Brief report on the United States Food and Drug Administration Blood Products Advisory Committee recommendations for management of donors and units testing positive for hepatitis B virus DNA.

BACKGROUND AND OBJECTIVES: This article briefly recounts the 21st July 2005, Blood Products Advisory Committee (BPAC) meeting concerning recommendations for management of donors and units testing positive for hepatitis B virus (HBV) DNA. MATERIALS AND METHODS: The author attended the meeting. The United States Food and Drug Administration (FDA) web site was used for meeting materials, and handouts were collected at the meeting to provide narrative information. Two European experts assisted with HBV subject matter. RESULTS: The proceedings of the advisory committee, the issue briefing materials, and testing algorithms are presented. CONCLUSION: BPAC voted concurrence with the FDA algorithm for Management of Donors and Units Testing Positive for Hepatitis B Virus DNA.

The gene expression sequence of radiated mucosa in an animal mucositis model.

Oral mucositis is a common, dose-limiting, acute toxicity of radiation therapy administered for the treatment of cancers of the head and neck. Accumulating data would suggest that the pathogenesis of mucositis is complex and involves the sequential interaction of all cell types of the oral mucosa, as well as a number of cytokines and elements of the oral environment. While a number of studies have reported on gene expression of particular cell types in response to radiation, the overall response of irradiated mucosa has only been evaluated in a limited way. The present study was undertaken to evaluate the expression of a target group of genes using RNA quantification assays and, more broadly, to assess patterns of mucosal gene expression using DNA microarray hybridization. Our results demonstrate the sequential upregulation of a series of genes that, when taken collectively, suggest an intricate functional interaction.

Daily smoking by Louisiana students: sixth through twelfth grades, 1996-1997.

OBJECTIVES: We sought to determine the prevalence of daily smoking in Louisiana in grades 6 through 12 and to compare Louisiana students' daily smoking to that of national student and Louisiana adult rates. METHODS: A statewide, randomized, stratified classroom-based survey of 11,736 subjects was done for the school year 1996-1997. RESULTS: We found that 17.3% of sixth grade students smoked daily, increasing to 36.1% in twelfth grade. Native American (43.7%), white (37.8%), and public school (28.5%) students had the highest rates of daily smoking. Males and females smoked at similar rates. Louisiana students in grades 8, 10, and 12 smoked daily at much higher rates (331%, 193%, and 146%, respectively) than comparable national samples. In 1997, Louisiana students smoked daily at higher rates than did Louisiana adults (28.9% vs 24.6%), primarily due to higher rates of smoking in student females (27.1%) compared to adult females (20.4%). CONCLUSIONS: Student smoking in Louisiana is a significant public health problem.

Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters.

Oral ulcerative mucositis is a common toxicity associated with drug and radiation therapy for cancer. It impacts on quality of life and economic outcomes, as well as morbidity and mortality. Mucositis is often associated with dose limitations for chemotherapy or is a cause for dose interruption for radiation. The complexity of mucositis as a biological process has only been recently appreciated. It has been suggested that the condition represents a sequential interaction of oral mucosal cells and tissues, pro-inflammatory cytokines and local factors such as saliva and the oral microbiota. The recognition that the pathophysiology of mucositis is a multifactorial process was partially suggested by the observation that interleukin-11 (IL-11), a pleotropic cytokine, favorably altered the course of chemotherapy-induced mucositis in an animal model. In the current study, we evaluated a series of biologic and morphologic outcomes to determine their roles and sequence in the development of experimental radiation-induced mucositis and to evaluate the effects of IL-11 in attenuating them. Our results suggest that IL-11 favorably modulates acute radiation-induced mucositis by attenuating pro-inflammatory cytokine expression. Data are also presented which help define the pathobiological sequence of mucositis.

The biological basis for the attenuation of mucositis: the example of interleukin-11.

Oral mucositis is common, painful, dose-limiting toxicity of drug and radiation therapy for cancer. In granulocytopenic patients, the ulcerations which accompany mucositis are frequent portals of entry for indigenous oral bacteria often leading to bacteremias or sepsis. The complexity of mucositis as a biological process has only recently been appreciated. The condition appears to represent a sequential interaction of the oral mucosal cells and tissues, pro-inflammatory cytokines, and local environmental factors in the mouth such as microorganisms and saliva. The recognition that the pathophysiology of mucositis is a multifactorial process has presented opportunities for intervention based on biological attenuation. Interleukin-11, a pleotropic cytokine, has a range of activities which is potentially relevant to mucositis. Consequently, it has been used successfully to modify the development, severity and course of mucositis in an animal model which closely mimics the equivalent human condition.

A comparison of physicians' and patients' attitudes toward pharmaceutical industry gifts.

OBJECTIVE: To compare physicians' and their patients' attitudes toward pharmaceutical gifts. DESIGN: Survey of physicians and their patients. SETTING: Two tertiary-care medical centers, one military and one civilian. PARTICIPANTS: Two hundred sixty-eight of 392 consecutively surveyed physicians, 100 of 103 randomly selected patients at the military center, and 96 patients in a convenience sample at the civilian center completed the survey. MEASUREMENTS: Participants rated 10 pharmaceutical gifts on whether they were appropriate for physicians to accept and whether they were likely to influence prescribing. Patients found gifts less appropriate and more influential than did their physicians. About half of the patients were aware of such gifts; of those unaware, 24% responded that this knowledge altered their perception of the medical profession. Asked whether they thought their own physician accepted gifts, 27% said yes, 20% no, and 53% were unsure. For patients, feeling that gifts were inappropriate was best predicted by a belief that gifts might influence prescribing, while for physicians, the best predictor was knowledge of guidelines. CONCLUSIONS: Patients feel pharmaceutical gifts are more influential and less appropriate than do their physicians. Physicians may want to consider this in deciding whether to accept particular gifts. Broader dissemination of guidelines may be one means of changing physician behavior. At the same time, future guidelines should further consider the potentially different viewpoints of patients and physicians.

New approach to administrative medical decision-making: evidence-based medicine using high dose chemotherapy/bone marrow transplant for breast cancer.

BACKGROUND: Payment for experimental treatments using medical necessity criteria has been controversial. The process of obtaining a decision on coverage of an experimental treatment can be distressful for the treating physician, the patient, and family members. METHOD: The techniques of evidence-based medicine were used to assist with treatment/coverage decisions concerning high dose chemotherapy with autologous bone marrow transplants (HDC/ABMT) for invasive breast cancer. RESULTS: We reviewed the literature, finding minimal evidence for effectiveness of HDC/ABMT for invasive breast cancer; therefore, it is our opinion that it remains an experimental therapy. Its cost utility is likely to be low (approximately $100,000 per additional quality year gained). Numerous patients have been treated with HDC/ABMT outside of clinical trials, impeding scientific analysis of the treatment's effectiveness. CONCLUSION: Data-based policies and procedures for funding experimental medical treatments need to be developed to eventually replace the medical necessity criteria.

Bedside teaching.

BACKGROUND: Clinical teachers have been exhorted to "return to the bedside" so that the three critical parties-teacher, trainee, and patient-can participate together in the educational encounter. The presence of the patient is deemed essential for the optimal demonstration and observation of physical examination, medical interviewing, and interpersonal skills, as well as role-modeling professional and humanistic behavior. METHODS: This essay reviews the challenges inherent in bedside teaching and proposes strategies to enhance both the effectiveness and efficiency of such teaching. RESULTS: Practical suggestions are provided regarding teaching issues (time constraints, group accommodation, selectivity, demonstration, observation, case presentations), learning climate for both teacher and learners, hospital and patient barriers, and selected other issues. CONCLUSIONS: Despite changes in the clinical setting and financing of medical education, patient-centered teaching will remain essential to the training of future clinicians. Techniques described in this paper can be useful in facilitating such bedside teaching.

Concerns and expectations in patients presenting with physical complaints. Frequency, physician perceptions and actions, and 2-week outcome.

BACKGROUND: Specific concerns and expectations may be a key reason that people with common physical complaints seek health care for their symptoms. OBJECTIVES: To determine the frequency of symptom-related patient concerns and expectations, physician perceptions and actions, and the relationship of these factors to patient satisfaction and symptom outcome. METHODS: This was a prospective cohort study of 328 adult outpatients presenting for evaluation of a physical complaint. The setting was a general medicine clinic in a teaching hospital. Measures included previsit patient questionnaire to identify symptom-related concerns and expectations; a postvisit physician questionnaire to determine physician perceptions and actions; and a 2-week follow-up patient questionnaire to assess symptom outcome and satisfaction with care. RESULTS: Pain of some type accounted for 55% of common symptoms, upper respiratory tract illnesses for 22%, and other physical complaints for 23%. Two thirds of patients were worried their symptom might represent a serious illness, 62% reported impairment in their usual activities, and 78%, 46%, and 41% hoped the physician would prescribe a medication, order a test, or provide a referral. Physicians often perceived symptoms as less serious or disabling and frequently did not order anticipated tests or referrals. While symptoms improved 78% of the time at 2-week follow-up, only 56% of patients were fully satisfied. Residual concerns and expectations were the strongest correlates of patient satisfaction. CONCLUSIONS: Improved recognition of symptom-related concerns and expectations might improve satisfaction with care in patients presenting with common physical complaints.

Can the clinical examination diagnose left-sided heart failure in adults?

We systematically reviewed the literature to ascertain how well clinicians determine the probability and type of left-sided heart failure in their patients. Left-sided heart failure is characterized by decreased left ventricular ejection fraction or increased filling pressure. The type of heart failure determines optimal treatment. Systolic dysfunction exists when ejection fraction is reduced. Diastolic dysfunction is presumed to be present when filling pressure is increased with a normal ejection fraction and without another explanatory diagnosis. Many findings are associated with heart failure, and wide variation exists in clinicians' ability to detect these findings. The best findings for detecting increased filling pressure are jugular venous distention and radiographic redistribution. The best findings for detecting systolic dysfunction are abnormal apical impulse, radiographic cardiomegaly, and q waves or left bundle branch block on an electrocardiogram. Diastolic dysfunction is especially difficult to diagnose, but is associated with an elevated blood pressure during heart failure.

Assessing mammography rates for Medicaid recipients age 50 to 65 years using claims data from a southeastern state.

A retrospective Medicaid claims data analysis for physician-submitted mammography procedure codes was performed for all continuously eligible female Louisiana Medicaid recipients in 1994. The study measured mammography screening and diagnostic radiology procedures, using CPT coding logic. The study population consisted of 19,688 female Medicaid recipients, age 50 to 65, comprising 55% of the total female Medicaid recipients within Louisiana. In this cohort, 18.3% received a mammogram, with approximately 50% being diagnostic mammography procedures. No significant racial difference in utilization of mammography was found for this population. This claims data analysis suggests that Louisiana's Medicaid population appears to be underserved with respect to mammography screening. The authors conclude that community, physician, and public health resources would be well served to place more emphasis on educational and other outreach programs. Louisiana has to increase its rates for Medicaid recipients by 50% to meet the goal of screening 60% of eligible women every 2 years as set forth in Healthy people 2000, by the United States Public Health Service.

What role does occupational and environmental health law have in graduate and continuing medical education?

A two-stage survey that used the Delphi technique was performed to determine the attitudes and needs of physicians that practice occupational and environmental medicine (OEM) regarding continuing medical education (CME) and Master of Public Health (MPH) curriculum in the area of health law. Forty-six of the 80 subjects (58%) responded to the first survey, and 39 of these 46 (85%) responded to the follow-up survey. The results showed that most subjects agreed with the need for CME to devote approximately 14 hours over the next two years (1993-1995) to occupational/environmental health laws and regulations. Interest was also expressed in some practical business law that would be helpful to medical practices. The survey's results showed agreement on the need for a three-credit hour MPH course for OEM residents. The differences between the subgroups of academic faculty-post-1990 graduates of MPH or occupational medicine residencies, pre-1990 graduates, and those with no formal OEM education-were also investigated. Pre-1990 graduates consistently desired more hours of CME for the topics surveyed. This study should be helpful for planners of OEM CME courses and for residency directors.

A controlled trial of a seminar to improve medical student attitudes toward, knowledge about, and use of the medical literature.

OBJECTIVE: To determine whether an interactive seminar could affect medical student knowledge of research design, basic critical appraisal skills, and attitudes toward and clinical use of the medical literature. DESIGN: Controlled, nonrandomized clinical trial. PARTICIPANTS: Third-year clinical clerks (n = 146) during their core medicine clerkship. INTERVENTIONS: Two 90-minute interactive seminars. MEASUREMENTS AND MAIN RESULTS: Pre- and postquestionnaires were used to assess knowledge and attitudes regarding the use of the medical literature among 65 study and 81 control students. Blinded review of write-ups assessed actual use of the medical literature. Overall, 80% of the students subscribed to one or more journals and reported reading three or more journal articles per month. After the intervention, the study students were more likely than the control students to consider: 1) study design important in article selection and 2) use of medical literature critical to patient care decisions. Knowledge scores were significantly improved in the study group (p = 0.0001). The intervention yielded no increase in the actual use of medical literature in patient write-ups over that encouraged by usual clerkship goals. 51% of the study and 48% of the control students cited literature at baseline, and 53% of all the students did so after the intervention. Of these citations, 50% were for journal articles and the remainder were for textbooks. The students infrequently mentioned the quality of the cited literature. CONCLUSIONS: An interactive seminar designed to introduce medical students to critical appraisal improved student knowledge and attitudes but did not increase the actual use of literature in patient write-ups.

Total lymphocyte count as a predictor of absolute CD4+ count and CD4+ percentage in HIV-infected persons.

OBJECTIVE: To determine whether the total lymphocyte count (TLC) accurately predicts a low absolute CD4+ T-cell count and CD4+ percentage in persons infected with human immunodeficiency virus (HIV). DESIGN: Retrospective analysis of data collected in the US Air Force HIV Natural History Study. SETTING: Military medical center that performs annual medical evaluation of all HIV-infected US Air Force personnel. PATIENTS: A total of 828 consecutive patients with no prior history of zidovudine use, evaluated from January 1985 through July 1991. For patients with multiple observations over time, a single data point within each 6-month interval was included in the analysis (N = 2866). MEASUREMENTS AND MAIN RESULTS: The sensitivity, specificity, and likelihood ratio (LR) of the TLC, in the range of 1.00 x 10(9)/L to 2.00 x 10(9)/L, in predicting an absolute CD4+ T-cell count less than 0.20 x 10(9)/L or a CD4+ percentage less than 20% were calculated. In addition, the LR and pretest probability of significant immunosuppression were used to calculate posttest probabilities of a low CD4+ count for a given TLC value. The LR of the TLC in predicting an absolute CD4+ count < 0.20 x 10(9)/L increased from 2.4 (95% confidence interval, 2.2 to 2.5) for all TLCs less than 2.00 x 10(9)/L, to 33.2 (95% confidence interval, 24.1 to 45.7) for all TLCs less than 1.00 x 10(9)/L. The specificity for this prediction increased from 57% to 97% over this range. The LR also increased from 1.4 (95% confidence interval, 1.3 to 1.6) for all TLCs less than 2.00 x 10(9)/L to 9.7 (95% confidence interval, 7.1 to 13.1) for all TLCs less than 1.00 x 10(9)/L in predicting a CD4+ percentage less than 20%. CONCLUSIONS: The TLC, between 1.00 x 10(9)/L and 2.00 x 10(9)/L, appears to be a useful predictor of significant immunosuppression as measured by a CD4+ T-cell count less than 0.20 x 10(9)/L in HIV-infected persons. The LR for a given TLC value and the pretest probability of immunosuppression can be used to determine the posttest probability of significant immunosuppression in individual patients. For example, in a patient with a TLC less than 1.50 x 10(9)/L and a pretest probability of 16%, the posttest probability of a low CD4+ T-cell count increases to 53%. In contrast, a TLC greater than 2.00 x 10(9)/L in an individual with a pretest probability of 30% will decrease the posttest probability of a low CD4+ T-cell count to less than 4%. Physicians should find these data useful to help predict the risk for opportunistic infection among HIV-infected persons who present with syndromes that are potentially compatible with opportunistic infection but who have not had recent or prior CD4+ T-cell analysis.

The challenge of deliberate self-harm by young adolescents.

This paper describes a model of crisis intervention to families of adolescents below the age of 16 who deliberately harm themselves and summarizes the premises which guide our practice. The adolescent's "overdose" is understood as an attempt to resolve relationship conflicts and so the initial interview aims to explore the predicament for the adolescent and the family and decide what further help may be required. Verbatim extracts from one session illustrate this process.

The J-curve phenomenon and the treatment of hypertension. Is there a point beyond which pressure reduction is dangerous?

We critically appraised the medical literature to evaluate whether there is a point beyond which blood pressure reduction in hypertensive subjects is no longer beneficial and possibly even deleterious. Thirteen studies that stratified cardiovascular outcomes by level of achieved blood pressure in treated hypertensive subjects who had been followed up for at least 1 year were critiqued by four independent reviewers. Data addressing population, protocol, and methodological characteristics were evaluated. Studies did not show a consistent J-shaped relationship between treated blood pressure and stroke, but they did demonstrate a consistent J-shaped relationship for cardiac events and diastolic blood pressure. The beneficial therapeutic threshold point was 85 mm Hg. We conclude that low treated diastolic blood pressure levels, ie, below 85 mm Hg, are associated with increased risk of cardiac events.