Osteoarthritis: rational approach to treating the individual

Osteoarthritis (OA) is the most common form of joint disease and the leading cause of pain and physical disability in older people. Risk factors for incidence and progression of osteoarthritis vary considerably according to the type of joint. Disease assessment is difficult and the relationship between the radiographic severity of joint damage and the incidence and severity of pain is only modest. Psychosocial and socio-economic factors play an important role. This chapter will discuss four main guiding principles to the management of OA: (1) to avoid overtreating people with mild symptoms; (2) to attempt to avoid doing more harm than good ('primum non nocere'); (3) to base patient management on the severity of pain, disability and distress, and not on the severity of joint damage or radiographic change; and (4) to start with advice about simple measures that patients can take to help themselves, and only progress to interventions that require supervision or specialist knowledge if simple measures fail. Effect sizes derived from meta-analyses of large randomized trials in OA are only small to moderate for most therapeutic interventions, but they are still valuable for patients and clinically relevant for physicians. Joint replacement may be the only option with a large effect size, but is only appropriate for the relatively small number of people with OA who have advanced disease and severe symptoms. The key to successful management involves patient and health professionals working together to develop optimal treatment strategies for the individual.

T2 mapping in the knee after microfracture at 3.0 T: correlation of global T2 values and clinical outcome - preliminary results

OBJECTIVE: The aim of our study was to correlate global T2 values of microfracture repair tissue (RT) with clinical outcome in the knee joint. METHODS: We assessed 24 patients treated with microfracture in the knee joint. Magnetic resonance (MR) examinations were performed on a 3T MR unit, T2 relaxation times were obtained with a multi-echo spin-echo technique. T2 maps were obtained using a pixel wise, mono-exponential non-negative least squares fit analysis. Slices covering the cartilage RT were selected and region of interest analysis was done. An individual T2 index was calculated with global mean T2 of the RT and global mean T2 of normal, hyaline cartilage. The Lysholm score and the International Knee Documentation Committee (IKDC) knee evaluation forms were used for the assessment of clinical outcome. Bivariate correlation analysis and a paired, two tailed t test were used for statistics. RESULTS: Global T2 values of the RT [mean 49.8ms, standards deviation (SD) 7.5] differed significantly (P<0.001) from global T2 values of normal, hyaline cartilage (mean 58.5ms, SD 7.0). The T2 index ranged from 61.3 to 101.5. We found the T2 index to correlate with outcome of the Lysholm score (r(s)=0.641, P<0.001) and the IKDC subjective knee evaluation form (r(s)=0.549, P=0.005), whereas there was no correlation with the IKDC knee form (r(s)=-0.284, P=0.179). CONCLUSION: These findings indicate that T2 mapping is sensitive to assess RT function and provides additional information to morphologic MRI in the monitoring of microfracture.

Kinematic biomechanical assessment of human articular cartilage transplants in the knee using 3-T MRI: an in vivo reproducibility study

The aims of this study were to examine the clinical feasibility and reproducibility of kinematic MR imaging with respect to changes in T (2) in the femoral condyle articular cartilage. We used a flexible knee coil, which allows acquisition of data in different positions from 40 degrees flexion to full extension during MR examinations. The reproducibility of T (2) measurements was evaluated for inter-rater and inter-individual variability and determined as a coefficient of variation (CV) for each volunteer and rater. Three different volunteers were measured twice and regions of interest (ROIs) were selected by three raters at different time points. To prove the clinical feasibility of this method, 20 subjects (10 patients and 10 age- and sex-matched volunteers) were enrolled in the study. Inter-rater variability ranged from 2 to 9 and from 2 to 10% in the deep and superficial zones, respectively. Mean inter-individual variability was 7% for both zones. Different T (2) values were observed in the superficial cartilage zone of patients compared with volunteers. Since repair tissue showed a different behavior in the contact zone compared with healthy cartilage, a possible marker for improved evaluation of repair tissue quality after matrix-associated autologous chondrocyte transplantation (MACT) may be available and may allow biomechanical assessment of cartilage transplants.

Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared

BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.

Individual versus standard quality of life assessment in a phase II clinical trial in mesothelioma patients: feasibility and responsiveness to clinical changes

In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial.

No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk factor for cirrhosis in alcoholic liver disease

BACKGROUND: As only a minority of alcoholics develop cirrhosis, polymorphic genes, whose products are involved in fibrosis development were suggested to confer individual susceptibility. We tested whether a functional promoter polymorphism in the gene encoding matrix metalloproteinase-3 (MMP-3; 1171 5A/6A) was associated liver cirrhosis in alcoholics. METHODS: Independent cohorts from the UK and Germany were studied. (i) UK cohort: 320 alcoholic cirrhotics and 183 heavy drinkers without liver damage and (ii) German cohort: 149 alcoholic cirrhotics, 220 alcoholic cirrhotics who underwent liver transplantation and 151 alcoholics without liver disease. Patients were genotyped for MMP-3 variants by restriction fragment length polymorphism, single strand confirmation polymorphism, and direct sequencing. In addition, MMP-3 transcript levels were correlated with MMP-3 genotype in normal liver tissues. RESULTS: Matrix metalloproteinase-3 genotype and allele distribution in all 1023 alcoholic patients were in Hardy-Weinberg equilibrium. No significant differences in MMP-3 genotype and allele frequencies were observed either between alcoholics with or without cirrhosis. There were no differences in hepatic mRNA transcription levels according to MMP-3 genotype. CONCLUSIONS: Matrix metalloproteinase-3 1171 promoter polymorphism plays no role in the genetic predisposition for liver cirrhosis in alcoholics. Stringently designed candidate gene association studies are required to exclude chance observations.

Comparison of voxel-based 3-D MRI analysis and subtraction ictal SPECT coregistered to MRI in focal epilepsy

While voxel-based 3-D MRI analysis methods as well as assessment of subtracted ictal versus interictal perfusion studies (SISCOM) have proven their potential in the detection of lesions in focal epilepsy, a combined approach has not yet been reported. The present study investigates if individual automated voxel-based 3-D MRI analyses combined with SISCOM studies contribute to an enhanced detection of mesiotemporal epileptogenic foci. Seven consecutive patients with refractory complex partial epilepsy were prospectively evaluated by SISCOM and voxel-based 3-D MRI analysis. The functional perfusion maps and voxel-based statistical maps were coregistered in 3-D space. In five patients with temporal lobe epilepsy (TLE), the area of ictal hyperperfusion and corresponding structural abnormalities detected by 3-D MRI analysis were identified within the same temporal lobe. In two patients, additional structural and functional abnormalities were detected beyond the mesial temporal lobe. Five patients with TLE underwent epileptic surgery with favourable postoperative outcome (Engel class Ia and Ib) after 3-5 years of follow-up, while two patients remained on conservative treatment. In summary, multimodal assessment of structural abnormalities by voxel-based analysis and SISCOM may contribute to advanced observer-independent preoperative assessment of seizure origin.

Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality. OBJECTIVES: Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials. SELECTION CRITERIA: We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy. DATA COLLECTION AND ANALYSIS: We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment. Patient-level data were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-effects meta-analysis. Analyses were according to the intention-to-treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports only the results for the primary endpoint. MAIN RESULTS: A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2) 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42). AUTHORS' CONCLUSIONS: ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.

Image quality of supine chest radiographs: intra-individual comparison of computed radiography and low-dose linear-slit digital radiography

The purpose of this retrospective study was to intra-individually compare the image quality of computed radiography (CR) and low-dose linear-slit digital radiography (LSDR) for supine chest radiographs. A total of 90 patients (28 female, 62 male; mean age, 55.1 years) imaged with CR and LSDR within a mean time interval of 2.8 days +/- 3.0 were included in this study. Two independent readers evaluated the image quality of CR and LSDR based on modified European Guidelines for Quality Criteria for chest X-ray. The Wilcoxon test was used to analyse differences between the techniques. The overall image quality of LSDR was significantly better than the quality of CR (9.75 vs 8.16 of a maximum score of 10; p < 0.001). LSDR performed significantly better than CR for delineation of anatomical structures in the mediastinum and the retrocardiac lung (p < 0.001). CR was superior to LSDR for visually sharp delineation of the lung vessels and the thin linear structures in the lungs. We conclude that LSDR yields better image quality and may be more suitable for excluding significant pathological features of the chest in areas with high attenuation compared with CR.

Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

INTRODUCTION: We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation. METHODS: Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. RESULTS: Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. CONCLUSIONS: The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. TRIAL REGISTRATION: clinicaltrials.gov Nr. NCT00641563.

Visualization and stereological characterization of individual rat lung acini by high-resolution X-ray tomographic microscopy

The small trees of gas-exchanging pulmonary airways which are fed by the most distal purely conducting airways are called acini and represent the functional gas-exchanging units. The three-dimensional architecture of the acini has a strong influence on ventilation and particle deposition. Due to the difficulty to identify individual acini on microscopic lung sections the knowledge about the number of acini and their biological parameters like volume, surface area, and number of alveoli per acinus are limited. We developed a method to extract individual acini from lungs imaged by high-resolution synchrotron radiation based X-ray tomographic microscopy and estimated their volume, surface area and number of alveoli. Rat acini were isolated by semiautomatically closing the airways at the transition from conducting to gas-exchanging airways. We estimated a mean internal acinar volume of 1.148mm(3), a mean acinar surface area of 73.9mm(2), and a mean of 8470 alveoli per acinus. Assuming that the acini are similarly sized throughout different regions of the lung, we calculated that a rat lung contains 5470±833 acini. We conclude that our novel approach is well suited for the fast and reliable characterization of a large number of individual acini in healthy, diseased, or transgenic lungs of different species including humans.

Phylogenetic relationship of equine Actinobacillus species and distribution of RTX toxin genes among clusters

Equine Actinobacillus species were analysed phylogenetically by 16S rRNA gene (rrs) sequencing focusing on the species Actinobacillus equuli, which has recently been subdivided into the non-haemolytic A. equuli subsp. equuli and the haemolytic A. equuli subsp. haemolyticus. In parallel we determined the profile for RTX toxin genes of the sample of strains by PCR testing for the presence of the A. equuli haemolysin gene aqx, and the toxin genes apxI, apxII, apxIII and apxIV, which are known in porcine pathogens such as Actinobacillus pleuropneumoniae and Actinobacillus suis. The rrs-based phylogenetic analysis revealed two distinct subclusters containing both A. equuli subsp. equuli and A. equuli subsp. haemolyticus distributed through both subclusters with no correlation to taxonomic classification. Within one of the rrs-based subclusters containing the A. equuli subsp. equuli type strain, clustered as well the porcine Actinobacillus suis strains. This latter is known to be also phenotypically closely related to A. equuli. The toxin gene analysis revealed that all A. equuli subsp. haemolyticus strains from both rrs subclusters specifically contained the aqx gene while the A. suis strains harboured the genes apxI and apxII. The aqx gene was found to be specific for A. equuli subsp. haemolyticus, since A. equuli subsp. equuli contained no aqx nor any of the other RTX genes tested. The specificity of aqx for the haemolytic equine A. equuli and ApxI and ApxII for the porcine A. suis indicates a role of these RTX toxins in host species predilection of the two closely related species of bacterial pathogens and allows PCR based diagnostic differentiation of the two.

Emotional contagion in team sports and its impact on individual performance – an experimental study

In sport psychology research about emotional contagion in sport teams has been scarce (Reicherts & Horn, 2008). Emotional contagion is a process leading to a specific emotional state in an individual caused by the perception of another individual’s emotional expression (Hatfield, Cacioppo & Rapson, 1994). Apitzsch (2009) described emotional contagion as one reason for collapsing sport teams. The present study examined the occurrence of emotional contagion in dyads during a basketball task and the impact of a socially induced emotional state on performance. An experiment with between-subjects design was conducted. Participants (N=81, ♀=38, M=21.33 years, SD=1.45) were randomly assigned to one of two experimental conditions, by joining a confederate to compose a same gender, ad hoc team. The team was instructed to perform a basketball task as quickly as possible. The between-factor of the experimental design was the confederate’s emotional expression (positive or negative valence). The within-factor was participants’ emotional state, measured pre- and post-experimentally using PANAS (Krohne, Egloff, Kohlmann & Tausch, 1996). The basketball task was video-taped and the number of frames participants needed to complete the task was used to determine the individual performance. The confederate’s emotional expression was appraised in a significantly different manner across both experimental conditions by participants and video raters (MC). Mixed between-within subjects ANOVAs were conducted to examine the impact of the two conditions on participants’ scores on the PANAS subscales across two time periods (pre- and post-experimental). No significant interaction effects but substantial main effects for time were found on both PANAS subscales. Both groups showed an increase in positive and a reduction in negative PANAS scores across these two time periods. Nevertheless, video raters assessment of the emotional states expressed by participants was significantly different between the positive (M=3.23, SD=0.45) and negative condition (M=2.39, SD=0.53; t=7.64, p<.001, eta squared=.43). An independent-samples t-test indicated no difference in performance between conditions. Furthermore, no significant correlation between the extent of positive or negative emotional contagion and the number of frames was observed. The basketball task lead to an improvement of the emotional state of participants, independently of the condition. Even though participants PANAS scores indicated a tendency to emotional contagion, it was not statistically significant. This could be explained by the low task duration of approximately three minutes. Moreover, the performance of participants was unaffected by the experimental condition or the extent of positive or negative emotional contagion. Apitzsch, E. (2009). A case study of a collapsing handball team. In S. Jern & J. Näslund (Eds.), Dynamics within and outside the lab. Proceedings from The 6th Nordic Conference on Group and Social Psychology, May 2008, Lund, pp. 35-52. Hatfield, E., Cacioppo, J. T. & Rapson, R. L. (1994). Emotional contagion. Cambridge: University Press. Krohne, H. W., Egloff, B., Kohlmann, C.-W. & Tausch, A. (1996). Untersuchungen mit einer deutschen Version der „Positive und Negative Affect Schedule“ (PANAS). Diagnostica, 42 (2), 139-156. Reicherts, M. & Horn, A. B. (2008). Emotionen im Sport. In W. Schlicht & B. Strauss (Eds.), Enzyklopädie der Psychologie. Grundlagen der Sportpsychologie (Bd. 1) (S. 563-633). Göttingen: Hogrefe.

Illegitimate tasks associated with higher cortisol levels among male employees when subjective health is relatively low: an intra-individual analysis

Objectives Illegitimate tasks refer to tasks that do not conform to what can appropriately be expected from an employee. Violating role expectations, they constitute “identity-stressors”, as one’s professional role tends to become part of one’s identity. The current study investigated the impact of illegitimate tasks on salivary cortisol. We analyzed data on an intra-individual level, that is, by examining fluctuations in illegitimate tasks and cortisol within individuals. Furthermore, we investigated the moderating role of perceived health, expecting that illegitimate tasks evoke stronger reactions when perceived health is relatively poor. Methods Illegitimate tasks, salivary cortisol, and perceived health were assessed in each of three waves (time lag: 6 months) in a sample of 104 male employees. Data were analyzed by multilevel analysis using group mean centering. Results Controlling for social stressors, work interruptions, and emotional stability, the experience of more illegitimate tasks was associated with increased cortisol release if personal health resources were low compared to one’s mean value of perceived health. Results cannot be explained by inter-individual differences. Conclusions This is the first study showing that illegitimate tasks predict a biological indicator of stress, thus confirming and extending previous research on illegitimate tasks. The moderating role of perceived health confirms its importance as a personal resource, implying augmented vulnerability when perceived health is below its usual value. It is plausible to assume that increased stress reactions due to relatively poor health may further weaken available personal resources. Both avoiding illegitimate tasks and restoring personal health seem to be crucial.