Correlation of Disease Severity, Proinflammatory Cytokines, and Reduced Brain Gray Matter Volumes in Patients with Atopic Dermatitis.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. However, few studies have investigated brain changes associated with chronic inflammation. We hypothesized that chronic inflammation might be related to brain structural alterations in patients with AD. Objectives: To investigate the association between disease severity (Eczema Area and Severity Index [EASI]), proinflammatory cytokines, and differences in brain gray matter (GM) volume in patients with AD. Methods: Nineteen patients with AD and 19 age- and sex-matched healthy subjects were enrolled. All participants underwent clinical assessment and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze GM volume differences. Results: Patients with AD exhibited significantly decreased GM volume in many brain regions, such as bilateral precentral gyrus, right frontal pole, and right middle temporal gyrus (P < 0.001), compared with healthy subjects. Notably, in patients with AD, the GM volume in right middle temporal gyrus was negatively associated with both EASI score and proinflammatory cytokines (sIL-2R [soluble interleukin 2 receptor] and TNF-α receptor-1), whereas the GM volume in left precentral gyrus was negatively associated with both EASI score and proinflammatory cytokines (sIL-2R and CRP). Conclusion: Patients with AD demonstrated significant brain GM volume reduction in many brain regions, which is related to disease severity and proinflammatory cytokines.

Associations of Atopic Dermatitis with Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Atopic dermatitis (AD) shares similarities with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) regarding pathogenesis involving neuroinflammation and genetics. Nevertheless, evidence on the associations of AD with ADHD and/or ASD is inconclusive. This study aimed to systematically examine the existing evidence on the associations between AD, ADHD, and ASD. METHODS: The Meta-Analysis of Observational Studies in Epidemiology guideline was followed. We searched MEDLINE, Embase, Cochrane Library, and Web of Science databases from their respective inceptions to March 4, 2022. Observational studies providing adjusted estimates and/or prevalences for ADHD and ASD in patients with AD were enrolled. A random-effects model meta-analysis was conducted to calculate pooled odds ratios (ORs) and confidence intervals (CIs). Subgroup analyses according to AD severity, age, geographic location, and study design were performed. RESULTS: Overall, a total of 24 studies with 71,373,639 subjects were enrolled. Our meta-analysis demonstrated significant associations of AD with ADHD (pooled OR: 1.28; 95% CI: 1.18-1.40) and ASD (pooled OR: 1.87; 95% CI: 1.30-2.68). Subgroup analyses revealed that the associations for ADHD were the most prominent in studies evaluating severe AD patients as well as in studies focusing on school-age children and adolescents. Among patients with AD, the pooled prevalence of ADHD was 6.6%, and the respective prevalence of ASD was 1.6%. CONCLUSION: The evidence to date suggests significant associations of AD with ADHD and ASD. Psychiatric consultation and an interdisciplinary approach would benefit patients with AD presented with behavioral symptoms suggestive of ADHD or ASD.

Violaceous Nodules on the Right Leg and Foot.

A patient with a history of bullous pemphigoid treated with oral prednisolone presented with multiple round, dark brown to violaceous-colored firm nodules on the right leg and 2 nodular masses with hemorrhagic crusts on the right foot. Complete blood cell count and creatinine and liver function test results were normal, and results of HIV antibody testing were negative. What is the diagnosis and what would you do next?

Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta-Analysis.

Background Bullous pemphigoid (BP) and pemphigus vulgaris (PV) share similar pathophysiology with venous thromboembolism (VTE) involving platelet activation, immune dysregulation, and systemic inflammation. Nevertheless, their associations have not been well established. Methods and Results To examine the risk of incident VTE among patients with BP or PV, we performed a nationwide cohort study using Taiwan's National Health Insurance Research Database and enrolled 12 162 adults with BP or PV and 12 162 controls. A Cox regression model considering stabilized inverse probability weighting was used to calculate the hazard ratios (HRs) for incident VTE associated with BP or PV. To consolidate the findings, a meta-analysis that incorporated results from the present cohort study with previous literature was also conducted. Compared with controls, patients with BP or PV had an increased risk for incident VTE (HR, 1.87 [95% CI, 1.55-2.26]; P<0.001). The incidence of VTE was 6.47 and 2.20 per 1000 person-years in the BP and PV cohorts, respectively. The risk for incident VTE significantly increased among patients with BP (HR, 1.85 [95% CI, 1.52-2.24]; P<0.001) and PV (HR, 1.99 [95% CI, 1.02-3.91]; P=0.04). In the meta-analysis of 8 studies including ours, BP and PV were associated with an increased risk for incident VTE (pooled relative risk, 2.17 [95% CI, 1.82-2.62]; P<0.001). Conclusions BP and PV are associated with an increased risk for VTE. Preventive approaches and cardiovascular evaluation should be considered particularly for patients with BP or PV with concomitant risk factors such as hospitalization or immobilization.

Risk of Venous Thromboembolism Among Adults With Atopic Dermatitis.

Importance: The associations of atopic dermatitis (AD) with multiple cardiovascular comorbidities have been investigated because of its pathomechanisms regarding chronic systemic inflammation and potential vascular effects. Nevertheless, the association between AD and incident venous thromboembolism (VTE) in adulthood is largely unknown. This study aimed to investigate the association of AD with incident VTE. Objective: To examine the risk of incident VTE among patients with AD. Design, Setting, and Participants: This population-based nationwide cohort study included adults 20 years or older (adults with AD newly diagnosed between 2003 and 2017 and matched controls) from the National Health Insurance Research Database. Patients with AD were subgrouped according to the severity of the disease. A Cox regression model was used to estimate hazard ratios (HRs) for VTE. Stratified analyses according to age and sex, and a sensitivity analysis excluding systemic steroid users were performed. Main Outcomes and Measures: Hazard ratios (HRs) for incident VTE associated with AD. Results: This analysis included a total of 284 858 participants, with 142 429 participants each in the AD (mean [SD] age, 44.9 [18.3] years; 78 213 women) and non-AD cohorts (mean [SD] age, 44.1 [18.1] years; 79 636 women). During the follow-up, 1066 patients (0.7%) in the AD cohort and 829 patients (0.6%) in the non-AD cohort developed VTE, with incidence rates of 1.05 and 0.82 per 1000 person-years, respectively. Adults with AD had a significantly increased risk of incident VTE (HR, 1.28; 95% CI, 1.17-1.40) compared with adults without AD. Individual outcome analyses suggested that AD was associated with higher risks of deep vein thrombosis (HR, 1.26; 95% CI, 1.14-1.40) and pulmonary embolism (HR, 1.30; 95% CI, 1.08-1.57). Conclusions and Relevance: The results of this cohort study suggest that AD in adulthood is associated with an increased risk of VTE; however, the absolute risk difference of VTE between adults with and without AD appears small. Nevertheless, cardiovascular examination and imperative management may be considered for adults with AD who present with symptoms suggestive of VTE. Future research is warranted to elucidate the pathophysiology underlying the association between AD and VTE.

Combined phacovitrectomy versus sequential surgery for idiopathic macular holes: systematic review and meta-analysis.

OBJECTIVE: To compare the best-corrected visual acuity (BCVA) change, idiopathic macular (IMH) closure, and complications in IMH patients receiving combined phacovitrectomy and sequential surgery (vitrectomy followed by phacoemulsification). DESIGN: Systematic review and meta-analysis. METHODS: PubMed, Ovid EMBASE, and Cochrane Library databases were searched from their inception through February 2022. Randomized, controlled trials and observational studies that presented results of BCVA change, IMH closure, and surgery-related complications were included. A random-effects meta-analysis was conducted to calculate effect estimates with 95% CIs. RESULTS: One randomized, controlled trials and 7 cohort studies with 585 patients were included. Overall, the meta-analyses of BCVA change (mean difference, -0.03; 95% CI, -0.10-0.04) and IMH closure (risk ratio = 1.04; 95% CI, 0.96-1.13) revealed no significant differences between combined phacovitrectomy and sequential surgery. The pooled risk ratios for various surgical complications such as postoperative retinal detachment, inflammation, and intraocular pressure elevation showed no significant differences between the 2 groups. CONCLUSIONS: Similar visual gain and IMH closure rates were achieved after both combined phacovitrectomy and sequential surgery, with similar complication risks. The anatomic and functional outcomes of combined surgery were not better than those of sequential surgery. These results could serve as a reference for future trials.

Risk of Subsequent Dementia or Alzheimer Disease Among Patients With Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

PURPOSE: Alzheimer disease (AD), a common form of dementia, shares several clinical and pathologic features with age-related macular degeneration (AMD). Epidemiologic reports on the association of AMD with subsequent dementia or AD are inconsistent. DESIGN: Systematic review and meta-analysis. METHODS: The Meta-analysis of Observational Studies in Epidemiology reporting guidelines were applied. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in the included cohort studies that examined the association of AMD with subsequent dementia or AD. We estimated the pooled hazard ratios (HRs) of dementia or AD using random effects model meta-analysis and subgroup analysis on different follow-up periods, AMD subtype, gender, age, study design, and methods to ascertain dementia or AD. RESULTS: A total of 8 223 581 participants were included in 8 studies published during 2000-2021. The meta-analysis showed that AMD was significantly associated with subsequent dementia (pooled HR 1.22, 95% CI 1.01-1.47) or AD (pooled HR 1.21, 95% CI 1.03-1.43). Our secondary analysis revealed that the association was more noticeable in dry AMD than wet AMD. CONCLUSIONS: Patients with AMD have higher risks of developing dementia or AD, and therefore identifying related comorbidities and retinal biomarkers is much warranted for older adults with AMD in ophthalmologic practice.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.

Purpose: Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results. Methods: The Ovid MEDLINE/Embase, Cochrane Library, and Web of Science databases were systematically searched from inception through August 3, 2022. Studies reporting the association between metformin use and odds of AMD were enrolled. Adjusted odds ratios (ORs) of AMD were extracted and pooled with random-effects model meta-analysis. Subgroup analyses based on AMD subtypes, ethnicity, study design, sex, and confirmation of AMD diagnosis were conducted. Results: A total of 9 observational studies with 1,446,284 participants were included in the analysis. The meta-analysis showed that metformin use was associated with a significant reduction in the odds of AMD (pooled ORs = 0.81, 95% confidence interval [CI] = 0.70-0.93). Subgroup analyses revealed that metformin use was not significantly associated with dry or wet AMD. Black (pooled ORs = 0.61, 95% CI = 0.58-0.64) and Hispanic populations (pooled ORs = 0.85, 95% CI = 0.81-0.89) demonstrated significantly lower odds of AMD. Conclusions: This systematic review and meta-analysis found that patients with DM with metformin usage were at lower odds of developing AMD. Future prospective clinical trials are needed to confirm this association.

Association of Risk of Incident Venous Thromboembolism With Atopic Dermatitis and Treatment With Janus Kinase Inhibitors: A Systematic Review and Meta-analysis.

Importance: The risk of venous thromboembolism (VTE) among patients with atopic dermatitis (AD), especially when receiving treatment with Janus kinase (JAK) inhibitors, is unclear. Objective: To determine the association of AD with incident VTE and evaluate the risk of incident VTE among patients with AD who were receiving treatment with JAK inhibitors. Data Sources: The MEDLINE, Embase, Cochrane Library, and Web of Science databases were searched with no restrictions on language nor geographic locations from their respective inception to February 5, 2022. Study Selection: Cohort studies examining the association of AD with incident VTE and randomized clinical trials (RCTs) reporting VTE events in participants with AD receiving JAK inhibitors were included. Around 0.7% of initially identified articles met the selection criteria. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The risk of bias of included cohort studies and RCTs was assessed by the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool 2, respectively. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratio (HR) and risk difference for incident VTE. Main Outcomes and Measures: The HRs for incident VTE associated with AD and risk difference for incident VTE between participants with AD who were receiving treatment with JAK inhibitors and controls receiving placebo or dupilumab. Results: Two cohort studies and 15 RCTs with a total of 466 993 participants were included. The meta-analysis found no significant association of AD with incident VTE (HR, 0.95; 95% CI 0.62-1.45; incidence rate of VTE, 0.23 events/100 patient-years). Overall, 3 of 5722 patients with AD (0.05%) who were receiving treatment with JAK inhibitors experienced VTE compared with 1 of 3065 patients with AD (0.03%) receiving placebo or dupilumab (Mantel-Haenszel risk difference, 0; 95% CI, 0-0). The incidence rate of VTE was 0.15 and 0.12 events per 100 patient-years in participants with AD receiving JAK inhibitors and placebo, respectively. The findings were similar in 4 unique JAK inhibitors (abrocitinib, baricitinib, upadacitinib, and SHR0302). Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that the currently available evidence does not detect an increased risk of VTE associated with AD or treatment with JAK inhibitors. These findings may provide a reference for clinicians in prescribing JAK inhibitors for patients with AD.

Efficacy of atropine, orthokeratology, and combined atropine with orthokeratology for childhood myopia: A systematic review and network meta-analysis.

BACKGROUND/PURPOSE: Orthokeratology (Ortho-K), atropine eye drops and combined atropine with Ortho-K are proven to be effective ways to prevent myopic progression in many studies, but there is scarce evidence regarding the comparative efficacy of different dosages of atropine,Ortho-K, and combined atropine with Ortho-K for childhood myopia. METHODS: We performed a network meta-analysis (NMA) to assess the relative efficacy of the aforementioned interventions for myopic progression; moreover, we calculated the surface under cumulative ranking area (SUCRA) to determine the relative ranking of treatments. RESULTS: We identified 19 randomized controlled trials (3435 patients). NMA revealed that 0.01%-1% atropine, Ortho-K, and 0.01% atropine combined with Ortho-K inhibited axial elongation (AL) over one year. For refractive change, SUCRA analysis revealed that the hierarchy was high-dose (0.5%-1%), moderate-dose (0.1%-0.25%), and low-dose (0.01%-0.05%) atropine. Regarding AL, SUCRA analysis revealed the following hierarchy: Ortho-K combined with 0.01% atropine, high-dose atropine, moderate-dose atropine, Ortho-K, and low-dose atropine. CONCLUSION: In conclusion, we found that atropine (0.01%-1%), Ortho-K, and 0.01% atropine combined with Ortho-K could significantly slow down myopia progression. The atropine efficacy followed a dose-related pattern; moreover, Ortho-K and low-dose atropine showed similar efficacy. There was a synergistic effect of using 0.01% atropine combined with Ortho-K, and it showed comparable efficacy to that of high-dose atropine.

Impact of integrated health care on elderly population: A systematic review of Taiwan's experience.

BACKGROUND: Care fragmentation in the elderly population prompted the need for integrated health care systems. However, evidence regarding the impact of the integrated care system in Taiwan is unclear. We aimed to conduct a systematic review to evaluate the impact of Taiwan's integrated health care programs on geriatric population. METHODS: We searched bibliographic databases MEDLINE, Embase, Web of Science, and Airiti Library for relevant publications throughout May 2022. Studies investigating the effectiveness of Taiwan's integrated care programs were included. We used the critical appraisal skills programme (CASP) checklist, to assess the risk of bias of included studies. RESULTS: Thirty-four studies, with a total of 838,026 study subjects, were assessed. The systematic review on 11 subthemes (diabetes mellitus, chronic kidney disease, hepatitis C virus, fractures, cancer, dementia, atrial fibrillation, chronic obstructive pulmonary disease, mechanical ventilation, terminal illness, outpatients and community-dwelling patients), demonstrated that the implementation of integrated health care could not only provide benefits on survival, self-care ability, health quality, physical, and functional rehabilitation outcomes, but also significantly reduce medical utilization and expenditures. CONCLUSION: The integrated health care system for multiple morbidities benefits the Taiwanese geriatric population in physical and functional outcomes. The thematic synthesis provides references for future rigorous clinical trials.

Effects of Biological/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis.

Inflammatory arthritis has been reported to be associated with the development of osteoporosis. Recent research has investigated the mechanisms of bone metabolism in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Progress in both animal and clinical studies has provided a better understanding of the osteoclastogenesis-related pathways regarding the receptor activator of nuclear factor-κB ligand (RANKL), anti-citrullinated protein antibodies (ACPAs), and Wnt signaling and Dickkopf-related protein 1 (Dkk-1). The complex interplay between inflammatory cytokines and bone destruction has been elucidated, especially that in the interleukin-17/23 (IL-17/23) axis and Janus kinase and signal transducer and activator of transcription (JAK-STAT) signaling. Moreover, advances in biological and targeted therapies have achieved essential modifications to the bone metabolism of these inflammatory arthritis types. In this narrative review, we discuss recent findings on the pathogenic effects on bone in RA and SpA. Proinflammatory cytokines, autoantibodies, and multiple signaling pathways play an essential role in bone destruction in RA and SpA patients. We also reviewed the underlying pathomechanisms of bone structure in biological and targeted therapies of RA and SpA. The clinical implications of tumor necrosis factor inhibitors, abatacept, rituximab, tocilizumab, Janus kinase inhibitors, and inhibitors of the IL-17/23 axis are discussed. Since these novel therapeutics provide new options for disease improvement and symptom control in patients with RA and SpA, further rigorous evidence is warranted to provide a clinical reference for physicians and patients.

High-Intensity Post-Stroke Rehabilitation Is Associated with Lower Risk of Pressure Ulcer Development in Patients with Stroke: Real-World Evidence from a Nationwide, Population-Based Cohort Study.

Background and Objectives: Multiple factors are associated with pressure ulcer (PU) development, including limited mobility following stroke. We performed a nationwide cohort study to investigate the impact of rehabilitation intensity on the incidence of post-stroke PU. Materials and Methods: Data of patients diagnosed with stroke between 2000 and 2012 were collected from the 2000 Longitudinal Health Insurance Database (Taiwan). Based on the number of rehabilitation sessions attended within 90 days of discharge, the rehabilitation intensity was classified as low, medium, or high. After adjusting for sociodemographic factors and comorbidities, the Cox proportional hazards model evaluated the risk of PU development during the 12-year follow-up period. Kaplan−Meier curves were used to estimate the cumulative incidence of PUs. Results: Our study included 18,971 patients who had their first episode of stroke. Of these, 9829 (51.8%) underwent rehabilitation therapy after discharge. Female patients and patients with a National Institutes of Health Stroke Scale (NIHSS) score >13 points, who commenced high-intensity post-stroke rehabilitation after discharge had a significantly lower risk of PU development than those who underwent low-intensity post-stroke rehabilitation after discharge. Cumulative survival analysis showed a significantly lower cumulative incidence of PU during the 12-year follow-up period in the high-intensity rehabilitation group. Conclusion: Compared with low-intensity post-stroke rehabilitation, high-intensity post-stroke rehabilitation after discharge from hospital is associated with a lower risk of post-stroke PU development, especially in female stroke patients and patients with a NIHSS score >13 points. High-intensity rehabilitation is also associated with a significantly lower cumulative incidence of PU events during the 12-year follow-up period.

Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation. However, the associations between psoriasis and VTE or PVD are unclear. OBJECTIVE: To determine the association of psoriasis with incident VTE and PVD. DATA SOURCES: MEDLINE, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for relevant publications from their respective inception through May 21, 2021. No restrictions on language or geographic locations were imposed. STUDY SELECTION: Two authors independently selected cohort studies that investigated the risk for incident VTE or PVD in patients with psoriasis. Any discrepancy was resolved through discussion with 2 senior authors until reaching consensus. Only 13 initially identified studies met the selection criteria for qualitative review, and only 9 of these for quantitative analysis. DATA EXTRACTION AND SYNTHESIS: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Two authors independently extracted data and assessed the risk of bias of included studies by using the Newcastle-Ottawa Scale. Disagreements were resolved by discussion with 2 other authors. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses based on arthritis status, psoriasis severity, sex, and geographic location were also performed. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident VTE and PVD associated with psoriasis. RESULTS: A total of 13 cohort studies with 12 435 982 participants were included. The meta-analysis demonstrated a significantly increased risk for incident VTE (pooled HR, 1.26; 95% CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95% CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses illustrated increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95% CI, 1.01-1.53), women (pooled HR, 1.89; 95% CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95% CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95% CI, 1.06-1.53). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found an increased risk for incident VTE and PVD among patients with psoriatic disease. Typical presentations of VTE or PVD should not be overlooked in patients with psoriasis. Risk factors, such as obesity, physical inactivity, smoking, and varicose veins, should be identified and treated in patients with psoriasis, and medications like hormone-related therapies should be prescribed with caution.

Face-Down Posture versus Non-Face-Down Posture following Large Idiopathic Macular Hole Surgery: A Systemic Review and Meta-Analysis.

Evidence regarding the effect of a face-down posture (FDP) for large idiopathic macular hole (IMH) is inconsistent. We conducted a systematic review and meta-analysis to determine whether a postoperative FDP is required for the treatment of large IMH. Eligible randomized controlled trials published before September 2021 were retrieved from the Medline, Embase, and Cochrane Library databases. The efficacy outcome was the IMH closure rate and the visual acuity improvement rate. A meta-analysis was performed using a random effects model. The "Grading of Recommendations Assessment, Development, and Evaluation" approach was implemented, and the numbers needed-to-treat (NNTs) were calculated. Seven studies comprising 640 patients were included. We performed a predefined subgroup analysis of IMH size using a cut-off point of 400 µm. Compared with non-FDP, a significant effect of FDP was found in the IMH > 400 µm group (OR = 3.34; 95% CI = 1.57-7.14; trial sequential analysis-adjusted CI = 1.20-11.58; NNTs = 7.9). After stratifying by the posturing periods, the beneficial effect of FDP lasting at least five days, but not three days was observed for large IMH. Maintaining a FDP for at least five days postoperatively is an effective strategy (certainty of evidence: "moderate") for treating large IMH.