Unresolved legal and ethical issues in research of adults with severe traumatic brain injury: analysis of an ongoing protocol

This paper synthesizes federal and state laws and bioethics literature with observations from an ongoing research protocol to identify, define, and clarify the unresolved legal and ethical issues regarding research involving adults with traumatic brain injury (TBI). Solutions that protect rights and minimize unnecessary impediments to valuable clinical and scientific inquiry are also illustrated using the same protocol. Research was performed at intensive care, inpatient rehabilitation, and long-term acute chronic hospitals. Our research protocol identified five areas of law impacting adults with TBI: advanced directives, healthcare surrogacy acts, probate acts, power of attorney acts, and the Health Insurance Portability and Accountability Act. The published bioethics literature and responses from local human subject institutional review boards (IRBs) suggest that some of the unresolved ethical issues in research include defining vulnerability, defining informed voluntary consent, determining competency and/or decision-making capacity, using caregivers as subjects, and conducting multisite cooperative studies. Collaboration with IRB members and administrators as well as legal and research ethic scholars developed procedures that protect rights while avoiding unnecessary impediments to research. Investigations of persons with TBI and other cognitive impairments are governed by complicated and inconsistent regulations within the Common Rule and federal and state statues. A need for clear and consistent regulatory guidance regarding multisite studies of TBI persists. In lieu of regulatory guidance, carefully researched solutions for critical peer review are needed to guide future multisite investigations of TBI.     

Treatment of Allergic Bronchopulmonary Aspergillosis with Fluconazole and Itraconazole

Treatment of allergic bronchopulmonary aspergillosis (ABPA) has remained both problematic as well as controversial. Although the sheet anchor in treatment of ABPA still remains steroids, various workers have tried oral antifungals (fluconazole and itraconazole) with encouraging results. This study evaluates the effect of fluconazole or itraconazole in the treatment of ABPA patients and compares them with the patients who had received palliative therapy other than antifungals. Case records of 44 proven cases of ABPA treated at our referral service hospital during February 1998 to April 2001 were analyzed. In addition to oral and inhaled bronchodilators, 16 patients received fluconazole 150 mg OD and 13 patients itraconazole 200 mg OD for six months. Response to therapy was assessed clinically, radiologically and by spirometry every 3 months. Patients who did not receive antifungals had chronic course characterized by airway obstruction, recurrent pulmonary consolidation and obstructive defect on pulmonary function test (PFT). Patients treated with itraconazole had better control of asthma symptoms, less requirement of reliever inhalers, steroids and lesser exacerbations of asthma during follow-up even after stopping antifungal. Fluconazole group had better control of symptoms but improvement in other parameters was not statistically significant. From this study it was evident that itraconazole improved the symptoms of airway obstruction, pulmonary functions, pulmonary opacities and decreased exacerbations during follow up.Key Words: Allergic bronchopulmonary aspergillosis, Fluconazole, Itraconazole     

Patient satisfaction with teledermatology: quantitative and qualitative results from a randomized controlled trial

As part of a randomized controlled trial involving 208 dermatology patients, a quantitative and qualitative study was undertaken to explore patients' satisfaction with a specialist dermatological opinion and further management obtained through either a traditional outpatient consultation (control group) or an asynchronous teleconsultation (telemedicine group). There was a response rate of 71% to the quantitative patient satisfaction survey (148 replies from 208 distributed questionnaires). The responders comprised 80 of the 111 telemedicine patients (72%) and 68 of the 97 control patients (70%). Overall levels of patient satisfaction were high in both groups, and there was no significant difference between them. Ninety per cent of patients in the control group were satisfied with their overall care, compared with 81% in the telemedicine group, and 87% of patients in the control group were satisfied with their overall management, compared with 84% in the telemedicine group. Follow-up qualitative interviews with 30 of the participants also suggested that patients were generally positive about their care and management, regardless of group, age or gender. Receiving a diagnosis, treatment and cure, receiving adequate information and explanations, the need to be taken seriously, the need for individualized personal care, and the importance of a short waiting time for an appointment and treatment were all aspects of care and management most likely to result in patient satisfaction, regardless of modality.     

General practitioners' perceptions of asynchronous telemedicine in a randomized controlled trial of teledermatology

We studied the perceptions of general practitioners (GPs) towards teledermatology, before and after its introduction into eight general practices for the purposes of a randomized controlled trial. A postal questionnaire was distributed before the trial and again one year later. Thirty-six of the 42 GPs responded on each occasion (a response rate of 86%). In the second survey, only 21% of respondents indicated that they were satisfied with teledermatology in their practice, while 47% said that they were dissatisfied. Thirty-one per cent said that they felt confident about diagnosis and management of care through teledermatology, and 28% reported that they were unconfident. Only 23% of respondents said that they would consider using a telemedicine system in the future, while 34% said they would not (43% were unsure). There were no significant findings to suggest that the GPs' perceptions changed over time. Less favourable responses to telemedicine were found than has been observed in previous studies, which suggests that the model of telemedicine described in this study would not be widely acceptable to GPs.     

Identification of putative gene based markers of renal toxicity

This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.     

Prevalence of comorbid psychiatric illness and substance misuse in primary care in England and Wales

STUDY OBJECTIVE: To estimate the annual period prevalence of co-occurring psychiatric illness and substance misuse among patients in primary care. DESIGN: Analysis of the general practice research database. SETTING: England and Wales, 1993-1998. PARTICIPANTS: Registered patients at 230 general practices representing 3.1% of the population. A comorbid case was defined as one with both a psychiatric diagnosis and substance misuse diagnosis (not including alcohol or tobacco) within a calendar year. A potentially chronic comorbid case was one that met this definition and, in addition, was treated in subsequent years for either a psychiatric condition or substance misuse. MAIN RESULTS: The annual period prevalence of comorbidity increased from 50/100 000 patient years of exposure (PYE) to 80/100 000 PYE, an increase of 62% during the study period. Rates of comorbid psychoses, comorbid schizophrenia, and comorbid paranoia increased by 147%, 128%, and 144%. The average age of comorbid cases decreased from 38 years to 34 years. Over 80% of comorbid cases were newly diagnosed in each study year, although many are treated in subsequent years for either psychiatric illness or substance misuse. CONCLUSIONS: This study provides data on the nature and extent of comorbidity in primary care in England and Wales. As the comorbidity rate is increasing by about 10% each year, and as comorbid cases are becoming younger, it is probable that the comorbidity rate will have increased beyond the study end point.