[Pharmaceutical supply of human plasminogen replacement therapy for the treatment of ligneous conjunctivitis: Logistics for a university hospital]. / Approvisionnement hospitalier en plasminogène humain substitutif pour le traitement de la conjonctivite ligneuse : comment faire en pratique ?

In order to treat a pediatric patient with ligneous conjunctivitis secondary to congenital plasminogen deficiency, a supply of topically administered replacement human plasminogen has been required. In the absence of market approval, this blood-derived drug is managed by a temporary authorisation for nominative use, allowing monthly hospital dispensations. To ensure regulatory compliance and proper use of the drug, it took two years of interactions between various hospital departments and the laboratory to define the pharmaceutical supply chain in our hospital and allow the patient to receive treatment. The main difficulties lie in respecting the cold chain of this drug stored frozen in the bottles not ready for use. Transportation from the laboratory to the patient's home via the hospital pharmacy is carried out in calibrated conditions, ensuring a temperature below -20°C for 72h. Reception and dispensing steps were combined into a single pharmaceutical service in order to optimise transport time while ensuring the safety and traceability of the drug lots. Each month, a date is scheduled between the hospital pharmacy, the laboratory and the family to ensure that delivery and dispensing take place on the same day. Appropriate use and handling are explained to the family. However, two issues remain to be addressed by the manufacturer to facilitate future use of human plasminogen: the thermostability problem, which does not allow stays away from home longer than three days, and self-administration by the child, which is unlikely to be feasible due to handling difficulties.

Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. METHODS: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. RESULTS: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. CONCLUSIONS: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Surto de conjuntivite aguda no período de 2017-2018 em Recife, Brasil / Outbreak of acute conjunctivitis in the period 2017-2018 in Recife, Brazil

RESUMO Objetivo: Avaliar o perfil clínico, epidemiológico e o impacto econômico do surto de conjuntivite no período 2017-2018 no município de Recife-PE. Métodos: Estudo transversal com base na análise de prontuários de pacientes com diagnóstico de conjuntivite, atendidos na emergência da Fundação Altino Ventura entre dezembro/2017 e março/2018. Os dados coletados incluíram manifestações oculares no exame, complicações subsequentes, manejo e dias de licença médica. Resultados: Dos 12.712 pacientes atendidos na FAV entre dezembro de 2017 e março de 2018, 6.359 (50,0%) foram diagnosticados com conjuntivite, dos quais 3.543 pacientes (55,7%) foram atendimentos únicos. A média de idade dos pacientes ao atendimento foi de 29,5 ± 14,1 anos (variação, 1-85 anos), com distribuição semelhante entre os sexos (2.288 casos [50,1%] masculino; 2.282 casos [49,9%] feminino). O diagnóstico mais comum foi conjuntivite sem pseudomembrana (5.645 casos [88,8%]). Hiperemia conjuntival (6.278 casos [98,7%]) e reação folicular (6.255 casos [98,4%]) foram os achados mais frequentes ao exame. A complicação mais frequente foi pseudomembrana (1.062 casos [16,7%]). Os colírios lubrificantes (4.308 [67,7%]) e os colírios de associação antibiótico com corticoide (2.033 [32%]) foram os mais prescritos no tratamento. A média de dias de atestado médico foi de 4,8 ± 2,9 dias (variação, 1- 47 dias) e a perda de produtividade estimada em R$1.159.329,14. Conclusão: O surto de conjuntivite em Pernambuco foi responsável por metade das consultas em um pronto-socorro oftalmológico. Surtos de conjuntivite podem causar um impacto econômico, uma vez que afeta principalmente adultos jovens em idade produtiva. As características clínicas observadas sugerem um surto de conjuntivite de etiologia viral.

Abstract Purpose: To evaluate the epidemiological and clinical profile and economic impact of the acute conjunctivitis outbreak in the period of 2017-2018 in Recife-PE. Methods: Cross-sectional study based on the analysis of medical records of patients diagnosed with conjunctivitis at the emergency room of the Altino Ventura Foundation (FAV) between December 2017 and March 2018. The collected data included ocular manifestations at examination, subsequent complications, management, and days of sick leave. Results: Out of 12,712 patients assisted at FAV from December 2017 to March 2018, 6,359 (50.0%) were diagnosed with conjunctivitis. The mean age of patients was 29.5 ± 14.1 years (range, 01-85 years), with similar distribution between sex (2,288 50.1% male; 2,282 49.9% female). The most common diagnosis was non-pseudomembranous conjunctivitis (5,645 cases 88.8%). Conjunctival hyperemia (6,278 cases 98.7%) and follicular reaction (6,255 cases 98.4%) were the most frequent ocular findings. The most common complication was pseudomembrane in 1,062 cases (16.7%). Lubricants (4,308 67.7%) and antibiotic associated to corticosteroid eyedrops (2,033 32.0%) were the most prescribed medications. The average days of sick leave per patient was 4.8 ± 2.9 days (range, 1- 47 days) and the productivity loss estimated in R$1.159.329,14. Conclusion: The conjunctivitis outbreak in Pernambuco, Brazil was responsible for half of the consultations in an ophthalmic emergency room. Conjunctivitis outbreaks may cause an economic impact as it mostly affects young adults in their productive ages and take in average a 5-day sick leave. The clinical characteristics observed suggest an outbreak of conjunctivitis of viral etiology.

Allergy to oak pollen in North America.

Background: Oak pollen is an important allergen in North America. The genus Quercus (oak) belongs to the family Fagaceae under the order Fagales. Objective: The objective of this article was to narratively review the oak pollen season, clinical and epidemiologic aspects of allergy to oak pollen, oak taxonomy, and oak allergen cross-reactivity, with a focus on the North American perspective. Methods: A PubMed literature review (no limits) was conducted. Publications related to oak pollen, oak-related allergic rhinitis with or without conjunctivitis, and oak-related allergic asthma were selected for review. Results: Oak species are common throughout the United States and contribute up to 50% to overall atmospheric pollen loads. Mean peak oak pollen counts can reach >2000 grains/m³. The start of the oak pollen season generally corresponds to the seasonal shift from winter to spring based on latitude and elevation, and may begin as early as mid February. The duration of the season can last > 100 days and, in general, is longer at lower latitudes. In the United States, ∼30% of individuals with allergy are sensitized to oak. The oak pollen season correlates with increased allergic rhinitis symptom-relieving medication use and asthma-related emergency department visits or hospitalizations. Oak falls within the birch homologous group. Extensive immunologic cross-reactivity has been demonstrated between oak pollen and birch pollen allergens, and, more specifically, their major allergens Que a 1 and Bet v 1. The cross-reactivity between oak and birch has implications for allergy immunotherapy (AIT) because guidelines suggest selecting one representative allergen within a homologous group for AIT, a principle that would apply to oak. Conclusion: Allergy to oak pollen is common in North America and has a substantial clinical impact. Oak pollen allergens are cross-reactive with birch pollen allergens, which may have implications for AIT.

SARS-COV-2 y su relación con el sistema visual / SARS-CoV-2 and its relationship to the visual system

RESUMEN El virus SARS-COV-2, un nuevo coronavirus en humanos, surgió a finales del pasado año en China y provocó la entidad COVID-19. Desde entonces su expansión a más de 6 millones de personas en todo el mundo ha constituido un reto para el personal de salud en la lucha por evitar el contagio y en la constante búsqueda de las mejores alternativas de tratamiento. Con el objetivo de describir las alteraciones oculares que se han reportado en la literatura por el virus y los potenciales efectos oculares de la medicación empleada, se realizó una búsqueda bibliográfica actualizada utilizando distintas bases de datos. La incidencia de conjuntivitis en pacientes positivos a la COVID-19 es con frecuencia baja y a pesar de que hay evidencia de la trasmisión por secreciones oculares no existe consenso en el mecanismo patogénico utilizado. Se justifica el uso de medios de protección ocular, sobre todo en el personal cuya labor es cercana a los pacientes. No está demostrada la transmisión vertical de la entidad de gestantes a sus bebés, ni la afección oftálmica de estos últimos. La cloroquina y la hidroxicloroquina son medicamentos con efecto antiviral que solo causarían toxicidad ocular con altas dosis y tratamientos prolongados. Se propone realizar el examen oftalmológico completo al paciente una vez superada la enfermedad y continuar los estudios para esclarecer las interrogantes vigentes(AU)

ABSTRACT SARS-CoV-2, a new coronavirus affecting humans and causing the disease COVID-19, emerged at the end of last year in China. Ever since then its spread to more than 6 million people worldwide has been a challenge for the health personnel in their struggle to prevent contagion and find the best treatment alternatives. An updated bibliographic search was conducted in various databases with the purpose of describing the ocular alterations reported in the literature which have been caused by the virus as well as the potential ocular effects of the medications used. The incidence of conjunctivitis in patients testing positive for COVID-19 is often low. Although there is evidence of transmission via ocular secretion, no consensus has been achieved about the pathogenic mechanism employed. Justification is provided for the use of ocular protection equipment, particularly by the personnel who should be close to the patients' faces while doing their work. Vertical transmission from mothers to their babies has not been demonstrated, and there is no evidence of ophthalmic disorders in the latter. Chloroquine and hydroxychloroquine are antiviral medications which would only cause ocular toxicity at high doses and lengthy courses. It is proposed to perform complete ophthalmological examination of patients upon recovery from the disease and conduct further studies to shed light on current points of debate(AU)

Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort.

BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.

[Right treatment of red eyes - prescription of topical antibiotics for infectious conjunctivitis is still common in Sweden]. / Rekommendationer följs inte vid okomplicerad konjunktivit - Tillståndet behandlas ofta med topikala antibiotika i strid mot aktuell kunskap.

Conjunctivitis is one of the most common ophthalmologic conditions in general medical practice. In most cases, it is self-limiting and do not require topical antibiotic therapy. In a retrospective, observational cohort study during 2013-2017 in a region in Sweden conjunctivitis was diagnosed in 32 000 cases in primary care. Antibiotics were prescribed in 66% of undefined and in 83% of purulent conjunctivitis. Fusidic acid was the most common medication with 81% followed by chloramphenicol with 17%. Although unnecessary, the treatment is probably harmless. Toxicity is uncommon and the cost is low. Increased consciousness of this issue may however decrease resistance to antibiotics and support evidence-based medical practice.

Microbial Keratitis After Accelerated Corneal Collagen Cross-Linking in Keratoconus.

PURPOSE: To assess the pattern of microbial keratitis after accelerated corneal collagen cross-linkage (aCXL) in patients with keratoconus. METHOD: The medical records of cases of keratoconus that underwent aCXL from June 2014 to May 2017 were reviewed. Cases that developed microbial keratitis after aCXL were included in the study. The clinical, microbiological profile and the treatment outcomes were evaluated. RESULTS: Of 532 eyes that underwent aCXL, 7 cases developed microbial keratitis during the study period. Median age at presentation was 11 years (range 8-17). Association with vernal keratoconjunctivitis was noted in 57.1% of cases (n = 4/7). The median time at the onset of infection was 3 days after aCXL (range 1-4). Microbiological reports revealed mixed infection in 3 cases [coagulase-negative Staphylococcus (CoNS) + Aspergillus fumigatus, Staphylococcus aureus and Mucor spp., Staph. aureus and Acanthamoeba], Staph. aureus in 2 cases, and CoNS and Alternaria spp. in 1 case each. Resistance to fourth-generation fluoroquinolones was noted in 83.3% of cases of bacterial keratitis (n = 5/6). All cases were initially managed with empirical antibiotic treatment that was later tailored based on microbiological reports. One case eventually required therapeutic penetrating keratoplasty for corneal perforation. At 6 months, the corrected distance visual acuity was >6/60 in 3 cases while 4 cases had corrected distance visual acuity <6/60. CONCLUSIONS: Microbial keratitis after aCXL is rare; however, the infection tends to be severe with high preponderance of mixed infection and resistance to fourth-generation fluoroquinolones.

Antibiotic Use in Early Life, Rural Residence, and Allergic Diseases in Argentinean Children.

BACKGROUND: Little is known about differential effects of antibiotic use on allergic diseases in rural versus urban environments. OBJECTIVE: To examine whether area of residence in the first year of life modifies the relation between antibiotic use in early life and allergic diseases during childhood. METHODS: Cross-sectional study of allergic diseases in 1517 children (ages 6-7 years) attending 101 schools in urban and rural areas of San Francisco (Córdoba, Argentina). Current asthma, wheeze, and allergic rhinoconjunctivitis were defined on the basis of responses to a validated questionnaire from the International Study of Asthma and Allergies in Childhood. Multivariate logistic regression was used for the analysis of antibiotic use and allergic diseases. RESULTS: After adjustment for paracetamol use, bronchiolitis, and other covariates, antibiotic use in the first year of life was associated with increased odds of current wheeze (odds ratio [OR], 1.8; 95% CI, 1.3-2.6) and allergic rhinoconjunctivitis (OR, 1.9; 95% CI, 1.3-2.7). After stratification by area of residence, antibiotic use was associated with current wheeze (OR, 2.4; 95% CI, 1.5-4.0) and allergic rhinoconjunctivitis (OR, 2.1; 95% CI, 1.3-3.4) among children who lived in an urban area in their first year of life, but not among those who lived in a rural area in their first year of life. CONCLUSIONS: Early-life antibiotic use is associated with current wheeze and allergic rhinoconjunctivitis in Argentinean children who lived in urban areas during their first year of life. Exposure to a rural environment early in life may protect against the adverse effects of antibiotics on atopic diseases in children.

Orbitopatía de Graves: una enfermedad poco conocida por el oftalmólogo. «El presente y el futuro está en los inhibidores de citoquinas. Cómo y cuándo utilizarlas» / Graves’ ophthalmopathy: A disease little-known by the ophthalmologist. The present and future is in cytokinase inhibitors. How and when to use them

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Pediatric investigation plans for specific immunotherapy: Questionable contributions to childhood health.

Allergen-specific immunotherapy (SIT) is the only disease-modifying treatment for children, adolescents, and adults with allergic diseases. The EU has a combined system of national and EU-wide marketing authorization for all medicines. Germany introduced a new therapy allergen ordinance in 2008. Allergen products manufacturers had to apply for marketing authorization application for the major allergen groups (grass group, birch group, mites group, bee/wasp venom). Due to the EU pediatric regulation, in force since 2007, manufacturers had also to submit a pediatric investigation plan (PIP) for each allergen product. We investigated the allergic rhinoconjunctivitis (ARC) standard PIP, developed jointly by the European Medicines Agency (EMA) and the German Paul Ehrlich Institut (PEI). We analyzed the 118 EMA PIP decisions, looked for SIT trials in children in www.clinicaltrials.gov, and further analyzed EMA/EU justifications. The PIPs request a 1-year dose-finding study in adults, a 5-year placebo-controlled (PC) efficacy & safety (E&S) study in adults, and a 5-year PC E&S study in children. Fifty-eight PIP development programs will have to be performed until 2031. But children benefit even more from SIT for ARC than adults. There is no convincing medical/scientific justification for PC E&S studies in children in the relevant EMA documents. The PIP requirement to withhold effective treatment to thousands of children in the placebo group over a 5-year period raises profound concerns. The EMA justifications are formalistic and lack scientific foundation. A critical academic review of the ARC PIPs and the entire PIP system is urgently needed.

Can Twitter Be a Source of Information on Allergy? Correlation of Pollen Counts with Tweets Reporting Symptoms of Allergic Rhinoconjunctivitis and Names of Antihistamine Drugs.

Pollen forecasts are in use everywhere to inform therapeutic decisions for patients with allergic rhinoconjunctivitis (ARC). We exploited data derived from Twitter in order to identify tweets reporting a combination of symptoms consistent with a case definition of ARC and those reporting the name of an antihistamine drug. In order to increase the sensitivity of the system, we applied an algorithm aimed at automatically identifying jargon expressions related to medical terms. We compared weekly Twitter trends with National Allergy Bureau weekly pollen counts derived from US stations, and found a high correlation of the sum of the total pollen counts from each stations with tweets reporting ARC symptoms (Pearson's correlation coefficient: 0.95) and with tweets reporting antihistamine drug names (Pearson's correlation coefficient: 0.93). Longitude and latitude of the pollen stations affected the strength of the correlation. Twitter and other social networks may play a role in allergic disease surveillance and in signaling drug consumptions trends.

New developments in the treatment of pediatric allergic rhinitis and conjunctivitis.

The primary care physician is the first line of treatment for allergic rhinitis, which affects approximately one-fourth of children in the United States. There is an increasing trend toward self-management by patients or parents due to high-deductible insurance plans and the over-the-counter availability of allergy medications. The primary care physician can offer guidance on appropriate selection of medications and potential adverse effects. Vitamin D deficiency has been proposed as a potential contributing factor in patients with allergic diseases, and studies are underway to determine whether supplementation with vitamin D is helpful for these conditions. Sublingual immunotherapy has recently received US Food and Drug Administration approval for grass and ragweed allergens; many children will be interested in this alternative to allergy shots. The relative advantages and disadvantages of sublingual vs subcutaneous immunotherapy are discussed.

Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases.

BACKGROUND: Whether probiotics, which can influence the microbiome, prevent infant eczema or allergic disease remains an open question. Most studies have focused on high-risk infants. OBJECTIVES: We sought to assess whether consumption of probiotic milk products protects against atopic eczema, rhinoconjunctivitis, and asthma in early childhood in a large population-based pregnancy cohort (the Norwegian Mother and Child Cohort study). METHODS: We examined associations between consumption of probiotic milk products in pregnancy and infancy with questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614 children. Relative risks (RRs) were calculated by using general linear models adjusted for potential confounders. RESULTS: Consumption of probiotic milk in pregnancy was associated with a slightly reduced relative risk (RR) of atopic eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78-0.98) compared with no consumption during pregnancy. Maternal history of allergic disease did not notably influence the associations. When both the mother (during pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no consumption by either. Probiotic milk consumption was not associated with asthma at 36 months. CONCLUSIONS: In this population-based cohort consumption of probiotic milk products was related to a reduced incidence of atopic eczema and rhinoconjunctivitis, but no association was seen for incidence of asthma by 36 months of age.

Analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in Spain.

BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease in children. The main objective of this study was to analyze the comorbidities and therapeutic approaches for AR in a Spanish pediatric population. METHODS: Children aged 6 to 12 years with AR were included in an observational, cross-sectional, multicenter study. RESULTS: 1,275 children were recruited from 271 centers. AR was intermittent in 59.5% of cases, persistent in 40.5%, seasonal in 60.7%, and perennial in 39.3% of patients. The most frequent comorbidities were conjunctivitis (53.6%), asthma (49.5%), atopic dermatitis (40%), rhinosinusitis(26.1%), otitis media (23.8%), and adenoid hypertrophy (17.3%). Overall, patients with persistent, moderate or severe, AR were more likely to present comobidities, except for food allergy and urticaria. The most common drugs used for treatment of AR were oral antihistamines(76%), nasal corticosteroids(49%) and a combination of both (45%). Antihistamines and nasal corticosteroids were used on demand (<18 days) in 38 and 41% of patients, respectively; for 18-30 days in 22 and 27%; for 1-3 months in 31 and 29%; and for more than 3 months in 8 and 3%, respectively. Eye drops were used in 32% and specific immunotherapy in 21% of patients. CONCLUSION: Comorbidities are frequent in children with AR, supporting the notion of allergy as a systemic disease. Severity and duration of AR were significantly associated with presence of most of comorbidities. The most common drugs used for AR treatment were oral antihistamines, followed by nasal corticosteroids and a combination of both used on demand.

Climate change and allergic disease.

Allergies are prevalent throughout the United States and impose a substantial quality of life and economic burden. The potential effect of climate change has an impact on allergic disorders through variability of aeroallergens, food allergens and insect-based allergic venoms. Data suggest allergies (ocular and nasal allergies, allergic asthma and sinusitis) have increased in the United States and that there are changes in allergies to stinging insect populations (vespids, apids and fire ants). The cause of this upward trend is unknown, but any climate change may induce augmentation of this trend; the subspecialty of allergy and immunology needs to be keenly aware of potential issues that are projected for the near and not so distant future.