Petri Virolainen

The Reliability of Diagnosis of Infection during Revision Arthroplasties

Background: Follow up studies have shown that 0.5 to 4 % of the total joint arthroplasties will be complicated by infection. Distinction between aseptic loosening and infection is important for prediction of the final outcome after revision arhtroplasty but also for the choice of operative treatment. However, diagnosis of low grade chronic infection is extremely demanding. Materials and Methods: 68 hip and knee revision arthroplasties were reviewed retrospectively in order to evaluate the reliability of pre- and perioperative analysis of infection during total joint revision arthroplasties. The sensitivity and specificity for clinical signs, blood white-cell count, C-reactive protein level, radiographic analysis, bone and leukocyte scans, joint aspirations, and gram staining were determined. Tissue sample were harvested and cultured in all cases. Positive cultures were regarded as a true infection. Results: We were not able to characterize the infection by clinical signs. Also no single test was able to show the presence of infection in all cases. The best results were obtained from pre- and perioperative joint aspirations. Joint aspiration showed 1.0 specificity and 0.75 sensitivity. Conclusion: It is clear from this study that no single test is able to show the presence of infection in every case. Classical clinical signs, laboratory tests, special imaging studies and joint aspirations have all yielded a notable rate of false negative results. Therefore, we recommend that, if arthroplasty patients have pain in prosthetic joint without clear radiological evidence of loosening, bone scans and preoperative joint aspirations should be undertaken. Also, if radiological evidence of loosening is accompanied with one or more of following criteria; C-reactive protein level elevated, radiologic evidence of infection, loosening within the first five years after implantation. In case of infection a delayed two-stage reconstruction should be managed.

Plasma Concentrations of Oral Oxycodone Are Greatly Increased in the Elderly

We compared the pharmacokinetics of 10 mg oral oxycodone in four groups of 10 patients each, aged 20–40, 60–70, 70–80, and 80–90 years. Patients aged 70–80 and 80–90 years had 50–80% higher mean exposure to oxycodone (P < 0.05) and a twofold higher plasma oxycodone concentration (P < 0.05) than the young adults 12 h after ingestion of the drug. Because oxycodone pharmacokinetics depend to a great extent on the age of the subject, it is important to titrate the analgesic dose individually, particularly in the elderly.

Histomorphometric and molecular biologic comparison of bioactive glass granules and autogenous bone grafts in augmentation of bone defect healing

The applicability of bioactive glass (BG) granules as a substitute for bone grafts was tested by comparing the histologic, histomorphometric, and molecular biologic healing patterns to those of bone autografts and ungrafted bone defects in a rat model. The cellular response in defects filled with BG granules was characterized by continuous overexpression of type III collagen. Osteogenic mesenchymal cells, prior to their differentiation to osteoblasts, organized as a dense periosteumlike layer on the surface of the BG granules. By day 14 new bone formation was more extensive in autografted defects than in BG filled defects (p = 0.039). No cartilage-specific type II collagen mRNA was detectable, confirming the uniformity of intramembranous bone formation. The difference in the initiation of new bone formation was further confirmed by the mRNA analyses of the de novo production of TGF-beta 1 and type I collagen. Autografted defects demonstrated the highest levels of TGF-beta 1 and type I collagen mRNAs during the first 2 weeks of healing, whereas BG-filled defects showed biphasic expression patterns of the same genes. Spontaneous new bone formation in ungrafted bone defects was also characterized by biphasic expression of type I collagen gene. Osteonectin mRNA declined gradually over time in autografted and BG filled defects, whereas unfilled defects showed a gradual increase of osteonectin mRNA during healing. By 8 weeks, about 70% of the BG surface showed evidence of direct new bone contact. Energy-dispersing X-ray analyses confirmed the presence of silica-rich and CaP-rich zones at the bonding interface. In conclusion, the osteoconductive surface of bioactive glass granules efficiently bonds to ongrowing new bone but the material does not reach the capacity of autogenous bone graft in promotion of osteogenesis.

Risk of cancer with metal-on-metal hip replacements: population based study

Objective To assess the risk of cancer associated with modern primary metal-on-metal hip replacements. Design Population based study. Setting Nationwide retrospective comparative register. Participants 10 728 patients who underwent metal-on-metal total hip arthroplasty and 18 235 patients who underwent conventional metal-on-polyethylene, ceramic-on-polyethylene, and ceramic-on-ceramic total hip arthroplasty (the non-metal-on-metal cohort) in the Finnish Arthroplasty Register 2001-10. Data on cancer cases up to 2010 for these cohorts were extracted from the Finnish Cancer Registry. Main outcome measures The relative risk of cancer was expressed as the ratio of observed to expected number of cases from the Finnish population—that is, the standardised incidence ratio. The relative risk of cancer in the metal-on-metal cohort compared with the non-metal-on-metal cohort was estimated with analyses of these ratios and Poisson regression. Results The overall risk of cancer in patients with metal-on-metal hip implants was similar to that in the Finnish population (378 observed v 400 expected, standardised incidence ratio 0.95, 95% confidence interval 0.85 to 1.04). The overall risk of cancer in patients with metal-on-metal hip implants was also no higher than in patients who had received non-metal-on-metal hip implants (relative risk 0.92, 0.81 to 1.05). Conclusions Metal-on-metal hip replacements are not associated with an increased overall risk of cancer during a mean follow-up of four years.

Conservative treatment or surgery for shoulder impingement: systematic review and meta-analysis

Abstract Objective: To investigate the evidence on effectiveness of surgery for shoulder impingement compared with conservative treatment. Data sources: Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and Science Citation Index databases were searched in March 2013 unrestricted by date or language. Study selection: Controlled randomized (RCT) or quasi-randomized clinical trials comparing surgery and conservative treatment of shoulder impingement were included. Data extraction: The methodological quality of each included trial was assessed according to the Cochrane Collaboration’s domain-based evaluation framework. Data synthesis: Of seven included RCTs, risk of systematic bias was considered to be low for two, high for four, and unclear for one RCT. The random-effect meta-analysis was conducted on four RCTs involving 347 subjects (173 surgically treated cases and 174 controls). There was no significant difference in changes in pain intensity between surgically and conservatively treated subjects (Hedges’s g = 0.01 in favor of conservative treatment, 95% CI −0.27 to 0.30). Conclusion: Based on the review of seven RCTs, the evidence on effectiveness of surgical or conservative treatment of shoulder impingement was found to be limited. There was, however, moderate evidence that surgical treatment is not more effective than active exercises on reducing pain intensity caused by shoulder impingement. Implications for Rehabilitation Based on the review of seven RCTs, the evidence on effectiveness of surgical or conservative treatment of shoulder impingement was found to be limited. There was moderate evidence that surgical treatment is not more effective than active exercises on reducing pain intensity caused by shoulder impingement. Because of surgery’s higher costs and susceptibility for complications compared with costs and risks of conservative treatment, conservative treatment can be recommended as a first choice of treatment of shoulder impingement in first or second grade.

Pharmacokinetics of Intravenous Paracetamol in Elderly Patients

Background and ObjectivesIntravenous paracetamol (N-acetyl-paraminophenol, acetaminophen) is a widely used nonopioid analgesic which has become popular in the treatment of pain in many patient groups, including the elderly. Although intravenous paracetamol has been studied widely in clinical analgesia studies, there is little information on its pharmacokinetics in the elderly. We designed this study to determine the pharmacokinetics of intravenous paracetamol in very old patients and to compare them with that of younger patients. We also considered the effect of adenosine triphosphate-binding cassette G2 protein (ABCG2) genotype and renal function on paracetamol pharmacokinetics in these patients.MethodsWe compared the pharmacokinetics of intravenous paracetamol in four groups of ten patients, aged 20–40, 60–70, 70–80 and 80–90 years, undergoing orthopaedic surgery. Paracetamol 1000 mg was given by infusion over 15 minutes. Plasma concentrations of paracetamol and its glucuronide and sulphate conjugates were measured for 24 hours with a high-performance liquid chromatographic method and ABCG2 genotype was determined. Glomerular filtration rate (GFR) was estimated from age, sex and serum creatinine of the patient.ResultsIn the group aged 80–90 years, the mean value of the area under the plasma concentration-time curve extrapolated to infinity (AUC∞) of paracetamol was 54–68% higher than in the two youngest groups. Paracetamol clearance showed a statistically significant dependence on age group, whereas volume of distribution during elimination and elimination half-life were associated with age group and sex, respectively. Based on mean AUC∞ of paracetamol glucuronide and paracetamol sulphate, the oldest patients had 1.3- to 1.5-fold greater exposure to these metabolites than patients aged 20–40 years. ABCG2 genotype did not affect paracetamol pharmacokinetics. There was a linear correlation between the values of AUC∞ of paracetamol, its glucuronide and sulphate metabolites and GFR.ConclusionAge and sex are important factors affecting the pharmacokinetics of paracetamol. The higher the age of the patient, the higher is the exposure to paracetamol. Female sex is associated with increased paracetamol concentrations but ABCG2 genotype does not seem to affect paracetamol pharmacokinetics.Trial registration number (EudraCT): 2006-001917-14

Effect of femoral head size on risk of revision for dislocation after total hip arthroplasty: A population-based analysis of 42,379 primary procedures from the Finnish Arthroplasty Register

Background and purpose Previous population-based registry studies have shown that larger femoral head size is associated with reduced risk of revision for dislocation. However, the previous data have not included large numbers of hip resurfacing arthroplasties or large metal-on-metal (> 36-mm) femoral head arthroplasties. We evaluated the association between femoral component head size and the risk of revision for dislocation after THA by using Finnish Arthroplasty Register data. Patients and methods 42,379 patients who were operated during 1996–2010 fulfilled our criteria. 18 different cup/stem combinations were included. The head-size groups studied (numbers of cases) were 28 mm (23,800), 32 mm (4,815), 36 mm (3,320), and > 36 mm (10,444). Other risk factors studied were sex, age group (18–49 years, 50–59 years, 60–69 years, 70–79 years, and > 80 years), and time period of operation (1996–2000, 2001–2005, 2006–2010). Results The adjusted risk ratio in the Cox model for a revision operation due to dislocation was 0.40 (95% CI: 0.26–0.62) for 32-mm head size, 0.41 (0.24–0.70) for 36-mm head size, and 0.09 (0.05–0.17) for > 36-mm head size compared to implants with a head size of 28 mm. Interpretation Larger femoral heads clearly reduce the risk of dislocation. The difference in using heads of > 36 mm as opposed to 28-mm heads for the overall revision rate at 10 years follow-up is about 2%. Thus, although attractive from a mechanical point of view, based on recent less favorable clinical outcome data on these large heads, consisting mainly of metal-on-metal prostheses, one should be cautious using these implants.

Cemented Versus Cementless Total Hip Replacements in Patients Fifty-five Years of Age or Older with Rheumatoid Arthritis

BACKGROUND results obtained from single-center studies indicate that a cemented total hip replacement is the treatment of choice for the management of patients over fifty-five years of age with rheumatoid arthritis. The aim of this study was to analyze population-based survival rates for cemented and cementless total hip replacements in patients aged fifty-five years or over with rheumatoid arthritis in Finland. METHODS between 1980 and 2006, a total of 6000 primary total hip replacements performed for the management of rheumatoid arthritis in patients who were fifty-five years of age or older were entered in the Finnish Arthroplasty Registry. 4019 of them fulfilled our inclusion criteria and were subjected to analysis. The implants were classified into one of three possible groups: (1) a cementless group (a noncemented proximally porous-coated stem and a noncemented porous-coated press-fit cup), (2) a cemented group 1 (a cemented, loaded-taper stem combined with a cemented, all-polyethylene cup), or (3) a cemented group 2 (a cemented, composite-beam stem with a cemented, all-polyethylene cup). RESULTS cementless stems and cups, analyzed separately, had a significantly lower risk of revision for aseptic loosening than cemented implants in patients who were fifty-five years of age or older with rheumatoid arthritis. The fifteen-year survival rate of cementless total hip replacements (80%) was comparable with the rates of the cemented groups (86% in cemented group 1 and 79% in cemented group 2) when revisions for any reason were used as the end point. CONCLUSIONS cementless and cemented total hip replacements produced comparable long-term results in patients who were fifty-five years of age or older with rheumatoid arthritis. LEVEL OF EVIDENCE therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

Hip resurfacing arthroplasty: short-term survivorship of 4,401 hips from the Finnish Arthroplasty Register

Background and purpose Population-based registry data from the Nordic Arthroplasty Register Association (NARA) and from the National Joint Register of England and Wales have revealed that the outcome after hip resurfacing arthroplasty (HRA) is inferior to that of conventional total hip arthroplasty (THA). We analyzed the short-term survival of 4,401 HRAs in the Finnish Arthroplasty Register. Methods We compared the revision risk of the 4,401 HRAs from the Register to that of 48,409 THAs performed during the same time period. The median follow-up time was 3.5 (0–9) years for HRAs and 3.9 (0–9) years for THAs. Results There was no statistically significant difference in revision risk between HRAs and THAs (RR = 0.93, 95% CI: 0.78–1.10). Female patients had about double the revision risk of male patients (RR = 2.0, CI: 1.4–2.7). Hospitals that had performed 100 or more HRA procedures had a lower revision risk than those with less than 100 HRAs (RR = 0.6, CI: 0.4–0.9). Articular Surface Replacement (ASR, DePuy) had inferior outcome with higher revision risk than the Birmingham Hip Resurfacing implant (BHR, Smith & Nephew), the reference implant (RR = 1.8, CI: 1.2–2.7). Interpretation We found that HRA had comparable short-term survivorship to THA at a nationwide level. Implant design had an influence on revision rates. ASR had higher revision risk. Low hospital procedure volume worsened the outcome of HRA. Female patients had twice the revision risk of male patients.

Elimination of intravenous oxycodone in the elderly: a pharmacokinetic study in postoperative orthopaedic patients of different age groups.

AbstractBackground and Objective: Oxycodone is a widely used opioid analgesic, the global use of which has increased several-fold during the last decade. This study was designed to determine the effect of age on the pharmacokinetics of intravenous oxycodone, with special reference to renal function in elderly patients. Methods: We compared the pharmacokinetics of 5 mg of intravenous oxycodone in four groups of 10–11 patients, aged 20–40, 60–70, 70–90 years, undergoing orthopaedic surgery. Plasma concentrations of oxycodone and its noroxycodone, oxymorphone and noroxymorphone metabolites were measured for 24 hours with a liquid chromatography-tandem mass spectrometric method. The cytochrome P450 (CYP) 2D6 genotype of the patients was determined. Glomerular filtration rate (GFR) was estimated on the basis of the age, sex and serum creatinine concentration of the patient. Results: The pharmacokinetics of oxycodone showed age dependency. In the oldest group, the mean area under the plasma concentration-time curve from time zero to infinity (AUC∞) of oxycodone was 80% greater (p < 0.001) and the apparent total body clearance of the drug from plasma (CL) was 34% lower (p < 0.05) than in the youngest group. The mean AUC∞ of oxycodone was also 30–41% greater in the oldest group than in the age groups of 60–70 and 70–80 years (p < 0.05). Oxycodone plasma concentrations from 8 hours post-dose were >2-fold higher (p < 0.01) in patients aged >80 years than in patients aged 20–40 years. Noroxycodone AUC∞ was increased in the oldest group compared with patients aged 20–40 and 60–70 years (p < 0.05). There were no significant sex-related differences in any of the pharmacokinetic parameters. Because 37 of the 41 patients were extensive metabolizers through CYP2D6, the effect of the CYP2D6 genotype on oxycodone pharmacokinetics could not be properly assessed. There was a linear correlation between GFR and CL (p < 0.01, coefficient of determination [r2] = 0.26), volume of distribution at steady state (p < 0.05, r2 = 0.19) and AUC∞ (p < 0.01, r2 = 0.29) of oxycodone. Conclusions: Age is an important factor affecting the pharmacokinetics of oxycodone. Following intravenous administration of oxycodone, patients aged >70 years are expected to have, on average, 40–80% higher exposure to oxycodone than young adult patients. Because oxycodone pharmacokinetics are greatly dependent on the age of the patient, it is important to titrate the analgesic dose individually, particularly in the elderly.