Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

<p>Abstract</p> <p>Background</p> <p>Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs).</p> <p>Methods</p> <p>Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared.</p> <p>Results</p> <p>Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs.</p> <p>Conclusions</p> <p>A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.</p

Characterisation of physico-mechanical properties and degradation potential of calcium alginate beads for use in embolisation

High molecular weight alginate beads with 59% mannuronic acid content or 68% guluronic acid were prepared using a droplet generator and crosslinked in calcium chloride. The alginate beads were compared to current embolisation microspheres for compressibility and monitored over 12 weeks for size and weight change at 37°C in low volumes of ringers solutions. A sheep uterine model was used to analyse bead degradation and inflammatory response over 12 weeks. Both the in vitro and in vivo data show good delivery, with a compressibility similar to current embolic beads. In vitro, swelling was noted almost immediately and after 12 weeks the first signs of degradation were noted. No difference was noted in vivo. This study has shown that high molecular weight alginate gel beads were well tolerated by the body, but beads associated with induced thrombi were susceptible to inflammatory cell infiltration. The beads were shown to be easy to handle and were still observable after 3 months in vivo. The beads were robust enough to be delivered through a 2.7 Fr microcatheter. This study has demonstrated that high molecular weight, high purity alginate bead can be considered as semi-permanent embolisation beads, with the potential to bioresorb over time

Subnormal vitamin B12 concentrations and anaemia in older people: a systematic review

<p>Abstract</p> <p>Background</p> <p>Pernicious anaemia is undeniably associated with vitamin B12 deficiency, but the association between subnormal vitamin B12 concentrations and anaemia in older people is unclear. The aim of this systematic review was to evaluate the association between subnormal vitamin B12 concentrations and anaemia in older people.</p> <p>Methods</p> <p>Clinical queries for aetiology and treatment in bibliographic databases (PubMed [01/1949-10/2009]; EMBASE [01/1980-10/2009]) were used. Reference lists were checked for additional relevant studies. Observational studies (≥50 participants) and randomized placebo-controlled intervention trials (RCTs) were considered.</p> <p>Results</p> <p>25 studies met the inclusion criteria. Twenty-one observational cross-sectional studies (total number of participants n = 16185) showed inconsistent results. In one longitudinal observational study, low vitamin B12 concentrations were not associated with an increased risk of anaemia (total n = 423). The 3 RCTs (total n = 210) were well-designed and showed no effect of vitamin B12 supplementation on haemoglobin concentrations during follow-up in subjects with subnormal vitamin B12 concentrations at the start of the study. Due to large clinical and methodological heterogeneity, statistical pooling of data was not performed.</p> <p>Conclusions</p> <p>Evidence of a positive association between a subnormal serum vitamin B12 concentration and anaemia in older people is limited and inconclusive. Further well-designed studies are needed to determine whether subnormal vitamin B12 is a risk factor for anaemia in older people.</p

SARS-CoV-2 infection in cats and dogs in infected mink farms

Animals like mink, cats and dogs are susceptible to SARS-CoV-2 infection. In the Netherlands, 69 out of 127 mink farms were infected with SARS-CoV-2 between April and November 2020 and all mink on infected farms were culled after SARS-CoV-2 infection to prevent further spread of the virus. On some farms, (feral) cats and dogs were present. This study provides insight into the prevalence of SARS-CoV-2-positive cats and dogs in 10 infected mink farms and their possible role in transmission of the virus. Throat and rectal swabs of 101 cats (12 domestic and 89 feral cats) and 13 dogs of 10 farms were tested for SARS-CoV-2 using PCR. Serological assays were performed on serum samples from 62 adult cats and all 13 dogs. Whole Genome Sequencing was performed on one cat sample. Cat-to-mink transmission parameters were estimated using data from all 10 farms. This study shows evidence of SARS-CoV-2 infection in 12 feral cats and 2 dogs. Eleven cats (18%) and two dogs (15%) tested serologically positive. Three feral cats (3%) and one dog (8%) tested PCR-positive. The sequence generated from the cat throat swab clustered with mink sequences from the same farm. The calculated rate of mink-to-cat transmission showed that cats on average had a chance of 12% (95%CI 10%–18%) of becoming infected by mink, assuming no cat-to-cat transmission. As only feral cats were infected it is most likely that infections in cats were initiated by mink, not by humans. Whether both dogs were infected by mink or humans remains inconclusive. This study presents one of the first reports of interspecies transmission of SARS-CoV-2 that does not involve humans, namely mink-to-cat transmission, which should also be considered as a potential risk for spread of SARS-CoV-2

Manifestation of SARS-CoV-2 Infections in Mink Related to Host-, Virus- and Farm-Associated Factors, The Netherlands 2020

SARS-CoV-2 outbreaks on 69 Dutch mink farms in 2020 were studied to identify risk factors for virus introduction and transmission and to improve surveillance and containment measures. Clinical signs, laboratory test results, and epidemiological aspects were investigated, such as the date and reason of suspicion, housing, farm size and distances, human contact structure, biosecurity measures, and presence of wildlife, pets, pests, and manure management. On seven farms, extensive random sampling was performed, and age, coat color, sex, and clinical signs were recorded. Mild to severe respiratory signs and general diseases such as apathy, reduced feed intake, and increased mortality were detected on 62/69 farms. Throat swabs were more likely to result in virus detection than rectal swabs. Clinical signs differed between virus clusters and were more severe for dark-colored mink, males, and animals infected later during the year. Geographical clustering was found for one virus cluster. Shared personnel could explain some cases, but other transmission routes explaining farm-to-farm spread were not elucidated. An early warning surveillance system, strict biosecurity measures, and a (temporary) ban on mink farming and vaccinating animals and humans can contribute to reducing the risks of the virus spreading and acquisition of potential mutations relevant to human and animal health

The effect of vitamin B12 and folic acid supplementation on routine haematological parameters in older people: an individual participant data meta-analysis.

BACKGROUND/OBJECTIVES: Low vitamin B12 and folate levels in community-dwelling older people are usually corrected with supplements. However, the effect of this supplementation on haematological parameters in older persons is not known. Therefore, we executed a systematic review and individual participant data meta-analysis of randomised placebo-controlled trials (RCTs). SUBJECTS/METHODS: We performed a systematic search in PubMed, EMBASE, Web of Science, Cochrane and CENTRAL for RCTs published between January 1950 and April 2016, where community-dwelling elderly (60+ years) who were treated with vitamin B12 or folic acid or placebo. The presence of anaemia was not required. We analysed the data on haematological parameters with a two-stage IPD meta-analysis. RESULTS: We found 494 full papers covering 14 studies. Data were shared by the authors of four RCTs comparing vitamin B12 with placebo (n = 343) and of three RCTs comparing folic acid with placebo (n = 929). We found no effect of vitamin B12 supplementation on haemoglobin (change 0.00 g/dL, 95% CI: -0.19;0.18), and no effect of folic acid supplementation (change -0.09 g/dL, 95% CI: -0.19;0.01). The effects of supplementation on other haematological parameters were similar. The effects did not differ by sex or by age group. Also, no effect was found in a subgroup of patients with anaemia and a subgroup of patients who were treated >4 weeks. CONCLUSIONS: Evidence on the effects of supplementation of low concentrations of vitamin B12 and folate on haematological parameters in community-dwelling older people is inconclusive. Further research is needed before firm recommendations can be made concerning the supplementation of vitamin B12 and folate

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG