Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males.

BACKGROUND: The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis. OBJECTIVES: The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture. METHODS: Four groups of sheep (n = 10-12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography/tandem mass spectroscopy. RESULTS: Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzo[a]anthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma-secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure. CONCLUSIONS: Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.

The Memokath-051 Stent for the Treatment of Ureteric Obstruction: A NICE Medical Technology Guidance.

Memokath-051 is a thermo-expandable, nickel-titanium alloy spiral stent used to treat ureteric obstruction resulting from malignant or benign strictures. The National Institute for Health and Care Excellence (NICE) selected Memokath-051 for evaluation. The company, PNN Medical, claimed Memokath-051 has clinical superiority and cost savings compared with double-J stents. It identified five studies reporting clinical evidence on Memokath-051 and constructed a de novo cost model comparing Memokath-051 to double-J stents. Results indicated that Memokath-051 generated cost savings of £4156 per patient over 2.5 years. The External Assessment Centre (EAC) critiqued the company's submission and completed substantial additional work. Sixteen studies were identified assessing Memokath-051 and all listed comparators in the scope (double-J stents, reconstructive surgery and metallic and alloy stents) except nephrostomy. Similar success rates were reported for Memokath-051 compared with double-J and Resonance stents and worse outcomes compared with other options with evidence available. The EAC updated the company's cost model structure and modified several inputs. The EAC's model estimated that Memokath-051 generated savings of at least £1619 per patient over 5 years compared with double-J stents, was cost neutral compared with other metallic stents and was cost saving compared with surgery up to month 55. Overall, Memokath-051 is likely to be cost saving in patients not indicated for reconstructive surgery and those expected to require a ureteral stent for at least 30 months. The Medical Technologies Advisory Committee (MTAC) reviewed the evidence and supported the case for adoption, issuing partially supportive recommendations published after public consultation as Medical Technologies Guidance 35.

Cost-effectiveness analysis of the use of high-flow oxygen through nasal cannula in intensive care units in NHS England.

OBJECTIVE: To estimate the cost-effectiveness of Nasal High Flow (NHF) in the intensive care unit (ICU) compared with standard oxygen or non-invasive ventilation (NIV) from a UK NHS perspective. METHODS: Three cost-effectiveness models were developed to reflect scenarios of NHF use: first-line therapy (pre-intubation model); post-extubation in low-risk, and high-risk patients. All models used randomized control trial data on the incidence of intubation/re-intubation, events leading to intubation/re-intubation, mortality and complications. NHS reference costs were primarily used. Sensitivity analyses were conducted. RESULTS: When used as first-line therapy, Optiflow™ NHF gives an estimated cost-saving of £469 per patient compared with standard oxygen and £611 versus NIV. NHF cost-savings for high severity sub-group were £727 versus standard oxygen, and £1,011 versus NIV. For low-risk post-intubation patients, NHF generates estimated cost-saving of £156 versus standard oxygen. NHF decreases the number of re-intubations required in these scenarios. Results were robust in most sensitivity analyses. For high-risk post-intubation patients, NHF cost-savings were £104 versus NIV. NHF results in a non-significant increase in re-intubations required. However, reduction in respiratory failure offsets this. CONCLUSIONS: For patients in ICU who are at risk of intubation or re-intubation, NHF cannula is likely to be cost-saving.