 mm, i.d., 1.7 μm particle size), using erlotinib (ERL) as an internal standard. Isocratic elution was performed with a mobile phase consisting of two solvents: solvent A (water with 0.1% formic acid) and solvent B (acetonitrile with 0.1% formic acid), in a ratio of 30 : 70, v/v, respectively. Quantitation was performed using MRM of the transitions from protonated precursor ions [M+H]+ to product ions at m/z 465.12 > 252.02 (SOR) and m/z 394.29 > 278.19 (ERL). The method was fully validated as per the FDA guidance for bioanalytical method validation in the concentration range of 2.5–500 ng/mL. Different PK parameters were calculated for SOR in all rat groups and groups administered with ITs and SOR, compared with groups with simply water and SOR. Experimental data revealed that ITs caused a general reduction in SOR bioavailability; an approximate reduction of 30% was recorded for all types of tested ITs. These data indicate that ITs could affect the PK profile of SOR in rats.

Individuals living with metabolic syndrome (MetS) such as diabetes and obesity are at high risk for developing chronic kidney disease (CKD). This study investigated the beneficial effect of whole grape powder (WGP) diet on MetS-associated CKD. Obese diabetic ZSF1 rats, a kidney disease model with MetS, were fed WGP (5%, w/w) diet for six months. Kidney disease was determined using blood and urine chemical analyses, and histology. When compared to Vehicle controls, WGP intake did not change the rat bodyweight, but lowered their kidney, liver and spleen weight, which were in parallel with the lower serum glucose and the higher albumin or albumin/globin ratio. More importantly, WGP intake improved the renal function as urination and proteinuria decreased, or it prevented kidney tissue damage in these diabetic rats. The renal protection of WGP diet was associated with up-regulation of antioxidants (Dhcr24, Gstk1, Prdx2, Sod2, Gpx1 and Gpx4) and downregulation of Txnip (for ROS production) in the kidneys. Furthermore, addition of grape extract reduced H2O2-induced cell death of cultured podocytes. In conclusion, daily intake of WGP reduces the progression of kidney disease in obese diabetic rats, suggesting a protective function of antioxidant-rich grape diet against CKD in the setting of MetS.

Highlights • Dentigerous cysts are commonly single lesions. Bilateral and multiple dentigerous cysts are very rare. • Ectopic tooth eruption outside the oral cavity is a rare entity. • The endonasal endoscopic approach has the advantages of avoiding external mucosal incision, oroantral fistula formation and recurrent sinusitis., Introduction Dentigerous cysts are the second most common form of benign odontogenic cysts. These cysts are commonly single lesions. Bilateral and multiple dentigerous cysts are very rare. Case presentation This article presents a rare case report of bilateral dentigerous cysts associated with two ectopic teeth located atypically in the maxillary sinuses in a 19-year-old male manifesting as bilateral upper jaw pain, post-nasal discharge and recurrent sinusitis which was managed via the endonasal endoscopic approach by enucleation of the cysts and teeth removal. Conclusion This paper presented our experience in the management of a rare case of bilateral dentigerous cysts associated with ectopic teeth in the maxillary sinuses. Ct scan of the paranasal sinuses confirmed the diagnosis and the endonasal endoscopic approach is superior to the external approaches in preserving physiological function in managing these patients.

Since the advent of antibiotics, major spontaneous tonsillar hemorrhage is extremely rare. The majority of the spontaneous tonsillar hemorrhage events is associated with acute or chronic tonsillitis, coagulopathies, or tonsillar cancer. Here, we report a very rare case of spontaneous tonsillar hemorrhage in a 7 year old girl managed by emergency tonsillectomy and IV antibiotic with no complications. Keywords: Pediatric spontaneous tonsillar hemorrhage, Emergency tonsillectomy, Bleeding tonsils

We aim to translate the Glasgow benefit inventory (GBI) questionnaire into Arabic language and assess its reliability in scoring the benefit of patients after otolaryngology interventions. This is a pilot study of an ongoing prospective cohort study. The original GBI questionnaire was translated into Arabic language and back-translated into English by two different experts. The questionnaire was given to patients who were asked to fill it themselves. A group of consecutive adult patients were included in the study. Fifty-one patients were included. Reliability using Cronbach’s α was higher than 0.70 for total score and the three subscales. Five loading factors explained 72.9% of the variance reached. The mean benefit of the GBI total score was 30.0 ± 36.37. Subscales scores were as follows: 35.21 ± 25.98 for the general health, 25.81 ± 45.98 for the physical benefit and 29.08 ± 34.45 for the social support. The Arabic GBI questionnaire is reliable to evaluate the quality of life after otolaryngology interventions for Arabic speaking population.

Introduction: There is a paucity of literature supporting the use of electronic alerts for patients with high frequency emergency department (ED) use. We sought to measure changes in opioid prescribing and administration practices, total charges and other resource utilization using electronic alerts to notify providers of an opioid-use care plan for high frequency ED patients. Methods: This was a randomized, non-blinded, two-group parallel design study of patients who had 1) opioid use disorder and 2) high frequency ED use. Three affiliated hospitals with identical electronic health records participated. Patients were randomized into “Care Plan” versus “Usual Care groups”. Between the years before and after randomization, we compared as primary outcomes the following: 1) opioids (morphine mg equivalents) prescribed to patients upon discharge and administered to ED and inpatients; 2) total medical charges, and the numbers of; 3) ED visits, 4) ED visits with advanced radiologic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) studies, and 5) inpatient admissions. Results: A total of 40 patients were enrolled. For ED and inpatients in the “Usual Care” group, the proportion of morphine mg equivalents received in the post-period compared with the pre-period was 15.7%, while in the “Care Plan” group the proportion received in the post-period compared with the pre-period was 4.5% (ratio=0.29, 95% CI [0.07-1.12]; p=0.07). For discharged patients in the “Usual Care” group, the proportion of morphine mg equivalents prescribed in the post-period compared with the pre-period was 25.7% while in the “Care Plan” group, the proportion prescribed in the post-period compared to the pre-period was 2.9%. The “Care Plan” group showed an 89% greater proportional change over the periods compared with the “Usual Care” group (ratio=0.11, 95% CI [0.01-0.092]; p=0.04). Care plans did not change the total charges, or, the numbers of ED visits, ED visits with CT or MRI or inpatient admissions. Conclusion: Electronic care plans were associated with an incremental decrease in opioids (in morphine mg equivalents) prescribed to patients with opioid use disorder and high frequency ED use.