Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic, multicenter, placebo-controlled GLORIA trial.

BACKGROUND: The GLORIA placebo-controlled trial found a favorable balance of benefit and harm for two years of prednisolone (5 mg/day) as add-on treatment for rheumatoid arthritis (RA) patients aged 65+. This study evaluated the cost-effectiveness of low-dose prednisolone in the treatment of RA. METHODS: The economic evaluation had a societal perspective with a time horizon of two years. Cost data were collected with questionnaires and from recorded events, and valued with standard Dutch unit prices of 2017. The primary effectiveness outcome was the disease activity score in 28 joints (DAS28). For cost-utility, quality-adjusted life years (QALYs) were estimated from the EuroQol-5 Dimension (EQ-5D) questionnaire. Bootstrapping assessed the uncertainty around the average differences in costs and health outcomes. RESULTS: In total, 444 of 451 randomized patients were included in the modified intention-to-treat analysis. Patients had median four active comorbidities at baseline. Mean total costs over two years were k€10.8 in the prednisolone group, k€0.5 (95% CI -4.0; 1.8) lower than in the placebo group. Total direct medical costs were k€0.5 (95% CI -4.0; 1.5) lower in the prednisolone group. The mean number of QALYs was similar in both groups (difference 0.02 [-0.03; 0.06] in favor of prednisolone). The DAS28 was 0.38 lower in the prednisolone group than in the placebo group (0.19; 0.56). CONCLUSION: With greater effectiveness (DAS28) at non-significantly lower costs, low-dose, add-on prednisolone is cost-effective for RA compared to placebo over two years. QALYs were equal in both groups, most likely due to the impact of multiple comorbidities.

Developing an ethics support tool for dealing with dilemmas around client autonomy based on moral case deliberations.

BACKGROUND: Moral Case Deliberations (MCDs) are reflective dialogues with a group of participants on their own moral dilemmas. Although MCD is successful as clinical ethics support (CES), it also has limitations. 1. Lessons learned from individual MCDs are not shared in order to be used in other contexts 2. Moral learning stays limited to the participants of the MCD; 3. MCD requires quite some organisational effort, 4. MCD deals with one individual concrete case. It does not address other, similar cases (it is case based). These limitations warrant research into complementary ways of providing CES to healthcare professionals. Our research objective was therefore to develop a low threshold CES tool based on a series of MCDs on autonomy in long-term care. METHODS: We used a qualitative research design in which we analyzed the process and content of a series of MCDs, combined with reflections on the theoretical background of MCD. In total 28 MCDs (10 transcripts and 18 summary reports) were analyzed by means of a thematic content analysis. In various rounds of development, the results of the analysis were combined with theoretical reflections on CES. Consequently, the tool was evaluated in three focus groups and adjusted. RESULTS: The CES tool, called 'moral compass', guides the users through a series of six subsequent questions in order to methodically reflect on their concrete moral dilemma, in the form of a booklet of 23 pages. It combines a methodical element that encourages and structures a reflection process with a substantive element, including norms, values, options, strategies, and insights regarding dealing with client autonomy. CONCLUSION: By using data from a series of MCDs, combined with theoretical reflections on MCD, ethics support and moral learning, we developed a thematic, low-threshold CES tool that supports healthcare professionals in daily practice in dealing with moral questions regarding client autonomy. It integrates examples and insights from earlier MCDs on the same topic. The moral compass is not a replacement of, but can be used complementary to MCD. The feasibility and impact of the moral compass need to be investigated in an evaluative follow-up study. The methodology presented in this paper may be used to develop moral compasses on different topics in various healthcare organizations.

Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall.

BACKGROUND AND AIM: Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and pleomorphic undifferentiated sarcoma. METHOD: We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)α using immunohistochemical staining and assessed microvessel density using CD31 in 73 high-grade leiomyosarcomas and undifferentiated pleomorphic sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival. RESULTS: Expression of HIF-1α was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither expression of the stromal markers CD163, CD16 and CSF-1 nor microvessel density was prognostically relevant in this series. CONCLUSIONS: There is increasing evidence for the prognostic role of hypoxia in high-grade soft tissue sarcoma, and these data suggest that HIF-1α expression represents a candidate prognostic biomarker for clinical application in high-grade leiomyosarcoma and undifferentiated pleomorphic sarcoma.

The Role of Vitality in the Relationship Between a Healthy Lifestyle and Societal Costs of Health Care and Lost Productivity: A Mediation Analysis.

PURPOSE: To examine the mediating effect of vitality in the relationship between healthy lifestyle characteristics and health-care and productivity-related costs. DESIGN: Observational prospective cohort study with 2 measurements. Online questionnaires were filled out in 2013 (T0) and 2014 (T1). SETTING: A random sample of a Dutch online interview panel was obtained. SUBJECTS: Data of 4231 Dutch adults who had complete data at T0 and T1 were used in the present study. Participants were representative for the Dutch adult population in terms of age, gender, and having chronic disease(s). MEASURES: Healthy Lifestyle Index (HLI), vitality, and health-care and productivity-related costs. The HLI consisted of the sum of 6 healthy lifestyle characteristics, including a healthy BMI (yes/no), meeting physical activity, fruit, vegetable, and alcohol consumption guidelines (yes/no), and smoking status (yes: non or former smoker/no: current smoker). Health-care and productivity-related costs were measured using a utilization questionnaire. ANALYSIS: Linear regression analysis. RESULTS: The HLI was related to vitality. In addition, vitality was related to health-care costs and productivity-related costs. Furthermore, vitality was found to transmit 28.4% of the effect of HLI on health-care costs and 39.4% of the effect of HLI on productivity-related costs. CONCLUSION: Lifestyle was related to vitality and vitality to health-care and productivity-related costs. Vitality mediated the relationship between lifestyle and health-care and productivity-related costs. Therefore, we recommend to sustain and improve both vitality and lifestyle.

Verwijzen naar het hospice: verwijsgedrag van artsen en ervaren belemmeringen in Deventer en omgeving.

UNLABELLED: PHYSICIANS' REFERRAL PATTERNS AND PERCEIVED BARRIERS IN THE DEVENTER REGION IN THE NETHERLANDS: OBJECTIVE: To examine physicians' perceived referral patterns and barriers to referral of terminally ill patients to a hospice (institute). DESIGN: Survey study among physicians practicing in hospital and other settings in the region of Deventer, The Netherlands, in 2011-2012. METHOD: We translated two available American instruments into Dutch. The questionnaire assessed hospice referral, knowledge about hospice, attitudes and barriers and reasons not to refer. We queried physicians who had referred patients to the local hospice about expectations and suggested areas for improvement with two open-ended items. RESULTS: In total, 240 physicians received the questionnaire. The response rate was 47%. The physicians were generally positive about hospice care. They indicated experiencing few barriers in hospice referrals, but 32% of the physicians (21% of those practicing in the hospital, and 39% in other settings), indicated the patient being unready as a strong barrier. Half of the physicians (51%) believed that hospice is being underutilized and 22% (35% and 14%, respectively) thought that they would refer more frequently if they had more knowledge about hospice care. Of the physicians, 35% answered all six knowledge questions correctly. Communication with the hospice may be improved. CONCLUSION: Despite positive attitudes toward hospice care, it may be underutilized due to poor knowledge and communication with the hospice. Perhaps, this is also due to limited patient-physician communication on prognosis, which further research may address.

Simple guidelines for efficient referral of soft-tissue sarcomas: a population-based evaluation of adherence to guidelines and referral patterns.

BACKGROUND: Optimal treatment of soft-tissue sarcoma requires multidisciplinary management at a sarcoma center. However, these rare tumors are often misinterpreted as benign and many are inadequately treated outside a sarcoma center, with an increased risk of local recurrence that often requires further extensive surgical treatment. To improve referral and centralization of soft-tissue sarcoma management in the southern Sweden health care region, an open-access outpatient clinic at our sarcoma center and simple referral guidelines have been established for the past thirty years. The guidelines call for referral of all deep-seated soft-tissue tumors and of all ≥5-cm superficial tumors before open biopsy or surgery. We evaluated adherence to these guidelines and characterized referral patterns. We also studied the consequences of our strategy with regard to the relative numbers of benign and malignant diagnoses among referred patients. METHODS: Adherence to guidelines, referral pathways, and time to referral to the sarcoma center were analyzed in a population-based series of 100 consecutive patients with soft-tissue sarcoma in the extremities or trunk wall. We also analyzed diagnosis and management of benign and malignant tumors in a second cohort consisting of 464 consecutive patients referred to the sarcoma center because of a soft-tissue tumor. RESULTS: Ninety-seven of the 100 patients with soft-tissue sarcoma were referred to the sarcoma center. All fifty-eight of the deep-seated soft-tissue sarcomas and twenty-eight of the forty-two superficial tumors were referred before open biopsy or surgery. Three-quarters of the patients with soft-tissue sarcoma first presented to a general practitioner. One-quarter of these patients were directly referred to the sarcoma center, which cut the referral time in half compared with patients initially referred to a local hospital. One-quarter of all patients referred to the outpatient clinic were diagnosed with a malignancy, with the majority of the malignancies being soft-tissue sarcoma. CONCLUSIONS: Our simple referral guidelines and open-access outpatient clinic resulted in nearly complete referral of patients with soft-tissue sarcoma to the sarcoma center. The "excess work" associated with referral of benign tumors according to our strategy was limited to the diagnosis of three benign tumors for each malignant tumor. We consider this surplus evaluation of benign tumors acceptable and probably necessary to achieve a high referral rate of soft-tissue sarcoma before initial surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Predictors of Clostridium difficile colitis infections in hospitals.

Hospital-level predictors of high rates of 'Clostridium difficile-associated disease' (CDAD) were evaluated in over 2300 hospitals across California, Arizona, and Minnesota. American Hospital Association data were used to determine hospital characteristics associated with high rates of CDAD. Significant correlations were found between hospital rates of CDAD, common infections and other identified pathogens. Hospitals in urban areas had higher average rates of CDAD; yet, irrespective of geographic location, hospital rates of CDAD were associated with other infections. In addition, hospitals with 'high CDAD' rates had slower turnover of beds and were more likely to offer transplant services. These results reveal large differences in rates of CDAD across regions. Hospitals with high rates of CDAD have high rates of other common infections, suggesting a need for broad infection control policies.

A long-term study comparing membrane filtration with Colilert defined substrates in detecting fecal coliforms and Escherichia coli in natural waters.

Assessment methods for determining the presence and number of fecal bacteria and Escherichia coli (E. coli) in waters, foodstuffs, sewage effluent, and soils have evolved from multiple tube fermentations (MTF's) to membrane filtrations (MF's) to, most recently, defined substrate technologies (DST's). Mounting evidence indicates Colilert DST (IDEXX, Westbrook, ME) to be a versatile assessment technique for detecting and enumerating E. coli over a range of applications. This study compared the performance of Colilert DST with a confirmed standard MF technique using m-FC broth (Millipore, Bedford, MA) in assessing E. coli in ten different environmental water samples obtained monthly over a 3-year period from the upper Appomattox River, VA. For the duration of the study, E. coli counts measured by Colilert DST were positively correlated (Pearson's correlation coefficient=0.956; slope=0.979; p<0.0001) with E. coli counts measured by confirmed MF procedures. The results of a two-factor ANOVA revealed that Colilert DST counts compared equally to confirmed MF counts by year (p=0.974), by stream sampled (p=1.0), and by season (p=0.696). E. coli counts were significantly lower during cold season months (Dec/Jan/Feb) than during warm season months (Jun/Jul/Aug) for each year contributing to marked variation in sample quality. Counts obtained by Colilert DST compared equally to those obtained by MF across all samples and dates for the three years. Colilert DST presents a laboratory protocol that is simpler to manage, quicker to process, and easier to quantify results than MF. These factors, plus the enhanced precision and versatility of Colilert DST over the span of this three-year study attests to its suitability for testing ambient surface waters.

Bradycardia and asystole with the use of vagus nerve stimulation for the treatment of epilepsy: a rare complication of intraoperative device testing.

PURPOSES: A 56-year-old man with mild mental retardation, right congenital hemiparesis, and refractory partial seizures was referred for vagus nerve stimulation (VNS). METHODS: Routine lead diagnostic testing during the surgical procedure (1.0 mA, 20 Hz, and 500 micros, for approximately 17 s) resulted, during the initial two stimulations, in a bradycardia of approximately 30 beats/min. A third attempt led to transient asystole that required atropine and brief cardiopulmonary resuscitation. RESULTS: The procedure was immediately terminated, the device removed, and the patient recovered completely. A postoperative cardiologic evaluation, including an ECG, 24-h Holter monitor, echocardiogram, and a tilt-table test, was normal. CONCLUSIONS: Possible mechanisms for the bradycardia/asystole include stimulation of cervical cardiac branches of the vagus nerve either by collateral current spread or directly by inadvertent placement of the electrodes on one of these branches; improper plugging of the electrodes into the pulse generator, resulting in erratic varying intensity of stimulation; reverse polarity; and idiosyncratic-type reaction in a hypersusceptible individual. The manufacturer reports the occurrence rate in approximately 3,500 implants for this intraoperative event to be approximately one in 875 cases or 0.1%.

A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers.

A randomized, double-blind, placebo-controlled, ascending-dose study was conducted to evaluate the pharmacokinetic and safety profiles of increasing modafinil doses (200 mg, 400 mg, 600 mg, 800 mg) administered orally over a 7-day period in normal healthy male volunteers. Eight subjects (six modafinil; two placebo) were randomized to each of the four dose groups. Modafinil or a placebo was administered once daily for 7 days. Serial blood samples were obtained following administration of the day 1 and day 7 doses for characterization of pharmacokinetics, and trough samples were obtained prior to dosing on days 2 through 6 to assess the time to reach the steady state. Pharmacokinetic parameters were calculated using noncompartmental methods. Modafinil steady state was reached after three daily doses. Modafinil pharmacokinetics were dose and time independent over the range of 200 mg to 800 mg. Steady-state pharmacokinetics of modafinil were characterized by a rapid oral absorption rate, a low plasma clearance of approximately 50 mL/min, a volume of distribution of approximately 0.8 L/kg, and a long half-life of approximately 15 hr. Modafinil was primarily eliminated by metabolism. Modafinil acid was the major urinary metabolite. Stereospecific pharmacokinetics of modafinil were demonstrated. The d-modafinil enantiomer was eliminated at a threefold faster rate than 1-modafinil. Modafinil 200 mg, 400 mg, and 600 mg doses were generally well tolerated. The modafinil 800 mg dose panel was discontinued after 3 days of treatment due to the observation of increased blood pressure and pulse rate. The safety data from this study suggest that the maximum tolerable single daily oral modafinil dose, without titration, may be 600 mg.

Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers.

An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of modafinil, the acid and sulfone metabolites of modafinil, and dextroamphetamine at intervals through 48 hours after administration for each treatment. Vital signs (blood pressure and pulse rate) were measured through 48 hours, and electrocardiograms were measured through 24 hours after administration. Pharmacokinetic parameters were determined using noncompartmental methods. The data collected in this study of 24 healthy volunteers suggest that concomitant administration of single oral doses of modafinil and dextroamphetamine has no clinically significant effects on the pharmacokinetic profile of either agent. Although there was a slightly greater incidence of adverse events when modafinil and dextroamphetamine were administered together, the concomitant administration of the two drugs was well tolerated.

Results and complications from the use of a frameless stereotactic microscopic navigator system.

We present a series of 21 patients, 12 males and 9 females, aged 41-76 years, with the preoperative diagnosis of a brain tumor. Both preoperatively and postoperatively, all of our patients underwent either a brain computed tomography (CT) or magnetic resonance imaging (MRI). All the radiographic studies were taped and loaded preoperatively in the Stereotactic Microscopic Navigator (SMN) workstation (Zeiss, Germany). The mean duration of this procedure was 25 +/- 6 min. All our patients were operated on in our institute with the use of the SMN system. The specificity of tumor localization using CT scan was 2.20 +/- 0.25 mm and for the MRI scan 2.6 +/- 0.25 mm. As assessed by postoperative radiographic studies, total gross tumor resection was possible in 20 patients (95.23%). No major intraoperative or early postoperative complications were noted in our series. We believe that the SMN system is a safe, well-tolerated by the patients and simple method with extremely high accuracy and specificity.

Clinical signs associated with Triple Antigen (DTP) vaccination in infants.

OBJECTIVE: The perceived reactogenicity of pertussis-containing vaccines is of considerable public health importance. The purpose of this study was to establish prospectively the incidence of systemic and local clinical signs associated with the first three doses of the diphtheria-tetanus-pertussis vaccine (DTP) currently used in Australia. In addition, in order to determine whether variability in reporting of such phenomena might be associated with variation in DTP batches, infant behaviour was studied with three batches for the first of the three DTP vaccinations. METHODOLOGY: Double blind, randomized controlled trial. There were 591 eligible infants who were recruited sequentially from centres for vaccination in three large Melbourne municipalities, of whom 531 (mean age 10 weeks, 45% female) were randomized and immunized. Of 181 subjects who received DTP from batch 1, 151 were studied at the time of their second DTP dose, and 98 at the third. Infants were assigned randomly to receive one of three batches of DTP vaccine. Parents were provided with a thermometer and a clinical sign diary. Research nurses visited the home 24 h after vaccination, and telephoned 7 days after vaccination to record local and systemic signs. RESULTS: There was no significant variation between DTP batches in rates of local or systemic signs. At the time of the first vaccination, the rates of local signs were: redness 16%, induration 29%, swelling 46%, and tenderness 54%. Systemic signs included: irritability 93%, intermittent inconsolable crying 43%, and persistent crying 12%. An axillary temperature of greater than 38 degrees C was recorded in 13% (CI 9-19%) of babies following the first immunization, 20% (CI 14-27%) following the second, and 14% (CI 8-23%) following the third immunization. There were significant reductions in the rates of observed signs over the immunization course for diarrhoea, irritability, intermittent inconsolable crying and persistent crying. CONCLUSIONS: There is little difference in the rates of clinical signs or presumed minor adverse effects associated with the DTP vaccine used in Australia today compared to that used 10 years ago, despite increases in the diphtheria and tetanus toxoid concentration, and the addition of aluminium phosphate adjuvant. Rates are comparable to those for other DTP vaccines manufactured in North America and Europe.

Possible endogenous regulators of steroid inactivating enzymes and glucocorticoid-induced Na+ retention.

Various endogenous substances which bear similar structural resemblances to glycyrrhetininc acid were screened for inhibitory activity against 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and 5 beta-reductase (5 beta-R). Among the compounds screened, 3 alpha, 5 beta-tetrahydroprogesterone (3 alpha,5 beta-THP) was a potent inhibitor of 11 beta-OHSD and a moderate inhibitor of 5 beta-R. Of the bile acids tested, chenodeoxycholic acid (CDCA) was the most potent inhibitor of both 11 beta-OHSD and 5 beta-R. Cholic acid (CA), a moderate inhibitor of 11 beta-OHSD was a weak inhibitor of 5 beta-R, whereas deoxycholic acid was a moderate inhibitor of 5 beta-R but a weak inhibitor of 11 beta-OHSD. 3 alpha, 5 beta-THP and bile acids were also tested to determine whether, like GA, they could confer mineralocorticoid actions upon corticosterone (B). In adrenalectomized rats pretreated with CDCA or 3 alpha,5 beta-THP, B caused a significant antinatriuresis; the effect of B plus CDCA was blocked by the antimineralocorticoid, RU 28318. Thus, we report on two structurally similar endogenous substances, 3 alpha, 5 beta-THP and CDCA, which inhibit both 11 beta-OHSD and 5 beta-R activity, and which can confer mineralocorticoid actions upon the glucocorticoid, B.

Induction of differentiation of the human myeloid cell line, ML3, by tumour necrosis factor and interferon-gamma is accompanied by enhanced expression of the CD4 protein and messenger RNA.

Tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) induce differentiation of human myeloid cell lines along the monocytic lineage. In this study we investigated the effects of TNF and IFN-gamma on the expression of the CD4 protein and messenger RNA (mRNA) in the two myeloid cell lines, ML3 and HL-60. We observed that CD4 antigen expression on ML3 cells is almost undetectable and that TNF and IFN-gamma induced CD4 antigen expression on these cells. HL-60 cells express surface CD4 antigen at high density and treatment with TNF and IFN-gamma caused a decrease of CD4 expression. We also investigated the expression of CD4 mRNA in ML3 and HL-60 cells. ML3 constitutively express, albeit at low levels, CD4 mRNA. TNF induced CD4 mRNA in ML3 cells and IFN-gamma synergistically potentiated the effect of TNF, thus indicating that the enhanced expression of the CD4 protein on ML3 cells is due, at least in part, to an enhanced accumulation of the CD4 mRNA. CD4 mRNA is constitutively expressed in HL-60 cells at high levels. TNF and IFN-gamma, alone or in combination, did not cause any significant change of CD4 mRNA expression in HL-60 cells, thus indicating that decrease of surface CD4, which accompanies differentiation with these cytokines, is likely due to alterations of the CD4 protein synthesis and/or transport to the plasma membrane. These results provide evidence that myeloid cell lines are heterogeneous in expression of CD4, and that in ML3 cells, which constitutively express low levels of CD4 mRNA and undetectable amounts of surface CD4, the predominant effect of the two cytokines is to induce both CD4 mRNA and protein.

Induction of expression of genes encoding components of the respiratory burst oxidase during differentiation of human myeloid cell lines induced by tumor necrosis factor and gamma-interferon.

In HL-60 and ML-3 human myeloid cell lines, gamma-interferon (IFN-gamma) and/or tumor necrosis factor (TNF) induce synergistic accumulation of transcripts of the genes encoding the heavy chain (gp91-phox) of cytochrome b558 and the cytosolic factors p47-phox and p67-phox, components of the superoxide-generating NADPH oxidase system. The accumulation of transcripts for gp91-phox and p47-phox, as quantitated at the single-cell level by in situ hybridization, is extremely heterogeneous; however, when the cells are stimulated by IFN-gamma and TNF together, most or all the cells in the induced cultures express higher accumulation of gp91-phox and p47-phox transcripts than cells from uninduced culture. In situ hybridization was performed on cellular subsets separated by fluorescence-activated cell sorting on the basis of surface expression of differentiation antigens or respiratory burst activity. The accumulation of gp91-phox and p47-phox transcripts correlated positively with the expression of the CD14 and CD11b antigens, two markers expressed on mature myelomonocytic cells. Similarly, accumulation of the two transcripts correlated with respiratory burst activity in cells separated by fluorescence-activated cell sorting after being loaded with dichlorofluorescein diacetate and stimulated with 12-O-tetradecanoylphorbol-13-acetate. These results suggest that all the cells in the culture are induced to differentiate by TNF and IFN-gamma but that at the time of analysis there is heterogeneity in the level of differentiation and a proportion of cells is present that shows more mature characteristics with a coordinate expression of the various differentiation markers and functions.

Canine intersegmental hip joint forces and moments before and after cemented total hip replacement.

Intersegmental forces and moments (i.e. resultant free body forces and moments computed at the joint centers) were studied in canine hindlimbs before and after cemented total hip replacement (THR). Five large, adult, mixed-breed dogs were selected. Their gait was recorded (while leash-walked) before surgery using high-speed cinematography and a force plate. Cemented total hip replacement was unilaterally performed on each dog. Gait was again recorded at one and four months after surgery. Segmental properties (mass, center of mass, and mass moment of inertia) of the hindlimbs were experimentally determined, and an inverse dynamics approach was used to compute intersegmental forces and moments in the sagittal plane. Significant reductions in intersegmental joint forces and moments were observed in the operated hindlimb one month after surgery, although kinematic gait parameters were unaltered. Decreases of 77.0% for vertical forces, 61.9% for craniocaudal forces, and 66.2% for extension moments were determined. Four months after surgery, the joint forces and moments had returned to their preoperative values. This experiment demonstrates that the dynamics of normal walking can be restored in a canine model by four months after THR. It also shows that kinetic (rather than kinematic) parameters are more descriptive of antalgic gait in the canine.