Prevalence of type 2 inflammatory diseases in pediatric patients with atopic dermatitis: Real-world evidence.

BACKGROUND: Patients with atopic dermatitis (AD) are considered at increased risk of developing other type 2 inflammatory diseases. However, real-world evidence based on large commercially insured pediatric populations in the United States is scarce. OBJECTIVE: To use a large claims database (IBM MarketScan 2013-2017) in the United States to assess prevalence and incidence of type 2 inflammatory diseases in pediatric patients with AD. METHODS: Pediatric patients with AD were matched 1:1 to patients without AD. Prevalence was assessed for conjunctivitis, rhinitis, urticaria, asthma, eosinophilic esophagitis, and chronic rhinosinusitis/nasal polyps at the 12 months' post-index date (the first AD diagnosis date for patients with AD; a randomly selected outpatient visit for control patients). The incidence of other type 2 inflammatory diseases post-index was assessed among patients 0-2 years of age. RESULTS: A total of 244,776 AD and matched non-AD patients were selected. The prevalence and incidence of type 2 inflammatory diseases were higher among patients with AD. Overall, the prevalence more than doubled for asthma, eosinophilic esophagitis, urticaria, and rhinitis, and increased with AD severity. LIMITATIONS: AD identification was based on billing diagnoses; the observation period was only 12 months; and the study was limited to commercially insured patients. CONCLUSION: The burden of type 2 inflammatory diseases in pediatric patients with AD is substantial, highlighting the need to optimize management of AD and its numerous associated morbidities.

Depression, Anxiety, Stress, and Insomnia amongst COVID Warriors across Several Hospitals after Second Wave: Have We Acclimatized? A Cross-sectional Survey.

Background: Coronavirus disease-2019 (COVID-19) pandemic has been a cause of significant mental health disturbances in medical health personnel. However, 18 months into the pandemic, healthcare workers (HCWs) have become accustomed to the heightened stress and anxiety that comes with caring for COVID patients. Through this study, we aim to measure depression, anxiety, stress, and insomnia in doctors with the help of validated scales. Materials and methods: This was a cross-sectional study with an online survey design conducted among doctors from major hospitals in New Delhi. The questionnaire included participant demographics, including designation, specialty, marital status, and living arrangements. This was followed by questions from the validated depression, anxiety, stress scale (DASS-21), and insomnia severity index (ISI). Depression, anxiety, stress, and insomnia scores were calculated for each participant, and the data were analyzed statistically. Results: The mean scores of the whole study population showed no depression, moderate anxiety, mild stress, and subthreshold insomnia. Female doctors exhibited more psychological issues (mild depression and stress, moderate anxiety, but only subthreshold insomnia) as compared to males (mild anxiety, but no depression, stress, and insomnia). Junior doctors also had higher depression, anxiety, and stress scores than senior doctors. Similarly, single doctors, those living alone, and those not having kids had higher DASS and insomnia scores. Discussion: HCWs have been under tremendous mental stress during this pandemic which is influenced by multiple factors. Female sex, junior doctors, working on the frontline, not being in a relationship, and living alone may be some of the factors recognized in our study and corroborated by many authors, which may increase the chances of depression, anxiety, and stress in them. HCWs need regular counseling, time off for rejuvenation, and social support to overcome this hurdle. How to cite this article: Kohli S, Diwan S, Kumar A, Kohli S, Aggarwal S, Sood A, et al. Depression, Anxiety, Stress, and Insomnia amongst COVID Warriors across Several Hospitals after Second Wave: Have We Acclimatized? A Cross-sectional Survey. Indian J Crit Care Med 2022;26(7):825-832.

A randomized comparative evaluation of C-MAC video-laryngoscope with Miller laryngoscope for neonatal endotracheal intubation.

Background and Aims: An efficient neonatal airway management is peculiarly challenging even in the most experienced hands. Considering the recent interest in assessing the performance of various video-laryngoscopes (VL) in pediatric cohort, the prospective randomized study was contemplated to stage a comparative evaluation of C-MAC with Miller laryngoscope for neonatal endotracheal intubation. Material and Methods: 150 neonates were randomized to undergo intubation with either the C-MAC VL (n = 75) or the Miller laryngoscope (n = 75) performed by an experienced anesthesiologist in a tertiary care perioperative setting. The percentage of glottic opening (POGO), time to best glottic view (TTBGV), time to intubation (TTI), number of attempts, optimal external laryngeal manipulation (OELM) employed, and the complications were assessed and compared between the two groups. Results: C-MAC group demonstrated a significantly higher POGO, compared to the Miller group (88 ± 26.7%;76.8 ± 32.1%, respectively, P = 0.022). TTBGV was significantly lower in the C-MAC (7.7 ± 0.1s) group as opposed to the Miller group (11.3 ± 1.1s). The C-MAC group displayed higher TTI values compared to the Miller group (25.4 ± 1.6s; 19.7 ± 1.2s, respectively, P < 0.01). The first-attempt intubation success rate and the number of attempts were comparable in both the groups. OELM was required in 24% of the patients in the Miller group as opposed to 10.7% in the C-MAC group (P = 0.031). Higher patient percentage in the C-MAC group required the need of stylet for assisting a successful intubation, although the difference between the two groups was not statistically significant. Conclusion: Despite an improved view of the glottis, the TTI was higher for C-MAC compared to direct laryngoscopy with a comparable first-attempt success rate in the two techniques.

Real-world persistence with dupilumab among adults with atopic dermatitis.

BACKGROUND: The real-world persistence with dupilumab therapy for atopic dermatitis (AD) is unknown. OBJECTIVE: To characterize adults with AD who initiated dupilumab and evaluate persistence with dupilumab therapy. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare database. Adults with AD who initiated dupilumab (first dispensation = index date) between March 28, 2017, and March 31, 2018, were identified and followed up until September 30, 2018, or disenrollment. Twelve months of continuous preindex enrollment were required to characterize baseline treatment history and comorbidities. Kaplan-Meier analysis was used to estimate dupilumab persistence at 6 and 12 months, assuming a 14-day injection frequency and a 30-day grace period. RESULTS: A total of 1963 adults were identified who initiated dupilumab (mean [SD] age 42.1 [15.7] years; 50.7% women; 49.8% with ≥1 atopic comorbidity). Baseline AD treatments included topical corticosteroids (81.6%), systemic corticosteroids (72.5%), and systemic immunosuppressants (22.8%). Dupilumab persistence (95% confidence interval) at 6 and 12 months was 91.9% (90.7%-93.2%) and 77.3% (75.0%-79.7%), respectively. Among 329 patients who discontinued dupilumab, the risk of reinitiation was 78.8% (95% confidence interval: 75.8%-81.7%) within an average of 4 months. CONCLUSION: Dupilumab persistence at 12 months was high, suggesting patient satisfaction with effectiveness, tolerability, and treatment regimen.

Treatment patterns of pediatric patients with atopic dermatitis: A claims data analysis.

BACKGROUND: Real-world evidence on treatment patterns of pediatric patients with atopic dermatitis (AD) is sparse. OBJECTIVE: To assess current treatment patterns in pediatric AD patients. METHODS: Retrospective observational analysis of commercial insurance and Medicaid administrative claims data (January 2011-December 2016) for pediatric AD patients, stratified by age and provider type. RESULTS: The analytic sample comprised 607,258 pediatric AD patients. Median observation period was 30.3 months. Overall, 78.6% were prescribed ≥1 AD medication; 86.7% were prescribed topical corticosteroids, and 5.4% were prescribed a calcineurin inhibitor. Systemic corticosteroids (SCSs) were prescribed for 24.4% of patients, 51.8% of whom did not have asthma or allergic comorbidities. Of the 46.6% prescribed an antihistamine and 16.2% prescribed montelukast, 62.0% and 41.3%, respectively, did not have asthma or allergic comorbidities. Systemic immunosuppressants were rarely prescribed (<0.5%). Higher potency topical corticosteroid and SCS use increased with age. Treatment patterns varied by provider type; specialists were more likely to prescribe higher potency topicals and/or systemics, regardless of patient age. A minority of patients were treated by or referred to a specialist. LIMITATIONS: Identification of AD patients relied on billing diagnoses; the disease severity was proxied by the treatment prescribed. CONCLUSION: Results indicate that SCSs, despite known risks, and other medications with disproven efficacy in AD are frequently prescribed, suggesting a need for safer and more effective alternatives.

Effects of variations in access to care for children with atopic dermatitis.

BACKGROUND: An estimated 50% of children in the US are Medicaid-insured. Some of these patients have poor health literacy and limited access to medications and specialty care. These factors affect treatment utilization for pediatric patients with atopic dermatitis (AD), the most common inflammatory skin disease in children. This study assesses and compares treatment patterns and healthcare resource utilization (HCRU) between large cohorts of Medicaid and commercially insured children with AD. METHODS: Pediatric patients with AD were identified from 2 large US healthcare claims databases (2011-2016). Included patients had continuous health plan eligibility for ≥6 months before and ≥12 months after the first AD diagnosis (index date). Patients with an autoimmune disease diagnosis within 6 months of the index date were excluded. Treatment patterns and all-cause and AD-related HCRU during the observation period were compared between commercially and Medicaid-insured children. RESULTS: A minority of children were evaluated by a dermatology or allergy/immunology specialist. Several significant differences were observed between commercially and Medicaid-insured children with AD. Disparities detected for Medicaid-insured children included: comparatively fewer received specialist care, emergency department and urgent care center utilization was higher, a greater proportion had asthma and non-atopic morbidities, high- potency topical corticosteroids and calcineurin inhibitors were less often prescribed, and prescriptions for antihistamines were more than three times higher, despite similar rates of comorbid asthma and allergies among antihistamine users. Treatment patterns also varied substantially across physician specialties. CONCLUSIONS: Results suggest barriers in accessing specialty care for all children with AD and significant differences in management between commercially and Medicaid-insured children. These disparities in treatment and access to specialty care may contribute to poor AD control, especially in Medicaid-insured patients.

Chemopreventive Synergism between Green Tea Extract and Curcumin in Patients with Potentially Malignant Oral Disorders: A Double-blind, Randomized Preliminary Study.

AIM: The aim of the study was to assess the synergistic effect of green tea extract and curcumin in patients with oral potentially malignant disorders (OPMDs) and to ascertain the mechanism of action of these chemopreventive agents through assessment of suitable biomarkers. MATERIALS AND METHODS: Subjects with OPMDs (n = 60) were randomized to receive green tea extract [topical + systemic (800 mg/day)] or curcumin [topical + Systemic (950 mg/day)] or a combination therapy with 20 patients in each group for 3 months. Biomarkers (Ki67, cyclin D1, and p53) were evaluated in baseline and 12-week biopsies. RESULTS: The clinical response rate observed in OPMDs was higher in the combination group (n = 13; 65%) as compared to the curcumin (n = 11; 55%) and the green tea extract group (n = 7; 35%) and was statistically highly significant. Treatment medications also improved histological grades, although not statistically significant. All the study drugs were well tolerated by patients and did not raise any safety concerns. There was statistically significant (p < 0.01) downregulation of p53, Ki67, and cyclin D1 expression at 3 months as compared to baseline in the combination group. CONCLUSION: Treatment of OPMDs with curcumin and green tea extract combination demonstrated a significant clinical response supported by downregulation of molecular biomarkers in the short-term (12 weeks). The present results warrant a long-term clinical testing of green tea and curcumin combination for oral cancer prevention. CLINICAL SIGNIFICANCE: Chemoprevention is a promising treatment strategy to reverse, stabilize, or arrest progression of these OPMDs. Use of natural dietary agents like green tea and curcumin, which are readily available, have low toxicity, and more importantly demonstrate a synergistic effect, is an attractive alternative in the chemoprevention of oral cancer. The assessment of biomarkers has helped us to understand the mechanism of action of these chemopreventive agents.

Validation of the Atopic Dermatitis Control Tool (ADCT©) using a longitudinal survey of biologic-treated patients with atopic dermatitis.

BACKGROUND: The Atopic Dermatitis Control Tool (ADCT©) is a brief patient self-administered instrument designed and validated to assess atopic dermatitis (AD) control; six AD symptoms and impacts are evaluated over the past week, including overall severity of symptoms, days with intense episodes of itching, intensity of bother, problem with sleep, impact on daily activities, and impact on mood or emotions. This study assessed the reliability, validity, and responsiveness of the ADCT in a longitudinal context, and provided thresholds to identify meaningful within-person change. METHODS: Data were from a prospective, longitudinal patient survey study of real-world effectiveness of dupilumab in patients with AD. Eligible patients completed a baseline survey before starting dupilumab and were followed at Months 1, 2, 3, and 6 post-initiation as they became eligible. RESULTS: Psychometric analyses confirmed internal consistency; Cronbach's α coefficients were consistently above the threshold of 0.70 across each follow-up; item-to-total correlations were above the threshold of r ≥ 0.50. High correlations between the ADCT and the Dermatology Life Quality Index (DLQI) and skin pain supported construct validity, while known-group validity was shown on Patient Global Assessment of Disease (PGAD) overall well-being subgroups with worse AD-related overall well-being having higher mean ADCT total scores at all time points. The ability of the ADCT to detect change was confirmed; the threshold for meaningful within-person change was estimated to be 5 points. Finally, test-retest reliability was confirmed in subgroups of patients with stable PGAD responses. CONCLUSIONS: Our findings confirm that the ADCT is a valid and reliable tool for assessing AD control.

Contemporary rates and correlates of statin use and adherence in nondiabetic adults with cardiovascular risk factors: The KP CHAMP study.

BACKGROUND: Statin therapy is highly efficacious in the prevention of fatal and nonfatal atherosclerotic events in persons at increased cardiovascular risk. However, its long-term effectiveness in practice depends on a high level of medication adherence by patients. METHODS: We identified nondiabetic adults with cardiovascular risk factors between 2008 and 2010 within a large integrated health care delivery system in Northern California. Through 2013, we examined the use and adherence of newly initiated statin therapy based on data from dispensed prescriptions from outpatient pharmacy databases. RESULTS: Among 209,704 eligible adults, 68,085 (32.5%) initiated statin therapy during the follow-up period, with 90.4% receiving low-potency statins. At 12 and 24 months after initiating statins, 84.3% and 80.2%, respectively, were actively receiving statin therapy, but only 42% and 30%, respectively, had no gaps in treatment during those time periods. There was also minimal switching between statins or use of other lipid-lowering therapies for augmentation during follow-up. Age≥50 years, Asian/Pacific Islander race, Hispanic ethnicity, prior myocardial infarction, prior ischemic stroke, hypertension, and baseline low-density lipoprotein cholesterol>100 mg/dL were associated with higher adjusted odds, whereas female gender, black race, current smoking, dementia were associated with lower adjusted odds, of active statin treatment at 12 months after initiation. CONCLUSIONS: There remain opportunities for improving prevention in patients at risk for cardiovascular events. Our study identified certain patient subgroups that may benefit from interventions to enhance medication adherence, particularly by minimizing treatment gaps and discontinuation of statin therapy within the first year of treatment.

Development and Validation of Algorithms to Identify Statin Intolerance in a US Administrative Database.

OBJECTIVES: To develop and validate algorithms to define statin intolerance (SI) in an administrative database using electronic medical records (EMRs) as the reference comparison. METHODS: One thousand adults with one or more qualifying changes in statin therapy and one or more previous diagnoses of hyperlipidemia, hypercholesterolemia, or mixed dyslipidemia were identified from the Henry Ford Health System administrative database. Data regarding statin utilization, comorbidities, and adverse effects were extracted from the administrative database and corresponding EMR. Patients were stratified by cardiovascular (CV) risk. SI was classified as absolute intolerance or titration intolerance on the basis of changes in statin utilization and/or the occurrence of adverse effects and laboratory testing for creatine kinase. Measures of concordance (Cohen's kappa [κ]) and accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value) were calculated for the administrative database algorithms. RESULTS: Half of the sample population was white, 52.9% were women, mean age was 60.6 years, and 35.7% were at high CV risk. SI was identified in 11.5% and 14.0%, absolute intolerance in 2.2% and 3.1%, and titration intolerance in 9.7% and 11.8% of the patients in the EMR and the administrative database, respectively. The algorithm identifying any SI had substantial concordance (κ = 0.66) and good sensitivity (78.1%), but modest PPV (64.0%). The titration intolerance algorithm performed better (κ = 0.74; sensitivity 85.4%; PPV 70.1%) than the absolute intolerance algorithm (κ = 0.40; sensitivity 50%; PPV 35.5%) and performed best in the high CV-risk group (n = 353), with robust concordance (κ = 0.73) and good sensitivity (80.9%) and PPV (75.3%). CONCLUSIONS: Conservative but comprehensive algorithms are available to identify SI in administrative databases for application in real-world research. These are the first validated algorithms for use in administrative databases available to decision makers.

N-[(1-Benzoyl-piperidin-4-yl)meth-yl]benzamide.

In the title compound, C20H22N2O2, the piperidine ring adopts a chair conformation. The phenyl rings are inclined to one another by 80.1 (1)° and make dihedral angles of 46.1 (1) and 40.2 (1)° with the mean plane of the piperidine ring. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers. C-H⋯O inter-actions further link the mol-ecules, forming a three-dimensional supramolecular network.

3,5-Dimethyl-2,6-di-phenyl-piperidine.

In the title compound, C19H23N, the piperidine ring has a chair conformation. The phenyl rings are inclined to one another by 52.76 (16)°. One of the methyl substituents on the piperidine ring is axial while the other is equatorial, like the phenyl rings. In the crystal, mol-ecules are linked via C-H⋯π inter-actions, forming zigzag chains along [001].

(E)-3-(4-Hy-droxy-3-meth-oxy-phen-yl)-1-(4-hy-droxy-phen-yl)prop-2-en-1-one.

In the title compound, C16H14O4, there is an intra-molecular O-H⋯O hydrogen bond. The benzene rings are inclined to one another by 13.89 (9)°. The prop-2-en-1-one group is twisted slightly, the O=C-Car-Car (ar = aromatic) and C=C-C=O torsion angles being -10.4 (3) and -7.4 (3)°, respectively. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains along [100]. These chains are further linked by O-H⋯O hydrogen bonds, forming corrugated sheets lying parallel to (010). There are C-H⋯π inter-actions present within the sheets.

(2E)-1-(3,5-Di-hydroxy-phen-yl)-3-(4-meth-oxy-phen-yl)prop-2-en-1-one.

In the title compound, C16H14O4, the benzene rings are inclined to one another by 4.91 (7)°. The conformation about the C=O and C=C bonds is trans and cis, respectively. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming inversion dimers with an R 2 (2)(14) ring motif. The dimers are linked via O-H⋯O and C-H⋯O hydrogen bonds, forming undulating two-dimensional networks lying parallel to (10-1). These networks are linked by further C-H⋯O hydrogen bonds, forming a three-dimensional structure.

5,5,7,12,12,14-Hexamethyl-1,8-bis-(4-nitro-benz-yl)-1,4,8,11-tetra-aza-cyclo-tetra-deca-ne.

The asymmetric unit of the title compound, C30H46N6O4, contains one half-mol-ecule. The C(benzene)-C(CH2)-N-C(-Me) torsion angle is -79.89 (13)° suggesting a synclinal orientation of the nitro-benzene ring with respect to the macrocycle. The conformation of the macrocycle is stabilized by intra-molecular N-H⋯N hydrogen bonds.

Crystal structure of 4-[(2E)-3-(4-meth-oxy-phen-yl)prop-2-eno-yl]phenyl benzoate.

In the title compound, C23H18O4, the meth-oxy-benzene ring and attached C=C grouping are disordered over two sets of sites in a 0.823 (5):0.177 (5) ratio. The dihedral angles between the central benzene ring and the pendant phenyl and meth-oxy-benzene ring (major orientation) are 51.21 (1) and 51.6 (1)°, respectively. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R 2 (2)(28) loops.

Crystal structure of 2-amino-4-methyl-pyridin-1-ium (2R,3R)-3-carb-oxy-2,3-di-hydroxy-propano-ate monohydrate.

The title mol-ecular salt, C6H9N2 (+)·C4H5O6 (-)·H2O, crystallized with two 2-amino-4-methyl-pyridin-1-ium cations, two l-(+)-tartaric acid monoanions [systematic name: (2R,3R)-3-carb-oxy-2,3-di-hydroxy-propano-ate] and two water mol-ecules in the asymmetric unit. In the crystal, the cations, anions and water mol-ecules are linked via a number of O-H⋯O and N-H⋯O hydrogen bonds, and a C-H⋯O hydrogen bond, forming a three-dimensional structure.

Crystal structure of 4-chloro-N-{[1-(4-chloro-benzo-yl)piperidin-4-yl]meth-yl}benzamide monohydrate.

In the title compound, C20H20Cl2N2O2·H2O, the piperidine ring adopts a chair conformation with the two substituent benzene rings inclined to one another [dihedral angle 84.63 (9)°]. In the crystal, the components are linked by Ow-H⋯O, N-H⋯Ow (w = water) and C-H⋯O hydrogen bonds, generating a sheet structure lying parallel to (101).

Crystal structure of 3-[4-(benz-yloxy)phen-yl]-2,3-di-hydro-1H-benzo[f]chromen-1-one.

In the title compound, C26H20O3, the pyran ring has a distorted half-chair conformation and its mean plane is inclined to the naphthalene ring system, to which it is fused, by 10.79 (9)°. The dihedral angles between the napthalene unit and the benzene and phenyl rings are 54.39 (9) and 52.65 (12)°, respectively, while the benzene and phenyl rings are inclined to one another by 74.80 (14)°. There is a short C-H⋯O contact in the chromen-1-one unit. In the crystal, mol-ecules are linked by two pairs of C-H⋯O hydrogen bonds, forming inversion dimers described by graph set motifs R 2 (2)(8) and R 2 (2)(10), giving rise to chains running parallel to (101). The chains are linked via C-H⋯π inter-actions, forming sheets lying parallel to (010).

Crystal structure of 4-methyl-N-{[1-(4-methyl-benzo-yl)piperidin-4-yl]meth-yl}benzamide.

In the title compound, C22H27N2O2, the piperidine ring adopts a half-chair conformation with the benzene rings inclined in a trans orientation with respect to the piperidine ring [dihedral angle between the benzene rings = 89.1 (1)°]. In the crystal, a three-centre asymmetric N-H⋯O/C-H⋯O hydrogen-bonding inter-action leads to the formation of chains extending along the a-axis direction.