A quantitative assessment of renal function utilizing albuminuria in pediatric heart transplant recipients.

INTRODUCTION: Kidney disease is common after pediatric heart transplantation. Serum creatinine-based glomerular filtration rate is the most frequently reported measure of kidney function. Albuminuria is an additional marker of kidney dysfunction and is not well described in this population. In this study, we evaluate the prevalence and degree of albuminuria and describe clinical factors associated with albuminuria in a cohort of pediatric heart transplant recipients. METHODS: This was a cross-sectional study of pediatric heart transplant recipients. Albuminuria was assessed using spot urine albumin-to-creatinine ratio collected at the most recent annual screening cardiac catheterization through August 2019. RESULTS: In 115 patients at a median duration of 10.2 years post-transplant, 39% had albuminuria. Stage 3 or greater chronic kidney disease was present in 6%. The immunosuppressive regimen at the time of measurement contained a calcineurin inhibitor (CNI) in 88% and a proliferation signal inhibitor (PSI) in 62%. In multivariable modeling, lower eGFR, PSI use, and younger age at transplant were associated with higher levels of albuminuria, whereas CNI use was associated with lower levels of albuminuria. CONCLUSION: Albuminuria is a prevalent finding in medium-term follow up of pediatric heart transplant recipients, reflecting kidney injury, and is associated with other markers of kidney dysfunction, such as low eGFR. Younger age at transplant, lower eGFR, and PSI use were among the associations with albuminuria.

Assessment of racial and ethnic differences of atopic dermatitis severity and treatment patterns in a diverse outpatient cohort in the United States: a retrospective observational study.

Previous population-based studies in the United States found racial/ethnic differences of atopic dermatitis (AD) severity and treatment patterns. It is unclear whether these differences are from differences of disease characteristics or disparities. To examine racial/ethnic differences in severity and treatment patterns in a diverse outpatient patient cohort of AD patients (n = 833). There were no significant associations of highest-reported body surface area (BSA; Fisher's exact test, P = 0.19 and P = 0.44) or physician's global assessment (PGA; P = 0.63 and P = 0.57) with race or ethnicity; nor interactions of race/ethnicity with gender or age as predictors of BSA or PGA. Asian and multiracial/other patients were more likely than White or Black patients to use topical calcineurin inhibitors (Chi-square, P = 0.01). Dupilumab use differed by race (Multiracial/other = 35.0%; White = 20.1%; Asian = 15.7%; Black = 13.6%; Chi-square, P = 0.03), but not ethnicity (P = 0.88). Use of oral corticosteroids (Chi-square, P = 0.74), immunosuppressants (P = 0.98) or GABAergics (P = 0.16) or NBUVB (P = 0.42) did not differ by race. There were no interactions of race/ethnicity with gender or age as predictors of treatment use. Similar treatment patterns were observed across racial/ethnic groups. Though, topical calcineurin inhibitors were more commonly used in Asian and multiracial/other patients; dupilumab use was more common in multiracial/other patients.

Assessment of the adverse effects of sirolimus versus everolimus in pediatric heart transplant recipients.

BACKGROUND: Literature is limited comparing adverse effects (AEs) of the proliferation signal inhibitors (PSIs) sirolimus (SRL) and everolimus (EVL) in pediatric heart transplant (HTx) recipients. METHODS: Single-center, observational cohort analysis assessing first use of SRL or EVL in pediatric HTx recipients <21 years of age with up to 2 years follow-up between 2009 and 2020. RESULTS: Eighty-seven patients were included, with 52 (59.8%) receiving EVL and 35 (40.2%) receiving SRL. Tacrolimus with PSI was the most common regimen. Intergroup comparison revealed lower baseline estimated glomerular filtration rate (eGFR) and greater increase in eGFR from baseline to 6 months and latest follow-up in SRL cohort compared to EVL cohort. There was greater increase in HDL cholesterol in SRL cohort compared to EVL cohort. Intragroup analysis revealed eGFR and HDL cholesterol increased significantly within SRL cohort, triglycerides and glycosylated hemoglobin increased in EVL cohort, and LDL cholesterol and total cholesterol increased in both cohorts (all p < .05). There were no differences in hematological indices or rates of aphthous ulcers, effusions, or infections between cohorts. Incidence of proteinuria was not significantly different among those screened within cohorts. Of those included in our analysis, one patient in SRL cohort (2.9%) and two in EVL cohort (3.8%) had PSI withdrawn due to AE. CONCLUSION: Low-dose PSIs in calcineurin inhibitor minimization regimens appear well-tolerated with low withdrawal rate secondary to AE in pediatric HTx recipients. While incidence of most AE was similar between PSI, our results suggest EVL may be associated with less favorable metabolic impact than SRL in this population.

Immunosuppressive Agent Options for Primary Nephrotic Syndrome: A Review of Network Meta-Analyses and Cost-Effectiveness Analysis.

Therapeutic options with immunosuppressive agents for glomerular diseases have widened with refinements to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines from 2012 to 2021. However, international guidelines do not necessarily match the reality in each country. Expensive therapies such as rituximab and calcineurin inhibitors are sometimes inaccessible to patients with refractory nephrotic syndrome due to cost or regulations. Under the Japanese medical insurance system, rituximab is accessible but still limited to steroid-dependent patients who developed idiopathic nephrotic syndrome in childhood. Based on international KDIGO guidelines and other national guidelines, possible applications of immunosuppressive agents for nephrotic syndrome are comprehensively examined in this review. While rituximab has become the mainstay of immunosuppressive therapy for nephrotic syndrome, clinical trials have indicated that options such as cyclophosphamide, calcineurin inhibitors, and mycophenolate mofetil would be preferable. Given the rising number of patients with nephrotic syndrome worldwide, KDIGO guidelines mention the need for further consideration of cost-effectiveness. If the new option of rituximab is to be the first choice in combination with steroids for nephrotic syndrome, its cost-effectiveness should also be verified. Among the few studies examining the cost-effectiveness of treatments for nephrotic syndrome, administration of rituximab to young adults has been shown to be cost-beneficial, at least in Japan. However, further large-scale studies involving multiple facilities are needed to verify such findings. Network meta-analyses have concluded that the efficacy of rituximab remains controversial and confirmation through high-quality studies of large cohorts is needed. To this end, the mechanisms of action underlying immunosuppressive agents, both old and new, need to be understood and experience must be accumulated to evaluate possible effects and side effects.

mTORi-based immunosuppression reduces HCC recurrence at the expense of increased adverse side effects: A systematic review and meta-analysis.

Sirolimus and everolimus are mammalian target of rapamycin inhibitors (mTORi) that can reduce relapse rates following liver transplantation (LT) for hepatocellular carcinoma (HCC). Herein, we performed a systematic review and meta-analysis to investigate the efficacy of mTORi and calcineurin inhibitors (CNI) in reducing HCC recurrence and survival adverse effects (AEs) in HCC patients after LT. Systematic literature searches were conducted using MEDLINE, EMBASE, and Cochrane Library databases up to October 2021. The primary outcomes of interest were tumor recurrence rates and overall survival. The secondary outcomes were the characterization and incidence of AEs. A total of 38 trials involving 10,607 participants was included in the analysis. The incidence of recurrence and overall mortality was significantly lower in the mTORi than in the CNI group (relative ratio [RR]: .78, 95% confidence interval [CI]: .68-.89 and RR: .76, 95% CI: .67-.86, respectively). The incidence of some AEs and complications such as acne, anemia, abnormal healing, dyslipidemia, depression, diarrhea, edema, headache/migraine, hypercholesterolemia, incisional hernia, infection, leukopenia, mouth ulceration, pyrexia, proteinuria, pruritis, rash, and thrombocytopenia were higher in the mTORi than in the CNI group. mTORi reduced the recurrence incidence and overall 5-year mortality rate but increased many other incidences of AEs compared with that by CNI. Therefore, clinicians should be aware of the risks and benefits of mTORi use when managing patients undergoing LT for HCC.

Usage of Topical Calcineurin Inhibitors in the Medicare Population from 2013 to 2018.

Topical calcineurin inhibitors are a family of drugs that have been touted for having high efficacy without the risks of cutaneous atrophy and systemic absorption seen with topical corticosteroids. They may play an important role in the elderly population, where preexisting cutaneous atrophy increases susceptibility to these adverse effects.

Eficacia y seguridad del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica / Efficacy and safety of calcipotriol and betamethasone dipropionate in adult patients with moderate or severe plaque psoriasis vulgaris, unresponsive to conventional topical and systemic therapy, and not amenable to biological therapy

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen que expone la evaluación de la eficacia y seguridad del calcipotriol y dipropionato de betametasona (DB) en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. Así, la médico dermatóloga, Dra. Lorraine Lía Málaga Medina del Servicio de Dermatología del Hospital Nacional Carlos Seguin Escobedo, siguiendo la Directiva N.° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso por fuera del petitorio farmacológico de EsSalud el producto farmacéutico calcipotriol en combinación con el (DB), para el tratamiento de los pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. ASPECTOS GENERALES: La psoriasis vulgar en placas es una enfermedad crónica de la piel que se presenta como placas eritematosas y escamosas que aparecen, mayoritariamente, en el cuero cabelludo, el tronco, los glúteos, y los miembros inferiores y superiores (de Rie et al., 2004). Esta enfermedad es considerada como un problema de salud pública por su alta prevalencia, alto riesgo de morbilidad y porque deteriora la calidad de vida y salud mental en los pacientes que la padecen (Boehncke & Schón, 2015). La psoriasis afecta del 1 % al 3 % de la población mundial; y la psoriasis vulgar en placas representa hasta el 90 % de todas las manifestaciones de la psoriasis (Augustin et al., 2010). Además, la presencia de esta enfermedad se asocia a mayor riesgo de sufrir artritis psoriásica, enfermedades cardiovasculares, diabetes mellitus, obesidad, enfermedad del hígado graso no alcohólico y enfermedades inflamatorias del intestino (Gisondi et al., 2020). Asimismo, el 75 % de estos pacientes percibe un deterioro en su calidad de vida y cerca del 10 % ha tenido ideación suicida (Bhosle et al., 2006). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad del CAL-DB, en comparación con mejor terapia de soporte, en pacientes adultos con psoriasis vulgar en placas moderada o severa no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica. La búsqueda se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish I ntercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de I ncorpornáo de Tecnologías no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o aún no publicados. RESULTADOS: Tras ampliar los criterios de selección de documentos, se incluyó una GPC publicada por el NICE (2012) que realiza recomendaciones sobre la evaluación y el tratamiento de pacientes con psoriasis vulgar de severidad moderada o severa. Además, se incluyeron dos ETS publicadas por la CONITEC (2012), y la HAS (2019) que tuvieron como objetivo evaluar la evidencia disponible acerca de la eficacia y seguridad del uso del Cal-DB en pacientes adultos con psoriasis vulgar en placas e incluyeron, en su cuerpo de evidencia, ECA donde participaron pacientes con psoriasis vulgar de severidad moderada a severa. También, se incluyó el estudio pivotal citado en la ficha técnica del Daivobet ® aprobada por DIGEMID (2018), el cual es un ECA de fase II que comparó la eficacia y seguridad del uso del CAL-DB versus el calcipotriol en monoterapia, el DB en monoterapia y placebo, en pacientes con psoriasis vulgar de cualquier severidad de enfermedad (Fleming et al., 2010). Por último, se incluyó un estudio observacional que comparó el uso de la fototerapia y el CAL-DB en pacientes con severidad de enfermedad de moderada a severa (Polanska et al., 2019). ONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación no aprueba el uso combinado del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar moderada o severa, no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud.

Recipient and Center Factors Associated With Immunosuppression Practice Beyond the First Year After Liver Transplantation and Impact on Outcomes.

BACKGROUND: Immunosuppression is a critical aspect of post-transplant management, yet practices at intermediate and late time points after liver transplantation (LT) are poorly characterized. METHODS: A retrospective cohort of 11 326 adult first LT alone recipients between 2007 and 2016 was identified by linking United Network for Organ Sharing transplant data to Medicare administrative claims. The immunosuppression regimen was obtained from Medicare billing claims. Factors associated with calcineurin inhibitor (CNI) monotherapy at 1-, 3-, and 5-y post-LT were investigated using mixed-effects logistic regression. Center practice heterogeneity was evaluated. The association of immunosuppression regimen (time-updating) with patient and graft survival was studied. RESULTS: CNI monotherapy was used in 51.9% at 1-y post-LT and 68.6% at 5-y post-LT. Center-specific rates ranged from 20.0%-79.9% to 15.4%-95.2%, respectively. CNI monotherapy at 1- and 3-y post-LT was less likely among Black recipients ( P = 0.027 and P = 0.015 versus White, respectively). CNI plus antimetabolite was associated with improved adjusted patient (hazard ratio, 0.59; P < 0.001) and graft (hazard ratio, 0.62; P < 0.001) survival versus CNI monotherapy. The benefit of CNI plus antimetabolite on patient and graft survival increased with older age. CONCLUSIONS: In this first longitudinal analysis of LT immunosuppression practices among Medicare beneficiaries, a CNI plus antimetabolite approach led to improved outcomes. Significant center heterogeneity in practice was observed.

Cost-effectiveness of cyclophosphamide and non-cyclophosphamide in the induction therapy of Malaysian lupus nephritis patients.

BACKGROUND: There is a paradigm shift in the induction therapy for proliferative lupus nephritis (LN). Apart from cyclophosphamide (CYC), mycophenolate mofetil and calcineurin inhibitors have emerged as an alternative option of treatment. OBJECTIVE: We aimed to compare the cost-effectiveness analysis (CEA) per year, adverse events and renal damage at 24 months between CYC and non-CYC agents (calcineurin inhibitors or mycophenolate) as induction treatment among proliferative lupus nephritis (LN) patients. METHODS: This was a retrospective and non-controlled study involving biopsy-proven proliferative LN patients (class III or IV with or without V) in the clinic registry from 2017 to 2019. Their medical records were reviewed to determine the date and type of induction, treatment effectiveness, adverse events and renal damage at 24 months. The total cost of treatment included capital cost (building, furniture and equipment) and recurrent cost (emolument, supply/drug, lab investigations, administrative cost and utilities). Treatment effectiveness was defined as renal remission (partial or complete) at 6 months without relapse up to 24 months. The cost-effectiveness analysis (CEA) was expressed as cost per remission per year in Malaysian Ringgit (MYR). RESULTS: There were a total of 95 inductions with CYC and 27 with non-CYC in 94 LN patients. There was no significant difference in the total mean cost per patient/year between CYC (MYR 18460.26 ± 6500.76) compared to non-CYC (MYR 19302.10 ± 6778.22), p = 0.569. The CEA for CYC was MYR 20,632.06 (GBP 3,538.78) while non-CYC was MYR 20,846.27 (GBP 3,575.52) and mean difference MYR 214.21 (GBP 37.44). There was significantly higher capital cost, consumables, utility, maintenance, administration (p < 0.001) and lab investigations (p = 0.046) in the CYC arm. There was a trend of a higher infection requiring outpatient antibiotic treatment in CYC group (p = 0.05), but similar renal damage outcome with the non-CYC group.Conclusion: For treatment of proliferative LN, there was no significant difference in the CEA and renal damage between CYC and non-CYC induction treatment. There was a trend of a higher rate of infections in the CYC group. Hence, the decision to treat patient with CYC or MMF should be tailored to individual patients, by considering the risk of infection in a particular patient.

Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

OBJECTIVE: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). MATERIALS AND METHODS: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Economic Burden of Chronic Hand Eczema: A Review.

There has been no extensive synthesis of studies evaluating the cost of chronic hand eczema (CHE). This review evaluated the societal costs, healthcare resource utilisation, missed work time and job loss due to CHE. MEDLINE and 16 other databases and websites were searched in October 2020 for studies meeting prespecified inclusion criteria. Studies conducted in Europe, Australia, New Zealand or the Americas were included. Two reviewers independently assessed titles and abstracts, and full-text papers published in English between 2000 and 2020, for relevance. Data extraction was carried out by one reviewer and checked by a second reviewer. All data were based on costs between 2001 and 2013 but have been inflated to 2020 prices and converted to US dollars and Euros. A total of 30 studies (reported in 33 publications) were included in the synthesis. Mean total societal costs per year per patient ranged from $2549 (€1813) to $10,883 (€7738). Pharmacological therapy was, on average, $28.34 (€20.15) per month in Italy and $36.49 (€25.94) per month for emollients in Switzerland. Yearly treatment costs were $599.05 (€425.92) for drugs, including topical corticosteroids, topical calcineurin inhibitors, other topical treatments and oral treatments, and $178.40 for emollients, in Germany. CHE was associated with hospitalisation costs ranging from $81.86 (€58.20) per patient per month (US) to $105.04 (€74.68) per patient per month (Italy) and $639.59 (€454.75) per year (Germany). Up to 57% of patients took sick leave and up to 25% reported job loss/job change due to CHE. This review confirms the significant cost burden of CHE. Given the paucity of studies estimating the monetary costs of absenteeism, presenteeism and job loss associated with CHE, current mean societal costs are likely underestimated. Uncontrolled disease may also lead to increased costs to patients and society.

[Epidemiology and treatment of adult patients with atopic dermatitis : Analysis of longitudinal data of the statutory health insurance scheme]. / Epidemiologie und Therapie von erwachsenen Patienten mit atopischer Dermatitis : Analyse von Längsschnittdaten der gesetzlichen Krankenversicherung.

BACKGROUND: The goal was to report incidence, prevalence, and treatment patterns in adult atopic dermatitis (AD) patients in the German statutory health insurance system. PATIENT AND METHODS: Anonymized claims data were evaluated at patient level for 3.3 million persons insured by six different statutory health insurance companies (SHI). Patients for whom the ICD-10 diagnosis code L20 (AD) was applied at least twice were analyzed and data on prescription patterns for AD were reported for the years 2011-2015. RESULTS: AD prevalence in adults was 1.6-1.9% in 2012-2015. Annual incidence was 0.28%. In Q3/Q4 2015, 44.2% of the adult population with AD diagnosis by a dermatologist received prescriptions for AD medications: 1.6% low-potency topical glucocorticoids (without previous prescription of systemic drugs), 46.9% moderate or high-potency topical glucocorticoids or topical calcineurin inhibitors, 23.9% current systemic therapy (systemic glucocorticoids, ciclosporin, methotrexate, azathioprine, mycophenolate mofetil) and 27.6% systemic therapy in the past. CONCLUSIONS: The AD prevalence estimate was in the range of previous reports (1.35-4%) that used different methodologies. Based on treatment proxy, it appeared that almost more than half of AD patients treated with prescription ready-to-use drugs had a severe form of AD which required treatment with systemic drugs.

Epidemiology and Treatment of Chronic Graft-versus-Host Disease Post-Allogeneic Hematopoietic Cell Transplantation: A US Claims Analysis.

Chronic graft-versus-host disease (cGVHD) is a complication of hematopoietic cell transplantation (HCT). Although the clinical outcomes of cGVHD are well documented, few studies have assessed treatment practices outside of clinical trials. The present study aimed to quantify the prevalence of cGVHD, examine provider prescribing patterns, and evaluate the healthcare cost and resource utilization (HCRU) in a US cGVHD population. We analyzed anonymized claims from the Medicare Fee-for-Service (FFS) 5% sample for beneficiaries enrolled between 2013 and 2016 and PharMetrics commercial 2013 to 2018 databases to identify cGVHD in allogeneic HCT recipients. cGVHD was identified based on International Classification of Diseases Ninth/Tenth Revision diagnosis codes for cGVHD or unspecified GVHD with a first diagnosis >180 days post-HCT or a maintained unspecified GVHD diagnosis for >12 months postindex of unspecified GVHD diagnosis. Longitudinal and line of therapy (LOT) analyses were based on the PharMetrics dataset for 2013 to 2018. Healthcare costs were calculated by adding the inpatient, outpatient, and pharmacy insurer and beneficiary paid amounts for the commercially insured population. Total HCRU was assessed using the number of inpatient and outpatient visits following the initial cGVHD diagnosis. In 2016, the projected prevalence of cGVHD in the United States based on the Medicare FFS and PharMetrics commercial databases was 14,017 individual patients. Within 3 years after undergoing allogeneic HCT, 42% of patients developed cGVHD; 66% of the cGVHD patients had a prior diagnosis of acute GVHD. The majority of cGVHD patients received at least one systemic therapy; 71% and 47% of cGVHD patients progressed to a second and third LOT, respectively. A total of 24 unique therapeutic agents and more than 150 combinations were used in the second and third LOTs. Corticosteroids and corticosteroid combination therapy were the most common forms of treatment across all examined LOTs. Furthermore, the most commonly used agents in the first LOT, second LOT, and third LOT were corticosteroids only, calcineurin inhibitors only, and corticosteroids only, respectively. In the 12 months postdiagnosis, cGVHD patients had an average of 21.0 cGVHD-related inpatient and outpatient visits (2.8 inpatient and 18.2 outpatient visits). A significant proportion of allogeneic HCT recipients continue to develop cGVHD, and despite advances in the understanding of cGVHD, corticosteroids remain the mainstay of therapy. Patients often progress beyond the first LOT, at which time the utilization of systemic therapies is highly variable, demonstrating the need for evidence-based treatment approaches.

Management of Atopic Dermatitis in Children Younger Than Two Years of Age by Community Pediatricians: A Survey and Chart Review.

OBJECTIVES: To characterize primary care providers' (PCPs) practice patterns for atopic dermatitis (AD) in children <2 years old and determine the need for AD guidelines for PCPs focused on this age group. STUDY DESIGN: This is a mixed-methods study consisting of a survey and a retrospective medical record review of PCP practices in the Chicago metropolitan area. The survey was analyzed using both quantitative and qualitative methods. RESULTS: In the survey (n = 52 respondents), PCPs reported management of AD is different in children <2 years compared with older children (88%). They were more likely to refer to a specialist (65%) and less likely to use high-potency topical corticosteroids (64%). In the chart review, PCP visits for children 2-5 years old (n = 50 914) vs those <2 years old (n = 71 913) for AD, older children had medium- and high-potency topical corticosteroids prescribed more frequently than younger children (0.66% vs 0.37%, P < .01 and .15% vs 0.05%, P < .01, respectively). In the subset of children <2 years of age who also were evaluated by a specialist (n = 109), medium- and high-potency topical corticosteroids were prescribed disproportionately at visits to providers in dermatology (57%) vs allergy (30%) vs pediatrics (15%) (P < .01). PCPs suggested that guidelines for this age group should include recommendations for preferred corticosteroids (39%), allergy management (35%), referral criteria (22%), and assessment of disease severity (11%). CONCLUSIONS: PCP management of AD in children <2 years is different from older children, with possible underuse of medium/high-potency topical corticosteroids. Clear guidelines for this age group are needed.

Prevalence, incidence and management of atopic dermatitis in Australian general practice using routinely collected data from MedicineInsight.

BACKGROUND/OBJECTIVES: The prevalence of atopic dermatitis (AD) has increased significantly in industrialised countries in recent decades but data about the incidence or prevalence of AD in Australia are sparse. We aimed to determine the prevalence and incidence of AD among patients seen in Australian general practice and the use of specified medicines. METHODS: This was a cross-sectional study of 2.1 million patients attending 494 general practices in the MedicineInsight program from 1 January 2017 to 31 December 2018. We assessed the prevalence (lifetime and current), incidence, management and severity of AD. RESULTS: The lifetime (ever diagnosed) prevalence of AD in this general practice population was 16.4% and was greater in females (17.3%) than males (15.3%). One in five patients with AD were classified as having moderate-to-severe disease. Prevalence over the last two years was 6.3%. The incidence of AD in 2018 was 2.0% and was greater in females (2.2%) and for patients aged 0-4 years (3.9%). Patients with AD had an increased risk of insomnia, anxiety and depression, compared to those with no recorded AD. For AD patients, topical corticosteroids were the most commonly prescribed AD medication (36.5%) and topical calcineurin inhibitors the least (0.1%), with systemic corticosteroids (15.6%) more commonly prescribed than other immunosuppressants (0.9%). CONCLUSIONS: Our findings provide important insights into the epidemiology of AD and its management in Australian general practice. This information is likely to be useful in planning effective interventions to support GPs in the optimal management of patients with AD.

Assessment of rejection risk following subtherapeutic calcineurin inhibitor levels after pediatric heart transplantation.

CNIs are the mainstay of immunosuppressive therapy after pediatric HTx. While regular laboratory surveillance is performed to ensure blood levels are within targeted range, the risk of acute rejection associated with subtherapeutic CNI levels has never been quantified. This is a retrospective single-center review of 8413 CNI trough levels in 138 pediatric HTx recipients who survived >1 year after HTx. Subtherapeutic CNI levels were defined as <50% of the lower limit of target range. The risk of acute, late (>12 months post-transplant) rejection following recipients' subtherapeutic CNI levels was assessed using time-varying multivariable Cox proportional hazards analysis. We found that 79 of 138 recipients (57%) had at least one subtherapeutic CNI level on routine surveillance laboratories during a mean follow-up of 5.5 ± 3.6 years. Following an episode of subtherapeutic levels, 17 recipients (22%) had biopsy-proven rejection within the next 3 months; the majority (9/17) within the first 2 weeks. After presenting with subtherapeutic CNI levels, recipients incurred a 6.1 times increased risk of acute rejection in the following 3 months (HR = 6.11 [2.41, 15.51], P = <.001). Age at HTx, HLA sensitization, or positive crossmatch were not associated with acute late rejection, but rejection in the first post-transplant year was (HR 2.61 [1.27, 5.35], P = .009). Thus, maintaining therapeutic CNI levels is the most important factor in preventing acute rejection in recipients who are >12 months after pediatric HTx. Recipients who present with subtherapeutic CNI levels on surveillance monitoring are 6.1 times more likely to develop rejection in the following 3 months.

Systematic Optimization, In Vitro Drug Release, and Preliminary Nonclinical Toxicity Assessment of Nonphospholipid-Based Topical Ophthalmic Emulsions Containing 0.05 or 0.1% w/w Cyclosporin A for Dry-Eye Syndrome Management.

The objectives of the present investigations are (1) to envisage a risk assessment plan for nonphospholipid-based topical ophthalmic emulsions with the help of failure mode and effect analysis (FMEA), (2) to screen the risky formulation and process variables by the Taguchi design, (3) to optimize systematically an emulsion formula by face-centered central composite design (CCD), (4) to incorporate cyclosporin A (0.05 or 0.1% w/w) into the optimized emulsions and predict the in vitro drug release kinetic via a particle diffusion-controlled mathematical model equation, and (5) to assess the emulsion's toxicity using in vitro hemolysis study. Through the risk priority number (RPN) scores of FMEA, half-normal and Pareto charts of the Taguchi design, 3D-response surface graphs, and overlay plots of CCD, the emulsion formula was systematically optimized. Irrespective of the two different drug loadings into optimized emulsions, the drug entrapment efficiency values ranged from 73.20 ± 0.13 to 74.42 ± 0.15%. The film diffusion or ion-exchange process fails to interpret the in vitro drug release kinetic profile. A permissible percentage hemolysis value of above 10% but below 25% guidance was observed for emulsions with or without cyclosporin A. The systematically optimized phospholipidless ophthalmic emulsions could further be exploited commercially for managing dry-eye syndrome.

Real-World Outpatient Prescription Patterns for Atopic Dermatitis in the United States.

Atopic dermatitis (AD) often requires combination treatment regimens. However, little is known about treatment combinations and polypharmacy in AD. We sought to characterize patterns of outpatient prescriptions and polypharmacy among US children and adults with AD. Data from the 1993-2015 National Ambulatory Medical Care Survey were analyzed, including 128,300 pediatric and 623,935 adult outpatient visits. Among AD visits, dermatologists prescribed more topical corticosteroids (TCSs, P = 0.01) than any other clinicians, particularly multiple TCSs (P < 0.0001), topical calcineurin inhibitors (TCI, P = 0.009), combination TCIs with TCSs (P = 0.004), and systemic immunosuppressants (P = 0.003). Prescriptions for multiple TCSs increased from ages 0 to 19 years, 20 to 39 years, and peaked at 40 to 59 years (P = 0.0002). Prescriptions for prednisone peaked at ages of 40 to 59 years (P = 0.003). A subset of AD patients was prescribed oral antibiotics (7.1%), although fewer than half had a diagnosis of bacterial infection (42.1%). The proportion of patients receiving multiple prescriptions was higher in visits to primary care practitioners versus dermatologists, those with private versus public insurance, and 50 years or older versus 20 to 49 years versus 0 to 19 years. Visits with 4 or more prescriptions by dermatologists increased between 1993-2000 (10%) and 2011-2015 (29%, P = 0.0001). In conclusion, significant treatment variation exists among specialists managing AD, with increasing polypharmacy over time.