Biomedical subjects
Publications and source records attributed to M Radford.
Bone is a frequent site of tumour metastasis and is the third most common site of metastatic carcinoma. With advances in the use of immunotherapy, hormonal manipulation, chemotherapy and radiation for the palliation of patients with metastatic bone disease, significant improvements in survival, wellbeing and overall quality of life have been achieved.
A 14-month-old boy presenting with Wilms tumor (WT) was found to have a small de novo deletion of the long arm of chromosome 12 (12q11-12q13.11). Microsatellite analysis of this region from constitutional DNA showed that the paternal allele was absent between the markers D12S331 and D12S1713 (inclusive). In the WT there was no evidence of loss of the maternal chromosome. Constitutional chromosome abnormalities can often point to the presence of genes that are important in disease, and the deletion of chromosome 12 in this patient may indicate a gene involved in WT. To determine whether a WT predisposition locus exists at 12q we examined the region in two familial Wilms tumor (FWT) pedigrees unlinked to the known FWT genes on chromosomes 17q (FWT1), 19q (FWT2), and 11p (WT1). In both families WT did not segregate with chromosome 12q markers located within the deletion boundaries.
The requirements for homologous blood transfusion in patients undergoing total knee replacements under tourniquet, before and after the introduction of autologous transfusion of blood collected from wound drains, are compared. In a control population of 93 patients undergoing total knee replacement, 67 required homologous transfusions of two units or more. In 160 patients who were re-transfused with blood from wound drains, only 30 required additional homologous transfusions. Re-transfusion of filtered drained blood reduces the need for homologous bank blood. This avoids the risks associated with donated blood and affords significant cost savings.
BACKGROUND: A multistate randomized study conducted under the Health Care Financing Administration's (HCFA's) Health Care Quality Improvement Program (HCQIP) offered the opportunity to compare the effect of a written feedback intervention (WFI) with that of an enhanced feedback intervention (EFI) on improving the anticoagulant management of Medicare beneficiaries who present to the hospital with venous thromboembolic disease. METHODS: Twenty-nine hospitals in five states were randomly assigned to receive written hospital-specific feedback (WFI) of feedback enhanced by the participation of a trained physician, quality improvement tools, and an Anticoagulant Management of Venous Thrombosis (AMVT) project liaison (EFI). Differences in the performance of five quality indicators between baseline and remeasurement were assessed. Quality managers were interviewed to determine perceptions of project implementation. RESULTS: No significant differences in the change from baseline to remeasurement were found between the two intervention groups. Significant improvement in one indicator and significant decline in two indicators were found for one or both groups. Yet 59% of all quality managers perceived the AMVT project as being successful to very successful, and more EFI quality managers perceived success than did WFI managers (71% versus 40%). In the majority of EFI hospitals, physician liaisons played an important role in project implementation. CONCLUSION: Study results indicated that the addition of a physician liaison, quality improvement tools, and a project liaison did not provide incremental value to hospital-specific feedback for improving quality of care. Future studies with larger sample sizes, lengthier follow-up periods, and interventions that include more of the elements shown to affect practice behavior change are needed to identify an optimal feedback model for use by external quality management organizations.
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OBJECTIVES: To test the hypothesis that physician errors (failure to diagnose appendicitis at initial evaluation) correlate with adverse outcome. The authors also postulated that physician errors would correlate with delays in surgery, delays in surgery would correlate with adverse outcomes, and physician errors would occur on patients with atypical presentations. METHODS: This was a retrospective two-arm observational cohort study at 12 acute care hospitals: 1) consecutive patients who had an appendectomy for appendicitis and 2) consecutive emergency department abdominal pain patients. Outcome measures were adverse events (perforation, abscess) and physician diagnostic performance (false-positive decisions, false-negative decisions). RESULTS: The appendectomy arm of the study included 1, 026 patients with 110 (10.5%) false-positive decisions (range by hospital 4.7% to 19.5%). Of the 916 patients with appendicitis, 170 (18.6%) false-negative decisions were made (range by hospital 10.6% to 27.8%). Patients who had false-negative decisions had increased risks of perforation (r = 0.59, p = 0.058) and of abscess formation (r = 0.81, p = 0.002). For admitted patients, when the inhospital delay before surgery was >20 hours, the risk of perforation was increased [2.9 odds ratio (OR) 95% CI = 1.8 to 4.8]. The amount of delay from initial physician evaluation until surgery varied with physician diagnostic performance: 7.0 hours (95% CI = 6.7 to 7.4) if the initial physician made the diagnosis, 72.4 hours (95% CI = 51.2 to 93.7) if the initial office physician missed the diagnosis, and 63.1 hours (95% CI = 47.9 to 78.4) if the initial emergency physician missed the diagnosis. Patients whose diagnosis was initially missed by the physician had fewer signs and symptoms of appendicitis than patients whose diagnosis was made initially [appendicitis score 2.0 (95% CI = 1.6 to 2.3) vs 6.5 (95% CI = 6.4 to 6.7)]. Older patients (>41 years old) had more false-negative decisions and a higher risk of perforation or abscess (3.5 OR 95% CI = 2.4 to 5.1). False-positive decisions were made for patients who had signs and symptoms similar to those of appendicitis patients [appendicitis score 5.7 (95% CI = 5.2 to 6.1) vs 6.5 (95% CI = 6.4 to 6.7)]. Female patients had an increased risk of false-positive surgery (2.3 OR 95% CI = 1.5 to 3.4). The abdominal pain arm of the study included 1,118 consecutive patients submitted by eight hospitals, with 44 patients having appendicitis. Hospitals with observation units compared with hospitals without observation units had a higher "rule out appendicitis" evaluation rate [33.7% (95% CI = 27 to 38) vs 24.7% (95% CI = 23 to 27)] and a similar hospital admission rate (27.6% vs 24.7%, p = NS). There was a lower miss-diagnosis rate (15.1% vs 19.4%, p = NS power 0.02), lower perforation rate (19.0% vs 20.6%, p = NS power 0.05), and lower abscess rate (5.6% vs 6.9%, p = NS power 0.06), but these did not reach statistical significance. CONCLUSIONS: Errors in physician diagnostic decisions correlated with patient clinical findings, i.e., the missed diagnoses were on appendicitis patients with few clinical findings and unnecessary surgeries were on non-appendicitis patients with clinical findings similar to those of patients with appendicitis. Adverse events (perforation, abscess formation) correlated with physician false-negative decisions.
Sural nerve injury is a complication of Achilles Tendon (TA) rupture. We dissected 30 cadaveric lower limbs to describe the course of the sural nerve in relation to the TA. At the level of insertion of the TA into the calcaneum, the sural nerve was a mean 18.8 mm from the lateral border of the TA. The proximal course of the nerve was towards the midline such that it crossed the lateral border of the TA at a mean distance of 9.8 cm from the calcaneum. The significant individual variation in the position of the sural nerve in relation to the achilles tendon should be borne in mind when placing sutures in the proximal part of the achilles tendon. Percutaneous sutures should not be placed in the lateral half of the TA.
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Causing "unnecessary suffering" has been widely adopted in legislation to define criminal liability in respect of the treatment of animals. This article examines the way in which the term has been interpreted and applied by the courts, and considers its effectiveness in affording animals protection from abuse.
BACKGROUND: Elderly patients with ischemic stroke and atrial fibrillation are at especially increased risk for recurrent stroke. Warfarin sodium is highly effective in reducing this risk. OBJECTIVE: To determine the use of warfarin among a population sample of elderly patients with atrial fibrillation hospitalized for ischemic stroke. METHODS: The Connecticut Peer Review Organization conducted a chart review of Medicare patients, aged 65 years or older, hospitalized in 1994 with a diagnosis of atrial fibrillation. Patients with a principal diagnosis of acute myocardial infarction or another indication for anticoagulation were excluded. RESULTS: Among 635 patients (402 women; 585 white; 218 > or =85 years old; 147 with a new diagnosis of atrial fibrillation), 334 had stroke as a principal diagnosis. Among those discharged alive after a stroke, only 147 (53%) of 278 were prescribed warfarin at discharge. Furthermore, among 130 (47%) of 278 patients not prescribed warfarin at discharge, 81 (62%) of 130 were also not prescribed aspirin. Increased potential benefit (additional vascular risk factors) was not associated with a higher rate of warfarin use. Low risk for anticoagulation (lack of risk factors for bleeding) was associated with a slightly higher rate of warfarin use. Among those with an increased risk of stroke and a low risk for bleeding (ideal candidates), 124 (62%) of 278 were discharged on a regimen of warfarin. CONCLUSION: Anticoagulation of elderly stroke patients with atrial fibrillation, even among ideal candidates, is underused. The increased use of warfarin among these patients represents an excellent opportunity for reducing the risk of recurrent stroke in this high-risk population.
BACKGROUND AND PURPOSE: Warfarin reduces the rate of stroke among patients with atrial fibrillation. We sought to determine warfarin use within a population sample of elderly patients with atrial fibrillation. METHODS: The Connecticut Peer Review Organization conducted a chart review of Medicare patients aged > or = 65 years with a history of atrial fibrillation before a hospitalization during the first 6 months of 1994. RESULTS: Among 488 patients (308 women; 457 white; 173 aged > or = 85 years), 38% (184/488) had a relative contraindication to anticoagulation (history of bleeding, dementia, alcohol use, falls, cancer, or the need for nonsteroidal anti-inflammatory drugs). Among the remaining patients (with known atrial fibrillation, but without a contraindication), only 38% (117/304) had been prescribed warfarin. Of those not prescribed warfarin, 63% (117/187) were also not taking aspirin. There were 272 patients with at least one additional vascular risk factor and no contraindication to anticoagulation. Among these patients at moderate to high risk for stroke, anticoagulation had been prescribed in 40% (109/272). Overal, among those not prescribed warfarin, 58% (95/163) were not taking aspirin. Patients admitted with a stroke were more likely to be significantly underanticoagulated (with international normalized ratio < 1.5) (43.5% versus 20.9% for those without stroke; P < .005). Anticoagulation was most effective for those with an international normalized ratio > or = 2.0. CONCLUSIONS: Warfarin anticoagulation with atrial fibrillation, even among "ideal" candidates, appears dramatically underutilized. In addition, among those prescribed warfarin, patients are often undertreated. Increased warfarin use among patients with atrial fibrillation represents an excellent opportunity for stroke prevention in the elderly.
PURPOSE: Histology has been identified as an important prognostic factor in Hodgkin's disease (HD) in adults. Information regarding the impact of histology on outcome in childhood HD is scarce. This study determines the effect of histology on the overall survival (OS) or progression-free survival (PFS) in a national series of children treated in a standardized manner. PATIENTS AND METHODS: The results of treatment of 331 assessable patients, treated between January 1, 1982 and June 30, 1992, in the United Kingdom Children's Cancer Study Group (UKCCSG) Hodgkin's study I were reviewed to evaluate OS, PFS, and deaths according to stage and histology. Treatment was either involved-field radiation alone (stage IA) or chlorambucil, vinblastine, procarbazine, and prednisolone (ChlVPP) chemotherapy with or without mediastinal radiation. All were clinically staged at diagnosis. RESULTS: Nodular sclerosing (NS) HD was the most common histologic subtype (155 of 331 patients [47%]) and was uniformly distributed through all stages. Lymphocyte-depletion (LD) HD was extremely uncommon (< 1%). Mixed-cellularity (MC) HD had the highest relapse rate, but this was only significant (P < .05) in stage I patients who received local irradiation alone. There was no other statistically significant difference in OS and PFS between the various histologic subtypes. Multivariate analysis for PFS and OS confirmed that stage was the most important prognostic factor and that histology did not have an effect after stratification by stage. CONCLUSION: This study demonstrates that with effective multiagent chemotherapy, histologic subtype does not influence outcome. The high relapse rates in stage I MC subtype indicates that MC HD is biologically aggressive and systemic treatment with or without local irradiation may be indicated. The high relapse rate in stage IV patients appeared to be independent of histology.
BACKGROUND: Although trials of amiodarone therapy in patients with congestive heart failure have produced discordant results with regard to effects on survival, most studies have reported a significant rise in left ventricular ejection fraction during long-term therapy. In the present study, we determined whether this increase in ejection fraction is associated with an improvement in the symptoms and/or physical findings of heart failure or a reduction in the number of hospitalizations for heart failure. METHODS AND RESULTS: In the Department of Veterans Affairs cooperative study of amiodarone in congestive heart failure, 674 patients with New York Heart Association class II through IV symptoms and ejection fractions of < or = 40% were treated with amiodarone or placebo for a median of 45 months in a randomized, double-blind, placebo-controlled protocol. Clinical assessments and radionuclide ejection fraction were performed at baseline and after 6, 12, and 24 months. Compared with the placebo group, ejection fraction increased more in the amiodarone group at each time point (8.1 +/- 10.2% [mean +/- SD] versus 2.6 +/- 7.9% at 6 months, 8.0 +/- 10.9% versus 2.7 +/- 8.0% at 12 months, and 8.8 +/- 10.1% versus 1.9 +/- 9.4% after 24 months, all P < .001). However, this difference was not associated with greater clinical improvement, lesser diuretic requirements, or fewer hospitalizations for heart failure (11.1% for amiodarone and 13.6% for placebo group; overall relative risk in the amiodarone group, 0.81 [95% CI, 0.56 to 1.10], P = .18). Of note is the trend toward a reduction in the combined end point of hospitalizations and cardiac deaths (relative risk, 0.82 [CI, 0.65 to 1.03], P = .08), which was significant in patients with nonischemic etiology (relative risk, 0.56 [CI, 0.36 to 0.87], P = .01) and absent in the ischemic group (relative risk, 0.95). CONCLUSIONS: Although amiodarone therapy resulted in a substantial increase in left ventricular ejection fraction in patients with congestive heart failure, this was not associated with clinical benefit in the population as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients.
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Gonadal function was assessed in 101 postpubertal subjects after chemotherapy for childhood Hodgkin's disease. All had received ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone) chemotherapy alone, with no radiotherapy below the diaphragm. Gonadotropin levels were available in 46 (79.3%) male and 32 (74.4%) female subjects. The mean age at diagnosis in the male cohort was 12.2 years (range 8.2-15.3) and in the females 13.0 years (9.0-15.2). The males and the females were studied at a median of 6 years (range 2.5-11.1) and 4.3 years (range 1.9-11.5) from diagnosis, respectively. Forty-one (89.1%) male subjects had elevated follicle-stimulating hormone (FSH) levels, confirming severe germinal epithelial damage. Germinal epithelial damage was seen in subjects up to 10 years out of therapy. Subtle Leydig cell dysfunction was identified in 24.4% with raised luteinzing hormone (LH) levels. All subjects, however, progressed spontaneously through puberty. Seventeen (53%) women had raised gonadotropin levels, with variable estradiol levels. Of these, 10 subjects presented with symptomatic ovarian failure and 6 received hormone replacement therapy (HRT). Nine women had 11 successful pregnancies, two of whom had previously had symptoms of ovarian failure with one requiring HRT. A much higher prevalence of ovarian failure has been observed, than has previously been considered in the prepubertal and pubertal female following combination chemotherapy. These conclusions have important implications for future counseling, management, and research in this population.
OBJECTIVE: To examine differences between frequent and infrequent users in decisions to seek medical care based on symptom type and duration of experience of the symptom. DESIGN: Retrospective study. SETTING: University family practice clinic. PATIENTS: Fifty-eight of 130 patients returned the completed instruments, a response rate of 45%. MAIN OUTCOME MEASURES: The following two instruments were used: the Intentions to Seek Care questionnaire, which measures intention to see a physician, self-treat, or use medications for 11 different symptoms after three time periods--1 day, 3 days, and 1 week of symptom duration--and the SF-36 Health Survey measure. RESULTS: Initial analyses suggested that patients perceive three clusters of symptoms, which we have labeled as serious, mild, and psychological. Scale scores for these groups of symptoms yielded significant reliability and were used in subsequent analyses. Multivariate analysis of variance comparing source of care, symptom duration, and frequent vs infrequent user groups indicated that both user groups are more likely to seek care from physicians for symptoms that are serious. Analysis of mild and psychological symptoms yielded significant three-way interactions, with frequent users more likely than infrequent users to seek care from physicians at a 1-day duration. Such differences disappear by 7 days. Significantly lower scores were obtained on five of the eight SF-36 Health Survey dimensions for the infrequent users. CONCLUSIONS: Frequent users are more likely than infrequent users to report that they would seek care for minor symptoms. Infrequent users tend to self-treat for 3 to 7 days, after which time physician advice is sought. Efforts to teach patients optimal timing of use for different symptoms may be an effective intervention.