Sten Rasmussen

A Placebo-Controlled, Double-Blind, Randomized Trial of Cyclosporine Therapy in Active Chronic Crohn's Disease

We randomly assigned 71 patients with active chronic Crohns disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohns Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohns disease and resistance to or intolerance of corticosteroids.

A Randomized, Controlled Trial of Total Knee Replacement

BACKGROUND More than 670,000 total knee replacements are performed annually in the United States; however, high-quality evidence to support the effectiveness of the procedure, as compared with nonsurgical interventions, is lacking. METHODS In this randomized, controlled trial, we enrolled 100 patients with moderate-to-severe knee osteoarthritis who were eligible for unilateral total knee replacement. Patients were randomly assigned to undergo total knee replacement followed by 12 weeks of nonsurgical treatment (total-knee-replacement group) or to receive only the 12 weeks of nonsurgical treatment (nonsurgical-treatment group), which was delivered by physiotherapists and dietitians and consisted of exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, activities of daily living, and quality of life (KOOS4); scores range from 0 (worst) to 100 (best). RESULTS A total of 95 patients completed the 12-month follow-up assessment. In the nonsurgical-treatment group, 13 patients (26%) underwent total knee replacement before the 12-month follow-up; in the total-knee-replacement group, 1 patient (2%) received only nonsurgical treatment. In the intention-to-treat analysis, the total-knee-replacement group had greater improvement in the KOOS4 score than did the nonsurgical-treatment group (32.5 vs. 16.0; adjusted mean difference, 15.8 [95% confidence interval, 10.0 to 21.5]). The total-knee-replacement group had a higher number of serious adverse events than did the nonsurgical-treatment group (24 vs. 6, P=0.005). CONCLUSIONS In patients with knee osteoarthritis who were eligible for unilateral total knee replacement, treatment with total knee replacement followed by nonsurgical treatment resulted in greater pain relief and functional improvement after 12 months than did nonsurgical treatment alone. However, total knee replacement was associated with a higher number of serious adverse events than was nonsurgical treatment, and most patients who were assigned to receive nonsurgical treatment alone did not undergo total knee replacement before the 12-month follow-up. (Funded by the Obel Family Foundation and others; MEDIC ClinicalTrials.gov number, NCT01410409.).

Shockwave therapy for chronic Achilles tendinopathy: A double-blind, randomized clinical trial of efficacy

Background and purpose Chronic Achilles tendinopathy is a painful condition and there are often unsatisfactory results with conservative treatment. Extracorporal shock-wave therapy (ESWT) has been introduced for the management of various soft tissue conditions. The objective of the study was to compare the effect of supplementing conservative treatment of chronic Achilles tendinopathy with ESWT or placebo. Patients and methods This was a randomized, double-blind, placebo-controlled trial. Patients assigned to nonoperative treatment of chronic achilles tendinopathy were randomized to receive either active ESWT or sham ESWT over 4 weeks. There were 48 patients (28 men) with a mean age of 47 (19–80) years. American Orthopaedic Foot and Ankle Society (AOFAS) score and pain were assessed before treatment, during the 4-week treatment period, and at 4, 8, and 12 weeks of follow-up. Results Both groups improved during the treatment and follow-up period. The mean AOFAS score increased from 74 (SD 12) to 81 (16) in the placebo group and from 70 (6.8) to 88 (10) in the intervention group (p = 0.05). Better results were seen in the intervention group at 8 and 12 weeks of follow-up (p = 0.01 and p = 0.04, respectively). Interpretation Extracorporal shock-wave therapy appears to be a supplement for the treatment of chronic Achilles tendinopathy.

Widespread sensitization in patients with chronic pain after revision total knee arthroplasty.

Summary Widespread sensitization is predominant in patients with pain after revision total knee arthroplasty. This is important when considering revision arthroplasty in the treatment of knee osteoarthritis. ABSTRACT Pain and sensitization are major issues in patients with osteoarthritis both before and after total knee arthroplasty (TKA) and revision TKA (re‐TKA). The aim of this study was to assess sensitization in patients with and without chronic pain after re‐TKAs. Twenty patients with chronic knee pain and 20 patients without pain after re‐TKA participated. Spreading of pain was evaluated as the number of pain sites using a region‐divided body chart. The pressure pain threshold (PPT) and pressure pain tolerance (PTT) were assessed by cuff algometry at the lower leg. Temporal summation of pain was assessed by recordings of the pain intensity on a visual analog scale (VAS) during repeated cuff pressure stimulations. Conditioning pain modulation (CPM) was recorded by experimental tonic arm pain by cuff pressure stimulation and assessment of PPTs on the knee, leg, and forearm using handheld pressure algometry. Participants with pain after re‐TKA compared to participants without pain demonstrated: (1) significantly more pain sites (P = .004), (2) decreased cuff PPTs and PTTs at the lower leg (P < .001), (3) facilitated temporal summation (P < .001), and (4) impaired CPM (P < .001). Additionally, significant correlations between knee pain intensity and cuff PPTs, temporal summation, and CPM and between total duration of knee pain and temporal summation were found (P < .05). This study demonstrated widespread sensitization in patients with pain after re‐TKA and highlighted the importance of ongoing nociceptive input for the chronification process. This has important implications for future revisions, and precautions should be taken if patients have widespread sensitization.

Intra-articular glucocorticoid, bupivacaine and morphine reduces pain, inflammatory response and convalescence after arthroscopic meniscectomy

Abstract Convalescence after arthroscopic meniscectomy is dependent on pain and the inflammatory response. The aim of the study was therefore to investigate the effect of intra‐articular bupivacaine+morphine+methylprednisolone versus bupivacaine+morphine or saline on post‐meniscectomy pain, mobilisation and convalescence. In a double‐blind randomized study 60 patients undergoing arthroscopic meniscectomy were allocated to intra‐articular saline, intra‐articular bupivacaine 150 mg+morphine 4 mg or the same dose of bupivacaine+morphine+intra‐articular methylprednisolone 40 mg. All patients were instructed to resume normal activities immediately after operation. Pain during movement and walking, leg muscle force and joint effusion, use of crutches and duration of sick leave were assessed. Combined bupivacaine and morphine significantly reduced pain, time of immobilisation and duration of convalescence. Addition of methylprednisolone further reduced pain, use of additional analgesics, joint swelling and convalescence, improved muscle function and prevented the inflammatory response (acute phase protein) (P<0.05). A multimodal analgesic and anti‐inflammatory treatment may enhance post‐arthroscopic convalescence, which depends on the trauma induced inflammatory response and pain.

Increased flexion and reduced hospital stay with continuous intraarticular morphine and ropivacaine after primary total knee replacement. Open intervention study of efficacy and safety in 154 patients

Background A single injection of bupivacaine after wound closure reduces the need for analgesics and increases flexion after total knee replacement (TKR). We have therefore studied the effect of continuous injection of morphine and ropivacaine after TKR on range of movement and length of hospital stay. Patients and methods In an open intervention study, we assigned 154 consecutive patients who had primary unilateral TKR for osteoarthrosis. The intervention was continuous intraarticular injection of morphine 20 mg/mL, 0.5 mL plus ropivacaine 2 mg/mL, 100 mL; bolus 20 mL and 2 mL/hour from 24 to 72 hours postoperatively. Group 1 (10 women and 8 men) received standard postoperative analgesics and group 2 (11 women and 7 men) also received continuous intraarticular morphine and ropivacaine as described above. Group 3 (14 women and 4 men) received double this dose (4 mL/hour) from 24 to 72 hours postoperatively. To assess the safety of the intraarticular treatment, an additional group of 100 consecutive patients was followed (group 4).Results At discharge, flexion was 70° (60–100) in group 1, 100° (70–115) in group 2 and 110° (90–130) in group 3. Hospital stay was reduced from 9 (7–11)days in group 1, to 7 (5–10) days in groups 2 and 3. Number of days elapsed until the patient was walking with crutches was reduced from 5 (3–8) to 4 (3–6) and 3 (3–9), respectively. In the intervention groups, the need for analgesics was reduced during the hospital stay. Deep infection was registered in 1 patient.Interpretation Continuous intraarticular morphine and ropivacaine reduce pain and enhance rehabilitation after total knee replacement. Before advocating this as a standard procedure, further large-scale randomized studies will be needed to assess the safety of this regimen.

Measurement of gastrointestinal pH and regional transit times in normal children

Summary: Gastrointestinal pH and regional intestinal transit times of a capsule were measured in twelve healthy children aged 8–14 years using a radiotransmitting pH-sensitive capsule. The location of the capsule was determined by fluoroscopy. pH in the stomach was 1.5, but rose to 6.4 in the duodenum (mean values). pH gradually rose in the small intestine and reached an alkaline peak value of 7.4 in the distal part. pH dropped to 5.9 in the cecum but rose to 6.5 in the rectum. Median gastric residence time of the capsule was 1.1 h. Small intestinal transit time was 7.5 h, and colonic transit time was 17.2 h. pH profile and intestinal transit times found in the present study are almost identical to values found in studies on healthy adults. It is therefore concluded that the release pattern of pH-dependent sustained-release tablets in children is likely to be equal to that of adults.

Lower Mechanical Pressure Pain Thresholds in Female Adolescents With Patellofemoral Pain Syndrome

STUDY DESIGN Cross-sectional study. OBJECTIVES To compare pressure pain thresholds (PPTs) between adolescent females diagnosed with patellofemoral pain syndrome (PFPS) and gender- and age-matched controls without musculoskeletal pain. BACKGROUND PFPS is prevalent among adolescents and may be associated with reduced PPT both locally and remotely from the site of reported pain. This may indicate altered central processing of nociceptive information. However, this has never been investigated in adolescents with PFPS. METHODS Adolescents with PFPS and a comparison group without musculoskeletal pain were recruited from a population-based cohort of students from 4 upper secondary schools, aged 15 to 19 years. All 2846 students within that age range were invited to answer an online questionnaire regarding musculoskeletal pain. The students who reported knee pain were contacted by telephone and offered a clinical examination by an experienced rheumatologist, who made a diagnosis. PPTs were measured at 4 sites around the knee and 1 site on the tibialis anterior in the 57 female adolescents diagnosed with PFPS and in 22 female adolescents without musculoskeletal pain. RESULTS Adolescents with PFPS, compared to controls, had significantly lower PPTs (26%-37% [100-178 kPa]) at each of the 4 sites around the knee, suggesting localized hyperalgesia. On the tibialis anterior, adolescents with PFPS had a 33% (159 kPa) lower PPT (distal hyperalgesia) compared with controls. CONCLUSION These findings suggest that adolescent females with PFPS have localized and distal hyperalgesia. These findings may have implications for treating PFPS, as both peripheral and central mechanisms may be driving the pain. Registered at clinicaltrials.gov (NCT01438762).

High prevalence of daily and multi-site pain – a cross-sectional population-based study among 3000 Danish adolescents

BackgroundDaily pain and multi-site pain are both associated with reduction in work ability and health-related quality of life (HRQoL) among adults. However, no population-based studies have yet investigated the prevalence of daily and multi-site pain among adolescents and how these are associated with respondent characteristics. The purpose of this study was to investigate the prevalence of self-reported daily and multi-site pain among adolescents aged 12–19 years and associations of almost daily pain and multi-site pain with respondent characteristics (sex, age, body mass index, HRQoL and sports participation).MethodsA population-based cross-sectional study was conducted among 4,007 adolescents aged 12–19 years in Denmark. Adolescents answered an online questionnaire during physical education lessons. The questionnaire contained a mannequin divided into 12 regions on which the respondents indicated their current pain sites and pain frequency (rarely, monthly, weekly, more than once per week, almost daily pain), characteristics, sports participation and HRQoL measured by the EuroQoL 5D. Multivariate regression was used to calculate the odds ratio for the association between almost daily pain, multi-site pain and respondent characteristics.ResultsThe response rate was 73.7%. A total of 2,953 adolescents (62% females) answered the questionnaire. 33.3% reported multi-site pain (pain in >1 region) while 19.8% reported almost daily pain. 61% reported current pain in at least one region with knee and back pain being the most common sites. Female sex (OR: 1.35-1.44) and a high level of sports participation (OR: 1.51-2.09) were associated with increased odds of having almost daily pain and multi-site pain. Better EQ-5D score was associated with decreased odds of having almost daily pain or multi-site pain (OR: 0.92-0.94).ConclusionIn this population-based cohort of school-attending Danish adolescents, nearly two out of three reported current pain and, on average, one out of three reported pain in more than one body region. Female sex, and high level of sports participation were associated with increased odds of having almost daily pain and multi-site pain. The study highlights an important health issue that calls for investigations to improve our understanding of adolescent pain and our capacity to prevent and treat this condition.

Foot pronation is not associated with increased injury risk in novice runners wearing a neutral shoe: a 1-year prospective cohort study

Objective To investigate if running distance to first running-related injury varies between foot postures in novice runners wearing neutral shoes. Design A 1-year epidemiological observational prospective cohort study. Setting Denmark. Participants A total of 927 novice runners equivalent to 1854 feet were included. At baseline, foot posture on each foot was evaluated using the foot-posture index and categorised into highly supinated (n=53), supinated (n=369), neutral (n=1292), pronated (n=122) or highly pronated (n=18). Participants then had to start running in a neutral running shoe and to use global positioning system watch to quantify the running distance in every training session. Main outcome measure A running-related injury was defined as any musculoskeletal complaint of the lower extremity or back caused by running, which restricted the amount of running for at least 1 week. Results During 1 year of follow-up, the 1854 feet included in the analyses ran a total of 326 803 km until injury or censoring. A total of 252 participants sustained a running-related injury. Of these, 63 were bilateral injuries. Compared with a neutral foot posture, no significant body mass index-adjusted cumulative risk differences (RD) were found after 250 km of running for highly supinated feet (RD=11.0% (−10% to 32.1%), p=0.30), supinated feet (RD=−1.4% (−8.4% to 5.5%), p=0.69), pronated feet (RD=−8.1% (−17.6% to 1.3%), p=0.09) and highly pronated feet (RD=9.8% (−19.3% to 38.8%), p=0.51). In addition, the incidence-rate difference/1000 km of running, revealed that pronators had a significantly lower number of injuries/1000 km of running of −0.37 (−0.03 to −0.70), p=0.03 than neutrals. Conclusions The results of the present study contradict the widespread belief that moderate foot pronation is associated with an increased risk of injury among novice runners taking up running in a neutral running shoe. More work is needed to ascertain if highly pronated feet face a higher risk of injury than neutral feet.