SPE-UHPLC-ESI-MS/MS Analysis of Cocaine and Its Metabolites in Conventional and Alternative Biological Specimens: Application to Real Samples.

An increase in cocaine abuse has been observed globally since the past decade. Cocaine is among the commonly abused stimulants used for recreational purposes. In this study, the SPE-UHPLC-MS/MS method was developed and validated to be applied on real specimens of 20 chronic cocaine abusers to quantify cocaine/metabolites in conventional as well as alternative biological matrices. Cocaine was extracted from biological specimens using solid-phase extraction followed by liquid chromatography tandem mass spectrometry analysis. Chromatographic separation was achieved on a Poroshell120EC-18 column (2.1 mm × 50 mm, 2.7 µm particle size) using water-acetonitrile in 0.1% formic acid as a mobile phase in gradient elution mode. The flow rate of the mobile phase was 0.5 mL/min with a gradient varying the percentage of acetonitrile linearity ranging 15-95% in 6.0 min acquisition time, and the injection volume was set at 5 µL. Positive electrospray ionization with multireaction ion monitoring mode using two ion transitions for cocaine/metabolites and one for cocaine-d3 was employed. The quantification method demonstrated good linear ranges of 0.025-250 ng/mL in blood, urine, and oral fluid (ng/mg for hair and nail) with a ≥0.991% determination coefficient. The detection limit and lower quantification limit were 0.005 and 0.025 ng/mL in all matrices, respectively. The mean extraction recovery and ionization suppression ranged from 89.3 to 99.8% and -4.6 to -14.4% in the studied matrices. Within-run and between-days precisions were 1.8-7.2% and 1.9-6.1%, respectively. This study will not only help in quantifying cocaine/metabolites in alternative specimens (hair, nail, and oral fluid) but also guide clinical and forensic toxicologists in interpretation of exhumation cases. Furthermore, multiple specimens' analyses can be of significance in estimating the time/manner of drug exposure, in confirming the results of laboratories in cases of doubtful clinical histories, or in aiding medico-legal investigations.

Patient Questions Surrounding Posterior Nasal Nerve Ablation for Chronic Rhinitis.

Objective: In-office ablation of the posterior nasal nerve (PNN) has emerged as an effective treatment option for chronic rhinitis patients. This study explored questions patients commonly search online regarding this therapy and the quality of content available. Study Design: A retrospective analysis of online search criteria and sources was performed with subsequent analysis of results. Setting: Search and data acquisition was in September of 2023. Methods: Most common search terms related to cryotherapy and radiofrequency neurolysis of the PNN were identified with associated People Also Ask (PAA) questions. Questions were categorized and organized into subtopics and sources evaluated using readability and quality metrics. Results: A total of 255 unique PAA questions and 175 unique websites were identified. The most common subtopics were related to facts about chronic rhinitis (26.7%) and rhinitis treatment options (25.1%). Nearly a quarter (24.3%) of websites were from commercial sources. Quality metrics indicate difficult-to-read and low-quality materials. Conclusion: Existing online resources need improvement to provide patients material that is easier to read. Physicians counseling patients should be aware of these areas for adequate shared decision making.

Posterior Nasal Nerve Ablation as a Viable Treatment Option for the Primary Symptom of Postnasal Drip.

BACKGROUND: Postnasal drip (PND) syndrome is a prevalent complaint encountered in otolaryngology practices. PND may be refractory to medical therapy, and surgical treatments are complicated by side effects. OBJECTIVE: While posterior nasal nerve (PNN) ablation has demonstrated efficacy for chronic rhinitis overall, we sought to examine the effect of PNN ablation for patients with PND as their primary complaint. METHODS: This is a retrospective case series study of 40 chronic rhinitis (CR) patients with a primary complaint of PND. Included patients had to have failed medical therapy such as anti-cholinergic nasal sprays, reflux treatments, and/or nasal steroids. Primary outcome measures included 22 item Sino-Nasal Outcome Test (SNOT-22) PND component and Total Nasal Symptom Score. Secondary outcome measure was subjective improvement, defined as a > 30% improvement in PND symptoms. RESULTS: Median follow-up was 138 days (interquartile range: 72-193). 72.5% (29/40) of patients reported at least a 30% improvement in PND symptoms. Mean PND SNOT-22 scores were 4.2/5 (SD = 0.8) pre-procedure versus 1.9/5 (SD = 1.3) post-procedure (P = .001). PNN ablation response did not correlate to ipratropium bromide nasal spray response, although younger and non-smoker patients had better response rates. CONCLUSION: This exploratory study of PNN ablation for the primary symptom of PND demonstrates efficacy as assessed by the PND component of SNOT-22 and subjective improvement. These results can be useful in guiding physician-patient discussions in determining treatment options for medically refractory PND.

Appraisal of clinical practice guidelines for salivary gland cancer management utilizing AGREE II instrument.

OBJECTIVE: Salivary gland cancers (SGC) are rare neoplasms which comprise 1-5 % of all head and neck cancers. SGCs can be managed by resection, radiosurgery, chemotherapy, or a combination of these. Our team appraised the quality of clinical practice guidelines (CPGs) for SGC treatment and management using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument. DATA SOURCES: PubMed, Scopus, & EMBASE were reviewed for CPGs regarding SGC management from database inception to January 1st, 2023. REVIEW METHODS: The AGREE-II instrument was used by 4 reviewers to independently evaluate guidelines. Domain scores were generated with a satisfactory threshold being >60 % - a "high" quality CPG required >4 satisfactory domains. Intraclass correlation coefficients (ICCs) were used, via R 4.2.1., to determine inter-reviewer variability. RESULTS: Literature review identified 645 articles, with six being included after applying inclusion and exclusion criteria. Of the six included articles, one CPG was "high" quality and 5 were "low" quality. The domains with the highest scores were "Editorial Independence" (72.57 ± 36.60) and "Clarity and Presentation" (63.19 ± 26.08), while the lowest were "Rigor of Development" (34.03 ± 30.63) and "Applicability" (30.21 ± 30.46). ICC scores for each domain ranged from 0.937 to 0.983, indicating a high level of inter-rater agreement. CONCLUSION: This study found that most CPGs for the treatment and management of SGC were of "low" quality, with only one guideline being considered "high" quality based on the standard set by the AGREE-II instrument. These findings indicate that there is a high level of variability and little standardization when it comes to the quality of CPGs.

Multi-Institutional Analysis of Insurance Denial Patterns Within Rhinology.

BACKGROUND: Obtaining insurance approval is a necessary component of healthcare in the United States and denials of these claims have been estimated to result in a loss of 3% to 5% of revenue. OBJECTIVE: Examine the trends in insurance denials for rhinological procedures. METHODS: A retrospective review of deidentified financial data of patients who were treated by participating physicians across 3 institutions from January 1, 2021, to June 30, 2023. The data was queried for rhinological and non-rhinological procedures via CPT codes. Cumulative insurance denials were calculated and stratified by procedure and insurance type. Write-offs were dollar amounts associated with final denials. RESULTS: A sample of 102,984 procedures and visits revealed a final denial rate between 2.2% and 2.9% across institutions (p = .72). The top three rhinological procedures for final write-offs were: nasal endoscopy (16.24%, $111,836.87), nasal debridement or polypectomy (6.48%, $79,457.51), and destruction of intranasal lesion (2.11%, $56,932.20). The write-off percentage for each procedure was highest among commercial insurance payers as opposed to Medicare or Medicaid. CONCLUSION: Final denial rates of rhinology procedures ranged between 2% and 3%. Common procedures such as nasal endoscopy and nasal debridement are among the highest written-off procedures. Insurance denials can lead to notable revenue loss. Rhinology practices must continue to remain knowledgeable of the changes and effects of insurance reimbursement on their practice.

Modified technique improves efficacy for in-office posterior nasal nerve ablation.

Objectives: Posterior nasal nerve (PNN) ablation is a minimally invasive treatment option for patients with chronic rhinitis. Recent evidence shows that parasympathetic innervation of the nasal cavity is more extensive and there are many fibers posterior to the lateral attachment of the middle turbinate. We describe a modified ablative technique that targets the extensive innervation of the posterior nasal nerves. Methods: Description of the technique and retrospective cohort analysis. In addition to the traditional radiofrequency and cryoablation targets, three additional treatment sites posterior to the middle turbinate were targeted using radiofrequency ablation, as well as one focused treatment posteroinferior to the middle turbinate attachment using cryotherapy ablation. The primary outcome collected was a 30% improvement in overall rhinitis symptoms. Results: Forty-five patients received treatment and completed 3-month follow-up using the modified technique for radiofrequency and cryotherapy PNN ablation. Previously, our institution documented a 64.5% responder rate at 3 months. After introducing the modified technique, the response rate at 3 months significantly improved (64.5% vs. 91.1%, p = .004). Conclusions: This report suggests improved efficacy with implementation of the modified technique for in-office PNN ablation. Given the extensive nature of the post-ganglionic parasympathetic fibers of the nasal cavity which often emerge posterior to the middle turbinate attachment, a modified technique to target these branches should be considered. Prospective randomized studies comparing this modified technique to the traditional technique are needed. Level of Evidence: III.

Perceptions and Understanding of Transgender Patient Care: A Survey of Practicing Facial Plastic Surgeons.

Transgender individuals face significant health disparities including deficiencies in physician education, knowledge, and comfort with care. The objective of this study was to determine the perceptions, practice patterns, and familiarity of facial plastic surgeons with transgender health care. An anonymous questionnaire was sent to facial plastic surgeons within the American Academy of Facial Plastic and Reconstructive Surgery list-serve. Primary datapoints included participant characteristics, transgender-related experience, and educational goals. Of the 66 facial plastic surgeons surveyed, 49% had treated 1 to 10 transgender patients during their career, and 70% were actively treating at least 1 transgender patient. The number of patients treated and surgeries performed was significantly associated with self-perceived competence, comfort counseling on gender-affirming surgeries, discussing gender identity, asking preferred pronouns, and a desire to learn more about transgender care. Most participants (61%) obtained transgender care training through real-world experience, with only 18% receiving formal training in residency or fellowship. In total, 50% of respondents believe transgender care training among facial plastic surgeons is inadequate and 60% support its incorporation into residency/fellowship curricula. Increased awareness is needed to address the disparities experienced by transgender patients. Many facial plastic surgeons desire to learn more and support incorporating transgender care into training. Understanding the current state of transgender care can assist the facial plastic community in promoting education that strengthens physicians' ability to deliver competent care that addresses the inequities faced by this diverse group.

Outcomes of Head and Neck Free Tissue Transfer Requiring Vein Grafting: Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the literature to determine the prevalence of free flap failure in head and neck free flaps requiring vein grafting. DATA SOURCES: Search strategies created in collaboration with a medical librarian were implemented using PubMed, Cochrane, Scopus, Web of Science, and Google Scholar from inception to August 2022. REVIEW METHODS: The population of interest included adult and pediatric patients undergoing reconstruction of oncologic or traumatic head and neck defects with a free flap requiring a vein graft that presents the success/failure rate. The primary outcome was the flap failure rate, and the secondary outcome was the flap compromise/revision rate. Inclusion and exclusion criteria were designed to capture all study designs. Initially, 2778 articles were identified by the search strategy. Two reviewers independently performed the review, data extraction for analysis, and a quality assessment. Primary Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Meta-analysis was performed using a random effects model. RESULTS: Eleven studies of 789 flaps were included for data extraction. Random effects meta-analysis resulted in an estimated prevalence of free flap failure of 12.30% (95% confidence interval: 6.39%-19.49%, I2 = 77.4%). CONCLUSION: Taking into account that head and neck free tissue transfers that require a vein graft are typically associated with more challenging reconstructions and the lack of a suitable alternative, vein grafts appear to be a reliable method for bridging the gap between the flap and recipient vessels in head and neck free tissue transfer when indicated.

Severe epistaxis after posterior nasal nerve ablation requiring surgical intervention: A multi-center case series.

KEY POINTS: Severe epistaxis occurs in 2% of PNN ablation cases, independent of method or device type. Major epistaxis requiring intervention after PNN ablation can occur on average 20 days post-procedure.

Extracervical Approaches to Substernal Thyroid Goiter Resection: A Systematic Review and Meta-Analysis.

Objective: To evaluate the prevalence of extracervical approaches (ECAs) for substernal goiter (SSG) excision. Data Sources: Search strategies created in collaboration with a medical librarian were implemented using PubMed, Cochrane, Scopus, Web of Science, and Google Scholar from inception to July 2021. Review Methods: Participants included adults ages >18 years undergoing SSG excision. The primary outcome was rate of ECA via sternotomy or thoracotomy. Studies were categorized into the 3 most common distinct definitions: goiter descending below the plane of the thoracic inlet (definition 1), ≥50% of thyroid mass extending below the sternal notch (definition 2), and goiter extending ≥3 cm below the suprasternal notch when the neck is hyperextended (definition 3). Two reviewers independently extracted data for analysis and performed a quality assessment using the Methodological Index for Non-Randomized Studies criteria. Results: Of the 551 studies identified, 69 studies were included for analysis. Definition 1 included 3441 patients from 31 studies; definition 2 included 2957 patients from 26 studies; and definition 3 included 2921 patients from 12 studies. A random-effect model estimating the pooled prevalence of ECA using definition 1 resulted in prevalence of 6.12% (95% confidence interval: 3.48-9.34, I 2 = 90.72%). Conclusion: Extension below the thoracic inlet is the most widely used definition of SSG. Approximately 6% of patients with a SSG undergo an ECA. Patients with SSG undergoing surgery should be counseled on the prevalence, risks, and morbidity of an ECA in the rare occurrence it is needed.

The COVID-19 impact on severe uncontrolled asthma costs and biologic use.

Background: Patients with severe uncontrolled asthma (SUA) overwhelmingly contribute to the economic burden of asthma and may require biologic therapy. However, the impact of the CoronaVirus Disease of 2019 (COVID-19) on asthma costs and biologic use has yet to be evaluated. Objective: The objective was to test the hypothesis that SUA costs and biologic use decreased during the pandemic. Methods: We analyzed medical costs and biologic use in patients with SUV from January 2017 to December 2021, by using claims data from a large managed care organization and electronic health record data from Robert Wood Johnson Barnabas Health, according to provider specialty. Results: Of the 3817 managed care organization enrollees within Robert Wood Johnson Barnabas Health with a primary diagnosis of asthma, 348 were identified as having SUA. A nested sample of 151 patients revealed that 50% were managed by primary care physicians (PCP) and specialists, 43% by PCPs only, and 4% by specialists only. The total costs of the claims were $10.8 million over 5 years ($2.2 million per year), with 60% generated from patients seeing PCPs and specialists, 27% from PCPs only, and 15% from specialists only. During the pandemic, total average costs decreased for all care groups (34% PCP-only patients and 45% for both specialist-only and PCP and specialist patients). Inpatient and outpatient costs also decreased and were lowest for patients who saw specialists and highest for patients who saw PCPs and specialists. In contrast, prescription costs increased during the pandemic. Biologic use was steadily increasing until a twofold decrease was observed during the pandemic. Thirteen patients were on biologics: two were managed by PCPs, four by specialists, and seven by both. Conclusion: Inpatient and outpatient costs decreased during the COVID-19 pandemic, but prescription costs increased. Biologic use was increasing among patients with SUA before the pandemic but then drastically decreased and remained lower during the observational interval.

Biomarker underuse contributes to an inability to phenotype patients with severe uncontrolled asthma.

Background: Biomarker measurements improve the phenotyping of patients with severe uncontrolled asthma (SUA) and predict therapeutic responses. The use of biomarkers in asthma, however, remains underused. Objective: To test the hypothesis that biomarker measurements of patients with SUA remain markedly underused and contributes to asthma morbidity and oral corticosteroid use. Methods: Leveraging claims data linked to electronic health record data, we calculated biomarker use by providers treating patients with SUA from January 2017 to August 2020. Results: From 3.6 million clients, 3817 had a primary diagnosis of asthma; most were between 50 and 60 years old. Also, 63.2% were female patients; those under ages 10 years were primarily boys. Of the 728 patients who reported race, 69.9% were white and 21.8% were African American. Of the 840 who reported ethnicity, 14% were Latinx. A predetermined definition of SUA identified 348 patients with SUA. In a nested sample of 151 patients with SUA, 43% were managed by primary care physicians (PCP), 4% by specialists, and 49.7% by both. Of this sample, 61.5% had a measurement of serum eosinophils, 9.9% total immunoglobulin E values, and 9.3% radioallergosorbent skin tests; 38% received no tests, whereas 9.9% had more than one. Specialists ordered a biomarker test 4.6 times more often than did PCPs, whereas PCPs ordered 70% of the prednisone prescriptions for recurrent asthma exacerbations. Conclusion: Specialists were more likely to order biomarkers than were PCPs. Patients managed exclusively by PCPs were more likely prescribed oral prednisone. Real-world evidence shows that biomarkers are infrequently used to characterize patients with SUA, especially among patients exclusively managed by PCPs. Programs that encouraged biomarker use may improve SUA management and oral corticosteroid burden.

Time to move from past to future by making present creative: A Scoping review.

Creativity is one of the tools in the toolkit of modern day learners. Scientific progress cannot be accomplished without developing creative capacities of individuals. The Muslim countries, despite their historical achievement in different creative and innovative discoveries and positive encouragement by Islam towards creativity, have paradoxically gone down from their position. Creativity is one of the priorities of modern age due to its role in the progress of humanity and future. The education system is spoon-feeding our learners and killing creativity. The main aim of the current scoping review is to summarise and disseminate research findings pertaining to the evidence on the definition of the concept of creativity, its importance in education, role of teachers and learners in making creativity a part of their educational endeavours, and their implications. Moreover, it provides a broad and detailed outline of the topic and exploring more general questions rather than providing answer to limited questions. It will help to determine how important it is to foster creativity as educators.

Schiff Bases of Pioglitazone Provide Better Antidiabetic and Potent Antioxidant Effect in a Streptozotocin-Nicotinamide-Induced Diabetic Rodent Model.

Pioglitazone is a Food and Drug Administration-approved thiazolidinedione (TZD) derivative and peroxisome proliferator-activated receptor gamma (PPARγ) agonist and used for the treatment of diabetes mellitus (DM). However, this drug is still associated with many adverse effects. In the present study, four new Schiff bases of pioglitazone (P1-P4) were synthesized and characterized using FTIR, 1HNMR, 13CNMR, mass spectrometry, and elemental analysis. For preliminary screening, the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and in vitro alpha-amylase antidiabetic inhibitory assay were performed. Further, P3 was used to investigate in vivo antioxidant and in vivo antidiabetic effects in a streptozotocin-nicotinamide-induced diabetic rat model. Diabetic rats were administered with an i.p dose of pioglitazone 10 mg/kg body weight for 21 days. Moreover, biochemical parameters and antioxidants were quantified from liver and kidney tissues of rodents. In the DPPH assay, compound P3 showed superior antioxidant effects. Using the in vitro α-amylase inhibitory assay, P3 exhibited potent effects as compared to other groups, that is, 93% inhibition, while pioglitazone showed 81% inhibition. Enzymatic and nonenzymatic antioxidants showed significant changes in P3 (10 mg/kg)-treated groups (p < 0.001). Similarly, compound P3 produced significant and better results in comparison to pioglitazone in the rodent model. This study confirmed potent antidiabetic and superior antioxidant potential of the newly synthesized Schiff base (P3), which could ultimately account for insulin sensitization and for cellular protection and hence provide a potential clue for dual therapeutics.

Biotinidase deficiency presenting as Neuromyelitis Optica Spectrum Disorder.

Biotinidase deficiency disorder is a rare inherited metabolic disorder with typical neurological manifestations of hypotonia, developmental delay, rashes, seizures, hearing and vision impairment. We present two cases with different and unusual clinical profiles, whose neuroimaging resembled Neuromyelitis Optica Spectrum Disorder. Case 1 was initially treated with immunomodulation with steroids and intravenous immunoglobulins, with partial improvement. However reinvestigation for worsening of symptoms showed more extensive changes on spine magnetic resonance imaging. Raised lactate and alanine levels on repeat cerebrospinal fluid testing resulted in further investigations that revealed a biotinidase deficiency. Case 2 presented mainly with respiratory symptoms: a barium swallow suggested bulbar dysfunction. Neuroimaging of brain and spine was similar to that in case 1 and the child was promptly investigated for and confirmed to have biotinidase deficiency. Both cases responded to biotin supplementation. It is important to be cognisant of atypical neurological presentations of biotinidase deficiency including those that mimic immune mediated neurodemyelination disorders, as biotinidase deficiency is potentially treatable.

Perceived stress and monetary burden among thalassemia patients and their caregivers.

OBJECTIVE: To find the perceived stress level and monetary burden in the thalassemia patients and their caregivers related to thalassemia treatment sessions. METHODS: A descriptive cross sectional study was conducted at Rawalpindi Thalassemia Centre and Military Hospital Rawalpindi of six months' duration from November 2016 to April 2017. A total of 87 sample size was calculated by using WHO sample size calculator. Participants were inducted through purposive sampling technique from thalassemia centers. A validated standardized Cohen's Perceived Stress score was used. Data were entered and analyzed in SPSS 22. RESULTS: Mean age of the participants was 30.42 ± 14.53 years. There were 30 (34.2%) males and 57 (65.8%) females. There were 39 (51.3%) patients and 48 (48.7%) caregivers. The mean income per month of the participants was 48706.9 ± 39492.68 PKR. The mean total expenditure per treatment session was 48706 ± 4037.12 PKR. Among the patients, there were 15 (38.5%) who were having average stress, while 4 (10.3%) were having moderate stress while 45 (51.7%0 were having severe stress. Among the caregivers, 10 (20.8%) were having mild stress, 13 (27.1%) were having moderate stress while 25 (52.1%) were having severe stress. The stress among the two groups was not statistically significant (p=0.066). CONCLUSION: More than half of the patients and caregivers were having a high perceived stress levels and there was a significant association between the two groups. The monetary burden was a lot to bear by the patients and the cost of treatment session most expensive.

Fungal biotransformation of ezetimibe.

Structural transformation of ezetimibe was performed by fungi Beauvaria bassiana and Cunninghamella blakesleeana. The metabolites were identified by different spectroscopic techniques as (3R,4S)-1-(4-fluorophenyl)-3-((E)-3-(4-fluorophenyl) allyl)-4-(4-hydroxyphenyl) azetidin-2-one (2), (3R, 4S)-1-(4-fluorophenyl)-3-(3-(4fluorophenyl)-3-oxopropyl)-4-(4-hydroxyphenyl) azetidin-2-one (3), (3R,4S) 1-(4-fluorophenyl)-3-(3-(4-fluorophenyl) propyl)-4-(4-hydroxyphenyl) azetidin-2-one (4) and (2R,5S)-N, 5-bis (4-fluorophenyl)-5-hydroxy-2-(4-hydroxybenzyl) pentanamide (5). This study displays two important features of these fungi, viz., their ability to metabolize halogenated compounds, and their capacity to metabolize drugs that are targets of the UDP-Glucuronyl Transferase System, a phenomenon not commonly observed.