The Self-Inflicted Burns - Typology and its Prognostic Relevance in a 14-Year Review of Self-Inflicted Burns in a Tertiary Referral Centre

Self-inflicted burns (SIB) are responsible for 2-6% of admissions to Burn Units in Europe and North America, and for as many as 25% of admissions in developing nations. Recently, a promising new tool was proposed to stratify SIB patients in the following subgroups: "typical", "delirious", and "reactive". However, as far as the authors know, the clinical usefulness of this instrument has not yet been validated by others. We retrospectively reviewed the clinical records of 56 patients admitted to our Burn Unit with the diagnosis of SIB injury in the past 14 years. The following parameters were evaluated: demographic features; psychiatric illness; substance abuse; mechanism of injury; burn depth, total body surface area (TBSA) involved, Abbreviated Burn Severity Index (ABSI); length of hospital stay, and mortality. All patients were followed up by a psychologist and a psychiatrist, and were classified according to the SIB-Typology Tool, into three classes: "typical", "delirious" and "reactive". There was a slight predominance of the "typical" type (44.6%), followed by the "delirious" type (30.4%), and, finally the "reactive" type (25.0%). Mortality was significantly higher in the "typical" subgroup. In conclusion, the SIB-Typology Tool appears to be a valuable instrument in the clinical management of SIB patients.

Evidence for Nevirapine Bioactivation in Man: Searching for the First Step in the Mechanism of Nevirapine Toxicity

Despite its efficacy, including in the prevention of vertical transmission, the antiretroviral nevirapine is associated with severe idiosyncratic hepatotoxicity and skin rash. The mechanisms underlying nevirapine toxicity are not fully understood, but drug bioactivation to reactive metabolites capable of forming stable protein adducts is thought to be involved. This hypothesis is based on the paradigm that drug reactive metabolites have the potential to bind to self-proteins, which results in drug-modified proteins being perceived as foreign by the immune system. The aim of the present work was to identify hemoglobin adducts in HIV patients as biomarkers of nevirapine haptenation upon bioactivation. The ultimate goal is to develop diagnostic methods for predicting the onset of nevirapine-induced toxic reactions. All included subjects were adults on nevirapine-containing antiretroviral therapy for at least 1month. The protocol received prior approval from the Hospital Ethics Committees and patients gave their written informed consent. Nevirapine-derived adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method and characterized on the basis of retention time and mass spectrometric fragmentation pattern by comparison with adduct standards prepared synthetically. The nevirapine adducts were detected in 12/13 patient samples, and quantified in 11/12 samples (2.58±0.8 fmol/g of hemoglobin). This work represents the first evidence of nevirapine-protein adduct formation in man and confirms the ability of nevirapine to modify self-proteins, thus providing clues to the molecular mechanisms underlying nevirapine toxicity. Moreover, the possibility of assessing nevirapine-protein adduct levels has the potential to become useful for predicting the onset of nevirapine-induced adverse reactions.

Fractures in Children and Adolescents with Spina Bifida: The Experience of a Portuguese Tertiary-Care Hospital

AIM: The morbidity associated with osteoporosis and fractures in children and adolescents with spina bifida highlights the importance of osteoporosis prevention and treatment in these patients. The aim of this study was to examine the occurrence and pattern of bone fractures in paediatric patients with spina bifida. METHOD: We reviewed the data of all paediatric patients with spina bifida who were treated in our centre between 1999 and 2008. RESULTS: One hundred and thirteen patients were included in the study (63 females, 50 males; mean age 10y 8mo, SD 4y 10mo, range 6mo-18y). The motor levels were thoracic in six, upper lumbar in 22, lower lumbar in 42, and sacral in 43 patients. Of the 113 patients, 58 (51.3%) had shunted hydrocephalus. Thirty-six (31.8%) were non-ambulatory (wheelchair-dependent [unable to self-propel wheelchair] n=3, wheelchair-independent [able to self-propel wheelchair] n=33), 13 were partial ambulators, 61 were full ambulators, and three were below the age of walking. Forty-five fractures were reported in 25 patients. The distal femur was the most common fracture site. Statistical analyses showed that patients with higher levels of involvement and in wheelchairs had a significantly increased risk of having a [corrected] fracture (p<0.001). Spontaneous fractures were the principal mechanism of injury, and an association was identified between fracture mechanism, type of ambulation, and lesion level: the fractures of patients with higher levels of motor functioning and those in wheelchairs were mainly pathological (p=0.01). We identified an association between risk of a second fracture, higher motor level lesion, and non-ambulation. There was an increased risk of having a second fracture after a previous spontaneous fracture (p=0.004). INTERPRETATION: Data in this study indicate a high prevalence of fractures in patients with spina bifida.

Osteoporosis in Paediatric Patients with Spina Bifida

The prevalence andmorbidity associated with osteoporosis and fractures in patients with spina bifida (SB) highlight the importance of osteoporosis prevention and treatment in early childhood; however, the issue has received little attention. The method for the selection of appropriate patients for drug treatment has not been clarified. Objective: To review the literature concerning fracture risks and low bone density in paediatric patients with SB. We looked for studies describing state-of-the-art treatments and for prevention of secondary osteoporosis. Methods: Articles were identified through a search in the electronic database (PUBMED) supplemented with reviews of the reference lists of selected papers. The main outcome measures were incidence of fractures and risk factors for fracture, an association between bone mineral density (BMD) and occurrence of fracture, risk factors of low BMD, and effects of pharmacological and non-pharmacological treatments on BMD and on the incidence of fractures. We considered as a secondary outcome the occurrence of fractures in relation to the mechanism of injury. Results: Results indicated that patients with SB are at increased risk for fractures and low BMD. Risk factors that may predispose patients to fractures include higher levels of neurological involvement, non-ambulatory status, physical inactivity, hypercalciuria, higher body fat levels, contractures, and a previous spontaneous fracture. Limitations were observed in the number and quality of studies concerning osteoporosis prevention and treatment in paediatric patients with SB. The safety and efficiency of drugs to treat osteoporosis in adults have not been evaluated satisfactorily in children with SB.