Commercial operations of uncrewed aerial vehicles (UAVs or drones) are expanding, with medical logistics using UAVs as part of health service supply chains being targeted. The ability to transport ...cargos that include items classified as Dangerous Goods (DG) is a significant factor in enabling UAV logistics to assist medical supply chains, but DG regulations for air transport have developed from the perspective of crewed aircraft and not UAVs. This paper provides an important audit of the current DG regulations, best practice in their application and the development of much-needed new governance that will be required to fully exploit UAVs for the safe transport of DG in medical logistics. Findings from the audit provide a summary of the circumstances and potential challenges resulting from the application of DG regulations as they stand to UAV operations, particularly for medical logistics, and convenient guidance on the practical implications of DG regulations for UAV operators. The main conclusion is that this is an under-researched domain, not yet given full consideration in a holistic way by regulators, governments, industry bodies, practitioners or academia.
This paper discusses the annual incidence of liver disease and resource costs in providing a hepatology service for all new outpatient referrals to a secondary care setting. In a retrospective study, ...we found that 200 patients (1 in 1,000 of the West Suffolk population) with a mean age of 52 years were referred per year. One-third of patients had cirrhosis (almost half due to alcohol). Annual incidence (per 100,000 population) were as follows: non-alcoholic fatty liver disease (29: of which 23.5 non-cirrhotic and 5.5 cirrhotic), hepatitis C (25), hepatitis B (3), alcohol-related cirrhosis (12.5), primary biliary cirrhosis (3.5), autoimmune hepatitis (3), primary sclerosing cholangitis (2), haemochromatosis (2), hepatocellular carcinoma (1.5) and oesophageal variceal haemorrhage (6.5). Using national indicative tariffs, the total annual hepatology budget was £130K (£58K for resources and £72K for clinic attendances). The greatest resource expenditure was on endoscopy (almost half for oesophageal varices) and radiological imaging (one-third of the total budget). These findings will help inform commissioners in hepatology service funding.
After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually ...studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct
ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease.
(Hepatology 2000;32:1117-1124.)
Abstract
Background/Aims
Hydrotherapy remains an important part of treatment for a range of rheumatological, musculoskeletal and other conditions. As there is little robust clinical evidence, ...hydrotherapy is scarcely included in national guidelines, with the exception of the National Institute for Health and Care Excellence (NICE) Guidance for Spondyloarthritis which recommends hydrotherapy as an adjunct therapy. In recent years, hydrotherapy services have often been targeted in cost-saving exercises by commissioners and providers. There was a concern that this would be further exacerbated by the pandemic with pools closing to become storage space and remaining closed beyond this.
Methods
Via the All Party Parliamentary Group (APPG) for axial spondyloarthritis (axial SpA), we submitted a Freedom of Information Request (FOI) to establish the status of hydrotherapy pools pre- and post-pandemic. The FOI was sent to all NHS trusts in England asking them about the status of their pool before and after COVID, future plans and reasons for any delay in re-opening.
Results
90 trusts (69%) responded. 72% of those had an onsite hydrotherapy pool prior to the pandemic, 90% of which were open. 27% of pools had already re-opened and there were plans to re-open 49%. 2% were due to remain permanently shut with 21% unsure of the future of their pool. The most common reasons for delays in pools re-opening were linked to infection prevention control restrictions, including changing area capacity (23%), social distancing and ventilation (38%). The most common reasons for the uncertainty of when they would re-open were changing area capacity (46%), staff to clean (23%), access to pool i.e., still being used for other purposes (30%), social distancing and ventilation (23%). Of those pools that were already open or due to re-open, 93% had a reduced capacity with an average capacity of 37%. This was largely due to changing area capacity (54%), staff to clean (44%), access to the pool (28%), social distancing and ventilation (55%). Of the pools that were open prior to the pandemic, the condition areas which used them included MSK (92%), neurology (74%), physical disability (77%) and children (77%). 8% of users had axial SpA.
Conclusion
There is a very real threat to NHS hydrotherapy facilities in England. A lack of robust clinical evidence often leaves therapists and patients in limbo, with anecdotal testimony as to the benefits often not being enough to convince of its value. A co-ordinated cross-condition alliance is needed to ensure: clear local pathways are established into hydrotherapy; pools are considered in new build and refurbishments; robust clinical evidence is produced; hydrotherapy is included in national guidelines; tools are available at local level to audit and promote hydrotherapy; local services can become self-funding via community and patient groups.
Disclosure
J. Hamilton: None. C. Jeffries: None. S. Whalley: None. D. Webb: None.
AbstractObjectivesTo quantify post-colonoscopy colorectal cancer (PCCRC) rates in England by using recent World Endoscopy Organisation guidelines, compare incidence among colonoscopy providers, and ...explore associated factors that could benefit from quality improvement initiatives.DesignPopulation based cohort study.SettingNational Health Service in England between 2005 and 2013.PopulationAll people undergoing colonoscopy and subsequently diagnosed as having colorectal cancer up to three years after their investigation (PCCRC-3yr).Main outcome measuresNational trends in incidence of PCCRC (within 6-36 months of colonoscopy), univariable and multivariable analyses to explore factors associated with occurrence, and funnel plots to measure variation among providers.ResultsThe overall unadjusted PCCRC-3yr rate was 7.4% (9317/126 152), which decreased from 9.0% in 2005 to 6.5% in 2013 (P<0.01). Rates were lower for colonoscopies performed under the NHS bowel cancer screening programme (593/16 640, 3.6%), while they were higher for those conducted by non-NHS providers (187/2009, 9.3%). Rates were higher in women, in older age groups, and in people with inflammatory bowel disease or diverticular disease, in those with higher comorbidity scores, and in people with previous cancers. Substantial variation in rates among colonoscopy providers remained after adjustment for case mix.ConclusionsWide variation exists in PCCRC-3yr rates across NHS colonoscopy providers in England. The lowest incidence was seen in colonoscopies performed under the NHS bowel cancer screening programme. Quality improvement initiatives are needed to address this variation in rates and prevent colorectal cancer by enabling earlier diagnosis, removing premalignant polyps, and therefore improving outcomes.
Using patient data from a unique single source outbreak of hepatitis B virus (HBV) infection, we have characterized the kinetics of acute HBV infection by monitoring viral turnover in the serum ...during the late incubation and clinical phases of the disease in humans. HBV replicates rapidly with minimally estimated doubling times ranging between 2.2 and 5.8 d (mean 3.7 +/- 1.5 d). After a peak viral load in serum of nearly 10(10) HBV DNA copies/ml is attained, clearance of HBV DNA follows a two or three phase decay pattern with an initial rapid decline characterized by mean half-life (t(1/2)) of 3.7 +/- 1.2 d, similar to the t(1/2) observed in the noncytolytic clearance of covalently closed circular DNA for other hepadnaviruses. The final phase of virion clearance occurs at a variable rate (t(1/2) of 4.8 to 284 d) and may relate to the rate of loss of infected hepatocytes. Free virus has a mean t(1/2) of at most 1.2 +/- 0.6 d. We estimate a peak HBV production rate of at least 10(13) virions/day and a maximum production rate of an infected hepatocyte of 200-1,000 virions/day, on average. At this peak rate of virion production we estimate that every possible single and most double mutations would be created each day.
Parallel optical interconnects on-board level requires low propagation loss in wavelength range between 850 and 1550 nm to be compatible with datacom and telecom optical engines. For highest ...integration density tight waveguide bends and a scalable number of optical layers should be manufacturable for 2D interfaces to optical fiber array connectors and photonic assembly I/O's. We developed a glass waveguide panel process for double-sided processing of commercial available display glass by applying a two-step thermal ion-exchange process for low-loss multi-mode graded-index waveguides. Multiple glass waveguide panels can be embedded between electrical layers. The generic concept enables fabrication of high-density integration (HDI) electro-optical circuit boards (EOCB) with high number of optical and electrical layers. Waveguides with high NA of 0.3 for low bend losses could be achieved in glass with propagation loss of 0.05 dB/cm for all key wavelengths. Four of those glass waveguide panels were embedded in an EOCB demonstrator with size of 280 x 233 mm² providing eight optical layers with 96 channels in an area of 2.8 x 1.5 mm². To the best of our knowledge it's the highest number of layers that has ever been demonstrated for an EOCB.
Background & Aims:
Acute hepatitis B is a highly dynamic human viral infection during which the hepatitis B virus can generate many genetic variants.
Methods:
We analyzed the evolution of the ...hepatitis B virus genome in sequential serum samples from a unique cohort of patients with acute infection acquired from a single source.
Results:
We showed that most mutations were nonsynonymous, that genetic diversity was greatest at the peak of viremia, and that patients who resolved their infection (“resolvers”) showed a significantly higher level of diversity in the core, surface, and polymerase genes compared with those who progressed to chronic infection. Overall, the core gene showed the greatest genetic diversity. In resolvers who possessed an HLA-A*0201 haplotype, the emergence of mutants in the immunodominant HLA-A*0201–restricted core 18–27 epitope was observed. Functional studies showed that these mutants were less able to stimulate interferon-γ release from core 18–27 specific CD8
+ T-cell lines. However, they appeared only as a transient low-abundance species and were rapidly displaced by wild-type sequences before resolution of infection, and their overall significance is uncertain.
Conclusions:
Overall, genetic evolution of the hepatitis B virus differs at early time points between patients who experience acute resolving hepatitis B and those who progress to chronicity. These observations suggest that the rapid development of broadly reactive host immune responses leads to clearance of hepatitis B virus, even in the presence of possible CD8
+ T-cell immune escape variants.
The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers ...associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA–treated external controls.
Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly between the first and last date (inclusive) on which eligibility criteria were met. Cox proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis.
During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) for the primary outcome were 0.29 (95% CI, 0.10–0.83) for POISE vs Global PBC and 0.30 (95% CI, 0.12–0.75) for POISE vs UK-PBC. In the Global PBC study, HR was 0.20 (95% CI, 0.03–1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09–1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21–0.85) including hepatic decompensation.
Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.
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Patients with primary biliary cholangitis treated with obeticholic acid in the POISE study had fewer deaths and liver transplants vs comparable patients in the Global PBC and UK-PBC disease registries.
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