Association of adrenal steroids with metabolomic profiles in patients with primary and endocrine hypertension.

Introduction: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT. Methods: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus. Results: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites. Discussions: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.

Curcumin-Based Ionic Liquid Hydrogel for Topical Transdermal Delivery of Curcumin To Improve Its Therapeutic Effect on the Psoriasis Mouse Model.

Psoriasis is a systemic, recurrent, chronic autoimmune skin disease. However, psoriasis drugs have poor skin permeability and high toxicity, resulting in low bioavailability and affecting their clinical application. In this study, we propose a curcumin-based ionic liquid hydrogel loaded with ilomastat (Cur-Car-IL@Ilo hydrogel), which can effectively maintain the sustained release of drugs and improve the skin permeability of drugs. We used a model of imiquimod-induced psoriasis and demonstrated that local application of Cur-Car-IL@Ilo hydrogel can improve skin lesions in mice with significantly reduced expression levels of inflammatory factors, matrix metalloproteinase 8, and collagen-I. The expressions of iron death-related proteins SLC7A11 and ASL4 were significantly decreased after treatment with Cur-Car-IL@Ilo hydrogel. Flora analysis showed that the content of anaerotruncus, proteus, and UCG-009 bacteria in the gut of psoriatic mice increased. The levels of paludicola, parabacteroides, prevotellaceae_UCG-001, escherichia-shigella, and aerococcus decreased, and the levels of some of the above bacteria tended to be normal after treatment. Therefore, the curcumin-based ionic liquid hydrogel can be used as a multifunctional, nonirritating, noninvasive, and highly effective percutaneous treatment of psoriasis.

Exploring Factors Impacting Engagement in Speech Pathology Intervention for Inducible Laryngeal Obstruction.

AIM: Speech pathology is the first-line treatment for inducible laryngeal obstruction (ILO) and involves behavioral techniques to address symptoms and modify maladaptive laryngeal postures. Benefit from speech pathology is reliant on patients engaging in treatment sessions, regular home practice, and generalizing techniques to everyday activities. There is limited research exploring engagement in speech pathology treatment for ILO, particularly from the patient perspective. This study aimed to explore the experiences of living with ILO and how this experience may impact the way patients engage in speech pathology treatment. STUDY DESIGN: Qualitative study. METHODS: Semistructured interviews were completed with seven participants exploring their experiences living with ILO, their diagnostic process and their experiences with speech pathology treatment. Data were analyzed using reflexive thematic analysis to determine shared meanings across participants and themes were developed. FINDINGS: Three major themes were identified - Life with ILO, Challenges of Speech Pathology Treatment, and What Matters to Me. Patients' reports of living with ILO and interacting with speech pathology suggested that these experiences impacted their readiness to start treatment and persist through the challenges of the treatment. Engagement appeared to be positively associated with significant ILO symptom burden and life impact, confidence in the diagnostic process, recommendation for speech pathology treatment, a tailored intervention by a patient-perceived expert in the field and working in a partnership with the speech pathologist to develop a sense of agency. Patients indicated their engagement was negatively influenced by competing time demands, social embarrassment when using symptom relief techniques and laryngeal exercises, and a low ILO symptom burden and life impact. CONCLUSION: The reasons behind engagement in speech pathology treatment for ILO appear to be a complex interaction between previous experiences of living with ILO including the diagnostic process and the experience of speech pathology treatment. A patient-centered approach to therapy may help to maximize engagement by exploring readiness and expectations for treatment. The greater understanding of the patient experience provided through this study may allow speech pathologists to devise meaningful ways to maximize engagement in treatment for people with ILO.

JTT-654, an 11-beta hydroxysteroid dehydrogenase type 1 inhibitor, improves hypertension and diabetic kidney injury by suppressing angiotensinogen production.

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) plays an important role in regulating the expression of glucocorticoid actions in target tissues. Overexpression of 11ß-HSD1 in mouse adipose tissue causes a metabolic syndrome-like phenotype, leading to hypertension. Although, many 11ß-HSD1 inhibitors have been studied, few have shown a clear ameliorative effect against hypertension. We investigated whether JTT-654, a novel 11ß-HSD1 inhibitor, ameliorated hypertension and elucidated the underlying mechanisms. JTT-654 showed inhibitory effects on angiotensinogen production in cortisone-treated 3T3-L1 adipocytes and in a rat model. JTT-654 improved hypertension not only in cortisone-treated rats and spontaneously hypertensive rats (SHR), but also in SHR/NDmcr-cp rats. In the SHR study, JTT-654 and losartan showed the same degree of antihypertensive efficacy. In addition, JTT-654 ameliorated diabetic nephropathy by suppressing renal angiotensinogen production in SHR/NDmcr-cp rats. These effects of JTT-654 were independent of its insulin-sensitizing effects, and similar effects were not observed for pioglitazone, an insulin sensitizer. Moreover, JTT-654 did not affect normotension or hypothalamus-pituitary-adrenal (HPA) axis function in normal Sprague-Dawley rats. Our results indicate that JTT-654 ameliorates hypertension and diabetic nephropathy by inhibiting 11ß-HSD1 in the adipose tissue, liver, and kidney.

Fear of violence and working department influences physical aggression level among nurses in northwest Ethiopia government health facilities.

Purpose: Violence is recognized as an extreme expression of aggressive behavior and physical violence is most recognized type among victims. Patients always come to the hospitals looking for a cure, remedy, or assurance; however, incompatibility of demand and service often results in violent incidents that become statuesque in health facilities. This study aims to investigate physical violence and associated factors among nurses in health facilities in Gondar town, Ethiopia. Method: The study was an institutional-based cross-sectional study among nurses in Gondar town from April to May 2017. Data were collected using a pretested modified version of the standard [ILO/ICN/WHO/PSI] questionnaire by trained data collectors among 339 nurses across health facilities. Multivariable logistic regression analysis with 95% confidence interval (CI) was used to identify the factors significantly associated with physical violence at p-value ≤0.05. Result: Over one fourth (28.9%) [95% CI: (24.8, 33.9)] of nurses were victims of violence in the past 12 months. Level of verbal abuse (AOR = 2.35; 95%CI, 1.26-4.40), working in emergency (AOR = 4.58; 95%CI, 1.47-14.30) and inpatient (AOR = 3.33; 95%CI, 1.15-9.66)departments; having moderate (AOR = 0.41; 95%CI, 0.18-0.90),high (AOR = 0.41; 95%CI, 0.18-0.90), optimal (AOR = 0.41; 95%CI, 0.18-0.90) level of concern of violence were significantly associated with physical violence. Conclusion: This study underlines findings nurses are at high-risk of physical violence and it is ranked second highest only to psychiatric and trauma facilities in Gondar town. Exposure to verbal abuse, working in emergency and inpatient departments and perceived level of concern are the precursors of experiencing physical violence. Therefore, investing time and capital in training like restraining and de-escalation, structural measures that deter the assailants are important.

An LC-MS/MS-based method for the simultaneous quantification of melatonin, cortisol and cortisone in saliva.

Disturbances in the diurnal pattern are associated with several clinical and psychological conditions, including depression and fatigue. Salivary sampling for melatonin, cortisol and cortisone provides a non-invasive method for frequent sampling and obtaining biochemical insight into the diurnal pattern of individuals. Therefore, a new liquid chromatography-tandem mass spectrometry-based method for the measurement of salivary melatonin, cortisol and cortisone was developed and validated. The method required 250 µl saliva, used isotope dilution methodology and was based on a liquid-liquid extraction for sample preparation, reversed-phase chromatography and multiple reaction monitoring on a mass spectrometer for quantitation. The lower limits of quantification obtained were 0.010 nmol/L for melatonin, 0.5 nmol/L for cortisol and 1.00 nmol/L for cortisone and the limits of detection were 0.003 nmol/L, 0.15 nmol/L and 0.1 nmol/L respectively. The method imprecision was ≤14% for all measurands, and the method comparison showed highly comparable results with high correlation coefficients (all ≥0.964). Potential interference of cortisol and cortisone by prednisolone was observed and could be detected by chromatogram review. Typical diurnal patterns for melatonin, cortisol and cortisone were observed in the saliva of 20 cancer survivors who collected saliva throughout the day.

Anxiety, Depression, and Posttraumatic Stress Disorder in Patients With Induced Laryngeal Obstruction.

Importance: Patients with induced laryngeal obstruction (ILO) present with a variety of behavioral health profiles. Identifying these profiles is crucial in that behavioral health conditions may affect treatment duration and outcomes. Objective: To characterize the prevalence of anxiety, depression, posttraumatic stress disorder (PTSD), and physical somatic symptoms in adult and pediatric patients with ILO and determine the factors associated with anxiety, depression, PTSD, and physical somatic symptoms in patients with ILO? Design, Setting, and Participants: This cross-sectional study included a nonprobability sample of 83 adult and 81 pediatric patients diagnosed with ILO at outpatient adult and pediatric otolaryngology clinics between 2021 and 2023. Exclusion criteria included a comorbid respiratory diagnosis other than asthma, head or neck cancer, or neurological impairments. Recruitment took place between September 2021 and March 2023. The analyses were run in January 2024. Main Outcome Measures: Patients were prospectively screened for anxiety, depression, PTSD, and somatic physical symptoms. In addition, any past behavioral health diagnoses were extracted from the medical record. Comorbidities, ILO symptoms triggers, and onset details were gathered from ILO evaluations. Adult patients completed the Screen for Adult Anxiety Related Disorders (SCAARED), depression (Patient Health Questionnaire [PHQ]-9), and somatic physical symptoms portions of the Patient Health Questionnaires (PHQ-15), and the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5). Pediatric patients completed the Screen for Child Anxiety Related Disorders (SCARED), depression (PHQ-9A) and somatic physical symptoms portions of the Patient Health Questionnaires for Adolescents (PHQ-15A), and the UCLA PTSD Reaction Index brief screeners. Results: Eighty-three adult patients participated in this study (mean [SD] age, 45.8 [14.3] years; 64 female, 19 male). Eighty-one pediatric patients participated (mean [SD] age, 13.83 [2.55] years; 67 female, 14 male). Adult and pediatric patients with ILO screened positive for elevated rates of anxiety (53 adults [63%]; 49 children [60%]), depression (27 adults [32%]; 25 children [30%]), and PTSD (29 adults [34%]; 13 children [16%]). Most of the patients with anxiety and depression symptoms were formally diagnosed prior to ILO evaluation, with rates of previously diagnosed anxiety, depression, and PTSD also above published norms. Adults were twice as likely as children to present with PTSD (odds ratio, 2.1; 95% CI, 0.05-4.48). Elevated rates of physical somatic symptoms were also evident, with 38 adults (45%) and 32 children (39%) scoring in the moderate to severe range. Conclusions and Relevance: This study found high rates of adult and pediatric patients with ILO screened positive for anxiety, depression, and PTSD symptoms. Future work should investigate how behavioral health and ILO treatments can best be coordinated to maximize treatment outcomes.

Persistent Shortness of Breath in Post-COVID-19 Patients: Inducible Laryngeal Obstruction Can Be a Cause.

BACKGROUND: Inducible laryngeal obstruction (ILO) is the adduction of the true vocal folds during inspiration or, less frequently, expiration. Its etiology is unknown. PURPOSE: This study aimed to identify ILO as a possible cause of shortness of breath (SOB) in post-COVID-19 patients. METHODS: A retrospective study was conducted on 59 post-COVID-19 adults complaining of SOB. We collected the cases' clinical and chest imaging data, including demographic data, pulmonary function test (PFT), CT chest, and laryngeal endoscopic examination. A visual score was used to assign the severity of the glottic obstruction. The grades of this score ranged from 0 (complete patency) to 3 (almost complete closure). RESULTS: ILO was detected in 8 out of 59 cases (13.5%). Two cases out of eight had glottic closure grade 1, while five cases had glottic closure grade 2, and one had glottic closure grade 3. There was a positive correlation between ILO grades (the severity of glottic closure) and PFT results (the degree of upper airway restriction). PFTs in ILO have a specific pattern. It was typical for the expiratory loop to be normal and the inspiratory loop to be flattened. CONCLUSION: ILO is a possible cause of SOB in post-COVID-19 adult cases. It should be considered during evaluation and management.

Stress Markers, Executive Functioning, and Resilience Among Early Adolescents With Complex Congenital Heart Disease.

Importance: Infants with complex congenital heart disease (cCHD) may experience prolonged and severe stress when undergoing open heart surgery. However, little is known about long-term stress and its role in neurodevelopmental impairments in this population. Objective: To investigate potential differences between early adolescents aged 10 to 15 years with cCHD and healthy controls in physiological stress markers by hair analysis, executive function (EF) performance, and resilience. Design, Setting, and Participants: This single-center, population-based case-control study was conducted at the University Children's Hospital Zurich, Switzerland. Patients with different types of cCHD who underwent cardiopulmonary bypass surgery during the first year of life and who did not have a genetic disorder were included in a prospective cohort study between 2004 and 2012. A total of 178 patients were eligible for assessment at ages 10 to 15 years. A control group of healthy term-born individuals was cross-sectionally recruited. Data assessment was between 2019 and 2021. Statistical analysis was performed from January to April 2023. Exposure: Patients with cCHD who underwent infant open heart surgery. Main Outcomes and Measures: Physiological stress markers were quantified by summing cortisol and cortisone concentrations measured with liquid chromatography with tandem mass spectrometry in a 3-centimeter hair strand. EFs were assessed with a neuropsychological test battery to produce an age-adjusted EF summary score. Resilience was assessed with a standardized self-report questionnaire. Results: The study included 100 patients with cCHD and 104 controls between 10 and 15 years of age (mean [SD] age, 13.3 [1.3] years); 110 (53.9%) were male and 94 (46.1%) were female. When adjusting for age, sex, and parental education, patients had significantly higher sums of hair cortisol and cortisone concentrations (ß, 0.28 [95% CI, 0.12 to 0.43]; P < .001) and lower EF scores (ß, -0.36 [95% CI, -0.49 to -0.23]; P < .001) than controls. There was no group difference in self-reported resilience (ß, -0.04 [95% CI, -0.23 to 0.12]; P = .63). A significant interaction effect between stress markers and EFs was found, indicating a stronger negative association in patients than controls (ß, -0.65 [95% CI, -1.15 to -0.15]; P = .01). The contrast effects were not significant in patients (ß, -0.21 [95% CI, -0.43 to -0.00]; P = .06) and controls (ß, 0.09 [95% CI, -0.11 to 0.30]; P = .38). Conclusions and Relevance: This case-control study provides evidence for altered physiological stress levels in adolescents with cCHD and an association with poorer EF. These results suggest that future studies are needed to better understand the neurobiological mechanisms and timing of alterations in the stress system and its role in neurodevelopment.

Baldia Factory Fire Tragedy: A Black Spot for Workplace Safety Standards in Pakistan.

BACKGROUND: The Baldia Factory (BF) fire incident in Pakistan was among the most tragic workplace fires in the world claiming the lives of more than 259 people. METHODS: A case study was conducted to evaluate the state of the safety measures, firefighting systems, building regulations, employees' documentation, and compensation structures. RESULTS: The case study found many deficiencies in the fire safety program and lack of adherence to and enforcement of existing fire regulations. CONCLUSION: Findings are discussed in the context of fire safety regulations and enforcement in low- and middle-income countries such as Pakistan.

[Introduction to carcinogenesis of nickel compounds in ILO criteria for Diagnosis and Exposure Standard for Occupational Diseases].

International Agency for Research on Cancer (IARC) classifies nickel compounds as Class Ⅰ carcinogens. International Labour Organization (ILO) also lists nickel compounds as carcinogenic factors of occupational cancer. At present, China is revising the Classification and Catalogue of Occupational Diseases, and cancer caused by nickel compounds may also be included in the statutory occupational diseases. The Diagnostic and Exposure Standards for Occupational Diseases published by ILO in 2022 discussed the pathogenic characteristics, occupational exposure, main health effects, diagnostic criteria and key preventive measures of nickel compounds in detail. This article mainly introduces its contents, in order to provid a basis for the formulation of relevant standards in China.

Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

Validation of a LC-MS/MS method for establishing reference intervals and assessing diagnostic performance of urinary free cortisol and cortisone.

BACKGROUND: 24-h urinary free cortisol (UFF) is recommended for screening of Cushing's syndrome (CS), a rare disease characterized by apparent cortisol and cortisone excess. We aimed to validate a simple LC-MS/MS method for accurate measurement of UFF and urinary free cortisone (UFE), establishment of reference ranges, and evaluation of performance for CS diagnosis. METHODS: Urine samples were processed using solid-phase extraction cartridges, followed by elution with methanol and acetonitrile. Analysis was performed via tandem mass spectrometry, utilizing multiple reaction monitoring and electrospray ionization source in positive ion mode. RESULTS: The assay displayed excellent linearity (r > 0.99) in the range of 0.05-100 ng/mL for cortisol and 0.25-500 ng/mL for cortisone, with lower limits of quantification (LLOQ) at 0.05 ng/mL for cortisol and 0.25 ng/mL for cortisone. The obtained results for intra-day and inter-day imprecision for both analytes were within the acceptable range of less than 10 %. The trueness values for both compounds were also within the acceptable limit of 15 %. No significant matrix effects or carry over observed in our method. The reference intervals of UFF, UFE and UFF:UFE ratio were 7.01-45.66 µg/24-h, 27.97-139.21 µg/24-h and 0.17-0.56, respectively. UFF > 56.75 µg/24-h showed 100 % specificity and 100 % sensitivity for CS diagnosis, which was superior to UFF:UFE ratio. CONCLUSIONS: We developed and validated a sensitive LC-MS/MS method to detect UFF and UFE. Our data indicate that UFF measured by the current LC-MS/MS assay exhibited high diagnostic performance for CS.

Protocol for a scoping review to map health outcomes in individuals with inducible laryngeal obstruction.

BACKGROUND: Inducible laryngeal obstruction causes narrowing of the laryngeal aperture in response to external triggers. Outcomes are measured in inducible laryngeal obstruction to monitor changes in health status over time. METHODS: This study is a scoping review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The review will be guided by the following research question: 'What health outcomes are measured in studies including people with inducible laryngeal obstruction?' The research question was validated using the Population-Concept-Context framework according to the methodology for Joanna Briggs Institution Scoping Reviews. Relevant peer-reviewed studies and grey literature conducted over the last 40 years will be identified from electronic databases including AMED, CINAHL, Embase, EMCARE, MEDLINE, OVID, PubMed and PsycINFO. The search strings 'inducible laryngeal obstruction', 'ILO', 'vocal cord dysfunction', 'VCD', 'paradoxical vocal fold motion', 'PVFM', 'outcome', 'measure', 'measurement instrument', 'assessment', 'scale', 'questionnaire' will be combined using Boolean logic. An independent reviewer will conduct title screening; two independent reviewers will conduct abstract and full article screening, followed by data extraction by two reviewers. Analyses will be conducted appropriate to the findings. DISCUSSION: The review will document evidence of health outcomes measured in inducible laryngeal obstruction, identifying measurement characteristics and potential utility. Collating studies may identify gaps in coverage, the need for novel tools, and for standardisation for clinical and research purposes. WHAT THIS PAPER ADDS: What is already known on the subject Inducible laryngeal obstruction causes narrowing of the laryngeal aperture in response to external triggers. Outcomes are measured in inducible laryngeal obstruction to monitor changes in health status over time. Currently, there are no standardised outcome measures for measuring the effects of interventions in inducible laryngeal obstruction (ILO). What this paper adds to existing knowledge Assessment of health can be measured in a variety of ways. Physiological, radiological and biochemical measurements of impairment are more common historically but there are a lot of outcomes of other factors now including subjective measures of functional status and health-related quality of life, with data collected directly from patients. This study will allow us to scope the literature to see the health outcomes being measured in ILO to attempt to standardise and develop future health outcomes. What are the potential or actual clinical implications of this work? The review will document evidence of health outcomes measured in inducible laryngeal obstruction, identifying measurement characteristics and potential utility. Collating studies may identify gaps in coverage, the need for novel tools and for standardisation for clinical and research purposes.

Whole-exome sequencing reveals causative genetic variants for several overgrowth syndromes in molecularly negative Beckwith-Wiedemann spectrum.

Background Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by (epi)genetic alterations at 11p15. Because approximately 20% of patients test negative via molecular testing of peripheral blood leukocytes, the concept of Beckwith-Wiedemann spectrum (BWSp) was established to encompass a broader cohort with diverse and overlapping phenotypes. The prevalence of other overgrowth syndromes concealed within molecularly negative BWSp remains unexplored.Methods We conducted whole-exome sequencing (WES) on 69 singleton patients exhibiting molecularly negative BWSp. Variants were confirmed by Sanger sequencing or quantitative genomic PCR. We compared BWSp scores and clinical features between groups with classical BWS (cBWS), atypical BWS or isolated lateralised overgrowth (aBWS+ILO) and overgrowth syndromes identified via WES.Results Ten patients, one classified as aBWS and nine as cBWS, showed causative gene variants for Simpson-Golabi-Behmel syndrome (five patients), Sotos syndrome (two), Imagawa-Matsumoto syndrome (one), glycosylphosphatidylinositol biosynthesis defect 11 (one) or 8q duplication/9p deletion (one). BWSp scores did not distinguish between cBWS and other overgrowth syndromes. Birth weight and height in other overgrowth syndromes were significantly larger than in aBWS+ILO and cBWS, with varying intergroup frequencies of clinical features.Conclusion Molecularly negative BWSp encapsulates other syndromes, and considering both WES and clinical features may facilitate accurate diagnosis.

Economic Burden of Induced Laryngeal Obstruction in Adolescents and Children.

PURPOSE: Diagnosing pediatric induced laryngeal obstruction (ILO) requires equipment typically available in specialist settings, and patients often see multiple providers before a diagnosis is determined. This study examined the financial burden associated with the diagnosis and treatment of ILO in pediatric patients with reference to socioeconomic disadvantage. METHODS: Adolescents and children (<18 years of age) diagnosed with ILO were identified through the University of Madison Voice and Swallow Outcomes Database. Procedures, office visits, and prescribed medications were collected from the electronic medical record. Expenditures were calculated for two time periods (1) pre-diagnosis (first dyspnea-related visit to diagnosis), and (2) the first year following diagnosis. The Area Deprivation Index (ADI) was used to estimate patient socioeconomic status to determine if costs differed with neighborhood-level disadvantage. RESULTS: A total of 113 patients met inclusion criteria (13.9 years, 79% female). Total pre-diagnosis costs of ILO averaged $6486.93 (SD = $6604.14, median = $3845.66) and post-diagnosis costs averaged $2067.69 (SD = $2322.78; median = $1384.12). Patients underwent a mean of 3.01 (SD = 1.9; median = 2) procedures and 5.8 (SD = 4.7; median = 5) office visits prior to diagnosis. Pharmaceutical, procedure/office visit, and indirect costs significantly decreased following diagnosis. Patients living in neighborhoods with greater socioeconomic disadvantage underwent fewer procedures and were prescribed more medication than those from more affluent areas. However, total expenditures did not differ based on ADI. CONCLUSIONS: Pediatric ILO is associated with considerable financial costs. The source of these costs, however, differed according to socioeconomic advantage. Future work should determine how ILO diagnosis and management can be more efficient and equitable across all patients. Laryngoscope, 2024.

Impacts for health and care workers of Covid-19 and other public health emergencies of international concern: living systematic review, meta-analysis and policy recommendations.

BACKGROUND: Health and care workers (HCW) faced the double burden of the SARS-CoV-2 pandemic: as members of a society affected by a public health emergency and as HWC who experienced fear of becoming infected and of infecting others, stigma, violence, increased workloads, changes in scope of practice, among others. To understand the short and long-term impacts in terms of the COVID-19 pandemic and other public health emergencies of international concern (PHEICs) on HCW and relevant interventions to address them, we designed and conducted a living systematic review (LSR). METHODS: We reviewed literature retrieved from MEDLINE-PubMed, Embase, SCOPUS, LILACS, the World Health Organization COVID-19 database, the ClinicalTrials.org and the ILO database, published from January 2000 until December 2021. We included quantitative observational studies, experimental studies, quasi-experimental, mixed methods or qualitative studies; addressing mental, physical health and well-being and quality of life. The review targeted HCW; and interventions and exposures, implemented during the COVID-19 pandemic or other PHEICs. To assess the risk of bias of included studies, we used the Johanna Briggs Institute (JBI) Critical Appraisal Tools. Data were qualitatively synthetized using meta-aggregation and meta-analysis was performed to estimate pooled prevalence of some of the outcomes. RESULTS: The 1013 studies included in the review were mainly quantitative research, cross-sectional, with medium risk of bias/quality, addressing at least one of the following: mental health issue, violence, physical health and well-being, and quality of life. Additionally, interventions to address short- and long-term impact of PHEICs on HCW included in the review, although scarce, were mainly behavioral and individual oriented, aimed at improving mental health through the development of individual interventions. A lack of interventions addressing organizational or systemic bottlenecks was noted. DISCUSSION: PHEICs impacted the mental and physical health of HCW with the greatest toll on mental health. The impact PHEICs are intricate and complex. The review revealed the consequences for health and care service delivery, with increased unplanned absenteeism, service disruption and occupation turnover that subvert the capacity to answer to the PHEICs, specifically challenging the resilience of health systems.

Clinical Characteristics and Impact of Inducible Laryngeal Obstruction in the UK National Registry.

BACKGROUND: Inducible laryngeal obstruction (ILO) describes inappropriate laryngeal closure during respiration, with airflow obstruction occurring at the glottic and/or supraglottic level, leading to breathlessness. OBJECTIVE: There is a paucity of data describing the demographics and impact of ILO. We aimed to report the clinical and demographic features of ILO in individuals entered prospectively in the UK national ILO registry. METHODS: Data were entered into a Web-based registry from participants with endoscopically confirmed ILO who were attending four established UK-wide specialist ILO centers between March 2017 and November 2019. All patients provided written informed consent. RESULTS: Data from 137 individuals were included. Most (87%) had inspiratory ILO and required provocation during endoscopy to induce symptoms. There was a female predominance (80%), mean age 47 years (SD, 15 years). The most common comorbidities included asthma (68%) and reflux (57%). Health care use was high: 88% had attended emergency health care with symptoms at least once in the previous 12 months and nearly half had been admitted to the hospital. A fifth had required admission to critical care owing to ILO symptoms. Patient morbidity was substantial; 64% reported impaired functional capacity (≥3 on the Medical Research Council Dyspnoea Scale) and a third stated that symptoms affected working capability. CONCLUSION: We describe the first multicenter prospective characterization of individuals with endoscopically diagnosed ILO. Analysis of our multicenter data set identified ILO as associated with a high burden of morbidity and health care use, comparable to severe asthma. These data will support the development of health care resources in the future and guide research priorities.

Endocannabinoids, endocannabinoid-like compounds and cortisone in head hair of health care workers as markers of stress and resilience during the early COVID-19 pandemic.

The pandemic caused by SARS-CoV-2 impacted health systems globally, creating increased workload and mental stress upon health care workers (HCW). During the first pandemic wave (March to May 2020) in southern Germany, we investigated the impact of stress and the resilience to stress in HCW by measuring changes in hair concentrations of endocannabinoids, endocannabinoid-like compounds and cortisone. HCW (n = 178) recruited from multiple occupation and worksites in the LMU-University-Hospital in Munich were interviewed at four interval visits to evaluate mental stress associated with the COVID-19 pandemic. A strand of hair of up to 6 cm in length was sampled once in May 2020, which enabled retrospective individual stress hormone quantifications during that aforementioned time period. Perceived anxiety and impact on mental health were demonstrated to be higher at the beginning of the COVID-19 pandemic and decreased significantly thereafter. Resilience was stable over time, but noted to be lower in women than in men. The concentrations of the endocannabinoid anandamide (AEA) and the structural congeners N-palmitoylethanolamide (PEA), N-oleoylethanolamide (OEA) and N-stearoylethanolamide (SEA) were noted to have decreased significantly over the course of the pandemic. In contrast, the endocannabinoid 2-arachidonoylglycerol (2-AG) levels increased significantly and were found to be higher in nurses, laboratory staff and hospital administration than in physicians. PEA was significantly higher in subjects with a higher resilience but lower in subjects with anxiety. SEA was also noted to be reduced in subjects with anxiety. Nurses had significantly higher cortisone levels than physicians, while female subjects had significant lower cortisone levels than males. Hair samples provided temporal and measurable objective psychophysiological-hormonal information. The hair endocannabinoids/endocannabinoid-like compounds and cortisone correlated to each other and to professions, age and sex quite differentially, relative to specific periods of the COVID-19 pandemic.