The effect of a full bladder on proportions of diagnostic ultrasound studies in children with suspected appendicitis

Objectives: We examined the effect of a full bladder on proportions of diagnostic ultrasound (US) studies in children with suspected appendicitis. We also examined the effect of a full bladder on proportions of fully visualized ovaries on US in children with suspected appendicitis. Methods: We conducted a retrospective health record review of children aged 2-17 years presenting to a tertiary pediatric emergency department (ED) with suspected appendicitis who had an ultrasound performed. We compared proportions of diagnostic US studies in children with full and sub-optimally filled bladders. We also compared proportions of ovarian visualization in females with full and sub-optimally filled bladders. Results: 678 children were included in our final analysis. The proportion of diagnostic US studies did not vary significantly between groups with a full (132/283, 47%, 95% confidence interval [CI] 38%-56%) or sub-optimally filled bladder (205/ 395, 52%, 95% CI 47%-57%) (p = 0.17). Rates of ovarian visualization were higher in females with a full bladder (196/ 205, 96%, 95% CI 93%-99%) compared to those with a suboptimally filled bladder (180/223, 81%, 95% CI 76%-86%) (p\u3c0.01). Conclusions: Administrators and clinical decision makers should consider removing routine bladder filling practice from current pediatric appendicitis protocols in males and in pre-pubertal females where ovarian pathology is not suspected. Selective bladder filling prior to US should be performed in females when ovarian pathology is suspected

Comparison of the National Early Warning Score in non-elective medical and surgical patients.

BACKGROUND: The National Early Warning Score (NEWS) is used to identify deteriorating patients in hospital. NEWS is a better discriminator of outcomes than other early warning scores in acute medical admissions, but it has not been evaluated in a surgical population. The study aims were to evaluate the ability of NEWS to discriminate cardiac arrest, death and unanticipated ICU admission in patients admitted to surgical specialties, and to compare the performance of NEWS in admissions to medical and surgical specialties. METHODS: Hospitalwide data over 31 months, from adult inpatients who stayed at least one night or died on the day of admission, were analysed. The data were categorized as elective or non-elective surgical or medical admissions. The ability of NEWS to discriminate the outcomes above in these different groups was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: There were too few outcomes to permit meaningful comparison of elective admissions, so the analysis was constrained to comparison of non-elective admissions. NEWS performed equally well, or better, for surgical as for medical patients. For death within 24 h the AUROC for surgical admissions was 0·914 (95 per cent c.i. 0·907 to 0·922), compared with 0·902 (0·898 to 0·905) for medical admissions. For the combined outcome of any of death, cardiac arrest or unanticipated ICU admission, the AUROC was 0·874 (0·868 to 0·880) for surgical admissions and 0·874 (0·871 to 0·877) for medical admissions. CONCLUSION: NEWS discriminated deterioration in non-elective surgical patients at least as well as in non-elective medical patients

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Altering Dynamics of Autonomic Processing Therapy (ADAPT) trial: a novel, targeted treatment for reducing anxiety in joint hypermobility

Background Hypermobility is a poorly recognised and understood musculoskeletal disorder thought to affect around 20% of the population. Hypermobility is associated with reduced physiological and psychological functioning and quality of life and is a known risk factor for the development of an anxiety disorder. To date, no evidence-based, targeted treatment for anxiety in the context of hypermobility exists. The present intervention (ADAPT—Altering Dynamics of Autonomic Processing Therapy) is a novel therapy combining bio-behavioural training with cognitive approaches from clinical health psychology targeting the catastrophisation of internal sensations, with aim to improve autonomic trait prediction error. Method Eighty individuals with diagnosed hypermobility will be recruited and the efficacy of ADAPT to treat anxiety will be compared to an Emotion-Focused Supportive Therapy (EFST) comparator therapy in a randomised controlled trial. The primary treatment target will be post therapy score on the Beck Anxiety Inventory, and secondary outcomes will also be considered in relation to interoception, depression, alexithymia, social and work adjustment, panic symptoms and dissociation. Due to COVID restrictions, the intervention will be moved to online delivery and qualitative assessment of treatment tolerance to online therapy will also be assessed. Discussion Online delivery of an intervention targeting anxiety would improve the quality of life for those experiencing anxiety disorder and help to reduce the £11.7 billion that anxiety disorders cost the UK economy annually. Trial registration World Health Organization ISRCTN17018615. Registered on 20th February 2019; trial protocol version

Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases.

Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on CDK4/6 and the mechanisms that may undermine such dependency are poorly understood. Here, we report that signalling engaging the MET proto-oncogene receptor tyrosine kinase/focal adhesion kinase (FAK) axis leads to CDK4/6-independent CDK2 activation, involving as critical mechanistic events loss of the CDKI p21CIP1 and gain of its regulator, the ubiquitin ligase subunit SKP2. Combined inhibition of MET/FAK and CDK4/6 eliminates the proliferation capacity of cancer cells in culture, and enhances tumour growth inhibition in vivo. Activation of the MET/FAK axis is known to arise through cancer extrinsic and intrinsic cues. Our work predicts that such cues support cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases and identifies MET/FAK as a tractable route to broaden the utility of CDK4/6 inhibitor-based therapies in the clinic.The work was supported by grants from Cancer Research UK (ref. C309/A11566, ref. C309/A8274 and ref. C309/A8992 (PW), ref. C423/A1421 and ref. C423/A15043 (SM)) and the World Cancer Research Fund (WCRF) (ref. 12-1280). CZ was supported by a Wellcome Trust studentship (ref. 094885/Z/10/Z)

Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases.

Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on CDK4/6 and the mechanisms that may undermine such dependency are poorly understood. Here, we report that signalling engaging the MET proto-oncogene receptor tyrosine kinase/focal adhesion kinase (FAK) axis leads to CDK4/6-independent CDK2 activation, involving as critical mechanistic events loss of the CDKI p21CIP1 and gain of its regulator, the ubiquitin ligase subunit SKP2. Combined inhibition of MET/FAK and CDK4/6 eliminates the proliferation capacity of cancer cells in culture, and enhances tumour growth inhibition in vivo. Activation of the MET/FAK axis is known to arise through cancer extrinsic and intrinsic cues. Our work predicts that such cues support cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases and identifies MET/FAK as a tractable route to broaden the utility of CDK4/6 inhibitor-based therapies in the clinic.The work was supported by grants from Cancer Research UK (ref. C309/A11566, ref. C309/A8274 and ref. C309/A8992 (PW), ref. C423/A1421 and ref. C423/A15043 (SM)) and the World Cancer Research Fund (WCRF) (ref. 12-1280). CZ was supported by a Wellcome Trust studentship (ref. 094885/Z/10/Z)

A Randomized Placebo-Controlled Prevention Trial of Aspirin and/or Resistant Starch in Young People with Familial Adenomatous Polyposis

Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 x 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin-mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 rum versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas. Cancer Prey Res; 4(5); 655-65. (c) 2011 AACR.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Exploring the interpersonal-, organization-, and system-level factors that influence the implementation and use of an innovation-synoptic reporting-in cancer care

<p>Abstract</p> <p>Background</p> <p>The dominant method of reporting findings from diagnostic and surgical procedures is the narrative report. In cancer care, this report inconsistently provides the information required to understand the cancer and make informed patient care decisions. Another method of reporting, the synoptic report, captures specific data items in a structured manner and contains only items critical for patient care. Research demonstrates that synoptic reports vastly improve the quality of reporting. However, synoptic reporting represents a complex innovation in cancer care, with implementation and use requiring fundamental shifts in physician behaviour and practice, and support from the organization and larger system. The objective of this study is to examine the key interpersonal, organizational, and system-level factors that influence the implementation and use of synoptic reporting in cancer care.</p> <p>Methods</p> <p>This study involves three initiatives in Nova Scotia, Canada, that have implemented synoptic reporting within their departments/programs. Case study methodology will be used to study these initiatives (the cases) in-depth, explore which factors were barriers or facilitators of implementation and use, examine relationships amongst factors, and uncover which factors appear to be similar and distinct across cases. The cases were selected as they converge and differ with respect to factors that are likely to influence the implementation and use of an innovation in practice. Data will be collected through in-depth interviews, document analysis, observation of training sessions, and examination/use of the synoptic reporting tools. An audit will be performed to determine/quantify use. Analysis will involve production of a case record/history for each case, in-depth analysis of each case, and cross-case analysis, where findings will be compared and contrasted across cases to develop theoretically informed, generalisable knowledge that can be applied to other settings/contexts. Ethical approval was granted for this study.</p> <p>Discussion</p> <p>This study will contribute to our knowledge base on the multi-level factors, and the relationships amongst factors in specific contexts, that influence implementation and use of innovations such as synoptic reporting in healthcare. Such knowledge is critical to improving our understanding of implementation processes in clinical settings, and to helping researchers, clinicians, and managers/administrators develop and implement ways to more effectively integrate innovations into routine clinical care.</p