A novel report of a fertile female with partial Y chromosome gain completing a healthy pregnancy.

We present a female patient with a complex sex chromosomal rearrangement [GRCh38] Xp22.33(10701_981101)x1,Yq11.221q11.23(13948013_26483746)x1 who conceived spontaneously and carried a healthy pregnancy to term. The patient presented with extreme short stature (more than 4SD below expected) and a bilateral Madelung deformity suggesting a possible SHOX deletion. The patient was otherwise medically well. This patient's short stature was found to be a result of a complex chromosome rearrangement involving a partial X chromosome deletion, which included the SHOX gene and a gain of Y chromosomal material. The Y chromosome material did not contain the SRY gene locus. This is the first recorded case to date of this rearrangement in a female who spontaneously conceived which resulted in a live birth. This patient had normal external and internal anatomy and normal endocrine evaluation with normal puberty. X-inactivation studies revealed no evidence of skewed inactivation.

Close intervention sessions complement intensive insulin therapy in paediatric diabetes: a longitudinal study.

OBJECTIVE: To examine the impact of multidisciplinary team input and intensive insulin therapy on glycaemic control in children and adolescents with diabetes over a 13-year period. DESIGN: Two statistical approaches were used to interrogate the dataset. First a matched pair analysis to compare insulin treatment-type effect (pump vs multiple daily injections (MDIs)), followed by panel data regression to assess the impact of intensive re-education on glycated haemoglobin (HbA1c), in addition to treatment type. SETTING: A large tertiary paediatric diabetes centre using a prospectively maintained database of clinical encounters from 2007 to 2020. MAIN OUTCOME MEASURES: Difference in HbA1c between treatment types (matching methodology) and expected change in HbA1c with treatment type and re-education (panel data). RESULTS: Compared with MDI, matched pump patients had a lower HbA1c 6 months after pump commencement (ΔHbA1c=-0.53%, CI -0.34% to -0.72%; n=106). This effect was robust in controlling for socioeconomic deprivation (ΔHbA1c=-0.74%, CI -0.40% to -1.08%; n=29). Panel data analysis demonstrated a -0.55% reduction in HbA1c with pump therapy compared with MDI therapy (CI -0.43% to -0.67%). Patients who had intensive re-education had recorded an HbA1c of 0.95% (CI 0.85% to 1.05%) greater than otherwise identical patients prior to re-education. Following these sessions, HbA1c dropped by a mean -0.81% (CI -0.68% to -0.95%) within 6 months. These were also robust in controlling for socioeconomic factors. CONCLUSIONS: Compared with matched peers on MDI regimens, patients on pump therapy have lower expected HbA1c, an effect sustained for up to 8 years. Intensive re-education is associated with a significant drop in previously elevated HbA1c levels.

Remote neuropsychological assessment: Acceptability and feasibility of direct-to-home teleneuropsychology methodology during the COVID-19 pandemic.

OBJECTIVE: To determine the acceptability and feasibility of telephone and video-conference calls to complete cognitive assessments during the COVID-19 pandemic. METHOD: In rapid response to the pandemic, evidence-based adaptations were made to routine face-to-face (FTF) practice, delivering teleneuropsychology (TNP) within a National Health Service (NHS) Scotland neuropsychology service. Caldicott guardian approval was obtained to complete a six month study (April to October 2020) from the early stages of the first United Kingdom (UK) lockdown. Assessments were completed with patients in their own homes (direct-to-home) via remote connections. Neuropsychology clinicians, service-users and referring agents were approached for structured feedback and qualitative comment. RESULTS: Data was captured for 212 referrals assessed by seven clinical psychologists; with responses from 70 (33%) service-users and 14 (58%) referring agents. 94% of referrals were assessed remotely and discharged. TNP reduced defaulted appointment discharge rates. Gender, socioeconomic deprivation and age did not affect access to information technology (IT) equipment.Clinicians agreed that remote assessment allowed them to complete initial interview (96%) and formulate (77%) cases appropriately. Service-users agreed they were comfortable with equipment (84%), the process was straightforward (74%), and would recommend TNP to others (68%). Referring agents were satisfied with the service provided (100%). Limitations included evidence-based remote test availability, technical issues and home distractions. CONCLUSIONS: Study findings evidence the acceptability and efficiency of TNP; increasing service accessibility, while reducing infection risk, defaulted appointments and travel. The results advocate for a post-pandemic mixed model of service delivery encompassing both FTF and TNP approaches.

What is the Economic Cost of Providing an All Wales Postpartum Haemorrhage Quality Improvement Initiative (OBS Cymru)? A Cost-Consequences Comparison with Standard Care.

BACKGROUND AND OBJECTIVE: A postpartum haemorrhage quality improvement initiative (the Obstetric Bleeding Strategy for Wales [OBS Cymru]), including about 60,000 maternities, was adopted across Wales (2017-2018). We performed a cost-consequences analysis to inform ongoing provision and wider uptake. METHODS: Analysis was based on primary data from the All Wales postpartum haemorrhage database, with a UK National Health Services perspective, a time horizon from delivery until hospital discharge and no discounting. Costs were based on UK published sources with viscoelastic haemostatic assay costs provided by the OBS Cymru national team. Mean costs per eligible patient (postpartum haemorrhage > 1000 mL) were calculated for OBS Cymru, using the early implementation period as a comparator. Modelling allowed comparisons of three scenarios (two predefined and one post hoc) and implementation in different sizes of maternity unit. RESULTS: All analyses demonstrated consistent savings in blood products, critical care and haematology time, and also a reduced occurrence of massive postpartum haemorrhage (> 2500 mL). Incremental postnatal length of stay varied between scenarios, substantially impacting on total costs. Mean incremental cost of OBS Cymru, compared with standard care, across Wales was £18.41 per patient (postpartum haemorrhage > 1000 mL) or - £10.66 if the length of stay was excluded. Modelling a maternity unit of 5000 births per annum, OBS Cymru incurred an incremental cost of £9.53 per patient with postpartum haemorrhage > 1000 mL. CONCLUSIONS: OBS Cymru reduces the occurrence of massive postpartum haemorrhage, need for transfusions, quantity of blood products and intensive care. In medium-to-large maternity units (>3000 maternities per annum), the OBS Cymru intervention approaches cost neutrality compared to standard care.

Hughes abdominal closure versus standard mass closure to reduce incisional hernias following surgery for colorectal cancer: the HART RCT.

BACKGROUND: Incisional hernias can cause chronic pain and complications and affect quality of life. Surgical repair requires health-care resources and has a significant associated failure rate. A prospective, multicentre, single-blinded randomised controlled trial was conducted to investigate the clinical effectiveness and cost-effectiveness of the Hughes abdominal closure method compared with standard mass closure following surgery for colorectal cancer. The study randomised, in a 1 : 1 ratio, 802 adult patients (aged ≥ 18 years) undergoing surgical resection for colorectal cancer from 28 surgical departments in UK centres. INTERVENTION: Hughes abdominal closure or standard mass closure. MAIN OUTCOME MEASURES: The primary outcome was the incidence of incisional hernias at 1 year, as assessed by clinical examination. Within-trial cost-effectiveness and cost-utility analyses over 1 year were conducted from an NHS and a social care perspective. A key secondary outcome was quality of life, and other outcomes included the incidence of incisional hernias as detected by computed tomography scanning. RESULTS: The incidence of incisional hernia at 1-year clinical examination was 50 (14.8%) in the Hughes abdominal closure arm compared with 57 (17.1%) in the standard mass closure arm (odds ratio 0.84, 95% confidence interval 0.55 to 1.27; p = 0.4). In year 2, the incidence of incisional hernia was 78 (28.7%) in the Hughes abdominal closure arm compared with 84 (31.8%) in the standard mass closure arm (odds ratio 0.86, 95% confidence interval 0.59 to 1.25; p = 0.43). Computed tomography scanning identified a total of 301 incisional hernias across both arms, compared with 100 identified by clinical examination at the 1-year follow-up. Computed tomography scanning missed 16 incisional hernias that were picked up by clinical examination. Hughes abdominal closure was found to be less cost-effective than standard mass closure. The mean incremental cost for patients undergoing Hughes abdominal closure was £616.45 (95% confidence interval -£699.56 to £1932.47; p = 0.3580). Quality of life did not differ significantly between the study arms at any time point. LIMITATIONS: As this was a pragmatic trial, the control arm allowed surgeon discretion in the approach to standard mass closure, introducing variability in the techniques and equipment used. Intraoperative randomisation may result in a loss of equipoise for some surgeons. Follow-up was limited to 2 years, which may not have been enough time to see a difference in the primary outcome. CONCLUSIONS: Hughes abdominal closure did not significantly reduce the incidence of incisional hernias detected by clinical examination and was less cost-effective at 1 year than standard mass closure in colorectal cancer patients. Computed tomography scanning may be more effective at identifying incisional hernias than clinical examination, but the clinical benefit of this needs further research. FUTURE WORK: An extended follow-up using routinely collected NHS data sets aims to report on incisional hernia rates at 2-5 years post surgery to investigate any potential mortality benefit of the closure methods. Furthermore, the proportion of incisional hernias identified by a computed tomography scan (at 1 and 2 years post surgery), but not during clinical examination (occult hernias), proceeding to surgical repair within 3-5 years after the initial operation will be explored. TRIAL REGISTRATION: This trial is registered as ISRCTN25616490. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 34. See the NIHR Journals Library website for further project information.

Bowel cancer treatment involves surgery for the majority of patients. A complication of this surgery is the formation of a hernia at the site of the incision in the abdominal wall, known as an incisional hernia. The lining of the abdomen, fat or the intestine can squeeze through the gap and form a lump under the skin. An incisional hernia can form any time after surgery and can cause serious complications and pain, and can also affect the patient's quality of life. Surgery to correct incisional hernias is not always successful, so finding a way of preventing them is important. This research compares the traditional way of sewing up the abdomen, where the two sides are brought together in one layer with a continuous thread, with an alternative method called the Hughes abdominal closure method/Hughes repair. In the Hughes repair, a series of horizontal and vertical stitches are arranged to spread the load and ease the tension across the wound. A total of 802 patients from 28 sites in the UK were recruited to the trial. Half of the patients were randomly allocated to have traditional abdominal closure and half were randomised to have Hughes abdominal closure. All were followed up for 1 year after surgery to assess whether or not an incisional hernia had occurred. We also assessed quality of life during follow-up, and we compared the costs and benefits of each procedure to see which option was the better value for money. By comparing the results from the two methods, it was hoped that the best method of abdominal closure to reduce the risk of an incisional hernia occurring would be found. The analysis of the data suggested that the risk of an incisional hernia was no different with either closure method. Furthermore, Hughes abdominal closure was more expensive and provided less value for money than standard abdominal closure.

Episcissors-60 for Mediolateral Episiotomy: Evaluation of Clinical and Economic Evidence to Inform NICE Medical Technologies Guidance.

Obstetric anal sphincter injury (OASI) occurs in 2.9% of all vaginal births in the UK and can result in faecal incontinence. Where there is a clinical need for episiotomy, OASI can be minimised by accurate selection of the optimum angle of mediolateral episiotomy. Episcissors-60 are adapted surgical scissors incorporating a guide-limb to help achieve an accurate angle of mediolateral episiotomy. The ability of Episcissors-60 to reduce OASI by preventing inaccurate visual estimates of episiotomy angles was considered by the National Institute of Health and Care Excellence (NICE) as part of the Medical Technologies Evaluation Programme (MTEP). NICE concluded that Episcissors-60 shows promise for mediolateral episiotomy both in terms of clinical effectiveness and potential cost savings, but that there was not enough evidence to support routine adoption into the NHS at this time. NICE MTG47 recommends that key gaps in the evidence including patient-reported outcomes and the addition of Episcissors-60 to care bundles be addressed through research with specific focus on potential equality considerations.

Does dietary fat cause a dose dependent glycemic response in youth with type 1 diabetes?

OBJECTIVE: To determine the glycemic impact of dietary fat alone consumed without prandial insulin in individuals with T1D. RESEARCH DESIGN AND METHODS: Thirty participants with T1D (aged 8-18 years) consumed a test drink with either 20 g glucose or 1, 13, 26, 39, 51 g of fat with negligible carbohydrate/protein on 6 consecutive evenings, in a randomized order without insulin. Continuous glucose monitoring was used to measure glucose levels for 8 h postprandially. Primary outcome was mean glycemic excursion at each 30 min interval for each test condition. Generalized linear mixed models with a random effect for people with diabetes were used to test for an increase in blood glucose excursion with increasing quantity of fat. RESULTS: Glycemic excursions after 20 g glucose were higher than after fat drinks over the first 2 h (p < 0.05). Glycemic excursion for the fat drinks demonstrated a dose response, statistically significant from 4 h (p = 0.026), such that increasing loads of fat caused a proportionally larger increase in glycemic excursion, remaining statistically significant until 8 h (p < 0.05). Overall, for every 10 g fat added to the drink, glucose concentrations rose by a mean of 0.28 mmol L-1 from 330 min (95% CI 0.15 to 0.39, p < 0.001). CONCLUSIONS: Fat ingested without other macronutrients increases glucose excursions from 4 to 8 h after ingestion, in a dose dependent manner. These observations may impact on insulin dosing for high-fat foods in individuals with T1D.

gammaCore for Cluster Headaches: A NICE Medical Technologies Guidance.

Cluster headaches are excruciating attacks of pain that can last between 15 min and 3 h. Cluster headaches can be episodic, where patients have long pain-free intervals between attacks, or chronic, where they do not. As part of the Medical Technologies Evaluation Programme, the UK National Institute for Health and Care Excellence (NICE) considered the clinical effectiveness and cost impact of gammaCore (electroCore), a handheld, patient-controlled device used to treat and prevent cluster headache. gammaCore is a non-invasive vagus nerve stimulator, the aim of which is to modify pain signals by stimulating the vagus nerve through the skin of the neck. Evidence suggests that gammaCore reduces the intensity and frequency of cluster headaches and that the addition of gammaCore to standard care is cost saving. Therefore, the guidance published by NICE in December 2019 recommends routine adoption of gammaCore into the UK national health service. However, the guidance noted that gammaCore does not work for everyone and recommended that treatment with gammaCore should stop after 3 months in patients whose symptoms do not improve.

Curos™ Disinfection Caps for the Prevention of Infection When Using Needleless Connectors: A NICE Medical Technologies Guidance.

Central line-associated bloodstream infections (CLABSIs) are primary, laboratory confirmed bloodstream infections in patients with a central line within 48 h of symptom onset. Catheter-related bloodstream infection (CRBSI) is a more specific term used when the cause of infection has been confirmed by catheter tip cultures. CLABSIs and CRBSIs occur as a result of bacteraemia originating from intravenous catheters. Bloodstream infections are associated with increased length of stay, mortality and increased cost in treatment. The ability of Curos™, a disinfecting cap for needleless connectors of vascular access lines, to prevent bloodstream infections was considered by the National Institute of Health and Care Excellence (NICE) as part of the Medical Technologies Evaluation Programme (MTEP). Curos is a single-use device that contains a foam that is impregnated with 70% isopropyl alcohol; use of Curos is claimed to avoid the need to manually disinfect needleless connectors. Curos disinfection caps may contribute to the prevention of CLABSIs and CRBSIs as part of a bundle of infection prevention processes; however, the evidence for Curos is limited in both quantity and quality and may not be generalisable to National Health Service (NHS) practice. Therefore, the guidance published by NICE in May 2019 recommended further research to address uncertainties regarding the clinical benefits of using Curos.

The incidence of transient infantile pseudohypoaldosteronism in Ireland: A prospective study.

AIM: To review the clinical course, outcome and incidence of infantile salt wasting associated with urinary tract infection (UTI) and/or urinary tract malformation (UTM) over a two-year surveillance period on the island of Ireland. METHODS: A two-year (2013-14) prospective surveillance undertaken via the Irish and Ulster Paediatric Surveillance Units. Monthly prepaid postcards were circulated to consultant paediatricians (n = 260) at all paediatric units on the island of Ireland. Infants under one year of age presenting for the first time with hyponatraemia (Na < 130 mmol/L) and/or hyperkalaemia (K > 5.0 mmol/L) associated with urosepsis/UTM were reported. RESULTS: All 7 reported patients (6 male) had culture-proven UTI, and 5 (71%) also had an underlying UTM (one diagnosed antenatally). Four (57%) patients had a documented elevated serum aldosterone supporting secondary pseudohypoaldosteronism (PHA) as the underlying diagnosis. Data on aldosterone were not reported in the other 3 patients, but clinical features were suggestive of secondary PHA. The estimated incidence for the Irish population of transient PHA is 1 per 13,200 total live births per year. CONCLUSIONS: Salt wasting is a rare complication of UTI, especially if associated with underlying UTM. Boys appear to be at particular risk.

Inheritance of a paternal ABCC8 variant and maternal loss of heterozygosity at 11p15 retrospectively unmasks the etiology in a case of Congenital hyperinsulinism.

Advances in genomics and 18F-DOPA PET-CT imaging have transformed the management of infants with Congenital Hyperinsulinism. Preoperative diagnosis of focal hyperinsulinism permits limited pancreatectomy with improved clinical outcomes while knowledge of the molecular etiology informs genetic counseling and provides a more accurate recurrence risk to families.

iFuse Implant System for Treating Chronic Sacroiliac Joint Pain: A NICE Medical Technology Guidance.

Treatment and management of sacroiliac joint pain is often non-surgical, involving packages of care that can include analgesics, physiotherapy, corticosteroid injections and radiofrequency ablation. Surgical intervention is considered when patients no longer respond to conservative management. The iFuse Implant System is placed across the sacroiliac joint using minimally invasive surgery, stabilising the joint and correcting any misalignment or weakness that can cause chronic pain. The iFuse system was evaluated in 2018 by the UK National Institute for Health and Care Excellence (NICE) as part of the Medical Technologies Evaluation Programme (MTEP). Clinical evidence for iFuse suggests improved pain, Oswestry disability index (ODI) and quality of life compared to non-surgical management. The company (SI-Bone®) submitted two cost models indicating that iFuse was cost saving compared with open surgery and non-surgical management. Clinicians advised that non-surgical management was the most appropriate comparator and Cedar (a health technology research centre) made changes to the model to test the impact of higher acquisition and procedure costs. Cedar found iFuse to be cost incurring by approximately £560 per patient at 7 years. During the consultation period, the company reduced the cost of some iFuse consumables, and Cedar extended the time horizon to test the assumption that iFuse would become cost saving over time. These changes indicated that iFuse becomes cost saving at 8 years (approximately £129 per patient), after which the cost saving continues to increase. NICE published guidance in October 2018 recommending that the case for adoption of the iFuse system in the UK National Health Service (NHS) was supported by the evidence.

The Effect of Breathing Retraining Using Metronome-Based Acoustic Feedback on Exercise Endurance in COPD: A Randomized Trial.

BACKGROUND: During exercise-training patients with chronic obstructive pulmonary disease (COPD) can entrain their breathing pattern to visual-feedback cues as to achieve a slower respiratory rate and prolong exhalation. The result is an improvement in exercise tolerance and a reduction in dynamic hyperinflation. Acoustic stimuli, including metronome-generated acoustic stimuli, can entrain human movements. Accordingly, we hypothesized that exercise duration and dynamic hyperinflation would be less after exercise-training plus breathing-retraining using a metronome-based acoustic-feedback system than after exercise-training alone. METHODS: Of 205 patients with COPD [FEV1 = 44 ± 16% predicted (± SD)] recruited, 119 were randomly assigned to exercise-training plus breathing-retraining using acoustic feedback (n = 58) or exercise-training alone (n = 61). Patients exercised on a treadmill thrice-weekly for 12 weeks. Before and at completion of training, patients underwent constant-load treadmill testing with inspiratory capacity measures every 2 min. RESULTS: At completion of training, improvements in exercise duration in the breathing-retraining plus exercise-training and exercise-training alone groups were similar (p = 0.35). At isotime, inspiratory capacity increased (less exercise-induced dynamic hyperinflation) by 3% (p = 0.001) in the breathing-retraining plus exercise-training group and remained unchanged in the exercise-alone group. The between-group change in inspiratory capacity, however, was not significant (p = 0.08). CONCLUSIONS: In patients with COPD, breathing-retraining using a metronome-based acoustic feedback did not result in improved exercise endurance or decreased dynamic hyperinflation when compared to exercise-training alone. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT NCT01009099; URL: http://www.clinicaltrials.gov.

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins.

Smartphone applications for triaging adults with skin lesions that are suspicious for melanoma.

BACKGROUND: Melanoma accounts for a small proportion of all skin cancer cases but is responsible for most skin cancer-related deaths. Early detection and treatment can improve survival. Smartphone applications are readily accessible and potentially offer an instant risk assessment of the likelihood of malignancy so that the right people seek further medical attention from a clinician for more detailed assessment of the lesion. There is, however, a risk that melanomas will be missed and treatment delayed if the application reassures the user that their lesion is low risk. OBJECTIVES: To assess the diagnostic accuracy of smartphone applications to rule out cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with concerns about suspicious skin lesions. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. SELECTION CRITERIA: Studies of any design evaluating smartphone applications intended for use by individuals in a community setting who have lesions that might be suspicious for melanoma or atypical intraepidermal melanocytic variants versus a reference standard of histological confirmation or clinical follow-up and expert opinion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). Due to scarcity of data and poor quality of studies, we did not perform a meta-analysis for this review. For illustrative purposes, we plotted estimates of sensitivity and specificity on coupled forest plots for each application under consideration. MAIN RESULTS: This review reports on two cohorts of lesions published in two studies. Both studies were at high risk of bias from selective participant recruitment and high rates of non-evaluable images. Concerns about applicability of findings were high due to inclusion only of lesions already selected for excision in a dermatology clinic setting, and image acquisition by clinicians rather than by smartphone app users.We report data for five mobile phone applications and 332 suspicious skin lesions with 86 melanomas across the two studies. Across the four artificial intelligence-based applications that classified lesion images (photographs) as melanomas (one application) or as high risk or 'problematic' lesions (three applications) using a pre-programmed algorithm, sensitivities ranged from 7% (95% CI 2% to 16%) to 73% (95% CI 52% to 88%) and specificities from 37% (95% CI 29% to 46%) to 94% (95% CI 87% to 97%). The single application using store-and-forward review of lesion images by a dermatologist had a sensitivity of 98% (95% CI 90% to 100%) and specificity of 30% (95% CI 22% to 40%).The number of test failures (lesion images analysed by the applications but classed as 'unevaluable' and excluded by the study authors) ranged from 3 to 31 (or 2% to 18% of lesions analysed). The store-and-forward application had one of the highest rates of test failure (15%). At least one melanoma was classed as unevaluable in three of the four application evaluations. AUTHORS' CONCLUSIONS: Smartphone applications using artificial intelligence-based analysis have not yet demonstrated sufficient promise in terms of accuracy, and they are associated with a high likelihood of missing melanomas. Applications based on store-and-forward images could have a potential role in the timely presentation of people with potentially malignant lesions by facilitating active self-management health practices and early engagement of those with suspicious skin lesions; however, they may incur a significant increase in resource and workload. Given the paucity of evidence and low methodological quality of existing studies, it is not possible to draw any implications for practice. Nevertheless, this is a rapidly advancing field, and new and better applications with robust reporting of studies could change these conclusions substantially.

Computer-assisted diagnosis techniques (dermoscopy and spectroscopy-based) for diagnosing skin cancer in adults.

BACKGROUND: Early accurate detection of all skin cancer types is essential to guide appropriate management and to improve morbidity and survival. Melanoma and cutaneous squamous cell carcinoma (cSCC) are high-risk skin cancers which have the potential to metastasise and ultimately lead to death, whereas basal cell carcinoma (BCC) is usually localised with potential to infiltrate and damage surrounding tissue. Anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Computer-assisted diagnosis (CAD) systems use artificial intelligence to analyse lesion data and arrive at a diagnosis of skin cancer. When used in unreferred settings ('primary care'), CAD may assist general practitioners (GPs) or other clinicians to more appropriately triage high-risk lesions to secondary care. Used alongside clinical and dermoscopic suspicion of malignancy, CAD may reduce unnecessary excisions without missing melanoma cases. OBJECTIVES: To determine the accuracy of CAD systems for diagnosing cutaneous invasive melanoma and atypical intraepidermal melanocytic variants, BCC or cSCC in adults, and to compare its accuracy with that of dermoscopy. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles. SELECTION CRITERIA: Studies of any design that evaluated CAD alone, or in comparison with dermoscopy, in adults with lesions suspicious for melanoma or BCC or cSCC, and compared with a reference standard of either histological confirmation or clinical follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities separately by type of CAD system, using the bivariate hierarchical model. We compared CAD with dermoscopy using (a) all available CAD data (indirect comparisons), and (b) studies providing paired data for both tests (direct comparisons). We tested the contribution of human decision-making to the accuracy of CAD diagnoses in a sensitivity analysis by removing studies that gave CAD results to clinicians to guide diagnostic decision-making. MAIN RESULTS: We included 42 studies, 24 evaluating digital dermoscopy-based CAD systems (Derm-CAD) in 23 study cohorts with 9602 lesions (1220 melanomas, at least 83 BCCs, 9 cSCCs), providing 32 datasets for Derm-CAD and seven for dermoscopy. Eighteen studies evaluated spectroscopy-based CAD (Spectro-CAD) in 16 study cohorts with 6336 lesions (934 melanomas, 163 BCC, 49 cSCCs), providing 32 datasets for Spectro-CAD and six for dermoscopy. These consisted of 15 studies using multispectral imaging (MSI), two studies using electrical impedance spectroscopy (EIS) and one study using diffuse-reflectance spectroscopy. Studies were incompletely reported and at unclear to high risk of bias across all domains. Included studies inadequately address the review question, due to an abundance of low-quality studies, poor reporting, and recruitment of highly selected groups of participants.Across all CAD systems, we found considerable variation in the hardware and software technologies used, the types of classification algorithm employed, methods used to train the algorithms, and which lesion morphological features were extracted and analysed across all CAD systems, and even between studies evaluating CAD systems. Meta-analysis found CAD systems had high sensitivity for correct identification of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in highly selected populations, but with low and very variable specificity, particularly for Spectro-CAD systems. Pooled data from 22 studies estimated the sensitivity of Derm-CAD for the detection of melanoma as 90.1% (95% confidence interval (CI) 84.0% to 94.0%) and specificity as 74.3% (95% CI 63.6% to 82.7%). Pooled data from eight studies estimated the sensitivity of multispectral imaging CAD (MSI-CAD) as 92.9% (95% CI 83.7% to 97.1%) and specificity as 43.6% (95% CI 24.8% to 64.5%). When applied to a hypothetical population of 1000 lesions at the mean observed melanoma prevalence of 20%, Derm-CAD would miss 20 melanomas and would lead to 206 false-positive results for melanoma. MSI-CAD would miss 14 melanomas and would lead to 451 false diagnoses for melanoma. Preliminary findings suggest CAD systems are at least as sensitive as assessment of dermoscopic images for the diagnosis of invasive melanoma and atypical intraepidermal melanocytic variants. We are unable to make summary statements about the use of CAD in unreferred populations, or its accuracy in detecting keratinocyte cancers, or its use in any setting as a diagnostic aid, because of the paucity of studies. AUTHORS' CONCLUSIONS: In highly selected patient populations all CAD types demonstrate high sensitivity, and could prove useful as a back-up for specialist diagnosis to assist in minimising the risk of missing melanomas. However, the evidence base is currently too poor to understand whether CAD system outputs translate to different clinical decision-making in practice. Insufficient data are available on the use of CAD in community settings, or for the detection of keratinocyte cancers. The evidence base for individual systems is too limited to draw conclusions on which might be preferred for practice. Prospective comparative studies are required that evaluate the use of already evaluated CAD systems as diagnostic aids, by comparison to face-to-face dermoscopy, and in participant populations that are representative of those in which the test would be used in practice.

Diagnosis and management of pancreatic cancer in adults: A summary of guidelines from the UK National Institute for Health and Care Excellence.

To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer.

Incidence of Congenital Hypothyroidism Over 37 Years in Ireland.

BACKGROUND AND OBJECTIVES: Congenital hypothyroidism (CHT) is one of the most common preventable causes of learning disability. Newborn screening with whole-blood thyroid-stimulating hormone measurements was introduced in the Republic of Ireland in 1979 and is coordinated from a single center with an unchanged protocol since its inception. Our objective in this study was to describe the incidence of CHT in the Republic of Ireland over the past 37 years in the context of a complete national population and an unchanged screening protocol. METHODS: The newborn screening records of all individuals who were diagnosed with CHT between 1979 and 2016 were reviewed. Infants with positive screening results had a whole-blood thyroid-stimulating hormone value of ≥15 mU/L at 72 to 120 hours of life; values of 8 to 15 mU/L required a repeat whole-blood screening test. RESULTS: Of 2 361 174 infants who were screened between July 1979 and December 2016, 1063 (662 girls) were diagnosed with CHT (incidence: 0.45 cases per 1000 live births). The number of detected cases increased from 0.27 cases per 1000 live births treated between 1979 and 1991 to 0.41 cases per 1000 live births treated between 1992 and 2004 to 0.65 cases per 1000 live births treated between 2005 and 2016. The increase in detected cases of CHT was predominantly in the normal or hyperplastic gland category. CONCLUSIONS: The incidence of CHT has increased significantly in the Republic of Ireland over the past 37 years despite a consistent screening cutoff. The increased rate was not explained by an increased survival rate of preterm infants or a changing population heterogeneity.

Subarachnoid and parenchymal haemorrhages as a complication of severe diabetic ketoacidosis in a preadolescent with new onset type 1 diabetes.

Diabetic ketoacidosis (DKA) is one of the most common causes of morbidity and mortality in new onset type 1 diabetes mellitus (T1DM). Children have a higher rate of neurological complications from DKA when compared to adults. The differential for sudden focal neurological deterioration in the setting of DKA is cerebral oedema followed by ischaemic and haemorrhagic stroke. Spontaneous intracranial haemorrhages can present with non-specific features frequently, for example, impaired consciousness, even when biochemical parameters are improving in the setting of DKA. We report the case of a girl with new onset T1D who presented in severe DKA and subsequently developed intracerebral parenchymal and subarachnoid haemorrhages. Our patient is unique in that no focal neurological or neuropsychological deficits have been found at 1-year follow up, compared to the literature which suggests poor outcomes. Our case contrasts with these previous cases as none of the other case reports demonstrated subarachnoid haemorrhages with survival.