Outliers from national audits: their analysis and use by the Care Quality Commission in quality assurance and regulation of healthcare services in England.

The Care Quality Commission (CQC) is the independent regulator of health and adult social care in England. As part of the intelligence-driven approach to regulation, the CQC works closely with national clinical audit bodies to identify key metrics which reflect quality of care and track the performance of providers against these metrics. Where outliers on national audits are identified that may reflect risks to patients, the CQC encourages the hospital to identify any learning points and implement changes to improve patient care.In this article, we describe the role of national audit outcomes in the regulatory process and how providers can use national audits to inform both quality assurance and quality improvement processes, with two illustrative case studies. We discuss the ongoing challenges with using audit data in the regulatory process and how these could be addressed.

Post-traumatic (and postsurgical) Guillain-Barré Syndrome: a rare, but treatable entity.

Guillain-Barré syndrome (GBS) is an acute, monophasic, polyradiculoneuropathy usually provoked by a preceding infection. The cardinal features are progressive weakness in the upper and lower limbs accompanied by loss of deep tendon reflexes. The diagnosis is made on the basis of the clinical history and examination findings, supported by typical cerebrospinal fluid and electrophysiology findings. Trauma and surgery are well understood but rare precipitants of GBS, which clinicians should be aware of, in order not to miss an opportunity to use immunomodulatory therapies. Furthermore, the presence of postsurgical or post-traumatic GBS should prompt careful assessment for underlying malignancy or autoimmune disease associated with an acute demyelinating polyradiculoneuropathy. Here, we present a case of post-traumatic GBS and discuss the potential mechanisms that might underlie this, as well as the investigations and treatment that should be considered.

Junior doctors and fitness to practice procedures in the UK: analysis of factors prompting tribunal referrals and outcomes.

PURPOSE OF THE STUDY: To ascertain factors influencing referral to, and outcomes from medical tribunals for junior doctors with less than 7 years of postgraduate training. STUDY DESIGN: A mixed methods analysis of 49 publicly available determinations from the UK Medical Practitioner Tribunal Service (MPTS) between 2014 and 2020 was undertaken. Data on demographics, training grade, type of case and outcomes from the tribunal were recorded. A qualitative thematic analysis of the determinations was also undertaken, with themes being identified based on frequency and pertinence to the process of determination. RESULTS: The largest group of junior doctors referred to an MPTS tribunal (38%) was those on the foundation programme; in their first 2 years postgraduation. Fifty-three per cent of all junior doctors referred to a tribunal were erased from the medical register. Erasure from the register was significantly associated with male gender, less than 4 years postqualification, non-attendance at the tribunal hearing, lack of legal representation and lack of insight or remorse at the tribunal hearing. Several cases involved dishonesty in relation to academic achievements and workplace-based assessments. CONCLUSION: Consideration should be given as to how best to support the transition in professional identity from student to doctor. Teaching medical professionalism should be a priority in undergraduate and early postgraduate education, with lessons from fitness to practice tribunals shared for educational purposes.

Clinical leadership fellow schemes for junior doctors: a brief overview of available schemes and how to apply.

Medical training in the UK provides limited exposure to formal training in leadership and management, and yet the role of a consultant or general practitioner requires such skills which deal with commissioning arrangements, service transformation, quality improvement, Care Quality Commission visits, complaints and supervision of junior colleagues. A number of clinical fellowships in leadership now exist to bridge this gap, and provide training in leadership and management, together with experiential learning in a complex organisation. Well-established leadership schemes suited to junior doctors include the National Medical Director's Clinical Fellow Scheme, the Royal College of Physicians' chief registrar scheme, the Darzi Fellowship scheme and local schemes run by Health Education England. Here we describe and compare our experience of these schemes, and outline what junior doctors should consider when applying for a clinical fellowship.

Regulators of adult neurogenesis in the healthy and diseased brain.

1. In recent decades evidence has accumulated demonstrating the birth and functional integration of new neurons in specific regions of the adult mammalian brain, including the dentate gyrus of the hippocampus and the subventricular zone. 2. Studies in a variety of models have revealed genetic, environmental and pharmacological factors that regulate adult neurogenesis. The present review examines some of the molecular and cellular mechanisms that could be mediating these regulatory effects in both the normal and dysfunctional brain. 3. The dysregulation of adult neurogenesis may contribute to the pathogenesis of neurodegenerative disorders, such as Huntington's, Alzheimer's and Parkinson's disease, as well as psychiatric disorders such as depression. Recent evidence supports this idea and, furthermore, also indicates that factors promoting neurogenesis can modify the onset and progression of specific brain disorders, including Huntington's disease and depression.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: effects of environmental enrichment.

Previous work has demonstrated that the transgenic R6/1 mouse model of Huntington's disease has decreased proliferation of neural precursor cells (NPCs) in the dentate gyrus of the hippocampus. This study therefore examined the survival and differentiation of NPCs in presymptomatic and symptomatic R6/1 mice and the effects of environmental enrichment on these variables. Here it is demonstrated that the survival of bromodeoxyuridine-positive (BrdU+) NPCs in the dentate gyrus is decreased in the transgenic mice. In addition, the number of doublecortin-positive (DCX+) cells is greatly reduced in these mice, as is the total number of new mature neurons, while the proportion of BrdU+ cells differentiating into mature neurons was not significantly different between genotypes. Furthermore, the DCX+ cells in the R6/1 mice had smaller and irregular-shaped somas, shorter neurites, and migrated a shorter distance into the granular cell layer compared with wild-type mice. Older symptomatic mice housed in an enriched environment had an increased number of BrdU+ and DCX+ cells as well as longer neurites and increased migration of DCX+ cells. There was no significant difference between genotypes or environments in the number of BrdU+ cells in the subventricular zone. These results suggest that decreased neurogenesis might be responsible, in part, for the hippocampal deficits observed in these mice and that environmental enrichment produces morphological changes in newborn granule neurons in both wild-type and R6/1 mice, which could underlie some of the beneficial effects of enrichment.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine.

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.

Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex. In parallel, there are deficits in barrel-cortex plasticity after a somatosensory whisker-deprivation paradigm. The present study demonstrates deficits in neocortical plasticity correlated with a specific learning impairment involving the same neocortical area, a finding that provides new insight into the cellular basis of early cognitive deficits in HD.

Gene-environment interactions, neuronal dysfunction and pathological plasticity in Huntington's disease.

Huntington's disease (HD) is a fatal autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. The dynamic mutation that causes the disease is common to numerous other brain disorders, which may share similar pathogenic mechanisms. Much progress has been made in the past decade in understanding how a trinucleotide (CAG) repeat expansion, encoding an expanded polyglutamine tract in the huntingtin protein, induces dysfunction at molecular and cellular levels. The present review integrates various lines of experimental evidence in an attempt to move towards a unifying mechanistic framework, which may explain the pathogenesis of HD, from molecular through to neuronal network and behavioural levels. Recent evidence, using transgenic mouse models, also suggests that environmental factors can modify the onset and progression of HD. The effects of specific environmental manipulations are discussed in the context of gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain, particularly the cerebral cortex.

Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.

Decreased hippocampal cell proliferation in R6/1 Huntington's mice.

In order to ascertain whether disturbances of neurogenesis occur in chronic neurodegenerative disorders, we assessed hippocampal cell proliferation in the R6/1 transgenic mouse model of Huntington's disease (HD). Using BrdU labelling for dividing cells at two different time points (5 and 20 weeks) in transgenic and wild type control mice, we have shown that cell proliferation in the hippocampus was similar in younger asymptomatic R6/1 mice and wild type controls, but that older R6/1 mice had significantly fewer BrdU cells than controls. Such a decrease in cell proliferation may be relevant to some of the deficits seen in these mice, although further work is needed to prove this.

Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Transgenic mice expressing a human huntingtin transgene containing an expanded CAG repeat (R6/1 model) develop a neurodegenerative disorder closely resembling human HD. Previous work demonstrated that environmental enrichment delays the onset of motor symptoms in this mouse model. We confirmed that at 5 months of age, enrichment ameliorates motor symptoms (assessed using the rotarod test) and prevents loss of body weight induced by the HD transgene. We further examined molecular consequences of enrichment by determining changes in protein levels in the neostriatum, hippocampus, and anterior cortex using quantitative Western blot analysis. Non-enriched HD mice have severe reductions in BDNF in the hippocampus and striatum at 5 months, which are entirely rescued by enrichment. BDNF levels are unaltered by HD in the anterior cortex, suggesting that enrichment might prevent HD-induced impairment of anterograde transport of this neurotrophin to the striatum. NGF is unaffected by HD. Non-enriched HD mice also exhibit deficits in dopamine and cAMP-regulated phosphoprotein (32 kDa) in striatum and anterior cortex. Environmental enrichment rescues the cortical but not the striatal deficit at 5 months. These results suggest that environmental enrichment benefits animals at early stages of the disease by rescuing protein deficits, possibly through rescuing transcription or protein transport problems.