Citations

Background Osteochondritis dissecans lesions of the knee in adult patients frequently require surgical intervention. However, the ideal method of osteochondral fragment fixation remains uncertain. Purpose This study was undertaken to determine the clinical, functional, and radiographic outcomes of bioabsorbable fixation for unstable osteochondritis dissecans lesions involving the femoral condyles of the knee in skeletally mature patients. Study Design Case series; Level of evidence, 4. Methods Skeletally mature patients with an unstable osteochondritis dissecans lesion of the femoral condyle (Ewing and Voto stages II-IV) treated with bioabsorbable internal fixation and minimum 1-year follow-up were included in this retrospective study cohort. Pre- and postoperative radiographs were reviewed and postoperative Lysholm and International Knee Documentation Committee (IKDC) scores were documented. Results A total of 21 knees in 21 patients satisfied the inclusion criteria, and 3 patients were lost to follow-up. The remaining 18 patients were evaluated at a mean of 59 months after surgery (range, 12-154 months). The 14 male and 4 female patients had a mean age of 19 years at the time of surgery (range, 14-39 years). Ewing and Voto classification included 8 stage II lesions, 9 stage III lesions, and 1 stage IV lesion. Fragment fixation methods included bioabsorbable nails (11), pins (3), darts (2), screws (1), and combined screws and darts (1). Mean postoperative Lysholm and IKDC scores were 85 and 82, respectively. Fragment union occurred in 12 knees (67%); the remaining 6 knees (33%) required removal of the loose fragment. Of the 11 patients treated with bioabsorbable nails, 2 (18%) required reoperation for nail back-out. Conclusion The authors recommend caution when using bioabsorbable fixation for osteochondritis dissecans lesions in skeletally mature patients because of the low rate of clinical healing and high complication rate. Failure with unthreaded fixation devices may be caused by inadequate compression and not necessarily be related to bioabsorbability.

Background A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. Purpose We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. Methods A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Results Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (<35% actual/predicted accrual rate) were consistently closed due to insufficient accrual. Limitations This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Conclusion Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining accrual benchmarks for early trial termination or redesign is feasible, but better accrual prediction methods are critically needed. Future studies should focus on identifying trial factors that allow more accurate accrual predictions and strategies that can salvage open trials experiencing slow accrual. Clinical Trials 2010; 7: 312—321. http://ctj.sagepub.com

With continued growth of the elderly population and improvements in cancer therapies, the number of patients with symptomatic spinal metastases is likely to increase, and this is a condition that commonly leads to debilitating neurological dysfunction and pain. Advancements in surgical techniques of resection and spinal reconstruction, improvements in clinical outcomes following various treatment modalities, generally increased overall survival in patients with metastatic spine disease, and a recent randomized trial by Patchell and colleagues demonstrating the superiority of a combined surgical/radiotherapeutic approach over a radiotherapy-only strategy have led many to suggest increasingly aggressive interventions for patients with such lesions. Optimal management of spinal metastases encompasses numerous medical specialties, including neurosurgery, orthopedic surgery, medical and radiation oncology, radiology, and rehabilitation medicine. In this review, the clinical presentation, diagnosis, and management of spinal metastatic disease are discussed. Ultimately, the goal of treatment in patients with spinal metastases remains palliative, and clinical judgment is required to select the appropriate patients for surgical intervention.

This study was performed to review the safety and outcome of total shoulder replacements in patients who are ≥ 80 years of age. A total of 50 total shoulder replacements in 44 patients at a mean age of 82 years (80 to 89) were studied. Their health and shoulder status, the operation and post-operative course were analysed, including pain, movement, patient satisfaction, medical and surgical complications, radiographs, the need for revision surgery, and implant and patient survival. A total of 27 patients had an ASA classification of III or IV and medical abnormalities were common. Of the 13 shoulders with bony deficiency of the glenoid, nine required grafting. The duration of hospital stay was prolonged and blood transfusions were common. There were no peri-operative deaths. The mean follow-up was for 5.5 years (2 to 12). Pain was significantly reduced (p < 0.001) and movement improved in active elevation and both external and internal rotation (p < 0.001). Using the Neer scale for assessing outcome, 40 (80%) shoulders had an excellent or satisfactory result. There were medical or surgical complications in 17 cases. Four shoulders developed radiological evidence of loosened glenoid components, and three of these had a poor outcome. Three other shoulders required revision, two for instability. By the time of this review 39 of the patients had died from unrelated causes at a mean of 7.5 years (0.8 to 16.4) after surgery. Total shoulder replacement is a relatively effective treatment in this elderly group of patients. However, there is a requirement for more intense patient care in the peri-operative period, and non-fatal medical or surgical complications are common. Most of these elderly patients will have a comfortable functional shoulder for the rest of their lives.

Background: Association of the HLA-DRB1*1501 allele with multiple sclerosis is well established, but its association with neuromyelitis optica has only been evaluated in small populations. Methods: We performed a case-control genetic association study to evaluate the association of HLA-DRB1*1501 with neuromyelitis optica. The single nucleotide polymorphism rs3135388, which tags HLA-DRB1*1501, was genotyped in 164 patients with neuromyelitis optica, 220 patients with multiple sclerosis and 959 controls matched for age, gender and ethnicity. Genotyping for rs3135388 was performed by Taqman-based 5' nuclease assay. Results: Rs3135388*A was positively associated with multiple sclerosis (OR = 3.93; 95% CI = 2.58—5.97, p = 1.18 × 10 -09 ) but negatively associated with NMO (OR = 0.57; 95% CI = 0.36—0.91, p = 0.01). Conclusions: Multiple sclerosis and neuromyelitis optica differ in their associations with DRB1*1501.

BACKGROUND Prucalopride (R093877) is a selective and specific 5HT 4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro. AIMS To evaluate the effects of prucalopride on gastrointestinal and colonic transit. METHODS A validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0.5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48 hours. RESULTS There were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p<0.05) and proximal colonic emptying t 1/2 (p<0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0.12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects. CONCLUSION Prucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation.

Background The pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood. Aims To compare gastric motor and sensory functions in Helicobacter pylori positive or negative patients with non-ulcer dyspepsia. Patients Seventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls. Methods The following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI). Results Gastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated to H pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent among H pylori positive patients (4/5 H pylori positive versus 4/12 H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI. Conclusion Impaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.

Background —Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT 3 ) antagonist restores postprandial colonic tone towards normal in carcinoid patients. Aims —To evaluate the medium term effects of an oral 5HT 3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. Methods —In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. Results —There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p<0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. Conclusions —Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT 3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.