Screening and treating pre-operative anaemia and suboptimal iron stores in elective colorectal surgery: a cost effectiveness analysis.

Our study investigated whether pre-operative screening and treatment for anaemia and suboptimal iron stores in a patient blood management clinic is cost effective. We used outcome data from a retrospective cohort study comparing colorectal surgery patients admitted pre- and post-implementation of a pre-operative screening programme. We applied propensity score weighting techniques with multivariable regression models to adjust for differences in baseline characteristics between groups. Episode-level hospitalisation costs were sourced from the health service clinical costing data system; the economic evaluation was conducted from a Western Australia Health System perspective. The primary outcome measure was the incremental cost per unit of red cell transfusion avoided. We compared 441 patients screened in the pre-operative anaemia programme with 239 patients not screened; of the patients screened, 180 (40.8%) received intravenous iron for anaemia and suboptimal iron stores. The estimated mean cost of screening and treating pre-operative anaemia was AU$332 (£183; US$231; €204) per screened patient. In the propensity score weighted analysis, screened patients were transfused 52% less red cell units when compared with those not screened (rate ratio = 0.48, 95%CI 0.36-0.63, p < 0.001). The mean difference in total screening, treatment and hospitalisation cost between groups was AU$3776 lower in the group screened (£2080; US$2629; €2325) (95%CI AU$1604-5947, p < 0.001). Screening elective patients pre-operatively for anaemia and suboptimal iron stores reduced the number of red cell units transfused. It also resulted in lower total costs than not screening patients, thus demonstrating cost effectiveness.

Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis.

OBJECTIVE: Deferiprone is an iron chelator that has recently been used to treat patients with infratentorial superficial siderosis (iSS). It is considered to have a generally favourable safety profile but concerns have been raised due to the risk of agranulocytosis. We aimed to evaluate the safety and tolerability of oral deferiprone as a treatment for patients with iSS. METHODS: We present a case series of 10 consecutive patients presenting with classical iSS treated with deferiprone. RESULTS: Ten patients were followed up for a mean period of 2.3 years (range 0.5-5.5 years). Four patients (40%) were withdrawn from treatment because of treatment-related side effects. The reasons for treatment discontinuation were neutropenic sepsis (n = 3) and fatigue (n = 1). In 2 out of the 3 cases of neutropenic sepsis, patients initially developed neutropenia without sepsis. The mean time to neutropenic sepsis following deferiprone was 1.2 years (range 0.3-2.5) with mean neutrophil count of 0.4 (range 0.3-0.5). Six patients (60%) reported no change in neurological function while on treatment, and four patients (40%) reported that their condition deteriorated. CONCLUSIONS: Deferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis, after an average of 2 years on treatment. This study increases the number of reported cases of agranulocytosis in patients with iSS treated with deferiprone. Clinicians treating iSS patients with deferiprone should be aware that this drug has a potentially life-threatening side effect of neutropenic sepsis, and should ensure that appropriate haematological monitoring is in place.

Patient blood management: A solution for South Africa.

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient's own blood. 'Real-world' studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation's workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa's health status while saving costs.

Did school characteristics affect the uptake of meningococcal quadrivalent vaccine in Greater Manchester, United Kingdom?

OBJECTIVES: The objective of this study was to assess if school characteristics were associated with the uptake of the meningococcal ACWY (MenACWY) vaccine in Greater Manchester in 2017/18. STUDY DESIGN: This is an ecological cross-sectional study. METHODS: We analysed data on all 129 schools in seven local authorities in Greater Manchester from the Department for Education and from local child health information systems to determine whether school characteristics, including school type and Ofsted effectiveness score, were associated with vaccine uptake. Schools with no eligible pupils were excluded. We undertook single-variable and multivariable analysis and considered key interactions. RESULTS: The overall uptake rate was 80.7%, with a median uptake per school of 80.6% (interquartile range, 69.0%-87.4%). Lower vaccination rates were associated with lower overall effectiveness scores (odds ratio [OR]: 3.54, 95% confidence interval [CI]: 3.00-4.19) and lower numbers of pupils eligible for vaccination (OR: 1.39, 95% CI: 1.28-1.51). Schools with a lower percentage of pupils for whom English is a second language and high deprivation were associated with lower uptake (OR: 1.58, 95% CI: 1.41-1.78). In addition, community schools (the schools with the most local authority oversight) had lower vaccination rates than other categories of schools. CONCLUSIONS: In this study, uptake rates of the MenACWY vaccine were associated with all five school characteristics considered. Effectiveness scores for schools had the largest association with vaccine uptake, with poorer schools having lower uptake. These characteristics should be used by vaccination providers to prioritise their interventions to increase immunisation rates.

Associations of nadir haemoglobin level and red blood cell transfusion with mortality and length of stay in surgical specialties: a retrospective cohort study.

Few studies have investigated if, and how, red cell transfusion and anaemia interact. We analysed 60,955 admissions to three metropolitan hospitals in Western Australia between 2008 and 2017 to determine whether the relationship between red cell transfusion and outcomes in surgical patients differed by lowest (nadir) level of haemoglobin. At levels above 100 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratios (ORs) (95%CI) being 8.80 (4.43-17.45) p < 0.001 and 3.68 (1.93-7.02) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.83 (1.28-2.61) p = 0.001, respectively. Likewise, between 90 g.l-1 and 99 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratio (95%CI) being 3.76 (2.23-6.34) p < 0.001 and 1.96 (1.23-3.12) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.34 (1.05-1.70) p = 0.017, respectively. Length of stay was longer with transfusion at nadir haemoglobin levels above 100 g.l-1 and in the following ranges: 90-99 g.l-1 , 80-89 g.l-1 , 70-79 g.l-1 and 60-69 g.l-1 , the adjusted rate ratio (95%CI) being 1.38 (1.25-1.53) p < 0.001, 1.18 (1.10-1.27) p < 0.001, 1.17 (1.13-1.22) p < 0.001, 1.07 (1.02-1.12) p = 0.003 and 1.24 (1.13-1.36) p < 0.001, respectively. Mortality was higher with red cell transfusion at haemoglobin levels greater than 90 g.l-1 , whereas at all levels below 90 g.l-1 mortality was not significantly higher or lower. Length of stay was longer with transfusion at nadir haemoglobin levels of 60 g.l-1 or above. Our results suggest that nadir haemoglobin modified the relationship between red cell transfusion and outcomes and adds to the evidence recommending caution before transfusing red cells.

Spores of Bacillus coagulans GBI-30, 6086 show high germination, survival and enzyme activity in a dynamic, computer-controlled in vitro model of the gastrointestinal tract.

The aim of this study was to assess the germination, survival and metabolic activity of the probiotic Bacillus coagulans GBI-30, 6086 [GanedenBC30] (BC30) in a dynamic, computer controlled in vitro model of the gastrointestinal (GI) tract, simulating human adults. Experiments were performed in the presence of a meal to maximise germination, due to the presence of germination-triggers. Both an upper GI tract (stomach and small intestine; TIM-1) and a colon model (TIM-2) were used, where material exiting TIM-1 was added to TIM-2. Spores of BC30 were introduced in the gastric compartment of TIM-1 and samples were taken immediately after the pylorus. Moreover, for 6 h, every hour the ileal efflux was collected and a subsample was plated for viable counts (spores and germinated cells). The remainder of the sample was fed to TIM-2, and after 24 h another sample was taken and tested for viable counts. In addition, samples were taken from the dialysates of the model and analysed using LC-MS/MS to determine bacterial metabolites and digestion products. Survival after transit through the gastric compartment was high (97%) and most cells were still in the spore form (76%). Survival after transit through TIM-1 was on average 51%, meaning that on average half of the orally provided spores was found back as cfu on the agar plates. Of these on average 93% were germinated cells and only 7% were spores. 24 h after the start of the experiments germination had increased in TIM-2 to 97% vegetative cells, and only 3% spores. No further loss of viability was observed in TIM-2. In terms of metabolic activity, increased levels of amino acids, dipeptides and citric acid cycle metabolites were found compared to experiments in the absence of BC30. In conclusion, BC30 spores germinate to a large extent (>90%) in the presence of germination triggers in the small intestine in a model that closely mimics the physiological conditions of human adults. Of the oral dose, as much as half of the cells survived transit through the upper GI tract, and based on the metabolite profile, these cells were metabolically active. Either these cells or the enzymes released from the dead cells aided in digestion of the meal. These insights help explain some of the observations in previous experiments, and support the understanding of the mechanism of action of the probiotic BC30.

Bacillus coagulans GBI-30, 6086 increases plant protein digestion in a dynamic, computer-controlled in vitro model of the small intestine (TIM-1).

The aim of this study was to assess the potential of the probiotic Bacillus coagulans GBI-30, 6086 [GanedenBC30] (BC30) to aid in protein digestion of alimentary plant proteins. To test this, three plant proteins, from pea, soy and rice, were digested in a validated in vitro model of the stomach and small intestine (TIM-1) in the absence and in the presence of BC30. Samples were taken from the TIM-1 fractions that mimic uptake of amino acids by the host and analysed for α-amino nitrogen (AAN) and total nitrogen (TN). Both were increased by BC30 for all three plant proteins sources. The ratio of TN/AAN indicated that for pea protein digestion was increased by BC30, but the degree of polymerisation of the liberated small peptides and free amino acids was not changed. For soy and rice, however, BC30 showed a 2-fold reduction in the TN/AAN ratio, indicating that the liberated digestion products formed during digestion in the presence of BC30 were shorter peptides and more free amino acids, than those liberated in the absence of BC30. As BC30 increased protein digestion and uptake in the upper gastrointestinal (GI) tract, it consequently also reduced the amount of protein that would be delivered to the colon, which could there be fermented into toxic metabolites by the gut microbiota. Thus, the enhanced protein digestion by BC30 showed a dual benefit: enhanced amino acid bioavailability from plant proteins in the upper GI tract, and a healthier environment in the colon.

Bone mineral density and microarchitecture in patients with essential thrombocythemia and polycythemia vera.

In this cross-sectional study of 45 patients with myeloproliferative neoplasms, we found no evidence of secondary osteoporosis. INTRODUCTION: Patients with essential thrombocythemia (ET) and polycythaemia vera (PV) are at increased risk of fractures but the underlying mechanisms have not been settled. We conducted a study to assess bone mineral density, microarchitecture, estimated bone strength and global bone turnover in 45 patients with ET or PV. METHODS: Patients were evaluated in a cross-sectional study with dual energy X-ray absorptiometry (DXA) at the hip and spine; high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia; and biochemical markers of bone turnover including pro-collagen type 1 N-terminal pro-peptide, osteocalcin, C-terminal cross-linking telopeptide of type 1 collagen and bone-specific alkaline phosphatase. Also, 45 healthy comparisons, matched on age, height and weight with each patient were included as control subjects. RESULTS: Patients and comparisons had almost identical BMDs: 0.96 (IQR: 0.85-1.07) g/cm2 and 0.96 g/cm2 (IQR: 0.86-1.05 g/cm2), respectively. As well all microarchitecture and estimated bone strength measures were highly similar in the two groups. Levels of bone turnover markers were within reference values in patients. CONCLUSION: These results reveal no evidence of secondary osteoporosis among patients with ET or PV. The mechanism behind the increased fracture risk in ET or PV patients remains unknown.

Effect of socioeconomic deprivation on uptake of measles, mumps and rubella vaccination in Liverpool, UK over 16 years: a longitudinal ecological study.

Suboptimal uptake of the measles, mumps and rubella (MMR) vaccine by certain socioeconomic groups may have contributed to recent large measles outbreaks in the UK. We investigated whether socioeconomic deprivation was associated with MMR vaccine uptake over 16 years. Using immunization data for 72,351 children born between 1995 and 2012 in Liverpool, UK, we examined trends in vaccination uptake. Generalized linear models were constructed to examine the relative effect of socioeconomic deprivation and year of birth on MMR uptake. Uptake of MMR1 by age 24 months ranged between 82·5% in 2003 [95% confidence interval (CI) 81·2-83·7] and 93·4% in 2012 (95% CI 92·7-94·2). Uptake of MMR2 by age 60 months ranged between 65·3% (95% CI 64·4-67·4) in 2006 and 90·3% (95% CI 89·4-91·2) in 2012. In analysis adjusted for year of birth and sex, children in the most deprived communities were at significantly greater risk of not receiving MMR1 [risk ratio (RR) 1·70, 95% CI 1·45-1·99] and MMR2 (RR 1·36, 95% CI 1·22-1·52). Higher unemployment and lower household income were significantly associated with low uptake. Contrary to concerns about lower MMR uptake in affluent families, over 16 years, children from the most socioeconomically deprived communities have consistently had the lowest MMR uptake. Targeted catch-up campaigns and strategies to improve routine immunization uptake in deprived areas are needed to minimize the risk of future measles outbreaks.

Randomized in vivo trial evaluating plaque inhibition benefits of an advanced stannous-containing sodium fluoride dentifrice used in conjunction with power brush technology.

OBJECTIVE: To compare the plaque inhibition efficacy of a novel stannous-containing sodium fluoride test dentifrice to a standard anticavity negative control dentifrice, when both were used in conjunction with an advanced oscillating-rotating (O/R) power toothbrush. METHODS: This was a randomized, two-treatment, three-period, double-blind crossover study conducted in a population using an O/R power brush. Subjects brushed twice per day with their assigned dentifrice during the three-treatment periods, each lasting for 17 consecutive days. Each period was separated by a 4-day washout period during which subjects continued to use their O/R power toothbrush. Plaque levels were assessed and averaged amongst three assessments taken on days 15, 16 and 17 at the end of each treatment period using digital plaque imaging analysis. Assessments were carried out on the facial anterior tooth surfaces in the morning before brushing (A.M. prebrush) following whole-mouth brushing (30 s per quadrant) with the assigned dentifrice (A.M. post-brush) and in the afternoon (P.M.). RESULTS: Twenty-seven subjects were randomized and completed the study. During the 17-day usage period, the stannous-containing test NaF dentifrice demonstrated a statistically significant lower mean plaque area versus the negative control dentifrice at each assessment timepoint; overnight A.M. prebrush was 33.8% lower (P < 0.0001), A.M. post-brush was 21.8% lower (P < 0.01), and P.M. was 29.2% lower (P < 0.0001). CONCLUSION: A population of O/R power toothbrush users had significantly less plaque coverage for all three measurements when using a stannous-containing NaF dentifrice than when using a negative control (fluoride) dentifrice.

Effectiveness of a patient blood management data system in monitoring blood use in Western Australia.

The aim of this paper is to describe a linked patient blood management (PBM) data system and to demonstrate its usefulness by presenting the blood usage data obtained. Our existing datasets already collected much of the required information in relation to PBM. However, these datasets were not linked. A patient identifier was used to link the Patient Administration System with the Laboratory Information System. Data linkage was achieved by linking the Laboratory Information System with the Patient Administration System records where blood transfusion or laboratory result date/time fell between admission and discharge date/time. The two datasets were then consolidated into the PBM data system. Blood usage data obtained from the system showed that between August 2008 and July 2009 there were 59,627 patient completed separations in the pilot hospital. Of the total transfused units, 62% were red blood cells (RBC), followed by fresh frozen plasma (22%), cryoprecipitate (9%) and platelets (8%). Around 50% of RBC transfusions were administered to patients >70 years of age. General medicine represented 21% of RBC usage, followed by haematology (19%), orthopaedics (17%) and general surgery (16%). Patients with 100 g/l pre-transfusion haemoglobin received 9% of RBC transfusions and patients with 71-100 g/l pre-transfusion haemoglobin received 73% of RBC transfusions. The post-transfusion haemoglobin in RBC transfusions exceeded 100 g/l in 33% of patients. Databases were successfully linked to produce a powerful tool to monitor blood utilisation and transfusion practices within a pilot PBM program. This will facilitate effective targeting of PBM strategies and ongoing monitoring of their impact.

Randomized digital plaque imaging trial evaluating plaque inhibition efficacy of a novel stabilized stannous fluoride dentifrice compared with an amine fluoride/stannous fluoride dentifrice.

OBJECTIVE: To assess the plaque inhibition efficacy ofa novel 0.454% stabilized stannous fluoride test dentifrice (SnF2) to an amine fluoride/stannous fluoride marketed control dentifrice (AmF/SnF2) using digital plaque imaging analysis (DPIA). METHODS: The 10-week study was a randomized, two-treatment, three-period, double-blind crossover design. Subjects brushed twice daily with their assigned dentifrice (SnF2 or AmF/SnF2) using a standard manual toothbrush during three treatment periods each lasting 17 days, separated by four-day washout periods. DPIA was used to analyze plaque coverage on facial surfaces of the 12 anterior teeth (canine to canine) by three assessments on Days 15, 16, and 17 at the end of each treatment period. Assessments were conducted the morning following no overnight brushing of facial surfaces (A.M. pre-brush), after 40 seconds of full mouth brushing with the assigned dentifrice (A.M. post-brush), and during the afternoon (P.M.). RESULTS: Twenty-seven subjects were randomized and completed the study. At each assessment time point, plaque levels for the SnF2 dentifrice were statistically significantly lower compared to those for the AmF/SnF2 dentifrice (21.4%, 22.6%, 24.3%, respectively; p < 0.0001 for all). CONCLUSION: Plaque coverage, as assessed by DPIA, was significantly lower with a novel SnF2 dentifrice than with the AmF/SnF2 dentifrice. The plaque control benefits of the SnF2 dentifrice seen at the morning and afternoon time points indicated significantly better inhibition of plaque re-growth.

Power-law distribution of phase-locking intervals does not imply critical interaction.

Neural synchronization plays a critical role in information processing, storage, and transmission. Characterizing the pattern of synchronization is therefore of great interest. It has recently been suggested that the brain displays broadband criticality based on two measures of synchronization, phase-locking intervals and global lability of synchronization, showing power-law statistics at the critical threshold in a classical model of synchronization. In this paper, we provide evidence that, within the limits of the model selection approach used to ascertain the presence of power-law statistics, the pooling of pairwise phase-locking intervals from a noncritically interacting system can produce a distribution that is similarly assessed as being power law. In contrast, the global lability of synchronization measure is shown to better discriminate critical from noncritical interaction.

Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia.

Cancer cachexia induces loss of fat mass that accounts for a large part of the dramatic weight loss observed both in humans and in animal models; however, the literature does not provide consistent information regarding the set point of weight loss and how the different visceral adipose tissue depots contribute to this symptom. To evaluate that, 8-week-old male Wistar rats were subcutaneously inoculated with 1 ml (2×10(7)) of tumour cells (Walker 256). Samples of different visceral white adipose tissue (WAT) depots were collected at days 0, 4, 7 and 14 and stored at -80 °C (seven to ten animals/each day per group). Mesenteric and retroperitoneal depot mass was decreased to the greatest extent on day 14 compared with day 0. Gene and protein expression of PPARγ2 (PPARG) fell significantly following tumour implantation in all three adipose tissue depots while C/EBPα (CEBPA) and SREBP-1c (SREBF1) expression decreased over time only in epididymal and retroperitoneal depots. Decreased adipogenic gene expression and morphological disruption of visceral WAT are further supported by the dramatic reduction in mRNA and protein levels of perilipin. Classical markers of inflammation and macrophage infiltration (f4/80, CD68 and MIF-1α) in WAT were significantly increased in the later stage of cachexia (although showing a incremental pattern along the course of cachexia) and presented a depot-specific regulation. These results indicate that impairment in the lipid-storing function of adipose tissue occurs at different times and that the mesenteric adipose tissue is more resistant to the 'fat-reducing effect' than the other visceral depots during cancer cachexia progression.

An ongoing large outbreak of measles in Merseyside, England, January to June 2012.

From 1 January to 30 June 2012, 359 confirmed and 157 probable cases of measles were reported in Merseyside, England. The most affected age groups were children under five years and young adults from 15 years of age. Most cases have been sporadic. There have been few outbreaks in nurseries; however, no outbreaks have been reported in schools. Of the cases eligible for vaccination, only 3% of the confirmed cases were fully immunised.

Adipose tissue inflammation and cancer cachexia: possible role of nuclear transcription factors.

Cancer cachexia is a multifaceted syndrome whose aetiology is extremely complex and is directly related to poor patient prognosis and survival. Changes in lipid metabolism in cancer cachexia result in marked reduction of total fat mass, increased lipolysis, total oxidation of fatty acids, hyperlipidaemia, hypertriglyceridaemia, and hypercholesterolaemia. These changes are believed to be induced by inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and other factors. Attention has recently been drawn to the current theory that cachexia is a chronic inflammatory state, mainly caused by the host's reaction to the tumour. Changes in expression of numerous inflammatory mediators, notably in white adipose tissue (WAT), may trigger several changes in WAT homeostasis. The inhibition of adipocyte differentiation by PPARγ is paralleled by the appearance of smaller adipocytes, which may partially account for the inhibitory effect of PPARγ on inflammatory gene expression. Furthermore, inflammatory modulation and/or inhibition seems to be dependent on the IKK/NF-κB pathway, suggesting that a possible interaction between NF-κB and PPARγ is required to modulate WAT inflammation induced by cancer cachexia. In this article, current literature on the possible mechanisms of NF-κB and PPARγ regulation of WAT cells during cancer cachexia are discussed. This review aims to assess the role of a possible interaction between NF-κB and PPARγ in the setting of cancer cachexia as well as its significant role as a potential modulator of chronic inflammation that could be explored therapeutically.

Peritonsillar abscess after tonsillectomy: a review of the literature.

INTRODUCTION: Peritonsillar abscess (PTA) is a common condition with a complicated aetiology. PTA after tonsillectomy is rare. This literature review of PTA in the absence of tonsil tissue aims to collate experience of these cases and examine the wider implications for understanding the aetiology of PTA formation. METHODS: A structured literature review was performed using Ovid MEDLINE®. Keywords 'quinsy' or 'peritonsillar abscess' were combined with 'tonsillectomy'. RESULTS: The search resulted in 212 citations and the identification of 11 cases of PTA formation in the absence of tonsil tissue. The most common indication for tonsillectomy was recurrent tonsillitis or PTA. Nine patients had no interval peritonsillar infection (ie a peritonsillar infection after a tonsillectomy) prior to presenting with the PTA. The mean interval between tonsillectomy and PTA was 16 years. All patients were managed either by incision and drainage or by needle aspiration with or without antibiotics. CONCLUSIONS: PTA in the absence of tonsil tissue is rare. Potential sources of infection include congenital branchial fistulas, Weber's glands and dental disease. These alternatives should also be considered in patients presenting with PTA formation in the absence of concurrent tonsillitis and may influence management decisions.