Evaluation of intermediate care for knee and hip osteoarthritis: a mixed-methods study.

BACKGROUND: To evaluate intermediate care for knee and hip osteoarthritis (KHOA) in the general practice that incorporate specialist services into general practice to prevent unnecessary referrals to hospitals. METHODS: We used a mixed methods approach including semi-structured interviews, patient experience questionnaires and data from medical records from three intermediate care projects. Semi-structured interviews were conducted with patients, general practitioners (GPs), orthopaedists and a healthcare manager in intermediate care. Satisfaction of patients who received intermediate care (n = 100) was collected using questionnaires. Referral data and healthcare consumption from medical records were collected retrospectively from KHOA patients before (n = 96) and after (n = 208) the implementation of intermediate care. RESULTS: GPs and orthopaedists in intermediate care experienced more intensive collaboration compared to regular care. This led to a perceived increase in GPs' knowledge enabling better selection of referrals to orthopaedics and less healthcare consumption. Orthopaedists felt a higher workload and limited access to diagnostic facilities. Patients were satisfied and experienced better access to specialists' knowledge in a trusted environment compared to regular care. Referrals to physiotherapy increased significantly after the implementation of intermediate care (absolute difference = 15%; 95% CI = 7.19 to 22.8), but not significantly to orthopaedics (absolute difference = 5.9%; 95% CI = -6.18 to 17.9). CONCLUSIONS: Orthopaedists and GPs perceived the benefits of an intensified collaboration in intermediate care. Intermediate care may contribute to high quality of care through more physiotherapy referrals. Further research with longer follow-up is needed to confirm these findings and give more insight in referrals and healthcare consumption.

Quality indicators for knee and hip osteoarthritis care: a systematic review.

To provide an overview of quality indicators (QIs) for knee and hip osteoarthritis (KHOA) care and to highlight differences in healthcare settings. A database search was conducted in MEDLINE (PubMed), EMBASE, CINAHL, Web of Science, Cochrane CENTRAL and Google Scholar, OpenGrey and Prospective Trial Register, up to March 2020. Studies developing or adapting existing QI(s) for patients with osteoarthritis were eligible for inclusion. Included studies were categorised into healthcare settings. QIs from included studies were categorised into structure, process and outcome of care. Within these categories, QIs were grouped into themes (eg, physical therapy). A narrative synthesis was used to describe differences and similarities between healthcare settings. We included 20 studies with a total of 196 QIs mostly related to the process of care in different healthcare settings. Few studies included patients' perspectives. Rigorous methods for evidence synthesis to develop QIs were rarely used. Narrative analysis showed differences in QIs between healthcare settings with regard to exercise therapy, weight counselling, referral to laboratory tests and 'do not do' QIs. Differences within the same healthcare setting were identified on radiographic assessment. The heterogeneity in QIs emphasise the necessity to carefully select QIs for KHOA depending on the healthcare setting. This review provides an overview of QIs outlined to their healthcare settings to support healthcare providers and policy makers in selecting the contextually appropriate QIs to validly monitor the quality of KHOA care. We strongly recommend to review QIs against the most recent guidelines before implementing them into practice.

Pelvic reconstruction with a free vascularized distal femur for revision total hip arthroplasty.

The reconstruction of massive structural acetabular defects after revision arthroplasty presents a unique challenge to the orthopedic surgeon. This report describes such a salvage procedure where an autologous vascularized distal femur was used to reconstruct acetabular bone stock with subsequent implantation of a total femoral endoprosthetic replacement that uses a constrained cup and a hinged total knee system. At 2 years of follow-up, there is a good functional result with full incorporation of the graft.

Bioartificial liver: its pros and cons.

Both the large variety of liver functions for maintaining body homeostasis and the proven effectivity of whole liver transplantation in the therapy of acute liver failure (ALF), are important reasons to presume that cell-free liver support systems will not be able to adequately support the failing liver. Accordingly, bioartificial liver (BAL) systems have shown their efficacy in experimental ALF models in small and large animals, and have shown to be suitable and safe in phase 1 studies in humans with ALF. However, the optimal BAL system is still under development. Important issues are the source of the cellular component and the configuration of the BAL system with regard to cell attachment, mass transfer characteristics and oxygenation at site. The deficiency of all BAL systems to excrete bile effectively is another important topic for improvement. The great challenge for the future is to develop a well-functioning and safe human hepatic cell line which can replace the widely used porcine (xenogeneic) hepatocytes. Theoretically, a combination of a cell-free liver support system and a BAL system might be optimal for the treatment of ALF patients in the near future.

No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the AMC-bioartificial liver.

BACKGROUND: Currently a number of bioartificial livers (BAL) based on porcine liver cells have been developed as a treatment to bridge acute liver failure patients to orthotopic liver transplantation or liver regeneration. These xenotransplantation related treatments hold the risk of infection of treated patients by porcine endogenous retrovirus (PERV) released from the porcine cells, as in vitro infection experiments and transplantations in immunocompromised mice have shown that PERV is able to infect human cells. The Academic Medical Center (AMC)-BAL, unlike other BALs, is characterized by direct contact between porcine liver cells and human plasma, and might therefore be permissive for PERV transfer. METHODS: Prior to a clinical phase I trial, human plasma perfused through the AMC-BAL was investigated for PERV DNA and RNA. Moreover productive infectivity was analyzed by exposing the plasma to HEK-293 cells that were subsequently tested for PERV DNA, PERV RNA and reverse transcriptase activity. RESULTS: Although PERV DNA was detected in the perfused plasma, no productive infectivity was detected. Consequently fourteen patients were treated with the AMC-BAL and monitored for PERV transmission. Immediately after treatment the plasma of the patients was positive for PERV DNA, most probably due to porcine liver cell lysis. The PERV DNA was cleared within 2 weeks post-treatment and no PERV RNA was detected. No productive infectivity in human embryonic kidney (HEK)-293 cells exposed to plasma of treated patients was detectable. CONCLUSION: To conclude, no release of infective PERV particles from the AMC-BAL was observed. Therefore we consider the AMC-BAL as safe, however careful surveillance of patients will be continued.

Evidence for Galalpha(1-3)Gal expression on primary porcine hepatocytes: implications for bioartificial liver systems.

BACKGROUND/AIMS: To bridge acute liver failure (ALF) patients to orthotopic liver transplantation, several bioartificial liver (BAL) systems have been developed. The bio-component of most BAL systems consists mainly of porcine hepatocytes. Plasma or blood of ALF patients is perfused through the BAL thereby contacting porcine hepatocytes. Xenogeneic BAL systems may suffer from hyperacute rejection similar to whole-organ xenotransplants. Hyperacute rejection is mediated by antibodies directed against Galalpha(1-3)Gal, a carbohydrate structure present on most mammalian cells. Galalpha(1-3)Gal is produced by the enzyme alpha1,3-galactosyltansferase (alphaGal-T). Conflicting data have been published concerning Galalpha(1-3)Gal expression on hepatocytes in intact porcine liver. We investigated whether isolated porcine hepatocytes express Galalpha(1-3)Gal. METHODS: Immunofluorescence, flow cytometry, RT-PCR and enzyme activity assays were performed on freshly isolated and cultured porcine hepatocytes and liver biopsies. Anti-Galalpha(1-3)Gal antibodies were measured in plasma from patients treated with BAL by ELISA. RESULTS: Isolated porcine hepatocytes express (alphaGal-T) at low levels and Galalpha(1-3)Gal is present in low quantities on these cells, in contrast to hepatocytes in situ. Furthermore, IgG and IgM anti-Galalpha(1-3)Gal are depleted from the plasma of ALF patients during BAL treatment. CONCLUSIONS: Isolation and culture of porcine hepatocytes induce Galalpha(1-3)Gal expression, which may elicit immunological responses potentially compromising BAL functionality.

Clinical application of bioartificial liver support systems.

OBJECTIVE: To review the present status of bioartificial liver (BAL) devices and their obtained clinical results. BACKGROUND: Acute liver failure (ALF) is a disease with a high mortality. Standard therapy at present is liver transplantation. Liver transplantation is hampered by the increasing shortage of organ donors, resulting in high incidence of patients with ALF dying on the transplantation waiting list. Among a variety of liver assist therapies, BAL therapy is marked as the most promising solution to bridge ALF patients to liver transplantation or to liver regeneration, because several BAL systems showed significant survival improvement in animal ALF studies. Until today, clinical application of 11 different BAL systems has been reported. METHODS: A literature review was performed using MEDLINE and additional library searches. Only BAL systems that have been used in a clinical trial were included in this review. RESULTS: Eleven BAL systems found clinical application. Three systems were studied in a controlled trial, showing no significant survival benefits, in part due to the insufficient number of patients included. The other systems were studied in a phase I trial or during treatment of a single patient and all showed to be safe. Most BAL therapies resulted in improvement of clinical and biochemical parameters. CONCLUSIONS: Bioartificial liver therapy for bridging patients with ALF to liver transplantation or liver regeneration is promising. Its clinical value awaits further improvement of BAL devices, replacement of hepatocytes of animal origin by human hepatocytes, and assessment in controlled clinical trials.

Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver.

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 x 10(9) viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.

MARS treatment in posthepatectomy liver failure.

Posthepatectomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver failure patients. This paper describes the initial experience in the Netherlands using the MARS liver assist device in five patients with PHLF. In all patients, improvement of biochemical parameters was observed during MARS treatment along with clinical improvement in three patients. One patient survived. No clear guidelines for MARS treatment and prognostic factors for outcome after MARS treatment with regard to this patient group are available. In this paper, a MARS treatment regimen for PHLF is suggested based on literature and our own experience.

Bridging a Patient with Acute Liver Failure to Liver Transplantation by the AMC-Bioartificial Liver.

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 × 109 viable primary porcine hepatocytes isolated from a specified pathogen-free (SPF) pig. Here we report a patient with ALF due to acute HBV infection. This patient was treated for 35 h by two AMC-BAL treatments and was bridged to OLT. There was improvement of biochemical and clinical parameters during the treatment. No severe adverse events were observed during treatment and follow-up of 15 months after hospital discharge. Possible porcine endogenous retrovirus (PERV) activity could not be detected in the patient's blood or blood cells up to 12 months after treatment.

Assessment of the AMC-bioartificial liver in the anhepatic pig.

BACKGROUND: The anhepatic pig model was used to evaluate a bioartificial liver developed in our institution (AMC-BAL). The bioartificial liver is based on oxygenated plasma perfusion of porcine hepatocytes attached to a polyester matrix. METHODS: Pigs (n=15) underwent total hepatectomy with restoration of caval continuity using a polyethylene, three-way prosthesis. In group I, pigs received limited intensive care under continuation of general anesthesia (n=5). Group II pigs (n=5) underwent, in addition, extracorporeal plasma perfusion of an AMC-BAL without hepatocytes (device control group). In group III (n=5), plasma perfusion occurred with an AMC-BAL loaded with autologous hepatocytes. Groups II and III were connected to the extracorporeal system 24 hr after hepatectomy, for a period of 24 hr. The main outcome parameters were as follows: survival time, liver enzymes (aspartate aminotransferase, alanine aminotransferase), blood ammonia, and total/direct bilirubin. RESULTS: Survival (mean +/- SD) of the anhepatic pigs was significantly increased in the BAL-treated group (group III: 65+/-15 hr), as compared with the control groups (group I: 46+/-6 hr and group II: 43+/-14 hr). Mean blood ammonia levels during BAL treatment were significantly lower in the BAL-treated group in comparison with both control groups (P=0.02). Total and direct bilirubin levels gradually increased after hepatectomy and reached maximum values of 1.98 mg/dl and 1.50 mg/dl, respectively, showing no differences between the three groups. CONCLUSIONS: (1) Treatment of anhepatic pigs with the AMC-BAL containing autologous hepatocytes significantly increases survival time, which is associated with a significant decrease in blood ammonia. 2) Anhepatic pigs demonstrate increasing direct bilirubin levels as a result of extrahepatic bilirubin conjugation.