Enhanced Engraftment of a Very Low-Dose Cord Blood Unit in an Adult Haemopoietic Transplant by Addition of Six Mismatched Viable Cord Units

The report describes the feasibility of the addition of multiple viable HLA-mismatched unrelated cord blood units, to a low cell number matched unrelated cord, to assist clinical engraftment. An ablative stem cell transplant was performed in an adult with relapsed acute lymphoblastic leukaemia (ALL), using a single HLA-matched cord blood unit (mononuclear cell dose 0.8 × 107), supported by six mismatched cord blood units (one unit per 10 kg recipient weight). No adverse reaction occurred following the infusion of mismatched units and engraftment of the suboptimal-dose matched unit occurred rapidly, with no molecular evidence of engraftment of mismatched cords. Early molecular remission of ALL was demonstrated using a novel PCR for a mitochondrial DNA mutation in the leukaemic clone. The cell dose of the matched cord was well below that recommended to engraft a 70 kg recipient. We suggest that a factor or factors in the mismatched cords enhanced/supported engraftment of the matched cord

Scabies outbreaks in ten care homes for elderly people: a prospective study of clinical features, epidemiology, and treatment outcomes

Background Scabies outbreaks in residential and nursing care homes for elderly people are common, subject to diagnostic delay, and hard to control. We studied clinical features, epidemiology, and outcomes of outbreaks in the UK between 2014 and 2015. Methods We did a prospective observational study in residential care homes for elderly people in southeast England that reported scabies outbreaks to Public Health England health protection teams. An outbreak was defined as two or more cases of scabies (in either residents or staff) at a single care home. All patients who provided informed consent were included; patients with dementia were included if a personal or nominated consultee (ie, a family member or nominated staff member) endorsed participation. Dermatology-trained physicians examined residents at initial clinical visits, which were followed by two mass treatments with topical scabicide as per local health protection team guidance. Follow-up clinical visits were held 6 weeks after initial visits. Scabies was diagnosed through pre-defined case definitions as definite, probable, or possible with dermatoscopy and microscopy as appropriate. Findings 230 residents were examined in ten outbreaks between Jan 23, 2014, and April 13, 2015. Median age was 86·9 years (IQR 81·5–92·3), 174 (76%) were female, and 157 (68%) had dementia. 61 (27%) residents were diagnosed with definite, probable, or possible scabies, of whom three had crusted scabies. Physical signs differed substantially from classic presentations. 31 (51%) of the 61 people diagnosed with scabies were asymptomatic, and only 25 (41%) had burrows. Mites were visualised with dermatoscopy in seven (11%) patients, and further confirmed by microscopy in three (5%). 35 (57%) cases had signs of scabies only on areas of the body that would normally be covered. Dementia was the only risk factor for a scabies diagnosis that we identified (odds ratio 2·37 [95% CI 1·38–4·07]). At clinical follow-up, 50 people who were initially diagnosed with scabies were examined. No new cases of scabies were detected, but infestation persisted in ten people. Interpretation Clinical presentation of scabies in elderly residents of care homes differs from classic descriptions familiar to clinicians. This difference probably contributes to delayed recognition and suboptimal management in this vulnerable group. Dermatoscopy and microscopy were of little value. Health-care workers should be aware of the different presentation of scabies in elderly people, and should do thorough examinations, particularly in people with dementia. Funding Public Health England and British Skin Foundation

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series

Background We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. Method We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review’s last literature search, screened the records using the review’s eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Results Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov’s inception date of 2000. Conclusion Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects

Characterisation of proguanylin expressing cells in the intestine – evidence for constitutive luminal secretion

Abstract: Guanylin, a peptide implicated in regulation of intestinal fluid secretion, is expressed in the mucosa, but the exact cellular origin remains controversial. In a new transgenic mouse model fluorescent reporter protein expression driven by the proguanylin promoter was observed throughout the small intestine and colon in goblet and Paneth(-like) cells and, except in duodenum, in mature enterocytes. In Ussing chamber experiments employing both human and mouse intestinal tissue, proguanylin was released predominantly in the luminal direction. Measurements of proguanylin expression and secretion in cell lines and organoids indicated that secretion is largely constitutive and requires ER to Golgi transport but was not acutely regulated by salt or other stimuli. Using a newly-developed proguanylin assay, we found plasma levels to be raised in humans after total gastrectomy or intestinal transplantation, but largely unresponsive to nutrient ingestion. By LC-MS/MS we identified processed forms in tissue and luminal extracts, but in plasma we only detected full-length proguanylin. Our transgenic approach provides information about the cellular origins of proguanylin, complementing previous immunohistochemical and in-situ hybridisation results. The identification of processed forms of proguanylin in the intestinal lumen but not in plasma supports the notion that the primary site of action is the gut itself

Quality improvement, implementation, and dissemination strategies to improve mental health care for children and adolescents: a systematic review

Abstract Background Some outcomes for children with mental health problems remain suboptimal because of poor access to care and the failure of systems and providers to adopt established quality improvement strategies and interventions with proven effectiveness. This review had three goals: (1) assess the effectiveness of quality improvement, implementation, and dissemination strategies intended to improve the mental health care of children and adolescents; (2) examine harms associated with these strategies; and (3) determine whether effectiveness or harms differ for subgroups based on system, organizational, practitioner, or patient characteristics. Methods Sources included MEDLINE®, the Cochrane Library, PsycINFO, and CINAHL, from database inception through February 17, 2017. Additional sources included gray literature, additional studies from reference lists, and technical experts. Two reviewers selected relevant randomized controlled trials (RCTs) and observational studies, extracted data, and assessed risk of bias. Dual analysis, synthesis, and grading of the strength of evidence for each outcome followed for studies meeting inclusion criteria. We also used qualitative comparative analysis to examine relationships between combinations of strategy components and improvements in outcomes. Results We identified 18 strategies described in 19 studies. Eleven strategies significantly improved at least one measure of intermediate outcomes, final health outcomes, or resource use. Moderate strength of evidence (from one RCT) supported using provider financial incentives such as pay for performance to improve the competence with which practitioners can implement evidence-based practices (EBPs). We found inconsistent evidence involving strategies with educational meetings, materials, and outreach; programs appeared to be successful in combination with reminders or providing practitioners with newly collected clinical information. We also found low strength of evidence for no benefit for initiatives that included only educational materials or meetings (or both), or only educational materials and outreach components. Evidence was insufficient to draw conclusions on harms and moderators of interventions. Conclusions Several strategies can improve both intermediate and final health outcomes and resource use. This complex and heterogeneous body of evidence does not permit us to have a high degree of confidence about the efficacy of any one strategy because we generally found only a single study testing each strategy. Trial registration PROSPERO, CRD42015024759

A prospective study of scabies outbreaks in ten residential care facilities for the elderly in South-East England, 2014-15

Introduction Scabies is a significant problem in UK elderly residential care facilities (RCF); outbreaks are common and difficult to control. Clinical presentations in the elderly are poorly understood. We studied scabies outbreaks in RCFs to investigate the clinical signs and risk factors in this population. Methods We visited RCFs with suspected scabies outbreaks. We examined residents, performed dermoscopy and skin scrapings, and classified their scabies diagnosis as definite (mite visualised)/probable (compatible symptoms, mite not visualised)/possible (non-specific rash + contact with case) or non-scabies. All residents were treated twice with a topical scabicide, and a second visit conducted. Results We examined 230 residents at 10 RCFs between 03/02/2014-11/02/2015. Their median age was 87 years, 76% were female, and 68% had dementia. 61 (27%) had scabies (13% definite); 41% with burrows, 51% had not reported symptoms. Dermoscopy identified the mite in 7 cases (11.5%), skin scrapings in 3. We diagnosed a median 6 cases/RCF. Dementia was strongly associated with scabies (OR=2.4, 95% CI 1.4-4.1). No new cases were identified at the second visit (median interval 44 days), 10 cases still had scabies (2 probable, 8 possible). Discussion Scabies diagnosis is difficult in this population; half of cases were asymptomatic, and dermoscopy and skin scrapings were of limited diagnostic value. Our study is the first to confirm that dementia is a risk factor for scabies in this group. Careful examination of elderly residents of RCFs with suspected scabies outbreaks is important, particularly those with dementia, as they may have no obvious clinical signs

Risk factors for progression from severe maternal morbidity to death: a national cohort study.

Women continue to die unnecessarily during or after pregnancy in the developed world. The aim of this analysis was to compare women with severe maternal morbidities who survived with those who died, to quantify the risk associated with identified factors to inform policy and practice to improve survival