Peripartum hysterectomy: an economic analysis of direct healthcare costs using routinely collected data.

OBJECTIVE: To estimate resource use and costs associated with peripartum hysterectomy for the English National Health Service. DESIGN/SETTING: Analysis of linked Clinical Practice Research Datalink and Hospital Episodes Statistics (CPRD-HES) data. POPULATION: Women undergoing peripartum hysterectomy between 1997 and 2013 and matched controls. METHODS: Inverse probability weighted generalised estimating equations were used to model the non-linear trend in healthcare service use and costs over time, accounting for missing data, adjusting for maternal age, body mass index, delivery year, smoking and socio-economic indicators. MAIN OUTCOME MEASURES: Primary care, hospital outpatient and inpatient attendances and costs (UK 2015 prices). RESULTS: The study sample included 1362 women (192 cases and 1170 controls) who gave birth between 1997 and 2013; 1088 (153 cases and 935 controls) of these were deliveries between 2003 and 2013 when all categories of hospital resource use were available. Based on the 2003-2013 delivery cohort, peripartum hysterectomy was associated with a mean adjusted additional total cost of £5380 (95% CI £4436-6687) and a cost ratio of 1.76 (95% CI 1.61-1.98) over 5 years of follow up compared with controls. Inpatient costs, mostly incurred during the first year following surgery, accounted for 78% excluding or 92% including delivery-related costs. CONCLUSION: Peripartum hysterectomy is associated with increased healthcare costs driven largely by increased post-surgery hospitalisation rates. To reduce healthcare costs and improve outcomes for women who undergo hysterectomy, interventions that reduce avoidable repeat hospitalisations following surgery such as providing active follow up, treatment and support in the community should be considered. TWEETABLE ABSTRACT: A large amount of NHS data on peripartum hysterectomy suggests active community follow up could reduce costs, #HealthEconomics.

Nature of events and alcohol-related content in marketing materials at a university freshers' fair: a summative content analysis.

Introduction: The transition to university is a potentially influential time upon students' drinking behaviour. This study explored the nature of activities and alcohol-related content in marketing materials from student-led societies and local businesses provided to students, at a university freshers' fair in the UK. Methods: All marketing materials handed out at the fair were collected across the 5-day event in September 2015. Written and visual content was analysed using a summative qualitative content analysis. Results: Most student-led societies promoted social events they were hosting (n = 530), most of which took place in a drinking venue or referred to drinking (n = 335). Only four explicitly alcohol-free events were promoted. Student-led societies also promoted activities relating to their interest, e.g. sports training (n = 519), a small proportion of which had references to drinking and drinking venues (n = 54). Three societies provided promotional handouts from local bars or nightclubs. Local bars, pubs and nightclubs promoted events they hosted (n = 81) as well as alcoholic drink promotions (n = 79) and alcohol branded advertising (n = 22), albeit infrequently for the latter. Conclusions: In the first week of university, students are exposed to alcohol-related events, promotions and advertising, which may act as an incentive to participate in drinking.

Short communication: Variation of total immunoglobulin G and ß-lactoglobulin concentrations in colostrum and milk from Canadian Holsteins classified as high, average, or low immune responders.

The objective of this study was to evaluate IgG and ß-lactoglobulin (ß-LG) concentrations in colostrum and milk of Canadian Holsteins (n=108) classified as high (H), average (A), or low (L) for antibody-mediated (AMIR) or cell-mediated immune responses (CMIR) based on estimated breeding values. It was hypothesized that H-AMIR and H-CMIR cows produce colostrum (first milking) and milk (d 5 postcalving) with higher concentrations of IgG and ß-LG. Data for IgG and ß-LG in colostrum and milk were analyzed independently using mixed linear models. Least squares means were compared using Tukey's test. Cows classified as H-AMIR had higher IgG and ß-LG concentrations in colostrum compared with A- and L-AMIR cows; 84% of H-AMIR, 69% of A-AMIR, and 68% of L-AMIR cows had over 5,000 mg/dL IgG in colostrum. No differences in IgG and ß-LG concentrations in colostrum were noted among cows ranked on CMIR or in milk of cows ranked on AMIR. ß-Lactoglobulin and IgG concentrations were positively correlated in colostrum. Breeding cows for H-AMIR status may reduce failure of passive transfer of IgG in their calves; ß-LG may play a role in bovine immune defenses. Colostrum from H-AMIR cows may serve as a more economical feedstock source for manufacturing natural health products.

Aboriginal street-involved youth experience elevated risk of incarceration.

OBJECTIVES: Past research has identified risk factors associated with incarceration among adult Aboriginal populations; however, less is known about incarceration among street-involved Aboriginal youth. Therefore, we undertook this study to longitudinally investigate recent reports of incarceration among a prospective cohort of street-involved youth in Vancouver, Canada. STUDY DESIGN: Prospective cohort study. METHODS: Data were collected from a cohort of street-involved, drug-using youth from September 2005 to May 2013. Multivariate generalized estimating equation analyses were employed to examine the potential relationship between Aboriginal ancestry and recent incarceration. RESULTS: Among our sample of 1050 youth, 248 (24%) reported being of aboriginal ancestry, and 378 (36%) reported being incarcerated in the previous six months at some point during the study period. In multivariate analysis controlling for a range of potential confounders including drug use patterns and other risk factors, Aboriginal ancestry remained significantly associated with recent incarceration (adjusted odds ratio [AOR] = 1.44; 95% confidence interval [CI]: 1.12-1.86). CONCLUSIONS: Even after adjusting for drug use patterns and other risk factors associated with incarceration, this study found that Aboriginal street-involved youth were still significantly more likely to be incarcerated than their non-Aboriginal peers. Given the established harms associated with incarceration these findings underscore the pressing need for systematic reform including culturally appropriate interventions to prevent Aboriginal youth from becoming involved with the criminal justice system.

Microstructural alterations of major thalamic nuclei in the chronic pediatric spinal cord injured population.

Background: The brain undergoes reorganization following spinal cord injury (SCI), but little is known about how the thalamus is affected in pediatric SCIs. Purpose: To characterize microstructural alterations in the thalamus after SCI with diffusion tensor imaging (DTI) metrics. Methods: 18 pediatric participants with chronic SCI (8-20 years) were stratified using the American Spinal Injury Association Impairment Scale (AIS) into groups: A, B, and C/D. DTI of the brain used a 3 T Siemens Verio MRI using the parameters: 20 directions, number of averages = 3, b = 1000 s/mm2, voxel size = 1.8 mm × 1.8 mm, slice thickness = 5 mm, TE = 95 ms, TR = 4300 ms, 30 slices, FOV = 230 × 230 mm2, matrix = 128 × 128, acquisition time = 4:45 min. Diffusion data was processed to generate DTI metrics FA, MD, AD, and RD. Data analysis: DTI metrics were acquired by superimposing the AAL3 thalamic atlas onto participant diffusion images registered to MNI152 space. We utilized a multiple Mann-Whitney U-test to compare between AIS groups, considering values of p ≤ 0.05 as significant. Results: FA, AD, RD, and MD significantly differed in thalamic nuclei between AIS groups A vs B and B vs C/D. Significant nuclei include the right ventral anterior, left intralaminar, bilateral lateral pulvinar, and right lateral geniculate. Conclusion: Our findings suggest the presence of microstructural alterations based on SCI severity in pediatric patients. These results are encouraging and warrant further study.

The rising incidence of idiopathic pulmonary fibrosis in the U.K.

BACKGROUND: Previous studies have shown that the incidence of idiopathic pulmonary fibrosis (IPF) is rising in the U.K. and U.S.A. Death registrations and primary care data were used to determine the current trends in IPF incidence in the U.K. Because routine clinical data sets were used, the term IPF clinical syndrome (IPF-CS) is used to describe individuals in this study. METHODS: Age- and stratum-specific death registration rates between 1968 and 2008 were calculated and these were applied to the 2008 population to generate annual standardised expected number of deaths. Annual mortality rate ratios were calculated using Poisson regression. Computerised primary care records were used to determine incidence rates of IPF-CS between 2000 and 2008 stratified by age, sex and geographical region, and survival rates between calendar periods were compared. RESULTS: Annual death certificate recording of IPF-CS rose sixfold across the study period from 0.92 per 100,000 in the 1968-1972 calendar periods to 5.10 per 100,000 in the 2006-2008 calendar period, and were higher in men and the older age groups. The incidence of IPF-CS in primary care increased by 35% from 2000 to 2008, with an overall incidence rate of 7.44 per 100,000 person-years (95% CI 7.12 to 7.77). Incidence was higher in men, the older population and in Northwest England. CONCLUSIONS: The incidence of IPF-CS in primary care and registered deaths from this cause in the U.K. continues to rise in the 21st century. The current findings suggest that there are >5000 new cases diagnosed each year in the U.K.

Enteric virus infection risk from intrusion of sewage into a drinking water distribution network.

Contaminants from the soil surrounding drinking water distribution systems are thought to not enter the drinking water when sufficient internal pressure is maintained. Pressure transients may cause short intervals of negative pressure, and the soil near drinking water pipes often contains fecal material due to the proximity of sewage lines, so that a pressure event may cause intrusion of pathogens. This paper presents a risk model for predicting intrusion and dilution of viruses and their transport to consumers. Random entry and dilution of virus was simulated by embedding the hydraulic model into a Monte Carlo simulation. Special attention was given to adjusting for the coincidence of virus presence and use of tap water, as independently occurring short-term events within the longer interval that the virus is predicted to travel in any branch of the distribution system. The probability that a consumer drinks water contaminated with virus is small, but when this happens the virus concentration tends to be high and the risk of infection may be considerable. The spatial distribution of infection risk is highly heterogeneous. The presence of a chlorine residual reduces the infection risk.

A population-based study of acute medical conditions associated with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is associated with poorly understood dramatically increased early mortality rates. OBJECTIVES: To assess the incidence of acute events predisposing to early mortality. METHODS: Computerized medical records from the Health Improvement Network, a large population-based U.K. general practice database, were used to conduct a cohort analysis. Outcome measures were incidence rates of myocardial infarction, pulmonary embolism, pneumonia and sepsis compared with a matched control population. RESULTS: People with bullous pemphigoid were three times as likely to develop pneumonia, adjusted rate ratio 2.94 [95% confidence interval (CI) 2.01-4.31] or pulmonary embolism, adjusted rate ratio 3.12 (95% CI 1.37-7.12) compared with matched controls. No statistically significant increase was seen for myocardial infarction, adjusted rate ratio 1.24 (95% CI 0.66-2.33), or sepsis, adjusted rate ratio 2.02 (95% CI 0.78-5.21). CONCLUSIONS: The risk of pulmonary embolism and pneumonia is increased following a diagnosis of bullous pemphigoid. It may be possible to reduce associated mortality through considering prophylaxis with either antithromboembolic measures or antibiotic therapy and vaccination.

Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario.

By minimising the effect of irradiation on surrounding tissue, intensity-modulated radiation therapy (IMRT) can deliver higher, more effective doses to the targeted tumour site, minimising treatment-related morbidity and possibly improving cancer control and cure. A multidisciplinary IMRT Expert Panel was convened to develop the organisational standards for the delivery of IMRT. The systematic literature search used MEDLINE, EMBASE, the Cochrane Database, the National Guidelines Clearing House and the Health Technology Assessment Database. An environmental scan of unpublished literature used the Google search engine to review the websites of key organisations, cancer agencies/centres and vendor sites in Canada, the USA, Australia and Europe. In total, 22 relevant guidance documents were identified; 12 from the published literature and 10 from the environmental scan. Professional and organisational standards for the provision of IMRT were developed through the analysis of this evidence and the consensus opinion of the IMRT Expert Panel. The resulting standards address the following domains: planning of new IMRT programmes, practice setting requirements, tools, devices and equipment requirements; professional training requirements; role of personnel; and requirements for quality assurance and safety. Here the IMRT Expert Panel offers organisational and professional standards for the delivery of IMRT, with the intent of promoting innovation, improving access and enhancing patient care.

A randomised controlled comparison of aspiration and non-aspiration fine-needle techniques for obtaining ultrasound-guided cytological samples from canine livers.

Ultrasound-guided fine-needle sampling to obtain cytological samples is a well-established technique. However, the application of suction during sampling is controversial. Evidence from the human literature and one previous veterinary study suggest that non-aspiration may be superior for a number of organs. This prospective study compared the quality and diagnostic value of cytological samples from canine livers obtained by fine-needle aspiration (FNA) and non-aspiration (FN-NA) techniques. A total of 119 dogs that required ultrasound-guided FNA of the liver as part of their clinical investigation were recruited and randomly assigned to either FNA (n=54) or FN-NA (n=65) sampling groups. Specimens were reviewed by external cytopathologists masked to the technique used. Cytological reports were reviewed for their overall diagnostic value, cellularity, cell preservation and haemodilution. Overall, 88.2% (95% confidence intervals [CI], 82.4-94.0) of samples were diagnostic. There was a significant difference, as demonstrated by Chi-squared statistical analysis, in the prevalence of diagnostic samples between the FNA (81.5%; 95% CI, 71.1-91.8) and FN-NA groups (93.9%; 95% CI, 88.0-99.7; P=0.037). Non-diagnostic samples were significantly associated with lower cellularity, poorer cell preservation and more severe haemodilution (P<0.001 for each). However, there were no significant differences in the frequency of these specific variables between the FNA and FN-NA groups. In this study, fine-needle non-aspiration was superior to an aspiration technique for sampling the canine liver, as it resulted in higher rates of diagnostic cytology samples, with greater cellularity, less haemodilution and better cytological preservation.

Dental and facial bone abnormalities in pyknodysostosis: CT findings.

Pyknodysostosis is an autosomal-recessive disorder of osteoclast dysfunction causing osteosclerosis, with associated maxillofacial anomalies. Multidetector CT with multiplanar and 3D reconstruction illustrated the pathologic findings in this case. Abnormalities included multiple retained deciduous teeth, unerupted teeth with associated follicles, an irregularly expanded alveolus and body of the mandible, and an obtuse mandibular angle. Volume-rendered imaging better delineated the irregular dentition, with crowding and retention of deciduous teeth.

Risk of hepatocellular carcinoma among individuals with different aetiologies of cirrhosis: a population-based cohort study.

BACKGROUND: Among patients with cirrhosis, only those determined to be at risk for hepatocellular carcinoma (HCC) should undergo surveillance. However, little is known about how different aetiologies of cirrhosis affect risk for HCC. AIM: To quantify the cumulative incidence of HCC among a representative population of people with cirrhosis of the liver of varying aetiology. METHODS: We identified subjects with hepatic cirrhosis from the UK's General Practice Research Database (1987-2006). Diagnoses of HCC were obtained from linked national cancer registries (1971-2006). Cox proportional hazards regression was used to estimate hazard ratios. The predicted 10-year cumulative incidence of HCC for each aetiology of cirrhosis was estimated while accounting for competing risks of death from any cause and liver transplant. RESULTS: Among 3107 people with cirrhosis, the adjusted relative risk of HCC was increased twofold to threefold among people with viral and autoimmune/metabolic aetiologies, compared to those with alcohol-associated cirrhosis. The 10-year predicted cumulative incidence estimates of HCC for each aetiology were alcohol, 1.2%; chronic viral hepatitis, 4.0%; autoimmune or metabolic disease, 3.2%; and cryptogenic, 1.1%. CONCLUSIONS: In a population-based study in the UK, people with cirrhosis have an estimated cumulative 10-year incidence of HCC of 4% or lower. Cumulative incidence varies with aetiology such that individuals with alcohol or cryptogenic cirrhosis have the lowest risk for HCC. These findings provide important information for cost-effectiveness analyses of HCC surveillance.

Cryopreservation of hematopoietic and non-hematopoietic stem cells.

Recent studies illustrate the potential for improving the cryopreservation of stem cells. Reduced DMSO concentrations in the cryopreservation medium, post thaw washing of cells and increased cell concentration have been actively studied. Standardization of cell processing has led to the study of liquid storage prior to cryopreservation, validation of mechanical (uncontrolled rate freezing) freezing, and cryopreservation bag failure. Finally, the need for the systematic study and optimization of preservation processes has not been fulfilled. As the sources and applications of stem cells (hematopoietic and non-hematopoietic) continue to be developed, the need for effective preservation methods will only grow.

A comparative evaluation of two head and neck immobilization devices using electronic portal imaging.

A study was performed to compare the positioning reproducibility and the cost efficiency for two head and neck immobilization devices: the Uvex (Uvex Safety, Smithfield, USA) plastic mask system and the Finesse Frame with Ultraplast System (PLANET Medical, Svendborg, Denmark). 20 patients treated with 3D conformal radiation therapy for head and neck cancers were randomly selected (10 for each of the two different immobilization systems) and electronic portal images acquired during their course of treatment were saved and used in this study. The anatomical landmark coordinates and their shifts in the anteroposterior (AP) and craniocaudal (CC) directions with respect to the digitized simulator films for lateral fields were analysed using an in-house developed portal image registration system. Statistically, no evidence was found to indicate that the systematic components of the displacement for the Uvex system and the Finesse Frame with Ultraplast System were different from each other or from zero. The random component of displacement was slightly smaller in the AP direction for the Uvex than the Ultraplast system (sigma = 1.9 mm and 2.9 mm, respectively, p = 0.007), but larger in the CC direction (sigma = 3.8 mm and 2.2 mm, respectively, p<10(-9)). Production time and required materials for a radiation therapy department were also quantified to assess costs for each system. The overall costs per patient were estimated at 141.50 dollars (CAD) and 82.10 dollars for the Uvex and Ultraplast systems, respectively. The Finesse Frame with Ultraplast System of immobilization for head and neck cancer treatment provides a field placement reproducibility that is equal to, or greater than, that of the Uvex plastic mask immobilization system and, while it requires more expensive materials, the workload and consequently overall cost is greatly reduced.

The effect of point mutations on the free energy of transmembrane alpha-helix dimerization.

Glycophorin A forms homodimers through interaction of the single, helical transmembrane domains of the monomers. The dimers are stable in sodium dodecylsulfate (SDS), permitting a number of studies that have identified a critical motif of residues that mediates dimer formation. We have used analytical ultracentrifugation to measure the energy of dimerization in a non-denaturing detergent solution and have observed the changes in energy arising from two of the mutants previously studied. Use of the detergent pentaoxyethylene octyl ether (C8E5) is a great advantage, since its micelles are neutrally buoyant and the detergent allows a reversible association to occur between monomer and dimer states of the glycophorin A transmembrane helices during the time-scale of sedimentation equilibrium. Use of this detergent in analytical ultracentrifugation may enable a wide range of studies of molecular association events in membrane proteins. We find that the glycophorin A transmembrane helix dimerizes with a dissociation constant of 240(+/-50) nM, corresponding to a free energy of dissociation of 9.0(+/-0.1) kcal mol-1. Point mutants that were found to be disruptive in SDS (L75A, I76A) reduced the dimer affinity in the C8E5 detergent environment (Kd=1.7(+/-0.2) microM and 4.2(+/-0.9) microM, respectively). Thus, the earlier findings are placed on a quantitative, relative energy scale of association by our measurements. Molecular modeling and simulations suggest that the energy differences can be accounted for as changes in van der Waals interactions between helices.

The effects of salt on the TATA binding protein-DNA interaction from a hyperthermophilic archaeon.

This study investigates the thermodynamics of the interaction of the TATA box binding protein (TBP) from Pyrococcus woesei (Pw) with an oligonucleotide containing a specific binding site. Pw is a hyperthermophilic archeal organism which exists under conditions of high salt and high temperature. A measurable protein-DNA interaction only occurs at high salt concentrations. Isothermal titration calorimetric binding studies were performed under a range of salts (potassium chloride, potassium phosphate, potassium acetate and sodium acetate) at varying concentrations (0.8 to 1.6 M). At the high salt concentrations used the observed equilibrium binding constant increases with increasing salt concentration. This is very different to the effect reported for all other protein-DNA interactions which have been studied at lower salt concentrations. Thermodynamic data suggest that the protein-DNA interaction at high salt concentration is accompanied by the removal of large numbers of water molecules from the buried hydrophobic surface area. In addition, the involvement of ions appears to influence the binding which can be explained by binding of cations in the interface between the electrostatically negative lateral lobes on the protein and the negatively charged DNA.

A zinc-binding domain involved in the dimerization of RAG1.

Recombination-activating gene 1 (RAG1), as well as RAG2, are the only lymphoid-specific genes required for V(D)J recombination. RAG1 protein contains a C3HC4 zinc-binding motif (zinc ring finger) that binds two zinc ions. We have found that RAG1 contains additional zinc-binding motifs in the form of two separate C2H2 zinc finger sequences. One of the zinc fingers, in combination with the C3HC4 subdomain, forms a highly specific dimerization domain. A combination of biophysical techniques has been used to determine the energetics of association, the overall shape of the dimerization domain, and the relative orientation of the monomeric subunits within the dimer. These results provide direct evidence that a C3HC4 motif is involved in a protein-protein interaction, in this case via homodimer formation. In addition, the observation that the dimerization domain includes multi-class zinc binding motifs, namely both a zinc finger and a C3HC4 subdomain, has important implications for other C3HC4-containing proteins. The position of this dimerization domain in the N-terminal third of the RAG1 sequence of 1040 amino acid residues may have a significant influence on the activities associated with the C-terminal domains of the protein.

Riding the wave: structural and energetic principles of helical membrane proteins.

Genome sequencing efforts have revealed that perhaps as many as 20-40% of open reading frames in complex organisms may encode proteins containing at least one helical transmembrane segment. Contrasting with this approaching tidal wave of helical membrane proteins is the fact that our understanding of the sequence-structure-function relationships for membrane proteins lags far behind that of soluble proteins. This looming reality emphasizes the tremendous biochemical and structural work that remains to be done on helical membrane proteins in order to elucidate the structural and energetic principles that specify and stabilize their folds, which define their functions. These facts are not lost on the pharmaceutical industry, where successful therapeutics and major discovery efforts are targeting membrane proteins.

What makes a protein a protein? Hydrophobic core designs that specify stability and structural properties.

Here we describe how the systematic redesign of a protein's hydrophobic core alters its structure and stability. We have repacked the hydrophobic core of the four-helix-bundle protein, Rop, with altered packing patterns and various side chain shapes and sizes. Several designs reproduce the structure and native-like properties of the wild-type, while increasing the thermal stability. Other designs, either with similar sizes but different shapes, or with decreased sizes of the packing residues, destabilize the protein. Finally, overpacking the core with the larger side chains causes a loss of native-like structure. These results allow us to further define the roles of tight residue packing and the burial of hydrophobic surface area in the construction of native-like proteins.