Low Hospital Volume Increases Re-Revision Rate Following Aseptic Revision Total Knee Arthroplasty: An Analysis of 23,644 Cases.

BACKGROUND: Along with rising numbers of primary total knee arthroplasty (TKA), the number of revision total knee arthroplasties (R-TKAs) has been increasing. R-TKA is a complex procedure requiring special instruments, implants, and surgical skills. Therefore it is likely that hospitals with more R-TKAs have more experience with this type of surgery and therefore fewer complications. The purpose of this study is to evaluate the relationship between hospital volume and re-revision rate following R-TKA. METHODS: Using nationwide healthcare insurance data for inpatient hospital treatment, 23,644 aseptic R-TKAs in 21,573 patients treated between January 2013 and December 2017 were analyzed. Outcomes were 90-day mortality, 1-year re-revision rate, and in-house adverse events. The effect of hospital volumes on outcomes were analyzed by means of multivariate logistic regression. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Hospital volume had a significant effect on 1-year re-revision rate (≤12 R-TKA/a: OR 1.44, CI 1.20-1.72; 13-24 R-TKA/a: OR 1.43, CI 1.20-1.71; 25-52 R-TKA/a: OR 1.13, CI 0.94-1.35; ≥53 R-TKA/a: reference). Ninety-day mortality and major in-house adverse events decreased with increasing volume per year, but after risk adjustment this was not statistically significant. CONCLUSION: We found evidence of higher risk for re-revision surgery in hospitals with fewer than 25 R-TKA per year. It might contribute to improved patient care if complex elective procedures like R-TKA which require experience and a specific logistic background were performed in specialized centers.

Low Hospital Volume Increases Revision Rate and Mortality Following Revision Total Hip Arthroplasty: An Analysis of 17,773 Cases.

BACKGROUND: With the number of primary total hip arthroplasty (THA), the amount of revision THA (R-THA) increases. R-THA is a complex procedure requiring special instruments, implants, and surgical skills. Therefore it is likely that hospitals performing a higher number of R-THAs have more experience with this type of surgery and therefore fewer complications. The purpose of this study was to evaluate the relationship between hospital volume and risk of postoperative complications following R-THA. METHODS: Using nationwide healthcare insurance data for inpatient hospital treatment, 17,773 aseptic R-THAs in 16,376 patients treated between January 2014 and December 2016 were included. Outcomes were 90-day mortality, 1-year revision procedures, and in-house adverse events. The effect of hospital volume on outcome was analyzed by means of multivariate logistic regression. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Hospital volume had a significant effect on 90-day mortality (≤12 cases per year: OR 2.13, CI 1.53-2.96; 13-24: OR 1.79, CI 1.29-2.50; 25-52: OR 1.53, CI 1.11-2.10; ≥53: reference) and 1-year revision procedures (≤12: OR 1.26, CI 1.09-1.47; 13-24: OR 1.18, CI 1.02-1.37; 25-52: OR 1.03, CI 0.90-1.19; ≥53: reference). There was no significant effect on risk-adjusted major in-house adverse events. CONCLUSION: We found evidence of higher risk for revision surgery and mortality in hospitals with fewer than 25 and 53 R-THA per year, respectively. To improve patient care, complex elective procedures like R-THA which require experience and a specific logistic background should be performed in specialized centers.

Obesity Increases the Risk of Postoperative Complications and Revision Rates Following Primary Total Hip Arthroplasty: An Analysis of 131,576 Total Hip Arthroplasty Cases.

BACKGROUND: The aim of our study is to evaluate the association of body mass index (BMI) and the risk of postoperative complications, mortality, and revision rates following primary total hip arthroplasty given other potentially confounding patient characteristics in a large cohort study. METHODS: Using nationwide billing data for inpatient hospital treatment of the biggest German healthcare insurance, 131,576 total hip arthroplasties in 124,368 patients between January 2012 and December 2014 were included. Outcomes were 90-day mortality, 1-year revision procedures (with and without removal or exchange of implants), 90-day surgical complications, 90-day femoral fractures, and overall complications. The effect of BMI on outcome was analyzed using multivariable logistic regression. Risk-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: BMI had a significant effect on overall complications (30-34 in kg/m2: OR 1.1, CI 1.0-1.2, P = .014; 35-39: OR 1.5, CI 1.3-1.6, P < .001; ≥40: OR 2.1, CI 1.9-2.3, P < .001; <30: reference). The OR for 1-year revision procedures (30-34: OR 1.2, CI 1.1-1.4, P = .001; 35-39: OR 1.6, CI 1.4-1.8, P < .001; ≥40: OR 2.4, CI 2.1-2.7, P < .001; <30: reference) and 90-day surgical complications increased with every BMI category. For mortality and periprosthetic fractures there was a higher risk only for patients with BMI ≥40. CONCLUSION: BMI increases the risk of revision rates in a liner trend. Therefore, the authors believe that patients with a BMI >40 kg/m2 should be sent to obesity medicine physicians in order to decrease the body weight prior elective surgery.

Are TKAs Performed in High-volume Hospitals Less Likely to Undergo Revision Than TKAs Performed in Low-volume Hospitals?

BACKGROUND: High-volume hospitals have achieved better outcomes for THAs and unicompartmental knee arthroplasties (UKAs). However, few studies have analyzed implant survival after primary TKA in high-volume centers. QUESTIONS/PURPOSES: Is the risk of revision surgery higher when receiving a TKA in a low-volume hospital than in a high-volume hospital? METHODS: Using nationwide billing data of the largest German healthcare insurer for inpatient hospital treatment, we identified 45,165 TKAs in 44,465 patients insured by Allgemeine Ortskrankenkasse who had undergone knee replacement surgery between January 2012 and December 2012. Revision rates were calculated at 1 and 2 years in all knees. The hospital volume was calculated using volume quintiles of the number of all knee arthroplasties performed in each center. We used multiple logistic regression to model the odds of revision surgery as a function of hospital volume. Age, sex, 31 comorbidities, and variables for socioeconomic status were included as independent variables in the model. RESULTS: After controlling for socioeconomic factors, patient age, sex, and comorbidities, we found that having surgery in a high-volume hospital was associated with a decreased risk of having revision TKA within 2 years of the index procedure. The odds ratio for the 2-year revision was 1.6 (95% CI, 1.4-2.0; p < 0.001) for an annual hospital volume of 56 or fewer cases, 1.5 (95% CI, 1.3-1.7; p < 0.001) for 57 to 93 cases, 1.2 (95% CI, 1.0-1.3; p = 0.039) for 94 to 144 cases, and 1.1 (95% CI, 0.9-1.2; p = 0.319) for 145 to 251 cases compared with a hospital volume of 252 or more cases. CONCLUSIONS: We found a clear association of higher risk for revision surgery when undergoing a TKA in a hospital where less than 145 arthroplasties per year were performed. The study results could help practitioners to guide potential patients in hospitals that perform more TKAs to reduce the overall revision and complication rates. Furthermore, this study underscores the importance of a minimum hospital threshold of arthroplasty cases per year to get permission to perform an arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.

V-region gene analysis of locally defined synovial B and plasma cells reveals selected B cell expansion and accumulation of plasma cell clones in rheumatoid arthritis.

OBJECTIVE: To elucidate the development of synovial tissue-specific B cell immune responses, the clonality of individual naive B cells, memory B cells, and plasma cells and their organization and histologic localization in the inflamed tissue were investigated in patients with rheumatoid arthritis (RA). METHODS: B and plasma cells were isolated by laser capture microdissection (LCM) from the synovial tissue of patients with RA. In addition, single naive B cells, memory B cells, and plasma cells were sorted from synovial tissue cell suspensions. RNA was extracted from the cells, and Ig VH genes were amplified, cloned, and sequenced. RESULTS: Both LCM and single cell sorting analyses showed that naive and memory B cells infiltrated the RA synovial tissue. Comparison of the V-gene repertoire of B and plasma cells suggested that synovial plasma cells were generated, by and large, from locally activated B cells, indicating that a selected population of memory B cells differentiates into large plasma cell clones that then accumulate in the inflamed tissue. Clonally related plasma cells were isolated from separate and distinct localized areas of the tissue, suggesting that the newly generated plasma cells have a high migratory capacity. CONCLUSION: These results support the idea of a continuous activation of selected B cell clones, and hence a massive accumulation of plasma cells, in RA synovial tissue. As B cells and their secreted antibodies are an important factor in controlling inflammatory processes, patients with RA displaying intensive synovial tissue lymphocytic infiltrations might benefit from B cell depletion therapy. Early treatment will prevent accumulation of pathogenic plasma cells.

Blood transfusion and venous thromboembolism trends and risk factors in primary and aseptic revision total hip and knee arthroplasties: A nationwide investigation of 736,061 cases.

BACKGROUND: Over the last years, new transfusion guidelines and pharmaceuticals have been introduced in primary and revision total hip and knee arthroplasty (P-THA, P-TKA, R-THA, R-TKA). In the US, a substantial decrease in transfusions has been observed in recent years. Little data exists on the subject in Europe. In this context we aimed to analyze: (1) Is there also a significant decrease in blood transfusion for these procedures in Germany? (2) Which patient and hospital related factors are associated with the risk of blood transfusion? (3) Is there a trend in complications, especially venous thromboembolism and stroke events that can be linked to tranexamic acid use? HYPOTHESIS: There is a significant trend in decreasing blood transfusions in hip and knee arthroplasty. METHODS: Using nationwide healthcare insurance data for inpatient hospital treatment, 736,061 cases treated between January 2011 and December 2017 were included (318,997 P-THAs, 43,780 R-THAs, 338,641 P-TKAs, 34,643 R-TKAs). Multivariable logistic regression was used to model the odds of transfusion as a function of the year of surgery. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: In each cohort the odds of transfusion decreased over time (2017 vs. 2011 (reference): P-THA: OR 0.42 (95%CI: 0.39-0.45), P-TKA: OR 0.41 (95%CI: 0.37-0.46), R-THA: OR 0.52 (95%CI: 0.47-0.58), R-TKA: OR 0.53 (95%CI: 0.46-0.61). Patient-related risk factors for blood transfusion included older age, female gender, lower Body Mass Index, comorbidities such as renal failure, cardiac arrhythmia, congestive heart failure, valvular disease, coagulopathy, depression, and antithrombotic medication prior to surgery. Venous thromboembolism or stroke events did not increase over the study period. DISCUSSION: The incidence of blood transfusions in primary and revision TKA and THA decreased over the study period. This may be due to new transfusion guidelines and the introduction of novel pharmaceuticals such as tranexamic acid. A further improved patient blood management and a focus on vulnerable patient groups might lead to a further future reduction of transfusions, especially in R-THA. LEVEL OF EVIDENCE: III; comparative observational study.

[Opportunities and limitations of risk adjustment of quality indicators based on inpatient administrative health data - a workshop report]. / Möglichkeiten und Grenzen der Risikoadjustierung von Qualitätsindikatoren aus Krankenhausabrechnungsdaten - ein Werkstattbericht.

INTRODUCTION: The quality indicators of the Initiative Qualitätsmedizin e. V. (IQM) have been developed as triggers to examine treatment processes for opportunities for improvement. Published quality results have partly been used for external quality comparisons in the media. Therefore, member hospitals of IQM demanded to investigate if methods of risk adjustment should be applied in the calculation of the quality indicators. After a hearing of experts had been held, a task force was founded to conduct test calculations on risk adjustment methods. METHODS: Specific risk adjustment models for mortality in myocardial infarction, heart failure, stroke, pneumonia, and colectomy in colorectal cancer were developed in the database of national German DRG data of the year 2016. These models were used to calculate standardized mortality ratios (SMR) per indicator in a sample of 172 member hospitals of IQM based on the data of the year 2018. Median SMR per indicator were compared to median SMR based on a standardization by age and gender, which is the standard procedure in IQM. Correlations between the different SMR were calculated. Quality of care was judged by two different approaches: a) a descriptive discrepancy of |0.1| from the SMR value of 1, and b) a significant discrepancy from 1 using the 95% confidence limits. The effect of using the specific risk adjustment in relation to the standard procedure was investigated for both approaches (a and b). RESULTS: The specific risk adjustment methods showed an area under the curve between 0.72 and 0.84. The median differences between the SMR based on standardization by age and gender and the SMR based on specific risk adjustment were small (between 0 and 0.4); Spearman's correlations were between 0.90 and 0.99. Changes in the judgement of quality of care in comparison to the national average occurred in 3.9% (mortality from pneumonia) to 20.6% of the hospitals (mortality from heart failure) in descriptive comparisons. When the judgement was based on confidence limits changes were observed in 1.6% (mortality after colectomy) to 17.4% of the hospitals (mortality from heart failure). DISCUSSION: Implementing specific risk adjustment models had only minor effects on the distribution of risk-adjusted mortality compared to the standard procedure, but the judgement of quality of care could change for a fifth of the hospitals in individual indicators. Concerning methodological and practical reasons, the task force recommends further development of risk adjustment methods for selected indicators. This should be accompanied by studies on the validity of inpatient administrative data for quality management as well as by efforts to improve the usefulness of these data for such purposes.

Time to Surgery and Outcome in the Treatment of Proximal Femoral Fractures.

BACKGROUND: It has not been conclusively established whether, or to what extent, the time to surgery affects mortality and the risk of complications after the surgical treatment of proximal femoral fractures. METHODS: Data on 106 187 hospitalizations over the period 2015-2017 involving insurees of the German AOK health insurance company aged 20 and above were drawn from pseudonymized billing data and stratified in three subgroups: osteosynthesis for pertrochanteric fracture (PTF-OS: N = 52 358), osteosynthesis for femoral neck fracture (FNF-OS: N = 7970), and endoprosthesis for femoral neck fracture (FNF-EP: N = 45 859). Multivariate regression models were used to analyze the relation between preoperative in-hospital stay (time to surgery, TTS: 0 days [reference category], 1, 2, 3, 4-7 days) and mortality and general complications within 90 days, with risk adjustment for fracture site, operative method, age, sex, accompanying illnesses, and antithrombotic medication in the preceding year. RESULTS: Mortality was significantly elevated only with PTF-OS, and only with a TTS of 2 days (odds ratio: 1.12 [95% confidence interval: (1.02; 1.23)]). General complications in relation to TTS were significantly elevated in the following situations: PTF-OS: 2 days: OR 1.24 [1.13; 1.37], 3 days: OR 1.33 [1.11; 1.60], 4-7 days: OR 1.47 [1.21; 1.78]; FNF-EP: 3 days: OR 1.21 [1.06; 1.37], 4-7 days: OR 1.42 [1.25; 1.62]; FNF-OS: 4-7 days: OR 1.86 [1.26; 2.73]. CONCLUSION: A prolonged time to surgery is associated with an elevated general complication risk depending on the site of the fracture and the type of surgical procedure used.

[Volume Growth of Inpatient Treatments for Spinal Disease - Analysis of German Nationwide Hospital Discharge Data from 2005 to 2014]. / Mengenentwicklung stationärer Behandlungen bei Erkrankungen der Wirbelsäule ­ Analyse der deutschlandweiten Krankenhausabrechnungsdaten von 2005 bis 2014.

BACKGROUND: Marked volume growth of inpatient treatments for spinal disease has been observed since diagnosis related groups (DRG) were introduced as payment for inpatient services in Germany. This study aims to analyse this increase by population and stratified by types of treatment. MATERIAL AND METHODS: Using German nationwide hospital discharge data (DRG statistics), inpatient treatments for spinal disease with or without surgery were identified. Trends in case numbers were analysed from 2005 to 2014 with consideration of demographic changes, in order to explore which age groups and which types of treatment are affected by volume growth. RESULTS: In 2014 (2005), 289 000 (177 000) inpatient treatments with surgery and 463 000 (287 000) treatments without surgery were identified. After adjusting for demographic factors, treatments with and without surgery exhibited a relative volume growth of + 50%. This increase affected higher age groups and women, in particular. Depending on the type of treatment, very different degrees of volume growth were observed. For example, disc surgeries adjusted for demographic change increased by about + 5%, whereas spinal fusion and vertebral replacement surgeries, kypho-/vertebroplasties and decompression of the spine more than doubled. Within the non-surgically treated cases, local pain therapies of the spine increased after adjustment for demographic changes by about + 142%. The conservatively treated cases showed a demographically adjusted increase of + 22%. CONCLUSION: Apart from demographic changes, this analysis cannot resolve the underlying causes of volume growth in treatments for spinal disease. However, the stratified analysis of various subgroups may help to classify these developments in a more differentiated manner. The results may support a more targeted debate about potential over- or misallocation of inpatient services in this area.

[Impact of Case Numbers on the 5-Year Survival Rate of Unicondylar Knee Replacements in Germany]. / Einfluss der Fallzahl pro Klinik auf die 5-Jahres-Überlebensrate des unikondylären Kniegelenkersatzes in Deutschland.

BACKGROUND: Reported survival rates of unicondylar knee arthroplasty (UKA) vary considerably. The influences of patient characteristics and the type of implant have already been examined. This analysis investigated the influence of hospital volume on 5-year-survival rate, using administrative claims data of Germany's largest health insurance provider. METHODS: We analysed administrative claims data for 20,946 UKAs covered by the German local healthcare funds (Allgemeine Ortskrankenkasse, AOK) between 2006 and 2012. Survival rates were estimated using Kaplan-Meier analysis. The influence of hospital case numbers on 5-year survival was analysed by means of multivariable Cox regression adjusted for patient characteristics. We estimated hazard ratios (HR) with 95% confidence intervals for five hospital volume categories: < 12 cases, 13 - 24 cases, 25 - 52 cases, 53 - 104 cases, > 104 cases (per hospital and year). RESULTS: The overall 5-year Kaplan-Meier survival rate was 87.8% (95%-CI: 87.3 - 88.3%). This increased with hospital volume (< 12 cases: 84.1% vs. > 104 cases: 93.2%). The analysis identified low hospital volume as an independent risk factor for surgical revision (< 12 cases: HR = 2.13 [95%-CI 1.83 - 2.48]; 13 - 24 cases: HR = 1.94 [95%-CI: 1.67 - 2.25]; 25 - 52 cases: HR = 1.66 [95%-CI: 1.41 - 1.96]; 53 - 104 cases: HR = 1.51 [95%-CI: 1.28 - 1.77]; > 104 cases: reference category). DISCUSSION: Our analysis revealed a significant relationship between hospital case numbers and 5-year survival rate, which increases with hospital volume. The risk of surgical revision within 5 years in hospitals with fewer than 25 UKAs per year is approximately twice as high as in hospitals with more than 104 cases.

Five-Year Survival of 20,946 Unicondylar Knee Replacements and Patient Risk Factors for Failure: An Analysis of German Insurance Data.

BACKGROUND: Improvements in implant design and surgical technique of unicondylar knee arthroplasty have led to reduced revision rates, but patient selection seems to be crucial for success of such arthroplasties. The purpose of the present study was to analyze the 5-year implant survival rate of unicondylar knee replacements in Germany and to identify patient factors associated with an increased risk of revision, including >30 comorbid conditions. METHODS: Using nationwide billing data of the largest German health-care insurance for inpatient hospital treatment, we identified patients who underwent unicondylar knee arthroplasty between 2006 and 2012. Kaplan-Meier survival curves with revision as the end point and log-rank tests were used to evaluate 5-year implant survival. A multivariable Cox regression model was used to determine factors associated with revision. The risk factors of age, sex, diagnosis, comorbidities, type of implant fixation, and hospital volume were analyzed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: During the study period, a total of 20,946 unicondylar knee arthroplasties were included. The number of unicondylar knee arthroplasties per year increased during the study period from 2,527 in 2006 to 4,036 in 2012. The median patient age was 64 years (interquartile range, 56 to 72 years), and 60.4% of patients were female. During the time evaluated, the 1-year revision rate decreased from 14.3% in 2006 to 8.7% in 2011. The 5-year survival rate was 87.8% (95% CI, 87.3% to 88.3%). Significant risk factors (p < 0.05) for unicondylar knee arthroplasty revision were younger age (the HR was 2.93 [95% CI, 2.48 to 3.46] for patient age of <55 years, 1.86 [95% CI, 1.58 to 2.19] for 55 to 64 years, and 1.52 [95% CI, 1.29 to 1.79] for 65 to 74 years; patient age of >74 years was used as the reference); female sex (HR, 1.18 [95% CI, 1.07 to 1.29]); complicated diabetes (HR, 1.47 [95% CI, 1.03 to 2.12]); depression (HR, 1.29 [95% CI, 1.06 to 1.57]); obesity, defined as a body mass index of ≥30 kg/m2 (HR, 1.13 [95% CI, 1.02 to 1.26]); and low-volume hospitals, denoted as an annual hospital volume of ≤10 cases (HR, 1.60 [95% CI, 1.39 to 1.84]), 11 to 20 cases (HR, 1.47 [95% CI, 1.27 to 1.70]), and 21 to 40 cases (HR, 1.31 [95% CI, 1.14 to 1.51]) (>40 cases was used as the reference). CONCLUSIONS: Apart from known risk factors, this study showed a significant negative influence of obesity, depression, and complicated diabetes on the 5-year unicondylar knee replacement survival rate. Surgical indications and preoperative patient counseling should consider these findings. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patient and physician satisfaction with rofecoxib in osteoarthritis: results of a post-marketing surveillance study in primary care in Germany.

A post-marketing surveillance study was conducted in Germany to assess the efficacy and tolerability of rofecoxib in the treatment of osteoarthritis (OA). Patients were eligible for inclusion in this study if they were being treated for the first time or being switched from other medications. More than three-quarters of the 80,371 patients enrolled in the study reported improved pain relief and function during treatment with rofecoxib (12.5 or 25 mg/day), including a reduction in pain experienced when walking on a flat surface or climbing or descending stairs. A majority of patients also considered that the duration of analgesia provided by rofecoxib was longer than with previous medications (predominantly non-steroidal anti-inflammatory drugs). Some 85% of patients reported an improvement in quality of life during rofecoxib therapy and a similar proportion considered once-daily rofecoxib to be a simpler regimen than their previous medications. Tolerability of rofecoxib was consistent with previous experience in controlled trials, with adverse events recorded in less than 1.5% of patients (n = 1090). No new or unexpected types of adverse events were recorded. A total of 81 serious adverse events were reported, corresponding to an event rate of approximately one per 1000 patient-years of treatment. Most of these serious events were not considered attributable to rofecoxib use. Physicians considered that rofecoxib provided better and more prolonged analgesia than previous medications and improved quality of life for more than 80% of patients, and regarded once-daily rofecoxib as a simpler treatment regimen than previous therapies in more than 90% of patients. Patient and physician satisfaction with rofecoxib was high in this survey. Most respondents regarded the drug as effective, easy to use, and a well-tolerated medication for the treatment of OA.

'Hip' pain.

'Hip' pain is usually located in the groin, upper thigh or buttock and is a common complaint. Slipped capital femoral epiphysis, avascular femoral head necrosis and apophyseal avulsion are the most common diagnoses in childhood and adolescents. Strains and fractures are common in sport-active adults. Osteoarthritis occurs in middle-aged and older adults. Trauma may result in femoral head fracture or typical muscle and tendon sprains and bursitis. Septic or inflammatory arthritis can occur at every age. Septic arthritis, fractures and acute epiphyseal slipping are real emergency cases. Congenital dysplasia of the hip joint may lead to labral tears and early osteoarthritis. The most important hip problems in children, adolescents, adult and older people are discussed; these problems originate from intra-articular disorders and the surrounding extra-articular soft tissues. Medical history, clinical examination and additional tests, including imaging, will be demonstrated. Principles of treatment are given for specific disorders.

Prevalence of self-reported pain, joint complaints and knee or hip complaints in adults aged ≥ 40 years: a cross-sectional survey in Herne, Germany.

BACKGROUND: Pain and musculoskeletal complaints are among the most common symptoms in the general population. Despite their epidemiological, clinical and health economic importance, prevalence data on pain and musculoskeletal complaints for Germany are scarce. METHODS: A cross-sectional survey of a random sample of citizens of Herne, Germany, aged ≥ 40 years was performed. A detailed self-complete postal questionnaire was used, followed by a short reminder questionnaire and telephone contacts for those not responding. The questionnaire contained 66 items, mainly addressing pain of any site, musculoskeletal complaints of any site and of knee and hip, pain intensities, the Western Ontario MacMaster Universities (WOMAC) index, medication, health care utilization, comorbidities, and quality of life. RESULTS: The response rate was 57.8% (4,527 of 7,828 individuals). Survey participants were on average 1.3 years older, and the proportion of women among responders tended to be greater than in the population sample. There was no age difference between the population sample and 2,221 participants filling out the detailed questionnaire. The following standardized prevalences were assessed: current pain: 59.7%, pain within the past four weeks: 74.5%, current joint complaints: 49.3%, joint complaints within the past four weeks and twelve month: 62.8% and 67.4%, respectively, knee as the site predominantly affected: 30.9%, knee bilateral: 9.7%, hip: 15.2%, hip bilateral: 3.5%, knee and hip: 5.5%. Pain and musculoskeletal complaints were significantly more often reported by women. A typical relationship of pain and joint complaints to age could be found, i.e. increasing prevalences with increasing age categories, with a drop in the highest age groups. In general, pain and joint pain were associated with comorbidity and body mass index as well as quality of life. CONCLUSIONS: Our data confirm findings of other recent national as well as European surveys. The high site specific prevalences of knee and hip complaints underline the necessity to further investigate characteristics and consequences of pain and symptomatic osteoarthritis of these joints in adults in Germany.

Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study.

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E(2) (PGE(2)) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs((O-24h))] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2-7%). Individual CSF lag times with respect to (50%) peak plasma concentration were

Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To measure the efficacy and safety of diclofenac sodium gel in patients with primary hand osteoarthritis (OA). METHODS: In a randomized, double-blind, placebo-controlled trial, men and women aged > or = 40 years diagnosed with primary OA in the dominant hand were randomly assigned to self-apply topical 1% diclofenac sodium gel (Voltaren Gel) (n = 198) or vehicle (n = 187) to both hands 4 times daily for 8 weeks. Primary outcome measures included OA pain intensity (100-mm visual analog scale), total Australian/Canadian Osteoarthritis Hand Index (AUSCAN) score, and global rating of disease activity at 4 and 6 weeks. Secondary outcomes included onset of efficacy in Weeks 1 and 2, durability of efficacy at 8 weeks, measures of disease activity in the dominant hand, pain intensity in the non-dominant hand, AUSCAN subindices, end of study rating of efficacy, and Osteoarthritis Research Society International response criteria. RESULTS: Diclofenac sodium gel decreased pain intensity scores by 42%-45%, total AUSCAN scores by 35%-40%, and global rating of disease by 36%-40%. Significant differences favoring diclofenac sodium gel over vehicle were observed at Week 4 for pain intensity and AUSCAN, with a trend for global rating of disease activity. At Week 6, diclofenac sodium gel treatment significantly improved each primary outcome measure compared with vehicle. Secondary outcomes generally supported the primary outcomes. The most common treatment-related adverse event (AE) was application-site paresthesia. Most AE were mild. No cardiac events, gastrointestinal bleeding, or ulcers were reported. CONCLUSION: Topical diclofenac sodium gel was generally well tolerated and effective in primary hand OA. (NCT ID: NCT00171665).

Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow.

OBJECTIVE: Previous histopathologic and magnetic resonance imaging studies suggest that the subchondral bone marrow might be the primary site of inflammation in patients with ankylosing spondylitis (AS) and that this might be reflected by inflammation found in hip joints. The aim of this study was to conduct an immunohistologic assessment of the bone-cartilage interface and subchondral bone marrow in AS patients with hip arthritis. METHODS: We collected femoral heads from patients with AS, osteoarthritis (OA), and rheumatoid arthritis (RA) who were undergoing hip replacement. The subchondral bone marrow and bone-cartilage interface were assessed immunohistochemically by evaluating infiltrating T cells, microvessel density, and osteoclasts. Areas of the femoral head surface with and without cartilage were assessed separately. RESULTS: At sites with surface cartilage, we found subchondral infiltration of CD3+ T cell aggregates at significantly higher numbers in AS patients as compared with OA patients, but not RA patients. At sites of complete cartilage destruction, the frequency of CD3+ T cell aggregates was significantly reduced as compared with sites with cartilage on the surface in AS patients, but not in RA patients. Similar differences were found for CD4+ and CD8+ T cells. Only at sites with surface cartilage, but not those without, angiogenesis and osteoclastic foci in the subchondral bone marrow in AS patients were significantly increased as compared with RA patients and with OA patients. CONCLUSION: These findings suggest that the subchondral bone marrow and bone-cartilage interface are primary sites of inflammation in AS and that cartilage might be necessary for the induction of inflammation.

Stimulation of collagenase 3 expression in synovial fibroblasts of patients with rheumatoid arthritis by contact with a three-dimensional collagen matrix or with normal cartilage when coimplanted in NOD/SCID mice.

OBJECTIVE: To study the expression of collagenase 3 (matrix metalloproteinase 13 [MMP-13]) and collagenase 1 (MMP-1) in synovial fibroblasts from patients with rheumatoid arthritis (RA) when cultured within 3-dimensional collagen gels or coimplanted with normal cartilage in immunodeficient NOD/SCID mice. METHODS: Messenger RNA (mRNA) and protein expression of collagenase 3 and collagenase 1 were characterized in synovial and skin fibroblasts by Northern blot and Western blot analysis. The mRNA expression of both collagenases in cell-cartilage implants in NOD/SCID mice was investigated by in situ hybridization in combination with immunohistochemistry of human fibroblasts. RESULTS: Synovial fibroblasts coimplanted with normal cartilage in NOD/SCID mice deeply invaded adjacent cartilage tissue. In this in vivo system of cartilage destruction, collagenase 3 mRNA was induced in synovial fibroblasts at sites of cartilage erosion, while the expression of collagenase 1 mRNA could not be detected. Culture of synovial fibroblasts within 3-dimensional collagen gels was associated with a marked increase in collagenase 3 mRNA expression and proenzyme production. This stimulatory effect was 1 order of magnitude higher in comparison with a 2-4-fold increase upon treatment with interleukin-1beta or tumor necrosis factor a. In contrast, mRNA expression and proenzyme production of collagenase 1 were increased strongly, and to a similar extent, either by contact with 3-dimensional collagen or by proinflammatory cytokines. CONCLUSION: The expression of collagenase 3, in contrast to that of collagenase 1, is preferentially stimulated in synovial fibroblasts by 3-dimensional collagen rather than by proinflammatory cytokines. The induction of collagenase 3 by cell-matrix interactions represents a potential mechanism contributing to the invasive phenotype of synovial fibroblasts at sites of synovial invasion into cartilage in RA.