Cost-effectiveness of 12 weeks of supervised treatment compared to written advice in patients with knee osteoarthritis: a secondary analysis of the 2-year outcome from a randomized trial.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Total knee replacement and non-surgical treatment of knee osteoarthritis: 2-year outcome from two parallel randomized controlled trials.

OBJECTIVES: To compare 2-year outcomes of total knee replacement (TKR) followed by non-surgical treatment to that of non-surgical treatment alone and outcomes of the same non-surgical treatment to that of written advice. DESIGN: In two randomized trials, 200 (mean age 66) adults with moderate to severe knee osteoarthritis (OA), 100 eligible for TKR and 100 not eligible for TKR, were randomized to TKR followed by non-surgical treatment, non-surgical treatment alone, or written advice. Non-surgical treatment consisted of 12 weeks of supervised exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the mean score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS: Patients randomized to TKR had greater improvements than patients randomized to non-surgical treatment alone (difference of 18.3 points (95% CI; 11.3 to 25.3)), who in turn improved more than patients randomized to written advice (difference of 7.0 points (95% CI; 0.4 to 13.5)). Among patients eligible for TKR, 16 (32%) from the non-surgical group underwent TKR during 2 years and among those initially ineligible, seven patients (14%) from the non-surgical group and ten (20%) from the written advice group underwent TKR. CONCLUSIONS: TKR followed by non-surgical treatment is more effective on pain and function than non-surgical treatment alone, which in turn is more effective than written advice. Two out of three patients with moderate to severe knee OA eligible for TKR delayed surgery for at least 2 years following non-surgical treatment. TRIAL REGISTRATION: ClinicalTrials.gov numbers NCT01410409 and NCT01535001.

No beneficial effect of Polidocanol treatment in Achilles tendinopathy: a randomised controlled trial.

PURPOSE: Polidocanol injections have been used to treat chronic Achilles tendinopathy in clinical settings, but the few studies published show inconsistent results. The aim of this study was to evaluate the mid-term effect of Polidocanol in patients with chronic Achilles tendinopathy. It was hypothesised that patients treated with Polidocanol would have significant improvements in the outcome measures investigated compared to patients treated with a placebo treatment at mid-term follow-up. METHODS: This randomised controlled trial included forty-eight patients aged 32-77 years with a history of Achilles tendinopathy for at least 3 months and with neovascularisation demonstrated by ultrasonography was included. A minimum of 3 months of eccentric exercise treatment was required before participating. The patients were allocated to a maximum of two injection of either Polidocanol or Lidocaine (placebo). The primary outcome measure was pain during walking reported on a visual analogue scale. Secondary outcome measures were Foot and Ankle Outcome Score (FAOS), patient satisfaction with treatment and, shortly after inclusion, the Victorian Institute of Sports Assessment-Achilles questionnaire (VISA-A) was also included. Follow-up examinations were performed after 3 and 6 months. RESULTS: Pain during walking decreased during the 6-month follow-up period, but no significant differences were seen between the two groups. The same tendency was seen for FAOS and VISA-A in which both groups showed an improvement at 3- and 6-month follow-up, but no mid-term differences between the groups were seen. An equal number of patients in the two groups were satisfied with the treatment at follow-up. CONCLUSIONS: The results indicate that Polidocanol is a safe treatment, but the mid-term effects are the same as a placebo treatment. This further questions the use of Polidocanol in the treatment of chronic Achilles tendinopathy. LEVEL OF EVIDENCE: I.

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study.

OBJECTIVES: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA). METHODS: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R2). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3). RESULTS: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R2-value obtained in Model 1 was R2 = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R2 = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R2 = 0.71. CONCLUSION: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA.

The efficacy of non-surgical treatment on pain and sensitization in patients with knee osteoarthritis: a pre-defined ancillary analysis from a randomized controlled trial.

OBJECTIVE: To report the efficacy of a 3-month treatment program consisting of neuromuscular exercise, education, diet, insoles and pain medication (MEDIC-treatment) compared to usual care (two leaflets with information and treatment advice) in reducing pain-related measures and sensitization in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). METHOD: A pre-defined ancillary analysis of the results at 3 months of a randomized controlled trial (RCT) of 100 patients randomized to MEDIC-treatment or usual care. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01535001). Outcomes were sensitization assessed at the knee, the lower leg and forearm using a handheld algometer, peak pain intensity in the previous 24 h, pain intensity after 30 min of walking, pain location and pattern, spreading of pain (a region-divided body chart) and the usage of pain medication. RESULTS: The MEDIC group had larger improvements from baseline to 3 months in peak pain intensity (P = 0.02) and pain after 30 min of walking (P < 0.001) and in the number of body sites with pain (P = 0.04). There was no difference in the change in sensitization from baseline to 3 months between groups (P = 0.87), but sensitization decreased in both groups (P < 0.001). CONCLUSION: A non-surgical treatment program is more efficacious in reducing pain-related measures than usual care, while both are equally efficacious in reducing sensitization, indicating that mechanisms other than pain sensitization contribute to the perceived pain. The patients did not have severe symptomatic knee OA and hence pain sensitization may not yet have developed into a clinically relevant parameter or subgroups with less sensitization may exist.

The efficacy of 12 weeks non-surgical treatment for patients not eligible for total knee replacement: a randomized controlled trial with 1-year follow-up.

OBJECTIVE: To compare the efficacy of a 12-week non-surgical treatment program with usual care in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). METHOD: This two-arm parallel group assessor-blinded randomized controlled trial (RCT) included 100 adults from secondary care with knee OA, confirmed by radiography (Kellgren-Lawrence grade ≥1), but not eligible for a TKR. The 12-week non-surgical treatment program consisted of individualized progressed neuromuscular exercise, patient education, insoles, dietary advice and prescription of pain medication if indicated, while usual care comprised two leaflets with information and advice on knee OA and recommended treatments. The primary outcome was the change from baseline to 12 months in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the KOOS subscales of pain, symptoms, activities of daily living (ADL), and quality of life (QOL). RESULTS: 91% of the patients completed the 12 months follow-up on the primary outcome. Compared with usual care, patients undergoing the treatment program improved more in KOOS4 (adjusted mean difference (95% CI) of 9.6 (4.4-14.8)) with no serious treatment-related adverse events (AE). The number needed to treat (NNT), defined as the number of patients needed to treat for one person to improve 15% was 7.2. Secondary outcomes supported the primary findings. CONCLUSION: In patients with mostly moderate to severe knee OA not eligible for TKR, a 12-week individualized, non-surgical treatment program is more efficacious at 12 months compared with usual care and has few treatment-related AE. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01535001).

Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover.

OBJECTIVES: Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive CRP (hsCRP)) and/or matrix metalloproteinase (MMP) derived inflammation (CRPM) and investigate the subpopulations' association with biomarkers of collagen degradation and Kellgren-Lawrence (KL) score. METHODS: hsCRP, CRPM and MMP-degraded type I, II and III collagen (type I collagen degraded by MMP (C1M), type II collagen degraded by MMP (C2M) and type III collagen degraded by MMP (C3M)) were quantified by enzyme linked immunosorbent assays (ELISA) in serum of 342 patients with symptomatic knee OA of which 60 underwent total knee replacement (TKR). KL was obtained. Patients were divided into quartiles by hsCRP and CRPM levels, where Q1 and Q4 were low or high in both. The biomarker levels of healthy adults provided in the ELISA kits were used as reference level. RESULTS: hsCRP was elevated in TKR (5.9(3.6-8.2 95% confidence interval (CI)) µg/mL) compared to reference level (3 µg/mL), while CRPM was highly elevated with OA independent of KL (10-14 ng/mL) compared to reference level (5 ng/mL). Q4 had higher KL than Q1 (P < 0.001), Q2 (P = 0.017) and Q3 (P < 0.001). C1M, C2M and C3M were lowest in Q1. C1M was elevated in Q3 compared to Q2 (P < 0.001), whereas C3M was lower (P = 0.019). CONCLUSION: A bigger proportion of patients were elevated in CRPM compared to hsCRP, indicating MMP-derived inflammation as a component of OA. Moreover, the levels of MMP-degraded collagens differed between the subgroups segregated by inflammation, indicating distinctively different subpopulation selected by inflammation.

The transverse forefoot arch demonstrated by a novel X-ray projection.

OBJECTIVE: Metatarsalgia is often treated by metatarsal osteotomy. Exact knowledge of the normal anatomy of the forefoot is essential for pre-operative planning. The objective of this study was to investigate the forefoot arch during maximal loading in a randomly selected population sample. METHODS: Two hundred subjects randomly selected from a municipality representative of Denmark were invited to interview and forefoot X-ray examination, including a novel horizontal X-ray projection by which the height of each metatarsal from the floor can be measured under maximal loading. RESULTS: One hundred and thirty-four subjects (79%) presented themselves for interview and X-ray examination. The study group was representative of the randomly selected population sample in terms of age, sex and incidence of metatarsalgia. The study verified that the interrelated geometry of the metatarsal heads in the AP plane corresponds to a parabola as suggested previously (Le Lièvre's parabola). Also in the horizontal plane, the metatarsal heads generally form an arch, the transverse forefoot arch (TFA). Mean height was 3.91mm (S.E.=0.10). The individual height of the TFA varied from -1 to 10mm and was dependent on the width of the forefoot. The relative height of the arch (arch height divided by forefoot width) was independent of age and sex. A non-significant tendency towards a lower arch among subjects with metatarsalgia was observed. CONCLUSION: This population study demonstrated that the metatarsal heads constitute arches in both planes (Le Lièvre's parabola in the AP plane and the transverse forefoot arch in the horizontal plane). This knowledge is essential for pre-operative planning in metatarsal osteotomy for metatarsalgia. Formulae for calculating the individual location of each metatarsal head were obtained.

Increased postural stiffness during challenging postural tasks in patients with knee osteoarthritis with high pain sensitization.

BACKGROUND: Postural stability is affected in knee osteoarthritis patients who present with pain but the link to pain sensitization is unclear. METHODS: Patients with knee osteoarthritis completed the Knee Injury and Osteoarthritis Outcome Score and pressure pain thresholds were assessed bilaterally at the knee, lower leg and forearm prior to standing quietly (1 min) on a force platform in four conditions: Firm surface with open eyes, firm surface with closed eyes, soft surface with open eyes, and soft surface with closed eyes. Pain intensity during standing was assessed via numerical rating scale. Postural stability was assessed by the range, velocity, and standard deviation of the Center of Pressure (CoP) extracted from the force platform. The means of three repeated measures per standing condition were analysed. High-sensitization and low-sensitization groups were defined based on bilateral pressure pain thresholds from leg and arm. FINDINGS: Fifty-six patients were included. Compared with the low-sensitization group, the high-sensitization group demonstrated 1) smaller pressure pain thresholds at the knee (P < 0.05) although the Knee Injury and Osteoarthritis Outcome Score and pain intensity were not significantly different between groups, and 2) smaller range of the CoP in the anterior-posterior direction during the soft surface with closed eyes condition (P < 0.05). INTERPRETATION: Smaller CoP range suggest that patients with more widespread pain sensitivity have increased postural stiffness compared with the low-sensitization group. The greater stiffness found in high-sensitization patients under sensory restrictions (closed eyes and reduced proprioception) might relate to restricted integration of sensory information due to widespread pain sensitization.

Can DXA predict fractures in renal transplant patients?

Renal transplant patients have a high prevalence of osteopenia, osteoporosis and fractures. The aim of the study was to investigate whether dual-energy x-ray absorptiometry (DXA) is of value to predict fractures. In 1995-2007, 238 renal transplant patients underwent 670 DXA investigations. Osteopenia (46.0%), osteoporosis (13.9%) and absolute bone mineral density (BMD) (median 0.9, range 0.4-2.0 g/cm(2)) in the hip region were used to evaluate fracture risk. Data on fractures were collected at the occasion of each DXA, and a questionnaire was filled in by 191 patients at regular outpatient visits. Reported fractures were verified by consultation of medical records. In all, 46 patients had 53 fractures. Cumulative hazard of fracture was significantly different among normal BMD, osteopenia and osteoporosis in the hip (p < 0.0001). A Cox proportional hazard analysis also including age, gender and diabetic nephropathy showed significantly increased fracture risk for osteoporosis (3.5 times, CI 1.8-6.4, p = 0.0001) as well as for osteopenia (2.7 times, 1.6-4.6, p = 0.0003). A significantly increased risk was also found with absolute BMD estimates below the median. Osteopenia and an absolute bone density below 0.9 g/cm(2) in the hip region confer an increased risk of fracture.

Pain and sensitization after total knee replacement or nonsurgical treatment in patients with knee osteoarthritis: Identifying potential predictors of outcome at 12 months.

BACKGROUND: This study is a secondary analysis of 12-month follow-ups from two parallel, randomized controlled trials (RCT) in painful knee osteoarthritis patients. RCT1: Total knee replacement (TKR) followed by nonsurgical treatment compared with nonsurgical treatment. RCT2: Nonsurgical treatment compared with usual care. The aims were to investigate (1) possible predictors of treatment outcome after TKR and nonsurgical interventions at 12 months, (2) associations between pain intensity and pressure pain thresholds (PPTs) (pain sensitization) at baseline and after 12 months and (3) possible gender differences. METHOD: Each RCT included 100 patients. Pain intensities, PPTs and number of painful sites were assessed at baseline and after 12 months. RESULTS: In all groups, pain improved and pain sensitization decreased. In RCT1, the TKR group had the greatest improvements in pain. In RCT2 the nonsurgical group had the greatest improvement, with no between-group differences in PPTs. Lower PPTs at baseline predicted higher pain after TKR. Baseline pain intensity and PPT levels were associated with the number of painful sites. Subjects with the highest pain and lowest PPTs at baseline showed the largest relative improvement in pain and sensitization but were still experiencing highest absolute pain and lowest PPTs after 12 months (combined cohorts). CONCLUSION: Low PPTs at baseline predicted worse pain outcome after TKR, but did not predict outcome after nonsurgical interventions. The number of painful sites was weakly associated with pain and PPTs, and the higher pain/lower PPTs, the higher pain/lower PPTs at 12 months with females showing the lowest PPT values. SIGNIFICANCE: Human experimental pain assessment was used to assess the degree of pain sensitization in patients with painful knee osteoarthritis. High sensitization before TKR predicted worse outcome. Outcome after nonsurgical interventions could not be predicted.

Cardiovascular effects of epinephrine during rewarming from hypothermia in an intact animal model.

Rewarming from accidental hypothermia is often complicated by "rewarming shock," characterized by low cardiac output (CO) and a sudden fall in peripheral arterial pressure. In this study, we tested whether epinephrine (Epi) is able to prevent rewarming shock when given intravenously during rewarming from experimental hypothermia in doses tested to elevate CO and induce vasodilation, or lack of vasodilation, during normothermia. A rat model designed for circulatory studies during experimental hypothermia and rewarming was used. A total of six groups of animals were used: normothermic groups 1, 2, and 3 for dose-finding studies, and hypothermic groups 4, 5, and 6. At 20 and 24 degrees C during rewarming, group 4 (low-dose Epi) and group 5 (high-dose Epi) received bolus injections of 0.1 and 1.0 microg Epi, respectively. At 28 degrees C, Epi infusion was started in groups 4 and 5 with 0.125 and 1.25 microg/min, respectively. Group 6 served as saline control. After rewarming, both CO and stroke volume were restored in group 4, in contrast to groups 5 and 6, in which both CO and stroke volume remained significantly reduced (30%). Total peripheral resistance was significantly higher in group 5 during rewarming from 24 to 34 degrees C, compared with groups 4 and 6. This study shows that, in contrast to normothermic conditions, Epi infused during hypothermia induces vasoconstriction rather than vasodilation combined with lack of CO elevation. The apparent dissociation between myocardial and vascular responses to Epi at low temperatures may be related to hypothermia-induced myocardial failure and changes in temperature-dependent adrenoreceptor affinity.

The effects of total knee replacement and non-surgical treatment on pain sensitization and clinical pain.

BACKGROUND: The objective was to compare the effect of total knee replacement (TKR) followed by a 3-month non-surgical treatment with the non-surgical treatment alone in reducing pain sensitization and other pain-related measures in patients with knee osteoarthritis. METHODS: One hundred patients were randomized to (1) TKR followed by a non-surgical treatment of neuromuscular exercise, education, diet, insoles and pain medication or (2) the non-surgical treatment alone. Outcomes assessed at baseline and after 3 months were as follows: (1) pain sensitization assessed as pressure-pain thresholds (PPTs) at the knee (localized sensitization) and the lower leg (spreading sensitization), (2) peak pain intensity during the previous 24 h, (3) pain intensity after 30 min of walking, (4) pain location and pattern, (5) spreading of pain on a region-divided body chart and (6) the usage of pain medication. RESULTS: There was a statistical significant mean difference (95% CI) in change in PPTs from baseline to 3 months between groups in the crude analysis of 71 kPa (21-121) and of 75 kPa (33-117) when adjusting for baseline PPT, age, gender and body mass index, favouring the group having TKR. There were no significant between-group differences in change in the pain-related measures from baseline to 3 months (p = 0.15-0.27). Both groups improved in most of the pain-related measures (p < 0.05). CONCLUSIONS: At 3 months, TKR followed by non-surgical treatment is more effective in reducing localized and spreading pain sensitization than non-surgical treatment alone. Both treatments are equally efficacious in reducing the pain-related measures of this study. WHAT DOES THIS STUDY ADD?: Knee replacement followed by non-surgical treatment is more effective in reducing pain sensitization, but not other pain-related measures, as compared to non-surgical treatment alone at 3 months.

A mechanism-based pain sensitivity index to characterize knee osteoarthritis patients with different disease stages and pain levels.

BACKGROUND: In a cohort of well-characterized patients with different degrees of knee osteoarthritis (OA) and pain, the aims were to utilize mechanism-based quantitative sensory testing (QST) to (1) characterize subgroups of patients; (2) analyse the associations between clinical characteristics and QST; and (3) develop and apply a QST-based knee OA composite pain sensitivity index for patient classification. METHODS: Two hundred seventeen OA pain patients and 64 controls were included. Kellgren and Lawrence (KL) grading scores were obtained, and pressure pain thresholds (PPTs), temporal summation of pain to repeated painful pressure stimulation and conditioning pain modulation (CPM) were assessed. Associations between pain score/area/duration, radiological findings and QST-related parameters were analysed. A pain sensitivity index was developed and applied based on PPT, temporal summation and CPM. z-Score, as statistical tool, was calculated for statistically comparing the pain index of a single patient with a healthy control group. RESULTS: High knee pain associated with low KL grade showed particular signs of pain sensitization. Patients showed significant associations between clinical knee pain intensity/duration and lowering of knee PPTs (p < 0.01), facilitation of temporal summation (p < 0.01), reduction of CPM function (p < 0.01) and high pain sensitivity index (p < 0.01). The index classified 27-38% of the OA patients and 3% of the controls as highly sensitive with no association to KL. The index increased for high knee pain intensities and long pain duration. CONCLUSIONS: Radiological scores, contrary to clinical pain intensity/duration, were poorly associated with QST parameters. The pain sensitivity index could classify OA patients with different degrees of OA and pain.

Fall-off in immunity following diphtheria revaccination--an 8 year follow-up study.

Diphtheria may occur even among previously vaccinated persons and knowledge of the duration of immunity is of crucial importance when designing effective vaccination programmes. In a follow-up study of 42 representative probands revaccinated 8 years previously, a continuous fall-off in antitoxic immunity was demonstrated. 98% were still protected (antitoxin concentration > 0.01 IU/ml). From the distribution of titres in the group the individual risk of susceptibility 8 years after revaccination was calculated to be 0.8/1000 (0.2-2.9/1000, 95% confidence limits). Thus, repeated revaccinations are required to secure continuous protection. The fall-off pattern for diphtheria antitoxin was approximately the same as for tetanus antitoxin. Peak values following revaccination are decisive for the duration of immunity. As peak values following vaccination depend on naturally acquired immunity and consequently decrease as indigenous diphtheria in a population disappears, highly potent vaccines are required to secure long-term immunity following diphtheria revaccination. The effects of dose and adjuvant are discussed.

The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.

Pyridoxine and folic acid supplementation in dialysis patients is a matter of debate. This study was performed to estimate the effects of pharmacologic doses of these vitamins on serum lipid and plasma homocysteine concentrations, which are known to be high in dialysis patients. Both hemodialysis and continuous ambulatory peritoneal dialysis patients were included in the study. Pyridoxine supplementation had a mild but significant cholesterol-lowering effect (7%). Folic acid supplementation significantly lowered plasma homocysteine concentrations by a mean of 30%. There was a strong, inverse correlation between blood folate and plasma homocysteine concentrations. These results indicate that daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial effect on the cardiovascular risk profile in dialysis patients.

Altered timing of hamstring muscle action in anterior cruciate ligament deficient patients.

Recent studies indicate that the hamstrings are essential antagonists in ACL deficient patients. In order to evaluate muscle coordination under physiologic conditions, nine patients with arthroscopically verified total ACL ruptures were compared with nine control volunteers. This comparison was made from electromyograms of the thigh muscles and heel contact recordings made while walking on a treadmill. While walking on a horizontal level, the patient's muscle activity did not differ from controls, but when the knee load was increased by walking uphill, the hamstring muscles in patients were activated significantly earlier than among controls. It is proposed that an altered muscle coordination is probably essential in ACL deficient patients to secure knee stability. This study suggests a new approach to investigate the coordination of muscles under physiologic conditions in ACL deficient patients, and may guide rehabilitation programs in the future.

Clinical and physiological effects of a new, less toxic and less acidic fluid for peritoneal dialysis.

OBJECTIVE: To report our first clinical experience with a new continuous ambulatory peritoneal dialysis (CAPD) fluid (PD-Bio), which is nearly devoid of glucose degradation products and has a higher pH (6.3) than conventional peritoneal dialysis (PD) solutions, and to discuss in general terms some acute and long-term effects of conventional acidic solutions containing glucose degradation products. DESIGN: 1) Pilot study on 4 patients investigated using a modified peritoneal equilibration test (PET) and cytobiology parameters. 2) Computer simulation study, assuming that conventional acidic solutions cause vasodilatation and recruitment of capillary surface area initially (during 0-60 minutes) in a PD dwell. PATIENTS: Four stable CAPD patients were chosen in an open cross-over study. After a period of three months using conventional PD fluid, the patients were switched to three months on the new PD fluid. RESULTS: Cancer antigen 125 increased significantly, and patients with discomfort/infusion pain during the control period improved during the period with the new fluid. No significant changes were observed in mass-transfer coefficients or drained volumes with the new solution. PH in the effluent dialysis was, however, higher for PD-Bio at all times during a two-hour dwell. In the computer simulation study, a less acidic solution caused an initially lower rate of glucose dissipation and improved ultrafiltration (UF) after a four-hour dwell, as compared to a conventional PD solution. CONCLUSIONS: A new, differently produced, less toxic and less acidic PD fluid (PD-Bio) seems to be better tolerated than a conventional acidic solution with respect to discomfort/infusion pain. Theoretically, neutralized solutions should show slightly improved UF profiles over conventional acidic solutions, according to the computer simulation analysis. Furthermore, it is speculated that a neutral, less acidic, less toxic fluid would cause less interstitial-mesothelial alterations and less impairment of UF capacity than conventional solutions during long-term CAPD.

Subcutaneous epoetin beta in renal anemia: an open multicenter dose titration study of patients on continuous peritoneal dialysis.

OBJECTIVE: To establish dose requirements (target hemoglobin > 100 g/L) and safety of subcutaneously administered epoetin beta. DESIGN: Open multicenter study. PATIENTS: Forty-five anemic patients (21 female, 24 male; mean age 55 years; range 20-79 years) who had been on continuous peritoneal dialysis for 1-157 months (mean 24 months). Thirty patients required blood transfusions during the year prior to the study. Mean hemoglobin concentration pretreatment was 75 g/L (range 57-89 g/L). INTERVENTION: After a pretreatment period of two weeks, 60 IU kg-1 week-1 divided into three weekly doses of epoetin beta was administered subcutaneously. The dose was increased by 60 IU kg-1 week-1 after ten weeks, and when necessary, every fourth week in patients with hemoglobin levels below 100 g/L. MAIN OUTCOME MEASURES: Hemoglobin concentration. Analysis of factors affecting the response to epoetin beta. Safety of epoetin beta. RESULTS: Thirty-eight of the 45 patients completed six months and 21 patients completed one year in the study. Twenty-six patients reached hemoglobin 100 g/L within six months and 8 patients did later on. The mean hemoglobin concentration after three months was 93 g/L (range 64-144 g/L) and after six months was 99 g/L (range 59-130 g/L; mean epoetin beta dose 122 IU kg-1 week-1). During the second six-month period of the study, hemoglobin levels were stable in most patients. After one year, the mean hemoglobin was 110 g/L (range 84-153 g/L) and the mean epoetin beta dose was 107 IU kg-1 week-1. Prolonged correction time and impaired response to epoetin were observed in patients with infections or hemorrhages and in patients with low hemoglobin concentration before starting epoetin treatment. Iron deficiency was controlled by iron supplementation, either orally or, in 10 patients, intravenously. Increased blood pressure, requiring intensified antihypertensive treatment, was observed in 13 patients. CONCLUSIONS: Continuous peritoneal dialysis patients with moderate anemia (Hb 75-90 g/L) and without complicating disorders can be managed with subcutaneous doses of epoetin < 120 IU kg-1 week-1. The epoetin beta dose should be adjusted after the first month of treatment since most patients required higher doses than the initial 60 IU kg-1 week-1.