Offering HCV treatment to prisoners is an important opportunity: key principles based on policy and practice assessment in Europe.

BACKGROUND: Prisoners have a high prevalence of hepatitis C virus (HCV) infection but may find it difficult to access healthcare services. This may be related to risk behaviour including history of injecting drugs and marginalisation related to problem drug use/ opioid use disorder (OUD). Direct-acting antiviral products with superior efficacy and safety compared to interferon-based regimens offer HCV cure. Many citizens in Europe have been treated, although few received therapy in prisons. METHODS: Analysis of prisoner HCV treatment need and policy determinants of clinical practice was completed for 5 EU countries. Evidence was collected from national statistical sources and peer-reviewed publications to describe prison populations and HCV prevalence, to map national prison/ HCV health policy or guidance. A consensus of important principles for prisoner HCV care was developed. RESULTS: Data from published sources describing prisoner HCV prevalence is limited. Prisoner population requiring HCV treatment is not known; estimated numbers based on analysis of evidence: England and Wales, 9000, France, 8000, Spain, 6000, Italy, 6000, Germany, 6000. Treatment access: national law defines right to equivalent care in all countries implying access to HCV therapy in prison similar to community; useful prisoner HCV guidance facilitating treatment decisions present in: 4 of 5 national/ regional HCV policy documents, 4 of 5 national prison healthcare policies. Four of five had practical prison HCV clinical guidelines. Despite existence of policy, implementation of guidance, and so HCV treatment, is suboptimal in many locations. CONCLUSIONS: Prison is an important location to detect, address and treat HCV infection in people who may be underserved for healthcare and find it difficult to navigate community treatment pathways. This is often related to problems with OUD and resulting social inequity. HCV management in prisons must be improved. Policy and clinical practice guidance must be set to promote treatment, and practical steps to make treatment easy should be followed including education to promote engagement, set-up of optimal screening and work up processes with modern tools to reduce time needed/ achieve efficiency; programs to make it easier to get specialists' input include remote working and nurse-led services.

Effects of high-dose aprotinin on renal function in aortocoronary bypass grafting.

BACKGROUND: To reduce blood consumption in cardiac surgery, aprotinin has been widely used for years. Because aprotinin is metabolized in the kidney, damage of the renal system has been discussed. METHODS: To study these possibly unfavorable effects of aprotinin, a prospective, randomized, placebo-controlled study of 20 patients undergoing aortocoronary bypass operations was performed. A placebo group P was compared with group A, in which patients received high-dose aprotinin according to the "Hammersmith" regimen. Renal function was assessed for 5 postoperative days using sodium dodecyl sulfate gel electrophoresis and quantitative protein analysis of the urine. RESULTS: During and after the operation, temporary renal dysfunction was found in all patients, with a substantial increase of all investigated indices. The alpha 1-microglobulin level in the urine was significantly increased in the aprotinin group for 5 days in comparison with the placebo group, with a maximum on the third postoperative day (64.8 +/- 13.7 versus 21.0 +/- 6.5 mg/L; p < 0.05). Similarly, after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the bands of proteins filtrated in the renal tubular system were almost tripled in the aprotinin group 5 days postoperatively (5.0 +/- 0.8 versus 2.1 +/- 0.2; p < 0.05). Although urine production was significantly increased in group A (4789 +/- 580 versus 3653 +/- 492 mL/24 h postoperatively; p < 0.05), no relevant changes in serum or urine creatinine levels could be observed in either group. CONCLUSIONS: Patients undergoing aortocoronary bypass operations demonstrate a temporary renal dysfunction. Aprotinin impairs renal function in addition by overloading the tubular reabsorption mechanisms. Patients with normal renal function preoperatively--as were included in this study--are able to compensate for both the perioperative renal dysfunction caused by the extracorporeal circulation and the additional tubular damage due to aprotinin.

Clinical experience with antagonist-induced opiate withdrawal under anaesthesia.

AIMS: The study describes experience with antagonist-induced opiate withdrawal under anaesthesia in standard clinical conditions. DESIGN: The study was restricted to patients who had undergone failed withdrawal treatments with usual methods over the past months. No control group was used. SETTING AND PROCEDURE: The patients were selected after history-taking and examination. A multi-axial diagnosis was performed. They were then admitted to an inpatient treatment unit for addicted patients. On the second day they were put into neurological intensive care. There they were intubated, ventilated and anaesthetized with propofol for 6 hours. Shortly after induction of anaesthesia, naloxone and naltrexone were administered. A high amount of fluid was used to balance changes in water and electrolytes. After anaesthesia the patients were transferred back to the addiction ward and sedated with clonidine. The patients were then fully mobilized. On discharge 50 mg naltrexone were given daily. PARTICIPANTS: Eighty-eight patients were treated. They were long-term opiate users. Preference was given to methadone-substituted patients who were unable to rid themselves of methadone. MEASUREMENTS: The account given is based solely on clinical observations. FINDINGS: The first 14 patients were observed in detail and it is on them that this report is based. It was found that withdrawal from codeine and methadone can be shortened to approximately 2-3 days. No patient was in a condition to go home immediately after anaesthesia. Twelve patients showed significant symptoms on the day following anaesthesia. The majority of patients treated by this method will continue to suffer withdrawal symptoms for a few days after detoxification, after which time most can be treated in an outpatient setting. Dysfunction of the cardiovascular system, the lungs, the kidneys or other organs was not observed. Taking into account all the 88 patients, five had to stay in hospital for a longer period (up to 2 weeks) because of a prolonged withdrawal syndrome.

Influence of standardized mobilization on the posteroanterior stiffness of the lumbar spine in asymptomatic subjects.

BACKGROUND AND PURPOSE: Spinal mobilization is commonly used to relieve pain and assist recovery of mobility in individuals with low back pain. Fundamental to this concept is the belief that spinal mobilization will influence the mechanical properties of the symptomatic motion segment. The objective of the present study was to examine the segmental effects of a standardized mobilization procedure on the posteroanterior (PA) stiffness of the lumbar spine. METHOD: Audio and visual feedback was used to train a physiotherapist to perform PA mobilization at a consistent load and frequency. After training, twenty-four subjects without low back pain were recruited for the intervention phase of the study. The spinal posteroanterior mobilization (SPAM) apparatus was used to measure the PA stiffness of the lumbar spine at three measurement sites (L1, L3 and L5). The trained physiotherapist then applied the standardized PA mobilization technique via the L3 spinous process for two minutes. Following mobilization, PA stiffness was measured three times at the three locations. RESULTS: The physiotherapist was able to apply a standardized mobilization with a mean force of 146 N (standard deviation (SD) 8 N) at a frequency of 1.5 Hz. The first trial on each assessment demonstrated a pre-condition effect. Two minutes' PA mobilization resulted in no significant change in the PA stiffness of the lumbar spine at the level to which the mobilization was applied, or at the L1 and L5 segments. The 95% confidence intervals (CI) of the difference in PA stiffness before and after testing included zero at each measurement site. CONCLUSIONS: Clinicians should pre-condition the spine when assessing PA stiffness both before and after interventions. A standardized mobilization of 150 N at 1.5 Hz for two minutes had no segmental effect on spinal PA stiffness. Subsequent studies need to consider other mechanisms that may contribute to the changes that occur after PA spinal mobilization.

The lipid/protein interface as xenobiotic target site: kinetic analysis of the nicotinic acetylcholine receptor.

Membrane proteins are known to be solvated and functionally activated by a fixed number of lipid molecules whose multiple binding can be described by Adair-type binding equations. Lipophilic xenobiotics such as general anesthetics may act by competitive displacement of protein-bound lipids. A kinetic equation is now presented for various binding stoichiometries of lipid and xenobiotic, and microscopic binding constants of anesthetics and organic solvents are derived from two independent assay systems for the enhancement of agonist binding to the nicotinic acetylcholine receptor. These constants lead to the first available free energy estimate (-6.4 kcal/mol) for the binding of membrane lipid to an integral membrane protein.