Skin infections during dupilumab monotherapy in moderate-to-severe atopic dermatitis - a meta-analysis of randomized clinical trials.

OBJECTIVE: Atopic dermatitis (AD) increases the risk of bacterial and viral cutaneous infections. This study assesses the risk of skin infections related to dupilumab monotherapy in moderate-to-severe AD. METHODS: We searched PubMed/Medline, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library. For gray literature, Google Scholar was searched. A meta-analysis of randomized clinical trials (RCTs) for overall skin infections, eczema herpeticum, nonherpetic skin infections and subgroup meta-analysis based on overall herpetic infection type was performed. RESULTS: We observed a statistically significant (p < 0.005) lower incidence rate in the dupilumab group compared to placebo for overall skin infections (Risk Ratio [RR] = 0.59, 95% confidence interval [CI]: [0.47, 0.75], P < 0.0001) and nonherpetic skin infections (RR = 0.42, 95% CI: [0.27, 0.66], P = 0.0001). For herpetic infections in 2b phase studies a meta-analysis demonstrated significantly higher events in dupilumab group compared to placebo (RR = 3.38, 95% CI: [1.98, 5.76], P < 0.00001, test for subgroup differences: P = 0.02, I2 = 65.6%). CONCLUSIONS: In moderate-to-severe AD, dupilumab in monotherapy may be an effective and safe therapeutic approach, not associated with an increased risk of overall skin infections and nonherpetic skin infections. Due to the lack of statistical significance in heterogeneity associated with potential confounders in some cases, results should be interpreted cautiously. REGISTRATION: The meta-analysis was registered in PROSPERO, ID: CRD42023441346.

Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study.

INTRODUCTION: Extrafine formulation of beclomethasone/formoterol fixed combination (BDP/F pMDI HFA) is approved for both fixed maintenance and maintenance and reliever therapy (MART) of asthma, and recent data has proven that BDP/F pMDI HFA maintenance and reliever therapy is an effective alternative to other regimens. OBJECTIVE: This study aimed to assess the level of asthma control in a real-life setting in adult patients using extrafine BDP/F pMDI HFA fixed combination in a pressurized metered-dose inhaler (pMDI) as fixed maintenance dosing as well as maintenance and maintenance and reliever therapy. Additionally, we examined patients' satisfaction with the inhaler device and compliance with therapy as essential factors determining asthma control. METHODS: This multicenter prospective non-interventional observational study lasted 4 months with 3 patient visits. We used the Asthma Control Questionnaire 7 (ACQ-7) to evaluate the degree of asthma control and Morisky Medication Adherence Scale (MMAS-4) to assess compliance. A self-developed questionnaire was used to assess satisfaction with the inhaler device. RESULTS: 2179 patients using BDP/F pMDI HFA fixed combination as maintenance and reliever therapy or BDP/F pMDI HFA as maintenance therapy and SABA (short-acting beta2-agonist) as a reliever for at least 2 months were included. During the prospective follow-up, we observed an upward trend in the FEV1% (forced expiratory volume in 1 s) predicted values, improvement in the control of symptoms as indicated by a decline in the mean ACQ-7 score was noted (1.62 at Visit 1 vs. 1.21 at Visit 2 vs. 0.94 at Visit 3, p < 0.001) and increase in patients' compliance (the number of patients that reported forgetting at times to take their medication was reduced from 49.7 % to 27.1 %, p < 0.001). At the same time, we noted a reduction in the number of as-needed doses used for symptom relief (p < 0.001). Most patients were satisfied with the pMDI, considered it easy and convenient to use, and preferred it to a dry powder inhaler (p < 0.001). CONCLUSIONS: The use of extrafine BDP/F pMDI HFA as maintenance as well as reliever therapy seems to be associated with increased asthma control and better compliance to therapy.

Resveratrol and Its Derivatives in Inflammatory Skin Disorders-Atopic Dermatitis and Psoriasis: A Review.

Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases whose prevalence has increased worldwide in recent decades. These disorders contribute to patients' decreased quality of life (QoL) and constitute a socioeconomic burden. New therapeutic options for AD and psoriasis based on natural compounds are being investigated. These include resveratrol (3,5,40-trihydroxystilbene) and its derivatives, which are produced by many plant species, including grapevines. Resveratrol has gained interest since the term "French Paradox", which refers to improved cardiovascular outcomes despite a high-fat diet in the French population, was introduced. Resveratrol and its derivatives have demonstrated various health benefits. In addition to anti-cancer, anti-aging, and antibacterial effects, there are also anti-inflammatory and antioxidant effects that can affect the molecular pathways of inflammatory skin disorders. A comprehensive understanding of these mechanisms may help develop new therapies. Numerous in vivo and in vitro studies have been conducted on the therapeutic properties of natural compounds. However, regarding resveratrol and its derivatives in treating AD and psoriasis, there are still many unexplained mechanisms and a need for clinical trials. Considering this, in this review, we discuss and summarize the most critical research on resveratrol and its derivatives in animal and cell models mimicking AD and psoriasis.

Assessment of the available therapeutic approaches for severe COVID-19: a meta-analysis of randomized controlled trials.

The study aimed to evaluate severe COVID-19 treatment approaches. We conducted a meta-analysis of randomized controlled trials (RTCs) with standard of care (SoC) as a control group and/or placebo. Database searching was performed separately for severe COVID-19 treatment such as anakinra, remdesivir, baricitinib, ivermectin, ritonavir, tocilizumab, sarilumab, sotrovimab, casirivimab/imdevimab. The results are presented as Risk Ratio (RR), 95% Confidence Interval (CI), and heterogeneity (I2). We obtained the most statistically significant outcomes favorable tocilizumab compared to SoC for death incidents RR 0.87 [95% CI 0.80, 0.95], overall effect p = 0.002, heterogeneity p = 0.85, I2 = 0%, need for mechanical ventilation RR 0.78 [95% CI 0.68, 0.89], overall effect p = 0.0004, heterogeneity p = 0.55, I2 = 0%, and number of patients discharged from hospital. RR 1.13 [95% CI 1.07, 1.20], overall effect p < 0.00001, heterogeneity p = 0.009, I2 = 85%. This meta-analysis has revealed that a considerable amount of research characterized by a very diverse methodology is available. Despite the limited data that met the criteria for inclusion in the meta-analysis, we showed that the available treatment options for severe COVID-19 are effective.

Pharmacotherapy and immunotherapy of allergic rhinitis induced by house dust mite, grass, and birch pollen allergens: a meta-analysis of randomized clinical trials.

BACKGROUND: The aim of this study was to assess the efficacy and safety of oral antihistamines (AHs), intranasal antihistamines (INAH) intranasal glucocorticosteroids (INCS), subcutaneous immunotherapy (SCIT), and sublingual immunotherapy (SLIT) in the management of allergic rhinitis (AR). The authors focused on the division into selected AR's triggers: house dust mites (HDMs), grass pollen, and birch pollen. METHODS: For each drug and allergen class, a meta-analysis of the efficacy and adverse events (AEs) was performed. The obtained results were presented as a therapeutic index (TIX-Score). RESULTS: Twenty-seven randomized clinical trials (RCTs) were included. The best total efficacy was observed for: HDMs for INCS and grass pollen for combination of INCS with INAH in a single device and for INAH. Considering the data that was obtained for birch pollen, SLIT showed statistically significant total efficacy. Summation scores for efficacy and AEs showed highest TIX-Score for combination of INCS and INAH in a single device in grass pollen. CONCLUSIONS: Treatment methods selected for this review may serve as an effective and safe treatment in reducing perennial and seasonal AR's symptoms. However, due to high heterogeneity probably associated with potential confounders existence in control in some cases, results should be interpreted with caution.

Real-life efficiency and safety comparison study of emollient ointment based on glycerophosphoinositol (GPI) salt of choline and other emollient products in patients with atopic dermatitis.

INTRODUCTION: The aim of this study was to investigate the effectiveness and safety of emollient preparations in comparison with the emollient ointment containing glycerophosphoinositol salt of choline in patients with atopic dermatitis (AD). METHODS: In a 'real-life' study, 300 patients with moderate AD were age-stratified and divided into two groups: patients applying GPI emollient and the comparator. We evaluated the effectiveness of AD treatment using: Eczema Area and Severity Index (EASI), Three Item Severity (TIS), Visual Analogue Scale (VAS) and Four-Item Itch Questionnaire. RESULTS: The GPI emollient was superior in reduction AD symptoms in children: VAS (-2.58 ± 0.25), TIS (-2.22 ± 0.22), EASI (-15.27 ± 1.77), and adults: VAS (-2.42 ± 0.19), TIS (-2.22 ± 0.17), EASI (-13.22 ± 1.53), as compared to the other emollient in children: VAS (-0.67 ± 0.19), TIS (0.47 ± 0.19), EASI (-3.71 ± 1.01) and adults: VAS (-0.86 ± 0.09), TIS (0.77 ± 0.09), EASI (-2.95 ± 0.46), p < .001. Similar results were observed in Four Item Itch Questionnaire. CONCLUSION: Both emollients showed good safety and tolerance profile and reduced AD symptoms. The GPI emollient seems to be more slightly effective in reducing AD symptoms as compared to the other commercially available emollient.

Can we safely use systemic treatment in atopic dermatitis during the COVID-19 pandemic? Overview of selected conventional and biologic systemic therapies.

Introduction: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical community has faced major challenges that affect disease management in all areas. Dermatologists and immunologists have to choose appropriate treatment strategy taking into consideration the risk of infection and possible exacerbation of the course of the disease in patients with confirmed infection. Management of atopic dermatitis (AD) in moderate to severe cases is based on systemic therapy such as cyclosporine, azathioprine, methotrexate and dupilumab.Areas covered: A literature search in PubMed database was performed until 6 March 2021. In this review, the authors discuss non-biologic and biologic systemic medications for AD and provide an overview of therapeutic recommendations during COVID-19 pandemic.Expert opinion: In case of an active COVID-19 infection, conventional systemic treatment and biological treatment needs to be stopped until clinical recovery. Noninfected patients with systemic treatment of AD should continue their therapy via self-application. The authors can conclude that understanding of dupilumab therapy is better recognized in context AD treatment during COVID-19 pandemic in comparison to cyclosporine, azathioprine and methotrexate. However, this systemic immunosuppressants still require further investigation and literature complementation.

Obesity and asthma: risk, control and treatment.

Asthma and obesity are currently one of the most common diseases. Observing an increase in morbidity of obesity and asthma, it can be concluded that there is a link between these diseases. But the mechanism of this relation is not well known. Due to reduced movement in patients and treatment, asthma is conducive to obesity, and obesity can exacerbate the symptoms associated with asthma. Obesity can affect bronchial hyperresponsiveness. Increasing body fat in obese people leads to systemic inflammation and elevated serum levels of many proinflammatory cytokines (e.g. leptin) and anti-inflammatory ones (e.g. adiponectin) that can have a causal relationship to bronchial asthma, but human studies are ambiguous. Obese asthmatics are characterized by a phenotype: heavier asthma, worse response to treatment and control of asthma. It has been found that in obese people, weight loss reduces the severity of asthma symptoms, so in these patients, treatment should include weight control.

An innovative health-care delivery model for children with medical complexity.

Children with medical complexity (CMC) account for a disproportionate share of pediatric health-care utilization and cost that is largely attributable to long hospitalizations, frequent hospital readmissions, and high use of emergency departments. In response, the Centers for Medicare and Medicaid Services Health Care Innovation Center supports the development and testing of innovative health-care payment and service delivery models. The purpose of this article is to describe the CMS-funded coordinated health care for complex kids (CHECK) program, an innovative system of health-care delivery that provides improved, comprehensive, and well-coordinated services to CMC. The CHECK program uses a combination of high-tech and low-tech interventions to connect patients, stakeholders, and providers. It is anticipated that the investment in additional support services to CMC will result in improved quality of care that leads to a reduction in unnecessary inpatient hospitalizations, readmissions, and emergency department visits and a total cost savings. The CHECK program has the potential to inform future cost-effective health-care models aimed at improving the quality of life and care for CMC and their families.

Randomized controlled trial of primary care physician motivational interviewing versus brief advice to engage adolescents with an Internet-based depression prevention intervention: 6-month outcomes and predictors of improvement.

We believe that primary care physicians could play a key role in engaging youth with a depression prevention intervention. We developed CATCH-IT (Competent Adulthood Transition with Cognitive Behavioral and Interpersonal Training), which is an adolescent Internet-based behavior change model. We conducted a randomized comparison of two approaches in engaging adolescents with the Internet intervention: primary care physician (PCP) motivational interview + CATCH-IT Internet program (MI) vs PCP brief advice + CATCH-IT Internet program (BA). The participants (N = 84) were recruited by screening for risk of depression in 13 primary care practices. We compared depressive disorder outcomes between groups and within groups over 6 months and examined the potential predictors and moderators of outcomes across both study arms. Depressive symptom scores declined from baseline to 6 weeks with these statistically significant reductions sustained at the 6 months follow-up in both groups. No significant interactions with treatment condition were found. However, by 6 months, the MI group demonstrated significantly fewer depressive episodes and reported less hopelessness as compared with the BA group. Hierarchical linear modeling regressions showed higher ratings of ease of use of the Internet program predicting lower depressive symptom levels over 6 months. In conclusion, a primary care/Internet-based intervention model among adolescents demonstrated reductions in depressed mood over 6 months and may result in fewer depressive episodes.

Development and pilot study of a marketing strategy for primary care/internet-based depression prevention intervention for adolescents (the CATCH-IT intervention).

BACKGROUND: Adolescent depression is both common and burdensome, and while evidence-based strategies have been developed to prevent adolescent depression, participation in such interventions remains extremely low, with less than 3% of at-risk individuals participating. To promote participation in evidence-based preventive strategies, a rigorous marketing strategy is needed to translate research into practice. OBJECTIVE: To develop and pilot a rigorous marketing strategy for engaging at-risk individuals with an Internet-based depression prevention intervention in primary care targeting key attitudes and beliefs. METHOD: A marketing design group was constituted to develop a marketing strategy based on the principles of targeting, positioning/competitor analysis, decision analysis, and promotion/distribution and incorporating contemporary models of behavior change. We evaluated the formative quality of the intervention and observed the fielding experience for prevention using a pilot study (observational) design. RESULTS: The marketing plan focused on "resiliency building" rather than "depression intervention" and was relayed by office staff and the Internet site. Twelve practices successfully implemented the intervention and recruited a diverse sample of adolescents with > 30% of all those with positive screens and > 80% of those eligible after phone assessment enrolling in the study with a cost of $58 per enrollee. Adolescent motivation for depression prevention (1-10 scale) increased from a baseline mean value of 7.45 (SD = 2.05) to 8.07 poststudy (SD = 1.33) (P = .048). CONCLUSIONS: Marketing strategies for preventive interventions for mental disorders can be developed and successfully introduced and marketed in primary care.

Adolescents in Primary Care with Sub-Threshold Depressed Mood Screened for Participation in a Depression Prevention Study: Co-Morbidity and Factors Associated with Depressive Symptoms.

PURPOSE: Adolescents in primary care with sub-threshold depression symptoms may be candidates for early intervention to prevent onset of full major depressive disorder. Little is known about this population. METHOD: We screened consecutive adolescents (ages 14-21) in 13 primary care sites for presence of depression symptoms for "at least a few days" or "nearly every day" in the last two weeks for possible enrollment in a primary care/Internet-based depression prevention intervention (CATCH-IT). We report illness severity, prevalence of self-harm ideation, prevalence correlates (automatic negative thoughts, generalized self-efficacy, perceived social support from family and friends) and co-occurring symptoms of other mental disorders with depressed mood. RESULTS: Twenty-one percent (N=293) of those screened reported a core symptom of depressive disorder of which 83 enrolled in the study and were analyzed. The sample was 40% ethnic minority with a mean zip code household income of $40,249 (SD=$14,500). Reporting at least one symptom of another mental disorder was common for anxiety (48%, N=40), substance abuse (31%, N=15), conduct disorder (71%, N=53), as were self-harm ideation (16%, N=12) and reporting school impairment (100%, N=83). Prevalence correlates for current depressive symptoms included low self-efficacy, automatic negative thoughts, perceived low peer acceptance, and school impairment. CONCLUSIONS: Adolescents with sub-threshold depressed mood have frequent co-morbid symptoms that may need to be considered in developing prevention interventions. Early intervention targets to reduce depressed mood include pessimistic thinking, low self-efficacy, low peer acceptance, and school impairment.

Adolescent Internet Depression Prevention: Preferences for Intervention and Predictors of Intentions and Adherence.

Adolescents in primary care with sub-threshold depression (not reaching criteria for disorder) symptoms may be candidates for early intervention to prevent onset of major depressive disorder. However, we know little about their attitudes toward such interventions or what may predict motivation or adherence for preventive interventions. We also describe preferences for different types of interventions and conduct exploratory analyses to identify predictors of motivation to prevent depression and subsequent adherence to an Internet-based intervention. Adolescents with sub-threshold depressed mood favored novel behavioral treatment approaches, such as Internet-based models for depression prevention. Adolescent beliefs about the intervention and perceived social norms predicted intention to participate in depression prevention. The most important significant predictors of adherence were beliefs about the intervention. Careful attention to the specific beliefs and attitudes of users toward intervention should be incorporated into intervention design as well as evolving public health strategies to prevent depressive disorders.

Adolescent Dose and Ratings of an Internet-Based Depression Prevention Program: A Randomized Trial of Primary Care Physician Brief Advice versus a Motivational Interview.

BACKGROUND: Internet-based interventions for education and behavior change have proliferated, but most adolescents may not be sufficiently motivated to engage in Internet-based behavior change interventions. We sought to determine how two different forms of primary care physician engagement, brief advice (BA) versus motivational interview (MI), could enhance participation outcomes in an Internet-based depression prevention intervention. METHODS: Eighty-three adolescents at risk for developing major depression were recruited by screening in primary care and randomized to two groups: BA (1-2 minutes) + Internet program versus MI (10-15 minutes) + Internet program. We compared measures of participation and satisfaction for the two groups for a minimum of 12 months after enrollment. RESULTS: Both groups engaged the site actively (MI: 90% versus BA: 78%, p=0.12). MI had significantly higher levels of engagement than BA for measures including total time on site (143.7 minutes versus 100.2 minutes, p=0.03), number of sessions (8.16 versus 6.00, p=0.04), longer duration of session activity on Internet site (46.2 days versus 29.34 days, p=0.04), and with more characters typed into exercises (3532 versus 2004, p=0.01). Adolescents in the MI group reported higher trust in their physician (4.18 versus 3.74, p=0.05) and greater satisfaction with the Internet-based component (7.92 versus 6.66, p=0.01). CONCLUSIONS: Primary care engagement, particularly using motivational interviewing, may increase Internet use dose, and some elements enhance and intensify adolescent use of an Internet-based intervention over a one to two month period. Primary care engagement may be a useful method to facilitate adolescent involvement in preventive mental health interventions.