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.

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.

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.

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.

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.

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.

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.

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.

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.

Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality.

Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC). Using short hairpin RNA (shRNA)-mediated suppression of NRP1, we demonstrate that NRP1 regulates the mesenchymal phenotype of mCRPC cell models and the invasive and metastatic dissemination of tumor cells in vivo. In patients, immunohistochemical staining of tissue microarrays and mRNA expression analyses revealed a positive association between NRP1 expression and increasing Gleason grade, pathological T score, positive lymph node status and primary therapy failure. Furthermore, multivariate analysis of several large clinical prostate cancer (PCa) cohorts identified NRP1 expression at radical prostatectomy as an independent prognostic biomarker of biochemical recurrence after radiation therapy, metastasis and cancer-specific mortality. This study identifies NRP1 for the first time as a novel androgen-suppressed gene upregulated during the adaptive response of prostate tumors to ATTs and a prognostic biomarker of clinical metastasis and lethal PCa.

Implementation of a 'care bundle' improves the management of patients admitted to hospital with decompensated cirrhosis.

BACKGROUND: Since 1970, there has been a 400% increase in liver-related deaths due to the increasing prevalence of chronic liver disease in the United Kingdom (UK). The 2013 UK National Confidential Enquiry into Patient Outcome and Death report found that only 47% of patients who died from alcohol-related liver disease received 'good care' during their hospital stay. AIM: To develop a 'care bundle' for patients with decompensated cirrhosis, aiming to ensure that evidence-based treatments are delivered within the first 24 h of hospital admission. METHODS: This work gives practical advice about how to implement the bundle and examines its effects on patient care at three National Health Service Hospital Trusts in the UK by collecting data on patient care before and after introduction of the bundle. RESULTS: Data were collected on 228 patients across three centres (59% male, median age 53 years). Alcohol-related liver disease was the aetiology of chronic liver disease in 85% of patients. The overall mortality rate during hospital admission was 15%. The audits demonstrated improvements in patient care for patients with a completed care bundle who were significantly more likely to have a diagnostic ascitic performed within the first 24 h (P = 0.020), have an accurate alcohol history documented (P < 0.0001) and be given antibiotics as prophylaxis against infection following a variceal haemorrhage (P = 0.0096). In Newcastle, the bundle completion rate increased from 25% to 90% during the review periods. CONCLUSIONS: The introduction of a care bundle was associated with increased rates of diagnostic paracentesis and antibiotic prophylaxis with variceal haemorrhage in patients with decompensated cirrhosis.

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.

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.

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.