Risk assessment for PFOA and kidney cancer based on a pooled analysis of two studies.

INTRODUCTION: Perfluorooctanoic acid (PFOA) has been associated with kidney cancer in human studies. METHODS: We conducted a pooled analysis of two large studies of PFOA and renal cell carcinoma (RCC, the most common type of kidney cancer); one from the National Cancer Institute (NCI) (324 cases and controls), and a second from the C8 Science Panel (103 cases and 511 controls). Serum PFOA levels were estimated a median of 8 years before diagnosis. Analyses were conducted via conditional logistic regression. Lifetime risk of kidney cancer per unit serum PFOA concentration and per unit dose were calculated. RESULTS: The 25th, 50th and 75th percentiles of serum PFOA levels were 4.8, 7.3, and 23.9 ng/ml for the pooled analysis. The preferred model for the pooled datawas a two-piece linear spline model (knot at 12.5 ng/ml serum PFOA); the log odds of RCC increased 0.1349 per 1 ng/ml increase in serum PFOA up to the knot (eg, an OR of 2.02 (1.45-2.80) from the median to the knot), and was flat thereafter. The estimated lifetime excess risk (cancer slope factor) with an exposure of 1 ng/ml was 0.0018, similar to the excess risk of 0.0026 recently reported by CalEPA based on different methods. Assuming a serum half-life of 2.3 years and a distribution volume of 170 ml/kg for PFOA, our results are equivalent to 0.0128 per ng/kg/d of PFOA intake. To limit excess lifetime kidney cancer risk to 1/1,000,000, our data suggest a limit of 0.0015 ng/L (0.0015 ppt) for PFOA in drinking water, similar to CalEPA's proposed Public Health Goal and the new US EPA Drinking Water Health Advisory. CONCLUSIONS: Our results correspond reasonably well with cancer slope factors developed by other investigators using published summary data, and suggest drinking water limits similar to new recommendations by the US EPA.

Assessment of dementia risk in aging adults using both FDG-PET and FDDNP-PET imaging.

BACKGROUND: In a previous study, positron emission tomography (PET) with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, identified three subgroups of non-demented subjects according to FDDNP binding patterns: low global (LG) binding; high frontal, parietal, medial temporal binding (HF/PA); and high medial and lateral temporal and posterior cingulate (HT/PC) binding. In this follow-up investigation, we compared 2-deoxy-2-[F-18]fluoro- d-glucose (FDG)-PET cerebral metabolic patterns in the three FDDNP-PET binding subgroups. METHODS: Fifty-four subjects with normal aging (N = 28) or amnestic forms of mild cognitive impairment (N = 26) underwent FDDNP-PET and FDG-PET scanning. Subjects in the LG, HF/PA, and HT/PC FDDNP subgroups were compared according to visual ratings, statistical parametric mapping, and automated region of interest analyses of their FDG-PET data. RESULTS: The FDDNP-PET subgroups demonstrated different glucose metabolic patterns according to visual ratings, region of interest, and statistical parametric mapping analyses of FDG-PET data. The LG FDDNP subgroup showed no areas of significant hypometabolism relative to the other subgroups and had low Alzheimer's disease risk by FDG-PET standards. The HF/PA FDDNP subgroup demonstrated hypometabolism in bilateral inferior parietal/parietotemporal, bilateral posterior cingulate, perisylvian, mid-temporal gyrus, and dorsolateral prefrontal regions, which is a pattern suggestive of high Alzheimer's disease risk. The HT/PC FDDNP subgroup demonstrated heterogeneous FDG-PET patterns with predominant anterior frontal and anterior temporal hypometabolism, suggestive of mixed etiologies, including fronto-temporal dementia risk. CONCLUSIONS: The FDG-PET data provided independent validation that different patterns of FDDNP-PET binding in non-demented individuals may be associated with differential dementia risk.

Assessment of lifetime exposure to trihalomethanes through different routes.

OBJECTIVES: To evaluate lifetime exposure to trihalomethanes (THM) through ingestion, inhalation, and dermal absorption in a hospital based case-control study of bladder cancer conducted between 1998 and 2001 in five areas of Spain. The study base was comprised of subjects living in the catchment areas of the participating hospitals. METHODS: Individual information on water related habits was obtained from personal interviews of 1219 cases and 1271 controls: residential and occupational history, drinking water source at each residence and job, amount of water consumption, frequency and duration of showering, bathing, and swimming pool attendance. THM levels, water source history, and year when chlorination started in study areas were ascertained through measurements in drinking water samples and questionnaires to water companies and local authorities. Estimates of THM levels covered 79% of the subjects' person-years of exposure. RESULTS: Current and historical average THM levels in water were correlated. Control subjects reported that drinking water source in the last residence was municipal for 63%, bottled for 22%, private well for 2%, and other sources for 13%. For the time window between age 15 and the time of interview, average residential THM level was 32.2 mug/l. THM exposure through ingestion was 23.7 mug/day on average, and was correlated with the ingestion THM level in the workplace. Overall, 79% usually took showers, 16% usually took baths, and 13% had ever attended a swimming pool. Between 21% and 45% of controls unexposed to THM through ingestion were evaluated as moderately or highly exposed through showering or bathing, and 5-10% were exposed through swimming in pools. CONCLUSION: The importance of evaluating different routes is underscored by findings from experimental studies showing substantial differences in THM uptake and internal distribution by route.

Cost-effectiveness of 18F-fluorodeoxyglucose positron emission tomography in the assessment of early dementia from a Belgian and European perspective.

(18)F-fluoro-deoxyglucose positron emission tomography (FDG PET) can aid to predict AD in an early stage. The aim of this study was to estimate the economic effects of incorporating FDG PET in the diagnostic work-up of AD in a Belgian and European setting. A decision tree analysis was followed comparing a conventional algorithm using diagnostic clinical criteria and one that also incorporates PET. Major outcome terms were overall cost per patient in either strategy; diagnostic accuracy and cost per accurate diagnosis. A sensitivity analysis was performed for four critical variables: cost of PET, sensitivity and specificity of PET and delay in cognitive decline because of appropriate medication. Cost-savings per accurate diagnosis ranged from 623-6110 Euro in favour of the proposed algorithm with PET. For the same cost, more accurate diagnoses were made, resulting in benefit for patients and society. The positive results were maintained over a wide range of values for the critical variables and were expandable to other European countries with a similar health system. Therefore, incorporation of FDG PET into the clinical diagnostic work up of patients with early symptoms of cognitive decline can be advocated.

Hemodynamic assessment of local anesthetic administration by laser Doppler flowmetry.

OBJECTIVE: The hemodynamic effects of local anesthetic administration with and without a vasoconstrictor were compared by using laser Doppler flowmetry. STUDY DESIGN: Seventeen people participated in a single study session in which they were given 2 intraoral injections. The injections, which were administered in random order, consisted of 1.8 mL lidocaine (2%) with epinephrine (1:100,000) and mepivacaine (3%). Hemodynamic parameters consisting of blood pressure, heart rate, and laser Doppler flowmetry were reordered at regular intervals. RESULTS: The laser Doppler flowmeter detected changes in the peripheral perfusion of the finger that were not detected by changes in blood pressure and heart rate. The greatest change was associated with anxiety and occurred just before the injection. The inclusion of epinephrine in the local anesthetic resulted in a persistence of these changes. CONCLUSION: This investigation has confirmed the sensitivity of laser Doppler flowmetry as an investigational tool for assessing hemodynamic changes associated with anxiety and the administration of local anesthesia.

Excess incidence of squamous cell esophageal cancer among US Black men: role of social class and other risk factors.

Data from a population-based case-control study were used to evaluate the relation between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and low income contribute to the higher incidence among Black men than among White men in the United States. A total of 347 male cases (119 White, 228 Black) and 1,354 male controls (743 White, 611 Black) were selected from three US geographic areas (Atlanta, Georgia, Detroit, Michigan, and New Jersey). Cases were residents of the study areas aged 30-79 years who had been diagnosed with histologically confirmed esophageal cancer between 1986 and 1989. The adjusted odds ratios for subjects with annual incomes less than $10,000 versus incomes of $25,000 or more were 4.3 (95% confidence interval: 2.1, 8.7) for Whites and 8.0 (95% confidence interval: 4.3, 15.0) for Blacks. The combination of all four major risk factors-low income, moderate/heavy alcohol intake, tobacco use, and infrequent consumption of raw fruits and vegetables-accounted for almost all of the squamous cell esophageal cancers in Whites (98%) and Blacks (99%) and for 99% of the excess incidence among Black men. Thus, lifestyle modifications, especially a lowered intake of alcoholic beverages, would markedly decrease the incidence of squamous cell esophageal cancer in both racial groups and would narrow the racial disparity in risk. Further studies on the determinants of social class may help to identify a new set of exposures for this tumor that are amenable to intervention.

The excess incidence of squamous cell esophageal cancer among us black men. Role of social class and other risk factors.

PURPOSE: To investigate the relationship between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and social class contribute to the five-fold higher incidence among black than white men in the United States.METHODS: Interviews were conducted with 347 incident cases of squamous cell esophageal cancer (119 white males and 228 black males) and 1354 population-based controls (743 white males and 611 black males) from Atlanta, Detroit, and New Jersey. Risks were estimated using unconditional logistic regression controlling for potential confounders.RESULTS: Elevated risks of squamous cell esophageal cancer were associated with indicators of low social class, especially low annual income. The adjusted odds ratios (ORs) for subjects with incomes < $10,000 versus incomes of $25,000 or more were 4.3 (95% CI = 2.1-8.7) for whites and 8.0 (95% CI = 4.3-15.0) for blacks. The combination of all four major risk factors: annual income less than $25,000, moderate/heavy use of alcohol, use of tobacco for six months or longer, and consumption of less than 2.5 servings of raw fruits and vegetables per day accounted for almost all of the squamous cell esophageal cancers in whites (98%) and blacks (99%), and for 99% of the excess incidence among black men.CONCLUSIONS: Lifestyle modifications, especially a lower intake of alcoholic beverages, would markedly decrease the incidence of this cancer in both races and narrow the racial disparity in risk. Further studies into the determinants of social class may help identify a new set of exposures for this tumor that are amendable to intervention.

Socioeconomic status and multiple myeloma among US blacks and whites.

OBJECTIVES: This study examined the relation between socioeconomic status (SES) and risk of multiple myeloma among Blacks and Whites in the United States. METHODS: This population-based case-control study included 573 cases (206 Blacks and 367 Whites) with new diagnoses of multiple myeloma identified between August 1, 1986, and April 30, 1989, and 2131 controls (967 Blacks and 1164 Whites) from 3 US geographic areas. Information on occupation, income, and education was obtained by personal interview. RESULTS: Inverse gradients in risk were associated with occupation-based SES, income, and education. Risks were significantly elevated for subjects in the lowest categories of occupation-based SES (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.16, 2.53), education (OR = 1.36, 95% CI = 1.06, 1.75), and income (OR = 1.43, 95% CI = 1.05, 1.93). Occupation-based low SES accounted for 37% of multiple myeloma in Blacks and 17% in Whites, as well as 49% of the excess incidence in Blacks. Low education and low income accounted for 17% and 28% of the excess incidence in Blacks, respectively. CONCLUSIONS: Our results indicate that the measured SES-related factors account for a substantial amount of the Black-White differential in multiple myeloma incidence.

Assessment of the economic impact of an overage reduction program in the operating room.

STUDY OBJECTIVES: To delineate excessive supply preparation in the operating rooms (ORs) of Yale-New Haven Hospital, and to measure the reduction in such overage as a result of nursing and administration cost-containment efforts. DESIGN: Before and after trial. SETTING: Inpatient ORs of Yale-New Haven Hospital. INTERVENTIONS: After the initial documentation of overage, several cost-containment measures were instituted, including nursing education, review of overage data, and updating of surgical request lists. MEASUREMENTS AND MAIN RESULTS: The hospital cost of case-specific overage generated by all surgical procedures performed during two 2.5-month periods in 1992 and 1994 (before and after the interventions) were compared. One-thousand three hundred eighteen cases in 1992 were compared with 1,367 cases in 1994. A 45% reduction in mean per case overage occurred between the two assessment periods. Extrapolation of the data to the incidence of similar cases throughout the United States projected a comparable savings. CONCLUSIONS: Efforts to increase the efficiency of OR supply management can be measured, in part, by overage evaluation, which can serve as a resource for focusing efforts at cost-containment.

Focused versus operating room-wide recovery of unused supplies for overseas reconstructive surgery.

Proliferation of programs that recover surplus operating room supplies may effectively address the needs of volunteer overseas surgical efforts. However, these programs tend to garner supplies highly heterogeneous in nature. In order to evaluate the nature and quantity of supplies generated by plastic and reconstructive procedures, we extrapolated the inventory of 71 consecutive cases from our 33,000-case database. Additionally, we examined the recovery of 7 specific supplies from all cases performed at Yale-New Haven Hospital over a 3-year period. Though consistency is unlikely when only plastic and reconstructive surgical cases are examined, operating room-wide recovery may be a reliable source of usable materials.

Pulse width, stimulus intensity, electrode placement, and polarity during assessment of neuromuscular block.

BACKGROUND: Although the intensity of neurostimulation (i.e., charge) is a product of current intensity and pulse duration, the effects of the latter on the amplitude of evoked response and subjective discomfort are unknown. Therefore, the authors investigated the effects of current intensity and pulse width, and their interaction with electrode placement and polarity, on force translation (FTR), accelerography (ACG), and electromyography (EMG) at the adductor pollics muscle. METHODS: Ulnar stimulating electrodes were applied in one of two configurations: over the distal forearm and olecranon groove ("A") or 5 cm apart on the distal forearm ("B"). Stimuli for FTR and EMG with current intensities of 20, 40, 60, and 70 mA and pulse widths of 0.05, 0.1, 0.2, and 0.4 msec resulted in 16 different charges. These combinations were delivered in each of four orientations: "A-" ("A" configuration with negative electrode distal); "A+", "B-", and "B+" (n = 64 stimuli). Eight stimulus combinations (n = 32 stimuli) were used for ACG. For each monitoring technique, the effects of current intensity, pulse width, electrode polarity, and placement were analyzed with repeated measures ANOVA. Pain responses were scored on a 0-100-mm verbal analog scale and analyzed with ANOVA and Fisher's exact test. RESULTS: The evoked response amplitude varied directly with current intensity and pulse width. In both electrode placement configurations, the response was greater when the negative electrode was distal. The electrode positioning ("A" vs. "B") had less of an impact on evoked responses than did polarity, regardless of monitoring technique. The evoked pain varied directly with the amplitude of evoked neuromuscular response in all electrode position-polarity combinations. CONCLUSIONS: The total current charge required for evoking a supramaximal neuromuscular response is much higher than previously appreciated, and electrode polarity is important in attaining a supramaximal plateau. Failure to attain (and maintain) a supramaximal stimulus allows changes in the effectiveness of neurostimulation, thus influencing the magnitude of the evoked neuromuscular response and confounding measurements of neuromuscular block.

Real time versus slow-motion train-of-four monitoring: a theory to explain the inaccuracy of visual assessment.

The present study was undertaken to determine why visual assessment of thumb adduction in response to train-of-four (TOF) stimulation of the ulnar nerve commonly overestimates the ratio that is obtained mechanographically. In patients undergoing general endotracheal anesthesia plus vecuronium for relaxation, 73 data sets were collected at different depths of neuromuscular block in response to supramaximal TOF stimulation. Each data set consisted of: (i) visual estimation of the TOF ratio by an experienced observer; (ii) mechanographic measurement of the TOF ratio with an adductor pollicis force transducer; and (iii) determination of the TOF ratio by measuring the slow-motion thumb displacement recorded on videotape. The last 23 data sets also included visual assessment and videotape recording of evoked responses at low stimulating current (30 mA). Visual inspection at 60 mA overestimated the mechanographic ratio by 0.20 units (48%). Videotape review provided a ratio that was 0.23 units (56%) greater than that determined mechanographically. However, after the first three twitches (T1-3), the thumb did not return to the same resting position as the (original) baseline prior to the first twitch. When the change in thumb position as a result of T1-3 was taken into account, the measured height of T4 was 40% less than it was when measured from the original baseline, and the T4/T1 ratio was identical to that obtained mechanographically. For the 23 data sets obtained at low current visual assessment overestimated the mechanographic value to a lesser degree than when obtained at high current. Again, correction for the T1-3 baseline shift improved the accuracy of videotape analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effective use of operating room supplies based on the REMEDY database of recovered unused materials.

It is estimated that $200 million worth of prepared materials are discarded unused in operating rooms in the United States each year. Although some of these materials have been successfully recovered for overseas donation, they nevertheless constitute an undesirable burden on health care efficiency. This situation has prompted a reevaluation of the procedures that result in the overpreparation of surgical supplies, in the hope of reducing hospital, patient, and third-party payer expenditures. A database, which was initially developed to track the overseas donation of recovered supplies from Yale-New Haven Hospital, is now being applied to measure approaches to waste reduction. This report summarizes the application of this database to an integrated program designed to modify nursing procedures and physician prespecified supply lists.

Peripheral assessment of phenylephrine-induced vasoconstriction by laser Doppler flowmetry and its potential relevance to homeostatic mechanisms.

BACKGROUND: Cutaneous laser Doppler flowmetry enables monitoring of changes in skin perfusion by quantifying the phase shift of laser light induced by moving red blood cells under a fiberoptic probe. It thus can identify the presence of and response to a vasoconstrictive stimulus. However, aspects of the technique must be defined before it can be used with maximum effectiveness. We evaluated the responses of two different laser Doppler outputs, the concentration of moving blood cells (CMBC) and red cell flux (CMBC times cell velocity), and the responses at two sites of probe application, the finger and forearm, during systemic infusions of phenylephrine. METHODS AND RESULTS: Eight healthy volunteers were monitored with a brachial blood pressure cuff, ECG, and laser Doppler flowmeter probes applied to the palmar surface of the fourth finger and volar forearm of the arm opposite the pressure cuff. After baseline readings were obtained, the subjects received three 10-minute intravenous infusions of phenylephrine at rates of 0.4, 0.8, and 1.6 micrograms.kg-1.min-1. The two parameters, flux and CMBC, trended similarly. Flux and CMBC at the finger declined significantly in response to each infusion (P < .05 using repeated-measures ANOVA with Duncan's multiple range test). In contrast, flux and CMBC of the forearm had highly variable responses, with an overall increase during each infusion (P < .05 for % delta of forearm versus % delta of finger readings during the 0.4 microgram.kg-1.min-1 infusion). Heart rate declined significantly during each infusion, consistent with a baroreceptor-mediated response, even though systolic and diastolic blood pressures each increased by less than 2 mm Hg during the 0.4 microgram.kg-1.min-1 infusion. CONCLUSIONS: As expected, laser Doppler readings at the finger decreased during infusion of an alpha 1-agonist. Although, like the digital vessels, forearm vessels have the potential to constrict, the increases in forearm readings suggest that these vessels are highly susceptible to homeostatic responses. The increase in CMBC (a parameter that is sensitive primarily to local changes in vascular caliber) suggested vasodilation of the underlying vessels. The forearm vasodilation and the concomitant decline in heart rate most likely represented vagally mediated baroreceptor activity, which was altered even though blood pressure changed minimally during the 0.4 microgram.kg-1.min-1 infusion. Thus, integrated assessment of skin perfusion at the finger and forearm may provide valuable information about the direct and indirect effects of a vasoactive stimulus. The present application of laser Doppler flowmetry suggests activation of vasodilatory reflexes despite minimal changes in blood pressure.

Visual and tactile assessment of neuromuscular fade.

The accuracy of visual and tactile assessment of the neuromuscular fade in response to train-of-four (TOF) and double-burst stimulation (DBS) were compared to assess their relative utility in the clinical setting. For each of 74 data sets with a mechanographic TOF ratio less than 0.70, an observer (blinded to the presence or degree of fade) performed visual and tactile assessments of fade in response to TOF, DBS3,3, and DBS3,2 stimuli at low current (20 and 30 mA) and high current (50 and 60 mA). For the range of mechanographic TOF ratios between 0.41 and 0.70, visual assessment failed to identify TOF, DBS3,3, and DBS3,2 fade in 46%, 18%, and 14% of cases at high current and in 23%, 5%, and 0% of cases at low current, respectively. Tactile assessments failed to identify fade in 55%, 23%, and 14% of cases at high current and in 23%, 14%, and 14% of cases at low current. Overall, the ability to detect fade was comparable for visual and tactile assessments regardless of the method of neurostimulation (P = NS with paired t-test). However, the degree of overestimation of the fade ratio (i.e., quantitative assessment) tended to be less when using tactile means; the difference achieved significance for TOF at low current and DBS3,3 at both low and high currents. We conclude that the differences between the visual and tactile means of assessment are relatively small compared to the differences among the TOF and DBS patterns of neurostimulation. Both subjective techniques are often inadequate in settings in which assurance of full recovery of neuromuscular function is critical.

Atrial ejection force: a noninvasive assessment of atrial systolic function.

OBJECTIVES: The purpose of this study was to define atrial ejection force and to develop a method for its noninvasive measurement from echocardiographic data. BACKGROUND: Assessment of diastolic function through measurement of the components of ventricular filling has largely neglected the vigor of atrial systole, in part because this has been difficult to quantify. However, atrial ejection force, defined as that force exerted by the left atrium to accelerate blood into the left ventricle during atrial systole, can be assessed noninvasively by combined two-dimensional imaging and Doppler echocardiography. This index of atrial function, based on classic newtonian mechanics, provides a physiologic assessment of atrial systolic function. METHODS: To evaluate the usefulness of atrial ejection force, we studied the return of left atrial ejection force in 29 patients after elective cardioversion for atrial fibrillation. Transmitral Doppler inflow patterns at rest were assessed immediately after cardioversion and at 24 h, 1 week, 1 month and > 3 months later. A healthy adult group (n = 10) served as control subjects. RESULTS: After successful cardioversion, atrial ejection force was significantly depressed compared with that in the control group (5.2 +/- 6.8 vs. 16.3 +/- 4.7 kdynes; p < 0.0001). Over successive weeks, atrial ejection force improved in the subgroup of patients who remained in sinus rhythm (n = 18), whereas no improvement was seen during the period of maintained sinus rhythm in the patients with subsequent reversion to atrial fibrillation (n = 11). CONCLUSIONS: Atrial ejection force provides a physiologic assessment of atrial systolic function and is a potentially useful index for assessing atrial contribution to diastolic performance. In patients who successfully underwent cardioversion from atrial fibrillation, atrial ejection force improved over several weeks only in the subgroup in which sinus rhythm was maintained.

Assessment of double-burst monitoring at 10 mA above threshold current.

We compared fade measurements in response to double-burst stimulation (DBS) at 10 mA above the threshold for the second response (D2) to that for DBS at 60 mA in order to determine the utility of low-current DBS testing. In 20 healthy adults undergoing general endotracheal anesthesia with isoflurane 0.5-1% end-tidal, a vecuronium infusion (0.25-1.5 micrograms.kg-1 x min-1) was delivered until a stable train-of-four (TOF) response to ulnar nerve stimulation was documented with an adductor pollicis force transducer. Then DBS responses were recorded, and the D2/D1 ratios were determined at 60 mA and at 10 mA above the D2 threshold current (TS + 10 mA). The mean difference (bias) between D2/D1 /TS+10 mA and D2/D1 / 60 mA was -0.02 (P < 0.05); the 95% limits of agreement were from -0.12 to +0.08. The bias and limits of agreement were similar to those for T4/T1 of train-of-four. A strong correlation was noted between the degrees of fade determined at the low and high currents (r = 0.95). We conclude that, although stimulation at 10 mA above the D2 threshold is associated with a slight negative bias, it is virtually interchangeable with testing at higher current in the clinical setting. This technique thus may be used effectively to monitor neuromuscular fade in settings where neurostimulation with low current is deemed desirable.

Psychosocial impact of HIV-related caregiving on health providers: a review and recommendations for the role of psychiatry.

OBJECTIVE: The author considers current knowledge about the stresses of HIV-related care and assesses available evidence for the presence of major occupational, physical, and psychiatric morbidity in health care providers involved in intensive HIV-related caregiving. METHOD: The review is based on anecdotal reports of AIDS-care-related psychosocial distress and the literature concerning caregivers' attitudes toward people with HIV illness and HIV-related caregiving, the psychosocial impact of HIV work, and stress related to the ethical and philosophical challenges facing HIV caregivers. RESULTS: Few of the current publications concerning HIV caregiver stress come from the psychiatric literature. Psychiatry appears to lack a strong clinical, educational, research, or policy presence regarding psychosocial stress in HIV care providers. The numerous studies in the nursing, medical, public health, and health education literature do not include any controlled investigations documenting the incidence and prevalence of physical, psychological, occupational, or interpersonal symptoms or disorders in health care professionals who devote a substantial amount of their clinical activities to patients with HIV illness. CONCLUSIONS: Major HIV-related stress in conjunction with other psychiatric morbidity, such as mood disorders, anxiety disorders, substance abuse, and relationship and occupational problems, seems likely in susceptible caregivers. Decisions about the structure and form of delivery of HIV-related care and programs for caregivers must be based on more carefully controlled psychiatric observations of occupational, physical, psychological, and social adaptation to HIV-related work. The author suggests several areas in which psychiatric clinicians, educators, researchers, and policy experts can make major contributions.