Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study.

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. OBJECTIVE: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. DESIGN, PATIENTS AND SETTING: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). INTERVENTIONS: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. MEASUREMENTS: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. RESULTS: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. INTERPRETATION: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.

The Role of Vitamin D in the Treatment of Carpal Tunnel Syndrome: Clinical and Electroneuromyographic Responses.

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.

Corticosteroid-depending effects on peripheral immune cell subsets vary according to disease modifying strategies in multiple sclerosis.

Background: The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date. Methods: We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY). Results: We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment. Conclusion: In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.

Therapeutic management of atopic dermatitis.

ABSTRACT: Atopic dermatitis (AD), a chronic inflammatory, pruritic skin disorder, is seen primarily in the pediatric population but can be found among all age groups. The symptoms of AD can cause embarrassment in patients and can interrupt daily activities and productivity, potentially resulting in avoidance of social situations. In addition to nonpharmacologic management, mainstay pharmacologic treatments for AD are topical medications including corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors, and topical Janus kinase (JAK) inhibitors. Promising new drugs-oral JAK inhibitors and monoclonal antibodies-have emerged as new treatment options for moderate-to-severe AD.

Can we measure whether asthma guidelines lead to improved care?

The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have previously produced separate asthma guidance differing in some key aspects in diagnosis and management leading to confusion, potentially hampering guideline dissemination and uptake. While there are inherent challenges, the upcoming release of new joint BTS/SIGN/NICE asthma guidance presents an opportunity to assess guideline adoption and its impact on clinical practice. The use of prescription data via databases such as OpenPrescribing can be used as a surrogate for guideline adoption and potentially linked to clinical outcomes such as hospital episode statistics (HES). The potential recommendation for anti-inflammatory reliever therapy (AIR) and maintenance and reliever therapy (MART) with inhaled corticosteroid/formoterol combination therapy in the next iteration of UK asthma guidance will require the accurate coding for the respective therapeutic approaches on prescribing platforms in order to assess their impact in real-life clinical practice. This could then direct targeted measures to improve wider guidance adoption leading to better clinical care in asthma based on up to date evidence.

Withdrawal of Inhaled Corticosteroids from Patients with COPD; Effect on Exacerbation Frequency and Lung Function: A Systematic Review.

Background: Inhaled corticosteroid (ICS) therapy has been demonstrated to reduce the risk of COPD exacerbations. It should only be prescribed to COPD patients who are not adequately controlled by dual long-acting bronchodilator therapy and who have ≥2 exacerbations per year and a blood eosinophil count ≥300cells/µL. ICS therapy is widely prescribed outside guidelines to COPD patients, making ICS withdrawal an important consideration. This systematic review aims to provide an up-to-date analysis of the effect of ICS withdrawal on exacerbation frequency, change in lung function (FEV1) and to determine the proportion of COPD patients who resume ICS therapy following withdrawal. Methods: Randomised controlled trials (RCTs) and observational studies which compared ICS withdrawal with ICS continuation treatment were included. Cochrane Central, Web of Science, CINHAL, Embase and OVID Medline were searched. Risk of bias was assessed using the Cochrane RoB2 tool and the Newcastle-Ottawa Scale. Quality assessment of RCTs was conducted using GRADE. Meta-analysis of post-hoc analyses of RCTs of ICS withdrawal, stratified by blood eosinophil count (BEC), was undertaken. Results: Ten RCTs (6642 patients randomised) and 6 observational studies (160,029 patients) were included in the results. When ICS was withdrawn and long-acting bronchodilator therapy was maintained, there was no consistent difference in exacerbation frequency or lung function change between the ICS withdrawal and continuation trial arms. The evidence for these effects was of moderate quality. There was insufficient evidence to draw a firm conclusion on the proportion of patients who resumed ICS therapy following withdrawal (estimated range 12-93% of the participants). Discussion: Withdrawal of ICS therapy from patients with COPD is safe and feasible but should be accompanied by maintenance of bronchodilation therapy for optimal outcomes.

Survival benefit of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a nationwide cohort study.

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83-0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.

Linguistic Validation and Reliability of the Croatian Version of the TOPICOP Questionnaire.

Background and Objectives: This study demonstrates the factor structure and reliability of the Croatian version of the TOPICOP (Topical Corticosteroid Phobia) questionnaire, thereby contributing to further validation and standardization of the measurement of topical corticophobia with dermatological patients or their parents, which directly affects patient or parent compliance, as well as the final therapeutic effect. Materials and Methods: The cross-sectional, observational study was conducted at the University Hospital Centre Split, Department of Dermatovenerology. The research involved inviting 120 participants (age 12-68) who attended the University Hospital Centre Split's Atopy School, patients examined in the Dermatology Outpatient Clinic of the University Hospital Centre Split and diagnosed with atopic dermatitis (AD) or allergic contact dermatitis (ACD), and parents or legal representatives of patients younger than 12 years old. The TOPICOP questionnaire consists of 12 items assessing the three different components of topical corticophobia (worries, beliefs, and behaviour). Respondents evaluated their perception of the correctness of each statement within 10 min of filling out the questionnaire on a four-point Likert scale. Results: The response rate was 94%, resulting in a sample of 113 respondents (109 adults and 4 children). Factor analysis yielded one common factor of relatively high reliability (Cronbach α = 0.85, 95% CI 0.81 to 0.89). No differences were found in questionnaire scores between male and female participants, nor between the parents/legal representatives of dermatological patients and other patients. Conclusions: This research contributes to further development of the appropriate measuring instrument, its practical application, and thus, the better recognition, resolution, and prevention of topical corticophobia as part of the better overall healthcare and treatment of chronic dermatological patients.

[Chronic obstructive pulmonary disease (COPD): eosinophilia and novel drug therapies]. / Chronisch-obstruktive Lungenerkrankung (COPD) ­ Eosinophilie und neue Arzneimitteltherapien.

BACKGROUND: The phenotyping of chronic obstructive pulmonary disease (COPD) has increasingly gained attention in recent years, as it leads to new and individualized therapeutic concepts. OBJECTIVE: The aim is to provide an overview of the heterogeneity of COPD and to summarize current drug therapy concepts, particularly in the context of eosinophilic airway inflammation. DATA: Several prospective, randomized, placebo-controlled studies have shown a reduction in exacerbations and overall mortality with inhaled triple therapy using an inhaled corticosteroid and dual bronchodilation. The higher the eosinophils in the blood, the greater the expected effect. In addition, a reduction in exacerbations with biologics in COPD with eosinophilia has been demonstrated for dupilumab. Eosinophil-guided therapy for acute exacerbations is the subject of current research. CONCLUSION: For COPD without exacerbations, dual bronchodilation forms the basis of inhaled therapy. With exacerbations, inhaled triple therapy is indicated for patients with a blood eosinophil count of ≥ 300/µl. This type of treatment may also be useful when eosinophils are between 100 and 300/µl. Therapy with dupilumab is a possible option for the eosinophilic phenotype in the near future.

Asthma management with triple ICS/LABA/LAMA combination to reduce the risk of exacerbation: an umbrella review compliant with the PRIOR statement.

INTRODUCTION: According to Global Initiative for Asthma (GINA) guidelines, long-acting muscarinic antagonists (LAMAs) should be considered as add-on therapy in patients with asthma that remains uncontrolled, despite treatment with medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS)/long-acting ß2-agonist (LABA) combinations. In patients ≥ 18 years, LAMA may be added in triple combination with an ICS and a LABA. To date, the precise efficacy of triple ICS/LABA/LAMA combination remains uncertain concerning the impact on exacerbation risk in patients with uncontrolled asthma. Therefore, an umbrella review was performed to systematically summarize available data on the effect of triple ICS/LABA/LAMA combination on the risk of asthma exacerbation. METHODS: An umbrella review has been performed according to the PRIOR statement. RESULTS: The overall results obtained from 5 systematic reviews and meta-analyses suggest that triple ICS/LABA/LAMA combination reduces the risk of asthma exacerbation. HD-ICS showed a greater effect particularly in reducing severe asthma exacerbation, especially in patients with evidence of type 2 inflammation biomarkers. CONCLUSIONS: The findings of this umbrella review suggest an optimization of ICS dose in triple ICS/LABA/LAMA combination, based on the severity of exacerbation and type 2 biomarkers expression.

Impact of sex and socioeconomic status on the likelihood of surgery, hospitalization, and use of medications in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the likelihood of bowel surgery, hospitalization, and use of corticosteroids and biologics among patients with IBD. METHODS: We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on the likelihood of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn's disease or ulcerative colitis) and age. Finally, meta-regression was undertaken for the year of publication. RESULTS: In total, 67 studies were included, of which 23 studies were eligible for meta-analysis. In the main meta-analysis, male sex was associated with an increased likelihood of bowel surgery (HR 1.42 (95% CI 1.13;1.78), which was consistent with the subgroup analysis for UC only (HR 1.78, 95% CI 1.16; 2.72). Sex did not impact the likelihood of hospitalization (OR 1.05 (95% CI 0.86;1.30), although the subgroup analysis revealed an increased likelihood of hospitalization in CD patients (OR 1.42, 95% CI 1.28;1.58). In 9 of 10 studies, no significant sex-based differences in the use of biologics were reported, although in 6 of 6 studies, female patients had lower adherence to biologics. In 11 of 13 studies, no significant sex-based difference in the use of corticosteroids was reported. The evidence of the impact of income and education on healthcare utilization was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type and age. CONCLUSIONS: The results of this systematic review indicate that male patients with IBD are significantly more likely to have surgery than female patients with IBD but are not, overall, more likely to be hospitalized, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on healthcare utilization. Evidence for income- and education-based differences remains sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022315788.

Impact of CYP3A5 Polymorphisms on Pediatric Asthma Outcomes.

Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography-tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51-11.3) years. CYP3A5*3/*3 frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with CYP3A5*3/*3, the CYP3A5*1/*x genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97-0.98; p < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56-9.07; p < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43-1.93; p < 0.001); analysis of 3/*3, *1/*1 and *1/*3 separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the CYP3A5*3/*3 genotype, as opposed to an effect on ICS PK. Detection of CYP3A5*3/3, CYPA35*1/*3, and CYP3A5*1/*1 could impact inhaled steroid treatment strategies for asthma in the future.

Role of FeNO in predicting the responsiveness of inhaled corticosteroids in COPD: a systematic review.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) as a predictor of inhaled corticosteroid (ICS) response in asthma has been established. However, the same has not been established in chronic obstructive pulmonary disease (COPD). An optimal value of FeNO for prescribing and monitoring ICS response has not been quantified. AIM: To examine the evidence for this association. METHOD: A systematic review was conducted of randomised controlled trials and observational studies examining the association between FeNO level and response to ICS in COPD patients. All studies examining this association were included. Five databases were searched thoroughly. Systematic screening, full-text reviews, and data extraction were carried out based on eligibility criteria. RESULTS: A total of 8690 studies were identified, 342 texts were screened fully, and six studies were included for the final review. One was a randomised controlled trial and the other five were non-randomised interventional trials. One study was conducted in asthma-COPD overlap (ACO patients). After ICS use, three studies found statistically significant correlations between FeNO and lung function improvement (FEV1), and three studies also found significant correlations between FeNO and COPD quality-of-life scores. CONCLUSION: Measurement of FeNO is non-invasive and standardised, with results available at the point of testing. Because of the small sample size and short duration of studies, exacerbation frequencies were not measured. Despite this, the review suggests that FeNO may be a potential biomarker for assessing ICS response in COPD. Further research that stratifies patients by FeNO levels and assesses the impact on acute exacerbations is needed to understand its potential value in routine clinical practice.

Serial changes in anxiety levels related to corticosteroid use: A single-center prospective study.

Patients with autoimmune diseases treated with corticosteroids sometimes display feelings of anxiety regarding corticosteroid use. In this single-center prospective study, we aimed to evaluate the serial changes in anxiety levels related to corticosteroid use in 18 patients with autoimmune diseases. The degree of anxiety toward corticosteroid use was assessed using the visual analogue scale. Comprehension of drug characteristics and use was assessed using the Likert scale. To assess the patients' levels of depression and anxiety we used the State-Trait Anxiety Inventory. These surveys were conducted immediately before the initiation of corticosteroid therapy and just before discharge from the hospital. We observed a decrease in anxiety levels related to corticosteroid use and State-Trait Anxiety Inventory scores before discharge. However, we did not detect a correlation between these score changes. Additionally, we found that patients who had a poor understanding of the drugs showed little or no changes in their anxiety levels related to corticosteroid use at discharge. These results suggest that some aspects of anxiety related to corticosteroids might be groundless and substantiated by assumptions without a complete understanding of corticosteroid functioning. Patient education regarding corticosteroid use may lead to reductions in anxiety levels and improvement in quality of life of the patients.

Steroids Used to Treat Acne Vulgaris: A Review of Efficacy, Safety, and Clinical Considerations.

Acne vulgaris is prevalent among adolescents and adults worldwide and can significantly impact patients' quality of life. Steroidal molecules, including oral and intralesional corticosteroids, combined oral contraceptives (COCs), oral spironolactone, and topical clascoterone, are an important part of the acne treatment armamentarium. The recommended use, mechanism of action, and available evidence supporting the use of steroids for acne treatment are reviewed, and differences in acne clinical presentation and treatment approaches based on patient characteristics relevant to the selection of an appropriate steroid are also discussed. Steroid-based approaches target the systemic or local hormones (ie, testosterone and androgens) and inflammation that contribute to acne pathogenesis. Oral corticosteroids are primarily used as a short-term adjunctive therapy early in treatment, whereas intralesional corticosteroid injections are used for individual acne lesions. COCs and oral spironolactone are limited to female patients who wish to avoid pregnancy. Topical clascoterone can be used by female and male patients 12 years of age and older. Patients' characteristics (including age and patients with darker skin color) and preferences for the route of administration can impact treatment response and adherence, respectively. Overall, healthcare providers must be aware of the differences among steroidal acne treatments and use shared decision-making to select the optimal therapy. J Drugs Dermatol. 2024;23(6):404-409.     doi:10.36849/JDD.7846.

[Modern asthma management]. / Modernes Asthma-Management.

Symptom prevention and remission are the goals of asthma treatment. Precise phenotyping of the patients, including history, lung function, allergology and measurement of type 2 biomarkers, is the essential prerequisite for treatment success. Basic measures, treatment with DMAADs ("disease-modifying anti-asthmatic drugs": predominantly inhaled corticosteroids, biologics, and allergen immunotherapy) and treatment of comorbidities are the cornerstones of modern asthma management. The treatment of upper airway diseases such as allergic rhinitis (often associated with early-onset asthma) or chronic rhinosinusitis (often associated with adult-onset asthma, with 2 forms: either with nasal polyps, CRSwNP, or without nasal polyps, CRSsNP) is of major importance in this regard.