Exercise promotes growth and rescues volume deficits in the hippocampus after cranial radiation in young mice.

Human and animal studies suggest that exercise promotes healthy brain development and function, including promoting hippocampal growth. Childhood cancer survivors that have received cranial radiotherapy exhibit hippocampal volume deficits and are at risk of impaired cognitive function, thus they may benefit from regular exercise. While morphological changes induced by exercise have been characterized using magnetic resonance imaging (MRI) in humans and animal models, evaluation of changes across the brain through development and following cranial radiation is lacking. In this study, we used high-resolution longitudinal MRI through development to evaluate the effects of exercise in a pediatric mouse model of cranial radiation. Female mice received whole-brain radiation (7 Gy) or sham radiation (0 Gy) at an infant equivalent age (P16). One week after irradiation, mice were housed in either a regular cage or a cage equipped with a running wheel. In vivo MRI was performed prior to irradiation, and at three subsequent timepoints to evaluate the effects of radiation and exercise. We used a linear mixed-effects model to assess volumetric and cortical thickness changes. Exercise caused substantial increases in the volumes of certain brain regions, notably the hippocampus in both irradiated and nonirradiated mice. Volume increases exceeded the deficits induced by cranial irradiation. The effect of exercise and irradiation on subregional hippocampal volumes was also characterized. In addition, we characterized cortical thickness changes across development and found that it peaked between P23 and P43, depending on the region. Exercise also induced regional alterations in cortical thickness after 3 weeks of voluntary exercise, while irradiation did not substantially alter cortical thickness. Our results show that exercise has the potential to alter neuroanatomical outcomes in both irradiated and nonirradiated mice. This supports ongoing research exploring exercise as a strategy for improving neurocognitive development for children, particularly those treated with cranial radiotherapy.

Mouse models of immune dysfunction: their neuroanatomical differences reflect their anxiety-behavioural phenotype.

Extensive evidence supports the role of the immune system in modulating brain function and behaviour. However, past studies have revealed striking heterogeneity in behavioural phenotypes produced from immune system dysfunction. Using magnetic resonance imaging, we studied the neuroanatomical differences among 11 distinct genetically modified mouse lines (n = 371), each deficient in a different element of the immune system. We found a significant and heterogeneous effect of immune dysfunction on the brains of both male and female mice. However, by imaging the whole brain and using Bayesian hierarchical modelling, we were able to identify patterns within the heterogeneous phenotype. Certain structures-such as the corpus callosum, midbrain, and thalamus-were more likely to be affected by immune dysfunction. A notable brain-behaviour relationship was identified with neuroanatomy endophenotypes across mouse models clustering according to anxiety-like behaviour phenotypes reported in literature, such as altered volume in brains regions associated with promoting fear response (e.g., the lateral septum and cerebellum). Interestingly, genes with preferential spatial expression in the most commonly affected regions are also associated with multiple sclerosis and other immune-mediated diseases. In total, our data suggest that the immune system modulates anxiety behaviour through well-established brain networks.

Understanding colorectal cancer patient follow-up: a qualitative interview study.

PURPOSE: There are increasing numbers of patients who have been treated for colorectal cancer (CRC) who struggle with ongoing physical and psychological symptoms. 'Cancer survivor' is often used to describe these patients but this terminology remains controversial. This study sought to understand the follow-up experience of CRC patients in the UK and identify the terminology they prefer following diagnosis and treatment. METHODS: Purposeful sampling of patients from specialist CRC follow-up clinics was performed until data saturation was achieved. Two 1:1 semi-structured qualitative interviews were performed for each participant. Data were analysed thematically. RESULTS: Seventeen participants, median age = 62, 53% male were interviewed. Several themes were identified. Of note, fear of cancer recurrence dominates patients' agendas at follow-up appointments. There are also clinical and administrative barriers to discussing symptoms including being embarrassed, feeling that their symptoms were not relevant or not having enough time to discuss issues. However, there are several methods which may improve this, such as through the use of video consultations and questionnaires. In addition, patients identified inadequate holistic support despite significant psychological and social distress. Our data suggest that labelling a diverse group of patients as 'cancer survivors' can be problematic. CONCLUSION: It is important that clinicians systematically screen patients for symptoms that are known to occur following treatment. Clinicians and patients should have routine access to pathways and programmes that can support patients in navigating their life after cancer therapy.

Examining the effect of chronic intranasal oxytocin administration on the neuroanatomy and behavior of three autism-related mouse models.

Although initially showing great potential, oxytocin treatment has encountered a translational hurdle in its promise of treating the social deficits of autism. Some debate surrounds the ability of oxytocin to successfully enter the brain, and therefore modify neuroanatomy. Moreover, given the heterogeneous nature of autism, treatment will only amerliorate symptoms in a subset of patients. Therefore, to determine whether oxytocin changes brain circuitry, and whether it does so variably, depending on genotype, we implemented a large randomized, blinded, placebo-controlled, preclinical study on chronic intranasal oxytocin treatment in three different mouse models related to autism with a focus on using neuroanatomical phenotypes to assess and subset treatment response. Intranasal oxytocin (0.6IU) was administered daily, for 28 days, starting at 5 weeks of age to the 16p11.2 deletion, Shank3 (exon 4-9) knockout, and Fmr1 knockout mouse models. Given the sensitivity of structural magnetic resonance imaging (MRI) to the neurological effects of interventions like drugs, along with many other advantages, the mice underwent in vivo longitudinal and high-resolution ex vivo imaging with MRI. The scans included three in vivo T1weighted, 90 um isotropic resolution scans and a T2-weighted, 3D fast spin echo with 40um isotropic resolution ex vivo scan to assess the changes in neuroanatomy using established automated image registration and deformation based morphometry approaches in response to oxytocin treatment. The behavior of the mice was assessed in multiple domains, including social behaviours and repetitive behaviours, among others. Treatment effect on the neuroanatomy did not reach significance, although the pattern of trending effects was promising. No significant effect of treatment was found on social behavior in any of the strains, although a significant effect of treatment was found in the Fmr1 mouse, with treatment normalizing a grooming deficit. No other treatment effect on behavior was observed that survived multiple comparisons correction. Overall, chronic treatment with oxytocin had limited effects on the three mouse models related to autism, and no promising pattern of response susceptibility emerged.

Characterization of mice bearing humanized androgen receptor genes (h/mAr) varying in polymorphism length.

The androgen receptor (AR) is known for masculinization of behavior and brain. To better understand the role that AR plays, mice bearing humanized Ar genes with varying lengths of a polymorphic N-terminal glutamine (Q) tract were created (Albertelli et al., 2006). The length of the Q tract is inversely proporitional to AR activity. Biological studies of the Q tract length may also provide a window into potential AR contributions to sex-biases in disease risk. Here we take a multi-pronged approach to characterizing AR signaling effects on brain and behavior in mice using the humanized Ar Q tract model. We first map effects of Q tract length on regional brain anatomy, and consider if these are modified by gonadal sex. We then test the notion that spatial patterns of anatomical variation related to Q tract length could be organized by intrinsic spatiotemporal patterning of AR gene expression in the mouse brain. Finally, we test influences of Q tract length on four behavioral tests.Altering Q tract length led to neuroanatomical differences in a non-linear dosage-dependent fashion. Gene expression analyses indicated that adult neu- roanatomical changes due to Q tract length are only associated with neurode- velopment (as opposed to adulthood). No significant effect of Q tract length was found on the behavior of the three mouse models. These results indicate that AR activity differentially mediates neuroanatomy and behavior, that AR activity alone does not mediate sex differences, and that neurodevelopmen- tal processes are associated with spatial patterns of volume changes due to Q tract length in adulthood. They also indicate that androgen sensitivity in adulthood is not likely to lead to autism-related behaviors or neuroanatomy, although neurodevelopmental processes may play a role earlier. Further study into sex differences, development, other behaviors, and other sex-specific mech- anisms are needed to better understand AR sensitivity, neurodevelopmental disorders, and the sex difference in their prevalence.

Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the visceral area. Additionally, this pattern of explained variation differed spatially across the brain, with transcriptomic similarity playing a larger role in the cortex than subcortex, while connectivity explains structural covariance best in parts of the cortex, midbrain, and hindbrain. These results suggest that both gene expression and connectivity underlie structural volume covariance, albeit to different extents depending on brain region, and this relationship is modulated by distance.

Spatial gene expression analysis of neuroanatomical differences in mouse models.

MRI is a powerful modality to detect neuroanatomical differences that result from mutations and treatments. Knowing which genes drive these differences is important in understanding etiology, but candidate genes are often difficult to identify. We tested whether spatial gene expression data from the Allen Brain Institute can be used to inform us about genes that cause neuroanatomical differences. For many single-gene-mutation mouse models, we found that affected neuroanatomy was not strongly associated with the spatial expression of the altered gene and there are specific caveats for each model. However, among models with significant neuroanatomical differences from their wildtype controls, the mutated genes had preferential spatial expression in affected neuroanatomy. In mice exposed to environmental enrichment, candidate genes could be identified by a genome-wide search for genes with preferential spatial expression in the altered neuroanatomical regions. These candidates have functions related to learning and plasticity. We demonstrate that spatial gene expression of single-genes is a poor predictor of altered neuroanatomy, but altered neuroanatomy can identify candidate genes responsible for neuroanatomical phenotypes.

What is the significance of a faecal elastase-1 level between 200 and 500µg/g?

Background: Pancreatic exocrine insufficiency is a cause of malabsorption. It is generally diagnosed if faecal elastase-1 (FE-1) levels are below 200 µg/g. Pancreatic function is assumed to be normal when faecal elastase levels are >500 µg/g. The significance of faecal elastase levels above 200 µg/g but less than 500 µg/g is unclear. Methods: This retrospective study reports the response to treatment in patients who had an FE-1 level between 200 and 500 µg/g. Results: Of these 82 patients, 28 were offered pancreatic enzyme replacement therapy (PERT). A clinical response, defined as an improvement in their initial symptoms after commencing PERT, was seen in 20 patients (71%), 7 with potentially predisposing conditions and 13 with functional diarrhoea. PERT particularly abolished or improved diarrhoea, steatorrhoea and flatulence. Conclusion: Clinicians should, therefore, be aware that a trial of PERT given to patients with FE-1 levels between 200 and 500 µg/g may lead to improvement in gastrointestinal symptoms.

The Role of the Human Gut Microbiome in Inflammatory Bowel Disease and Radiation Enteropathy.

The human gut microbiome plays a key role in regulating host physiology. In a stable state, both the microbiota and the gut work synergistically. The overall homeostasis of the intestinal flora can be affected by multiple factors, including disease states and the treatments given for those diseases. In this review, we examine the relatively well-characterised abnormalities that develop in the microbiome in idiopathic inflammatory bowel disease, and compare and contrast them to those that are found in radiation enteropathy. We discuss how these changes may exert their effects at a molecular level, and the possible role of manipulating the microbiome through the use of a variety of therapies to reduce the severity of the underlying condition.

Sacral osteomyelitis as a rare cause of anorectal pain several years following treatment for rectal carcinoma.

A 66-year-old man was treated for a moderately differentiated T3 N1 M0 adenocarcinoma of the rectum in 2015 with preoperative short course radiotherapy, anterior resection and then adjuvant chemotherapy with oxaliplatin and capecitabine. Following ileostomy reversal, he complained of intense, unremitting anorectal pain. After repeated scans, computed tomography (CT) showed findings suggestive of a longstanding anastomotic leak. Subsequent, magnetic resonance imaging (MRI) revealed osteomyelitis of the sacrum, with the development of sacral osteomyelitis in this context unusual. Our case highlights the importance of appropriate radiological imaging and that clinicians should consider osteomyelitis as a differential diagnosis in patients presenting with severe anorectal pain after treatment for rectal cancer.

Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities.

Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked on a functional and genetic level. Most work has investigated CHD-related neurodevelopmental abnormalities. Cardiac abnormalities in ASD have been less studied. We investigated the prevalence of cardiac comorbidities relative to ASD genetic contributors. Using high frequency ultrasound imaging, we screened 9 ASD-related genetic mouse models (Arid1b(+/-) , Chd8(+/-) , 16p11.2 (deletion), Sgsh(+/-) , Sgsh(-/-) , Shank3 Δexon 4-9(+/-) , Shank3 Δexon 4-9(-/-) , Fmr1(-/-) , Vps13b(+/-) ), and pooled wild-type littermates (WTs). We measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, mitral inflow Peak E and A velocity ratio, ascending aorta velocity time integral (VTI). Mutant groups presented small-scale alterations in cardiac structure and function compared to WTs (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in structural measures (LV chamber diameter and anterior wall thickness, HR, AoD). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmr1(-/-) , Arid1b(+/-) . The mutant groups with most differences from other mutant groups were 16p11.2 (deletion), Sgsh(+/-) , Fmr1(-/-) . Our results recapitulate the associated clinical findings. The characteristic ASD heterogeneity was recapitulated in the cardiac phenotype. The type of abnormal measures (morphological, functional) can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal abnormalities impact normal development. LAY SUMMARY: Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked functionally and genetically. ASD cardiac phenotyping is limited. We assessed the cardiac phenotype of 9 ASD-related mouse models. We found subtle heterogenous cardiac abnormalities compared to controls, with more differences within ASD than between ASD and controls, mirroring clinical findings. Clinically, knowing the cardiac abnormalities in ASD is vital as even non-lethal cardiac abnormalities can impact development.

A functional cerebral endothelium is necessary to protect against cognitive decline.

A vascular insult occurring early in disease onset may initiate cognitive decline leading to dementia, while pharmacological and lifestyle interventions can prevent this progression. Mice with a selective, tamoxifen-inducible deletion of NF-κB essential modulator (Nemo) in brain endothelial cells were studied as a model of vascular cognitive impairment. Groups included NemoFl controls and three NemobeKO groups: One untreated, and two treated with simvastatin or exercise. Social preference and nesting were impaired in NemobeKO mice and were not countered by treatments. Cerebrovascular function was compromised in NemobeKO groups regardless of treatment, with decreased changes in sensory-evoked cerebral blood flow and total hemoglobin levels, and impaired endothelium-dependent vasodilation. NemobeKO mice had increased string vessel pathology, blood-brain barrier disruption, neuroinflammation, and reduced cortical somatostatin-containing interneurons. These alterations were reversed when endothelial function was recovered. Findings strongly suggest that damage to the cerebral endothelium can trigger pathologies associated with dementia and its functional integrity should be an effective target in future therapeutic efforts.

Nuclear import of serum response factor in airway smooth muscle.

We have previously shown that the transcription-promoting activity of serum response factor (SRF) is partially regulated by its extranuclear redistribution. In this study, we examined the cellular mechanisms that facilitate SRF nuclear entry in canine tracheal smooth muscle cells. We used in vitro pull-down assays to determine which karyopherin proteins bound SRF and found that SRF binds KPNA1 and KPNB1 through its nuclear localization sequence. Immunoprecipitation studies also demonstrated direct SRF-KPNA1 interaction in HEK293 cells. Import assays demonstrated that KPNA1 and KPNB1 together were sufficient to mediate rapid nuclear import of SRF-GFP. Our studies also suggest that SRF is able to gain nuclear entry through an auxiliary, nuclear localization sequence-independent mechanism.

Spatiotemporal Mapping of Early Volume Loss in the Mouse Brain after Cranial Irradiation.

Sequelae after pediatric cranial radiotherapy (CRT) result in long-term changes in brain structure. While past evidence indicates regional differences in brain volume change, it remains unclear how these manifest in the time course of change after CRT. In this study, we spatiotemporally characterized volume losses induced by cranial irradiation in a mouse model, with a dense sampling of measurements over the first week postirradiation. Wild-type mice received whole-brain irradiation (7 Gy) or sham irradiation (0 Gy) at 16 days of age. In vivo magnetic resonance imaging was performed at one time point before, and 2-4 time points postirradiation in each mouse, with a particular focus on sampling during the first week after cranial irradiation. Volume changes across the brain were measured, and the degree and timing of volume loss were quantified across structures from a predefined atlas. Volume measurements across the brain after cranial irradiation revealed a ∼2-day delay in which volume is not significantly altered, after which time volume change proceeds over the course of four days. Volume losses were 3% larger and emerged 40% slower in white matter than in gray matter. Large volume loss was also observed in the ventricles. Differences in the timing and magnitude of volume change between gray and white matter after cranial irradiation were observed. These results suggest differences in the mechanism and/or kinetics underlying the associated radio-response, which may have implications in development.

Exposure to maternal high-fat diet induces extensive changes in the brain of adult offspring.

Maternal environmental exposures, such as high-fat diets, diabetes and obesity, can induce long-term effects in offspring. These effects include increased risk of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), depression and anxiety. The mechanisms underlying these late-life neurologic effects are unknown. In this article, we measured changes in the offspring brain and determined which brain regions are sensitive to maternal metabolic milieu and therefore may mediate NDD risk. We showed that mice exposed to a maternal high-fat diet display extensive brain changes in adulthood despite being switched to a low-fat diet at weaning. Brain regions impacted by early-life diet include the extended amygdalar system, which plays an important role in reward-seeking behaviour. Genes preferentially expressed in these regions have functions related to feeding behaviour, while also being implicated in human NDDs, such as autism. Our data demonstrated that exposure to maternal high-fat diet in early-life leads to brain alterations that persist into adulthood, even after dietary modifications.

Chronic diarrhoea in an oncology patient - Clinical assessment and decision making.

Cancer survival is improving rapidly due to advances in treatments that will often involve radiotherapy, chemotherapy and novel biological agents in addition to surgery. This comes at the price of living with chronic symptoms, of which diarrhoea is particularly common. There is good evidence that for many patients these symptoms become part of everyday life, their "normality" is adjusted and symptoms are tolerated even when limiting activities severely. Clinicians often fail to appreciate the impact of these problems, as the focus of follow up tends to be on cancer recurrence. However, the rapid identification of patients in significant trouble can lead to earlier diagnosis of treatable pathologies and improvement of patients' symptoms. The aim of this review is to highlight the mechanisms which cause oncology patients to develop diarrhoea and highlight useful investigational and treatment strategies.

What is the cost of delayed diagnosis of bile acid malabsorption and bile acid diarrhoea?

INTRODUCTION: 75Selenium taurocholic acid (SeHCAT) scanning diagnoses bile acid malabsorption/bile acid diarrhoea (BAM/BAD) and defines optimal treatment. Approximately 2% of the population have BAM/BAD. AIM: To evaluate the cost of delayed diagnosis of BAM/BAD. METHODS: Patients' notes who underwent SeHCAT scanning in three hospitals over a 1-year period were reviewed retrospectively. Scan results and treatment response were recorded. Package-of-care costs were calculated using costing tools from the National Institute for Health and Care Excellence and from United Lincolnshire Hospitals Trust business unit. RESULTS: Between June 2016 and May 2017, 19 men and 37 women (median age 58 (range 19-83)) of 3860 new patients seen in gastroenterology clinics were referred for SeHCAT scanning. Sixty-four per cent of scans were abnormal: 13 demonstrated severe (<5% 7-day SeHCAT retention), 13 moderate (5%-10%), 5 mild (10%-15%) and 5 borderline (15%-20%) BAD/BAM. Likely causes included primary BAD (n=16), cholecystectomy (n=13), inflammatory bowel disease (n=4) and other (n=3). If SeHCAT scanning was ordered at first consultation (n=11), patients reported 24 months (median) of symptoms (range 6-360) and the median diagnostic package-of-care cost was £811.40 (95% CI £625.59 to £1508.20). If SeHCAT scanning was booked later (n=25), patients reported symptoms for 30 months (median, range 0.5-360) and the cost was £1568.31 (95% CI £1200.55 to £1713.18). Following diagnosis, treatment led to symptom improvement (n=24), no change/deterioration (n=3) and not reported (n=9). CONCLUSIONS: SeHCAT is underused. Late diagnosis leads to unnecessary demands for other services and treatment delay. Early diagnosis achieves health benefits while reducing costs.

An unusual finding of obstructive jaundice-a case report and review of the literature.

Biliary ascariasis is a tropical infectious disease, endemic in regions such as the Far East, Indian subcontinent and parts of the Middle East. The responsible organism is the Ascaris lumbricoides worm. This case study presents a 54-year-old British Caucasian female patient, admitted with a 1-week history of generalized abdominal pain. Ultrasound scan of the abdomen showed a collapsed and abnormal image of the gallbladder. Further imaging for better visualization by magnetic resonance cholangiography showed a 6 cm linear structure in the gallbladder. The morphology was characteristic of gallbladder ascariasis. Detailed history revealed that 6 months ago she had travelled to Turkey. Stool cultures confirmed the presence of ascaris eggs. She was treated conservatively with a 500 mg stat dose of Mebendazole. She was followed up in 6 weeks showing complete resolution of her symptoms.

Mouse MRI shows brain areas relatively larger in males emerge before those larger in females.

Sex differences exist in behaviors, disease and neuropsychiatric disorders. Sexual dimorphisms however, have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. Here, we use manganese-enhanced MRI (MEMRI) to longitudinally image male and female C57BL/6J mice across 9 time points, beginning at postnatal day 3. We recapitulate findings on canonically dimorphic areas, demonstrating MEMRI's ability to study neuroanatomical sex differences. We discover, upon whole-brain volume correction, that neuroanatomical regions larger in males develop earlier than those larger in females. Groups of areas with shared sexually dimorphic developmental trajectories reflect behavioral and functional networks, and expression of genes involved with sex processes. Also, post-pubertal neuroanatomy is highly individualized, and individualization occurs earlier in males. Our results demonstrate the ability of MEMRI to reveal comprehensive developmental differences between male and female brains, which will improve our understanding of sex-specific predispositions to various neuropsychiatric disorders.

Electronic Printed Ward Round Proformas: Freeing Up Doctors' Time.

The role of a junior doctor involves preparing for the morning ward round. At a time when there are gaps on rotas and doctors' time is more stretched, this can be a source of significant delay and thus a loss of working time. We therefore looked at ways in which we could make the ward round a more efficient place by introducing specific electronic, printed ward round proformas. We used the average time taken to write proformas per patient and the average time taken per patient on the ward round. This would then enable us to make fair comparisons with future changes that were made using the plan, do, study, and act principles of quality improvement. Our baseline measurement found that the average time taken to write up the proforma for each patient was 1 minute 9 seconds and that the average time taken per patient on the ward round was 8 minutes 30 seconds. With the changes we made during our 3 PDSA cycles and the implementation of an electronic, printed ward round proforma, we found that we were able to reduce the average time spent per patient on the ward round to 6 minutes 32 seconds, an improvement of 1 min 58 seconds per patient. The project has thus enabled us to reduce the time taken per patient during the ward round. This improved efficiency will enable patients to be identified earlier for discharge. It will also aid in freeing up the time of junior doctors, allowing them to complete discharge letters sooner, order investigations earlier and enable them to complete their allocated tasks within contracted hours.