Heart rate variability alterations in Dravet Syndrome: The role of status epilepticus and a possible association with mortality risk.

PURPOSE: Preliminary data suggest that patients with Dravet Syndrome (DS) have a reduced heart rate variability (HRV). This seems particularly evident in patients who experienced sudden unexpected death in epilepsy (SUDEP). This study aims at confirming these findings in a larger cohort and at defining clinical, genetic or electroencephalographic predictors of HRV impairment in DS patients. METHODS: DS patients followed at our Institution performed a 24h-ECG Holter to derive HRV parameters. We used as control population patients with epilepsy (PWEs) and healthy controls (HCs). In DS patients, we assessed the impact of different clinical, neurophysiological and genetic features on HRV alterations through multiple linear regression. After a mean follow-up of 7.4 ± 3.2 years since the HRV assessment, all DS patients were contacted to record death or life-threatening events. RESULTS: 56 DS patients had a significantly reduced HRV compared to both HCs and PWEs. A recent history of status epilepticus (SE) was the only significant predictor of lower HRV in the multivariate analysis. At follow-up, only one patient died; her HRV was lower than that of all the controls and was in the low range for DS patients. CONCLUSION: We describe for the first time an association between SE and HRV alterations in DS. Further studies on other SCN1A-related phenotypes and other epilepsies with frequent SE will help clarify this finding. Compared to the literature, our cohort showed better HRV and lower mortality. Although limited, this observation reinforces the role of HRV as a biomarker for mortality risk in DS.

Symptomatic partial and transitional atrioventricular septal defect repaired in infancy.

OBJECTIVES: Infants with symptomatic partial and transitional atrioventricular septal defect undergoing early surgical repair are thought to be at greater risk. However, the outcome and risk profile of this cohort of patients are poorly defined. The aim of this study was to investigate the outcome of symptomatic infants undergoing early repair and to identify risk factors which may predict mortality and reoperation. METHODS: This multicentre study recruited 51 patients (24 female) in three tertiary centres between 2000 and 2015. The inclusion criteria were as follows: (1) partial and transitional atrioventricular septal defect, (2) heart failure unresponsive to treatment, (3) biventricular repair during the first year of life. RESULTS: Median age at definitive surgery was 179 (range 0-357) days. Sixteen patients (31%) had unfavourable anatomy of the left atrioventricular valve: dysplastic (n=7), double orifice (n=3), severely deficient valve leaflets (n=1), hypoplastic left atrioventricular orifice and/or mural leaflet (n=3), short/poorly defined chords (n=2). There were three inhospital deaths (5.9%) after primary repair. Eleven patients (22%) were reoperated at a median interval of 40 days (4 days to 5.1 years) for severe left atrioventricular valve regurgitation and/or stenosis. One patient required mechanical replacement of the left atrioventricular valve. After median follow-up of 3.8 years (0.1-11.4 years), all patients were in New York Heart Association (NYHA) class I. In multivariable analysis, unfavourable anatomy of the left atrioventricular valve was the only risk factor associated with left atrioventricular valve reoperation. CONCLUSIONS: Although surgical repair is successful in the majority of the cases, patients with partial and transitional atrioventricular septal defect undergoing surgical repair during infancy experience significant morbidity and mortality. The reoperation rate is high with unfavourable left atrioventricular valve anatomy.

Grass pollen sublingual immunotherapy and paediatric allergic rhinitis: A patient-oriented decision.

Guidelines and systematic review report that allergen immunotherapy (AIT) is, in general, effective in the treatment of allergic rhinitis. However, experts suggest not generalising the results of different clinical studies: for example, it would not be advisable to translate the results found in an adult population to a paediatric population or the results on the efficacy of AIT against a specific allergen to the AIT against a different allergen. Moreover, according to Evidence Based Medicine (EBM), clinical decisions are individualised and should derive from the "integration of best research evidence with clinical expertise and patient values". Taking into account the high specificity of the AIT and EBM principles, we tried to answer the question on how advisable it is to prescribe the AIT for the management of grass allergic rhinitis in children. To do this, we revised the scientific literature in order to solve a specific case scenario.

Ondansetron for food protein-induced enterocolitis syndrome.

Recently, a study on 5 patients [Holbrook et al.: J Allergy Clin Immunol 2013;132:1219-1220] documented the efficacy of the intravenous administration of ondansetron in children with acute symptoms due to food protein-induced enterocolitis syndrome (FPIES). We report on the experience at our institution using ondansetron during oral food challenge (OFC) in 5 children affected by FPIES. In all 5 cases, the use of intramuscular ondansetron led to a complete and rapid resolution of symptoms within 15 min. Intramuscular administration, without the need for intravenous access for an infusion or steroid administration, enables this therapy to be easily performed, even at home (i.e. out of a hospital setting). A home treatment with ondansetron cannot be considered as an alternative to a medical examination with eventual treatment in hospital, which is advised after any acute episode of FPIES. We consider ondansetron to be very useful in the management of acute FPIES. Further study is required to confirm its efficacy.

Incidence, clinical features and management of hypersensitivity reactions to chemotherapeutic drugs in children with cancer.

PURPOSE: Hypersensitivity reactions (HSRs) may occur in children with cancer during the use of almost all chemotherapeutic drugs. HSRs may also produce a negative impact on treatment intensity and, as a consequence, worsen patients' outcome. The aim of this review is to summarize the incidence and the clinical features of HSRs occurring in children with cancer treated with chemotherapeutic drugs and their impact on treatment efficacy, in order to outline possible adequate prevention and management strategies. METHODS: Data were collected by searching for relevant studies about incidence, clinical features and management of hypersensitivity reactions that may occur with the use of chemotherapeutic agents in children aged 0-18 years, published from January 1976 to December 2012 in the PubMed database. RESULTS: In children with cancer treated with chemotherapeutic drugs (especially platinum compounds, methotrexate, L-asparaginase), HSRs commonly present with mild/moderate to severe clinical patterns. Multiple factors appear to affect reaction rates, including route, rate of administration, previous exposure, drug form, presence of excipients. The occurrence of hypersensitivity to a chemotherapeutic agent can include the avoidance of re-exposure. For sensitized patients who have derived clinically meaningful benefit from a particular agent, however, continuation of treatment with the agent is desirable. Options may include attempting a trial of desensitization or treatment with a related compound. CONCLUSIONS: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions to antineoplastic drugs are commonly encountered. Clinicians must not underestimate the potential risk and occurrence of HSRs in the pediatric population. Knowledge of the different presentations of these reactions can help to develop strategies for the prevention and the management of HSRs in order to ensure treatment outcome, to improve the quality of patient care and to reduce healthcare costs.

Azole interactions with multidrug therapy in pediatric oncology.

Patients with cancer receive multidrug therapy. Antineoplastic agents and supportive care drugs are often administered together, leading to potential drug-drug interactions. These interactions may have significant clinical implications in terms of toxicity or a decrease in the efficacy of the treatment administered. Here, we focus on the role of azoles and their main pharmacokinetic interactions with the principal classes of drugs used in pediatric oncology. The co-administration of azoles and antineoplastic agents, corticosteroids, immunosuppressants, antacids, antiemetics, antiepileptic drugs and analgesics was investigated, and a practical guide on the management of these drugs when administered together is provided.

Efficacy and safety of transdermal buprenorphine in the management of children with cancer-related pain.

BACKGROUND: The current study investigated the efficacy, safety, tolerability, and compliance of a transdermal buprenorphine delivery system for the management of chronic cancer pain in the pediatric population. PROCEDURE: Sixteen pediatric patients with moderate to severe cancer-related pain not satisfactorily controlled with previous non-opioid therapies were enrolled. Transdermal buprenorphine was administered following a 72 hour schedule and rescue medication (tramadol) was allowed for breakthrough pain. Pain intensity was assessed using the Wong-Baker faces pain rating scale (WBS) and other parameters related to the global quality of life were evaluated. Children's evaluations of efficacy, compliance, and tolerability were recorded using numerical scales. Adverse events were monitored during the study and the medications needed to control opioid-related nausea and constipation were recorded. RESULTS: Eleven patients (68.75%) responded to transdermal buprenorphine after 2 weeks of treatment. Pain intensity measured with WBS decreased from 6.25 at baseline to 1.38 at Day +60 (P < 0.001). All outcome measures of global quality of life (quality of sleep, alimentation, play and activity, speech, and crying) significantly improved over the 60-day study period. Children's evaluations of compliance and tolerability of the drug were always positive over the entire period of treatment. No severe adverse events were recorded. Opioid-related nausea was well controlled with medication on request, and the need for laxative therapy was greater at the end of the second month of treatment. CONCLUSIONS: Transdermal buprenorphine was found to represent an efficient, safe and well tolerated approach to the management of children's chronic cancer pain.

How to manage vaccinations in children with cancer.

The optimal use of routine childhood immunizations in children with malignancy is still a matter of debate. Despite their higher risk of contracting vaccine preventable diseases and of suffering important complications, there is little understanding of the magnitude of the possible benefit of administering active immunization in this population due to a paucity of clinical trial data. Our review focuses on the management of children with cancer and offers some suggestions regarding their vaccination schedules.