Prognostic value of B-score for predicting joint replacement in the context of osteoarthritis phenotypes: Data from the osteoarthritis initiative.

Objective: Developing new therapies for knee osteoarthritis (KOA) requires improved prediction of disease progression. This study evaluated the prognostic value of clinical clusters and machine-learning derived quantitative 3D bone shape B-score for predicting total and partial knee replacement (KR). Design: This retrospective study used longitudinal data from the Osteoarthritis Initiative. A previous study used patients' clinical profiles to delineate phenotypic clusters. For these clusters, the distribution of B-scores was assessed (employing Tukey's method). The value of both cluster allocation and B-score for KR-prediction was then evaluated using multivariable Cox regression models and Kaplan-Meier curves for time-to-event analyses. The impact of using B-score vs. cluster was evaluated using a likelihood ratio test for the multivariable Cox model; global performances were assessed by concordance statistics (Harrell's C-index) and time dependent receiver operating characteristic (ROC) curves. Results: B-score differed significantly for the individual clinical clusters (p â€‹< â€‹0.001). Overall, 9.4% of participants had a KR over 9 years, with a shorter time to event in clusters with high B-score at baseline. Those clusters were characterized clinically by a high rate of comorbidities and potential signs of inflammation. Both phenotype and B-score independently predicted KR, with better prediction if combined (P â€‹< â€‹0.001). B-score added predictive value in groups with less pain and radiographic severity but limited physical activity. Conclusions: B-scores correlated with phenotypes based on clinical patient profiles. B-score and phenotype independently predicted KR surgery, with higher predictive value if combined. This can be used for patient stratification in drug development and potentially risk prediction in clinical practice.

Salmon calcitonin: a review of current and future therapeutic indications.

Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.

Serum growth hormone (GH) profiles after nasally administered GH in normal subjects and GH deficient patients.

OBJECTIVE: GH-deficient patients are at present treated with daily subcutaneous GH injections. Further improvements in patient compliance and effects of treatment may occur with nasal administration. We have examined the absorption of nasally administered GH in healthy subjects and in GH deficient patients in two separate studies. DESIGN: Healthy subjects and GH deficient patient were examined in the morning after an overnight fast. Twelve IU of GH in a powder containing didecanoyl-L-alpha-phosphatidylcholine as enhancer were administered in the nostrils (6 IU in each nostril) at the beginning of the study in the healthy subjects. The GH deficient subjects received a total of 6 IU GH/m2 intranasally. Blood was frequently sampled for up to 4 hours. Before and after nasal application anterior rhinoscopy was performed. PATIENTS: Eight normal subjects and 7 GH deficient patients. MEASUREMENTS: Serum GH. RESULTS: (mean +/- SD) Mean maximum concentration (Cmax) in the normal group was 57.6 mU/l +/- 36.9 with a mean time to obtain Cmax (Tmax) of 65 +/- 47 min. In the GH deficient group Cmax was 56.1 +/- 26.1 mU/l with a mean Tmax of 45 +/- 15 min. The subjects did not report any major inconvenience during the study. Anterior rhinoscopy did not reveal changes. CONCLUSION: Nasally administered GH is absorbed to a significant degree from the nasal mucosa without obvious untoward effects in the short term. These data encourage further studies with nasal GH administration.

Ultrasound examination in jaundiced patients. Is computer-assisted preclassification helpful?

In this study we attempted to determine the diagnostic accuracy and reproducibility of ultrasonography (US) for jaundice and to see how US can best be combined with preliminary clinical-biochemical diagnoses to plan the invasive work-up. US proved reproducible in two diagnostic departments (127 agreements in 135 cases). But, since obstruction was underdiagnosed (15 double-false negatives), the predictive value of a negative result was only 0.83. By adding a term which represents the US conclusion, obstruction or not, to the Copenhagen pocket diagnostic chart score (based on the logistic model) we found that an obstructive conclusion increases the odds of obstruction by a factor of 25, and a non-obstructive conclusion decreases the odds by a factor of only 1.9. We conclude that the preliminary diagnosis is frequently sufficiently certain to be unalterable by US. This leaves only 40% of the jaundice cases in which US is necessary to plan invasive work-up. The US workload can even, it appears, be reduced to about 22% without appreciable penalty in terms of unrewarding invasive procedures. Using these strict indications, four US examinations seem to suffice to avoid one such error. Relying on either US or clinical-biochemical data alone is inferior to the combined strategy.

A decision tree for early differentiation between obstructive and non-obstructive jaundice.

We present a method for early differentiation between obstructive and non-obstructive jaundice. On the basis of 14 variables (clinical data and clinical chemical tests, all available within 48 h) a simple decision tree or flow chart has been constructed. The diagnostic yield was as follows: 857 of 982 consecutive jaundiced patients (87%) in a data base and 98 of 108 patients in an independent test sample (91%) were correctly classified. Decision trees for the differentiation between benign or malignant causes within the obstructive group and between acute or chronic causes within the non-obstructive group are also presented. The resulting four-way classification was correct for 77% of the patients in the data base and for 72% of the patients in the test sample. The decision trees are compared with previous methods founded on Bayes' rule and logistic discrimination. The decision trees enable a quick and reliable classification of jaundiced patients, thus providing a valid basis for rational planning of the further diagnostic study.

Differential diagnosis of jaundice: junior staff experience with the Copenhagen pocket chart.

Originally published in 1984, the Copenhagen Pocket Chart for early differentiation between causes of jaundice has been tested with success in centres outside Denmark. Using a logistic discrimination model, it estimates probabilities of obstruction and non-obstruction in each case (and provides a further subdivision if desired). Here we evaluate its performance in the hands of young clinicians on a consecutive series of 173 jaundiced patients from two Danish hospitals. The chart performed as well as in the original series: confident diagnoses (probability greater than or equal to 0.80) were assigned to 124 patients; of these 115 proved correct (93%). In 46 patients diagnostic probabilities were less than 0.80, and 3 patients had an unknown cause of jaundice. There were 108 cases in which physician and chart were in agreement, both with a confident diagnosis, and only one of these cases was wrong. In one hospital, contributing 107 cases, each patient was independently examined by a medical student in addition to the physician's examination. Student performance was equally good, practically speaking, in particular when taking the scores on the chart into consideration. As to observer disagreement, the student and the physician typically differed on 0-2 of the chart's 21 items. In no case, however, did this lead to a confident obstructive diagnosis being changed into a confident diagnosis of non-obstruction, or vice versa.

Computer diagnosis in jaundice. Bayes' rule founded on 1002 consecutive cases.

Extensive clinical and clinical chemical information was collected from 1002 consecutive jaundiced patients. Initial selection of variables based on Chi 2-tests or Mann-Whitney U-test allowed the removal of 64 of the 107 variables originally collected. A further selection of variables was carried out using a modified version of Bayes' rule thus reducing the number of variables from 43 to 22. Of the 982 patients with a final diagnosis 743 patients (76%) could be classified correctly into one of 13 diagnostic categories. The Bayes' rule was also applied to a test group of a further 110 jaundiced patients and found to perform equally well: of 108 patients with a final diagnosis 81 (75%) were correctly classified. A comparison between the clinician's diagnosis and the computer-aided diagnosis according to Bayes' rule demonstrated agreement with regard to one of the 13 diagnostic alternatives in 734 patients (75%), of whom 81 patients were wrongly diagnosed. In the test group agreement upon diagnosis was found in 80 patients (74%). By plausibly combining the computer-aided and the clinician's preliminary diagnoses, more correct classifications were obtained than with either method alone. Many diagnostic modalities such as ultrasound examination, CT-scan, and direct cholangiography are at hand today for the differential diagnosis of jaundice. Computer-aided diagnosis using Bayes' rule has proved a reliable tool for the clinician and can be used in the planning of a diagnostic strategy for the individual jaundiced patient.