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An editorial is presented on the mitigating the July effect. Topics include the arrival of a crop of newly graduated medical students beginning their internships, the influx of so many freshly trained physicians arriving at the same time always triggers concern, and the belief in a July effect with presumed adverse consequences for patient safety and quality of care.

Alternating Hemiplegia of Childhood (AHC) is a rare neurological disease characterized by early-onset recurrent paroxysmal events and persistent neurological deficits. TBC1D24 gene variants have been associated with a phenotypic spectrum having epilepsy as the main clinical manifestation. Herein, we report the case of a child affected by developmental delay, polymorphic seizures, and nonepileptic episodes characterized by hemiplegia or bilateral plegia, pallor, hypotonia, and dystonic postures without loss of consciousness that resolved with sleep. Noteworthy, the patient fulfills all the diagnostic criteria for AHC. An epilepsy gene panel revealed a novel TBC1D24 mutation. This variant may be considered a PM5, according to the American College of Medical Genetics and Genomics guidelines. TBC1D24 gene variants are associated with various clinical features, and increasing data confirms the association with permanent and paroxysmal movement disorders. Our report suggests that the TBC1D24 molecular analysis could be considered in the diagnostic workup of AHC patients.

Objectives Selective dorsal rhizotomy (SDR) is used to improve spasticity, gait, and pain in children with spastic diplegia. There is growing evidence supporting its long-term benefits in terms of functional outcomes, independence, and quality of life. There is, however, little contemporary work describing the surgical morbidity of this irreversible procedure. The purpose of this study is to evaluate the surgical outcomes and complications of SDR at a single United Kingdom center. Methods Demographics, surgical, postoperative, and follow-up data for all patients undergoing SDR between 2011 and 2016 were collected from medical records. Results Preoperative Gross Motor Function Classification System levels in 150 consecutive patients were II (35%), III (65%), and IV (1%). Median age was 6 years and 58% were male patients. There were no deaths, cerebrospinal fluid leaks, returns to theater, or readmissions within 30 days. There were no new motor or sphincter deficits. Postoperative neuropathic pain was reported by 5.3% and sensory symptoms by 8.7%. Other complications included: postoperative nausea and vomiting (19.3%), superficial wound infection (3.3%), urinary retention (1.3%), headache (6.7%), and urine or chest infection (4.7%). Follow-up data were available for all patients (93% to 12 months, 72% to 24 months). Persistent neuropathic symptoms were reported in 6.5% at 24 months. Conclusions SDR using a single-level approach is a safe procedure with low surgical morbidity. This study complements the growing evidence base in support of SDR for spastic diplegia and should help inform decisions when considering treatment options.

Damage to the cerebellum during posterior fossa surgery can lead to ataxia and in paediatric cases, the risk of cerebellar mutism syndrome. Animal electrophysiological and human imaging studies have shown compartmentalisation of sensorimotor and cognitive functions within the cerebellum. In the present study, electrophysiological monitoring of sensory and motor pathways was carried out to assess the location of limb sensorimotor representation within the human cerebellum, as a potential approach for real time assessment of neurophysiological integrity to reduce the incidence of cerebellar surgical morbidities.Thirteen adult and paediatric patients undergoing posterior fossa surgery were recruited. For sensory mapping (n=8), electrical stimulation was applied to the median nerves, the posterior tibial nerves, or proximal and distal limb muscles and evoked field potential responses were sought on the cerebellar surface. For motor mapping (n=5), electrical stimulation was applied to the surface of the cerebellum and evoked EMG responses were sought in facial and limb muscles.Evoked potentials on the cerebellar surface were found in two patients (25% of cases). In one patient, the evoked response was located on the surface of the right inferior posterior cerebellum in response to stimulation of the right leg. In the second patient, stimulation of the extensor digitorum muscle in the left forearm evoked a response on the surface of the left inferior posterior lobe. In the motor mapping cases no evoked EMG responses could be found.Intraoperative electrophysiological mapping, therefore, indicates it is possible to record evoked potentials on the surface of the human cerebellum in response to peripheral stimulation.

Aim A new-onset seizure clinic (NOSC) was established at our hospital in 2011, with the aim to provide accurate diagnosis and appropriate management to children with new-onset seizures or seizure mimics. Methods We report on the data analysis of the first 200 children seen in NOSC. A paediatric neurologist or paediatric/neurology trainee under supervision of a neurologist reviewed all the children. A detailed history and clinical examination were undertaken. Electroencephalogram (EEGs) were undertaken prior to clinic review in most emergency departments. Children were classified as 'epilepsy positive' (EP+) or 'epilepsy negative' (EP-) after the first consultation. Results Of 200 patients, 109 were classified as EP+: generalised epilepsy in 57 of 109, focal in 36, childhood seizure susceptibility syndrome in 26 and epileptic encephalopathy in 5. EEG was available in 192: in 117, it was abnormal - 23 with background abnormalities and 109 with epileptiform activity. Of the 109 patients, 80 were commenced on anti-epileptic drugs (AEDs): 12 were able to come off medication after seizure-free period, 61 were controlled on AEDs and 7 were refractory. Children were followed up for 12-48 months. None of the children had diagnosis revised on follow-up. Conclusions This is the first Australian study to report on a large cohort of children from a NOSC. An EEG and a paediatric neurologist assessment is a good combination to enable diagnostic accuracy: In the first 200 patients seen, there were no revisions of the initial diagnosis on follow-up.

Stroke is among the top 10 causes of death in children and survivors carry resulting disabilities for decades, at substantial cost to themselves and their families. Children are not currently able to access reperfusion therapies, due to limited evidence supporting safety and efficacy and long diagnostic delays. The Australian Clinical Consensus Guideline for the Diagnosis and Acute Management of Childhood Stroke was developed to minimize unwarranted variations in care and document best evidence on the risk factors, etiologies, and conditions mimicking stroke that differ from adults. Clinical questions were formulated to inform systematic database searches from 2007 to 2017, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grades of Recommendation, Assessment, Development, and Evaluation system (GRADE) was used to grade evidence as strong or weak. The Guideline provides more than 60 evidence-based recommendations to assist prehospital and acute care clinicians in the rapid identification of childhood stroke, choice of initial investigation, to confirm diagnosis, determine etiology, selection of the most appropriate interventions to salvage brain at risk, and prevent recurrence. Recommendations include advice regarding the management of intracranial pressure and congenital heart disease. Implementation of the Guideline will require reorganization of prehospital and emergency care systems, including the development of regional stroke networks, pediatric Code Stroke, rapid magnetic resonance imaging and accreditation of primary pediatric stroke centers with the capacity to offer reperfusion therapies. The Guideline will allow auditing to benchmark timelines of care, access to acute interventions, and outcomes. It will also facilitate the development of an Australian childhood stroke registry, with data linkage to international registries, to allow for accurate data collection on stroke incidence, treatment, and outcomes.

BackgroundEstimates suggest that, in NHS hospitals, incidents causing harm to patients occur in 10% of admissions, with costs to the NHS of > £2B. About one-third of harmful events are believed to be preventable. Strategies to reduce patient safety incidents (PSIs) have mostly focused on changing systems of care and professional behaviour, with the role that patients can play in enhancing the safety of care being relatively unexplored. However, although the role and effectiveness of patient involvement in safety initiatives is unclear, previous work has identified a general willingness among patients to contribute to initiatives to improve health-care safety.AimOur aim in this programme was to design, develop and evaluate four innovative approaches to engage patients in preventing PSIs: assessing risk, reporting incidents, direct engagement in preventing harm and education and training.Methods and resultsWe developed tools to report PSIs [patient incident reporting tool (PIRT)] and provide feedback on factors that might contribute to PSIs in the future [Patient Measure of Safety (PMOS)]. These were combined into a single instrument and evaluated in the Patient Reporting and Action for a Safe Environment (PRASE) intervention using a randomised design. Although take-up of the intervention by, and retention of, participating hospital wards was 100% and patient participation was high at 86%, compliance with the intervention, particularly the implementation of action plans, was poor. We found no significant effect of the intervention on outcomes at 6 or 12 months. The ThinkSAFE project involved the development and evaluation of an intervention to support patients to directly engage with health-care staff to enhance their safety through strategies such as checking their care and speaking up to staff if they had any concerns. The piloting of ThinkSAFE showed that the approach is feasible and acceptable to users and may have the potential to improve patient safety. We also developed a patient safety training programme for junior doctors based on patients who had experienced PSIs recounting their own stories. This approach was compared with traditional methods of patient safety teaching in a randomised controlled trial. The study showed that delivering patient safety training based on patient narratives is feasible and had an effect on emotional engagement and learning about communication. However, there was no effect on changing general attitudes to safety compared with the control.ConclusionThis research programme has developed a number of novel interventions to engage patients in preventing PSIs and protecting them against unintended harm. In our evaluations of these interventions we have been unable to demonstrate any improvement in patient safety although this conclusion comes with a number of caveats, mainly about the difficulty of measuring patient safety outcomes. Reflecting this difficulty, one of our recommendations for future research is to develop reliable and valid measures to help efficiently evaluate safety improvement interventions. The programme found patients to be willing to codesign, coproduce and participate in initiatives to prevent PSIs and the approaches used were feasible and acceptable. These factors together with recent calls to strengthen the patient voice in health care could suggest that the tools and interventions from this programme would benefit from further development and evaluation.Trial registrationCurrent Controlled Trials ISRCTN07689702.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Place-based interventions (PBI) are a model of care introduced to support children from disadvantaged neighbourhoods, where their access to services may be limited despite their increased support needs. We conducted a systematic review of the effectiveness of PBI in improving development, health, and well-being outcomes in children aged 0-6 years living in disadvantaged neighbourhoods. Electronic databases (Medline, PsycInfo, EmCare, EmBase, Cochrane) (January 1996-July 2019), bibliographies and grey literature were searched. The 13 included studies had a total of 25,195 children. Individual studies demonstrated improvements in dental health, parenting, and child behaviour. Some studies reported improvement in child development outcomes for those children attending PBI, whilst others found no significant difference. There was no significant impact of PBI on other child health and behaviour outcomes. There was moderate to high levels of bias in the majority of papers. Meta-analysis was not undertaken due to study heterogeneity. There is insufficient evidence of the effectiveness of PBI in improving development, health, and well-being outcomes in children. Further rigorous evaluation of PBI is required with clear implementation evaluation describing the key components of the PBI.

Copy Number Variations (CNVs) comprising the distal 1q region 1q43-q44 are associated with neurological impairments, structural brain disorder, and intellectual disability. Here, we report an extremely rare, de novo case of a 1q43-q44 deletion with an adjacent duplication, associated with severe seizures, microcephaly, agenesis of the corpus callosum, and pachygyria, a consequence of defective neuronal migration disorder. We conducted a literature survey to find that our patient is only the second case of such a 1q43-q44 CNV ever to be described. Our data support an association between 1q43-q44 deletions and microcephaly, as well as an association between 1q43-q44 duplications and macrocephaly. We compare and contrast our findings with previous studies reporting on critical 1q43-q44 regions and their constituent genes associated with seizures, microcephaly, and corpus callosum abnormalities [Ballif et al., 2012; Hum Genet 131:145-156; Nagamani et al., 2012; Eur J Hum Genet 20:176-179]. Taken together, our study reinforces the association between 1q43-q44 CNVs and brain disorder.

The promising utility of multi-modality evoked potential batteries to objectively measure multi-tract dysfunction has been evaluated by several groups using different methods.To independently evaluate the use of multi-modality evoked potential batteries as surrogate biomarkers for both physical and cognitive status in a cohort of Primary Progressive Multiple Sclerosis patients and identify the most potentially useful scoring method of those described.28 Patients with Primary Progressive Multiple Sclerosis underwent clinical evaluation with Kurtzke's Modified EDSS and the Multiple Sclerosis Functional Composite (MSFC). 19 Participants also underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Visual, Brainstem Auditory, Somatosensory and Motor Evoked Potentials were recorded on all. Results were graded by variants of the Global Evoked Potential Score, Multiple Evoked Potential Score and Summation of Z transformed Evoked Potential Latencies for correlation against the clinical scores.Multi-modal evoked potential batteries generally show moderate and useful correlation with clinical status as measured by the regulatory standard of EDSS (r = .65 vs. mEPS p.005) and MSFC (r = .39 vs. mEPS p.05). The graded qualitative mEPS scoring system displayed the strongest relationship although the influence of scoring system applied appeared reassuringly minimal. Non-association with cognitive impairment is an important limitation however.

Purpose To assess the role of resective brain surgery in childhood epilepsy. Methodology We retrospectively analysed the seizure outcomes in 55 children with epilepsy who had resective brain surgery between 1997 and 2012, at our centre. The children were 1.5–18 years at the time of surgery; their seizure onset was between 0.2 andto 15 years of age. 48 had refractory epilepsy. One child died of tumour progression. Follow-up duration in the survivors ranged from 2 to −16 years (mean: 9).Presurgical evaluation included clinical profiles, non-invasive V-EEG monitoring, neuroimaging with MRIs in all; SPECT and PET in selected patients. 54 had intraoperative ECoG. Results An Engel Class 1 outcome was seen in 78% of the cohort, with 67% being off all AEDs at the most recent follow-up. Children with tumours constituted the majority (56%), with 87% of this group showing a Class 1 outcome and 84% being off AEDs. Children with cortical dysplasia had a Class 1 outcome in 56%. Conclusion Resective brain surgery is an efficacious option in some children with epilepsy. We found ECoG useful to tailor the cortical resection and in our opinion ECoG contributed to the good seizure outcomes.

The development of “child aware” practice is about the capacity and capability of adult health and social service providers to identify and respond to the needs of children. A scoping review of the literature considered five adult adversities associated with family stress and reduced parenting capacity: mental illness, alcohol and substance abuse, homelessness, intellectual disability, and domestic violence. Although there are specific needs for children pertaining to particular adversities, there was substantial commonality of potential effects. These included emotional and psychological difficulties, physical and mental health problems, academic difficulties, language delays, peer difficulties, stigma, trauma reactions, loss and grief, instability, and social exclusion. How children react to difficulties in their family depends upon various protective factors, a child's frame of reference, and other dynamics within the family that can offset risks. The findings aim to inform policy, program deve...

Aims Lacosamide (LCM) is a novel anti-epileptic drug (AED) that enhances the slow inactivation of voltage-gated sodium channels. Its efficacy as adjunctive therapy for focal seizures is confirmed in adult placebo controlled trials with >50% reduction in seizure frequency in up to 50% patients. There is paucity of data on its efficacy and tolerance in treatment-resistant epilepsy in childhood (TREC). This study aims to assess efficacy and tolerance of LCM as adjunct therapy in TREC. Methods Audit of medical records and seizure diaries in children with TREC on LCM. A response (RR) was defined as ≥50% reduction in seizure frequency. Results Forty children (age range: 2–19 years) with TREC received LCM as add-on therapy. All had abnormal electroencephalograms, and 36 had abnormal neuroimaging. All children failed >2 AED trials, nine had trialled the ketogenic diet, five had failed the vagal nerve stimulator and 11 had failed resective epilepsy surgery. Median dose and duration of LCM therapy were 5.7 mg/kg/day and 10.5 months, respectively. RR was seen in 20% with persistence of RR in 8/36, 8/30 and 8/26 children on LCM at 3-, 6- and 9-month follow-up. Two children became seizure free. Retention on LCM was 65% at 9 months. LCM was well tolerated with minor side effects in seven children; no child discontinued LCM because of side effects. Conclusion LCM is a well-tolerated AED with RR in 20%: in 5%, it resulted in seizure freedom. LCM may be useful even in TREC when seizures have not responded to intervention with multiple modalities.

Background: Vincristine is a chemotherapeutic agent frequently used in the treatment of childhood cancer. Peripheral neuropathy is an important side effect of Vincristine. We assessed the incidence, severity and type of peripheral neuropathy in children on Vincristine using clinical parameters and nerve conduction studies. Methods : Children with cancer treated with Vincristine were enrolled. Symptoms and signs of motor, sensory and autonomic peripheral neuropathy at baseline and at 3, 6 and 12 month follow up were documented. A modified total neuropathy score grading was undertaken. Nerve conduction studies (NCS) were undertaken and vitamin E levels measured at the time of these assessments. Results: 28 patients were enrolled over 12 months. 93% had evidence of neuropathy clinically and/or electrophysiologically. Weakness, pain and constipation were the most common symptoms and the most common sign was loss of ankle reflexes. The peripheral neuropathy was mild in most cases. Plasma levels of vitamin E remained in the normal range, however they dropped significantly from the baseline value. Conclusions: Peripheral neuropathy assessed clinically and electrophysiologically, occurs in the majority of children on Vincristine treatment. The neuropathy is sensory-motor and generally mild. There was a statistically significant drop in average vitamin E levels during treatment. Keywords: Vincristine, peripheral neuropathy, vitamin E

BackgroundIn 2009 the UK National Patient Safety Agency relaunched its Being Open framework to facilitate the open disclosure of adverse events to patients in the NHS. The implementation of the framework has been, and remains, challenging in practice.AimThe aim of this work was to both critically evaluate and extend the current evidence base relating to open disclosure, with a view to supporting the implementation of a policy of open disclosure of adverse events in the NHS.MethodsThis work was conducted in three phases. The first phase comprised two focused systematic literature reviews, one summarising empirical research on the effectiveness of interventions to enhance open disclosure, and a second, broader scoping review, looking at reports of current opinion and practice and wider knowledge. The second phase involved primary qualitative research with the objective of generating new knowledge about UK-based stakeholders’ views on their role in and experiences of open disclosure. Stakeholder interviews were analysed using the framework approach. The third phase synthesised the findings from the first two phases to inform and develop a set of short pragmatic suggestions for NHS trust management, to facilitate the implementation and evaluation of open disclosure.ResultsA total of 610 papers met the inclusion criteria for the broad review. A large body of literature discussed open disclosure from a number of related, but sometimes conflicted, perspectives. Evidential gaps persist and current practice is based largely on expert consensus rather than evidence. There appears to be a tension between the existing pragmatic guidance and the more in-depth critiques of what being consistent and transparent in health care really means. Eleven papers met the inclusion criteria for the more focused review. There was little evidence for the effectiveness of disclosure alone on organisational or individual outcomes or of interventions to promote and support open disclosure. Interviews with stakeholders identified strong support for the basic principle of being honest with patients or relatives when someone was seriously harmed by health care. In practice however, the issues are complex and there is confusion about a number of issues relating to disclosure policies in the UK. The interviews generated insights into the difficulties perceived within health care at individual and institutional levels, in relation to fully implementing the Being Open guidance.ConclusionsThere are several clear strategies that the NHS could learn from to implement and sustain a policy of openness. Literature reviews and stakeholder accounts both identified the potential benefits of a culture that was generally more open (not just retrospectively open about serious harm). Future work could usefully evaluate the impact of disclosure on legal challenges within the NHS, best practice in models of support and training for open disclosure, embedding disclosure conversations in critical incident analysis and disclosure of less serious events.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

This article, taken from a presentation to the Medico-Legal Society, discusses the prospects for patient safety and access to justice in the wake of the Mid Staffordshire NHS Foundation Trust public inquiry and the Legal Aid Sentencing and Punishment of Offenders Act. Particular reference is made to the arguments for and against a statutory Duty of Candour; clinical negligence litigation; patient complaints and specialist advice and support for people affected by medical accidents.

With a high prevalence of well-established risk dementia risk factors (e.g. tobacco, alcohol use, hypertension, and diabetes), there is a dire need for data on prevalence and correlates of cognitive impairment and related service utilization among older Korean Americans. Memory and Aging study of Koreans (MASK) is a two-stage epidemiological survey with two-step sampling strategy to obtain a representative sample. We screened 1,118 older Korean Americans (mean age: 70.7, female: 67.2%) with a Korean version of the Mini-Mental State Exam, and 118 persons sampled from two levels of performance on the MMSE underwent the second stage clinical evaluation that included the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Preliminary analysis estimated that community prevalence of mild cognitive impairment in this population was 28.4% (CI: 18.2%-41.5%) and dementia was 7.2% (3.8% - 13.2%). Correlates of cognitive impairment, and potential barriers to the services will be discussed during this presentation.

Age-standardized rates of hip fracture in Canada declined during the period 1985 to 2005. We investigated whether this incidence pattern is explained by period effects, cohort effects, or both. All hospitalizations during the study period with primary diagnosis of hip fracture were identified. Age- and sex-specific hip fracture rates were calculated for nineteen 5-year age groups and four 5-year calendar periods, resulting in 20 birth cohorts. The effect of age, calendar period, and birth cohort on hip fracture rates was assessed using age-period-cohort models as proposed by Clayton and Schiffers. From 1985 to 2005, a total of 570,872 hospitalizations for hip fracture were identified. Age-standardized rates for hip fracture have progressively declined for females and males. The annual linear decrease in rates per 5-year period were 12% for females and 7% for males (both p

Objectives The number of hospital discharges involving type 1 or type 2 diabetes as the first-listed diagnosis has increased over the past few decades. Such cases are commonly associated with various comorbidities. We analyzed data collected from hospital separations in Canada to determine the number and proportion of comorbid conditions in Canadians hospitalized because of diabetes. Methods The most responsible diagnosis (MRDx) of diabetes (ICD-10-CA: E10 [type 1 diabetes] or E11 [type 2 diabetes]) was identified from acute care hospital separations (Discharge Abstract Database) from 2013 to 2014 in all Canadian jurisdictions except Quebec. Hospital separations were calculated by 5-year age groups and sex. The most common comorbid (secondary) diagnoses were identified for hospital separations with diabetes as the MRDx, and the average lengths of stay associated with diabetes were determined. Results The total number of hospital separations in 2013–2014 in Canada (excluding Quebec) with diabetes as the MRDx in all ages was 30,422, and males represented more than half (58.7%) of the separations. The median age group when diabetes is the MRDx is 60 to 64. For all patients hospitalized with an MRDx of diabetes, there were 2.2% deaths. Hypertension was the most common comorbid diagnosis in patients with diabetes as the MRDx, followed by glomerular disorders, peripheral angiopathy and acute renal failure. Conclusions Hospitalizations resulting from diabetes are associated with vascular comorbidities, and hypertension is the most common. Prevention of shared predisposing factors should reduce the burden of hospitalizations associated with diabetes.

Introduction The Public Health Agency of Canada, in collaboration with bone health and osteoporosis experts from across Canada (n = 12), selected a core set of indicators for the public health surveillance of osteoporosis using a formal consensus process. Methods A literature review identified candidate indicators that were subsequently categorized into an osteoporosis-specific indicator framework. A survey was then administered to obtain expert opinion on the indicators’ public health importance. Indicators that scored less than 3 on a Likert scale of 1 (low) to 5 (high) were excluded from further consideration. Subsequently, a majority vote on the remaining indicators’ level of public health importance was sought during a face-to-face meeting. Results The literature yielded 111 indicators, and 88 were selected for further consideration via the survey. At the face-to-face meeting, more than half the experts considered 39 indicators to be important from the public health perspective. Conclusion This core set of indicators will serve to inform the development of new data sources and the integration, analysis and interpretation of existing data into surveillance products for the purpose of public health action.

Background Heart failure (HF) is a leading morbid cause of hospitalization and death. HF is often accompanied by comorbid conditions, increasing the health care burden. This study describes hospital mortality and identifies comorbid conditions associated with HF. Methods Acute care hospital separations in 2005-2006, with a diagnosis of HF I50, I500, I501, I509 ( The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canada [ICD-10-CA]) were identified from all Canadian jurisdictions except Quebec. Results A total of 2,457,527 hospital separations among 1,812,923 individuals, identifying 8,212,869 diagnoses were reported. Among those, a total of 33,693 (1.9%) of all hospitalized individuals had a most responsible diagnosis of HF, accounting for 42,399 hospital separations. Further, HF was coded 77,049 times as a comorbid diagnosis, altogether occurring in 4.9% of all hospitalizations. The most common primary diagnoses associated with comorbid HF were acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD), and pneumonia. Seniors had a much higher hospitalization rate due to HF. Hospitalized individuals with a primary diagnosis of HF had an almost 3-fold higher 30-day in-hospital mortality rate and nearly double the mean hospital stay than that for all causes. On average, hospitalizations with a primary diagnosis of HF had 3.9 comorbidities, most commonly chronic ischemic heart disease (IHD), atrial fibrillation and flutter, diabetes, renal failure, etc.; 1.7 times greater for HF than for all causes. Conclusions HF has a high in-hospital mortality rate particularly among the elderly and is associated with many cardiac and noncardiac conditions. HF necessitates long hospital stays, which increases the burden on the health care system in Canada.

Galloway-Mowat syndrome is a rare condition that is likely hereditary though the underlying offending gene has not been identified, and is characterized by microcephaly and severe nephrotic syndrome culminating in childhood death. Some of the reported cases have abnormalities in neuronal migration and intractable seizures, but many of the described cases focus on the renal pathology and emphasize a diversity of clinical and pathological features. The case described herein includes a thorough neuropathological description, and when the neuroradiology and neuropathology of the previously published cases is scrutinized, a fairly consistent clinical and neuropathological phenotype emerges.

Most of the time care provided to people in the National Health Service (NHS) and by other care providers such as those in the independent and voluntary sectors is of a high standard with positive outcomes. However, things do go wrong from time to time and complaints are made. This article provides an understanding of how concerns and complaints should be managed in health and social care settings, with the aim to make the organisation that employs Health Care Assistants (HCA) and Assistant Practitioners (AP) an organisation that listens, responds and learns from peoples' experiences, these can be in the form of compliments, complaints or concerns. The article focuses primarily upon the NHS and England. Health and social care providers in other countries of the United Kingdom may have their own complaints procedures as do the independent and voluntary sectors, nevertheless the principles discussed here can apply across the board.

Many child protection practitioners struggle with the complexity of problems and the limited casework time for adolescent cases. However, there is little research on child protection practice or case management that can guide a practitioner working with adolescents in the child protection system. The aim of this study was to explore and describe the nature of effective child protection practice with adolescents from the perspective of statutory child protection practitioners in one state in Australia. Data were collected through focus group discussions and interviews with child protection practitioners and managers currently working with adolescents (n= 44). A grounded theory approach was used to identify the dominant themes or categories and form linkages and relationships through constant comparison techniques. Seven key categories emerged from this analysis: characteristics of the young person and their family; ‘walking it together’– the centrality of relationships; ‘looking back/looking forward’– practice strategies; practitioner attributes and skills; ‘walking a fine line’– working with the families of adolescents; ‘walking with services’– effective inter‐agency work; and organizational context in effective child protection practice with adolescents. Key implications for practice and areas for further research were discussed.

We identified hospitalizations throughout Canada during 2000–2005 in which the most responsible diagnosis was a proximal femoral fracture. Use of the US fracture risk assessment tool (FRAX) would be inappropriate for Canada as it would overestimate fracture risk in Canadian women and older men. It is recommended that the WHO fracture risk assessment tool should be calibrated to the target population. We identified hospitalizations for women and men throughout Canada during the study period 2000–2005 in which the most responsible diagnosis was a proximal femoral fracture (147,982 hip fractures). Age-standardized hip fracture rates were compared between Canadian provinces, and national rates were compared with those reported for the USA and Germany. There were relatively small differences in hip fracture rates between provinces, and most did not differ appreciably from the Canadian average. Hip fracture rates for women in Canada in 2001 were substantially lower than in the USA (population-weighted rate ratio 0.70) and were also lower than in Germany for 2004 (population-weighted rate ratio 0.74). Overall hip fracture rates for Canadian women were found to be substantially lower than those for the USA and Germany. This study underscores the importance of assessing country-specific fracture patterns prior to adopting an existing FRAX tool.

Neurophysiological techniques have a long history of clinical and research use in the setting of Multiple Sclerosis. With the output of evoked potential and electroencephalographic recordings being a direct consequence of the underlying functional integrity and activity of the nervous system it is unsurprising there is currently a resurgent interest in their possible use as biomarkers of disease related dysfunction. Herein we discuss the promise and possible pitfalls associated with their use in translational research of MS therapeutics. The numerous advantages of these methods are touched upon as demonstrated by their application to date. A number of obstacles which must be overcome prior to their successful widespread implementation are also outlined and readily achievable solutions discussed.

This study evaluates the characteristics of photoparoxysmal responses elicited with intermittent photic stimulation during a routine electroencephalogram in childhood and correlated this with the clinical profile of the child. Photoparoxysmal responses occurred in 8% (21/263) of children where activation was undertaken. Photoparoxysmal responses were often brief and had a variable onset latency. This study suggests increasing the duration of the stimulus train to 10 seconds or more will increase the diagnostic yield. Photoparoxysmal responses very rarely outlasted the stimulus, and self-limited photoparoxysmal responses probably have greater significance than previously attributed to them. They are highly correlated with epilepsy.

Objectives - To study the efficacy, tolerability and safety of the vagus nerve stimulation (VNS) therapy in clinical practice, in 16 children and adolescents with refractory epilepsy Methodology - We assessed the efficacy of VNS therapy, retrospectively by comparing seizure frequency, duration and severity at the time of most recent follow up (av: 24.9 months) to that in the 4 weeks prior to VNS surgery. Changes in quality of life, sleep and behaviour at last review was compared with that prior to VNS. Adverse effects elicited by specific questioning, spontaneous reporting and clinical examination are described. Results - Vagus nerve stimulation resulted in a > 50% reduction in seizure frequency in 62.5% of children with 25% achieving a > 90% % reduction. Vagus nerve stimulation was well tolerated in all hut one of our cohort, with no serious side-effects. Conclusion - Our results support its role as one of the options in intractable childhood epilepsy.

The notion of place management is emerging in public sector discourse as a potential solution to improve governments' responses to issues confronting local communities, particularly those experiencing high levels of economic and social disadvantage. Despite the increased currency of the term, there is a degree of confusion surrounding what it actually means. And it is not always clear what is meant by the notion of ‘place’. This article attempts to clarify a working definition of ‘place management’ and to explore the policy and administrative implications for governments in adopting a place management approach.

We present a case of recurrent vago-glossopharyngeal neuralgia after previous surgery, treated successfully with microvascular decompression using intra-operative neurophysiology monitoring.

TGF-β family members play a relevant role in tumorigenic processes, including hepatocellular carcinoma (HCC), but a specific implication of the Bone Morphogenetic Protein (BMP) subfamily is still unknown. Although originally isolated from fetal liver, little is known about BMP9, a BMP family member, and its role in liver physiology and pathology. Our results show that BMP9 promotes growth in HCC cells, but not in immortalized human hepatocytes. In the liver cancer cell line HepG2, BMP9 triggers Smad1,5,8 phosphorylation and inhibitor of DNA binding 1 (Id1) expression up- regulation. Importantly, by using chemical inhibitors, ligand trap and gene silencing approaches we demonstrate that HepG2 cells autocrinely produce BMP9 that supports their proliferation and anchorage independent growth. Additionally, our data reveal that in HepG2 cells BMP9 triggers cell cycle progression, and strikingly, completely abolishes the increase in the percentage of apoptotic cells induced by long-term incubation in low serum. Collectively, our data unveil a dual role for BMP9, both promoting a proliferative response and exerting a remarkable anti-apoptotic function in HepG2 cells, which result in a robust BMP9 effect on liver cancer cell growth. Finally, we show that BMP9 expression is increased in 40% of human HCC tissues compared with normal human liver as revealed by immunohistochemistry analysis, suggesting that BMP9 signaling may be relevant during hepatocarcinogenesis in vivo. Our findings provide new clues for a better understanding of BMPs contribution, and in particular BMP9, in HCC pathogenesis that may result in the development of effective and targeted therapeutic interventions.

In the course of investigating children with hypotonia, muscle biopsy of the vastus lateralis frequently demonstrates greater than 55% predominance of the aerobic type 1 fibers of "type 1 fiber predominance" (T1FP). The clinical significance of T1FP is not well known. T1FP can be associated with a variety of neurological disorders but a significant proportion has no apparent cause. We followed up 23 children with T1FP to establish whether a neurological disorder subsequently became apparent or whether a distinct clinical entity of T1FP could be identified. Sixty percent of the children were found to have a specific neurological disorder, while 40% did not and may represent a distinct clinical entity. The majority of children with the clinical entity of T1FP improved although some were left with mild motor disability. Such information is important for counseling when patients with T1FP are first assessed.

Balamuthia amebic encephalitis is rarely reported in infants. To the best of our knowledge, amebic encephalitis complicated by a mycotic aneurysm was only described once. We report on an 8-month-child with laboratory-confirmed Balamuthia mandrillaris meningoencephalitis, complicated by a mycotic aneurysm of the middle cerebral artery.

The mitochondrion is an essential cellular compartment in eukaryotes. The mitochondrial proteins Tom20 and Tom22 are receptors that ensure recognition and binding of proteins imported for mitochondrial biogenesis. Comparison of the sequence for the Tom20 and Tom22 subunits in the yeasts Saccharomyces cerevisiae and Saccharomyces castellii, show a rare case of domain stealing, where in Saccharomyces castellii Tom22 has lost an acidic domain, and Tom20 has gained one. This example of domain stealing is a snapshot of evolution in action and provides excellent evidence that Tom20 and Tom22 are subunits of a single, composite receptor that binds precursor proteins for import into mitochondria.

Vascular stenosis is defined as a narrowing or constriction to the body or opening of a vessel conduit. Stenosis and thrombus formations are the result of vascular injury and inflammation due to vascular cell dysfunction, resulting in any of the following pathological or healing injury responses: an initial coagulation/thrombus (blood clot) on the vascular inner wall to promote healing or further injury and inflammation; vascular smooth muscle cell proliferation and migration into the blood vessel lumen promoting stenosis following an initial disruption to the endothelium; atherosclerosis in which both early thrombus and smooth muscle cell proliferation and migration participate; and atherothrombosis that interacts with a mature atherosclerotic plaque to form a blood clot on the surface of the plaque resulting in further stenosis or possible emboli. Changes in vascular function are governed by the dynamic mechanical environment consisting of shear stress, wall stresses, and pressure imposed on the cells within the vascular wall as a result of blood flow. Endothelial cells in the intima and the smooth muscle cells within the vessel media are stimulated with these mechanical stresses that alter their behavior. Atherosclerosis and other causes of stenosis develop at localized regions within the vasculature that correlate to localized mechanical conditions. Disease typically occurs at arterial sites where endothelial cells would be exposed to low and oscillatory shear stress. Localized variations in the inner to outer wall stresses also appear to be related to disease-formation. This chapter reviews studies integrating biology with vascular mechanical events that explain the current theories on stenosis and thrombosis. Keywords: atherosclerosis; endothelial cells; blood flow; shear; stretch; smooth muscle cells; thrombosis; stenosis

One of the thorniest issues in the relationship between doctors and patients has been how to deal with a dispute. The rhetoric of the past few governments, both Conservative and Labour, has emphasised the need to treat patients as consumers of services provided by the NHS. Patients need to be “at the centre” of all arrangements for planning, delivery, and accountability. At the same time, the private healthcare system in Britain has grown by aggressively marketing its service as modern and responsive to patients' needs as “customers,” and patients are becoming used to making choices both about who provides their services and the nature of the treatment they are to have. The growth in consumerism has been accompanied by an explosion in information systems, most notably the internet, which have made patients more knowledgeable customers when it comes to disease, treatments, and patients' rights. Recently, information on the performance of hospitals has become available through private initiatives such as the Good Hospital Guide ,1 and the Department of Health plans to publish more detailed information on the performance of individual consultants. When there is a dispute, however, the relationship between doctors and patients can still seem rather paternalistic. Feedback from community health councils, which support people with complaints, suggests that many patients still get removed from general practitioners' lists for no other reason than having dared to complain about their doctor's service or attitude. This is in spite of guidance from the Royal College of General Practitioners that all attempts to resolve disputes should be exhausted before declaring the doctor-patient relationship and trust irretrievably damaged.2 In …

MS is difficult to measure. Limited sensitivity of clinical measures has prohibited conducting adequately powered trials in PPMS. Neurophysiological evaluation using EPs to evaluate long tract integrity and EEG Coherence Analysis to gauge cortical network functional connectivity may provide markers which correlate with patients9 clinical status and prove sufficiently sensitive to be effective interim measures in smaller/shorter trials. 31 PPMS patients [35–70 y, m=f, EDSS 5.7 (3.5–8)] were recruited (2007–2011). 6, 12, 24 and 36 months after baseline participants underwent combined clinical assessment with EDSS, MSFC and RMI with subjective evaluation by MSQLI and underwent an EP battery comprising bilateral VEP and BSAEP, with SSEPs and MEPs for all four limbs. EEG from 5 bipolar electrode pairs (Cz–Fz, O1–A1, C3–A1, O2–A2 and C4–A2) was attained for coherence based network modelling. Normalisation of EP results generated Z scores for summation. Waveforms were also qualitatively evaluated according to the GEPS System. Cross sectional evaluation suggests good correlation between the GEPS and Summed Z with respect to clinical measures (rho=0.63 p= Multimodal evaluation may sensitively provide meaningful measurements across many domains affected by PPMS and facilitate trials.

The nucleotide sequence of Hepatitis E virus (HEV) serous isolates (G-9 and G-20) from Guangzhou, South China, which has been reported previously, are divergent significantly from those of other reported HEV isolates. In order to investigate more extensively the Guangzhou isolate, the 93G strain was isolated from the faecal sample of the same individual as G-9 by A549 cell culture and identified immunologically and by molecular biological techniques. The results showed that strain 93G could be propagated in an A549 cell line causing cytopathic effects. The viral particles were aggregated by a specific antibody to HEV Chinese Xinjiang strain (87A) observed using immunoelectron microscopy and were similar morphologically to HEV from other sources. In this study, an indirect fluorescent antibody assay was first developed to examine HEV antigen in the infected cells, by immunofluorescence in the cytoplasm and on the surface membrane of the cells. The 58-kDa and 82-kDa native structural proteins of HEV were also identified in this study by Western blotting. The 93G genome showed high homology (93%) with G-9 previously reported but was also as divergent from the Burmese, Mexican, Chinese Xinjiang isolates and the recently reported US-1 isolate, as was G-9. The data presented indicate that 93G propagated in A549 cells, together with its related serum isolate G-9, represents another HEV strain circulating in China and is responsible for some sporadic hepatitis E infections.

The end-plate species of acetylcholinesterase (AChE) is an asymmetric enzyme consisting of a collagenic tail subunit composed of three collagenic strands (ColQ), each attached to a tetramer of the T isoform of the catalytic subunit (AChE(T)) via a proline-rich attachment domain. The principal function of the tail subunit is to anchor asymmetric AChE in the synaptic basal lamina. Human end-plate AChE deficiency was recently shown to be caused by mutations in COLQ. We here report nine novel COLQ mutations in 7 patients with end-plate AChE deficiency. We examine the effects of the mutations on the assembly of asymmetric AChE by coexpressing each genetically engineered COLQ mutant with ACHE(T) in COS cells. We classify the newly recognized and previously reported COLQ mutations into four classes according to their position in ColQ and their effect on AChE expression. We find that missense mutations in the proline-rich attachment domain abrogate attachment of catalytic subunits, that truncation mutations in the ColQ collagen domain prevent the assembly of asymmetric AChE, that hydrophobic missense residues in the C-terminal domain prevent triple helical assembly of the ColQ collagen domain, and that other mutations in the C-terminal region produce asymmetric species of AChE that are likely insertion incompetent.