Standardising personalised diabetes care across European health settings: A person-centred outcome set agreed in a multinational Delphi study.

OBJECTIVE: Standardised person-reported outcomes (PRO) data can contextualise clinical outcomes enabling precision diabetes monitoring and care. Comprehensive outcome sets can guide this process, but their implementation in routine diabetes care has remained challenging and unsuccessful at international level. We aimed to address this by developing a person-centred outcome set for Type 1 and Type 2 diabetes, using a methodology with prospects for increased implementability and sustainability in international health settings. METHODS: We used a three-round questionnaire-based Delphi study to reach consensus on the outcome set. We invited key stakeholders from 19 countries via purposive snowball sampling, namely people with diabetes (N = 94), healthcare professionals (N = 65), industry (N = 22) and health authorities (N = 3), to vote on the relevance and measurement frequency of 64 previously identified clinical and person-reported outcomes. Subsequent consensus meetings concluded the study. RESULTS: The list of preliminary outcomes was shortlisted via the consensus process to 46 outcomes (27 clinical outcomes and 19 PROs). Two main collection times were recommended: (1) linked to a medical visit (e.g. diabetes-specific well-being, symptoms and psychological health) and (2) annually (e.g. clinical data, general well-being and diabetes self management-related outcomes). CONCLUSIONS: PROs are often considered in a non-standardised way in routine diabetes care. We propose a person-centred outcome set for diabetes, specifically considering psychosocial and behavioural aspects, which was agreed by four international key stakeholder groups. It guides standardised collection of meaningful outcomes at scale, supporting individual and population level healthcare decision making. It will be implemented and tested in Europe as part of the H2O project.

Which diabetes specific patient reported outcomes should be measured in routine care? A systematic review to inform a core outcome set for adults with Type 1 and 2 diabetes mellitus: The European Health Outcomes Observatory (H2O) programme.

OBJECTIVES: The objective was to identify candidate patient reported outcomes with potential to inform individual patient care and service development for inclusion in a digital outcome set to be collected in routine care, as part of an international project to enhance care outcomes for people with diabetes. METHODS: PubMed, COSMIN and COMET databases were searched. Published studies were included if they recommended patient reported outcomes that were clinically useful and/or important to people with diabetes. To aid selection decisions, recommended outcomes were considered in terms of the evidence endorsing them and their importance to people with diabetes. RESULTS: Twenty-seven studies recommending 53 diabetes specific outcomes, and patient reported outcome measures, were included. The outcomes reflected the experience of living with diabetes (e.g. psychological well-being, symptom experience, health beliefs and stigma) and behaviours (e.g. self-management). Diabetes distress and self-management behaviours were most endorsed by the evidence. CONCLUSIONS: The review provides a comprehensive list of candidate outcomes endorsed by international evidence and informed by existing outcome sets, and suggestions for measures. PRACTICE IMPLICATIONS: The review offers evidence to guide clinical application. Integrated measurement of these outcomes in care settings holds enormous potential to improve provision of care and outcomes in diabetes.

Outcomes of Patients with Severe Obesity and Cirrhosis with Portal Hypertension Undergoing Bariatric Surgery: a Systematic Review.

PURPOSE: Thus far, little attention has been paid to bariatric surgery (BS) in patients with severe obesity (SO) and cirrhosis with portal hypertension (PH). To address this knowledge gap, we systematically reviewed the available literature and evidence about BS in patients with SO and cirrhosis with PH. We inform on the perioperative and long-term outcomes of this intervention. MATERIALS AND METHODS: Articles were identified in MEDLINE, SCOPUS, LILACS, and SCIELO, and included if they analyzed SO patients with clinically significant PH and reported the characteristics and outcomes of BS. RESULTS: Six articles, including 32 patients, were included. The most frequent type of BS was sleeve gastrectomy performed in 27 patients. Perioperative transfusions were often not required, with only one case report describing the use of 1 unit of packed red blood cells post-operatively. Neither intraoperative nor post-op deaths were reported. All patients reported significant weight loss with improvements in comorbidities during the follow-up periods. Overall, 27 out of 29 patients had T2DM resolution, and 13 out of 23 had arterial hypertension resolution. One study reported improvements in the parameters of fibroscan. CONCLUSION: This systematic review described the outcomes of BS among patients with SO with cirrhosis and PH. Performing this kind of surgery among these patients appears safe and associated with acceptable perioperative and long-term outcomes. However, further studies are required to provide evidence-based, strong recommendations.

Mortality in patients treated for COVID-19 in the emergency department of a tertiary care hospital during the first phase of the pandemic: Derivation of a risk model for emergency departments. / Análisis de mortalidad de los pacientes atendidos por COVID-19 en el servicio de urgencias de un hospital de tercer nivel en la fase incial de la pandemia. Derivación de un modelo de riesgo para urgencias.

OBJECTIVES: To develop a risk model to predict 30-day mortality after emergency department treatment for COVID-19. MATERIAL AND METHODS: Observational retrospective cohort study including 2511 patients with COVID-19 who came to our emergency department between March 1 and April 30, 2020. We analyzed variables with Kaplan Meier survival and Cox regression analyses. RESULTS: All-cause mortality was 8% at 30 days. Independent variables associated with higher risk of mortality were age over 50 years, a Barthel index score less than 90, altered mental status, the ratio of arterial oxygen saturation to the fraction of inspired oxygen (SaO2/FIO2), abnormal lung sounds, platelet concentration less than 100 000/mm3, a C-reactive protein concentration of 5 mg/dL or higher, and a glomerular filtration rate less than 45 mL/min. Each independent predictor was assigned 1 point in the score except age, which was assigned 2 points. Risk was distributed in 3 levels: low risk (score of 4 points or less), intermediate risk (5 to 6 points), and high risk (7 points or above). Thirty-day risk of mortality was 1.7% for patients who scored in the low-risk category, 28.2% for patients with an intermediate risk score, and 67.3% for those with a high risk score. CONCLUSION: This mortality risk stratification tool for patients with COVID-19 could be useful for managing the course of disease and assigning health care resources in the emergency department.

OBJETIVO: Derivar un modelo de riesgo para estimar la probabilidad de mortalidad a los 30 días de la visita a urgencias de pacientes con COVID-19. METODO: Estudio observacional de cohortes retrospectivo de 2.511 pacientes con COVID-19 atendidos en el servicio de urgencias hospitalario (SUH) del 1 de marzo al 30 de abril de 2020. Se realizó análisis de supervivencia mediante Kaplan Meier y regresión de Cox. RESULTADOS: La mortalidad por cualquier causa a los 30 días fue de un 8%. Los factores asociados de forma independiente a mayor mortalidad fueron: edad 50 años, índice de Barthel 90 puntos, alteración del nivel de consciencia, índice de SaO2/FIO2 400, auscultación respiratoria anómala, cifra de plaquetas 100.000/mm3, PCR 5 mg/dL y filtrado glomerular 45 mL/min. A estos factores se les asignó una puntuación de 1, excepto a la edad, que se le asignó un valor de 2 puntos. Se dividió el modelo de riesgo en 3 categorías: riesgo bajo (menor o igual a 4 puntos), riesgo intermedio (5-6 puntos) y riesgo alto (igual o superior a 7 puntos). Para los pacientes clasificados como de bajo riesgo la probabilidad de mortalidad a los 30 días fue del 1,7%, en los casos de riesgo intermedio fue del 28,2% y para los de alto riesgo fue del 67,3%. CONCLUSIONES: Disponer de una herramienta para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH podría ser de utilidad para la gestión de los recursos sanitarios disponibles.

Endogenous cortisol excess confers a unique lipid signature and metabolic network.

Chronic cortisol excess induces several alterations on protein, lipid and carbohydrate metabolism resembling those found in the metabolic syndrome. However, patients exposed to prolonged high levels of cortisol in Cushing syndrome (CS) present exceeding cardiometabolic alterations not reflected by conventional biomarkers. Using 3 ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) platforms, we aimed to characterise the serum metabolome of 25 patients with active endogenous CS and 25 control subjects matched by propensity score (sex, BMI, diabetes mellitus type 2 (T2D), high blood pressure (HBP) and dyslipidaemia) to search for potential disease-specific biomarkers and pathways associated to the clinical comorbidities. A total of 93 metabolites were significantly altered in patients with CS. Increased levels of sulfur amino acids (AA), triacylglycerols, glycerophospholipids, ceramides and cholesteryl esters were observed. Contrarily, concentrations of essential and non-essential AA, polyunsaturated fatty acids, conjugated bile acids and second messenger glycerolipids were decreased. Twenty-four-hour urinary free cortisol (24h-UFC) independently determined the concentration of 21 lipids and 4 AA. A metabolic signature composed by 10 AA and 10 lipid metabolites presented an AUC-ROC of 95% for the classification of CS patients. Through differential network analysis, 152 aberrant associations between metabolites involved in the Lands cycle and Kennedy pathway were identified. Our data indicates that chronic hypercortisolemia confers a unique lipidomic signature and several alterations in numerous AA even when compared to patients with similar metabolic comorbidities providing novel insights of the increased cardiometabolic burden of CS. KEY MESSAGES: • Cortisol excess induces metabolic alterations beyond conventional biomarkers. • The hypercortisolism extent determines the concentration of 21 lipids and 5 aa. • Cortisol excess confers a unique metabolic signature of 20 metabolites. • Kennedy and Lands cycle are profoundly disturbed by cortisol excess.

Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department. / Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario.

OBJECTIVES: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 months and were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given in the ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit were compared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99; P = .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63; P = .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06; P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21, P = .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67; P = .002) and fever (OR, 4.73; 95% CI, 1.99-11.27; P = .001). CONCLUSION: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization.

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66 (38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria $ 20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias [OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad $ 48 años [OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIONES: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria $ 20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad $ 48 años de necesidad de ingreso.

Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario / Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). MÉTODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66(38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria>=20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias[OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad>=48 años[OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIÓN: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria>=20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad>=48 años de necesidad de ingreso

OBJECTIVE: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease2019 (COVID-19). METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 monthsand were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given inthe ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit werecompared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99;P= .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63;P= .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06;P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21,P= .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67;P= .002) and fever (OR, 4.73; 95% CI, 1.99-11.27;P= .001). CONCLUSIONS: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization

Efecto de la estrategia chance de vida en la prevención y tratamiento de niños menores de cinco años con sobrepeso u obesidad / Effect of the strategy chance for life in the prevention and treatment children under five years with overweight/obesity

OBJETIVO: evaluar efecto de la estrategia chance de vida (C: colores del fuego, H: horarios (reloj de día), AN: antropometría, C: plato a colores de payaso, E: estimulación (ejercicios) incluyendo en el entorno VIDA en niños con sobrepeso/ obesidad entre 6 meses y 5 años. MÉTODO: se incluyeron 23 pacientes (12 niños, 11 niñas) con sobrepeso/obesidad de acuerdo a criterios de inclusión, previa toma de medidas antropométricas, ecografía del timo y muestra sanguínea para determinar glicemia y perfil lipídico, los niños fueron monitorizados a domicilio con la estrategia chance de vida por 6 meses. RESULTADOS: edad promedio: 27,0± 18,5 meses, Z score IMC: 2,6±0,83 al ingreso, a las dos semanas 2,59±0,88 (ns), cuarta semana 1,93±0,67 (p≤0,001) 12ava semana 1,27±0,52 (p≤0,001) y 24ava semana 0,87±0, 52(p≤0,001). La ingesta calórica: 1803,9±382 Kcal al ingreso, egreso: 1017,3±164,6kcal/día (p≤0,000). El grado desarrollo psicomotor: 76,5±4,8 % al inicio, al concluir: 97,6±1,96% (p≤0,001). Las LDL fueron: 130,0±9,1 mg/dl al ingreso, egreso 91,2±5,9mg/dl (p≤0,000), HDL: 30,9±3,2 mg/dl al ingreso, egreso: 45,0±5,9mg/dl (p≤0,000), triglicéridos 160,4±9,1mg/dl ingreso, egreso: 130,8±10,1mg/dl (p≤0,000), colesterol: 179,8±5,5 mg/dl ingreso, egreso: 146,9±7,7 y la glicemia: 88,2±5,7 mg/dl al ingreso y egreso: 77,2±6,3 mg/dl. La superficie del timo: 378±64,9 mm2 ingreso, egreso: 637,7 ± 80,13mm2(p≤0,001). Las madres 86,9 % (20) tuvieron sobrepeso/ obesidad y en 13,0 % fueron los padres, la edad promedio de estas madres: 22,6±3,4 años El promedio de IMC para las madres llego a 27,5±2,5 kg/m2, al concluir el seguimiento: 25,3±2,3kg/m2. Se correlacionaron significativamente el IMC a las 12 semanas, instrumentos: colores del fuego, aporte de calórico, la frecuencia de alimentación, reloj de día, uso de plato de payaso (p<0,001). Incremento de LDH, pliegue cutáneo tricipital (p<0,001), la medida del timo al ingreso con LDH (p<0,01). En la relación madre-niño(a) encontramos correlaciones del aporte calórico de la madre con el del niño a las 2, 8 y 12 semanas; el timo con el PCT de la madre a las 12 semanas y aporte de calorías de la madre con el desarrollo del niño (p<0,001). CONCLUSIONES: la estrategia chance de vida fue útil para la recuperación de niños con sobrepeso u obesidad.

OBJECTIVE: to evaluate the effect of chance for life (C strategy: colors of fire, H: Hours (Day Watch), AN: Anthropometry, C: Plate to colors clown, E: Stimulation (exercises) including the environment LIFE in overweight / obese between 6 months and 5 years. METHOD: 23 patients (12 boys, 11 girls) overweight / obese according to inclusion criteria were included, after taking anthropometric measurements, ultrasound thymus and blood sample to determine glucose and lipid profile, children were monitored at home with the chance of life strategy for 6 months. RESULTS: average age: 27.0 ± 18.5 months BMI Z score: 2.6 ± 0.83 at admission, two weeks 2.59 ± 0.88 (ns), fourth week 1.93 ± 0.67 (p≤0.001), 1.27 ± 0.52 12th week (p≤0.001) and week 24 0.87 ± 0.52 (p≤0.001) .The caloric intake: 1803.9 ± 382 Kcal to entry, exit: 1017.3 ± 164,6kcal / day (p≤0.000). The degree psychomotor development: 76.5 ± 4.8% at the beginning, at the end: 97.6 ± 1.96% (p≤0.001). LDL were: 130.0 ± 9.1mg / dl at admission, discharge 91.2 ± 5.9mg / dl (p≤0.000), HDL: 30.9 ± 3.2 mg/dl at admission, discharge: 45.0 ± 5.9mg / dl (p≤0.000), triglycerides 160.4 ± 9.1mg / dl entry, exit: 130.8 ± 10,1mg / dl (p≤0.000) cholesterol: 179.8 ± 5.5 mg / dl entry, exit: 146.9 ± 7.7 and glycemia: 88,2 ± 5,7 mg / dl at admission and discharge: 77.2 ± 6.3 mg / dl. The surface of the thymus: 378 ± 64.9 mm2 entry, exit: 637.7 ± 80.13mm2 (p≤0.001) .The mothers 86.9% (20) were overweight / obese and 13.0% were parents the average age of these mothers: 22.6 ± 3.4 years, the average BMI for mothers came to 27.5 ± 2.5 kg / m2, at the end of follow-up: 25.3 ± 2.3kg / m2. BMI was significantly correlated at 12 weeks, instruments colors of fire, caloric intake, feeding frequency, clock day use dish clown (p <0.001). LDH increase, triceps skinfold (p <0.001), the measure thymus income LDH (p <0.01). In the mother-child relationship (a) found correlations of caloric intake from mother to child at 2, 8 and 12 weeks; thymus PCT mother at 12 weeks and calorie intake from mother to child development (p <0.001). CONCLUSIONS: Life chance strategy was useful for the recovery of children are overweight or obese.

Implementación el rediseño organizacional del Departamento de Tecnología de Información y Comunicación de la UMSA

Menciona que uno de los principales objetivos del DTIC para la presente gestión, es el de implementar el rediseño organizacional, el que debe estar orientado a formalizar la ejecución óptima de los servicios induciendo al pensamiento estratégico del Departamento...

Currant allergy and the Rosaceae-grass pollen allergy syndrome: a case report.

BACKGROUND: Despite the increasing use of currants in culinary recipes, currant allergy has rarely been reported. OBJECTIVES: To study a case of currant allergy and to explore cross-reactivity between grass pollen and Rosaceae family fruit allergens. METHODS: Skin prick tests to pollen and skin prick-to-prick tests with currants and peach were performed. Specific IgE levels were determined using the CAP method. We prepared a protein extract of 0.1 mg/mL in phosphate-buffered saline using red currant in the presence of protease inhibitors. Immunoblot inhibition studies were performed to explore cross-reactivity between grass pollen and currant allergens. RESULTS: Skin prick test results were positive to Dactylis, arizonic, and olive pollens. Results of skin prick-to-prick tests with fresh red and black currants were negative and positive, respectively, to peach. The specific IgE level was 5.7 KU/L to red currant and 2.92 KU/L to peach (CAP). Western blot analysis with red currant extract revealed specific IgE protein bands of 37 and 26 kDa. Preincubation of sera with extracts from red currant and peach inhibited both IgE bands, and preincubation with Dactylis pollen inhibited the 37-kDa band only. CONCLUSIONS: We report a case of allergy to grass pollen with an oral allergy syndrome involving several fruits from 2 different families of the Rosidae subclass confirmed by in vitro tests. Inhibition studies demonstrated cross-reactivity between different fruits (currant and raspberry) from the Rosidae subclass and were incomplete with grass pollen allergens.