Bird's-eye view of GnRH analog use in a pediatric endocrinology referral center

OBJECTIVE: Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. METHODS: We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. RESULTS: A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). CONCLUSION: Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP

Prioritising neonatal medicines research: UK Medicines for Children Research Network scoping survey

BACKGROUND: The dosing regimen and indications for many medicines in current use in neonatology are not well defined. There is a need to prioritise research in this area, but currently there is little information about which drugs are used in UK neonatal units and the research needs in this area as perceived by UK neonatologists. METHODS: The Neonatal Clinical Studies Group (CSG) of the Medicines for Children Research Network (MCRN) undertook a 2 week prospective scoping survey study to establish which medicines are used in UK neonatal units; how many babies are receiving them; and what clinicians (and other health professionals) believe are important issues for future research. RESULTS: 49 out of 116 units responded to at least one element of the survey (42%). 37 units reported the number of neonates who received medicines over a 2 week period. A total of 3924 medicine-patient pairs were reported with 119 different medicines. 70% of medicine-patient pairs involved medicines that were missing either a license or dose for either term or preterm neonates. 4.3% of medicine-patient pairs involved medicines that were missing both license and dose for any neonate. The most common therapeutic gap in need of additional research identified by UK neonatologists was chronic lung disease (21 responding units), followed by patent ductus arteriosus and vitamin supplements (11 responding units for both) CONCLUSION: The research agenda for neonatal medicines can be informed by knowledge of current medicine use and the collective views of the neonatal community

Use of Continuous Renal Replacement Therapy for Removal of Dabigatran in a Patient in Need of Emergent Surgery

Purpose. To report the ability to remove serum dabigatran using continuous renal replacement therapy (CRRT) in a patient with life-threatening bleeding. Summary. A 77-year-old female with history of atrial fibrillation who takes dabigatran for stroke prevention presented with abdominal pain. Patient was found to have bleeding and possible mesenteric ischemia and was taken to the operating room and had continued bleeding postoperatively. CRRT was initiated for the removal of any remaining dabigatran, with serum dabigatran levels collected to evaluate removal of dabigatran with CRRT. This patient had an increased dabigatran level prior to intervention, which decreased to an undetectable level after use of CRRT. Greater than 80% of the drug was removed due to 4 hours of CRRT and residual kidney function. Reversal of dabigatran is an area of current research with recent FDA approval of idarucizumab for use. Conclusion. Bleeding may occur as a result of the use of dabigatran and change in patient’s clinical condition. Use of CRRT may be an option in removing serum dabigatran in the case of a life-threatening bleed

Use of Continuous Renal Replacement Therapy for Removal of Dabigatran in a Patient in Need of Emergent Surgery

Purpose. To report the ability to remove serum dabigatran using continuous renal replacement therapy (CRRT) in a patient with life-threatening bleeding. Summary. A 77-year-old female with history of atrial fibrillation who takes dabigatran for stroke prevention presented with abdominal pain. Patient was found to have bleeding and possible mesenteric ischemia and was taken to the operating room and had continued bleeding postoperatively. CRRT was initiated for the removal of any remaining dabigatran, with serum dabigatran levels collected to evaluate removal of dabigatran with CRRT. This patient had an increased dabigatran level prior to intervention, which decreased to an undetectable level after use of CRRT. Greater than 80% of the drug was removed due to 4 hours of CRRT and residual kidney function. Reversal of dabigatran is an area of current research with recent FDA approval of idarucizumab for use. Conclusion. Bleeding may occur as a result of the use of dabigatran and change in patient’s clinical condition. Use of CRRT may be an option in removing serum dabigatran in the case of a life-threatening bleed

Northern Bobwhite Habitat Use in a Forest-Dominated System (Poster Abstract)

Changes in land use that reduce habitat availability and quality for northern bobwhites (Colinus virginianus) are thought to be the major cause of bobwhite population decline in the Southeast. Increased conversion of open habitats to densely stocked pine plantations has contributed to habitat loss. We examined bobwhite habitat use in the Upper Coastal Plain of Georgia, a landscape dominated by forests and agriculture. The purposes of this study were to monitor habitat selection by bobwhites in this forest and agriculture system and to determine what role pine plantations, including those established as a conservation practice of the Conservation Reserve Program, have within bobwhite’s selection of habitat types. To date little research has been conducted to determine bobwhite habitat selection within this forest and agriculture dominated system. Many bobwhite research studies have been undertaken on intensively managed lands in the southeastern United States. Many landowners and land managers may not have the resources necessary to manage their lands exclusively for bobwhites. This study was conducted on lands where landowners had multiple objectives in mind, such as agriculture, timber, and wildlife. We determined home range sizes and habitat selection of 55 radiomarked bobwhites during 1997–2000. Selection of habitats by radiomarked bobwhites supported our hypotheses that they would prefer early-successional habitats within the forest-dominated study area. Selected habitats included fallow fields and open-canopy planted pines whereas agricultural areas and closed-canopy planted pines were avoided. Thinning to create open-canopy planted pine stands will benefit bobwhites by providing additional early successional habitat. Bobwhites selected open canopy planted pine and fallow field habitats in preference to closed-canopy planted pine and agricultural areas. Our results suggest that managing fallow fields and open canopy planted pine habitat for bobwhites will provide preferred habitat within this landscape and is feasible for the average landowner

Insights from genetic studies of cerebral palsy

Cohort-based whole exome and whole genome sequencing and copy number variant (CNV) studies have identified genetic etiologies for a sizable proportion of patients with cerebral palsy (CP). These findings indicate that genetic mutations collectively comprise an important cause of CP. We review findings in CP genomics and propose criteria for CP-associated genes at the level of gene discovery, research study, and clinical application. We review the published literature and report 18 genes and 5 CNVs from genomics studies with strong evidence of for the pathophysiology of CP. CP-associated genes often disrupt early brain developmental programming or predispose individuals to known environmental risk factors. We discuss the overlap of CP-associated genes with other neurodevelopmental disorders and related movement disorders. We revisit diagnostic criteria for CP and discuss how identification of genetic etiologies does not preclude CP as an appropriate diagnosis. The identification of genetic etiologies improves our understanding of the neurobiology of CP, providing opportunities to study CP pathogenesis and develop mechanism-based interventions

Lifestyle and personal wellness in particle physics research activities

Finding a balance between professional responsibilities and personal priorities is a great challenge of contemporary life and particularly within the HEPAC community. Failure to achieve a proper balance often leads to different degrees of mental and physical issues and affects work performance. In this paper, we discuss some of the main causes that lead to the imbalance between work and personal life in our academic field. We present some recommendations in order to establish mechanisms to create a healthier and more equitable work environment, for the different members of our community at the different levels of their careers

Physiotherapy for adults with joint hypermobility syndrome: A pilot randomised controlled trial

Background: Joint Hypermobility Syndrome (JHS) is a heritable disorder associated with laxity and pain in multiple joints. Physiotherapy is the mainstay of treatment but there is little research investigating its effectiveness. The aim of this study was therefore to conduct a pilot randomised controlled trial (RCT) to determine the feasibility of conducting a future definitive RCT. Methods: A comprehensive physiotherapy intervention was developed in conjunction with patients and healthcare professionals. It was then piloted and refined on the basis of patient and physiotherapist feedback. A parallel two-arm pilot RCT in two UK secondary care NHS Trusts compared 'Advice' against 'Advice & Physiotherapy'. Inclusion criteria were: >16 years, a diagnosis of JHS, and no other musculoskeletal conditions causing pain. The Advice intervention was a one-off session, supplemented by advice booklets from the Hypermobility Syndromes Association and Arthritis Research UK. All patients could ask questions specific to their circumstances and received tailored advice. Participants were then randomly allocated to 'Advice' (no further advice or physiotherapy) or 'Advice & Physiotherapy' (an additional six 30 minute sessions over 4 months). The Physiotherapy intervention was supported by a patient handbook and delivered on a one-to-one patient-therapist basis. It aimed to increase patients’ physical activity through developing knowledge, understanding and skills to better manage their condition. The primary outcome related to the feasibility of conducting a future definitive RCT. Qualitative interviews with patients and physiotherapists therefore formed a major component of data collection. Secondary outcomes included clinical measures (physical function, pain, global status, self-reported joint count, quality of life, exercise self-efficacy and adverse events); resource use (to estimate cost-effectiveness); and an estimate of the value of information from a future RCT. Outcomes were recorded at baseline, 4 months (at the end of physiotherapy) and 7 months (3 months following physiotherapy). Results: A total of n=29 participants were recruited to the pilot RCT. Recruitment was challenging, primarily due to a perceived lack of equipoise between Advice and Physiotherapy. The qualitative evaluation provided very clear guidance to inform a future RCT, including enhancement of the Advice intervention. Some patients reported that the Advice intervention was useful and the Physiotherapy intervention was evaluated very positively. The rate of return of questionnaires was low within the Advice group but reasonable in the Physiotherapy group. The Physiotherapy intervention showed evidence of promise in terms of primary and secondary clinical outcomes. The Advice arm experienced more adverse events. The value of information estimate indicated the potential for high value from a future RCT. Conclusion: A future definitive RCT of physiotherapy for JHS seems feasible, although the Advice intervention should be made more robust to address perceived equipoise and subsequent attrition

Complexity of multi-dimensional spontaneous EEG decreases during propofol induced general anaesthesia

Emerging neural theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, causal interactions between brain regions are both integrated (all regions are to a certain extent connected) and differentiated (there is inhomogeneity and variety in the interactions). In support of this, recent work by Casali et al (2013) has shown that Lempel-Ziv complexity correlates strongly with conscious level, when computed on the EEG response to transcranial magnetic stimulation. Here we investigated complexity of spontaneous high-density EEG data during propofol-induced general anaesthesia. We consider three distinct measures: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability in the constitution of the set of active channels; and (iii) the novel synchrony coalition entropy (SCE), which measures the variability in the constitution of the set of synchronous channels. After some simulations on Kuramoto oscillator models which demonstrate that these measures capture distinct ‘flavours’ of complexity, we show that there is a robustly measurable decrease in the complexity of spontaneous EEG during general anaesthesia