Intravenous and subcutaneous immunoglobulin replacement: a two-way road. Optimizing healthcare quality in patients with primary immunodeficiencies.

PURPOSE: To evaluate the alternate use of subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) in patients with primary immunodeficiencies (PID) in a third-level Pediatric University Hospital. METHODS: Retrospective study of all patients receiving SCIG from 2006 to 2012. Data collected included demographics, date SCIG was started, date of switch to IVIG and reasons, administration tolerance, and related adverse events. Effectiveness was defined as the lack of severe infections. RESULTS: Twenty-three patients (15 male, 8 female) with PID were studied. SCIG was initiated at a median age of 14.2 years (8.4 months-25.7 years) and median duration on SCIG treatment was 41 months (4-68). Nine patients (39.1%) temporarily switched from SCIG to IVIG for the following reasons: vacation (8), administration issues (1), and transient need for immunomodulatory therapy (1). A mean of 5.2 IVIG infusions/patient (SD=2.86) was administered while on SCIG. IVIG-related adverse events were documented in 3 patients with 6 infusions. Eight (34.8%) patients definitively discontinued SCIG use for the following reasons: convenience (5), adverse effects (1), coagulopathy (1), and autoimmune thrombocytopenia (1). There were no severe infections requiring hospital admission in any patient during the study period. CONCLUSIONS: Alternating SCIG and IVIG use in patients with PID was associated with considerable advantages in terms of convenience for the patients and their caregivers, while maintaining the effectiveness and safety of this therapy. Healthcare units treating these patients should show flexibility with this dual therapy in order to optimize patients' quality of life.

[Quality of care indicators for the care of human immunodeficiency virus-infected individuals, adapted to the pediatric age]. / Indicadores de calidad asistencial para la atención de personas que viven con el virus de la inmunodeficiencia humana, adaptados a la edad pediátrica.

INTRODUCTION: Since infection with human immunodeficiency virus (HIV) was first described, there have been many advances in its diagnosis, monitoring and treatment. However, few contributions are related to the area of health care quality. In this sense, the Spanish Study Group on AIDS (GESIDA) has developed a set of quality care indicators for adult patients living with HIV infection that includes a total of 66 indicators, 22 of which are considered to be relevant. Standards were calculated for each of them in order to reflect the level of the quality of care offered to these patients. Similar documents for pediatric patients are currently lacking. METHODS: Preparation of a set of quality care indicators applicable to pediatric patients based on the GESIDA document and the Spanish Guidelines for monitoring of pediatric patients infected with HIV. Each indicator was analysed with respect to the required standards in all patients under 18 years of age followed-up in our Unit, with the aim of evaluating the quality of care provided. RESULTS: A total of 61 indicators were collected (51 from the GESIDA document and 10 from currently available pediatric guidelines), 30 of which were considered to be relevant. An overall compliance of 81%-83% was obtained when assessing the relevant indicators. CONCLUSION: The availability of health care quality standards is essential for the care of pediatric HIV-infected patients. The assessment of these indicators in our Unit yielded satisfactory results.

Voriconazole drug monitoring in the management of invasive fungal infection in immunocompromised children: a prospective study.

OBJECTIVES: To evaluate voriconazole plasma level monitoring in immunocompromised children and determine the relationship of plasma levels with dose, safety and efficacy. METHODS: We used a prospective study including all consecutive children with invasive fungal infection (IFI) treated with voriconazole between August 2008 and May 2010. IFI diagnosis and clinical outcome evaluation were based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group ('EORTC/MSG') definitions. RESULTS: A total of 196 voriconazole plasma trough measurements from 30 patients (median age 10 years) obtained during 2135 days of voriconazole therapy were analysed. Nineteen patients (63%) presented with proven or probable IFI. Voriconazole plasma levels varied widely and 73% of patients required dose adjustment. The median voriconazole dose was 20 mg/kg/day and the median duration of therapy was 6 weeks. Age 5 was the smallest value defining two groups on which the correlation between dose and plasma levels had a different behaviour, and this relationship was especially significant for patients <5 years old (Spearman's rank correlation coefficient=0.38213, P=0.008). For patients <5 years old the median dose to achieve therapeutic levels was 38.0 mg/kg/day (12-40.0) and for those ≥5 years old it was 15 mg/kg (4-52). Voriconazole plasma levels showed a significant relationship with early outcome (P=0.0268), but not late outcome (P=0.2015). Overall mortality was 42% and a significant relationship with voriconazole therapeutic plasma levels was not demonstrated. A significant relationship was established between plasma levels above normal range and skin and neurological toxicity (P=0.0001), but this could not be demonstrated for liver toxicity. CONCLUSIONS: Our study confirms the large variability in voriconazole trough plasma levels in children and a trend to non-linear pharmacokinetics in older patients. In addition, doses significantly higher than those recommended in younger children seem warranted and a significant relationship between plasma voriconazole above the normal range and some adverse events is confirmed.

Clinical and epidemiological characteristics of patients with influenza A (H1N1) 2009 attended to at the emergency room of a children's hospital.

In June 2009, the first influenza pandemic of the twenty-first century, due to the swine origin influenza A (H1N1) 2009 virus, was declared. This study aimed to describe the epidemiological and clinical features, complications, lethality and risk factors for hospital admission of microbiologically confirmed cases of influenza A (H1N1) 2009 infection seen at the emergency department of a children's hospital. All cases of children with influenza A (H1N1) 2009 viral infection, confirmed microbiologically by real-time reverse transcription polymerase chain reactions and treated in the emergency room between July and December 2009, were prospectively included. Patients were compared according to admission requirement to study variables associated with the risk of hospitalisation. Oseltamivir was the antiviral used for the treatment and its safety was analysed. Four hundred and twelve patients with influenza A (H1N1) 2009 infection were included. The most frequent symptoms were: fever (96%), cough (95%) and coryza (90%). Eighty-five patients (20.6%) were admitted: three to the paediatric intensive care unit and two died. Hospitalised children were younger than those not admitted (median age 5 vs 8 years; p = 0.001). Age under 1 year (OR 6.01; CI 95% 2.77-13.05), pneumonia (OR 7.99; CI 95% 3.50-18.22) and haemoglobinopathy or underlying blood disorders (OR 5.99; CI 95% 1.32-27.30) were statistically significant risk factors for admission. No differences were observed regarding onset of antiviral treatment among admitted and non-admitted patients. Treatment with oseltamivir was well tolerated. In conclusion, the incidence of severe cases and lethality of influenza A (H1N1) 2009 infection were low in our setting, even in a population with risk factors for developing complications.

[Patient characteristics and health care burden during the influenza A (H1N1) 2009 pandemic in the university Hospital Vall d'Hebron of Barcelona]. / Características de los pacientes y carga asistencial durante la pandemia de gripe A (H1N1) 2009 en el Hospital Universitario Vall d'Hebron de Barcelona.

BACKGROUND AND OBJECTIVE: The influenza A (H1N1) 2009 pandemic initially had a mild impact in Catalonian hospitals, but in the autumn there was an important pandemic wave. We describe the main characteristics of patients seen in the Vall d'Hebron University Hospital in Barcelona (HUVH) during this pandemic, the risk factors associated with hospitalization and the health-care burden generated. MATERIAL AND METHOD: We included all cases of influenza A (H1N1) 2009 with laboratory confirmation seen in the HUVH from July 2, 2009 to January 22, 2010. We performed a descriptive analysis of the cases and a multivariate analysis to identify variables associated with the risk of hospitalization. RESULTS: The diagnosis was confirmed in 741 patients; 56.8% were under 16 years, while only 2.8% were 65 and over. Thirty three per cent of children had no risk factor for complications, whereas in adults it was 45%. One hundred and ninety cases were hospitalized, 26 of them in the intensive care unit (ICU) with 5 deaths. The factors associated with risk of hospitalization were, age less than one year, immunodeficiency, and neuromuscular disease in children; and chronic lung disease in adults. The diagnosis of pneumonia in the emergency department was an important predictor of hospitalization in both children and adults. The maximum caseload was recorded on November 19, with 43 hospital admissions, 6 of them in the ICU. CONCLUSIONS: Between July and September 2009 the pandemic had a low impact on hospital resources, but in autumn there was a marked increase in emergency department visits and hospitalizations. Children had higher rates of confirmed cases, while adults had higher rates of hospitalizations. The risk of hospitalization was higher in patients with certain conditions especially in those with pneumonia. The pandemic wave was a moderate work load for HUVH, since it did not involve any modification of the usual health care programs.

[Community-acquired methicillin-resistant Staphylococcus aureus infections in children]. / Infecciones por Staphylococcus aureus resistente a meticilina adquirido en la comunidad en niños.

INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections were first reported in the 1990s. Young, healthy individuals are frequently affected. The incidence of CA-MRSA in Spain is increasing. METHODS: All children seen between August 2006 and January 2009 with CA-MRSA infections were included. The S. aureus isolates were studied by conventional techniques, their antibiotic susceptibility by agar disk diffusion, the presence of mecA gene was detected by multiplex polymerase chain reaction (PCR) and the gene encoding the Panton-Valentine leukocidin (PVL) by conventional PCR. CA-MRSA colonization was studied both in patients and their family members. RESULTS: CA-MRSA was isolated in 15 samples from 12 patients, aged between 6 days and 14 years. Half of them were not native. Eight patients required hospital admission. The most common clinical presentation was skin and soft tissue infection (92%). Secondary CA-MRSA bacteraemia was present in two patients. All strains were PVL producers and two were resistant to macrolides associated to methicillin resistance and one of them was also resistant to lincosamides. An intra-familial transmission was identified. The clinical outcome was favourable in all patients. CONCLUSION: CA-MRSA infections are emerging in Spain. Empirical treatment of skin and soft tissue infections should not be changed, since their incidence is still low. The drainage of CA-MRSA suppurative infections plays an important role in their treatment. Clindamycin or trimethoprim-sulfamethoxazole should be used for mild or moderate skin and soft tissue infections. Controlling the spread of these strains presents a challenge in the community today.

Adiponectin, Leptin and Inflammatory Markers in HIV-associated Metabolic Syndrome in Children and Adolescents.

BACKGROUND: Metabolic syndrome (MetS) is more common in HIV-infected adults and children than in the general population. Adipocytokines and inflammatory markers may contribute to the pathophysiology of this condition and could be useful indices for monitoring MetS. The objective of this study was to provide information on the prevalence of MetS and investigate the role of adipocytokines and other biomarkers in this syndrome in HIV-infected pediatric patients. METHODS: A cross-sectional study was conducted between October 2013 and March 2014 in the outpatient clinics of 2 tertiary pediatric referral hospitals. Fifty-four HIV-infected children and adolescents were included. MetS was defined according to the International Diabetes Federation and modified National Cholesterol Education Program Adult Treatment Panel III criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin, adiponectin, leptin, interleukin-6, vitamin D and C-reactive protein and clinical lipodystrophy assessment. RESULTS: Among the total, 3.7% of patients met the International Diabetes Federation criteria for MetS and 7.4% met the National Cholesterol Education Program Adult Treatment Panel III criteria. C-reactive protein and leptin levels were significantly higher and adiponectin level significantly lower in patients with MetS, regardless of the criteria used. Insulin resistance was observed in 40.7% of patients; abnormal quantitative insulin sensitivity check index values were found in 88.9%. Eighteen patients (33.3%) had vitamin D deficiency. CONCLUSIONS: The prevalence of MetS was similar to that observed in larger cohorts of HIV-infected patients in our setting. Adipocytokine dysregulation seems to be related to MetS in HIV-infected children. A high percentage of patients showed insulin resistance, which should be strictly monitored.

Hyperlactatemia and in utero exposure to antiretrovirals: is the control group the clue?

Perinatal antiretroviral (ARV) exposure has been related to hyperlactatemia and lactic acidosis in infants born to HIV-infected mothers. Our objective was to determine the incidence of these conditions during the first year of life in uninfected infants born to HIV-infected mothers and compare the data with infants born to mothers with hepatitis C virus (HCV) infection. We investigated the relationships between hyperlactatemia and neurological and neurodevelopmental disorders by conducting a prospective, comparative cohort study (October 2004 to October 2007) consecutively including children of HIV- and HCV-infected mothers. Liver enzymes, pH, lactic acid, and plasma amino acids were determined at 1.5, 3, 6, and 12 months of life. Pathological hyperlactatemia was defined as lactate >2.1 mmol/liter together with alanine >475 µmol/liter. Seventy-nine patients (39 HIV-exposed patients and 40 unexposed patients) were included. Baseline maternal characteristics in the two groups were similar. Almost 90% of HIV-infected mothers received HAART during gestation, while 10.3% were given AZT monotherapy. Eight newborns received combined therapy and 31 received AZT-based monotherapy. Twelve patients (five exposed and seven nonexposed) had some neurological disorder, and four other patients (one vs. three) showed signs of neurodevelopmental delay, with no significant differences between the groups (p=0.34). Pathological hyperlactatemia was detected in 56.4% (95% CI 39.6-72.2) and 57.5% (95% CI 40.9-73.0) of patients, respectively (p=0.92), and this condition was more frequent in preterm children (p<0.05). ARV use during pregnancy and the neonatal period was not associated with pathological hyperlactatemia. The presence of hyperlactatemia was not associated with neurological or neurodevelopmental disorders. No association was established between the use of ARV agents and the development of hyperlactatemia or neurological disorders in HIV-exposed children during their first year of life.

Prospective study of renal function in HIV-infected pediatric patients receiving tenofovir-containing HAART regimens.

AIM: to describe the impact of tenofovir disoproxil fumarate (TDF) use on renal function in HIV-infected pediatric patients. DESIGN: it is a prospective, multicenter study. The setting consisted of five third-level pediatric hospitals in Spain. The study was conducted on patients aged 18 years and younger who had received TDF for at least 6 months. The intervention was based on the study of renal function parameters by urine and serum analyses. The main outcome measures were renal function results following at least 6 months of TDF therapy. RESULTS: forty patients were included (32 were white and 26 were diagnosed with AIDS). Median (range) duration of TDF treatment was 77 months (16-143). There were no significant changes in the estimated creatinine clearance. Urine osmolality was abnormal in eight of 37 patients, a decrease in tubular phosphate absorption was documented in 28 of 38 patients, and 33 of 37 patients had proteinuria. A statistically significant decrease in serum phosphate and potassium concentrations was observed during treatment (P = 0.005 and P = 0.003, respectively), as well as a significant relationship between final phosphate concentration and tubular phosphate absorption (P = 0.010). A negative correlation was found between phosphate concentration and time on TDF. CONCLUSIONS: TDF use showed a significant association with renal tubular dysfunction in HIV-infected pediatric patients. Periodic assessment of tubular function may be advisable in the follow-up of this population.

Congenital rubella syndrome, hyper-IgM syndrome and autoimmunity in an 18-year-old girl.

Congenital rubella syndrome can be associated with disgammaglobulinaemia and autoimmune phenomena in adult and paediatric population. The aim of this article is to present the association between a congenital rubella syndrome with hypogammaglobulinaemia and hyper IgM diagnosed at the age of 8 months and autoimmune manifestations in an 18-year-old girl. A medical chart review of this patient since admission at our institution at 8 months of age was carried out. During infancy she presented the classical manifestations of a rubella syndrome (sensorineural deafness and brain calcifications in basal ganglia) with respiratory and gastrointestinal infections. She was also diagnosed of localised scleroderma and thyroiditis. She has been on intravenous immunoglobulin since diagnosis, with rapid normalisation of IgG and IgM levels, decreased incidence of infectious processes, but with persistent autoimmune phenomena. At 18 years of age she was admitted because of a thyroid mass. Fine needle aspiration biopsy was not conclusive and thyroidectomy was performed. Pathology studies showed no malignancy. She is now on replacement therapy with thyroid hormones. Our aim is to emphasise the importance of the association between autoimmune phenomena in patients with immunodeficiencies, even secondary to some infections, and the increased frequency of malignancies owing to the persistent immunologic defect in this syndrome.