Correlation between radiological assessment of acute ankle fractures and syndesmotic injury on MRI.

OBJECTIVE: Owing to the shortcomings of clinical examination and radiographs, injury to the syndesmotic ligaments is often misdiagnosed. When there is no indication requiring that the fractured ankle be operated on, the syndesmosis is not tested intra-operatively, and rupture of this ligamentous complex may be missed. Subsequently the patient is not treated properly leading to chronic complaints such as instability, pain, and swelling. We evaluated three fracture classification methods and radiographic measurements with respect to syndesmotic injury. MATERIALS AND METHODS: Prospectively the radiographs of 51 consecutive ankle fractures were classified according to Weber, AO-Müller, and Lauge-Hansen. Both the fracture type and additional measurements of the tibiofibular clear space (TFCS), tibiofibular overlap (TFO), medial clear space (MCS), and superior clear space (SCS) were used to assess syndesmotic injury. MRI, as standard of reference, was performed to evaluate the integrity of the distal tibiofibular syndesmosis. The sensitivity and specificity for detection of syndesmotic injury with radiography were compared to MRI. RESULTS: The Weber and AO-Müller fracture classification system, in combination with additional measurements, detected syndesmotic injury with a sensitivity of 47% and a specificity of 100%, and Lauge-Hansen with both a sensitivity and a specificity of 92%. TFCS and TFO did not correlate with syndesmotic injury, and a widened MCS did not correlate with deltoid ligament injury. CONCLUSION: Syndesmotic injury as predicted by the Lauge-Hansen fracture classification correlated well with MRI findings. With MRI the extent of syndesmotic injury and therefore fracture stage can be assessed more accurately compared to radiographs.

An assessment of structured care assistance in the management of patients with type 2 diabetes in general practice.

OBJECTIVE: To study differences in diabetes-related parameters in type 2 diabetic patients treated with the support of a Diabetes Service compared to conventional general practice care. DESIGN: Parallel clinical trial with randomisation at practice level. SETTING: Fifteen general practices. PATIENTS: Type 2 diabetic patients, aged < 76 years, treated by a GP. MAIN OUTCOME MEASURES: Level of glycated haemoglobin (HbA1c). RESULTS: 246 patients entered the study. Final mean HbA1c of all evaluable patients allocated to the intervention (n = 84) was 7.1+/-1.2%, vs 7.5+/-1.8% in the controls (n = 140) (p = 0.06). Patients who were initially poorly controlled (Fasting Blood Glucose > 10 mmol/l) had a significantly lower final HbA1c if they were in an intervention practice (p=0.001). Fewer patients in intervention practices were referred to hospital specialists (1 vs 14). CONCLUSIONS: Support by the Dutch Diabetes Service did not significantly influence glycated haemoglobin. The subgroup of initially poorly controlled patients developed a significantly lower HbA1c in intervention practices (supported by a Diabetes Service) than in control practices.

Value and cost of follow-up after adjuvant treatment of patients with Dukes' C colonic cancer.

BACKGROUND: The clinical value and costs of different diagnostic tools used to identify potentially curable recurrent disease in patients treated adjuvantly for curatively resected Dukes' C colonic cancer were examined. METHODS: The study group comprised 496 patients treated with chemotherapy over a 1-year interval. Follow-up consisted of interim history, physical examination, liver ultrasonography or computed tomography (CT), measurement of carcinoembryonic antigen (CEA) levels, chest radiography and colonoscopy. RESULTS: Two hundred and thirteen patients had recurrent disease (median follow-up 43 months). Forty-two patients with recurrence (20 per cent) were treated with curative intent (median survival 38 months; 5-year survival rate 40 per cent). Recurrence was identified by liver ultrasonography or CT (n = 14), evaluation of symptoms (n = 12), colonoscopy (n = 8), CEA measurement (n = 3), chest radiography (n = 2), physical examination (n = 1) and other modalities in two patients. The mean cost of diagnostic procedures per curative resected recurrence for patients amenable to salvage surgery was US$9011. Of all treatable recurrences, 12 of 42 were identified by evaluation of symptoms only. Ultrasonography and colonoscopy identified 22 recurrences at a cost of US$11 790 per patient, while routine follow-up by CEA measurement, chest radiography and physical examination identified a further six at a cost of US$19 850 per patient. CONCLUSION: Potentially curable recurrences were detected primarily by liver imaging and colonoscopy. The yield of CEA measurement, chest radiography and physical examination was relatively low; such methods were expensive and should not be recommended in the routine follow-up of these patients.

Risk assessment in patients with Ph+ chronic myelogenous leukemia at first relapse after allogeneic stem cell transplant: an EBMT retrospective analysis. The Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Patients with Ph+ chronic myelogenous leukemia who relapse after a first allogeneic stem cell transplant still have a possibility of long-term survival. To assess the value of the individual therapeutic options, the factors predicting outcome should be identified. We investigated data from 500 patients who relapsed before July 1996; follow-up was updated during 1998. The actuarial survival from relapse was 34.2% (95% confidence interval [CI]: 29. 9%-38.5%) at 5 years and 23.4% (95% CI: 18.9%-27.9%) at 10 years. Survival after relapse was significantly related to 5 factors: time from diagnosis to transplant (< 2 years vs >/= 2 years), disease phase at transplant (first chronic phase vs other), disease stage at relapse (cytogenetic or chronic phase vs advanced phase), time from transplant to relapse (< 1 year vs >/= 1 year), and donor type (HLA-identical sibling vs volunteer unrelated donor). The effects of individual adverse risk factors were cumulative: The probability of survival at 10 years decreased stepwise from 42% (0 factors), 32% (1 factor), 14% (2 factors), 3% (3 factors), to 0% (4 or 5 factors). Novel strategies for high-risk patients are warranted. We conclude that these 5 factors should be taken into account when comparing results of salvage therapies in patients with Ph+ chronic myeloid leukemia relapsing after allogeneic stem cell transplant.

ES/IS: estimation of conformational free energy by combining dynamics simulations with explicit solvent with an implicit solvent continuum model.

This paper reviews a recently developed method for calculating the total conformational free energy of a solute macromolecule in water solvent. The method consists of a relatively short simulation by molecular dynamics with explicit solvent molecules (ES) to produce a set of microstates of the macroscopic conformation. Conformational internal solute energy and entropy are obtained from the simulation, the latter in the quasi-harmonic approximation by analysis of the covariance matrix. The implicit solvent (IS) surface energy-dielectric continuum model is used to calculate the average solvation free energy as the sum of the free energies of creating the solute-size hydrophobic cavity, of the van der Waals solute-solvent interactions and of the polarization of water solvent by the solute's charges. We have earlier applied this method to calculate the conformational free energy of native and intentionally misfolded globular conformations of proteins (the EMBL set of deliberately misfolded proteins), and have obtained good discrimination in favor of the native conformations in all instances. These results are summarized and further analyzed to show that, on average, three major component terms of the free energy all contribute in favor of discrimination. We discuss possible improvements of the ES/IS method. It is shown how the force field can be made self-consistent by adapting the parameters for calculation of surface and polarization free energies closely to the molecular mechanics force field used in the dynamics simulation, using established simulation methods to compute free energies for cavity formation and a charging process with the molecular mechanics force field to provide a set of (quasi-experimental) reference data that can be used to refine the parameters of the continuum models. The molecular surface area together with a microscopic surface free energy near 70 cal/(mol A2) is found to be a consistent descriptor of the cavity free energy. Preliminary results indicate that a linear-response approximation for the polarization of water solvent reaction near typical polar and charged protein groups is accurate to within approximately 90%.

Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: Transplantation of blood or bone-marrow stem cells is the treatment of choice for selected patients with chronic myeloid leukaemia (CML). Transplantation is used with increasing frequency and success, but remains associated with substantial risks of morbidity and mortality. Other treatments with satisfactory short-term outcome are available. For appropriate counselling of patients, a rapid and simple way to assess risk is needed. METHODS: Data from 3142 patients (1873 [60%] male, 1269 [40%] female; mean age 34 years, range <1-60 years) treated with allogeneic blood or marrow transplants for CML between 1989 and 1997, reported to the European Group for Blood and Marrow Transplantation (EBMT), were used to develop and test a simple risk score based on previously reported major pretransplant risk factors: histocompatibility, stage of disease at time of transplantation, age and sex of donor and recipient, and time from diagnosis to transplantation. We analysed probabilities of survival, leukaemia-free survival, transplant-related mortality, and relapse incidence with respect to these risk factors. FINDINGS: At the time of analysis, 1922 (61%) of the 3142 patients were alive-1567 (65%) of those with HLA-identical sibling donors and 417 (57%) of those with unrelated donors. 1682 (54%) were alive without relapse. 1220 (39%) patients had died, 1013 (83%) of transplant-related causes, 207 (17%) of relapse. 447 (14%) patients had relapsed. The final scoring system was highly predictive for leukaemia-free survival, survival and transplant-related mortality. Survival at 5 years was 72%, 70%, 62%, 48%, 40%, 18%, and 22% for patients with scores 0, 1, 2, 3, 4, 5, and 6, respectively. Risk of transplant-related mortality was 20%, 23%, 31%, 46%, 51%, 71%, and 73%. Data showed the same trends for HLA-identical sibling transplants and unrelated transplants for transplants done in 1989-93 and 1994-96. INTERPRETATION: Pretransplant risk factors are cumulative for individual patients with CML having blood or marrow transplantation. A simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions.

Markers for assessment of nodal metastasis in laryngeal carcinoma.

BACKGROUND: Regional metastasis is an important factor in the treatment and prognosis of patients with head and neck squamous cell carcinoma. Although in recent years imaging techniques have improved, it is still impossible to detect small metastatic deposits. Metastasis is mainly determined by properties of the primary tumor and its interaction with surrounding structures. OBJECTIVE: To identify markers that predict the presence of metastasis based on the features of the primary tumor. DESIGN: Correlation of the results of histological, immunohistochemical, and molecular biological analysis with clinical and histopathological data. MATERIALS AND METHODS: Several histological features and biological markers were examined in 31 laryngeal carcinomas. The following markers were selected on their putative role in the process of metastasis and were studied using immunohistochemical and/or Southern blot techniques: proliferating cell nuclear antigen (PCNA), p53, retinoblastoma tumor-suppressor gene (Rb), myc, bcl-2 (inhibitor of apoptosis), epidermal growth factor (EGF), EGF-receptor (EGFR), neu, nm23 (also known as NME1, putative metastasis suppressor), desmoplakin, neuron cell-adhesion molecule (N-CAM), epithelial cell-adhesion molecule (Ep-CAM), E-cadherin, cyclin D1 (CCND1), and EMS1. RESULTS: The presence of an inflammatory reaction surrounding the tumor (P = .07), eosinophilic infiltration (P = .16), positive immunostaining for Rb (P = .02), negative immunostaining for Ep-CAM (P = .13), and amplification of CCND1 and EMS1 (P = .05) correlated with nodal metastasis. The combination of an inflammatory reaction, eosinophilic infiltration, and staining for Rb and Ep-CAM resulted in a superior accuracy in assessing nodal metastasis. CONCLUSIONS: These results indicate that it is possible to predict and exclude lymph node metastasis by studying the features of the primary tumor only. When these results are confirmed in a larger series, biological markers may be powerful diagnostic tools with great impact on clinical decision making.

Cost-effectiveness of 6 and 12 months of interferon-alpha therapy for chronic hepatitis C.

BACKGROUND: Interferon-alpha is effective in only a small number of patients with chronic hepatitis C, although prolonged treatment may increase the response rate. There is concern that the expense of interferon-alpha therapy may not be justified by the low response rates and uncertain long-term benefit. OBJECTIVE: To compare clinical and economic outcomes after 6 months and 12 months of interferon-alpha therapy for chronic hepatitis C. DESIGN: A Markov model depicting the natural progression of chronic hepatitis C. On the basis of this model, a simulated trial compared no therapy with 6 and 12 months of interferon-alpha therapy at standard doses (3 million U three times weekly). PATIENTS: Four age-specific cohorts (30, 40, 50, and 60 years of age) with chronic hepatitis C. MEASUREMENTS: Number of deaths from liver disease, total costs, and cumulative quality-adjusted life-years (QALYs). RESULTS: Six and 12 months of interferon-alpha treatment gained 0.25 QALYs at an incremental cost of $1000 and 0.37 QALYs at an incremental cost of $1900, respectively. Thus, although 6 months of interferon-alpha therapy was less efficacious than 12 months of therapy, it was more cost-effective ($4000 per QALY gained compared with $5000 per QALY gained). Nonetheless, in patients younger than 60 years of age, both 6 and 12 months of therapy compared favorably with other established medical interventions, such as screening mammography and cholesterol reduction programs. Important variables affecting the cost-effectiveness of interferon-alpha treatment included the cost and efficacy of interferon-alpha, the cost of treatment for decompensated cirrhosis, and quality of life in patients with chronic hepatitis C. CONCLUSION: From the standpoint of cost-effectiveness, interferon-alpha therapy for 6 or 12 months may be justified in patients with chronic hepatitis C. The possible exception is patients older than 60 years of age.

[Techniques for thyroid imaging]. / Les techniques d'imagerie thyroïdienne.

Advances in imaging techniques has improved our understanding of diseases. The different imaging techniques for visualizing the thyroid parenchyma, including cytopuncture, sonography, CT-scan, scintigraphy, magnetic resonance imaging, have provided various types of information. Do these techniques really provide the clinician with the answers to his question? The information provided by the different imaging techniques is presented together with the insufficiencies of each method. Faced with the rising cost of health services, we developed analysis instruments which should help the clinician in a more rational use of diagnostic examinations. The question which most often arises is that of an isolated nodule within a multinodular goiter: is it malignant or benign? the analysis of the available techniques shows that the cost-effective strategy uses conventional Tc99m or I123 scintigraphy and thallium 201 scintigraphy. With this strategy, the risk of missing a thyroid cancer is approximately 1.75%. With cytopuncture, this risk is multiplied by a factor of 2.5 reaching 4.5%.

Anterior rectocele: assessment with radiographic defecography, dynamic magnetic resonance imaging, and physical examination.

PURPOSE: The aim of this study was to devise a measuring method for an anterior rectocele on standardized defecographies and magnetic resonance images (MRI) to quantify anterior rectocele and to test whether this could substantiate clinical decision making for operative treatment for anterior rectocele. METHODS: Quantitative analysis by the measuring method as proposed was compared with qualitative scores on defecographies and MRI from the same patients. Thirty-eight patients with symptoms compatible with an anterior rectocele were subjected to physical examination in the left decubitis position and supine position and to defecography. Findings on defecography were compared with findings on physical examination. Thirteen patients were examined before and after surgical correction of the anterior rectocele for a total of 51 qualitative and quantitative examinations. The group of operated patients was analyzed for treatment results. Nineteen controls were included. RESULTS: Sixty-six radiographs of 33 defecographies were qualified in three grading classes and quantified with the proposed method by two observers. The mean measured value of the anterior rectocele in the three subjective grading classes is significantly different (P < 0.001). Anterior rectoceles qualified as severe had a measured value of 20 mm or more in 96 percent of the radiographs. Lower gradings were never > 20 mm. On MRI severe anterior rectoceles were not scored and measured values did not correlate with qualitative scores. When findings on physical examination were compared with defecographic measurement, the coefficient of correlation (r) between the radiologic assessment and clinical examination in the left decubitis position is r = 0.87, for the examination in the supine position, r = 0.77. All 15 cases scored as severe anterior rectocele in the left decubitis position had a measured anterior rectocele of > or = 20 mm. In the 13 cases that received surgery, there was a significant reduction of the anterior rectocele (P < 0.001) and clinical improvement. Patients with small or moderate anterior rectocele on physical examination with a size > or = 20 mm on defecography were cured by surgical correction. None of the controls had an anterior rectocele on physical examination or an anterior rectocele > or = 20 mm on defecography. CONCLUSIONS: An anterior rectocele with a size of 20 mm or more corresponds with a qualitative score of "severe" on radiographic defecography. Physical examination for anterior rectocele in the left decubitis position corresponds best with quantitative radiographic assessment and anterior rectocele with a size > or = 20 mm on defecography is pathologic. Patients with complaints compatible with anterior rectocele can be assessed in objective and quantitative terms by radiography and can be successfully surgically treated, even if at physical examination the anterior rectocele is not classified as large, provided that dynamic defecography shows an anterior rectocele of > or = 20 mm. The potential of dynamic MRI with regard to anterior rectoceles presently seems absent.

[Economic analysis of diagnostic and therapeutic methods in cases of cold thyroid nodules]. / Analyse économique des approaches diagnostiques et thérapeutiques du nodule froid de la thyroïde.

This article studies how two diagnostic tests (cytological puncture and 201thallium scanning) can be combined to obtain a more efficient approach of cold thyroid nodules. Diagnostic and therapeutic approaches are compared on the basis of four criteria: financial cost (immediate and delayed), number of labelled cancers, pre- and postoperative death rates and number of complications.

Assessment of resectability of carcinoma of the pancreatic head by ultrasonography and computed tomography. A retrospective analysis.

In order to establish the reliability of the assessment of tumour stage and hence of resectability of carcinoma of the pancreatic head by ultrasonography (US) and computed tomography (CT) a retrospective analysis was performed on 41 patients. Both direct imaging techniques were very accurate in detecting non-resectable disease, 100 and 85% respectively, but were much less accurate in predicting resectable cancer, 18 and 15% respectively. False-resectable results were established in 58% of US examinations and 42% of CT examinations. As demonstrated in this study, predicting resectability of carcinoma of the pancreatic head with US and CT is an inadequate method of assessing tumour stage and should be complemented by other techniques to ensure a reliable result.

Assessment of patient-staff and intrastaff problems in psychiatric consultations.

In a study of 249 consecutive inpatient consultations, the occurrence of patient--staff or intrastaff problems as determined by the psychiatric consultation team was compared with questionnaire answers, provided by the consultant following each consultation, and interpreted as indications for such staff problems. According to the consultation team, staff problems played a role in 33% of the consultations. In the questionnaires, of the nine criteria statistically significantly related to the occurrence of staff problems, the following were the most relevant: 1) emotional tone or wording of request; 2) abnormal timing of referral; 3) request unclear; 4) unjustified urgency of referral; and 5) existence of hidden questions. If none or only one of these criteria were positive, then there was little chance that staff problems were present. If three or four criteria were positive, then the probability of staff problems was much higher. If the first three criteria were negative, then staff problems were hardly ever encountered.

Variations in histopathological evaluation of non-neoplastic colonic mucosal abnormalities; assessment and clinical significance.

The variation between three pathologists examining histological features seen in non-neoplastic colonic mucosa from 40 biopsies was analysed. Several procedures to express observer variation were used and compared, with emphasis on kappa statistics. Only five features, the presence of ulceration, villous surface, epithelioid granulomas, severe mucus depletion and crypt abscesses were sufficiently reproducible by the three pairs of pathologists. These findings suggest that other criteria used for the classification of inflammatory bowel disease are potentially unsatisfactory. When results from different studies on biopsies are being compared, influence of observer variation should be identified. Comparison of statistical techniques showed overall variation to be less useful than other statistical procedures. There was little difference between results from kappa statistics and other measures of agreement (overall agreement excluded).

Interlaboratory oral anticoagulant quality assessment by the Netherlands Federation of Thrombosis Services.

The 50 laboratories of the Netherlands Federation of Thrombosis Services, covering a population of 9 million and responsible for the laboratory control of approximately 150,000 patients under oral anticoagulation, have participated since 1974 in a voluntary external and internal quality control program. The external program comprises a monthly distribution to the member laboratories of a series of artificially prepared control blood samples, two of which are identical. The overall variation of the coagulation times found were 10% (CV) in 1974 and 8% (CV) in 1975. Performance improved rather abruptly at the beginning of 1975, after the application of a tight methodological standardization and improvement by the manufacturer of the thromboplastin preparation (Thrombotest) used by the great majority of the laboratories involved. The main source of variation was found to be random error in the Thrombotest determination, approximately 6%. Interbatch variation of Thrombotest and inter-aliquot variation of control blood samples both do amount to approximately 3%(CV). In terms of rabbit tissue thromboplastins, which have a lower sensitivity than Thrombotest (i.e., a flatter slope of the correlation between the PT and the anticoagulant effect), the total variation in the performance of the Dutch laboratories is 2.2--5.6% (CV), which is unusually low. The main reason for this is the fact that the laboratories can rely not only on the services of the manufacturer but also on a central information office and a reference laboratory responsible for the preparation of the control blood as well as the standardization (calibration) of thromboplastin.

The sub-acute center: a proposal for relocating elderly mental patients.

Both researchers and practitioners have become increasingly concerned with the plight of elderly mental hospital patients who are often inappropriately confined in state hospitals and then discharged from these facilities with little preparation for survival or attention given to the quality of community resources. This paper proposes the establishment of a new community care setting, a sub-acute center (SAC), which is designed to meet present inadequacies in the mental care system for the aged and combines elements of a foster home and a protective setting with a mental health aftercare component for more effectively preparing the elderly for independent community living. The SAC combines at least three concepts which are discussed: (a) the receiving station; (b) continuity of care; and (c) advocacy. The professional SAC staff and aides have many potential roles to play as practitioners, spokesmen, educators, consultants, and researchers.