Postconceptual Neonatal Dating by Transmastoid Ultrasound of Transcerebellar Diameter-Comparison to Crown Rump Length Measurement: A Proof of Concept Paper.

OBJECTIVES: Transcerebellar diameter (TCD) has been utilized prenatally as a tool to estimate gestational age (GA) when fetal growth aberrations are suspected. Traditionally, first trimester ultrasound (1TUS) has been the gold standard of dating a pregnancy in spontaneous pregnancies. We sought to determine if neonatal TCD measurement was as accurate as 1TUS in the estimation of postconceptual gestational age (PCGA). METHODS: A retrospective cohort from a registry of high-quality transmastoid views of consecutive patients from July 2019 to November 2020, delivered from 24 to 34 weeks GA, and with a 1TUS were included. The reference PCGA was the sum of the GA at delivery by 1TUS and day of life. The PCGA by TCD was calculated from Chang et al for GA by TCD. Reference and experimental values were compared by correlation, agreement within 7 days, and Bland-Altman analysis. RESULTS: Of the 154 individual patients in the registry of high-quality transmastoid views during the study period, 62 met inclusion and exclusion criteria. PCGA by 1TUS and TCD were highly correlated (r = 0.86, P < .001; κ = 47% agreement within 7 days of PCGA). The bias of PCGA by TCD was 4.6 days earlier than the PCGA by 1TUS (95% confidence interval of agreement: -29.2, 20). CONCLUSIONS: PCGA estimation by neonatal transmastoid TCD was highly correlated with that of 1TUS. It generally underestimates GA by 4.6 days. This relationship warrants further investigation to determine if this method of estimating PCGA in undated gestations is generalizable.

Supporting active engagement of adults with intellectual disabilities in lifestyle modification interventions: a realist evidence synthesis of what works, for whom, in what context and why.

BACKGROUND: Lifestyle modification interventions for adults with intellectual disabilities have had, to date, mixed effectiveness. This study aimed to understand how lifestyle modification interventions for adults with intellectual disabilities work, for whom they work and in what circumstances. METHODS: A realist evidence synthesis was conducted that incorporated input from adults with intellectual disabilities and expert researchers. Following the development of an initial programme theory based on key literature and input from people with lived experience and academics working in this field, five major databases (MEDLINE, EMBASE, CINAHL, PsycINFO and ASSIA) and clinical trial repositories were systematically searched. Data from 79 studies were synthesised to develop context, mechanism and outcome configurations (CMOCs). RESULTS: The contexts and mechanisms identified related to the ability of adults with intellectual disabilities to actively take part in the intervention, which in turn contributes to what works, for whom and in what circumstances. The included CMOCs related to support involvement, negotiating the balance between autonomy and behaviour change, fostering social connectedness and fun, accessibility and suitability of intervention strategies and delivery and broader behavioural pathways to lifestyle change. It is also essential to work with people with lived experiences when developing and evaluating interventions. CONCLUSIONS: Future lifestyle interventions research should be participatory in nature, and accessible data collection methods should also be explored as a way of including people with severe and profound intellectual disabilities in research. More emphasis should be given to the broader benefits of lifestyle change, such as opportunities for social interaction and connectedness.

Lifestyle modification interventions for adults with intellectual disabilities: systematic review and meta-analysis at intervention and component levels.

BACKGROUND: Adults with intellectual disabilities (IDs) are susceptible to multiple health risk behaviours such as alcohol consumption, smoking, low physical activity, sedentary behaviour and poor diet. Lifestyle modification interventions can prevent or reduce negative health consequences caused by these behaviours. We aim to determine the effectiveness of lifestyle modification interventions and their components in targeting health risk behaviours in adults with IDs. METHODS: A systematic review and meta-analysis were conducted. Electronic databases, clinical trial registries, grey literature and citations of systematic reviews and included studies were searched in January 2021 (updated February 2022). Randomised controlled trials and non-randomised controlled trials targeting alcohol consumption, smoking, low physical activity, sedentary behaviours and poor diet in adults (aged ≥ 18 years) with ID were included. Meta-analysis was conducted at the intervention level (pairwise and network meta-analysis) and the component-level (component network meta-analysis). Studies were coded using Michie's 19-item theory coding scheme and 94-item behaviour change taxonomies. Risk of bias was assessed using the Cochrane Risk of Bias (ROB) Version 2 and Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I). The study involved a patient and public involvement (PPI) group, including people with lived experience, who contributed extensively by shaping the methodology, providing valuable insights in interpreting results and organising of dissemination events. RESULTS: Our literature search identified 12 180 articles, of which 80 studies with 4805 participants were included in the review. The complexity of lifestyle modification intervention was dismantled by identifying six core components that influenced outcomes. Interventions targeting single or multiple health risk behaviours could have a single or combination of multiple core-components. Interventions (2 RCTS; 4 non-RCTs; 228 participants) targeting alcohol consumption and smoking behaviour were effective but based on limited evidence. Similarly, interventions targeting low physical activity only (16 RCTs; 17 non-RCTs; 1413 participants) or multiple behaviours (low physical activity only, sedentary behaviours and poor diet) (17 RCTs; 24 non-RCTs; 3164 participants) yielded mixed effectiveness in outcomes. Most interventions targeting low physical activity only or multiple behaviours generated positive effects on various outcomes while some interventions led to no change or worsened outcomes, which could be attributed to the presence of a single core-component or a combination of similar core components in interventions. The intervention-level meta-analysis for weight management outcomes showed that none of the interventions were associated with a statistically significant change in outcomes when compared with treatment-as-usual and each other. Interventions with core-components combination of energy deficit diet, aerobic exercise and behaviour change techniques showed the highest weight loss [mean difference (MD) = -3.61, 95% credible interval (CrI) -9.68 to 1.95] and those with core-components combination dietary advice and aerobic exercise showed a weight gain (MD 0.94, 95% CrI -3.93 to 4.91). Similar findings were found with the component network meta-analysis for which additional components were identified. Most studies had a high and moderate risk of bias. Various theories and behaviour change techniques were used in intervention development and adaptation. CONCLUSION: Our systematic review is the first to comprehensively explore lifestyle modification interventions targeting a range of single and multiple health risk behaviours in adults with ID, co-produced with people with lived experience. It has practical implications for future research as it highlights the importance of mixed-methods research in understanding lifestyle modification interventions and the need for population-specific improvements in the field (e.g., tailored interventions, development of evaluation instruments or tools, use of rigorous research methodologies and comprehensive reporting frameworks). Wide dissemination of related knowledge and the involvement of PPI groups, including people with lived experience, will help future researchers design interventions that consider the unique needs, desires and abilities of people with ID.

Use of real-time electronic extremity dosimeters for monitoring and optimisation of radiopharmacy technique.

Radiopharmacy staff members are subject to extremity radiation doses, particularly to the fingertips. Dosemeters, such as, thermoluminescent detectors (TLDs) are currently used for monitoring fingertip doses. This study aimed to use real-time dosemeters to monitor radiopharmacy extremity doses to identify specific procedural steps associated with higher fingertip doses and, subsequently, reduce dose through promotion of optimised radiation protection practises. Five radiopharmacy operators were monitored using an ED3 active extremity dosemeter with a detector attached to each tip of the index fingers. Dose rate and accumulated dose data were matched to the handled radioactivity data, of99mTc-labelled radiopharmaceuticals only, with the dose per activity (µSv MBq-1) calculated for each step. Once baseline dose data was established, an educational session identified technique adjustments toward improved radiation protection. A subsequent monitored session was undertaken with the dose data compared to quantify changes in operator doses. Radiopharmacy steps which significantly contributed to extremity doses were identified. The average accumulated dose per activity across all procedural steps for the99mTc-labelled radiopharmaceuticals for all operators before the educational session was 0.042 ± 0.045µSv MBq-1and 0.042 ± 0.041µSv MBq-1(n= 89) for non-dominant and dominant index fingertips, respectively, and 0.030 ± 0.044µSv MBq-1and 0.031 ± 0.032µSv MBq-1(n= 97), respectively, afterwards. Overall, there was an average 40.7% reduction in the total extremity dose received after the educational session. Real-time electronic extremity dosemeters for monitoring radiopharmacy extremity dose presented as a useful tool for incorporation into radiation protection education and training, towards optimised radiopharmacy technique.

Pediatric Heart Network Trial of Losartan vs. Atenolol in Children and Young Adults with Marfan Syndrome: Impact on Prescription Practices.

The Pediatric Heart Network (PHN) trial showed similar efficacy of ß-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months-25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p < 0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p < 0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p = 0.37] and ARB [OR 1.91 (0.55, 6.69), p = 0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.

ChatGPT and the Future of Journal Reviews: A Feasibility Study.

The increasing volume of research submissions to academic journals poses a significant challenge for traditional peer-review processes. To address this issue, this study explores the potential of employing ChatGPT, an advanced large language model (LLM), developed by OpenAI, as an artificial intelligence (AI) reviewer for academic journals. By leveraging the vast knowledge and natural language processing capabilities of ChatGPT, we hypothesize it may be possible to enhance the efficiency, consistency, and quality of the peer-review process. This research investigated key aspects of integrating ChatGPT into the journal review workflow. We compared the critical analysis of ChatGPT, acting as an AI reviewer, to human reviews for a single published article. Our methodological framework involved subjecting ChatGPT to an intricate examination, wherein its evaluative acumen was juxtaposed against human-authored reviews of a singular published article. As this is a feasibility study, one article was reviewed, which was a case report on scurvy. The entire article was used as an input into ChatGPT and commanded it to "Please perform a review of the following article and give points for revision." Since this was a case report with a limited word count the entire article could fit in one chat box. The output by ChatGPT was then compared with the comments by human reviewers. Key performance metrics, including precision and overall agreement, were judiciously and subjectively measured to portray the efficacy of ChatGPT as an AI reviewer in comparison to its human counterparts. The outcomes of this rigorous analysis unveiled compelling evidence regarding ChatGPT's performance as an AI reviewer. We demonstrated that ChatGPT's critical analyses aligned with those of human reviewers, as evidenced by the inter-rater agreement. Notably, ChatGPT exhibited commendable capability in identifying methodological flaws, articulating insightful feedback on theoretical frameworks, and gauging the overall contribution of the articles to their respective fields. While the integration of ChatGPT showcased immense promise, certain challenges and caveats surfaced. For example, ambiguities might present with complex research articles, leading to nuanced discrepancies between AI and human reviews. Also figures and images cannot be reviewed by ChatGPT. Lengthy articles need to be reviewed in parts by ChatGPT as the entire article will not fit in one chat/response. The benefits consist of reduction in time needed by journals to review the articles submitted to them, as well as an AI assistant to give a different perspective about the research papers other than the human reviewers. In conclusion, this research contributes a groundbreaking foundation for incorporating ChatGPT into the pantheon of journal reviewers. The delineated guidelines distill key insights into operationalizing ChatGPT as a proficient reviewer within academic journal frameworks, paving the way for a more efficient and insightful review process.

Fetal imaging of congenital lung lesions with postnatal correlation.

Congenital lung lesions are a rare group of developmental pulmonary abnormalities that are often first identified prenatally on routine second-trimester US. Congenital pulmonary airway malformation (CPAM) is the most common anomaly while others include bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and bronchial atresia. Clinical presentation is highly variable, ranging from apparent in utero resolution to severe mass effect with resultant hydrops fetalis and fetal demise. Differentiation among these lesions can be challenging because overlapping imaging features are often present. The roles of the radiologist are to identify key imaging findings that help in diagnosing congenital lung lesions and to recognize any ominous features that might require prenatal or perinatal intervention. High-resolution US and complementary rapid-acquisition fetal MRI provide valuable information necessary for lesion characterization. Postnatal US and CT angiography are helpful for lesion evaluation and for possible surgical planning. This article reviews the embryology of the lungs, the normal prenatal imaging appearance of the thorax and its contents, and the prenatal and neonatal imaging characteristics, prognosis and management of various congenital lung lesions.

Acute Pulmonary Embolism in an Intensive Care Unit Setting in Sierra Leone.

INTRODUCTION: In Sierra Leone, the lack of information on pulmonary embolism (PE) limits the access to evidence-based standard of diagnostic work-up and management of the disease. The objective of this study was to describe the clinical characteristics and management of acute pulmonary embolism in our setting and to determine whether the pre-test probability scoring algorithms were used prior to Computed Tomography Pulmonary Angiogram (CTPA) request. METHODS: This retrospective observational study was conducted on CTPA-confirmed PE patients admitted to the Intensive Care Unit, Choithrams Memorial Hospital, in Freetown, Sierra Leone between July 2014 to June 2019. Clinical data, and pertinent investigations related to PE were determined. CTPA findings were correlated with the patient's hemodynamic status. The calculated pretest clinical probability scores (PCPS) for each patient were compared to the CTPA results. RESULTS: CTPA-confirmed PE in the study cohort was 79, with a rate of 16 new PE per year. The frequency of PE was 1.9% of the total hospital admission per year. The mean age was 64.1 ± 17.9 years, median age was 63.3years (range: 23-89 years), with 55.7% of the cohort being females. Dyspnea (78.5%) and tachycardia (69.6%) were the commonest signs and symptoms documented, with immobilization (34.2%) being the prevalent risk factor, while hypertension (48.1%) was the most common co-morbidity. The PCPS algorithm was underutilized, as "Wells Score" was documented in only 9.5% while "modified Geneva score" was never used by hospital physicians. PE with hemodynamic stability was significantly more common than PE with unstable hemodynamic status [55 (69.6%) vs 24 (30.4%), p=0.015]. All patients were managed only with anticoagulants. The overall in-hospital mortality was 17.7%. CONCLUSION: Since PCPS was hardly calculated by doctors in the diagnosis of PE, the study showed that the diagnostic algorithm for suspected PE was infrequently used in clinical practice. The use of empirical judgement by doctors in requesting for CTPA may have accounted for low rate in the diagnosis of PE per year. The establishment of P.E registry in Sierra Leone is imperative.

INTRODUCTION: En Sierra Leone, le manque d'informations sur l'embolie pulmonaire (EP) limite l'accès à des normes de diagnostic et de prise en charge de la maladie fondées sur des preuves. L'objectif de cette étude était de décrire les caractéristiques cliniques et la prise en charge de l'embolie pulmonaire aiguë dans notre établissement et de déterminer si les algorithmes de notation de la probabilité pré-test étaient utilisés avant la demande d'angiographie pulmonaire par tomodensitométrie (CTPA). MÉTHODES: Cette étude observationnelle rétrospective a été menée sur des patients atteints d'EP confirmée par CTPA admis à l'unité de soins intensifs, Choithrams Memorial Hospital, à Freetown, Sierra Leone, entre juillet 2014 et juin 2019. Les données cliniques, et les investigations pertinentes liées à l'EP ont été déterminées. Les résultats du CTPA ont été corrélés avec l'état hémodynamique du patient. Les scores de probabilité clinique prétest (PCPS) calculés pour chaque patient ont été comparés aux résultats du CTPA. RÉSULTATS: Le nombre d'EP confirmées par CTPA dans la cohorte étudiée était de 79, avec un taux de 16 nouvelles EP par an. La fréquence de l'EP était de 1,9 % du nombre total d'hospitalisations par an. L'âge moyen était de 64,1 ± 17,9 ans, l'âge médian de 63,3 ans (fourchette : 23-89 ans), 55,7 % de la cohorte étant des femmes. La dyspnée (78,5 %) et la tachycardie (69,6 %) étaient les signes et symptômes les plus fréquemment documentés, l'immobilisation (34,2%) étant le facteur de risque prévalent, tandis que l'hypertension (48,1 %) était la comorbidité la plus courante. L'algorithme PCPS était sous-utilisé, le " score de Wells " n'étant documenté que dans 9,5 % des cas, tandis que le " score de Genève modifié " n'était jamais utilisé par les médecins hospitaliers. L'EP avec stabilité hémodynamique était significativement plus fréquente que l'EP avec état hémodynamique instable [55 (69,6 %) vs 24 (30,4 %), p=0,015]. Tous les patients ont été traités uniquement par anticoagulants. La mortalité globale à l'hôpital était de 17,7 %. CONCLUSION: Étant donné que le PCPS était rarement calculé par les médecins pour le diagnostic de l'EP, l'étude a montré que l'algorithme diagnostique pour l'EP suspectée était rarement utilisé dans la pratique clinique. L'utilisation d'un jugement empirique par les médecins pour demander un CTPA peut expliquer le faible taux de diagnostic de l'EP par an. L'établissement d'un registre de l'E.P. en Sierra Leone est impératif. Mots-clés: Embolie pulmonaire, caractéristiques cliniques, gestion, Sierra Leone.

Virtual endoluminal aortic root views determined at coronary CT angiography - an important tool for improving anomalous coronary artery visualization and surgical planning.

Anomalous origin of the coronary arteries, though uncommon, is of great clinical concern. It can be the cause of sudden cardiac death and abnormal cardiac hemodynamics. Advances in electrocardiographically (ECG)-gated multi-detector CT have increased diagnostic accuracy in detecting anomalous origin of coronary arteries and their interarterial and intramural courses. Recent advances in multi-detector CT image processing software have allowed the creation of virtual endoluminal views of the aortic root and improved assessment of the intramural course (the length and relationship to the intercoronary commissure) of the coronary artery, which is of considerable surgical importance. We review our experience with virtual endoluminal imaging in our first 19 cases of interarterial coronary artery anomalies (17 cases of interarterial with intramural segment and 2 cases of purely interarterial course) diagnosed preoperatively and proven surgically.

Cost-Effectiveness of Transitional Care Services After Hospitalization With Heart Failure.

Background: Patients with heart failure (HF) discharged from the hospital are at high risk for death and rehospitalization. Transitional care service interventions attempt to mitigate these risks. Objective: To assess the cost-effectiveness of 3 types of postdischarge HF transitional care services and standard care. Design: Decision analytic microsimulation model. Data Sources: Randomized controlled trials, clinical registries, cohort studies, Centers for Disease Control and Prevention life tables, Centers for Medicare & Medicaid Services data, and National Inpatient Sample (Healthcare Cost and Utilization Project) data. Target Population: Patients with HF who were aged 75 years at hospital discharge. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Disease management clinics, nurse home visits (NHVs), and nurse case management. Outcome Measures: Quality-adjusted life-years (QALYs), costs, net monetary benefits, and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis: All 3 transitional care interventions examined were more costly and effective than standard care, with NHVs dominating the other 2 interventions. Compared with standard care, NHVs increased QALYs (2.49 vs. 2.25) and costs ($81 327 vs. $76 705), resulting in an ICER of $19 570 per QALY gained. Results of Sensitivity Analysis: Results were largely insensitive to variations in in-hospital mortality, age at baseline, or costs of rehospitalization. Probabilistic sensitivity analysis confirmed that transitional care services were preferred over standard care in nearly all 10 000 samples, at willingness-to-pay thresholds of $50 000 or more per QALY gained. Limitation: Transitional care service designs and implementations are heterogeneous, leading to uncertainty about intervention effectiveness and costs when applied in particular settings. Conclusion: In older patients with HF, transitional care services are economically attractive, with NHVs being the most cost-effective strategy in many situations. Transitional care services should become the standard of care for postdischarge management of patients with HF. Primary Funding Source: Swiss National Science Foundation, Research Council of Norway, and an Intermountain-Stanford collaboration.

Contrast-enhanced ultrasound of the kidneys and adrenals in children.

Pediatric applications of contrast-enhanced ultrasound (CEUS) are growing. Evaluation of the kidneys and adrenal glands in children using intravenous administration of US contrast agents, however, is still an off-label indication. Pediatric CEUS applications for kidneys are similar to those in adults, including ischemic disorders, pseudo- versus real tumors, indeterminate lesions, complex cystic lesions, complicated pyelonephritis, and abscesses. CEUS applications for evaluation of adrenal glands in children are limited, mainly focusing on the assessment and follow-up of adrenal trauma and the differentiation between an adrenal hemorrhage and a mass. This review addresses the current experience in pediatric CEUS of the kidneys and adrenal glands. By extrapolating the established knowledge for US contrast evaluations in the adult kidney to the pediatric context we can note opportunities for CEUS clinical use in children.

Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH trial (EAY131) subprotocol Q.

BACKGROUND: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. METHODS: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. RESULTS: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. CONCLUSION: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.

Phylogenetic Analysis of Mycobacterium tuberculosis Strains in Wales by Use of Core Genome Multilocus Sequence Typing To Analyze Whole-Genome Sequencing Data.

An inability to standardize the bioinformatic data produced by whole-genome sequencing (WGS) has been a barrier to its widespread use in tuberculosis phylogenetics. The aim of this study was to carry out a phylogenetic analysis of tuberculosis in Wales, United Kingdom, using Ridom SeqSphere software for core genome multilocus sequence typing (cgMLST) analysis of whole-genome sequencing data. The phylogenetics of tuberculosis in Wales have not previously been studied. Sixty-six Mycobacterium tuberculosis isolates (including 42 outbreak-associated isolates) from south Wales were sequenced using an Illumina platform. Isolates were assigned to principal genetic groups, single nucleotide polymorphism (SNP) cluster groups, lineages, and sublineages using SNP-calling protocols. WGS data were submitted to the Ridom SeqSphere software for cgMLST analysis and analyzed alongside 179 previously lineage-defined isolates. The data set was dominated by the Euro-American lineage, with the sublineage composition being dominated by T, X, and Haarlem family strains. The cgMLST analysis successfully assigned 58 isolates to major lineages, and the results were consistent with those obtained by traditional SNP mapping methods. In addition, the cgMLST scheme was used to resolve an outbreak of tuberculosis occurring in the region. This study supports the use of a cgMLST method for standardized phylogenetic assignment of tuberculosis isolates and for outbreak resolution and provides the first insight into Welsh tuberculosis phylogenetics, identifying the presence of the Haarlem sublineage commonly associated with virulent traits.

Octreotide Added to a Proton Pump Inhibitor Versus a Proton Pump Inhibitor Alone in Nonvariceal Upper-Gastrointestinal Bleeds.

Background: Literature indicating clinically relevant benefits of an adjunctive somatostatin analog to standard therapies in nonvariceal upper-gastrointestinal bleeding (NVUGIB) is lacking. Objective: The primary objective of this study was to find the association between outcomes in patients with NVUGIB treated with octreotide and a proton pump inhibitor (PPI; combination group) compared with those treated with a PPI alone. Methods: We conducted a retrospective cohort study of adults admitted within a 5-hospital health care system with a NVUGIB treated with a PPI continuous infusion with or without an octreotide infusion. Notable exclusion criteria included varices, history of cirrhosis without endoscopy, or active gastrointestinal cancer. The primary outcome was association of combination treatment versus PPI alone with hospital length of stay (LOS). Results: A total of 180 patients were included (combination group: n = 90; PPI: n = 90). In univariate analyses, the median hospital and intensive care unit (ICU) LOS in the combination group versus PPI was 6.1 versus 4.9 days (P = 0.25) and 2.3 versus 1.9 days (P = 0.24), and rebleeding and mortality occurred in 9% versus 12% (P = 0.63) and 6.7% versus 5.6% (P = 1.00) of patients. Median units of packed red blood cells in the combination therapy versus PPI group was 3 vs 2 units (P = 0.43). After propensity score adjustment in multivariable analyses, hospital and ICU LOS, rebleeding, and mortality all remained nonsignificant. Conclusion and Relevance: Our study observed no difference in clinical end points. This suggests that octreotide provides no additional major clinical benefit in NVUGIB, and PPI therapy alone may be sufficient.

Capsaicin-induced pain and sensitisation in the postpartum period.

BACKGROUND: Recovery from Caesarean delivery in women and surgical nerve injury in animals after delivery is more rapid than expected, an effect reversed in animals by spinal injection of an oxytocin receptor antagonist. We hypothesised that endogenous modulation of acute pain is altered postpartum. METHODS: Endogenous inhibition of acute pain in a conditioned pain modulation paradigm or endogenous sensitisation by topical capsaicin was tested in women who were breastfeeding 10-14 days after Caesarean delivery and age-matched controls (n=80 total: 20 per group and 20 per test). The study was powered to detect a difference in area of hyperalgesia after capsaicin of 33%. Capsaicin-evoked pain was recorded in women, and capsaicin-evoked mechanical hypersensitivity was measured in rats 48 h after delivery and in age-matched female and male animals. RESULTS: There was no effect of the postpartum period in the endogenous sensitisation assay in women, and the conditioned pain modulation assay failed to produce analgesia in either group. Postpartum women, however, reported less intense pain than controls at the end of topical capsaicin exposure (1.3 [1.4] vs 2.0 [2.0] on 0-10 verbal scale), and acute hypersensitivity after capsaicin was less in postpartum than control rats (withdrawal threshold 25 [15] vs 3.6 [1] g). CONCLUSIONS: These results agree with a recent report that oxytocin may desensitise the transient receptor potential for vanilloid-1 channel, although other explanations, including hormone effects, are possible. These results do not, however, support the inhibition of capsaicin-evoked spinal sensitisation in the postpartum period. CLINICAL TRIAL REGISTRATION: NCT01843517.

Process evaluation of a cluster-randomised controlled trial of multi-component weight management programme in adults with intellectual disabilities and obesity.

BACKGROUND: Providing effective weight management to adults with intellectual disabilities is necessary to challenge the high rates of obesity. The aim of this process evaluation was to explore the feasibility of conducting a full-scale clinical trial of the TAKE 5 multi-component weight management programme. METHODS: The study was a 12-month pilot cluster-randomised controlled trial. Adults with intellectual disabilities and obesity were randomised to either TAKE 5, which included an energy deficit diet (EDD) or Waist Winners Too, based on health education principles. A mixed-methods process evaluation was conducted focussing on the reach, recruitment, fidelity, implementation, dose (delivered/received) and context. RESULTS: The study successfully recruited adults with intellectual disabilities. Both weight management programmes were delivered with high fidelity and implemented as intended. Only one weight management programme, TAKE 5, demonstrated potential efficacy in reducing body weight and body composition. The effectiveness was largely attributed to the EDD and social support from carers. CONCLUSIONS: The extensive process evaluation illustrated that a full-scale trial of a multi-component programme including an EDD is feasible and an acceptable approach to weight management for adults with intellectual disabilities and obesity.

PREVENTION-ACHD: PRospEctiVE study on implaNTable cardioverter-defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease; Rationale and Design.

BACKGROUND: Many adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). An implantable cardioverter-defibrillator (ICD) may prevent SCD, but the evidence for primary prevention indications is still unsatisfactory. STUDY DESIGN: PREVENTION-ACHD is a prospective study with which we aim to prospectively validate a new risk score model for primary prevention of SCD in ACHD patients, as well as the currently existing guideline recommendations. Patients are screened using a novel risk score to predict SCD as well as current ICD indications according to an international Consensus Statement. Patients are followed up for two years. The primary endpoint is the occurrence of SCD and sustained ventricular arrhythmias. The Study was registered at ClinicalTrials.gov (NCT03957824). CONCLUSION: PREVENTION-ACHD is the first prospective study on SCD in ACHD patients. In the light of a growing and aging population of patients with more severe congenital heart defects, more robust clinical evidence on primary prevention of SCD is urgently needed.

Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes.

HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10-26, n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers. A higher ALT case incidence plus weaker HLA association observed during concurrent administration of lapatinib and taxane suggested a subset of liver injury in this combination group that was HLA-DRB1*07:01 independent. Furthermore, the incidence of ALT elevation demonstrated an expected correlation with geographic HLA-DRB1*07:01 carriage frequency. Robust ALT elevation risk estimates for HLA-DRB1*07:01 may support causality discrimination and safety risk management during the use of lapatinib combination therapy for the treatment of metastatic breast cancer.

Twenty-Five Diagnoses on Midline Images of the Brain: From Fetus to Child to Adult.

Midsagittal images of the brain provide a wealth of anatomic information and may show abnormalities that are pathognomonic for particular diagnoses. Using an anatomy-based approach, the authors identify pertinent anatomic structures to serve as a checklist when evaluating these structures. Subregions evaluated include the corpus callosum, pituitary gland and sellar region, pineal gland and pineal region, brainstem, and cerebellum. The authors present 25 conditions with characteristic identifiable abnormalities at midsagittal imaging. Midsagittal views from multiple imaging modalities are shown, including computed tomography, ultrasonography, and magnetic resonance (MR) imaging. Standard MR imaging sequences are shown, as well as fetal MR and sagittal diffusion-weighted images. To demonstrate these conditions, fetal, neonatal, childhood, adolescent, and young adulthood images are reviewed. The differentiation of normal variants is guided by the understanding of anatomy and pathology. When a specific diagnosis is not possible, the authors present information to evaluate differential considerations and discuss when follow-up imaging may be indicated. The authors hope each case will clarify a pertinent differential diagnosis, appropriately guide patient management, and improve understanding of normal anatomy and identification of pathologic entities. It is in these hopes that the authors have presented a checklist of pertinent anatomy and pathologic entities that can build on existing search patterns. Improved confidence and accuracy in the evaluation of midsagittal images will benefit physicians and patients. ©RSNA, 2018.

A systematic review and meta-analysis of interventions to increase physical activity in children and adolescents with intellectual disabilities.

BACKGROUND: Increasing physical activity (PA) through intervention can promote physical and mental health benefits in children and adolescents. However, children and adolescents with intellectual disabilities (ID) have consistently been shown to engage in low levels of PA, which are insufficient for long-term health. Despite this, little is known about the effectiveness of interventions to increase PA in children and adolescents with ID. The aims of this study were therefore to systematically review how effective interventions are at increasing PA levels in children and adolescents with ID and to further examine what components have been used in these interventions. METHOD: A systematic search of MEDLINE, EMBASE, Education Resources Information Center, Cumulative Index to Nursing and Allied Health Literature, PsychINFO, Cochrane Central Register for Controlled Trials and International Standard Randomised Controlled Trial Number trials registry was conducted (up to July 2016). Articles were included if they met the following eligibility criteria: children and adolescents (<18 years) with ID, measurement of PA at baseline and post-intervention and intervention studies. Effect sizes were calculated as standardised mean difference (d) and meta-analysis calculated between intervention and no treatment control intervention. RESULTS: Five studies met the eligibility criteria and were included in the review. Study design, methodological quality and intervention components were varied. Interventions did not support sufficient changes in PA to improve health. The meta-analysis demonstrated that intervention groups were not more effective at increasing PA levels post-intervention (d: 2.20; 95% CI -0.57 to 0.97) compared with control. However, due to a decrease in PA in the control intervention, a moderate significant effect was demonstrated at follow-up (d: 0.49; 95% CI 0.14 to 0.84). CONCLUSIONS: There is a lack of studies which aim to increase PA levels in children and adolescents with ID, with current interventions ineffective. Future studies are required before accurate recommendations for appropriate intervention design and components can be made.