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Biomedical subjects

Charles Scott

Publications and source records attributed to Charles Scott.

17 recordsLinked to original sources
PubMed2006

A modified Hammersmith functional motor scale for use in multi-center research on spinal muscular atrophy.

The Hammersmith functional motor scale for children with spinal muscular atrophy was modified to establish a standard measure of functional ability in children with non-ambulant spinal muscular atrophy types 2 and 3 in a longitudinal multi-center clinical trial. This study assessed the intra- and interrater reliability and the test-retest stability of a modified version of the scale. Both intra- and interrater reliability were established. Results indicate that the scale is reliable and stable over a 6 month period. Reliability was maintained when patient sample criteria were expanded to include children younger than 30 months and children with popliteal angles greater than 20 degrees . These data establish the modified Hammersmith functional motor scale for children with spinal muscular atrophy as a reliable instrument for use in multi-center treatment trials in non-ambulant spinal muscular atrophy children. Our data provides additional support for the use of original scale items in terms of ease of administration, usefulness and reliability, while incorporating modifications to optimize its use in a multi-center clinical research setting.

Child, Preschool↗
PubMed2006

Pretreatment factors significantly influence quality of life in cancer patients: a Radiation Therapy Oncology Group (RTOG) analysis.

PURPOSE: The purpose of this analysis was to assess the impact of pretreatment factors on quality of life (QOL) in cancer patients. METHODS AND MATERIALS: Pretreatment QOL (via Functional Assessment of Cancer Therapy [FACT], version 2) was obtained in 1,428 patients in several prospective Radiation Therapy Oncology Group (RTOG) trials including nonmetastatic head-and-neck (n = 1139), esophageal (n = 174), lung (n = 51), rectal (n = 47), and prostate (n = 17) cancer patients. Clinically meaningful differences between groups were defined as a difference of 1 standard error of measurement (SEM). RESULTS: The mean FACT score for all patients was 86 (20.7-112) with SEM of 5.3. Statistically significant differences in QOL were observed based on age, race, Karnofsky Performance Status, marital status, education level, income level, and employment status, but not by gender or primary site. Using the SEM, there were clinically meaningful differences between patients </=50 years vs. >/=65 years. Hispanics had worse QOL than whites. FACT increased linearly with higher Karnofsky Performance Status and income levels. Married patients (or live-in relationships) had a better QOL than single, divorced, or widowed patients. College graduates had better QOL than those with less education. CONCLUSION: Most pretreatment factors meaningfully influenced baseline QOL. The potentially devastating impact of a cancer diagnosis, particularly in young and minority patients, must be addressed.

Adenocarcinoma↗
PubMed2005

Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer.

PURPOSE: Efaproxiral (RSR13) reduces hemoglobin oxygen-binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10. RESULTS: Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%). CONCLUSION: Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.

Adult↗
PubMed2005

Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol.

PURPOSE: This phase II noncomparative randomized trial was conducted to determine the optimal sequencing and integration of paclitaxel/carboplatin with standard daily thoracic radiation therapy (TRT), in patients with locally advanced unresected stage III non-small-cell lung cancer (NSCLC). Survival data were compared with historical standard sequential chemoradiotherapy data from the Radiation Therapy Oncology Group. PATIENTS AND METHODS: Patients with unresected stages IIIA and IIIB NSCLC, with Karnofsky performance status > or = 70% and weight loss < or = 10%, received two cycles of induction paclitaxel (200 mg/m2)/carboplatin (area under the plasma concentration time curve [AUC] = 6) followed by TRT 63.0 Gy (arm 1, sequential) or two cycles of induction paclitaxel (200 mg/m2)/carboplatin (AUC = 6) followed by weekly paclitaxel (45 mg/m2)/carboplatin (AUC = 2) with concurrent TRT 63.0 Gy (arm 2, induction/concurrent), or weekly paclitaxel (45 mg/m2)/carboplatin (AUC = 2)/TRT (63.0 Gy) followed by two cycles of paclitaxel (200 mg/m2)/carboplatin (AUC = 6; arm 3, concurrent/consolidation). RESULTS: With a median follow-up time of 39.6 months, median overall survival was 13.0, 12.7, and 16.3 months for arms 1, 2, and 3, respectively. During induction chemotherapy, grade 3/4 granulocytopenia occurred in 32% and 38% of patients on study arms 1 and 2, respectively. The most common locoregional grade 3/4 toxicity during and after TRT was esophagitis, which was more pronounced with the administration of concurrent chemoradiotherapy on study arms 2 and 3 (19% and 28%, respectively). CONCLUSION: Concurrent weekly paclitaxel, carboplatin, and TRT followed by consolidation seems to be associated with the best outcome, although this schedule was associated with greater toxicity.

Aged↗
PubMed2005

Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01.

PURPOSE: To test the ability of the cytoprotectant, amifostine, to reduce chemoradiotherapy-induced esophagitis and evaluate its influence on quality of life (QOL) and swallowing symptoms. PATIENTS AND METHODS: A total of 243 patients with stage II to IIIA/B non-small-cell lung cancer received induction paclitaxel 225 mg/m(2) intravenously (IV) days 1 and 22 and carboplatin area under the curve (AUC) days 1 and 22, followed by concurrent weekly paclitaxel (50 mg/m(2) IV) and carboplatin (AUC 2), and hyperfractionated radiation therapy (69.6 Gy at 1.2 Gy bid). Patients were randomly assigned at registration to amifostine (AM) 500 mg IV four times per week or no AM during chemoradiotherapy. Beyond standard toxicity end points, physician dysphagia logs (PDLs), daily patient swallowing diaries, and QOL (EORTC QLQ-C30/LC-13) were also collected. Swallowing AUC analyses were calculated from patient diaries and PDLs. RESULTS: A total of 120 patients were randomly assigned to receive AM, and 122, to receive no AM (one patient was ineligible); 72% received AM per protocol or with a minor deviation. AM was associated with higher rates of acute nausea (P = .03), vomiting (P = .007), cardiovascular toxicity (P = .0001), and infection or febrile neutropenia (P = .03). The rate of >/= grade 3 esophagitis was 30% with AM versus 34% without AM (P = .9). Patient diaries demonstrated lower swallowing dysfunction AUC with amifostine (z test P = .025). QOL was not significantly different between the two arms, except for pain, which showed more clinically meaningful improvement and less deterioration at 6 weeks follow-up (v pretreatment) in the AM arm (P = .003). The median survival rates for both arms were comparable (AM, 17.3 v no AM, 17.9 months; P = .87). CONCLUSION: AM did not significantly reduce esophagitis >/= grade 3 in patients receiving hyperfractionated radiation and chemotherapy. However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies.

Aged↗
PubMed2005

Liquid-core capsules via interfacial polymerization: a free-radical analogy of the nylon rope trick.

Liquid-core capsules have wide-ranging applications in the high-efficiency encapsulation and controlled release of drugs, dyes, enzymes, and other substrates. Their great utility has driven the rapid development of various preparation techniques. However, there remains no convenient technique for the preparation of submicrometer liquid-core capsules with shell thicknesses less than 100 nm. Here, we demonstrate a new interfacial free-radical polymerization approach for the straightforward preparation of liquid-core polymer capsules. Conceptually, this interfacial free-radical polymerization is analogous to the classical "nylon rope trick" wherein hydrophobic and hydrophilic monomers alternately copolymerize to constrain the polymerization at interfaces, but its free-radical mechanism allows precise control of initiation, which makes it possible to finely disperse the immiscible phases prior to polymerization.

Journal Article↗
PubMed2004

Bad reporting does not mean bad methods for randomised trials: observational study of randomised controlled trials performed by the Radiation Therapy Oncology Group.

OBJECTIVE: To determine whether poor reporting of methods in randomised controlled trials reflects on poor methods. DESIGN: Observational study. SETTING: Reports of randomised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968. PARTICIPANTS: The Radiation Therapy Oncology Group. Outcome measures Content of reports compared with the design features described in the protocols for all randomised controlled trials. RESULTS: The methodological quality of 56 randomised controlled trials was better than reported. Adequate allocation concealment was achieved in all trials but reported in only 42% of papers. An intention to treat analysis was done in 83% of trials but reported in only 69% of papers. The sample size calculation was performed in 76% of the studies, but reported in only 16% of papers. End points were clearly defined and alpha and beta errors were prespecified in 76% and 74% of the trials, respectively, but only reported in 10% of the papers. The one exception was the description of drop outs, where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group. CONCLUSIONS: The reporting of methodological aspects of randomised controlled trials does not necessarily reflect the conduct of the trial. Reviewing research protocols and contacting trialists for more information may improve quality assessment.

Clinical Trials, Phase III as Topic↗
PubMed2004

Quality-of-life trials in lung cancer: past achievements and future challenges.

Much work has been done regarding QOL in lung cancer trials. There are now several validated QOL instruments, particularly for patients with lung cancer. Past accomplishments include key trials demonstrating a benefit of chemotherapy or radiation in patients with advanced NSCLC not only regarding traditional endpoints but also by improving palliation and aspects of QOL such as pain and dyspnea. More recently, studies have emerged that incorporate QOL in patients with locally advanced disease. Key challenges relate to the optimal design and successful completion of these QOL studies. Missing data remains a key problem in many QOL studies, particularly in lung cancer trials. Future studies should focus on incorporating QOL into phase III studies with clear hypotheses that can ultimately lead to clinically meaningful interventions.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Phase III quality-of-life study results: impact on patients' quality of life to reducing xerostomia after radiotherapy for head-and-neck cancer--RTOG 97-09.

PURPOSE: To determine whether prevention of hyposalivation after curative radiotherapy (RT) to the head and neck improves patients' quality of life (QOL). METHODS AND MATERIALS: Patients were to receive at least 50 Gy to 50% of the volume of the major salivary glands, provide unstimulated and stimulated saliva samples, and complete the University of Washington head-and-neck QOL tool before RT and 3 and 6 months after RT. Patients were randomized to receive pilocarpine 5 mg or placebo q.i.d. RESULTS: A total of 249 patients was randomized between March 1998 and January 2000. Of these, 214 were eligible for QOL analysis. Patients were evenly distributed between arms by race, gender, tobacco use, tumor site, T stage (50% T2-T3), and salivary function. A Karnofsky performance status of 90% was more common in the pilocarpine arm. Twenty percent of the patients on the pilocarpine arm and 29% of the patients on the placebo arm were taking nutritional supplements. The placebo arm patients had greater mouth pain and chewing difficulties. Compliance for the QOL tool at 3 and 6 months was 65% and 50%, respectively. Despite statistically significant (p = 0.047 and p = 0.049, respectively) preservation of salivary function in the pilocarpine arm, patients on the pilocarpine arm reported difficulties with swallowing (75%), activity (80%), hyposalivation (64%), and taste (81%). No difference was noted between arms at 3 months in mucositis scores, with both arms demonstrating increased requirement for oral nutrients. CONCLUSION: Objective prevention of hyposalivation did not affect patients' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT.

Female↗
PubMed2003

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.

Adult↗
PubMed2003

The impact of regional nodal radiotherapy (dose/volume) on regional progression and survival in unresectable non-small cell lung cancer: an analysis of RTOG data.

PURPOSE: To evaluate in-field progression and survival of patients with unresectable non-small cell lung cancer (NSCLC) in relation to adequacy of coverage of thoracic regional nodal areas in the radiotherapy volume. MATERIALS AND METHODS: A total of 1705 patients from four large RTOG trials (78-11, 79-17, 83-11 and 84-07) were analyzed for this purpose. For each of these trials, the dose delivered to nodal regions was recorded and an assessment of adequacy of field borders was made. Each nodal site was assessed for progression, defined as in-field or out-of-field. In patients who had adequate borders on nodal regions, the results were analyzed according to the dose delivered. RESULTS: The majority (74%) of patients were between the age of 55-75. Forty-six percent of the patients had KPS of 60-80 and 52% had KPS of 90-100. Sixty percent of patients had a weight loss of less than 5% in the 6 months prior to diagnosis. Deviations from the protocol in field borders (borders not per protocol) were most frequent for the contralateral hilum (25.2%) and least frequent in the ipsilateral hilum (6.3%). The adequacy of ipsilateral hilar coverage was important for preventing the in-field progression (11.6 vs. 22% for adequately vs. inadequately covered ipsilateral hilum, respectively, P=0.01), however, did not influence the 2-year-survival (35 vs. 37%) or median survival (1.3 vs. 1.1 year). Neither the in-field progression nor the 2-year-survival were affected by adequacy of nodal coverage in the mediastinum, ipsilateral supraclavicular area and contralateral hilum, even when different doses were analyzed. CONCLUSION: These data suggest that elective irradiation of mediastinal, contralateral hilar and supraclavicular lymph nodes may not be necessary in the treatment of unresectable NSCLC.

Aged↗
PubMed2003

Prevalence of violent victimisation in severe mental illness.

BACKGROUND: Since de-institutionalisation, much has been written about the risk posed to the community by those with severe mental illness. However, violent victimisation of people with mental illnesses has received little attention. AIMS: To establish the 1-year prevalence of violent victimisation in community-dwelling patients with psychosis and to identify the socio-demographic and clinical correlates of violent victimisation. METHOD: A total of 691 subjects with established psychotic disorders were interviewed. The past-year prevalence of violent victimisation was estimated and compared with general population figures. Those who reported being violently victimised were compared with those who did not on a range of social and clinical characteristics. RESULTS: Sixteen per cent of patients reported being violently victimised. Victims of violence were significantly more likely to report severe psychopathological symptoms, homelessness, substance misuse and previous violent behaviour and were more likely to have a comorbid personality disorder. CONCLUSIONS: Those with psychosis are at considerable risk of violent victimisation in the community. Victimisation experience should be recorded in the standard psychiatric interview.

Adolescent↗
PubMed2002

Prospective randomized study of four novel chemotherapy regimens in patients with advanced nonsmall cell lung carcinoma: a minnie pearl cancer research network trial.

BACKGROUND: The authors compared the toxicity, response rate, and progression free survival of four chemotherapy regimens for patients with advanced (Stage IIIB and IV) nonsmall cell lung carcinoma. METHODS: A total of 267 patients entered this randomized Phase II trial on one of four arms: paclitaxel, carboplatin, and gemcitabine (Arm A); paclitaxel, carboplatin, and vinorelbine (Arm B); paclitaxel and gemcitabine (Arm C); and gemcitabine and vinorelbine (Arm D). Patient characteristics were similar in all treatment arms. At the time of tumor progression, patients were removed from study and were treated at the discretion of their physician. RESULTS: Patients received a median of four courses of chemotherapy in all arms, and there was no difference in the dose delivered. There were no statistical differences in response rates (range, 32-45%), median progression free survival (range, 4.9-6.6 months), or progression free survival at 1 year (range, 8-19%). Actuarial survival in all four arms was not different, with a median survival ranging from 8.7 months to 10.7 months and a 1-year survival rate of 38-44%. Each arm was compared with a historic control with a median survival of 8 months. Arm D (gemcitabine and vinorelbine) approached significance at the 0.05 level. CONCLUSIONS: Two-drug combinations containing the newer drugs without a platinum drug were less toxic than three-drug, platinum-based regimens. There were no significant differences in objective response rates or progression free survival when the four regimens were compared. The two-drug combination of gemcitabine and vinorelbine was the least toxic and, thus, may be superior. A Phase III trial comparing combined gemcitabine and vinorelbine with combined paclitaxel, carboplatin, and gemcitabine is ongoing.

Adult↗
PubMed2002

Statistical issues in studies of toxicity modifiers.

The primary focus of oncology is the search for a cure. In pursuit of this goal, therapeutic regimens have increased in intensity, often causing increased normal tissue morbidity. Pharmacologic agents are being developed to ameliorate or prevent these toxicities. The stepwise investigation of these agents requires a different paradigm from standard drug development. Traditionally, phase I studies are designed to find the maximum tolerated dose of an experimental drug; however, in pharmacologic agents that aim to reduce toxicity, defining the maximum tolerated dose, may not be necessary. The focus of phase I studies in these agents is the establishment of the maximum effective dose. Phase II studies traditionally are designed to establish efficacy of an experimental regimen before advancing to a phase III study. To determine potential efficacy, predictable efficacy levels must be available in the literature for standard therapy. In this manner, the phase II study can be evaluated against the historical control to determine if a phase III study should be conducted. This generally is not possible in the context of toxicity modifiers. Because of variability in toxicity assessment, prior rates of toxicity may not be reliable when evaluated against a phase II study focusing on toxicity amelioration. Because the assessment of toxicity is subjective, retrospective comparisons may be biased and lead to the wrong conclusion. One method to correct for this bias is to conduct placebo-controlled, randomized phase II studies. Phase III studies of toxicity modifiers have toxicity amelioration or prevention as the primary objective. These studies should be designed to assess the subjective and objective components of toxicity, evaluate quality of life, and assess possible adverse effects on therapeutic outcomes. Design and analysis issues are discussed in this report.

Clinical Trials, Phase III as Topic↗
PubMed2002

Group vs individual approaches to understanding the clinical significance of differences or changes in quality of life.

This article focuses on the traversing of group and individual levels of quality-of-life data. A deductive approach is used to address the extent to which group data can be used to estimate clinical significance at the individual level. An inductive approach is used to evaluate the extent to which individual change data can be brought to the group level to define clinical significance. Both approaches have benefits and drawbacks. This article addresses how clinical significance can be defined for an individual when the threshold for meaningfulness is drawn from group data. It also addresses the condition under which one can use the same threshold difference for group vs individual differences or changes. A sample inductive approach explores the means to identify a clinically significant result or change, with use of insights from cognitive psychology. In most deductive approaches, the identification of a clinically significant difference or change requires identification of a criterion (or at least an interpretable anchor) against which the significance of a change in respondent score is compared.

Confidence Intervals↗
PubMed2002

AAPL practice guideline for forensic psychiatric evaluation of defendants raising the insanity defense. American Academy of Psychiatry and the Law.

The insanity defense is a legal construct that excuses certain mentally ill defendants from legal responsibility for criminal behavior. This practice guideline has delineated the forensic psychiatric evaluation of defendants raising the insanity defense. The document describes acceptable forensic psychiatric practices. Where possible, standards of practice and ethical guidelines have been specified. And where appropriate, the practice guideline has emphasized the importance of analyzing the individual case, the jurisdictional case law and the state (or federal) statute. This practice guideline is limited by the evolving case law, statutory language and legal literature. The authors have emphasized the statutory language of current legal standards, as well as the state or federal courts' interpretation of those standards because the same statutory language has been interpreted differently in different jurisdictions. Similarly, this practice guideline has reviewed the state and federal trends that determine which diagnoses meet the criteria for mental disease or defect. These trends yield to jurisdictional court interpretations. Finally, the authors hope this practice guideline has begun the dialogue about formulating a forensic psychiatric opinion by surveying the various approaches used to analyze case data. The forensic psychiatrist's opinion in each case requires an understanding of the current jurisdictional legal standard and its application, as well as a thorough analysis of the individual case. The psychiatrist's analysis and opinion should be clearly stated in the forensic psychiatric report. It should be noted that the role of a psychiatric expert witness in the criminal justice system is predicated on the law's interest in individualizing the criteria of mitigation and exculpation. Forensic psychiatric analyses and formulations of opinions are, therefore, subject to change as the legal guidance changes.

Ethics, Medical↗