Antipsychotic Overdosing and Polypharmacy in Schizophrenic Delinquents Explored.

A logistic regression model for 289 cases of schizophrenic offenders in a Swiss forensic hospital between 1995 and 2016 revealed the following factors for above average levels of antipsychotic overdosing and polypharmacy: Odds for overdosing increased in absence of a personality disorder (237%), for each point increase in emotional withdrawal (63.5%) and motor retardation (71.7%), and decreased for poor rapport (42.3%) recorded at admission. Odds for polypharmacy increased with complaints about physicians (157%), for each point increase in IQ (3.6%; range = 65-131, M = 92, SD = 14), reduction of the security level of the ward (36.8%; four levels), and for each point increase in poor attention (27.6%) at admission. It decreased with each previous conviction (10.9%; range = 1-21, M = 3, SD = 2), breaking of rules (46.4%) and the administration of compulsory measures (55.7%) on the ward, a poor legal prognosis (29.4%, four levels), and each point increase in grandiosity (40.3%), passive social withdrawal (42.3%), and depressive symptoms (38.7%) at admission.

Feasibility of enhancing well-child visits with family nutrition and physical activity risk assessment on body mass index.

OBJECTIVE: Integration of behavioural risk assessment into well-child visits is recommended by clinical guidelines, but its feasibility and impact is unknown. METHODS: A quasi-experimental study evaluated the feasibility and effectiveness of risk assessment on body mass index (BMI) at 1-year follow-up. Children with assessments (intervention) were compared with those who did not complete assessments (non-respondent) and those who received standard care (non-exposed). RESULTS: Analyses included 10,647 children aged 2-9 years (2,724 intervention, 3,324 non-respondent and 4,599 non-exposed). Forty-five per cent of parents completed the assessments. Intervention and non-respondent groups differed in change in BMI z-score at 1 year by -0.05 (confidence interval [CI]: -0.08, -0.02; P = 0.0013); no difference was observed with non-exposed children. The intervention group had a smaller increase in BMI z-score (0.07 ± 0.63) than non-respondent group (0.13 ± 0.63). For children with normal weight at baseline, intervention versus non-respondent groups differed in BMI z-score change by -0.06 (CI: -0.10, -0.02; P = 0.0025). However, children with overweight at baseline in the intervention versus the non-exposed group differed in BMI z-score change (0.07 [CI: 0.02, 0.14]; P = 0.016). When analysed by age, results were similar for 2- to 5-year-olds, but no differences were found for 6- to 9-year-olds. CONCLUSION: Automating risk assessment in paediatric care is feasible and effective in promoting healthy weight among preschool but not older children.

Latent class analysis identified phenotypes in individuals with schizophrenia spectrum disorder who engage in aggressive behaviour towards others.

Prior research on Hodgins' (2008) typology of offenders with schizophrenia spectrum disorders (SSD) has revealed inconsistencies in the number of subgroups and the operationalization of the concept. This study addressed these inconsistencies by applying latent class analysis (LCA) based on the most frequently explored variables in prior research. This novel case-centred methodology identified similarities and differences between the subjects contained in the sample instead of the variables explored. The LCA was performed on 71 variables taken from data on a previously unstudied sample of 370 case histories of offenders with SSD in a centre for inpatient forensic therapies in Switzerland. Results were compared with Hodgins' theoretically postulated patient typologies and confirm three separate homogeneous classes of schizophrenic delinquents. Previous inconsistencies and differences in operationalizations of the typology of offenders with SDD to be found in the literature are discussed.

Ethical considerations in the application of cell and gene therapies in children.

Rapidly evolving fields such as cell and gene therapies that involve state-of-the-art technology hold out possibilities that may be ahead of what ethics, guidelines and the law have considered. This results in a regulatory lag. Furthermore, ethical and legal considerations are often debated in real time as issues pertaining to these technologies that were previously not considered begin to come to the fore. Finding the appropriate balance between facilitating potential therapeutic gains and ensuring the safety interests of recipients of the new treatments requires close attention, especially for minors. This vulnerable population frequently has off-label treatment prescribed on the basis of extrapolation of clinical trial data derived from adults, which is ethically and scientifically questionable. In this article we discuss how best to maintain ethical integrity while introducing innovative cell and gene therapies to minors. We advocate that clinical trials of promising innovative therapies should be designed so that testing in adults is followed as soon as possible by testing in minors, given the impressive gains that have recently been reported.

Diagnosing diffuse lung disease in children in a middle-income country: the role of open lung biopsy.

SETTING: A tertiary care hospital situated in a middle-income country with a high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine the diagnostic yield of open lung biopsy (OLB) in children with diffuse lung disease (DLD), comparing findings in HIV-infected and non-HIV-infected children. DESIGN: This 9-year retrospective study included 51 children with DLD (oxygen-dependent or on artificial ventilation), who required an OLB where the diagnosis remained uncertain after extensive investigations. RESULTS: The median age was 7 months, median body weight was 6.6 kg (61% were severely malnourished) and 30% were HIV-infected (62% on antiretroviral treatment). The diagnostic yield of the OLB was 86% (n = 44) and was significantly higher in HIV-infected (77%) than in non-HIV-infected (48%) children (P = 0.01). Pneumonia was the most common diagnosis (n = 25, 57%), with common agents being cytomegalovirus (CMV), viruses other than CMV, Pneumocystis jiroveci pneumonia and previously undiagnosed TB (10%). Mycobacterium tuberculosis as a cause of DLD was not suspected before the OLB, as all investigations for TB were negative. Non-infectious causes of DLD were established in 10% of cases. CONCLUSION: The OLB is a useful diagnostic tool to diagnose idiopathic DLD, including TB, in young children.

Guideline for the management of acute asthma in children: 2013 update.

BACKGROUND: Acute asthma exacerbations remain a common cause of hospitalisation and healthcare utilisation in South African children. AIM: To update the South African paediatric acute asthma guidelines according to current evidence, and produce separate recommendations for children above and below 2 years of age. METHODS: A working group of the South African Childhood Asthma Group was established to review the published literature on acute asthma in children from 2000 to 2012, and to revise the South African guidelines accordingly. RECOMMENDATIONS: Short-acting inhaled bronchodilators remain the first-line treatment of acute asthma. A metered-dose inhaler with spacer is preferable to nebulisation for bronchodilator therapy to treat mild to moderate asthma. Two to four puffs of a short-acting bronchodilator given every 20 - 30 minutes, depending on clinical response, should be given for mild attacks; up to 10 puffs may be needed for more severe asthma. Children with severe asthma or oxygen saturation (SpO2) <92% should receive oxygen and frequent doses of nebulised beta-2-agonists, and be referred to hospital. Nebulised ipratropium bromide (via nebulisation or multidosing via pMDI-spacer combination) should be added if there is a poor response to three doses of ß2-agonist or if the symptoms are severe. Early use of corticosteroids reduces the need for hospital admission and prevents relapse; oral therapy is preferable. Assessment of acute asthma in children below the age of 2 years can be difficult, and other causes of wheezing must be excluded. Treatment of acute asthma in this age group is similar to that of older children. CONCLUSION: Effective therapy for treatment of acute asthma - primarily inhaled short-acting ß2-agonists, oral corticosteroids and oxygen with appropriate delivery systems - should be available in all healthcare facilities and rapidly instituted for treatment of acute asthma in children. ENDORSEMENT: The guideline document was endorsed by the Allergy Society of South Africa (ALLSA), the South African Thoracic Society (SATS), the National Asthma Education Programme (NAEP), the South African Paediatric Association (SAPA) and the South African Academy of Family Practice.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Tracheostomy home care: in a resource-limited setting.

INTRODUCTION: Home tracheostomy care for children in South Africa dates back to 1989. OBJECTIVE: This study aimed to describe the tracheostomy home programme at Tygerberg Children's Hospital (TCH), situated in a resource-limited setting in Cape Town, South Africa. DESIGN: Retrospective descriptive study. SETTING: Tracheostomy home programme at TCH. The primary care giver is trained by nurses. RESULTS: Fifty-six children (29 girls) were discharged to the home programme (47 to home and 9 to institutions). The median age at tracheostomy was 3 months, mainly for airway obstruction. The mean duration of home care was 26.6 months. Twenty-seven children (43%) were successfully decannulated. Seven children lived in informal housing. The 56 children generated 745 social work contacts. The overall survival was 82%. CONCLUSION: Children with tracheostomies can be safely cared for at home, even in a resource-constrained environment, provided training, appropriate technology and social support services are available.

The diagnostic value and safety of transbronchial needle aspiration biopsy in children with mediastinal lymphadenopathy.

INTRODUCTION: Anterior mediastinal masses in children can have different causes which includes, Mycobacterium tuberculosis (MTB) or malignant lymphadenopathy. Transbronchial needle aspiration (TBNA) has been described as a safe and effective diagnostic procedure in adult patients with lung cancer. AIM: To describe the use of TBNA as a diagnostic test in children with large subcarinal lymphadenopathy and to determine the safety of the procedure in children. PATIENTS AND METHODS: Prospective descriptive study of children with subcarinal mediastinal lymph nodes who underwent TBNA. The majority of the children were referred due to treatment failure. Children were enrolled if the diagnosis remained unclear after computer tomography of the chest. RESULTS: Thirty patients were enrolled in this study; TBNA was done in 28 patients. A definitive diagnosis was made by TBNA in 54% (n = 15) of patients; MTB lymphadenopathy (n = 13), metastatic nephroblastoma (n = 1), and fibrosing mediastinitis (n = 1). In seven (25%) cases the TBNA was the sole source of the specimens from which the definitive diagnosis was made. No serious complications were encountered during or after the procedure. CONCLUSION: TBNA is a safe procedure in children with mediastinal lymphadenopathy of unknown cause resulting in a definitive diagnosis in 57% of cases. TBNA adds additional value to flexible bronchoscopy in the diagnosis of mediastinal lymphadenopathy in children.

CMV pneumonia in HIV-infected ventilated infants.

BACKGROUND: The contributing role of cytomegalovirus (CMV) in infants treated for Pneumocystis jiroveci pneumonia (PJP) is unknown. High dose steroids used in the treatment of PJP may further immunocompromise these infants contributing to the development of CMV pneumonia. AIM: The aim of this study was to determine the role of CMV pneumonia in infants being ventilated for suspected PJP. METHODS: In this prospective study HIV infected infants being treated with trimethoprim-sulfamethoxazole (TMP/SMX) and ventilated for suspected PJP were included if they had not responded to treatment. Open lung biopsy was performed if there was no improvement in ventilatory requirements. RESULTS: Twenty-five HIV positive infants with a mean age of 3.3 months were included. Lung biopsy was performed in 17 (68%) and post-mortem lung tissue was obtained in 8 (32%). After evaluation of the histology, immunohistochemistry, and viral cultures from lung tissue, the most likely causes of pneumonia were: CMV and PJP dual infection 36% (n = 9), CMV pneumonia 36% (n = 9), and PJP 24% (n = 6). The pp65 test for CMV antigen was falsely negative in 24%. The mean blood CD4 count was 287/microl. There was an association between the CD4 lymphocyte status and the final diagnosis, with the CMV and PJP group (CD4 110/microl) having the lowest CD4 status (P = 0.0128). Pediatric Intensive Care Unit (PICU) mortality was 72% (n = 18) and in hospital mortality 88%. CONCLUSION: Of the ventilated infants failing to respond to treatment, 72% had histologically confirmed CMV pneumonia, probably accounting for the high mortality in this cohort. The incidence of CMV disease in HIV infected infants being ventilated for severe pneumonia warrants that ganciclovir is used empirically until CMV disease is excluded. The role of lung biopsy in these circumstances needs to be researched.

Phrenic nerve palsy in children associated with confirmed intrathoracic tuberculosis: diagnosis and clinical course.

In this descriptive retrospective cases series of eight cases phrenic nerve palsy in children caused by tuberculosis lymph gland infiltration of the phrenic nerve. The lymph gland enlargement was in all cases caused by culture confirmed Mycobacterium tuberculosis. The phrenic nerve palsy was on the left side in all eight cases with the presenting feature a raised diaphragm on chest radiography that was accompanied by consolidation of the left upper lobe (88%) The diagnosis of phrenic nerve palsy was confirmed by fluoroscopy of the chest. On computer tomography the outstanding features were left sided hilar and paratracheal lymph gland enlargement with displacement of the mediastinum to the right. Mediastinal displacement lead to anterior displacement of the descending aorta, which further compressed the left main bronchus. Two children had accompanying respiratory failure requiring assisted ventilation and in two additional cases the airway compression was so severe that glandular enucleation of the enlarged glands was indicated. Of the eight children five remained symptomatic after completion of TB treatment to which steroids were added for the initial month. Diaphragmatic plication was indicated in all five cases. On clinical follow-up two children had repeated respiratory tract infections secondary to underlying lung damage while the other six remained asymptomatic.

Fibrin glue closure of persistent bronchopleural fistula following pneumonectomy for post-tuberculosis bronchiectasis.

We report a case of a persistent bronchopleural fistula following a pneumonectomy for post-tuberculosis bronchiectasis. The patient had two unsuccessful surgical attempts at closing of the fistula. Further surgical attempts were technically were not possible. Bronchoscopic closure was achieved by injecting human fibrin glue into the fistula via a catheter. Closure of the broncho-pleural fistula was confirmed by repeated ventilation scan over a period of 2 months. Endoscopic closure of small bronchopleural fistulae is an attractive option in children with significant underlying lung disease.

The outcome of infants younger than 6 months requiring ventilation for pneumonia caused by Mycobacterium tuberculosis.

INTRODUCTION: The outcome of young infants (<6 months) being ventilated for respiratory failure caused by Mycobacterium tuberculosis (MTB) has not been recorded. PATIENTS AND METHODS: A descriptive study of children <6 months admitted to the PICU from 1 February 1999 to 31 December 2005 with MTB causing respiratory failure. RESULTS: Seventeen infants were ventilated for respiratory failure caused by MTB: ten had ventilatory respiratory failure and seven had hypoxic failure. An index case was found in 47%. All chest radiographs (CXRs) were highly suggestive of tuberculosis. MTB was cultured in 15 cases. In the other two cases MTB was confirmed by histopathology. The median duration of ventilation was 6 days (range: 1-35 days) with a median PaO2/FiO2 of 85 and ventilatory index of 58. Transthoracic glandular enucleation was required to facilitate extubation in six babies. All the infants survived. At 6-month follow-up 35% had a normal CXR and all were asymptomatic. One child had CXR changes suggestive of bronchiectasis but was asymptomatic. CONCLUSION: The outcome of infants <6 months ventilated for respiratory failure caused by MTB is very good if TB is recognized timeously and appropriate management started. The diagnosis of TB in these infants can be made with a high index of suspicion and careful evaluation of the CXR.

Esophageal stent improves ventilation in a child with a broncho-esophageal fistula caused by Mycobacterium tuberculosis.

The deployment of an esophageal stent to aid in the ventilation of a child who had developed an acquired broncho-esophageal fistula caused by Mycobacterium tuberculosis (MTB) is described. The 12-month-old boy presented with respiratory failure requiring ventilation. The air leak via the fistula led to inadequate mechanical ventilation. The deployment of the stent resulted in successful ventilation, closure of the fistula, and eventual successful treatment.

Pasteurella multocida lung and liver abscess in an immune-competent child.

We report on a 20-month-old infant with a complicated lung and liver abscess caused by Pasteurella multocida after the child had been in close contact with a domestic cat. Surgical drainage confirmed lung and liver abscesses connected to each other, with involvement of the diaphragm.

Persistence of rhinovirus RNA after asthma exacerbation in children.

BACKGROUND: Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus-host interactions is also not clear. OBJECTIVE: We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF). METHODS: Patients aged 4-12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months. RESULTS: Fifty children with acute asthma (mean age+/-SD, 7.4+/-2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4+/-16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER. CONCLUSION: RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.

Expansile pneumonia in children caused by Mycobacterium tuberculosis: clinical, radiological, and bronchoscopic appearances.

A cohort of 24 children with expansile pneumonia caused by Mycobacterium tuberculosis is described in mostly HIV-noninfected children (n = 22). The children presented with nonresolving pneumonia and a swinging fever (83%). On chest radiography, they had dense opacification with bulging fissures mainly in the upper lobes (75%). On computed tomography, the lobes are consolidated, with areas of liquefacation. Other features visible are enlarged mediastinal lymph adenopathy with ring enhancement (100%), cavities (63%), and tracheal compression (71%). On bronchoscopy, bronchi were obstructed by more than 75% in 20 (83%) of cases. Lymph gland enucleation was required in 42% of cases. Phrenic nerve palsy was present in 3 children, of whom 2 underwent diaphragmatic plication. The children received standard antituberculous therapy, to which prednisone (2 mg/kg/day) was added for 1 month. The mortality was 4% after 6 months of therapy.

Polymorphisms in the 5'-UTR of the tissue factor gene are associated with altered expression in human endothelial cells.

BACKGROUND: Enhanced tissue factor (TF) expression mediates many disease processes. Recently, four completely concordant polymorphisms were detected in the 5'-UTR of the TF gene. Three were single base changes and one was an 18-bp insertion/deletion at -1208. OBJECTIVES: This study was undertaken to determine if the I-allele or the D-allele would associate with elevated TF expression in human umbilical vein endothelial cells (HUVEC). METHODS: HUVEC were genotyped by polymerase chain reaction for 18-bp insert status. TF expression was induced by interleukin (IL)-1 or phorbol 12-myristate 13-acetate (PMA). Total TF activity was determined by a one-stage clotting assay and surface TF activity by a chromogenic assay. Protein binding differences between the I- and D-alleles were examined by gel shift assays. RESULTS: IL-1- or PMA-induced total TF activity in D-allele HUVEC was increased 2.0-2.5-fold above that seen in II HUVEC. Surface clotting activity in D-allele cells was 1.3-1.7-fold greater than in II-allele cultures. Experiments with consensus site mutation oligos suggested that the 18-bp insert creates GATA and CCAAT-enhancer binding protein (C/EBP) transcription factor recognition sites. CONCLUSIONS: The D-allele is associated with enhanced TF activity in HUVEC. The differences in TF expression between the alleles may be due to variant transcription factor binding in the -1208 region. Further studies are warranted to investigate whether the D-allele is associated with increased incidence of pathological processes that involve TF.