The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Making tiestalls more comfortable: IV. Increasing stall bed length and decreasing manger wall height to heal injuries and increase lying time in dairy cows housed in deep-bedded tiestalls.

Poor stall configuration can negatively affect cow welfare by impairing lying behavior and leading to injuries in dairy cows. The comfort of the stall bed in tiestalls is affected by the material components of the stall bed (stall base and bedding), but also by the amount of space provided. The amount of space cows are able to access lengthwise in a tiestall is determined by the stall bed length and the height of the manger wall (the front limit of the stall bed), which can limit access into the space available at the front of the stall. This project aimed to maximize cow comfort in deep-bedded tiestalls by investigating the combined effect of increased bed length and decreased manger wall height in a crossover experiment (2 periods with 1 wk habituation + 6 wk data collection). Two rows of 12 tiestalls were modified (n = 24 cows). Each row was a different length, short (178 cm; length commonly found in Quebec) or long (188 cm), and cows remained on the same row (same stall bed length) for the entire experiment. In each row, there were 6 stalls of each manger wall height treatment: high (20 cm, upper limit recommended) or low (5 cm). During period 2, cows switched manger wall height treatments. A 7.6-cm-deep straw bedding layer was added to all stalls by adding a bedding keeper to the ends of stalls. All initially injured locations healed over the 14-wk study, and 2 patterns of healing emerged. Improvement in hock injury (lateral tarsal and calcanei) was observed from wk 1 to 6 for all treatments. A plateau in injury severity score reduction was observed in period 2 for the hock (lateral, dorsal, and medial calcanei), anatomical knee, carpal joints (front knees), and proximal and medial neck, which was likely the result of the insensitivity of the injury scoring scheme rather than healing not occurring. Cows in long stalls were found to spend more time lying (14.1 vs. 13.3 h/d) and had longer lying bouts than cows in short stalls (74.1 vs. 52.9 min/bout). Manger wall height did not affect injury or lying time, but may affect how cows position themselves while lying. Higher lying times in our study were comparable to those reported in deep-bedded loose pens, indicating that cows with more bedding, especially those in long stalls, were more comfortable. Our results suggest that deep-bedded straw stalls with bedding keepers have the potential to be beneficial to cow comfort on tiestall farms.

From Neutral Aniline to Aniline Trication: A Computational and Experimental Study.

We report density functional theory computations and photoionization mass spectrometry measurements of aniline and its positively charged ions. The geometrical structures and properties of the neutral and singly, doubly, and triply positively charged aniline are computed using density functional theory with the generalized gradient approximation. At each charge, there are multiple isomers closely spaced in total energy. Whereas the lowest energy states of both neutral and cation have the same topology C6H5-NH2, the dication and trication have the C5NH5-CH2 topology with the nitrogen atom in the meta- and para-positions, respectively. We compute the dissociation pathways of all four charge states to NH or NH+ and NH2 or NH2+, depending on the initial charge of the aniline precursor. Dissociation leading to the formation of NH (from the neutral and cation) and NH+ (from the dication and trication) proceeds through multiple transition states. On the contrary, the dissociation of NH2 (from the neutral and cation) and NH2+ (from the dication and trication) is found to proceed without an activation energy barrier. The trication was found to be stable toward abstraction on NH+ and NH2+ by 0.96 and 0.18 eV, respectively, whereas the proton affinity of the trication is substantially higher, 1.98 eV. The mass spectra of aniline were recorded with 1300 nm, 20 fs pulses over the peak intensity range of 1 × 1013 to 3 × 1014 W cm-2. The analysis of the mass spectra suggests high stability of both dication and trication to fragmentation. The formation of the fragment NH+ and NH2+ ions is found to proceed via Coulomb explosion.

Endovascular management of mycotic aortic aneurysms- A 20-year experience from a single UK centre.

AIM: To present the authors' experience of endovascular treatment of confirmed and presumed (microbiology negative) mycotic aortic aneurysms (MAA). MATERIALS AND METHODS: Patients undergoing endovascular aortic repair were identified retrospectively from 1998 using the radiology information system and an internally kept database until 2018. The primary aim was to assess the technical success and peri-operative morbidity and mortality. The secondary aim was to assess progression of infection, re-interventions, late mortality, and correlation to antibiotic duration pre- and post-procedure. RESULTS: Thirty-four endovascular aortic procedures were performed for MAA, excluding aorto-enteric fistulas, inflammatory aneurysms, and infected grafts without a new aneurysm. Seventy-six percent of these were thoracic and 24% abdominal. The technical success was 100%. Additional procedures were undertaken in four patients with two requiring a further endovascular procedure. There were two inpatient aneurysm-related mortalities and no inpatient conversions to open repair. The 30-day re-admission and re-intervention rate was 0%. Blood cultures were positive in 45%. There were no secondary graft infections. CONCLUSION: This is the largest European single-centre study. It supports endovascular management of MAA as a lower-risk alternative to open surgery with the majority of patients presenting acutely, later in life and requiring emergency management.

Graduate Student Literature Review: The effects of bedding, stall length, and manger wall height on common outcome measures of dairy cow welfare in stall-based housing systems.

Understanding and improving dairy cow welfare in stall-based housing systems is an important issue for the dairy industry, and one area of the stall that has a large impact on cow welfare is the stall bed. The stall bed is defined both by its size and by the material components of the stall bed (bedding depth, bedding type, and stall base type). This review examines the current literature to determine how the material components of the stall bed, as well as bed length and manger wall/brisket board height (which together define the length of the stall bed) can affect cow welfare through lying time, injuries, lameness, and cow and stall cleanliness. Of the material components of the stall bed, bedding depth appears to have the largest potential positive impact on dairy cow welfare, as deeper levels of bedding in stalls, regardless of the bedding type, can improve compressibility to the extent that the stall base type is negligible. As such, deeper levels of bedding have been associated with increased lying time and a reduced likelihood of a cow developing injuries or becoming lame. Longer stall bed lengths have been shown to increase lying time and decrease the prevalence of injury and lameness. The effect of manger wall or brisket board height on cow welfare has not been studied extensively, but they may work in conjunction with other stall components to define the resting space available to the cow. Overall, the material components of the stall bed, stall length, and manger wall/brisket board height, as well as their combination, all influence cow welfare and need to be taken in consideration to improve the overall welfare of cows in stall-based housing systems.

Distance to treatment as a factor for loss to follow up of hepatitis C patients in North East England.

BACKGROUND: A large proportion of the 200 000 HCV-infected individuals in the UK are undiagnosed or lost to follow-up. Engaging known infected individuals in treatment is essential for elimination. METHODS: Using PHE surveillance data and HCV treatment registers from North East of England (NE) treatment centres for 1997-2016, we estimated the number of HCV cases not linked to treatment and the proportion with active infection. We compared distances of treated and untreated cases to treatment services, and assessed the effect of expanding HCV treatment into existing drug and alcohol treatment centres in the NEE on treatment accessibility. RESULTS: The odds of being treated was associated with distance to treatment services. Confirmatory results for ~50% were not reported to PHE NE. Overall, 3385 patients reported to PHE NE had no record of treatment; we estimated 1621 of these may have been lost to follow-up after confirmation of active infection. CONCLUSIONS: Poor access to healthcare services may contribute to under-diagnosis or loss to follow-up. Expanding HCV treatment delivery into NEE drug and alcohol treatment centres would improve the accessibility of treatment services to people infected with/at risk of HCV. This may increase the proportion receiving treatment and support progress towards elimination.

Lessons from a national audit of acute pancreatitis: A summary of the NCEPOD report 'Treat the Cause'.

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) is an independent organisation whose remit is to review the quality of medical and surgical care provided in the United Kingdom. We undertook a review into the care provided to patients treated for acute pancreatitis during a 6 month study period between 1st January and 30th June 2014. This included assessment of care at an organisational level, clinical level within hospitals and external peer review. From a random sample, 712 patients underwent hospital clinician review and 418 patients had external peer review. Overall, we found that there was room for improvement in care in over 50% of patients with acute pancreatitis. Case reviewers felt that efforts to prevent recurrent episodes due to gallstones and alcohol were inadequate as 21% of patients in the study had one or more previous episodes of acute pancreatitis. Aspects of general care where improvements could be made include better antibiotic stewardship; as 1/5 of patients were considered to have been given antibiotics unnecessarily. Overall management of the patients' nutrition was considered adequate by the case reviewers in only 85% of cases. The use of an early warning score was omitted in 31% of emergency department admissions. Recommendations include standardised early warning scoring systems to be used throughout the hospital and commenced in the emergency department. The development of better networking arrangements and regional pancreatitis units, with shared management guidelines, is also essential to improve the coordination of care.

Republished: Non-alcoholic fatty liver disease: a practical approach to treatment.

Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population in many developed countries. Between 10% and 30% of patients with NAFLD have non-alcoholic steatohepatitis (NASH) that can progress to cirrhosis. There are metabolic risk factors common to both NAFLD and cardiovascular disease, so patients with NASH have an increased risk of liver-related and cardiovascular death. Management of patients with NAFLD depends largely on the stage of disease, emphasising the importance of careful risk stratification. There are four main areas to focus on when thinking about management strategies in NAFLD: lifestyle modification, targeting the components of the metabolic syndrome, liver-directed pharmacotherapy for high risk patients and managing the complications of cirrhosis.

Republished: Non-alcoholic fatty liver disease: non-invasive investigation and risk stratification.

Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum of liver disease, from simple steatosis through to cirrhosis. As the worldwide rates of obesity have increased, NAFLD has become the commonest cause of liver disease in many developed countries, affecting up to a third of the population. The majority of patients have simple steatosis that carries a relatively benign prognosis. However, a significant minority have non-alcoholic steatohepatitis, and have increased liver related and cardiovascular mortality. Identifying those at risk of progressive disease is crucial. Liver biopsy remains the gold standard investigation for assessing stage of disease but its invasive nature makes it impractical for widespread use as a prognostic tool. Non-invasive tools for diagnosis and disease staging are required, reserving liver biopsy for those patients where it offers clinically relevant additional information. This review discusses the non-invasive modalities available for assessing steatosis, steatohepatitis and fibrosis. We propose a pragmatic approach for the assessment of patients with NAFLD to identify those at high risk of progressive disease who require referral to specialist services.

A preliminary study on the feasibility of two different cow-calf contact systems in a pasture-based, seasonal calving dairy system: effects on cow production and health.

Internationally, consumer dissatisfaction with cow-calf separation at birth has led to increased interest in alternative calf-rearing methods, specifically cow-calf contact (CCC) systems. The objectives of this preliminary study were to estimate whether CCC could be incorporated into an Irish spring-calving, pasture-based system, and to investigate the effects on cow milk production and health. Three systems were compared: the conventional Irish system (CONV;18 cows), cow and calf were separated < 1 h postbirth, cows were pasture-based and milked twice-a-day; a full-time access system (FT;14 cows), cow and calf were allowed constant, unrestricted access, were pasture-based, and cows were milked twice-a-day; and a part-time access system (PT;18 cows), cow and calf had unrestricted access when indoors at night, cows grazed outdoors by day while calves remained indoors, and cows were milked once-a-day in the morning. Cows were blocked and balanced across the three systems by previous lactation machine milk yield (MMY), BW, and body condition score (BCS). Following an 8-week CCC period, all calves were weaned (FT and PT underwent a 7-d gradual weaning and separation process) and all cows were milked twice-a-day. Cow MMY was recorded daily and milk composition was recorded weekly; milk data were analysed from weeks 1 to 8 (CCC period), weeks 9 to 35 (post-CCC period), and weeks 1 to 35 (cumulative lactation). Cow BW and BCS were taken weekly for weeks 1-12, and at the end of the lactation. During the CCC period, all systems differed (P < 0.001) in MMY (mean ± SEM; 24.0, 13.6, and 10.3 ± 0.50 kg/d for CONV, FT, and PT cows, respectively). After the CCC period, CONV MMY (20.2 ± 0.48 kg/d) remained higher (P < 0.001) than the FT (16.6 kg/d) and PT cows (15.7 kg/d). The FT and PT cows yielded 24 and 31% less in cumulative lactation MMY and 26 and 35% less in cumulative lactation milk solids yield, respectively, compared to CONV (5 072 ± 97.0 kg and 450 ± 8.7 kg). During the CCC period, somatic cell score was higher (P = 0.030) in PT cows (5.15 ± 0.118) compared to FT cows (4.70 ± 0.118), while CONV (4.94 ± 0.118) were inconclusive to both. The PT cows (523 ± 4.9 and 520 ± 6.8 kg) were heavier than the CONV (474 ± 4.9 and 479 ± 6.8 kg) and FT (488 ± 4.9 and 487 ± 6.8 kg) cows at week 4 and week 8 (both P < 0.001). The PT cows had higher BCS than CONV and FT at all observed times. This preliminary research suggests that although CCC was incorporated without impacting cow health, the two CCC systems investigated negatively affected cow production.

Targeted case finding for hepatitis B using dry blood spot testing in the British-Chinese and South Asian populations of the North-East of England.

Chronic infection with the hepatitis B virus (HBV) is a frequent cause of cirrhosis and liver cancer. Targeted HBV screening is recommended by the Centre for Disease Control (CDC) and Prevention for subjects born in countries with >2% HBV prevalence. However, there are no UK guidelines. Here, we applied the (CDC) recommendations to the British-Chinese and British-South Asian community of North-East (NE) England. British-Chinese and South Asian subjects were invited to attend for HBV education and screening sessions held in community centres. Hepatitis B surface antigen (HBsAg) and hepatitis B core total antibody (HBcAb) were tested with dry blood spot tests. South Asians were also tested for hepatitis C antibody (HCVAb). A total of 1126 subjects (606 Chinese and 520 South Asian) were screened. Sixty-two (5.5%) were HBsAg positive. Ten of these reported a previous diagnosis of HBV. The prevalence of HBsAg positivity was 4.6% when previously diagnosed individuals were excluded. The HBsAg prevalence was significantly higher in the Chinese subjects compared with South Asians (8.7% VS. 1.7% P < 0.001). In Chinese subjects, HBsAg positivity was highest in subjects born in Vietnam (17.4%), followed by China (11%), Hong Kong (7.8%) and the UK (6.7%). Subjects from Pakistan had the highest HBsAg and HCV Ab prevalence in the South Asians (3.1% and 1.8%, respectively). Ten percentage of HBsAg positive patients who had follow-up assessment had active disease requiring antiviral treatment. Undiagnosed HBV infection was above the 2% threshold for screening suggested by the CDC in the British-Chinese and Pakistani community of NE England, which provides evidence for a UK HBV-targeted screening programme.

NICE rapid guidelines: exploring political influence on guidelines.

The National Institute for Health and Care Excellence (NICE) has been presented as politically independent, asserting it is free from industry influence and conflicts of interest so that its decisions may be led by evidence and science. We consider the ways in which soft political factors operate in guideline development processes at NICE such that guidelines are not truly led by science. We suggest that while NICE procedures explicitly incorporate scientific principles and mechanisms, including independent committees and quality assurance, these fail to operate as scientific practices because, for example, decisions may only be challenged through the courts, which regard NICE as a scientific authority. We then examine what the NICE rapid guideline procedure for COVID-19 reveals about the practical reality of claims about the scientific integrity of NICE guidelines. Changes to guideline development processes during the COVID-19 emergency demonstrated how easy it is to undermine the scientific integrity of NICE's decision-making. The cancellation of the guideline programme and the publication of a rapid guideline process specifically to address the COVID-19 pandemic removed scientific checks and balances, including independent committees, stakeholder consultation and quality assurance, demonstrating that the relationship between NICE and the UK government is more complex than a scientific principle truism. We suggest that NICE is not (and indeed cannot be) truly independent of government in practice, nor can it be truly led by science, in part because of its relationship to the state, which it is simultaneously constituted by and constitutive of.

Embolization for non-variceal upper gastrointestinal tract haemorrhage: a systematic review.

AIM: To assess the published evidence on the endovascular treatment of non-variceal upper gastrointestinal haemorrhage. MATERIALS AND METHODS: An Ovid Medline search of published literature was performed (1966-2009). Non-English literature, experimental studies, variceal haemorrhage and case series with fewer than five patients were excluded. The search yielded 1888 abstracts. Thirty-five articles were selected for final analysis. RESULTS: The total number of pooled patients was 927. The technical and clinical success of embolization ranged from 52-100% and 44-100%, respectively. The pooled mean technical/clinical success rate in primary upper gastrointestinal tract haemorrhage (PUGITH) only, trans-papillary haemorrhage (TPH) only, and mixed studies were 84%/67%, 93%/89%, and 93%/64%, respectively. Clinical outcome was adversely affected by multi-organ failure, shock, corticosteroids, transfusion, and coagulopathy. The anatomical source of haemorrhage and procedural variables did not affect the outcome. A successful embolization improved survival by 13.3 times. Retrospective comparison with surgery demonstrated equivalent mortality and clinical success, despite embolization being applied to a more elderly population with a higher prevalence of co-morbidities. CONCLUSIONS: Embolization is effective in this very difficult cohort of patients with outcomes similar to surgery.

Cortical localization of a calcium release channel in sea urchin eggs.

We have used an antibody against the ryanodine receptor/calcium release channel of skeletal muscle sarcoplasmic reticulum to localize a calcium release channel in sea urchin eggs. The calcium release channel is present in less than 20% of immature oocytes, where it does not demonstrate a specific cytoplasmic localization, while it is confined to the cortex of all mature eggs examined. This is in contrast to the cortical and subcortical localization of calsequestrin in mature and immature eggs. Immunolocalization of the calcium release channel reveals a cortical reticulum or honeycomb staining network that surrounds cortical granules and is associated with the plasma membrane. The network consists of some immunoreactive electron-dense material coating small vesicles and elongate cisternae of the endoplasmic reticulum. The fluorescent reticular staining pattern is lost when egg cortices are treated with agents known to affect sarcoplasmic reticulum calcium release and induce cortical granule exocytosis (ryanodine, calcium, A-23187, and caffeine). An approximately 380-kD protein of sea urchin egg cortices is identified by immunoblot analysis with the ryanodine receptor antibody. These results demonstrate: (a) the presence of a ryanodine-sensitive calcium release channel that is located within the sea urchin egg cortex; (b) an altered calcium release channel staining pattern as a result of treatments that initiate the cortical granule reaction; and (c) a spatial and functional dichotomy of the ER which may be important in serving different roles in the mobilization of calcium at fertilization.

Assessment of apparent internal carotid occlusion on ultrasound: prospective comparison of contrast-enhanced ultrasound, magnetic resonance angiography and digital subtraction angiography.

OBJECTIVES: Modern conventional ultrasound is sensitive to slow flow, but may misclassify some tight stenoses as occlusion. Symptomatic patients with tight proximal internal carotid artery stenoses may benefit from carotid endarterectomy but those with occlusion or long-segment disease do not. DESIGN: A prospective study of the diagnostic accuracy of contrast-enhanced ultrasound (CE-US), 2D time-of-flight magnetic resonance angiography (2D-TOF MRA) and contrast-enhanced magnetic resonance angiography (CE-MRA) against a reference standard of digital subtraction angiography (DSA) in patients with apparent carotid occlusion on conventional ultrasound. MATERIALS AND METHODS: Thirty-one patients with apparent carotid occlusion on conventional ultrasound and with recent ispilateral hemispheric transient ischaemeic attacks (TIAs) were studied. The primary endpoint was confirmation of occlusion with a secondary endpoint of identification of a surgically correctible lesion. RESULTS: The sensitivity and specificity of CE-US, 2D-TOF MRA and CE-MRA for patency were 1 & 1, 0.33 & 1 and 0.6 & 1 respectively and for the detection of a surgically correctible lesion were 1 & 0.96, 0.67 & 1 and 1 and 0.96 respectively. CE-US was difficult to interpret, precluding confident diagnosis in 5 cases. CONCLUSIONS: 2D-TOF MRA had poor sensitivity for patency and cannot be recommended as a second-line investigation to assess vessels apparently occluded on conventional ultrasound. Confident diagnosis on CE-US and CE-MRA accurately identified occlusion. If occlusion is confirmed by either of these modalities, no further imaging is required. The relative advantages of CE-US or CE-MRA in this situation are uncertain.

The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation.

OBJECTIVES: To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research. DATA SOURCES: Major electronic databases were searched up to December 2005. REVIEW METHODS: Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken. RESULTS: Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3-4% in 40 year olds with a screening interval of 10 years to approach cost-effectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as 669 pounds. If annual societal costs were 8800 pounds, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of 30,000 pounds per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty. In particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective. CONCLUSIONS: While population screening is not cost-effective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing.

Biomechanical evaluation of fetal calf skull as a model for testing halo-pin designs for use in children.

Rigid immobilization of the cervical spine in children is normally accomplished with a halo ring attached to the skull with pins. Concern exists about the risk of halo pin complications in small children due to their diminished skull thickness. More data are needed on biomechanical properties of the immature skull and on safe levels for halo pin penetration forces. The study included halo pin penetration tests on 43 skull samples obtained from eight fetal calves, radial compression tests of 11 skull samples, and histology. Compressive composite elastic modulus (15-139MPa), yield stress (1-5MPa) and composite consolidation modulus (188-479MPa) were measured in the skull's radial direction. Pin penetration force (F) in Newtons at a pin-penetration depth equal to the original skull thickness (T) in mm, was related to T as: F=100+4.3e(T) (R(2)=0.76, p<0.0001). However, the 95% confidence limits on individual predictions were wide, e.g., 0-475MPa for T=1.5mm and 0-700MPa for T=4mm. These results suggest that skull thickness cannot be reliably used to predict halo pin penetration loads in a skull with similar structural and mechanical properties to that of the fetal calf. Due to the lack of available human data for comparison, the relevance of using the fetal calf skull as a model for human infants and young children remains inconclusive. Clinical recommendations regarding pediatric halo pin penetration loads cannot be made without further study of children's skull structure and biomechanical properties.

Cytokine production in motor neurons by poliovirus replicon vector gene delivery.

Poliovirus replicon vectors transiently express foreign proteins selectively in motor neurons of the anterior horn of the spinal cord. Here we intraspinally inoculated mice transgenic for the poliovirus receptor (PVR) with replicons encoding murine tumor necrosis factor alpha (mTNF-alpha). We detected high-level expression of mTNF-alpha in the spinal cords of these animals at 8-12 h post inoculation; this returned to background by 72 h. The mice exhibited ataxia and tail atony, whereas animals given a replicon encoding green fluorescent protein (GFP) exhibited no neurological symptoms. Histology of spinal cords from mice given the replicon encoding mTNF-alpha revealed neuronal chromatolysis, reactive astrogliosis, decreased expression of myelin basic protein, and demyelination. These animals recovered with only slight residual damage. This study shows that replicon vectors have potential for targeted delivery of therapeutic proteins to the central nervous system and provide a new approach for treatment of spinal cord trauma and neurological disease.

Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis.

BACKGROUND: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA. AIM: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS. METHODS: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded. RESULTS: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month. CONCLUSIONS: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427.