Outcomes Research in Orthopaedics

A new agenda in outcomes research has developed in the past decade. The stimulus has come as the result of rapidly increasing health care costs, marked variations in utilization of health care services, and deficiencies in the research literature. Outcomes research includes methods such as analysis of large databases, small-area analysis, structured literature reviews (meta-analysis), prospective clinical trials, decision analysis, and guideline development. Clinical research should be prospective and should employ modern statistical and assessment methods. The focus of this research is on patient-oriented outcomes of care rather than on assessments of the process of care. To illustrate these applications in orthopaedics, lumbar spine fusion with internal fixation for "spinal instability" is presented as an example. Completed large-database analyses, small-area variation studies, and a meta-analysis indicate the need for clinical studies. An outline of the form and content of such a study is presented.     

Effects of methylphenidate (Ritalin) on auditory performance in children with attention and auditory processing disorders.

A double-blind, placebo-controlled study was used to investigate the effects of methylphenidate (Ritalin) on tests of auditory processing in children diagnosed with both Attention Deficit Hyperactivity Disorder (ADHD) and Central Auditory Processing Disorder (CAPD). Thirty-two subjects received three Central Auditory Processing (CAP) tests and the Auditory Continuous Performance Test (ACPT), a measure of attention/impulsivity, at two separate test sessions: once when medicated with Ritalin and once when nonmedicated (placebo). Sixteen subjects were assigned randomly to receive their medication first and 16 to receive the placebo first. A counterbalanced 2 x 2 mixed factorial analysis of variance was conducted for each of the four dependent variables: Staggered Spondaic Word (SSW), Phonemic Synthesis (PS), Speech-in-Noise (SN), and ACPT measures. Analyses revealed that Ritalin did not have a significant effect on any of the three CAP measures. However, ACPT performance was significantly better (p < .000) for the Ritalin versus placebo condition.     

A retrospective clinicopathological study of 37 patients with chordoma: a danish national series

Purpose. There are, in general, few published series on chordoma. It is a rare disease and further data are still needed.Patients/methods. The data of 37 patients with chordoma were retrospectively analyzed. Treatment was surgical excision in 11, radical radiotherapy in 9 and a combination of the two in 16 cases. The male to female ratio was 2.7 : 1. Median age was 59 years (range 1-89 years).Results. The most common symptoms at diagnosis were pain (98%), neurological disturbances (42%) and incontinence (33%). The tumours were located in the sacro-coccygeal region in 68%, the spheno-occipital region in 16% and the vertebrae in 16% of the patients. Median tumour.size was 7 cm (range 1-30 cm). Local recurrence occurred in 21/36 treated cases and distant metastases developed in eight patients (23%). The median time to recurrence/progression after primary treatment was 2 years (range 1-10 years). The actuarial 5-year rates of overall, progression-free and symptom-free survival were 40%, 31% and 20%, respectively. The corresponding 10-year rates were 26%, 21% and 14%, respectively. At the time of analysis, seven patients were alive, six without evidence of disease. Four of the six patients without active disease were symptom free. A univariate analysis showed that age, sex, tumour size, histopathology, surgical safety margin, treatment modality and radiation dose did not significantly affect overall, progression-free or symptom-free survival. Only turnout site had a prognostic value with turnouts in the spheno-occipital region carrying the worst prognosis.Discussion. We conclude that effective treatment against chordomas is still lacking and a prospective multi-institutional registration study may provide more information on the optimal work-up and treatment of this rare disease.     

Remission and relapse in subjects with panic disorder and panic with agoraphobia: a prospective short-interval naturalistic follow-up

This article reports on the course of uncomplicated panic disorder and panic with agoraphobia on 309 patients participating in the Harvard/Brown Anxiety Research Project, a prospective longitudinal study of patients with DSM-III-R-defined anxiety disorders. At 1 year, there was a .39 probability of full remission for uncomplicated panic disorder and a .17 probability of full remission for panic disorder with agoraphobia Similar differences in time to remission for these syndromes were still found when criteria for remission were made less stringent. However, even requiring less improvement for remission left a large percentage of subjects in an episode, and for those that remitted, relapse occurred quickly, indicating a chronic and recurrent course of illness. This is the first longitudinal, prospective, naturalistic study on a large cohort of subjects with anxiety disorders to have regular, structured, short-interval follow-up. Our results are consistent with the view that panic disorder has a chronic course with high rates of relapse after remission and longer episodes when agoraphobia is a part of the constellation of symptoms.     

Non-insulin-dependent diabetes mellitus and hypertriglyceridemia impair lipoprotein metabolism in chronic hemodialysis patients

Patients with diabetes mellitus undergoing chronic hemodialysis treatment have the worst outcome on dialysis due to an increased rate of cardiovascular complications. Nearly all patients present with dyslipidemia, a prominent vascular risk factor, probably responsible for the high rate of vascular injury. Since both uremia and diabetes predispose to hypertriglyceridemia, the present study was conducted to investigate the influence of diabetes mellitus and/or hypertriglyceridemia on lipoprotein metabolism in hemodialysis patients. LDL was isolated and characterized from hyper- and normotriglyceridemic diabetic and nondiabetic hemodialysis patients (n = 40; 10 in each group); also, LDL-receptor-dependent uptake and intracellular cholesterol metabolism were studied in HepG2 cells. In addition, scavenger-receptor-mediated uptake was examined in mouse peritoneal macrophages. LDL isolated from nondiabetic normotriglyceridemic hemodialysis patients exhibited impaired cellular uptake via the LDL receptor. Additionally, intracellular sterol synthesis was less inhibited and cholesterol esterification was reduced compared with LDL from healthy control subjects. Reduction of catabolic capacities was more marked in hemodialysis patients who were either diabetic or hypertriglyceridemic and even more pronounced in patients presenting with a combination of both diabetes and hypertriglyceridemia. Hypertriglyceridemic and diabetic patients showed reduced lipase activity and increased LDL oxidation. Furthermore, they accumulated a fraction of small, dense LDL, and LDL was predominantly taken up via the scavenger-receptor pathway in peritoneal macrophages. This study elucidates the distinct influence of diabetes and/or hypertriglyceridemia in hemodialysis patients on cellular LDL metabolism via specific and nonspecific metabolic pathways. Furthermore, it underscores the cumulative impact of these pathologic entities on impairment of lipoprotein metabolism and increase of cardiovascular risk.     

Why does postpsychotic IQ decline in childhood-onset schizophrenia?

OBJECTIVE: The authors' goal was to examine whether the postpsychotic decline in full scale IQ during adolescence for patients with childhood-onset schizophrenia is due to a dementing process or simply failure to acquire new information and skills. METHOD: Linear regression was used to determine the rate of change for scaled and raw scores on subtests of 31 patients with childhood-onset schizophrenia. The resulting slopes were examined and related to changes in the patients' brains determined by magnetic resonance imaging. RESULTS: Three postpsychotic subtest scaled scores declined significantly: picture arrangement, information, and block design. In contrast, there was no decline in the non-age-corrected (raw) scores for any subtest. A significant correlation was found between decrease in hippocampal volume and a smaller increase in raw score on the information subtest. CONCLUSIONS: The decline during adolescence in the full-scale IQ of patients with childhood-onset schizophrenia does not reflect dementia but, rather, an inability to acquire new information and abilities.     

Association of IGF-I and IGF-II with myofiber regeneration in vivo

This study examined expression of insulinlike growth factor (IGF) in the myofibers and nonmyofibrillar structures of murine soleus muscle following contraction-induced damage. Identifying the cellular sources of this myogenic growth factor could improve muscle rehabilitation strategies. Immunohistochemical analysis of muscle sections indicated that the number of myofibers expressing both IGF-I and IGF-II increased significantly at 4, 7, and 10 days following injury, compared with control. Muscle spindles and vascular tissue expressed only IGF-II, and staining intensity did not change following injury. The number of fibers expressing developmental myosin heavy chain increased significantly at 7 and 10 days postinjury, and these usually coexpressed IGF. No IGF-specific staining of interstitial/inflammatory cells was observed. Therefore, expression of IGF after mechanically induced fiber damage occurs exclusively within regenerating fibers without supplemental delivery of IGF to the tissue by inflammatory cells or changes in constitutive expression of IGF-II in vascular tissue.     

MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease. Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999     

Individualized drug dosage in patients treated with continuous hemofiltration

BACKGROUND: Subtherapeutic drug dosing may be even more dangerous than overdosage, especially for intensive care patients requiring hemofiltration. PROPOSAL: According to Dettli's fundamental equation, body clearance of any drug (Cl) is a linear function of creatinine clearance (Cl = Cl anur + a x C(Cr)), with [a = (Cl norm - Cl anur)/C(Cr), norm]. We propose to individualize drug dosage during high-flux hemofiltration by basing it on Dettli's equation and on total C(Cr) (C(Cr) tot = C(Cr) ren + C(Cr) filt). Using this approach, drug clearance will eventually be overestimated for drugs with substantial tubular secretion and for high-efficiency hemofiltration (C(Cr) tot > 30 ml/min). CONCLUSION: In patients undergoing hemofiltration, the total C(Cr) approach might be a practical alternative to standardized dosing schemes for deriving an individualized dosage from published pharmacokinetic data and functions.