Point of Care CD4 Testing in National Household Surveys - Results and Quality Indicators from Eleven Population-Based HIV Impact Assessment (PHIA) Surveys.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm3) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

Medial minimally invasive helical plate osteosynthesis of the distal femur - a new technique.

INTRODUCTION: The goal of this study was to evaluate distal femoral minimally invasive plate osteosynthesis (MIPO) from a distal medial approach by use of a pre-bent helical implant. MATERIAL & METHODS: A total of 18 lower extremities was evaluated. A 29.6 cm steel plate was constructed and pre-bent on bone specimens with a torsion of 55.7° A 5 cm incision was performed from the tip of the medial epicondyle alongside its centre in a proximal direction. The medial border of the vastus medialis was retracted anteriorly. The level of the proximal skin incision was determined using the length of the pre-bent plates. The proximal incision was performed at a length of 4 cm at the described height at a line between the lateral epicondyle and the tip of the greater trochanter. A raspatory was advanced beneath the vastus medialis in a proximal direction to create an extraperiosteal tunnel for plate insertion. The plate was fixed to the bone at its proximal and distal portion via screws. Following dissection, the distance between the nearest perforator to the proximal plate end was evaluated. The vertical distances between the medial border of the plate and the femoral artery and femoral nerve were measured at the level of the proximal plate end and at the level of the proximal margin of the vastoadductor membrane. RESULTS: The most proximal perforating artery was located at a mean distance of 20.15 mm starting from the proximal plate margin. The mean interval between the medial border of the plate at the level of its proximal tip and the femoral artery was 51.9 mm. The average distance between the femoral nerve and the medial border of the proximal part of the plate was 42.3 mm. Regarding the interval between the medial border of the plate and the femoral artery, this was at a mean of 40.5 mm at the level of the proximal margin of the vastoadductor membrane. During dissection, none of the specimens showed any lesions of the adjacent anatomical characteristics. CONCLUSION: Our results indicate MIPO of the distal femur from a medial approach as a safe technique.

Returning HIV-1 viral load results to participant-selected health facilities in national Population-based HIV Impact Assessment (PHIA) household surveys in three sub-Saharan African Countries, 2015 to 2016.

INTRODUCTION: Logistical complexities of returning laboratory test results to participants have precluded most population-based HIV surveys conducted in sub-Saharan Africa from doing so. For HIV positive participants, this presents a missed opportunity for engagement into clinical care and improvement in health outcomes. The Population-based HIV Impact Assessment (PHIA) surveys, which measure HIV incidence and the prevalence of viral load (VL) suppression in selected African countries, are returning VL results to health facilities specified by each HIV positive participant within eight weeks of collection. We describe the performance of the specimen and data management systems used to return VL results to PHIA participants in Zimbabwe, Malawi and Zambia. METHODS: Consenting participants underwent home-based counseling and HIV rapid testing as per national testing guidelines; all confirmed HIV positive participants had VL measured at a central laboratory on either the Roche CAP/CTM or Abbott m2000 platform. On a bi-weekly basis, a dedicated data management team produced logs linking the VL test result with the participants' contact information and preferred health facility; project staff sent test results confidentially via project drivers, national courier systems, or electronically through an adapted short message service (SMS). Participants who provided cell phone numbers received SMS or phone call alerts regarding availability of VL results. RESULTS AND DISCUSSION: From 29,634 households across the three countries, 78,090 total participants 0 to 64 years in Zimbabwe and Malawi and 0 to 59 years in Zambia underwent blood draw and HIV testing. Of the 8391 total HIV positive participants identified, 8313 (99%) had VL tests performed and 8245 (99%) of these were returned to the selected health facilities. Of the 5979 VL results returned in Zimbabwe and Zambia, 85% were returned within the eight-week goal with a median turnaround time of 48 days (IQR: 33 to 61). In Malawi, where exact return dates were unavailable all 2266 returnable results reached the health facilities by 11 weeks. CONCLUSIONS: The first three PHIA surveys returned the vast majority of VL results to each HIV positive participant's preferred health facility within the eight-week target. Even in the absence of national VL monitoring systems, a system to return VL results from a population-based survey is feasible, but it requires developing laboratory and data management systems and dedicated staff. These are likely important requirements to strengthen return of results systems in routine clinical care.

HIV drug resistance in infants increases with changing prevention of mother-to-child transmission regimens.

OBJECTIVES: The objectives of this study were to determine HIV drug resistance (HIVDR) prevalence in Zambian infants upon diagnosis, and to determine how changing prevention of mother-to-child transmission (PMTCT) drug regimens affect drug resistance. DESIGN: Dried blood spot (DBS) samples from infants in the Lusaka District of Zambia, obtained during routine diagnostic screening, were collected during four different years representing three different PMTCT drug treatment regimens. METHODS: DNA extracted from dried blood spot samples was used to sequence a 1493 bp region of the reverse transcriptase gene. Sequences were analyzed via the Stanford HIVDRdatabase (http://hivdb.standford.edu) to screen for resistance mutations. RESULTS: HIVDR in infants increased from 21.5 in 2007/2009 to 40.2% in 2014. Nonnucleoside reverse transcriptase inhibitor resistance increased steadily over the sampling period, whereas nucleoside reverse transcriptase inhibitor resistance and dual class resistance both increased more than threefold in 2014. Analysis of drug resistance scores in each group revealed increasing strength of resistance over time. In 2014, children with reported PMTCT exposure, defined as infant prophylaxis and/or maternal treatment, showed a higher prevalence and strength of resistance compared to those with no reported exposure. CONCLUSION: HIVDR is on the rise in Zambia and presents a serious problem for the successful lifelong treatment of HIV-infected children. PMTCT affects both the prevalence and strength of resistance and further research is needed to determine how to mitigate its role leading to resistance.

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014, 150,000 children died from HIV-related causes worldwide (2). Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment (3). Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV (2), and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.

Postcoital administration of RU486 induces a hormonally under-stimulated rat endometrium.

RU486 is a partial progesterone and estrogen receptor antagonist, functioning to actively silence progesterone receptor gene-associated transcription. For this reason, it has been used as both a contraceptive and an abortive agent. In the present study, cellular and gene specific effects of RU486 were investigated in a rat model of early pregnancy, including key phases of the window of receptivity and early implantation. As these stages are hormonally regulated by progesterone and estrogens, the focus here was to elucidate the mechanism of action of a single dose of RU486, used as a postcoital contraceptive, to successfully prevent implantation of a viable blastocyst. Immunofluorescent techniques were used to examine the change in protein levels of PR in RU486-treated endometria at days 4.5, 5.5 and 6.5 of pregnancy. Changes in the Pgr gene expression level as a consequence of RU486 administration was evaluated using quantitative real-time reverse transcription polymerase chain reaction. The progesterone receptor gene and protein expression was ubiquitously decreased throughout pregnancy as a direct consequence of RU486 administration. The overall effects of postcoital RU486 administration during early pregnancy indicate highly effective inhibition of progesterone and estrogen effects on the endometrium, mediated by their receptors. More specifically, the expression and localization of the progesterone receptor mirrors that described in ovariectomized animal models, suggesting a hormonally under-stimulated endometrium. Clearly from the present study, the precise priming of the endometrium by progesterone, in preparation for blastocyst implantation, is severely impaired by RU486, thus predisposing the uterus to pregnancy failure.

The Bax/Bcl-2 apoptotic pathway is not responsible for the increase in apoptosis in the RU486-treated rat uterus during early pregnancy.

An increase in apoptotic activity has been observed in both the rabbit and the rat endometria following treatment with RU486. The aim of this study was to assess whether Bax and Bcl-2 signaling, in response to RU486, could be crucial role players mediating apoptosis in the rat uterus during early pregnancy. RU486 is a partial progesterone (P4) and estrogen receptor antagonist, functioning to actively silence P4 receptor gene-associated transcription. Although an increase in apoptosis as a result of RU486 administration has been previously reported in rabbits, the specific apoptotic factors and pathways involved in driving this process have not yet been established. Immunofluorescent techniques were used to determine protein expression levels of both Bax and Bcl-2 in RU486-treated endometria at days 4.5, 5.5 and 6.5 of pregnancy. The Bax/Bcl-2 index was used to determine the overall pro- or anti-apoptotic setting at each day of pregnancy, following RU486 administration. Changes in the Bax and Bcl-2 gene expression levels as a consequence of RU486 administration were evaluated using RT-qPCR. Both the protein and gene expression analyses suggest that RU486 induces a change toward an overall anti-apoptotic signal within the Bax/Bcl-2 pathway. These results suggest that the observed increase in apoptosis following RU486 administration is not driven by a shift in the Bax/Bcl-2 ratio toward cell death, when the P4 and estrogen receptors are partially inactivated by RU486, but is possibly regulated by another apoptotic pathway.

Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept.

PURPOSE: To evaluate the impact of dosimetry based on MAA SPECT/CT for the prediction of response, toxicity and survival, and for treatment planning in patients with hepatocellular carcinoma (HCC) treated with (90)Y-loaded glass microspheres (TheraSphere®). METHODS: TheraSphere® was administered to 71 patients with inoperable HCC. MAA SPECT/CT quantitative analysis was used for the calculation of the tumour dose (TD), healthy injected liver dose (HILD), and total injected liver dose. Response was evaluated at 3 months using EASL criteria. Time to progression (TTP) and overall survival (OS) were evaluated using the Kaplan-Meier method. Factors potentially associated with liver toxicity were combined to construct a liver toxicity score (LTS). RESULTS: The response rate was 78.8%. Median TD were 342 Gy for responding lesions and 191 Gy for nonresponding lesions (p < 0.001). With a threshold TD of 205 Gy, MAA SPECT/CT predicted response with a sensitivity of 100% and overall accuracy of 90%. Based on TD and HILD, 17 patients underwent treatment intensification resulting in a good response rate (76.4%), without increased grade III liver toxicity. The median TTP and OS were 5.5 months (2-9.5 months) and 11.5 months (2-31 months), respectively, in patients with TD <205 Gy and 13 months (10-16 months) and 23.2 months (17.5-28.5 months), respectively, in those with TD >205 Gy (p = 0.0015 and not significant). Among patients with portal vein thrombosis (PVT) (n = 33), the median TTP and OS were 4.5 months (2-7 months) and 5 months (2-8 months), respectively, in patients with TD <205 Gy and 10 months (6-15.2 months) and 21.5 months (12-28.5 months), respectively, in those with TD >205 Gy (p = 0.039 and 0.005). The median OS was 24.5 months (18-28.5 months) in PVT patients with TD >205 Gy and good PVT targeting on MAA SPECT/CT. The LTS was able to detect severe liver toxicity (n = 6) with a sensitivity of 83% and overall accuracy of 97%. CONCLUSION: Dosimetry based on MAA SPECT/CT was able to accurately predict response and survival in patients treated with glass microspheres. This method can be used to adapt the injected activity without increasing liver toxicity, thus defining a new concept of boosted selective internal radiation therapy (B-SIRT). This new concept and LTS enable fully personalized treatment planning with glass microspheres to be achieved.

Lobar hepatocellular carcinoma with ipsilateral portal vein tumor thrombosis treated with yttrium-90 glass microsphere radioembolization: preliminary results.

Portal vein tumor thrombosis (PVTT) is a common complication of hepatocellular carcinoma (HCC) and has a negative impact on prognosis. This characteristic feature led to the rationale of the present trial designed to assess the efficacy and the safety of yttrium-90 glass-microsphere treatment for advanced-stage lobar HCC with ipsilateral PVTT. 18 patients with unresectable lobar HCC and ipsilateral PVTT were treated in our institution with (90)Y-microS radioembolization. Patients were evaluated every 3 to 6 months for response, survival, and toxicity. Mean follow-up was 13.0 months (2.2-50.6). Outcomes were: complete response (n = 2), partial response (n = 13), stable disease (n = 1), and progressive disease (n = 2) giving a disease control rate of 88.9%. Four patients were downstaged. Treating lobar hepatocellular carcinoma with ipsilateral portal vein thrombosis with yttrium-90 glass-microsphere radioembolization is safe and efficacious. Further clinical trials are warranted to confirm these results and to compare (90)Y-microS with sorafenib, taking into account not only survival but also the possibility of secondary surgery for putative curative intention after downstaging.

Infectivity of macrophages and the histopathology of cutaneous lesions, liver and spleen is attenuated by leaf extract of Vernonia amygdalina in Leishmania major infected BALB/c mice.

Preliminary investigation of the in vitro and in vivo efficacies of different extracts from the leaves of Vernonia amygdalina (VA), a plant widely used in Nigeria was evaluated in Balb/C mice infected with a laboratory strain of Leishmania major (L. major). The ability of the methanol, hexane and aqueous extracts of the plant to suppress the infection rate and its cytotoxicity on macrophages and L929 cells were determined in the in vitro study. The in vivo study evaluated time course of infection, lesion progression and the histopathology of cutaneous lesions, liver and spleen after inoculation with metacyclic promastigotes. Methanolic extract of VA containing high levels of flavanoids, was the most potent extract as it showed the highest suppression on infectivity and viability of intracellular amastigotes at a concentration lower than that which elicited cytotoxicity on macrophages. Treatment of infected mice with methanolic extract of VA showed delayed onset of disease with a significant reduction in lesion size and attenuation of the histopathological outcome characterised by intact epidermis and less tissue destruction in skin, spleen and liver. In conclusion, these results demonstrate that VA has potent antileishmanial properties which warrants further investigation into the immunological mechanism.

Blocking Wnt signaling by SFRP-like molecules inhibits in vivo cell proliferation and tumor growth in cells carrying active ß-catenin.

Constitutive activation of Wnt/ß-catenin signaling in cancer results from mutations in pathway components, which frequently coexist with autocrine Wnt signaling or epigenetic silencing of extracellular Wnt antagonists. Among the extracellular Wnt inhibitors, the secreted frizzled-related proteins (SFRPs) are decoy receptors that contain soluble Wnt-binding frizzled domains. In addition to SFRPs, other endogenous molecules harboring frizzled motifs bind to and inhibit Wnt signaling. One of such molecules is V3Nter, a soluble SFRP-like frizzled polypeptide that binds to Wnt3a and inhibits Wnt signaling and expression of the ß-catenin target genes cyclin D1 and c-myc. V3Nter is derived from the cell surface extracellular matrix component collagen XVIII. Here, we used HCT116 human colon cancer cells carrying the ΔS45 activating mutation in one of the alleles of ß-catenin to show that V3Nter and SFRP-1 decrease baseline and Wnt3a-induced ß-catenin stabilization. Consequently, V3Nter reduces the growth of human colorectal cancer xenografts by specifically controlling cell proliferation and cell cycle progression, without affecting angiogenesis or apoptosis, as shown by decreased [(3)H]-thymidine (in vitro) or BrdU (in vivo) incorporation, clonogenesis assays, cell cycle analysis and magnetic resonance imaging in living mice. Additionally, V3Nter switches off the ß-catenin target gene expression signature in vivo. Moreover, experiments with ß-catenin allele-targeted cells showed that the ΔS45 ß-catenin allele hampers, but does not abrogate, inhibition of Wnt signaling by SFRP-1 or by the SFRP-like frizzled domain. Finally, neither SFRP-1 nor V3Nter affect ß-catenin signaling in SW480 cells carrying nonfunctional Adenomatous polyposis coli. Thus, SFRP-1 and the SFRP-like molecule V3Nter can inhibit tumor growth of ß-catenin-activated tumor cells in vivo.

Metabolism and distribution of two highly potent and selective peptidomimetic inhibitors of matriptase.

Matriptase is a serine protease expressed by several types of cancer cells and it participates in tumour growth and progression through the activation of hepatocyte growth factor (HGF) and urokinase-type plasminogen activator (uPA). The metabolism of two potent and selective peptidomimetic inhibitors of matriptase (CJ-1737 and CJ-672) was examined in vitro with enzyme preparations (9000g supernatants, microsomes, and plasma) from dog, pig, rat, and human. It was found that both compounds displayed interesting species-dependent differences. Though CJ-1737 was not metabolized by microsomes, by 9000g supernatants from all species, or by human or rat plasma, canine and porcine plasma enzymes rapidly hydrolysed this compound. In contrast, CJ-672 was metabolized exclusively by enzymes from human liver (microsomes and 9000g supernatants) via a two-step metabolic pathway. Additionally, the distribution of both compounds was investigated in mice. The highest amounts were measured in the kidney and liver, followed by the spleen, lung, and heart. In contrast to CJ-1737, high concentrations of CJ-672 were detected in the colon, indicating an additional biliary excretion. In summary, this work clarifies both the metabolism and distribution of two new matriptase inhibitors and demonstrates important metabolic differences between human enzymes and those from commonly used laboratory animals.

[Fundamental and translational research on hepatocellular carcinoma in 2008: forces and priorities]. / Recherche fondamentale et translationnelle sur le carcinome hépatocellulaire en 2008 : avancées récentes et perspectives.

Hepatocellular carcinogenesis is usually the result of a muti-step process. It begins with an exposure to various risk factors; followed by the development of a chronic hepatitis and cirrhosis that is a pre-neoplastic step; and finally after the occurrence of an hepatocellular carcinoma (HCC), different molecular events control aggressiveness of the tumors. The aim of this work was to identify in the international context, forces and priorities of the fundamental and translational HCC research.

[Study of pupillary motility after implantation of an iris claw lens (Artisan) in a phakic population with severe myopia]. / Etude de la motilité pupillaire chez le sujet phaque porteur d'un implant Artisan.

PURPOSE: To assess the effect of the Artisan lens on pupillary motility in a highly phakic myopic population. PATIENTS AND METHODS: Eleven patients (21 eyes) were enrolled in a nonrandomized prospective study between September 2002 and August 2003, with a 6- to 11-month follow-up. A portable Colvard pupillometer was used to measure pupil diameters before and after surgery under two different light conditions: one with scotopic surroundings with absolute darkness in the examination room and the other maximal simulated photopic surroundings, caused by the instillation of a pilocarpine 2% drug until a nonreactive myosis could be observed. Under such light conditions, both the horizontal and vertical pupil motion ranges were measured. Measures were then sorted into five temporal segments in order to have enough samples per temporal segment for a cohesive data analysis. Mean values and confidence intervals were then derived per temporal segment according to Student's law. Constraints on the pupil motion range were identified. RESULTS: After implantation of an Artisan lens, the pupil motion range was limited to both horizontal and vertical axes. For the horizontal axis, the motion range was 4.3+/-0.2mm (p=0.1) before claw implantation and was 2.7+/-0.5mm (p=0.1) 9 months after claw implantation. For the vertical axis, the motion range was 4.46+/-0.28mm before claw implantation and 3.08+/-0.89mm 9 months after claw implantation. CONCLUSIONS: The Artisan lens durably restrains the pupil in its motion range and introduces a noticeable oval deformation under extreme light condition variations. This side effect is, however, not visible under regular conditions but only in maximal photopic surroundings.

Metabolism of cytostatically active 6-aminobenzo[c]phenanthridines by human and porcine hepatic microsomes and recombinant cytochrome P450 enzymes.

A new and convenient two-step synthesis of 11-substituted 6-amino-11,12-dihydrobenzo[c]phenanthridines and 6-aminobenzo[c]phenanthridines (BPs and BP-Ds) was developed recently in the authors' laboratory. These compounds revealed a high antitumoral activity in in vitro and in vivo test systems. In particular, 11-phenyl-substituted derivatives with two or three methoxy groups showed good activity. It was not clear if the dihydro-derivatives (BPs) were transformed enzymatically into the phenanthridines (BP-Ds), thus acting as prodrugs. The in vitro metabolism of several of these cytostatically active 6-aminobenzo[c]phenanthridines was investigated using human and porcine liver microsomes and a range of expressed human cytochrome P450 enzymes. High-performance liquid chromatography and liquid chromatography-mass spectrometry analysis were used for the quantification and structural identification of the observed metabolites. Aromatic hydroxylation was observed to be the major metabolic pathway in addition to a number of other metabolites. The formation of N-hydroxy- and 6-oxo-derivatives was detected only in very small amounts. BP derivatives are not prodrugs of BP-Ds and no significant differences between human and porcine microsomes were observed, confirming the pig as a good model for metabolism studies of these compounds.

Patient expectations regarding total knee arthroplasty: differences among the United States, United Kingdom, and Australia.

BACKGROUND: Total knee arthroplasty is an effective treatment for severe osteoarthritis of the knee. Our aim was to determine whether patients from the United Kingdom, United States, and Australia have different preoperative expectations regarding total knee arthroplasty and whether these expectations have an impact on outcomes and patient satisfaction. METHODS: Patients from the United Kingdom, the United States, and Australia were recruited into a prospective observational study of primary total knee arthroplasty for the treatment of osteoarthritis. Preoperative expectations, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF-36) scores, and demographic, socioeconomic, and follow-up data, including satisfaction with outcome, were obtained from self-administered patient questionnaires. RESULTS: A total of 598 patients with a mean age of sixty-nine years at the time of the index arthroplasty were recruited; 58% were women. The majority of patients expected to have no pain at twelve months after the surgery, and with the numbers available there was no significant difference among the countries with regard to pain expectations. Australian patients were more likely than patients in the United Kingdom or the United States to expect better function at twelve months after the surgery. With the numbers available, satisfaction scores at twelve months did not differ significantly among the countries and were not influenced by preoperative expectations. Australian patients were more likely than patients in the United Kingdom or the United States to be unwilling to undergo total knee arthroplasty again at twelve months under similar circumstances. CONCLUSIONS: Patients from different countries have different expectations regarding total knee arthroplasty, which are not fully explained by differences in sociodemographic factors, clinical characteristics, and pain and functional status. Australian patients had the highest expectations but, despite reporting similar outcomes and satisfaction following total knee arthroplasty, they were more likely not to want to have the surgery again under similar circumstances.

Patient-reported outcome and survivorship after Kinemax total knee arthroplasty.

BACKGROUND: We examined the long-term survivorship and patient-reported outcomes at a minimum of ten years following primary total knee arthroplasty. We hypothesized (1) that the survival rate would be at least 90% at ten years; (2) that age, gender, body-mass index, and primary diagnosis would not affect the survival rate; and (3) that the functional status of patients would be comparable with that of an age and gender-matched normal population. METHODS: A total of 407 patients (523 knees) who had had primary total knee arthroplasty between January 1988 and April 1991 were identified. The mean age of the patients at the time of surgery was sixty-nine years, and 68% of the patients were women. At ten years, 165 patients (211 knees) had died; seven of these 211 knees had been revised before the time of death. Of the remaining 242 patients, 208 (86%) completed a questionnaire, which included the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), the Short Form-36 (SF-36), and questions regarding patient satisfaction and revision surgery. In the group of patients who participated in the study, ten patients (eleven knees) had had a revision before the review. RESULTS: A total of eighteen knees were revised. Twelve knees were revised because of aseptic failure and, of these, nine were revised because of polyethylene wear. The probability of survival at ten years was 96.1% with revision for any reason as the end point (and 97.2% when only aseptic failures were considered). Because of the small number of failures, we were unable to draw conclusions about associations between failure and age, gender, diagnosis, and body-mass index. The mean WOMAC scores (and standard deviation) at the time of the evaluation were 88 +/- 17 for pain and 79 +/- 20 for function. The SF-36 scores were similar to those for an age and gender-matched normal population, with only the physical functioning score being significantly lower (p < 0.001) and with the general health score being significantly higher (p < 0.001). Patients generally were very satisfied with all aspects of the outcome. CONCLUSIONS: At ten years, the survival of the prosthesis was excellent and the majority of patients were functionally independent, had very little knee pain, and were very satisfied with the result. The health benefits of this total knee arthroplasty were maintained after a minimum duration of follow-up of ten years.

Predicting the outcome of total knee arthroplasty.

BACKGROUND: The relief of pain and the restoration of functional activities are the main outcomes of primary total knee arthroplasty for the treatment of osteoarthritis. This paper examines the preoperative predictors of pain and functional outcome at one and two years following total knee arthroplasty. METHODS: Patients were recruited for a prospective observational study of primary total knee arthroplasty for the treatment of osteoarthritis from centers in the United States, the United Kingdom, and Australia. Research assistants recruited the patients and collected the clinical history and physical examination data preoperatively and at three, twelve, and twenty-four months postoperatively. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Short Form-36 (SF-36), and demographic data were obtained by self-administered patient questionnaires. RESULTS: We recruited 860 patients and obtained one-year WOMAC data on 759 patients (88%) and two-year data on 701 (82%). The mean age was seventy years, and 59% of the patients were female. Using hierarchical regression models, we found that the most significant preoperative predictors of worse scores on the pain and function domains of the WOMAC scale and on the physical functioning domain of the SF-36 at one and two years postoperatively were low preoperative scores, a higher number of comorbid conditions, and a low SF-36 mental health score. After adjusting for these predictors, we found that the functional status of the patients from the United Kingdom was significantly worse than that of the patients from the other countries and the difference was clinically important at both the one-year and two-year follow-up examination (p < 0.0005). The mean WOMAC pain scores for the three countries were not significantly different at one year, and, although they were significantly different at two years (p = 0.025), the difference was not clinically important. CONCLUSIONS: Patients who have marked functional limitation, severe pain, low mental health score, and other comorbid conditions before total knee arthroplasty are more likely to have a worse outcome at one year and two years postoperatively. After adjusting for these predictors, it was found that patients from the United Kingdom had significantly worse functional outcomes but similar pain relief compared with those from the United States and Australia.