Cetuximab,bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial

The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard treatment (radiotherapy and temozolomide). Bevacizumab and irinotecan were administered IV every 2 weeks. The first 10 patients received bevacizumab 5 mg/kg, but this was increased to 10 mg/kg after interim safety analysis. Irinotecan dose was based on whether patients were taking enzyme-inducing antiepileptic drugs or not: 340 and 125 mg/m², respectively. Cetuximab 400 mg/m² as loading dose followed by 250 mg/m² weekly was administered IV. Forty-three patients were enrolled in the trial, of which 32 were available for response. Radiographic responses were noted in 34%, of which 2 patients had complete responses and 9 patients had partial responses. The 6-month progression-free survival probability was 30% and median overall survival was 29 weeks (95% CI: 23–37 weeks). One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity, for which 1 patient needed plastic surgery. One patient was excluded due to suspicion of interstitial lung disease. Three patients had deep-vein thrombosis; all continued on study after adequate treatment. Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except for skin toxicity, with an encouraging response rate. However, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone.     

Allergy and Sensitization during Childhood Associated with Prenatal and Lactational Exposure to Marine Pollutants

Background

Breast-feeding may affect the risk of developing allergy during childhood and may also cause exposure to immunotoxicants, such as polychlorinated biphenyls (PCBs), which are of concern as marine pollutants in the Faroe Islands and the Arctic region.

Objectives

The objective was to assess whether sensitization and development of allergic disease is associated with duration of breast-feeding and prenatal or postnatal exposures to PCBs and methylmercury.

Methods

A cohort of 656 singleton births was formed in the Faroe Islands during 1999–2001. Duration of breast-feeding and history of asthma and atopic dermatitis were recorded at clinical examinations at 5 and 7 years of age. PCB and mercury concentrations were determined in blood samples obtained at parturition and at follow-up. Serum from 464 children (71%) at 7 years of age was analyzed for total immunoglobulin E (IgE) and grass-specific IgE.

Results

The total IgE concentration in serum at 7 years of age was positively associated both with the concomitant serum PCB concentration and with the duration of breast-feeding. However, the effect only of the latter was substantially attenuated in a multivariate analysis. A raised grass-specific IgE concentration compatible with sensitization was positively associated with the duration of breast-feeding and inversely associated with prenatal methylmercury exposure. However, a history of asthma or atopic dermatitis was not associated with the duration of breast-feeding, although children with atopic dermatitis had lower prenatal PCB exposures than did nonallergic children.

Conclusions

These findings suggest that developmental exposure to immunotoxicants may both increase and decrease the risk of allergic disease and that associations between breast-feeding and subsequent allergic disease in children may, at least in part, reflect lactational exposure to immunotoxic food contaminants.     

EVOLVE: The Australian Rheumatology Association’s ‘top five’ list of investigations and interventions doctors and patients should question

Background

The EVOLVE (evaluating evidence, enhancing efficiencies) initiative aims to drive safer, higher‐quality patient care through identifying and reducing low‐value practices.

Aims

To determine the Australian Rheumatology Association’s (ARA) ‘top five’ list of low‐value practices.

Methods

A working group comprising 19 rheumatologists and three trainees compiled a preliminary list. Items were retained if there was strong evidence of low value and there was high or increasing clinical use and/or increasing cost. All ARA members (356 rheumatologists and 72 trainees) were invited to indicate their ‘top five’ list from a list of 12‐items through SurveyMonkey in December 2015 (reminder February 2016).

Results

A total of 179 rheumatologists (50.3%) and 19 trainees (26.4%) responded. The top five list (percentage of rheumatologists, including item in their top five list) was: Do not perform arthroscopy with lavage and/or debridement for symptomatic osteoarthritis of the knee nor partial meniscectomy for a degenerate meniscal tear (73.2%); Do not order anti‐nuclear antibody (ANA) testing without symptoms and/or signs suggestive of a systemic rheumatic disease (56.4%); Do not undertake imaging for low back pain for patients without indications of an underlying serious condition (50.8%); Do not use ultrasound guidance to perform injections into the subacromial space as it provides no additional benefit in comparison to landmark‐guided injection (50.3%) and Do not order anti‐double‐stranded DNA antibodies in ANA negative patients unless the clinical suspicion of systemic lupus erythematosus remains high (45.3%).

Conclusions

This list is intended to increase awareness among rheumatologists, other clinicians and patients about commonly used low‐value practices that should be questioned.     

Measures of Parent Engagement for Children Receiving Developmental or Rehabilitation Interventions: A Systematic Review

Aim: To examine the conceptual and clinometric properties of measures for parent engagement in developmental or rehabilitation interventions for children and youth (<18 years of age). Methods: Four electronic databases were searched. Studies were included if they reported measures of at least one domain of parent engagement (i.e. affective, cognitive or behavioral). Reviewers independently identified measures and evaluated studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and the CanChild Outcome Measures Rating Form. Results: A total of 9,500 unique papers were retrieved, and 36 reported parent engagement measurement. Four measures met inclusion criteria: the Parent Involvement Index (PII), the Parent Participation Measure (PPM), the General Adherence subscale of the Medical Outcomes Study (GAMOS) and the Triadic Intervention and Evaluation Rating Scale (TIERS). No measure captured all domains of in-session parent engagement. Two addressed out-of-session parent engagement. There were limitations in validity and reliability. Conclusions: Few measures of parent engagement are available. Existing measures mostly captured the behavioral domain of in-session engagement, and none assessed cognitive or affective aspects of engagement. Out-of-session engagement was infrequently captured. There is currently no comprehensive measure of parent engagement in pediatric developmental and rehabilitation services that demonstrates good clinical utility or is conceptually and psychometrically sound.     

Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

Background

Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis.

Methods

Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO₂) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O₂ and CO₂. Pigs were monitored for 60 min at baseline and 240 min after LPS/NaCl injection.

Results

After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p = 0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO₂ or ICP was registered. No changes in physiological variables were observed.

Conclusions

The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO₂, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.

     

Quality of paediatric blood transfusions in two district hospitals in Tanzania: a cross-sectional hospital based study

Background  

Blood transfusion (BT) can be lifesaving for children; however, monitoring the quality of BT is important. The current study describes the quality of paediatric BT delivered in two district hospitals in north-east Tanzania in order to identify areas for quality assurance and improvement in the administration of BT.