Improving SDG Classification Precision Using Combinatorial Fusion.

Combinatorial fusion algorithm (CFA) is a machine learning and artificial intelligence (ML/AI) framework for combining multiple scoring systems using the rank-score characteristic (RSC) function and cognitive diversity (CD). When measuring the relevance of a publication or document with respect to the 17 Sustainable Development Goals (SDGs) of the United Nations, a classification scheme is used. However, this classification process is a challenging task due to the overlapping goals and contextual differences of those diverse SDGs. In this paper, we use CFA to combine a topic model classifier (Model A) and a semantic link classifier (Model B) to improve the precision of the classification process. We characterize and analyze each of the individual models using the RSC function and CD between Models A and B. We evaluate the classification results from combining the models using a score combination and a rank combination, when compared to the results obtained from human experts. In summary, we demonstrate that the combination of Models A and B can improve classification precision only if these individual models perform well and are diverse.

What are the best endpoints for Eczema Area and Severity Index and Scoring Atopic Dermatitis in clinical practice? A prospective observational study.

BACKGROUND: Multiple strategies have been used to evaluate the minimal important change (MIC) of the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). The meaningfulness of these MICs is not well established across all severities of atopic dermatitis (AD). OBJECTIVES: To determine the MIC of percentage and absolute improvement of EASI and SCORAD scores in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 826). An anchor-based approach was used to determine thresholds for the percentage and absolute MICs of EASI, SCORAD and objective SCORAD (O-SCORAD) at follow-up from baseline. RESULTS: One-grade improvements of Physician's Global Assessment (PGA) and validated Investigator Global Assessment scale for AD (vIGA-AD) were associated with 50%, 35% and 35% decreases of EASI, SCORAD and O-SCORAD, respectively. The thresholds for percentage MIC of EASI (Kruskal-Wallis test, P = 0·61), SCORAD (P = 0·07) and O-SCORAD (P = 0·09) were similar across baseline AD severities. One-grade improvements of PGA and vIGA-AD were associated with 14·0- and 14·9-point decreases of EASI, 19·9- and 14·9-point decreases of SCORAD, and 15·5- and 17·4-point decreases of O-SCORAD. The thresholds for the absolute MIC of EASI (P < 0·001), SCORAD (P < 0·001) and O-SCORAD (P < 0·001) significantly differed by baseline AD severity. Percentage and absolute MICs for EASI and SCORAD were associated with improvements of AD symptoms and quality of life. CONCLUSIONS: EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.

Improving Data and Prediction Quality of High-Throughput Perovskite Synthesis with Model Fusion.

Combinatorial fusion analysis (CFA) is an approach for combining multiple scoring systems using the rank-score characteristic function and cognitive diversity measure. One example is to combine diverse machine learning models to achieve better prediction quality. In this work, we apply CFA to the synthesis of metal halide perovskites containing organic ammonium cations via inverse temperature crystallization. Using a data set generated by high-throughput experimentation, four individual models (support vector machines, random forests, weighted logistic classifier, and gradient boosted trees) were developed. We characterize each of these scoring systems and explore 66 possible combinations of the models. When measured by the precision on predicting crystal formation, the majority of the combination models improves the individual model results. The best combination models outperform the best individual models by 3.9 percentage points in precision. In addition to improving prediction quality, we demonstrate how the fusion models can be used to identify mislabeled input data and address issues of data quality. In particular, we identify example cases where all single models and all fusion models do not give the correct prediction. Experimental replication of these syntheses reveals that these compositions are sensitive to modest temperature variations across the different locations of the heating element that can hinder or enhance the crystallization process. In summary, we demonstrate that model fusion using CFA can not only identify a previously unconsidered influence on reaction outcome but also be used as a form of quality control for high-throughput experimentation.

Measurement properties of the product of investigator's global assessment and body surface area in children and adults with atopic dermatitis.

BACKGROUND: Multiple clinician-reported outcome measures exist for atopic dermatitis (AD) severity. However, there is no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the product of validated Investigator's Global Assessment for AD (vIGA) and body surface area (BSA) overall or divided into six categories (cBSA: 0%/0.1, <10%/10, <30%/30, <50%/50, <70%/70 and <90%/90-100%) and compare with other clinician-reported and patient-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 653). RESULTS: vIGA*BSA and vIGA*cBSA had good convergent validity with BSA (Spearman's ρ = 0.97 and 0.93), eczema area and severity index (ρ = 0.94 and 0.92), and objective SCORAD (ρ = 0.88 and 0.89); and weak-to-good convergent validity with Numeric Rating Scale average itch (ρ = 0.22 and 0.22) and worst itch (ρ = 0.27 and 0.28), Patient-Oriented Eczema Measure (ρ = 0.44 and 0.43), Dermatology Life Quality Index (ρ = 0.48 and 0.49), ItchyQOL (ρ = 0.45 and 0.46), PROMIS Sleep Disturbance (ρ = 0.46 and 0.37) and sleep-related impairment (ρ = 0.31 and 0.31) in adults and/or children; very good discriminant validity for physician-reported global AD severity; good responsiveness to change of severity of AD and itch; and good reliability (intraclass correlation coefficient [95% confidence interval]: 0.72 [0.60-0.81] and 0.74 [0.62-0.82]) with no floor or ceiling effects. Thresholds for interpretability bands and clinically important difference were established. CONCLUSIONS: vIGA*BSA and vIGA*cBSA scores showed good convergent and discriminant validity, reliability, responsiveness and interpretability in adults and children with AD, and were feasible for use in clinical practice. vIGA*BSA and vIGA*cBSA had slightly lower convergent validity than EASI or objective SCORAD, but might be more efficient to collect and score.

Validation of Patient-Reported Outcomes Information System Sleep Disturbance and Sleep-Related Impairment in adults with atopic dermatitis.

BACKGROUND: Sleep disturbances are common in adults with atopic dermatitis (AD). Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) are validated questionnaires to assess sleep in adults. Little is known about their measurement properties in adults with AD. OBJECTIVES: To assess the measurement properties of the PROMIS SD and SRI eight-item short forms in AD. METHODS: We performed a prospective dermatology-practice-based study using questionnaires and evaluation by a dermatologist (n = 420). RESULTS: PROMIS SD and SRI showed moderate correlations to each other (ρ = 0·67), and weak correlations with Patient-Oriented Eczema Measure (ρ = 0·43 and 0·39, respectively); average (ρ = 0·31/0·30) and worst numerical rating scale for itch (ρ = 0·32/0·30); Eczema Area and Severity Index (ρ = 0·41/0·31); and Scoring Atopic Dermatitis (SCORAD) (ρ = 0·44/0·30) (Spearman correlations, P < 0·001). PROMIS SD and SRI increased significantly and stepwise with more frequent sleep disturbance, severe itch and self-reported global AD severity (ancova, P < 0·001). PROMIS SD and SRI showed good internal consistency (Cronbach alpha 0·84 and 0·91). Changes from baseline in PROMIS SD and SRI were weakly to moderately correlated with each other and with changes of multiple patient-reported and clinician-reported AD outcomes. There were no floor or ceiling effects for PROMIS SD or SRI. The median completion time for PROMIS SD and SRI was 2 min. CONCLUSIONS: PROMIS SD and SRI showed good construct validity, internal consistency, responsiveness and feasibility to assess sleep in adult patients with AD. What is already known about this topic? The Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) scales were found to be valid in adults with chronic disease. However, the validity and feasibility of PROMIS SD and SRI in atopic dermatitis remain unknown. What does this study add? This study demonstrated that PROMIS SD and SRI had good content, concurrent, convergent and discriminant validity; feasibility; and responsiveness, with no floor or ceiling effects observed. What are the clinical implications of this work? The PROMIS SD and SRI eight-item bank short forms appear to have sufficient validity and feasibility to be used as assessments for burden of sleep in adults with atopic dermatitis in clinical practice.

Measurement properties of the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire: itch severity assessments in adults with atopic dermatitis.

BACKGROUND: Little is known about the validity of numeric rating scales (NRS) and verbal rating scales (VRS) for itch and itch frequency for assessing itch severity in atopic dermatitis (AD). We evaluated the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessment, including multiple NRS, VRS and frequency of itch assessments, in adults with AD and compared their performance. METHODS: Self-administered questionnaires and skin examinations were performed in 410 patients with AD (aged 18-90 years) in a dermatology practice setting. RESULTS: PIQ NRS, VRS and frequency of itch had good content validity, strong correlations with one another (Spearman correlations P < 0·001) and weak-to-moderate correlations with patient-oriented eczema measure (POEM), Eczema Area and Severity Index (EASI), objective SCORing AD (SCORAD) and Dermatology Life Quality Index (DLQI) (P < 0·001) and very good discriminant validity. Changes from baseline in NRS, VRS and frequency of itch were moderately to strongly correlated with one another, and weakly to moderately correlated with other patient-reported (POEM, SCORAD itch, DLQI) and clinician-reported outcomes (EASI, objective SCORAD). NRS and VRS worst itch and average itch showed moderate-to-good test-retest reliability. There were no floor or ceiling effects for NRS or VRS itch, but there were ceiling effects for itch frequency. Each assessment was completed in < 1 min by all patients. CONCLUSIONS: NRS, VRS and frequency of itch items from PIQ - itch severity showed good content and construct validity, reliability, and/or responsiveness in adults with AD, and were feasible for use in clinical trials and practice. What is already known about this topic? Numeric rating scales (NRS), verbal rating scales (VRS) and frequency of itch have been used to assess the burden of itch. However, there have been limited results demonstrating their validity, responsiveness, interpretability and feasibility, particularly in atopic dermatitis (AD). What does this study add? This study demonstrated that NRS, VRS and frequency of itch items from the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessments had good construct validity, responsiveness, reliability and feasibility in the assessment of adult AD. PIQ NRS, VRS and frequency of itch all appear to have sufficient validity, reliability and feasibility for use as assessments of itch in adults with AD in clinical practice and trials. What are the clinical implications of this work? PIQ NRS and VRS are all simple, valid, reliable and feasible for use in clinical practice and trials to assess itch in adults with AD. Linked Comment: Oosterhaven. Br J Dermatol 2020; 183:802-803.

Measurement properties of three assessments of burden used in atopic dermatitis in adults.

BACKGROUND: Standardized quality-of-life (QoL) assessments can provide important and clinically relevant information. There is currently a lack of standardization in QoL assessments used in atopic dermatitis (AD). OBJECTIVES: To determine the content validity, construct validity, internal consistency, differential reporting, responsiveness, floor or ceiling effects and feasibility of the Dermatology Life Quality Index (DLQI), Itchy Quality of Life (ItchyQoL) and 5-dimensions (5-D) itch scales for assessing burden of AD in adults and to compare their performance. METHODS: Self-administered questionnaires and skin examination were performed in 340 adults with AD in a dermatology practice setting. RESULTS: DLQI, ItchyQoL and 5-D all had good content validity. DLQI, mean ItchyQoL and 5-D itch all had strong correlations with frequency of AD symptoms (Patient-Oriented Eczema Measure) and intensity of itch (numerical rating scale for itch), and moderate correlations with AD severity (Eczema Area and Severity Index and Scoring Atopic Dermatitis) (Spearman correlations, P < 0·001 for all). DLQI and 5-D itch showed good internal consistency (Cronbach's alpha = 0·89 and 0·84), although ItchyQoL appeared to have several redundant items (alpha = 0·96). Uniform and nonuniform differential item functioning by age, sex and/or race/ethnicity was found for multiple items in DLQI, ItchyQoL and 5-D itch. DLQI, ItchyQoL and 5-D itch scores all demonstrated responsiveness, although ItchyQoL demonstrated the greatest responsiveness. There were no floor or ceiling effects for total scores. The median times for completion of DLQI, ItchyQoL and 5-D itch were 2 min. CONCLUSIONS: The DLQI, ItchyQoL and 5-D itch scales all showed good content and construct validity, and responsiveness in the assessment of AD in adults, and were feasible for use in clinical trials and practice.

Association between climate, pollution and hospitalization for pemphigus in the USA.

BACKGROUND: Little is known about the impact of ultraviolet exposure, climate factors and pollutants on pemphigus. AIM: To determine whether these factors are associated with pemphigus exacerbation resulting in hospitalization. METHODS: The analysis used data from the 2002-2012 National Inpatient Sample in the USA, including 68 476 920 children and adults, and measurements of relative humidity (%), ultraviolet (UV) index, outdoor air temperature and particulate matter of ≤ 2.5 or ≤ 10 µm (PM2.5 and PM10). RESULTS: Higher rates of admission primarily for pemphigus occurred during the summer and autumn months (June-November), with the highest admission rates in July and October (both 19.7 per million). There was significant statewide variation of the prevalence of hospitalization for pemphigus, with apparent hotspots located in the southwest and northeast states. Hospitalization for a primary diagnosis of pemphigus vs. other diagnosis was associated with significantly lower humidity [mean (95% confidence interval): 64.8% (63.2-66.4%) vs. 66.4% (65.6-67.3%); analysis of variance, P < 0.01) and higher temperature [58.7 (57.1-60.2) vs. 56.3 (55.8-56.7)°F, P = 0.001], UV index [6.0 (5.7-6.2) vs. 5.7 (5.6-5.7), P = 0.02], PM2.5 [12.9 (12.0-13.7) vs. 11.8 (11.5-12.0) mg/m3 , P < 0.001] and PM10 [26.2 (24.5-27.9) vs. 23.1 (22.6-23.6) mg/m3 , P < 0.001]. All associations remained significant in multilevel regression models that controlled for age, sex and race/ethnicity, except for ultraviolet index, which was associated with pemphigus hospitalization only for Hispanic patients [odds ratio (95% CI) for quartile 4: 2.07 (1.02-4.21)]. CONCLUSION: Increasing temperature, UV exposure and small particle air pollution are associated with increased hospitalization for pemphigus. Patients with pemphigus may benefit from avoidance of these potential environmental triggers.

Pediatric heart transplantation across a positive crossmatch: First year results from the CTOTC-04 multi-institutional study.

Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement-dependent cytotoxicity crossmatch (CDC-crossmatch) positive or negative and as donor-specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC-crossmatch-positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1 year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC-crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P = .2354. The primary endpoint also did not differ by DSA status. Freedom from antibody-mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow-up will determine if acceptable outcomes can be achieved long-term.

Validation of patient-reported global severity of atopic dermatitis in adults.

BACKGROUND: Atopic dermatitis (AD) is associated with a heterogeneous presentation and clinical course. There is a lack of simple and validated severity assessments that are feasible for clinical practice and epidemiological research. OBJECTIVES: We sought to validate patient-reported global AD severity in adults. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 265). RESULTS: At baseline and follow-up, patient-reported global AD severity significantly correlated with oSCORAD (Spearman ρ = 0.56 and 0.49), SCORAD (0.64 and 0.56), EASI (0.56 and 0.50), BSA (0.52 and 0.45), NRS-itch (0.60 and 0.53), POEM (0.50 and 0.48), and DLQI (0.50 and 0.49) (P < .0001 for all). Patient-reported moderate and severe AD vs mild AD were associated with significantly higher oSCORAD, SCORAD, EASI, BSA, NRS-itch, POEM, and DLQI (P < .0001 for all). There was moderate concordance between patient-reported AD severity (mild, moderate, and severe) and previously developed severity strata for oSCORAD (κ = 0.39), SCORAD (κ = 0.47), EASI (κ = 0.37), NRS-itch (κ = 0.49), POEM (κ = 0.37), and DLQI (κ = 0.40). Among patients with severe disease at baseline, those who reported mild or moderate disease on follow-up had significantly greater absolute reductions of oSCORAD (-23.4/-9.7/-1.8), SCORAD (-33.0/-13.2/-2.3), EASI (-17.1/-9.8/-3.2), BSA (-46%/-15%/-4%), NRS-itch (-5/-2/0), POEM (-5/-2/0), and DLQI (-8/-6/-1) than those who continued to report severe disease (Kruskal-Wallis, P ≤ .0003 for all). CONCLUSIONS: Patient-reported AD severity appears to be sufficiently valid for assessing AD severity in the clinical and epidemiological setting.

Epidemiology of staphylococcal scalded skin syndrome in U.S. children.

BACKGROUND: Staphylococcal scalded skin syndrome (SSSS) is a blistering dermatosis caused by exfoliative toxins released from Staphylococcus aureus. OBJECTIVES: To describe the incidence, costs, length of stay (LOS), comorbidities and mortality of SSSS in U.S. children. METHODS: The Nationwide Inpatient Sample 2008-2012 was analysed, including a 20% sample of U.S. hospitalizations and 589 cases of SSSS. RESULTS: The mean annual incidence of SSSS was 7·67 (range 1·83-11·88) per million U.S. children, with 45·1 cases per million U.S. infants age < 2 years. In multivariable logistic regression models, SSSS was significantly associated with the following (shown as adjusted odds ratio and 95% confidence interval): female sex (1·12, 1·00-1·25), age (2-5 years: 13·31, 11·82-14·99; 6-10 years: 2·93, 2·35-3·66; 11-17 years: 0·44, 0·31-0·63); race/ethnicity (black: 0·69, 0·58-0·84) and season (winter: 2·04, 1·66-2·50; summer: 3·47, 2·86-4·22; autumn: 3·04, 2·49-3·70), with increasing odds over time (2010-2011: 2·28, 2·07-2·51; 2012: 2·98, 2·69-3·30). The geometric mean (95% confidence interval) LOS and cost of hospitalization for patients with vs. without SSSS were 3·2 (3·0-3·4) vs. 2·4 (2·4-2·5) days and $4624·0 ($4250-$5030) vs. $1872 ($1782·7-$1965). Crude inpatient mortality rates (with 95% confidence intervals) were similar for children with vs. without SSSS (0·33%, 0·00-0·79% vs. 0·36%, 0·34-0·39%). SSSS was associated with other infections, including in the upper respiratory tract and skin. CONCLUSIONS: The prevalence of SSSS appears to be increasing over time, and was associated with a number of sociodemographic factors and other infections. Further studies are needed to confirm these findings and reduce rising rates of SSSS.

Severity strata for five patient-reported outcomes in adults with atopic dermatitis.

BACKGROUND: Several patient-reported outcomes have been used to assess the burden of atopic dermatitis (AD). Some are disease specific, such as the Patient-Oriented Eczema Measure (POEM), while others pertain to itch, for example the numerical rating scale (NRS)-itch, ItchyQoL and 5-D itch, or dermatological disease in general, for example the Dermatology Life Quality Index (DLQI). Development of severity strata is essential for proper interpretability of these assessments. OBJECTIVES: To confirm previously developed strata for POEM, DLQI and raw ItchyQoL, and develop strata for the NRS-itch, mean ItchyQoL and 5-D itch scale for use in adults with AD. METHODS: Self-administered questionnaires were completed by 210 adults with AD in a dermatology practice setting. Strata were selected using an anchoring approach based on patient-reported disease severity. RESULTS: We confirmed the existing strata for POEM (mild 0-7, moderate 8-16, severe 17-28; κ = 0·440), DLQI (mild 0-5, moderate 6-10, severe 11-30; κ = 0·398) and NRS-itch (mild 0-3, moderate 4-6, severe 7-10; κ = 0·499). However, the preferred band for raw ItchyQoL was mild 22-58, moderate 59-74 and severe 75-110 (κ = 0·379) and for mean ItchyQoL, mild 1-2·9, moderate 3·0-3·9, severe 4·0-5·0 (κ = 0·374). The preferred band for 5-D itch scale was mild 0-11, moderate 12-17 and severe 18-25 (κ = 0·331). CONCLUSIONS: Existing strata for POEM and DLQI performed well in adult AD. Previously reported strata for visual analogue scale-itch performed best for NRS-itch. We identified banding for the raw ItchyQoL for our AD population that varies slightly from the banding published for a more heterogeneous population. Finally, we proposed strata for mean ItchyQoL and 5-D itch scale in adult AD.

The impact of flow PRA on outcome in pediatric heart recipients in modern era: An analysis of the Pediatric Heart Transplant Study database.

Data from patients in the Pediatric Heart Transplant Study (PHTS) registry transplanted between 2010 and 2014 were analyzed to determine the association between HLA antibody (PRA) determined by SPA using Luminex or flow cytometry with a positive retrospective cross-match and the post-transplant outcomes of acute rejection and graft survival. A total of 1459 of 1596 (91%) recipients had a PRA reported pretransplant; 26% had a PRA > 20%. Patients with a PRA > 20% were more likely to have CHD, prior cardiac surgery, ECMO support at listing, and waited longer for transplantation than patients with a PRA <20%. Patients with higher PRA% determined by SPA were predictive of a positive retrospective cross-match determined by flow cytometric method (P < .001). A PRA > 50% determined by SPA was independently associated with worse overall graft survival after first month of transplant in both unadjusted and adjusted for all other risk factors. In this large multicenter series of pediatric heart transplant recipients, an elevated PRA determined by SPA remains a significant risk factor in the modern era.

Association of serious infections with pemphigus and pemphigoid: analysis of the Nationwide Inpatient Sample.

BACKGROUND: Pemphigus and pemphigoid are blistering disorders associated with barrier disruption, immune dysregulation and use of immunosuppressing systemic therapy, all of which may predispose towards serious infections. OBJECTIVES: To determine whether pemphigus and pemphigoid are associated with increased likelihood of serious infections and the impact of such infections on mortality and cost of care. METHODS: We analysed data from the 2002 to 2012 Nationwide Inpatient Sample, including a representative 20% sample of all hospitalizations in the US (total n = 72 108 077 adults). RESULTS: Overall, 54.6% (95% CI: 53.6-55.6%) and 50.4% (49.0-51.8%) of inpatients with either pemphigoid or pemphigus had a diagnosis of serious infection, respectively, compared with 25.4% (25.2-25.6%) in those without either diagnosis. In multivariable logistic regression models controlling for gender, age, race/ethnicity and insurance status, pemphigoid or pemphigus was associated with 26 or 21 of 48 infections examined, respectively. In particular, both pemphigoid and pemphigus were associated with higher odds of infections of the skin, bones, respiratory, gastrointestinal, genitourinary and central nervous system, septicaemia and antibiotic-resistant infections. Pemphigus was also associated with aspergillus, pharyngitis and Pneumocystis Carinii pneumonia. Associations of any serious infection in both pemphigoid and pemphigus patients were older age, non-White race, lower median household income, government or no insurance, higher number of chronic conditions, and those with a diagnosis of Cushing's syndrome, diabetes, cancer or autoimmune disease. The diagnosis of any serious infection vs. no infection was associated with increased inpatient mortality and costs in both pemphigoid (mortality: 7.85% vs. 2.84%; cost: $16 115 vs. $10 653) and pemphigus (mortality: 6.78% vs. 1.88%; cost: $17 707 vs. $11 545) inpatients (P < 0.0001 for all). CONCLUSIONS: Adults with pemphigus or pemphigoid had increased cutaneous, respiratory, multi-organ and systemic infections, which were associated with considerable inpatient mortality and cost burden. Moreover, there were significant clinical and healthcare disparities with respect to infections in patients with pemphigus or pemphigoid.

Validation of International Classification of Disease Ninth Revision codes for atopic dermatitis.

BACKGROUND: Evaluation of large-scale data sets is needed to better understand the epidemiology, cost, and burden of atopic dermatitis (AD). We sought to validate the use of ICD-9-CM codes for identifying AD. METHODS: Patients from a large metropolitan quaternary care medical center with a diagnostic code of either 691.8 (AD) or 692.9 (eczema and contact dermatitis) were queried. Medical records were reviewed for demographics, Hanifin & Rajka (H&R) and United Kingdom Working Party (UKWP) criteria. Sensitivity, specificity, and positive predictive values (PPV) of the codes were calculated. RESULTS: Of 43 278 patients identified with associated ICD-9 codes of 691.8 or 692.9, 519 and 253 with 691.8 and 692.9 were randomly selected for chart review. There was extensive overlap: 34.3% had ≥1 occurrences of 691.8 and 692.9 and 25.6% had multiple occurrences of both codes. Among patients with ≥1 occurrence of 691.8, 29.9% and 30.8% met the H&R and UKWP criteria, respectively. Similarly, among patients with ≥1 occurrence of 692.9, 33.7% and 32.2% met the H&R and UKWP criteria. Increased PPV was associated with concomitant diagnoses of asthma, hay fever, and food allergy and increased disease severity. CONCLUSIONS: In the outpatient setting, the ICD-9-CM codes 691.8 and 692.9 alone have poor PPV. Incorporation of diagnoses of asthma, hay fever, and food allergy improves PPV and specificity. In the inpatient setting, a primary discharge diagnosis of 691.8 had excellent PPV. Although ICD-10 has been adopted in Europe and more recently in the USA, the same systematic errors would likely occur unless providers standardize their coding.

Hospitalization, inpatient burden and comorbidities associated with bullous pemphigoid in the U.S.A.

BACKGROUND: Bullous pemphigoid (BP) is associated with significant disability and comorbid health disorders that may lead to or result from hospitalization. However, little is known about the inpatient burden and comorbidities of BP. OBJECTIVES: To obtain data on the inpatient burden and comorbidities of BP in the U.S.A. METHODS: We analysed data from the 2002 to 2012 National Inpatient Sample, including a representative 20% sample of all hospitalizations in the U.S.A. (72 108 077 adults). RESULTS: The prevalence of hospitalization for BP increased from 25·84 to 32·60 cases per million inpatients from 2002 to 2012. In multivariate logistic regression models with stepwise selection, increasing age, nonwhite ethnicity, higher median household income, being insured with Medicare or Medicaid, and increasing number of chronic conditions were all associated with hospitalization for BP (P < 0·05 for all). The top three primary discharge diagnoses for patients with a secondary diagnosis of BP were septicaemia (prevalence 5·51%, 95% confidence interval 5·03-5·99), pneumonia (4·60%, 4·19-5·01) and urinary tract infection (3·52%, 3·15-3·89). Patients with BP also had numerous autoimmune, infectious, cardiovascular and other comorbidities. Interestingly, BP was associated with multiple neuropsychiatric disorders, including demyelinating disorders, dementias (presenile, senile, vascular and other), paralysis, neuropathy (diabetic, other polyneuropathy), Parkinson disease, epilepsy, psychoses and depression. The mean annual age- and sex-adjusted in-hospital mortality rate was significantly higher in patients with a secondary diagnosis of BP compared with no BP (2·9%, range 2·8-3·9% vs. 2·1%, range 1·9-2·2%). Significant predictors of mortality in patients with BP included increasing age, nonwhite ethnicity and insurance with Medicaid or other payment status (P < 0·05 for all). CONCLUSIONS: Hospitalization for BP increased significantly between 2002 and 2012. Moreover, there were significant ethnic and healthcare disparities with respect to hospitalization and inpatient mortality from BP.

Severity strata for Eczema Area and Severity Index (EASI), modified EASI, Scoring Atopic Dermatitis (SCORAD), objective SCORAD, Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis.

BACKGROUND: Scoring systems for assessing the signs of atopic dermatitis (AD) are complex and difficult to interpret. Severity strata are helpful to interpret these assessments properly. OBJECTIVES: To confirm previously reported strata for the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) and the objective component of SCORAD (oSCORAD), and to develop strata for the modified EASI (mEASI), Atopic Dermatitis Severity Index (ADSI) and body surface area (BSA) for use in adults with AD. METHODS: Skin examination was performed in 673 adolescents and adults (age ≥ 13 years) with diagnosed AD, in a dermatology practice setting. Strata were selected using an anchoring approach based on a four-point Investigator's Global Assessment of severity (clear of active skin lesions, mild, moderate or severe disease). RESULTS: We determined potential severity strata for EASI (0 clear, 0·1-5·9 mild, 6·0-22·9 moderate, 23·0-72 severe; κ = 0·69), mEASI (0-0·9 clear, 1-8·9 mild, 9·0-29·9 moderate, 30·0-90 severe; κ = 0·71), oSCORAD (0-7·9 clear, 8·0-23·9 mild, 24·0-37·9 moderate, 38·0-83 severe; κ = 0·70), SCORAD (0-9·9 clear, 10·0-28·9 mild, 29·0-48·9 moderate, 49·0-103 severe; κ = 0·68), ADSI (0-1·9 clear, 2-5·9 mild, 6·0-8·9 moderate, 9·0-15 severe; κ = 0·55) and BSA (0 clear, 0·1-15·9 mild, 16·0-39·9 moderate, 40·0-100 severe; κ = 0·66). oSCORAD values > 0 were found in clear skin due to the presence of xerosis, which is scored in oSCORAD. Similarly, SCORAD values > 0 were found in clear skin due to the scoring of xerosis, pruritus and sleeplessness. Similarly, mEASI and ADSI scores > 0 occurred in patients with clear skin due to scoring of pruritus. CONCLUSIONS: We recommend using these strata for interpretation of their respective measures in clinical trials of AD. There are important differences between the five assessments, which profoundly impact the interpretation of their scores.

Aberrant intrinsic functional connectivity within and between corticostriatal and temporal-parietal networks in adults and youth with bipolar disorder.

BACKGROUND: Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas. METHOD: We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10-50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks. RESULTS: Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group × diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation. CONCLUSIONS: These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.

Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder.

BACKGROUND: Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes. METHOD: Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted. RESULTS: Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN. CONCLUSIONS: This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.

It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder.

The µ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen 'social pain.' We used positron emission tomography scanning with the selective MOR radioligand [(11)C]carfentanil to test the hypothesis that MOR system activation (reflecting endogenous opioid release) in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n=17) compared with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced endogenous opioid release in brain regions regulating stress, mood and motivation, and slower emotional recovery compared with HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with endogenous opioid release in the nucleus accumbens, a reward structure. Altered endogenous opioid activity in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse and contribute to poor treatment outcomes.